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	<title>Healing Light Seminars</title>
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	<description>Training and Resources for Clinical Excellence in Energetic Therapies</description>
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		<title>Pemphigus Vulgaris</title>
		<link>http://www.healinglightseminars.com/uncategorized/pemphigus-vulgaris/</link>
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		<pubDate>Mon, 30 Apr 2012 01:14:51 +0000</pubDate>
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		<description><![CDATA[Lasers Med Sci.  2012 Apr 27. [Epub ahead of print] Low-level laser therapy on the treatment of oral and cutaneous pemphigus vulgaris: case report. Minicucci EM, Miot HA, Barraviera SR, Almeida-Lopes L. Source Department of Dermatology and Radiotherapy, Botucatu School of Medicine of São Paulo State University-UNESP, Distrito de Rubião Júnior s/n, 18 618-000, Botucatu, [...]]]></description>
			<content:encoded><![CDATA[<div>Lasers Med Sci.  2012 Apr 27. [Epub ahead of print]</div>
<h1>Low-level laser therapy on the treatment of oral and cutaneous pemphigus vulgaris: case report.</h1>
<div>Minicucci EM, Miot HA, Barraviera SR, Almeida-Lopes L.</div>
<div>
<p><strong>Source</strong></p>
<p>Department of Dermatology and Radiotherapy, Botucatu School of Medicine of São Paulo State University-UNESP, Distrito de Rubião Júnior s/n, 18 618-000, Botucatu, SP, Brazil, <a href="mailto:eminicucci@hotmail.com">eminicucci@hotmail.com</a>.</p>
<p><strong>Abstract</strong></p>
</div>
<div>
<p>Pemphigus vulgaris is a chronic autoimmune mucocutaneous disease that initially is manifested by painful intraoral erosions and ulcers which spread to other mucosa and the skin, generally more than 5 months after oral lesion manifestation. The treatment consists of prednisone alone or in combination with an immunosuppressive agent, and the clinical response is perceived within 2 to 4 weeks. Low-level laser therapy has been effective in accelerating the healing of injured tissue, thus inducing cell proliferation and increasing ATP, nucleic acid, and collagen synthesis. We reported two cases of pemphigus vulgaris that received systemic treatment associated with low-level laser therapy for oral and cutaneous lesions. We observed prompt analgesic effect in oral lesions and accelerated healing of oral and cutaneous wounds. Therefore, the present report suggests LLLT as a noninvasive technique that should be considered as an adjuvant therapy in oral and skin disorders in patients with PV.</p>
</div>
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		<title>Antimicrobial Photoinactivation</title>
		<link>http://www.healinglightseminars.com/laser-research-library/antimicrobial-photoinactivation/</link>
		<comments>http://www.healinglightseminars.com/laser-research-library/antimicrobial-photoinactivation/#comments</comments>
		<pubDate>Sat, 31 Mar 2012 19:03:16 +0000</pubDate>
		<dc:creator>Hldavid</dc:creator>
				<category><![CDATA[Laser Research Library]]></category>

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		<description><![CDATA[Virulence. 2011 Nov-Dec;2(6):509-20. Epub 2011 Nov 1. All you need is light: antimicrobial photoinactivation as an evolving and emerging discovery strategy against infectious disease. St Denis TG, Dai T, Izikson L, Astrakas C, Anderson RR, Hamblin MR, Tegos GP. Source Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA. Abstract The story of prevention [...]]]></description>
			<content:encoded><![CDATA[<div>Virulence. 2011 Nov-Dec;2(6):509-20. Epub 2011 Nov 1.</div>
<h1>All you need is light: antimicrobial photoinactivation as an evolving and emerging discovery strategy against infectious disease.</h1>
<div>St Denis TG, Dai T, Izikson L, Astrakas C, Anderson RR, Hamblin MR, Tegos GP.</div>
<div>
<p><strong>Source</strong></p>
<p>Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p>The story of prevention and control of infectious diseases remains open and a series of highly virulent pathogens are emerging both in and beyond the hospital setting. Antibiotics were an absolute success story for a previous era. The academic and industrial biomedical communities have now come together to formulate consensus beliefs regarding the pursuit of novel and effective alternative anti-infective countermeasures. Photodynamic therapy was established and remains a successful modality for malignancies but photodynamic inactivation has been transformed recently to an antimicrobial discovery and development platform. The concept of photodynamic inactivation is quite straightforward and requires microbial exposure to visible light energy, typically wavelengths in the visible region, that causes the excitation of photosensitizer molecules (either exogenous or endogenous), which results in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation. It is an area of increasing interest, as research is advancing i) to identify the photochemical and photophysical mechanisms involved in inactivation; ii) to develop potent and clinically compatible photosensitizer; iii) to understand how photoinactivation is affected by key microbial phenotypic elements (multidrug resistance and efflux, virulence and pathogenesis determinants, biofilms); iv) to explore novel delivery platforms inspired by current trends in pharmacology and nanotechnology; and v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants.</p>
<p>Mini Rev Med Chem.  Jul;9(8):974-83.</p>
</div>
<h1>A new strategy to destroy antibiotic resistant microorganisms: antimicrobial photodynamic treatment.</h1>
<div>Maisch T.</div>
<div>
<p><strong>Source</strong></p>
<p>Antimicrobial PDT, Clinic and Polyclinic for Dermatology, Regensburg University Hospital, Germany, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. <a href="mailto:tim.maisch@klinik.uni-regensburg.de">tim.maisch@klinik.uni-regensburg.de</a></p>
<p>Abstract</p>
</div>
<div>
<p>Photodynamic activity of chemical compounds towards microorganisms was first published at the turn of 20th century and it is based on the concept that a chemical compound, known as the photosensitizer, is localized preferentially in the microorganism and subsequently activated by low doses of visible light of an appropriate wavelength to generate reactive oxygen species that are toxic to the target microorganisms. Processes, in which absorption of light by a photosensitizer induces chemical changes in another molecule, are defined as photosensitizing reactions. Since the middle of the last century, antibacterial photosensitizing reactions were forgotten because of the discovery and the beginning of the Golden Age of antibiotics. Certainly, in the last decades the worldwide rise in antibiotic resistance has driven research to the development of new anti-microbial strategies. Different classes of molecules including phenothiazine, porphyrines, phthalocyanines, and fullerenes have demonstrated antimicrobial efficacy against a broad spectrum of antibiotic resistant microorganisms upon illumination. Due to their extended pi-conjugated system these molecules absorb visible light, have a high triplet quantum yield and can generate reactive oxygen species upon illumination. This mini-review will focus on some major advances regarding physical and chemical properties of photosensitizers and light sources that appear to be suitable in the field of antimicrobial photodynamic therapy. Currently, topical application of a photosensitizer on infected tissues and subsequent illumination seems to be the most promising feature of antimicrobial photodynamic therapy, thereby not harming the surrounding tissue or disturbing the residual bacteria-flora of the tissue.</p>
</div>
<p>Photochem Photobiol. 2009 Nov-Dec;85(6):1364-74.</p>
<h1>Near-infrared photoinactivation of bacteria and fungi at physiologic temperatures.</h1>
<p>Bornstein E&lt;&gt;, Hermans W&lt;&gt;, Gridley S&lt;&gt;, Manni J&lt;&gt;.</p>
<p>Nomir Medical Technologies, Waltham, MA, USA. <a href="mailto:ebornstein@nomirmedical.com">ebornstein@nomirmedical.com</a></p>
<p>We examined a laser system (870 and 930 nm), employing wavelengths that have exhibited cellular photodamage properties in optical traps. In vitro, with 1.5 cm diameter flat-top projections (power density of 5.66 W cm(-2)), at physiologic temperatures, we achieved photoinactivation of Staphylococcus aureus, Escherichia coli, Candida albicans and Trichophyton rubrum. Using nonlethal dosimetry, we measured a decrease in trans-membrane potentials (DeltaPsimt and DeltaPsip) and an increase in reactive oxygen species (ROS) generation in methicillin-resistant S. aureus (MRSA), C. albicans and human embryonic kidney cells. We postulate that these multiplexed wavelengths cause an optically mediated mechano-transduction of cellular redox pathways, decreasing DeltaPsi and increasing ROS. The cellular energetics of prokaryotic and fungal pathogens, along with mammalian cells, are affected in a similar manner when treated with these multiplexed wavelengths at the power densities employed. Following live porcine thermal tolerance skin experiments, we then performed human pilot studies, examining photodamage to MRSA in the nose and fungi in onychomycosis. No observable damage to the nares or the nail matrix was observed, yet photodamage to the pathogens was achieved at physiologic temperatures. The selective aspect of this near-infrared photodamage presents the possibility for its future utilization in human cutaneous antimicrobial therapy.</p>
<p>Acta Odontol Latinoam. 2009;22(2):93-7.</p>
<h1>In vitro lethal photosensitization of S. mutans using methylene blue and toluidine blue O as photosensitizers.</h1>
<p>Araújo PV&lt;&gt;, Teixeira KI&lt;&gt;, Lanza LD&lt;&gt;, Cortes ME&lt;&gt;, Poletto LT&lt;&gt;.</p>
<p>Departamento de Odontologia Restauradora da Faculdade de Odontologia da Universidade Federal de Minas Gerais, Brazil. <a href="mailto:patbhz@terra.com.br">patbhz@terra.com.br</a></p>
<p>Abstract</p>
<p>The purpose of this in vitro study was to evaluate the antimicrobial effect of photodynamic therapy on Streptococcus mutans (A TCC 25175) suspensions, using a red laser for one minute in combination with toluidine blue O (TBO) or methylene blue (MB). Both photosensitizers were used in three concentrations (25, 10 and 5 mg/L). The activity of photosensitizers and laser irradiation were tested separately on the bacteria, as well as the irradiation of this light source in the presence of the TBO or MB. These groups were compared to a control group, in which the microorganism did not receive any treatment. The activity of both TBO and MB or laser irradiation, alone, were not able to reduce the number of S. mutans. In the groups of lethal photosensitization, a bacterial reduction of 70% for TBO and 73% for MB was observed when these photosensitizers were used at 25 mg/L and a reduction of 48% was observed for MB at 5mg/L. In other concentrations there were no significant differences in comparison to the control group. Both the TBO and the MB at 25 mg/L associated with a red laser had an excellent potential for use in PDT in lethal sensitization of S. mutans.</p>
<p>Photomed Laser Surg. 2007 Jun;25(3):150-8</p>
<h1>Antiinfectives and low-level light: a new chapter in photomedicine.</h1>
<p>Sommer AP&lt;&gt;.</p>
<p>Materials Division, University of Ulm, Ulm, Germany. <a href="mailto:samoan@gmx.net">samoan@gmx.net</a></p>
<p>OBJECTIVE: The purpose of this study was to identify synergistic effects in the interaction of light with biosystems in the presence of chemical agents. Their systematic analysis promises therapeutic strategies.</p>
<p>BACKGROUND DATA: Light intensities around 1000 Wm(2) potentially induce density variations in nanoscopic water layers adhering to surfaces in air or subaquatically. In permeable nanoscopic compartments in the interior of biosystems, this could result in powerful flow processes and bidirectional flows for repetitive applications of light. Consequently, external stimulation with light will force microorganisms and cells to incorporate a suitable antiinfective. Nanoscale biosystems, which respond to both light stimulation and antibiotics, are nanobacteria. Responses include growth, inhibition, and slime secretion. Slime secretion was provoked in vitro by gentamycin, an agent proposed for in vivo eradication, and blocked by light. Depending on the field of action, co-operative effects between light and an antiinfective can be exploited by considering two properties of the drug: transmission of light and resorption by the tissue. Antiinfectives can be administered in an active form or via drug delivery systems. In the latter case, a double action of the light could be exploited: stimulated release from the carrier and subsequent uptake by the targeted biosystem.</p>
<p>METHODS: The attenuation of laser light (670 nm) by antiinfectives was measured in films of different thickness of a vaginal suppository. The effect of 670-nm laser light &#8211; not absorbed by water &#8211; on nanoscopic water layers was examined by comparing the evaporation time of irradiated drops of water-based nanosuspensions with non-irradiated controls.</p>
<p>RESULTS: The 6-microm-thick suppository films were virtually transparent to the laser light, and the 1-mm-thick films totally attenuated it. Nanosuspension drops irradiated with 670-nm light needed more time to evaporate than controls.</p>
<p>CONCLUSION: Low-level light (LLL) therapy is compatible with antiinfectives, and even capable of boosting effects of superficially applied and/or absorbed antiinfectives. Temporal coordination between light treatment and drug administration maximizes drug effects and minimizes possible adverse effects. Irradiation should start when the drug concentration has reached its maximum in the desired field of action. Light-induced flow in nanoscale cavities could represent one mechanism of LLL therapy.</p>
<p>Vopr Kurortol Fizioter Lech Fiz Kult. 2006 Sep-Oct;(5):20-3.</p>
<h1> Low intensity effects on local immunity of female reproductive system affected with chlamidia infection</h1>
<p>[Article in Russian]</p>
<p>Gizinger OA&lt;&gt;, Dolgushin II&lt;&gt;.</p>
<p>Low-intensity laser impact on the main effector functions of the cervical secretion neutrophils in females suffering from Chlamidia infection has been studied. Dysfunction of neutrophil granulocytes of the cervical secretion was revealed. This manifested in the decreased number of phagocytes and lower rates of phagocytosis. The study of cervical secretion neutrophils has found that the content of active intracellular forms of oxygen was decreased in patients compared to healthy subjects. Low-intensity laser stimulated not only phagocytosis but also intracellular generation of active oxygen forms. Thus, low-intensity laser eliminates dysfunction of cervical secretion neutrophils.</p>
<p>Zh Mikrobiol Epidemiol Immunobiol. 2006 Jul-Aug;(4):105-9.</p>
<h1>Immunological and microbiological aspects of low intensity laser effect on the factors of local immunity of the reproductive tract in women with chlamydia infection.</h1>
<p><strong> </strong>[Article in Russian]</p>
<p>Dolgushin II&lt;&gt;, Gizinger OA&lt;&gt;, Telesheva LF&lt;&gt;.</p>
<p>Assessment of immunological and microbiological efficacy of Chlamydia cervicitis management was made by a complex method with a low intensity laser. The total number of leukocytes, percentage of viable cells and the number of neutrophils were detected in cervical secrets. Functional status of neutrophils was studied by a content of lysosomes on the ground of spontaneous and induced by latex HCT-reducing capacity, phagocytic activity. A system of cytokines was studied by interleukine level (IL-1 alpha, IL-1 beta, TNF-alpha, IL-8) and IFN-gamma content in cervical mucus. Positive clinical effect of the local use of the low intensity laser for Chlamydia cervicitis treatment was accompanied by positive changes in immunological indices of cervical secret, normal concentration of cytokines in cervical secret, restoration of the number and functions of neutrophils. Local use of the low intensity laser contributed to decreased number of opportunistic pathogenic microorganisms and their associations, and restored local flora.</p>
<p>J Photochem Photobiol B. 2006 May 1;83(2):87-93. Epub 2006 Feb 7.</p>
<h1>Effect of low-level helium-neon laser therapy on the healing of third-degree burns in rats.</h1>
<p><strong> </strong>Bayat M&lt;&gt;, Vasheghani MM&lt;&gt;, Razavi N&lt;&gt;.</p>
<p>Cell and Molecular Biology Research Center, Department of Anatomy, School of Medicine, Shaheed Beheshti University of Medical Sciences, P.O. Box 19395/4719, Tehran, Evin 1985717443, Iran. <a href="mailto:bayat_m@yahoo.com">bayat_m@yahoo.com</a></p>
<p>This paper presents the results of a study on the effects of low-level helium-neon laser therapy (LL He-Ne LT) on the healing of burns. Seventy-eight adult male rats, having been subjected to third-degree burns, were randomly divided into four groups: two laser treated groups (n=20, each), one control group (n=19) and one nitrofurazone treated group (n=19). In the two laser treated groups, the burns were treated on a daily basis with LL He-Ne LT with an energy density of 1.2 and 2.4 J/cm(2), respectively. The response to treatment was assessed histologically at 7, 16 and 30 days after burning, and microbiologically at day 15. Analysis of variance showed that the mean of blood vessel sections in the 1.2J/cm(2) laser group was significantly higher than those in the other groups and the mean of the depth of new epidermis in the 2.4 J/cm(2) laser group on day 16 was significantly lower than in the nitrofurazone treated group (P=0.025, P=0.047, respectively). When Staphylococcus aureus and Pseudomonas aeruginosa grew in more than 50% of samples obtained from control group, there were no S. aureus and P. aeruginosa in the samples of 2.4 J/cm(2) laser group. It is concluded that LL He-Ne LT induced the destruction of S. aureus and P. aeruginosa in third-degree burns of rats, yet at the same time our histological findings showed that LL He-Ne LT caused a significant increase in the mean of blood vessel sections on day 7 after third degree burns and a decrease in the mean of the depth of new epidermis on day 16 after the same burns in rats.</p>
<p>Photomed Laser Surg. 2005 Dec;23(6):571-4.</p>
<h1>Helium-neon and nitrogen irradiation accelerates the phagocytic activity of human monocytes.</h1>
<p>Hemvani N&lt;&gt;, Chitnis DS&lt;&gt;, Bhagwanani NS&lt;&gt;.</p>
<p>Department of Microbiology and Immunology, Choithram Hospital &amp; Research Centre, Indore, India.</p>
<p>OBJECTIVE: Intracellular survival of mycobacteria within monocytes is a crucial stage in the pathogenesis of tuberculosis. The aim was to check intracellular survival of Mycobacterium fortuitum within the human monocytes exposed to He-Ne and nitrogen laser irradiation.</p>
<p>BACKGROUND DATA: Tuberculosis remains one of the most important infectious diseases for developing countries. Low-level laser therapy (LLLT) has been tried to treat tubercular cavitory lung disease with encouraging results. The in vitro photobiological effect of low level laser radiation on the intracellular mycobacteria needs to be evaluated before we could go for large clinical trials.</p>
<p>METHODS: The aliquots of human monocytes from peripheral blood of healthy volunteers and tuberculosis cases were exposed to He-Ne or nitrogen laser beam. The non-irradiated monocytes from the same source served as controls. The monocytes were then challenged with M. fortuitum, and surviving mycobacteria within monocytes were subjected to viable counts.</p>
<p>RESULTS: Enhanced killing of mycobacterial cells was seen among monocytes exposed to He-Ne and nitrogen laser irradiation.</p>
<p>CONCLUSIONS: He-Ne and nitrogen laser irradiation activates the monocytes to increase intracellular killing of mycobacteria.</p>
<p>J Periodontal Res. 2003 Aug;38(4):428-35.</p>
<h1>Lethal photosensitization of periodontal pathogens by a red-filtered Xenon lamp in vitro.</h1>
<p><strong> </strong>Matevski D&lt;&gt;, Weersink R&lt;&gt;, Tenenbaum HC&lt;&gt;, Wilson B&lt;&gt;, Ellen RP&lt;&gt;, Lépine G&lt;&gt;.</p>
<p>Faculty of Dentistry, University of Toronto, University of Toronto, Ontario, Canada.</p>
<p>Abstract</p>
<p>BACKGROUND: The ability of Helium-Neon (He-Ne) laser irradiation of a photosensitizer to induce localized phototoxic effects that kill periodontal pathogens is well documented and is termed photodynamic therapy (PDT).</p>
<p>OBJECTIVES: We investigated the potential of a conventional light source (red-filtered Xenon lamp) to activate toluidine blue O (TBO) in vitro and determined in vitro model parameters that may be used in future in vivo trials.</p>
<p>MATERIALS AND METHODS: Porphyromonas gingivalis 381 was used as the primary test bacterium.</p>
<p>RESULTS: Treatment with a 2.2 J/cm2 light dose and 50 micro g/ml TBO concentration resulted in a bacterial kill of 2.43 +/- 0.39 logs with the He-Ne laser control and 3.34 +/- 0.24 logs with the lamp, a near 10-fold increase (p = 0.028). Increases in light intensity produced significantly higher killing (p = 0.012) that plateaued at 25 mW/cm2. There was a linear relationship between light dose and bacterial killing (r2 = 0.916); as light dose was increased bacterial survival decreased. No such relationship was found for the drug concentrations tested. Addition of serum or blood at 50% v/v to the P. gingivalis suspension prior to irradiation diminished killing from approximately 5 logs to 3 logs at 10 J/cm2. When serum was washed off, killing returned to 5 logs for all species tested except Bacteroides forsythus (3.92 +/- 0.68 logs kill).</p>
<p>CONCLUSIONS: The data indicate that PDT utilizing a conventional light source is at least as effective as laser-induced treatment in vitro. Furthermore, PDT achieves significant bactericidal activity in the presence of serum and blood when used with the set parameters of 10 J/cm2, 100 mW/cm2 and 12.5 micro g/ml TBO.</p>
<p>J Chemother. 2003 Aug;15(4):329-34.</p>
<h1>Comparative antistreptococcal activity of photobactericidal agents.</h1>
<p><strong> </strong>O&#8217;Neill J&lt;&gt;, Wilson M&lt;&gt;, Wainwright M&lt;&gt;.</p>
<p>Department of Microbiology, Eastman Dental Institute, University College London, 256 Gray&#8217;s Inn Road, London WC1X 8LD, UK.</p>
<p>Abstract</p>
<p>In order to establish a comparative order of efficacy among established photosensitising compounds currently under investigation, the in vitro photobactericidal activities of six commercially available photosensitisers were investigated at equal concentration against Streptococcus sanguis using a Helium Neon (HeNe) laser (632.8 nm). Of the photosensitisers used, the four phenothiazinium compounds were efficient photobactericidal agents as was the protoporphyrin IX salt. However, the zinc phthalocyaninetetrasulfonate was less effective. Of the active agents, 1,9-dimethyl Methylene Blue (DMMB) was notable in achieving complete bacterial kill when used at a concentration of 40.85 microM in conjunction with a light energy dose of 21.8 J cm(-2), although there was inherent dark activity associated with this compound. Since each of the photosensitisers is well known to produce singlet oxygen, the relative activities exhibited are thought to be due to differences in bacterial cell uptake, which in turn are related to the physicochemical properties of the photosensitisers, in particular, to the combination of lipophilicity and ionic character.</p>
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<td>J Clin Laser Med Surg. 2003 Oct;21(5):283-90.</td>
<td> </td>
</tr>
</tbody>
</table>
<h1>Effects of low-level laser therapy (LLLT) of 810 nm upon in vitro growth of bacteria: relevance of irradiance and radiant exposure.</h1>
<p>Nussbaum EL, Lilge L, Mazzulli T.</p>
<p>Rehabilitation Services, Mount Sinai Hospital and Department of Physical Therapy, University of Toronto, Toronto, Ontario, Canada. e.nussbaum@utoronto.ca&lt;&gt;</p>
<p>OBJECTIVE: The aim of this study was to investigate the irradiance-dependency of low-level laser therapy (LLLT) effects on bacterial growth.</p>
<p>BACKGROUND: LLLT is applied to open wounds to improve healing; however, its effect on wound bacteria is not well understood.</p>
<p>MATERIALS AND METHODS: Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were irradiated using a wavelength of 810 nm at irradiances of 0.015 W/cm2 (0-50 J/cm2) and 0.03 W/cm2 (0-80 J/cm2). Bacteria were counted after 20 h of incubation.</p>
<p>RESULTS: LLLT effects varied significantly with species. P.aeruginosa growth decreased overall dependent on an interaction of irradiance and radiant exposure; greatest inhibition was produced using high irradiance delivering radiant exposures in the range of 1-20 J/cm2 (p = 0.001-0.04). In contrast, E. coli growth increased overall (p = 0.01), regardless of irradiance; greatest effects were produced using low radiant exposures (1-20 J/cm2). There was a main effect for irradiance (p = 0.03) on S. aureus growth; however, growth was not different compared with controls. Additional analysis showed that there were differences in growth of P.aeruginosa when comparing samples that were matched by exposure times (66, 329, 658, 1316, 1974, and 2632 sec) rather than radiant exposure; this suggests that irradiance rather than exposure time was the significant factor in P. aeruginosa inhibition.</p>
<p>CONCLUSION: These findings have immediate relevancy in the use of LLLT for infected wounds. Exposure to 810-nm irradiation (0.03 W/cm2) could potentially benefit wounds infected with P. aeruginosa. However, increased E. coli growth could further delay recovery.</p>
<p>J Clin Laser Med Surg. 2003 Aug;21(4):231-5.</p>
<h1>A preliminary investigation into light-modulated replication of nanobacteria and heart disease.</h1>
<p>Sommer AP&lt;&gt;, Oron U&lt;&gt;, Pretorius AM&lt;&gt;, McKay DS&lt;&gt;, Ciftcioglu N&lt;&gt;, Mester AR&lt;&gt;, Kajander EO&lt;&gt;, Whelan HT&lt;&gt;.</p>
<p>Central Institute of Biomedical Engineering, University of Ulm, 89081 Ulm, Germany. <a href="mailto:samoan@gmx.net">samoan@gmx.net</a></p>
<p>OBJECTIVE: The purpose of this preliminary study is to evaluate the effect of various wavelengths of light on nanobacteria (NB).</p>
<p>BACKGROUND DATA: NB and mitochondria use light for biological processes. NB have been described as multifunctional primordial nanovesicles with the potential to utilize solar energy for replication. NB produce slime, a process common to living bacteria. Slime release is an evolutionary important stress-dependent phenomenon increasing the survival chance of individual bacteria in a colony. In the cardiovascular system, stress-induced bacterial colony formation may lead to a deposition of plaque.</p>
<p>METHODS: Cultured NB were irradiated with NASA-LEDs at different wavelengths of light: 670, 728 and 880 nm. Light intensities were about 500k Wm(-2), and energy density was 1 x 10(4) J m(-2).</p>
<p>RESULTS: Monochromatic light clearly affected replication of NB. Maximum replication was achieved at 670 nm.</p>
<p>CONCLUSIONS: The results indicate that suitable wavelengths of light could be instrumental in elevating the vitality level of NB, preventing the production of NB-mediated slime, and simultaneously increasing the vitality level of mitochondria. The finding could stimulate the design of cooperative therapy concepts that could reduce death caused by myocardial infarcts.</p>
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<td>J Clin Laser Med Surg. 2002 Dec;20(6):325-33.</td>
<td> </td>
</tr>
</tbody>
</table>
<h1>Effects of 630-, 660-, and 905-nm laser irradiation delivering radiant exposure of 1-50 J/cm2 on three species of bacteria in vitro.</h1>
<p>Nussbaum EL, Lilge L, Mazzulli T.</p>
<p>Rehabilitation Services, Mount Sinai Hospital and Department of Physical Therapy, University of Toronto, Toronto, Ontario, Canada. <a href="mailto:e.nussbaum@utoronto.ca">e.nussbaum@utoronto.ca</a></p>
<p>OBJECTIVE: To examine the effects of low-intensity laser therapy (LILT) on bacterial growth in vitro.</p>
<p>BACKGROUND DATA: LILT is undergoing investigation as a treatment for accelerating healing of open wounds. The potential of coincident effects on wound bacteria has received little attention. Increased bacterial proliferation could further delay recovery; conversely inhibition could be beneficial.</p>
<p>MATERIALS AND METHODS: Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus were plated on agar and then irradiated with wavelengths of 630, 660, 810, and 905 nm (0.015 W/cm(2)) and radiant exposures of 1-50 J/cm(2). In addition, E. coli was irradiated with 810 nm at an irradiance of 0.03 W/cm(2) (1-50 J/cm(2)). Cells were counted after 20 h of incubation post LILT. Repeated measures ANOVA and Tukey adjusted post hoc tests were used for analysis.</p>
<p>RESULTS: There were interactions between wavelength and species (p = 0.0001) and between wavelength and radiant exposure (p = 0.007) in the overall effects on bacterial growth; therefore, individual wavelengths were analyzed. Over all types of bacteria, there were overall growth effects using 810- and 630-nm lasers, with species differences at 630 nm. Effects occurred at low radiant exposures (1-20 J/cm(2)). Overall effects were marginal using 660 nm and negative at 905 nm. Inhibition of P. aeruginosa followed irradiation using 810 nm at 5 J/cm(2) (-23%; p = 0.02). Irradiation using 630 nm at 1 J/cm(2) inhibited P. aeruginosa and E. coli (-27%). Irradiation using 810 nm (0.015 W/cm(2)) increased E. coli growth, but with increased irradiance (0.03 W/cm(2)) the growth was significant (p = 0.04), reaching 30% at 20 J/cm(2) (p = 0.01). S. aureus growth increased 27% following 905-nm irradiation at 50 J/cm(2).</p>
<p>CONCLUSION: LILT applied to wounds, delivering commonly used wavelengths and radiant exposures in the range of 1-20 J/cm(2), could produce changes in bacterial growth of considerable importance for wound healing. A wavelength of 630 nm appeared to be most commonly associated with bacterial inhibition. The findings of this study might be useful as a basis for selecting LILT for infected wounds.</p>
<p>J Appl Microbiol. 2002;92(4):618-23.</p>
<h1>Factors influencing the susceptibility of Gram-negative bacteria to toluidine blue O-mediated lethal photosensitization.</h1>
<p><strong> </strong>Kömerik N&lt;&gt;, Wilson M&lt;&gt;.</p>
<p>Department of Microbiology, Eastman Dental Institute for Oral Health Care Sciences, University College London, UK.</p>
<p>Abstract</p>
<p>AIMS: Bacteria can be killed by red light in the presence of a photosensitizer. The purpose of this study was to evaluate the effect of physiological and environmental factors on the susceptibility of some bacteria associated with oral infections in immunocompromised patients to killing by the photosensitizer toluidine blue O (TBO).</p>
<p>METHODS AND RESULTS: Suspensions of Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae in human saliva, horse serum or saline were exposed to light from a helium/ neon laser in the presence of TBO. Additional suspensions at various growth phases and pHs were treated in an identical manner. Survivors were enumerated by viable counting. All three species were susceptible to lethal photosensitization under all of the conditions tested. The presence of serum and, to a lesser extent, saliva decreased the level of kill attained. The bactericidal effect was reduced at acid pHs but was unaffected by the growth phase of the organism.</p>
<p>CONCLUSIONS: The composition and pH of the fluid in which bacteria are suspended influenced the effectiveness of TBO-mediated lethal photosensitization, whereas killing was unaffected by the growth phase of the organism.</p>
<p>SIGNIFICANCE AND IMPACT OF THE STUDY: Environmental factors operating in the mouths of patients with mucositis could reduce the effectiveness of TBO-mediated lethal photosensitization of bacteria associated with this condition.</p>
<p><strong>2002. 91f.</strong></p>
<h1>Low-intensity laser coupled with photosensitizer to reduce bacteria in root canals compared to chemical control.</h1>
<p>SEGUNDO, A. S. G.</p>
<p>Dissertation (Professional Master&#8217;s Degree &#8220;Lasers in Dentistry&#8221;) &#8211; Nuclear and Energy Research Institute / School of Dentistry, University of São Paulo, São Paulo. Advisor: Martha Simões Ribeiro, DDS, PhD, José Luiz Lage-Marques. DDS, PhD</p>
<p>The photodynamic therapy is a process in which a dye is associated with an appropriate wavelength of light and this dye goes to an excited state. The excited photosensitizer reacts with oxygen to form the highly reactive compound singlet oxygen, and this compound can kill bacteria and tumor cells. The purpose of this study was to evaluate the bacterial reduction in root canal contaminated with Enterococcus Faecalis. Thirty teeth with their root canals prepared were contaminated with E. faecalis. Ten teeth have received the chemical substance sodium hypochlorite for 30 minutes; ten teeth have received the azulene dye paste for 5 minutes and have been irradiated with a diode laser, output power 10mW and ?= 685nm for 3 minutes. Ten teeth have not received treatment (control group). The bacterial reduction was significantly higher for laser group when compared to chemical and control groups. These results indicate that photodynamic therapy was an effective method to kill bacteria.</p>
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<td>Lasers Med Sci. 2001;16(4):267-75.</td>
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<h1>The effect of He-Ne laser (632.8 nm) and Solcoseryl in vitro.</h1>
<p>al-Watban FA, Andres BL.</p>
<p>Laser Medicine Section, Biological and Medical Research Department, MBC-03, King Faisal Specialist Hospital and Research Centre, PO Box 3354, 11211 Riyadh, Saudi Arabia. <a href="mailto:watban@kfshrc.edu.sa">watban@kfshrc.edu.sa</a></p>
<p>He-Ne laser (632.8 nm) and Solcoseryl (SS), a non-protein calf haemodialysate, were used in the enhancement of wound healing. Nonetheless, a study on the use of He-Ne laser with SS has not been done. The purpose of this study is to determine the effect of He-Ne laser biostimulation in combination with SS on Chinese hamster ovary (CHO) and human skin fibroblast (HSF). A dose response for the cloning efficiency (CE) of CHO and HSF cells in 5% fetal bovine serum in minimum essential medium (FBS-MEM) with 6-125 micrograms/ml SS and He-Ne laser using an optimum power density of 1.25 mW/cm2 and cumulative doses (CD) of 60-600 mJ/cm2 given for three consecutive days, were done. The combined effects of He-Ne laser 180 mJ/cm2 with 6 and 12 micrograms/ml SS were determined. Quadruplicate cultures were done. Student t-test was used to determine differences of treatment groups from controls. CHO and HSF CE were increased using 180 mJ/cm2 laser by 13.1% +/- 4.5% (p &lt; 0.0025) and 39.1% +/- 7.9% (p &lt; 0.0005); SS 6 micrograms/ml by 14.4% +/- 8.7% (p = 0.01) and 20.7% +/- 10.9% (p = 0.01); SS 12 micrograms/ml by 17.7% +/- 6.3% (p = 0.001) and 23.9% +/- 5.6% (p &lt; 0.0025); laser + SS 6 micrograms/ml by 15.1% +/- 8.8% (p &lt; 0.01) and 60.9% +/- 9.4% (p &lt; 0.0001); laser + SS 12 micrograms/ml by 23.0% +/- 1.5% (p &lt; 0.0001) and 70.7% +/- 11.4% (p &lt; 0.0001), respectively. Additional significant increases in CE were observed on CHO using laser + SS 12 micrograms/ml by 8.6% +/- 1.3% (p &lt; 0.025) and on HSF using laser + SS 6 micrograms/ml and laser + SS 12 micrograms/ml by 15.6% +/- 6.8% (p &lt; 0.025) and 22.7% +/- 10.6% (p = 0.01), respectively, when compared to the effect of 180 mJ/cm2 laser. Results suggest that further stimulation can be achieved by using He-Ne laser with SS. This could be exploited as a new treatment modality.</p>
<p>Urologiia. 2000 Jan-Feb;(1):11-5.</p>
<h1>Low-intensity laser radiation in preoperative preparation of patients with benign prostatic hyperplasia</h1>
<p>[Article in Russian]</p>
<p>Ne?mark AI&lt;&gt;, Muzalevskaia NI&lt;&gt;.</p>
<p>Low-intensity laser therapy administered in the form of intravenous blood irradiation, transrectal and transurethral prostatic irradiation and their combination as preoperative preparation and correction of immunity disturbances in patients with benign prostatic hyperplasia (BPH) were studied. The response to the treatment was evaluated by positive changes in the immune status and bacterial contamination of the urine and prostatic tissue. Conventional preoperative preparation (uroantiseptics, antibiotics and phytotherapy) fails to correct signs of T-cell immunodeficiency, depression of phagocytic activity of neutrophils, significantly reduce bacteriurea. Laser therapy as intravenous laser blood radiation acts immunomodulatorily on cellular immunity and normalized the proportion of T-helpers of the first and second order (T-suppressors) and neutrophil phagocytosis. The antibacterial effect of this technique on urinary microflora and prostatic tissue is not very high. Local laser therapy is a potent immunostimulator of T- and B-lymphocytes, increased the index of immunoregulatory cells&#8217; proportion, activated phagocytosis of neutrophils. It has pronounced antibacterial effect against gram-negative urinary microflora and tissue of the prostate. Combined laser therapy produced the highest immunomodulating action on T-lymphocytes and immunostimulating one on B-lymphocytes, potentiated phagocytic ability of neutrophils, elevated index of the immunoregulatory cells, but was unable to correct their imbalance completely. Antibacterial effects of combined laser therapy were the highest, including the bacterial group Proteus-Providencia. Preoperative low-intensity laser therapy of BPH reduced the number of postoperative pyoinflammatory complications, hospital stay, severity of postoperative period.</p>
<p>Phys Ther. 1999 Sep;79(9):839-46.</p>
<h1>Bactericidal effect of 0.95-mW helium-neon and 5-mW indium-gallium-aluminum-phosphate laser irradiation at exposure times of 30, 60, and 120 seconds on photosensitized Staphylococcus aureus and Pseudomonas aeruginosa in vitro.</h1>
<p><strong> </strong>DeSimone NA&lt;&gt;, Christiansen C&lt;&gt;, Dore D&lt;&gt;.</p>
<p>Veterans Administration Medical Center, 507 Fulton St, Durham, NC 27705, USA. <a href="mailto:noelledes@aol.com">noelledes@aol.com</a></p>
<p>Erratum in:</p>
<p>Phys Ther 1999 Nov;79(11):1082.</p>
<p>Abstract</p>
<p>BACKGROUND AND PURPOSE: Studies have demonstrated a bactericidal effect of laser irradiation when lasers with power outputs of (6 mW are directed toward pathogenic or opportunistic bacteria previously treated with a photosensitizing agent. The purpose of this study was to determine the bactericidal capabilities of irradiation from lasers with power outputs of less than 6 mW on photosensitized microorganisms.</p>
<p>METHODS: Two bacteria that commonly infect skin lesions, Staphylococcus aureus and Pseudomonas aeruginosa, were used. The 2 lasers used, the 0.95-mW helium -neon laser and the 5-mW indium-gallium-aluminum-phosphate laser, emit light at a wavelength close to the absorption maxima of the sensitizing agent chosen, toluidine blue O. This agent was used because of its proven effectiveness in sensitizing bacteria. For each bacterial strain, toluidine blue O was added to a 108 cells/mL solution until a 0.01% weight/volume ratio was obtained. These mixtures were spread on agar-coated petri dishes, which were then exposed to 1 of the 2 lasers for 30, 60, and 120 seconds. The cultures were then grown overnight and examined for one or more visible zones of inhibition. The areas surrounding the irradiated zone provided a control for the effects of toluidine blue O alone. To determine the effects of laser irradiation without prior toluidine blue O sensitization, separate plates were established using unsensitized bacteria.</p>
<p>RESULTS: Although inconsistencies between plates were noted, both lasers produced at least one zone of inhibition in both bacterial species at all 3 time periods. The 5-mW laser, however, produced a greater number of these zones.</p>
<p>CONCLUSION AND DISCUSSION: Laser-induced microbial killing of photosensitized organisms could have clinical applications in the treatment of infected skin lesions, pending in vivo studies.</p>
<p>J Antimicrob Chemother. 1997 Dec;40(6):873-6.</p>
<h1>Killing of methicillin-resistant Staphylococcus aureus in vitro using aluminum disulphonated phthalocyanine, a light-activated antimicrobial agent.</h1>
<p>Griffiths MA&lt;&gt;, Wren BW&lt;&gt;, Wilson M&lt;&gt;.</p>
<p>Department of Microbiology, Eastman Dental Institute for Oral Health Care Sciences, University of London, UK.</p>
<p>Abstract</p>
<p>The aim of this study was to determine whether 16 epidemic methicillin-resistant strains of Staphylococcus aureus (EMRSA) could be killed by the light-activated antimicrobial agent aluminium disulphonated phthalocyanine (AIPcS2). EMRSA suspensions were irradiated with light from a laser diode in the presence of AIPcS2 and survivors enumerated. All strains were susceptible to killing, the bactericidal effect being dependent on the AIPcS2 concentration and the light dose. AIPcS2 rendered the bacteria light-sensitive almost immediately and killing was unaffected by the growth phase of the organism. Scavengers of singlet oxygen and free radicals protected the bacteria from killing. These results imply that light-activated antimicrobial agents may be useful in eliminating EMRSA from wounds or carriage sites.</p>
<p>Photochem Photobiol. 1997 Jun;65(6):1026-31.</p>
<h1>Effect of dosimetric and physiological factors on the lethal photosensitization of Porphyromonas gingivalis in vitro.</h1>
<p>Bhatti M&lt;&gt;, MacRobert A&lt;&gt;, Meghji S&lt;&gt;, Henderson B&lt;&gt;, Wilson M&lt;&gt;.</p>
<p>Department of Microbiology, Eastman Dental Institute for Oral Health Care Sciences, University of London, UK.</p>
<p>Abstract</p>
<p>The aims of this study were to (1) determine the effect of dosimetric and physiological factors on the lethal photosensitization of Porphyromonas gingivalis using toluidine blue O (TBO) and light from a helium/neon (HeNe) laser; (2) determine the influence of sensitizer concentration, preirradiation time, serum and growth phase on sensitizer uptake by P. gingivalis. The dosimetric factors studied were concentration of TBO, light dose and preirradiation time. The physiological factors were presence of serum, pH and bacterial growth phase. Sensitizer uptake by P. gingivalis under various conditions was determined using tritiated TBO (3H-TBO). In the presence of TBO, a light dose-dependent increase in kill was attained (100% kill at 4.4 J). There was no significant effect on the numbers killed when TBO was increased from 12.5 to 50 micrograms/mL. An increase in preirradiation time gave slightly increased kills. High kills were achieved at all three pH (6.8-8.0). Although kills were substantial in the presence of serum, they were significantly less than those obtained in the presence of saline. Cells in all three growth phases were susceptible to lethal photosensitization, although stationary phase cells were slightly less susceptible. Maximum uptake of TBO occurred within 60 s and uptake in serum was less than in saline. The uptake by the log phase cells was greater at lower concentrations of sensitizer (50 micrograms/mL), compared to the other two phases.</p>
<p>Med Microbiol. 1996 Apr;44(4):245-52.</p>
<h1>The killing of Helicobacter pylori by low power laser light in the presence of a photosensitiser.</h1>
<p><strong> </strong>Millson CE&lt;&gt;, Wilson M&lt;&gt;, Macrobert AJ&lt;&gt;, Bedwell J&lt;&gt;, Bown SG&lt;&gt;.</p>
<p>The National Medical Laser Centre, University College London Medical School, UK.</p>
<p>Abstract</p>
<p>Helicobacter pylori is associated with various gastrointestinal disorders. Lethal photosensitisation was investigated as a possible technique for killing H. pylori which might offer a better alternative to antibiotics. The susceptibility of H. pylori to lethal photosensitisation was determined by mixing suspensions of H. pylori with various photosensitisers and plating out on blood agar before irradiation with low-power laser light. Five sensitisers were studied further by mixing them with H. pylori in a tissue-culture plate and counting survivors after irradiation as a function of laser exposure time, dye concentration and pre-irradiation time. Crystal violet and thionine were ineffective as sensitisers, but zones of inhibition appeared with methylene blue (MB), protoporphyrin IX (PPIX), haematoporphyrin derivative (HPD), toluidine blue O (TBO) and disulphonated aluminium phthalocyanine (S2). Laser light or sensitiser alone did not affect bacterial viability. S2 (100 microg/ml) with a laser light energy density of 16 J/cm2, HPD (10O microg/ml) with 160 J/cm2, MB (100 microg/ml) with 21 J/cm2, PPIX (150 microg/ml) with 320 J/cm2 and TBO (50 microg/ml) with 160 J/cm2 all reduced bacterial viability by &gt;99%. The killing of sensitised H. pylori by laser light offers a new approach to the treatment of localised infections when all colonised areas are accessible to light.</p>
<p>J Antimicrob Chemother. 1996 Feb;37(2):377-81.</p>
<h1>Killing of Streptococcus sanguis in biofilms using a light-activated antimicrobial agent.</h1>
<p><strong> </strong>Wilson M&lt;&gt;, Burns T&lt;&gt;, Pratten J&lt;&gt;.</p>
<p>Department of Microbiology, Eastman Dental Institute of Oral Health Care Sciences, University of London, UK.</p>
<p>Abstract</p>
<p>The aim of this study was to determine whether Streptococcus sanguis, when in a biofilm, could be killed using a light-activated antimicrobial agent. Biofilms were grown on hydroxyapatite, irradiated with up to 12.2 J of light from a gallium aluminium arsenide laser in the presence of aluminium disulphonated phthalocyanine (AlPcS2) and survivors enumerated. No significant decrease in the viable count was found when either the AlPcS2 or the laser light was used alone. There was a light dose related decrease in the viable counts of irradiated AlPcS2-treated biofilms. No viable streptococci were detectable following irradiation with 12.2 J of laser light.</p>
<p>J Photochem Photobiol B. 1996 Jan;32(1-2):59-65.</p>
<h1>Ex-vivo treatment of gastric Helicobacter infection by photodynamic therapy.</h1>
<p><strong> </strong>Millson CE&lt;&gt;, Wilson M&lt;&gt;, MacRobert AJ&lt;&gt;, Bown SG&lt;&gt;.</p>
<p>National Medical Laser Centre, University College London Medical School, UK.</p>
<p>Abstract</p>
<p>Attempts to develop PDT for eradication of Helicobacter infection have only been successful in vitro. We have investigated the effect of topical sensitization (except ALA) of Helicobacter mustelae on explanted ferret gastric mucosa using one of five sensitizers (methylene blue (MB), toluidine blue O (TBO), phthalocyanine, haematoporphyrin derivative and 5-aminolavulinic acid), followed by irradiation with an appropriately tuned copper vapour pumped dye laser. A 90% reduction in counts of bacteria sensitized with 0.75 mg TBO kg-1 were seen after irradiation with 200 J cm-2. Concentrations of MB of 0.75 mg kg-1 and 7.5 mg kg-1 were not toxic to H. mustelae, but the further addition of 20 J cm-2 laser light reduced colony counts by more than 99%. MB at a concentration of 75 mg kg-1 exhibited significant dark toxicity towards H. mustelae, but further addition of 20 J cm-2 laser light resulted in near eradication of all colonies. The remaining three compounds were ineffective. Finally, we studied the microscopic fluorescence distribution of MB (7.5 mg kg-1) on ferret gastric mucosa after topical administration. Fluorescence was greatest in the superficial mucosal layer, upon which lies the bacteria. However, from experiments on rats, the energy required to kill the sensitized bacteria was insufficient to damage the underlying mucosa. We conclude that Helicobacter can be killed on host mucosal epithelium following topical administration of MB and subsequent exposure to laser light.</p>
<p>Acta Univ Palacki Olomuc Fac Med. 1996;140:43-6.</p>
<h1>In vitro He-Ne laser effect on some immunological functions of polymorphonuclears and monocytes in rabbits.</h1>
<p>Luza J&lt;&gt;, Hubácek J&lt;&gt;.</p>
<p>Department of Physiology, Medical Faculty, Palacký University, Olomouc, Czech Republic.</p>
<p>The aim of this study is to evaluate in vitro the effect of Helium-Neon (He-Ne) laser irradiation on the viability, adherence, phagocytic activity of the polymorphonuclears and monocytes. Also the level of metabolic processes in phagocytizing blood cells, monocytes and polymorphonuclears was estimated and evaluated by the INT-test. Evaluation of the leukocyte adherence, the method of MacGregor was used. Phagocytic activity was examined by classical method using microspherical hydrophilic particles (Hema-particles). He-Ne laser in a small dosage (&lt; or = 0.8 J) increases the leukocyte adherence, after higher laser irradiation dosage (&gt; 1.2 J) the leukocyte adherence is decreased. The laser effect on the phagocytic activity of both types of blood cells, polymorphonuclears and monocytes is similar. Small dosage of the laser irradiation increases the phagocytic activity, and after higher laser irradiation phagocytic activity is decreased. Also the changes of the level of metabolic processes in the phagocytizing cells are very similar with the changes of phagocytic activity. The viability of the blood cells examined after higher laser irradiation is gradually decreased.</p>
<p>Caries Res. 1995;29(3):192-7.</p>
<h1>Effect of dentine and collagen on the lethal photosensitization of Streptococcus mutans.</h1>
<p><strong> </strong>Burns T&lt;&gt;, Wilson M&lt;&gt;, Pearson GJ&lt;&gt;.</p>
<p>Department of Microbiology, Eastman Dental Institute for Oral and Dental Health Care Sciences, London, UK.</p>
<p>Abstract</p>
<p>Suspensions of the cariogenic bacterium, Streptococcus mutans were treated with either toluidine blue O or aluminium disulphonated phthalocyanine and then exposed to light from a helium-neon or gallium-aluminium-arsenide laser, respectively, after passing through demineralized dentine slices. Bacteria were also embedded in a collagen matrix prior to sensitization and exposure to the laser light. When dentine slices were interposed between the laser light and the bacterial suspension, substantial kills (10(7) CFU) were achieved at energy doses of 876, 1,752, and 3,504 mJ with the helium-neon laser and of 1,188, 2,376, and 4,752 mJ with the gallium-aluminium-arsenide laser. There was no apparent relationship between the extent of killing and the degree of demineralization of the dentine. Prolonging the exposure of the sensitized bacteria to the laser light increased the kill achieved. Substantial numbers (10(8) to 10(10) CFU) of S. mutans were also killed when embedded in a collagen matrix and exposed to 438 and 1,314 mJ of helium-neon laser light and 594 and 1,782 mJ of light from the gallium-aluminium-arsenide laser. These results imply that lethal photosensitization may be effective at killing S. mutans in a carious lesion, even when the organism is embedded in demineralized dentine.</p>
<p>J Appl Bacteriol. 1995 May;78(5):569-74.</p>
<h1>Bacteria in supragingival plaque samples can be killed by low-power laser light in the presence of a photosensitizer.</h1>
<p><strong> </strong>Wilson M&lt;&gt;, Burns T&lt;&gt;, Pratten J&lt;&gt;, Pearson GJ&lt;&gt;.</p>
<p>Department of Microbiology, Eastman Dental Institute for Oral Health Care Sciences, University of London, UK.</p>
<p>Abstract</p>
<p>The purpose of this study was to determine whether bacteria in supragingival plaque samples could be killed by low-power laser light in the presence of a suitable photosensitizer. Plaque samples were obtained from 10 volunteers, treated with either toluidine blue O (TBO) or aluminum disulphonated phthalocyanine (AlPcS2), and then exposed to light from a helium/neon (HeNe) or gallium aluminium arsenide (GaAs) laser respectively. Following irradiation, substantial reductions were achieved in the total anaerobic count as well as in the number of viable streptococci and actinomyces present in the samples. In the absence of laser light, the sensitizers themselves had little effect on the viability of the bacteria in the plaque samples. The HeNe/TBO combination appeared to be more effective than the GaAs/AlPcS2 combination, achieving log10 reductions of 2.95, 5.40 and 3.34 in the total anaerobic count, streptococci and actinomyces respectively with a light energy dose of 1.31 J. If effective in vivo, lethal photosensitization may be useful as a means of eliminating plaque bacteria from a carious lesion prior to its restoration.</p>
<p>J Med Microbiol. 1995 Jan;42(1):62-6.<strong> </strong></p>
<h1>Killing of methicillin-resistant Staphylococcus aureus by low-power laser light.</h1>
<p><strong> </strong>Wilson M&lt;&gt;, Yianni C&lt;&gt;.</p>
<p>Department of Microbiology, Eastman Dental Institute for Oral Health Sciences, University of London.</p>
<p>Abstract</p>
<p>The purpose of this study was to determine whether a methicillin-resistant strain of Staphylococcus aureus (MRSA) could be sensitised by toluidine blue O (TBO) to killing by light from a low-power helium/neon (HeNe) laser. Suspensions containing c. 10(10) cfu of MRSA were irradiated with light from a 35 mW HeNe laser (energy dose: 0.5-2.1 J) in the presence of TBO (1.6-12.5 micrograms/ml) and the survivors were enumerated. The kills attained depended on both the light energy dose and concentration of TBO employed. A 4.47 log10 reduction in the viable count was achieved with a TBO concentration of 12.5 micrograms/ml and a light dose of 2.1 J (energy density 43 J/cm2). MRSA were susceptible to killing by the laser light within 30 s of exposure to the TBO. The results of this study have demonstrated that MRSA can be rapidly sensitised by TBO to killing by HeNe laser light and that killing depends on the light energy dose and sensitiser concentration.</p>
<p>J Dent. 1994 Oct;22(5):273-8.</p>
<h1>Killing of cariogenic bacteria by light from a gallium aluminum arsenide diode laser.</h1>
<p>Burns T&lt;&gt;, Wilson M&lt;&gt;, Pearson GJ&lt;&gt;.</p>
<p>Department of Microbiology, Institute of Dental Surgery, London, UK.</p>
<p>Abstract</p>
<p>Suspensions of Streptococcus mutans, S. sobrinus, Lactobacillus casei and Actinomyces viscosus were exposed to light from a gallium aluminium arsenide laser in the presence of aluminium disulphonated phthalocyanine and the numbers of survivors determined. Exposure to the laser light in the absence of the dye, or the dye in the absence of the laser light, had no significant effect on the viability of the organisms. However, a light-dose-related decrease in the viable count of all four target organisms was found on exposure to the laser light in the presence of the dye. The kills attributable to lethal photosensitization amounted to approximately 10(6) CFU in the case of each organisms. As appreciable kills were achieved within clinically convenient exposure times (30-90 s), these results imply that lethal photosensitization may be a useful technique for eliminating bacteria from carious lesions prior to restoration.</p>
<p>Int Dent J. 1994 Apr;44(2):181-9.</p>
<h1>Bactericidal effect of laser light and its potential use in the treatment of plaque-related diseases.</h1>
<p><strong> </strong>Wilson M&lt;&gt;.</p>
<p>Department of Microbiology, Institute of Dental Surgery, University of London, UK.</p>
<p>Abstract</p>
<p>Chemical antibacterial agents are increasingly being used in prophylactic and therapeutic regimes for plaque-related diseases. As these agents can be rendered ineffective by the development of resistance in the target organisms there is a need to develop alternative antimicrobial approaches. Light from high-power lasers is known to be bactericidal and investigations have shown that it is effective against organisms implicated in caries and inflammatory periodontal diseases. However, the adverse effects of such light on dental hard tissues argue against its use solely as an antibacterial agent. Although light from low-power lasers has no adverse effect on bacterial viability, bacteria can be sensitised to killing by such light by prior treatment with a chemical photosensitising agent. Lethal photosensitisation of a wide range of cariogenic and periodontopathogenic bacteria has been demonstrated using light from a helium/neon or gallium aluminium arsenide laser in conjunction with a dye such as toluidine blue or aluminium disulphonated phthalocyanine as a photosensitiser. The advantages of the technique are that killing is achieved in very short periods of time (&lt; 60 s), resistance development in the target bacteria would be unlikely and damage to adjacent host tissues can be avoided. This approach may be a useful alternative to antibiotics and antiseptics in eliminating cariogenic and periodontopathogenic bacteria from disease lesions.</p>
<p>Microbios. 1994;78(316):163-8.</p>
<h1>Lethal photosensitisation of Staphylococcus aureus.</h1>
<p>Wilson M&lt;&gt;, Pratten J&lt;&gt;.</p>
<p>Department of Microbiology, Institute of Dental Surgery, University of London, Great Britain.</p>
<p>Abstract</p>
<p>The purpose of this study was to determine whether toluidine blue O (TBO) could sensitise Staphylococcus aureus to killing by light from a low-power helium/neon (HeNe) laser. Suspensions of the organism were irradiated with light from a HeNe laser in the presence and absence of TBO and the survivors enumerated. A 95% reduction (9 x 10(7) cfu) in the viable count was achieved following irradiation with 0.88 J of HeNe laser light in the presence of 12.5 micrograms/ml TBO whereas no significant reductions in viability were found when suspensions were exposed to this dose of laser light in the absence of TBO. With higher doses (3.5 J) of laser light statistically significant kills (3 x 10(7) cfu) were obtained in the absence of TBO implying the presence of an endogenous photosensitiser in the organism.</p>
<p>J Med Microbiol. 1993 Jun;38(6):401-5.</p>
<h1>Sensitisation of cariogenic bacteria to killing by light from a helium-neon laser.</h1>
<p><strong> </strong>Burns T&lt;&gt;, Wilson M&lt;&gt;, Pearson GJ&lt;&gt;.</p>
<p>Department of Microbiology, Institute of Dental Surgery, London.</p>
<p>Abstract</p>
<p>Suspensions of the cariogenic bacteria Streptococcus mutans, S. sobrinus, Lactobacillus casei and Actinomyces viscosus were exposed to light from a 7.3-mW helium-neon laser in the presence of toluidine blue O. A substantial killing rate (c. 10(6) cfu) of all four species was achieved with a dye concentration of 50 micrograms/ml and a light energy dose of 33.6 J/cm2. This was achieved in 60 s, an exposure time that is clinically acceptable. Exposure to laser light in the absence of the dye did not significantly affect the viability of any of the organisms. This approach may be useful in dentistry to sterilise a carious lesion prior to its repair.</p>
<p>Oral Microbiol Immunol. 1993 Jun;8(3):182-7.</p>
<h1>Sensitization of periodontopathogenic bacteria to killing by light from a low-power laser.</h1>
<p><strong> </strong>Wilson M&lt;&gt;, Dobson J&lt;&gt;, Sarkar S&lt;&gt;.</p>
<p>Microbiology Department, Institute of Dental Surgery, London, United Kingdom.</p>
<p>Abstract</p>
<p>Cultures of Porphyromonas gingivalis, Fusobacterium nucleatum and Actinobacillus actinomycetemcomitans were treated with a range of photosensitizers and then exposed to light from a 7.3 mW helium/neon laser for up to 80 s. Toluidine blue O (25 micrograms/ml) and methylene blue (25 micrograms/ml) were effective lethal photosensitizers of all 3 target organisms, enabling substantial light dose-related reductions in viable counts. Dihaematoporphyrin ester and aluminium disulphonated phthalocyanine were lethal photosensitizers only of P. gingivalis. In the absence of a photosensitizer, exposure to laser light had no significant effect on the viability of the cultures. If such low doses of light (22 J/cm2) are effective at killing bacteria in vivo, the technique may be useful as a means of eliminating periodontopathogenic bacteria from diseased sites.</p>
<p>J Periodontal Res. 1993 May;28(3):204-10.</p>
<h1>Lethal photosensitization of bacteria in subgingival plaque from patients with chronic periodontitis.</h1>
<p><strong> </strong>Sarkar S&lt;&gt;, Wilson M&lt;&gt;.</p>
<p>Department of Microbiology, Institute of Dental Surgery, London, England.</p>
<p>Abstract</p>
<p>Subgingival plaque samples from patients with chronic periodontitis were exposed to light from a 7.3 mW Helium/Neon laser for 30 s in the presence and absence of 50 micrograms/ml toluidine blue O as a photosensitizer. Viable counts of various groups and species of bacteria were carried out before and after irradiation. The median numbers of viable bacteria initially present in the 30-microliters aliquots irradiated were 1.13 x 10(5) cfu (aerobes), 4.08 x 10(5) cfu (anaerobes), 4.92 x 10(3) cfu (black-pigmented anaerobes), 4.75 x 10(2) cfu (Porphyromonas gingivalis), 6.15 x 10(3) cfu (Fusobacterium nucleatum) and 1.7 x 10(4) cfu (streptococci). The dye/laser combination achieved significant reductions in the viability of these organisms, the median reductions in the viable counts being 91.1% for aerobes, 96.6% for anaerobes, 100% for black-pigmented anaerobes, P. gingivalis and F. nucleatum and 94.2% for streptococci. Overall, the viability of bacteria in the 20 plaque samples was not significantly decreased by the dye alone. However, in a small minority of samples there were indications of light-independent, dye-induced toxicity. Low-power lasers, in conjunction with appropriate photosensitizers, may be a useful adjunct to mechanical debridement in the treatment of inflammatory periodontal diseases if a similar effectiveness against subgingival plaque bacteria can be achieved in vivo.</p>
<p>Arch Oral Biol. 1992 Nov;37(11):883-7.</p>
<h1>Sensitization of oral bacteria in biofilms to killing by light from a low-power laser.</h1>
<p><strong> </strong>Dobson J&lt;&gt;, Wilson M&lt;&gt;.</p>
<p>Microbiology Laboratory, Institute of Dental Surgery, London, U.K.</p>
<p>Abstract</p>
<p>Biofilms of Streptococcus sanguis, Porphyromonas gingivalis, Fusobacterium nucleatum and Actinobacillus actinomycetemcomitans were prepared on the surfaces of agar plates and a number of compounds were screened for their ability to sensitize bacteria in these biofilms to killing by light from a 7.3 mW Helium/Neon (He/Ne) laser. Toluidine blue O and methylene blue enabled detectable killing of all four target organisms after exposure to He/Ne light for 30 s. Aluminium disulphonated phthalocyanine, haematoporphyrin HCl and haematoporphyrin ester were effective photosensitizers of only some of the target organisms. These findings suggest that lethal photosensitization may be an effective means of eliminating periodontopathogenic bacteria from dental plaque.</p>
<p>Curr Microbiol. 1992 Aug;25(2):77-81.</p>
<h1>Sensitization of oral bacteria to killing by low-power laser radiation.</h1>
<p>Wilson M&lt;&gt;, Dobson J&lt;&gt;, Harvey W&lt;&gt;.</p>
<p>Microbiology Laboratory, Institute of Dental Surgery, London, UK.</p>
<p>Abstract</p>
<p>Twenty-seven compounds were screened for their ability to sensitize Streptococcus sanguis to killing by light from a 7.3-mW Helium/Neon (HeNe) laser. Bacteria were mixed with various concentrations of the test compounds, spread over the surfaces of agar plates, and then exposed to light from the HeNe laser for various time periods. The plates were then incubated and examined for zones of inhibition. Those compounds found to be effective photosensitizers were then tested against Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Fusobacterium nucleatum. Toluidine blue O, azure B chloride, and methylene blue at concentrations of 0.005% (wt/vol) were effective photosensitizers of all four species, enabling killing of bacteria following exposure to laser light for only 30 s.</p>
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		<title>Oncology</title>
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		<pubDate>Sat, 31 Mar 2012 18:55:24 +0000</pubDate>
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		<description><![CDATA[Technol Health Care. 2011;19(6):455-67. Solid Ehrlich tumor growth treatment by magnetic waves. Ali FM, El Gebaly RH, El Hag MA, Rohaim AM. Source  Department of Biophysics, Faculty of Science, Cairo University, Giza, Egypt.  Abstract  In this work the retardation of Ehrlich tumor growth implanted in mice was studied by employing 4.5 Hz magnetic field. Eighty [...]]]></description>
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<p>Technol Health Care. 2011;19(6):455-67.</p>
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<h1>Solid Ehrlich tumor growth treatment by magnetic waves.</h1>
<div>Ali FM, El Gebaly RH, El Hag MA, Rohaim AM.</div>
<div>
<p><strong>Source</strong> </p>
<p>Department of Biophysics, Faculty of Science, Cairo University, Giza, Egypt. </p>
<div>
<p><strong>Abstract</strong> </p>
<p>In this work the retardation of Ehrlich tumor growth implanted in mice was studied by employing 4.5 Hz magnetic field. Eighty female Balb/c mice were used, twenty as normal group; the other sixty mice were inoculated with Ehrlich tumor, then they were divided equally into three groups namely A, B and C. Group A (control group) animals were not exposed to the magnetic field. The tumors in the thigh of the animals of group B were exposed to 4.5 Hz, 2 Gauss square wave magnetic field by using a small solenoid connected to a power square wave generator. Group C animals were whole body exposed inside a large solenoid to 4.5 Hz, 2 Gauss square wave magnetic field. Both groups B and C were exposed for a period of 2 weeks at a rate 2 hours per day. Tumor volume, survival period, histological examination and dielectric relaxation of the tumor were measured to investigate the activity of the tumor of the exposed and the unexposed animals. The results indicated that exposing the tumor tissue to 4.5 Hz square wave magnetic field for 2 weeks at a rate 2 hours/day inhibited tumor growth and increased the survival period of the animals. However, group B showed more improvements than did group C. This was attributed to some distortions in the square waveform in the large solenoid (group C). By comparing data from current and previous work, it was concluded that the use of magnetic waves showed better results over previously published work using amplitude modulated electromagnetic waves with the same frequency. </p>
<p>/Expert Opin Investig Drugs. 2011 Aug;20(8):1099-106. doi: 10.1517/13543784.2011.583236. Epub 2011 May 9. </p>
<h1>Tumor treating fields: concept, evidence and future.</h1>
<div>Pless M, Weinberg U.</div>
<div>
<p><strong>Source</strong> </p>
<p>Medical Oncology, Department of Internal Medicine, and Tumor Center, Kantonsspital Winterthur, Brauerstrasse, Switzerland. <a href="mailto:miklos.pless@ksw.ch">miklos.pless@ksw.ch</a> </p>
<p><strong>Abstract</strong> </p>
<div>
<p>INTRODUCTION: Local control is fundamental, both for the curative as well as the palliative treatment of cancer. Tumor treating fields (TTFields) are low intensity (1 ? 2 V/cm), intermediate frequency (100 ? 200 kHz) alternating electric fields administered using insulated electrodes placed on the skin surrounding the region of a malignant tumor. TTFields were shown to destroy cells within the process of mitosis via apoptosis, thereby inhibiting tumor growth. TTFields have no effect on non-dividing cells. </p>
<p>AREAS COVERED: This article reviews in vitro and in vivo preclinical studies, demonstrating the activity of TTFields both as a monotherapy as well as in combination with several cytotoxic agents. Furthermore, it summarizes the clinical experience with TTFields, mainly in two indications: one in recurrent glioblastoma multiforme: in a large prospective randomized Phase III trial TTFields was compared with best standard care (including chemotherapy): TTFields significantly improved median overall survival (OS) compared with standard therapy (7.8 vs 6.1 months) for the patients treated per protocol. Importantly, quality of life was also better in the TTFields group. The second indication was a Phase II study in second-line non-small cell lung cancer, where TTFields was administered concomitantly with pemetrexed. This combination resulted in an excellent median OS of 13.8 months. Interestingly, the progression-free survival (PFS) within the area of the TTFields was 28, however, outside the TTFields the PFS was only 22 weeks. </p>
<p>EXPERT OPINION: The proof of concept of TTFields has been well demonstrated in the preclinical setting, and the clinical data seem promising in various tumor types. The side effects of TTFields were minimal and in general consisted of skin reaction to the electrodes. There are a number of ways in which TTFields could be further evaluated, for example, in combination with chemotherapy, as a maintenance treatment, or as a salvage therapy if radiotherapy or surgery is not possible. While more clinical data are clearly needed, TTFields is an emerging and promising novel treatment concept. </p>
<p>Electromagn Biol Med. 2010 Dec;29(4):132-43. </p>
<h1>Bioelectromagnetic field effects on cancer cells and mice tumors.</h1>
<div>Berg H, Günther B, Hilger I, Radeva M, Traitcheva N, Wollweber L.</div>
<div>
<p><strong>Source</strong> </p>
<p>Laboratory Bioelectrochemistry, Beutenberg Campus, Jena, Germany. </p>
<div>
<p><strong>Abstract</strong> </p>
<p>We present possibilities and trends of ELF bioelectromagnetic effects in the mT amplitude range on cancer cells and on mice bearing tumors. In contrast to invasive electrochemotherapy and electrogenetherapy, using mostly needle electrodes and single high-amplitude electropulses for treatment, extremely low-frequency (ELF) pulsating electromagnetic fields (PEMF) and sinusoidal electromagnetic fields (SEMF) induce tumor cell apoptosis, inhibit angiogenesis, impede proliferation of neoplastic cells, and cause necrosis non invasively, whereas human lymphocytes are negligibly affected. Our successful results in killing cancer cells-analyzed by trypan blue staining or by flow cytometry-and of the inhibition of MX-1 tumors in mice by 15-20?mT, 50?Hz treatment in a solenoid coil also in the presence of bleomycin are presented in comparison to similar experimental results from the literature. In conclusion, the synergistic combinations of PEMF or SEMF with hyperthermia (41.5°C) and/or cancerostatic agents presented in the tables for cells and mice offer a basis for further development of an adjuvant treatment for patients suffering from malignant tumors and metastases pending the near-term development of suitable solenoids of 45-60?cm in diameter, producing &gt;20?mT in their cores. </p>
<div>Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2010 Oct;27(5):1128-32.</div>
<h1>Focusing properties of picosecond electric pulses in non-invasive cancer treatment.</h1>
<div>[Article in Chinese]</div>
<div>Long Z, Yao C, Li C, Mi Y, Sun C.</div>
<div>
<p>S<strong>ource</strong> </p>
<p><strong>S</strong>tate Key Laboratory of Power Transmission Equipment &amp; System Security and New Technology, Chongqing University, Chongqing 400044, China. <a href="mailto:longzaiquan@foxmail.com">longzaiquan@foxmail.com</a> </p>
<div>
<p>A<strong>bstract</strong> </p>
<p><strong>I</strong>n the light of optical theory, we advanc an ultra-wideband impulse radiating antenna (IRA) which is composed of an ellipsoidal reflector and a cone radiator. The high-intensity ultra-short electric pulses radiated by IRA can be transferred into the deep target in tissue non-invasively and be focused effectively. With the focused picosecond electric pulses, the organelles (mitochondria) transmembrane potential shall change to collapse under which the tumor cells will be targetly induced to apoptosis, so the method of non-invasive treatment of tumors would be achieved. Based on the time-domain electromagnetic field theory, the propagation characteristics of picosecond electric pulses were analyzed with and without the context of biological tissue, respectively. The results show that the impulse characteristics of input pulse were maintained and the picosecond electric pulses can keep high resolution in target areas. Meanwhile, because of the dispersive nature of medium, the pulse amplitude of the pulses will attenuate and the pulse width will be broadened. </p>
<p>BMC Cancer. 2010 Apr 24;10:159. </p>
<h1>Anti-proliferative effect of extremely low frequency electromagnetic field on preneoplastic lesions formation in the rat liver.</h1>
<p>Jiménez-García MN, Arellanes-Robledo J, Aparicio-Bautista DI, Rodríguez-Segura MA, Villa-Treviño S, Godina-Nava JJ. </p>
<p>Department of Physics Center of Research and Advanced Studies of the National Polytechnic Institute, Mexico City, Mexico. <span style="text-decoration: underline;"><a href="mailto:jj@fis.cinvestav.mx">jj@fis.cinvestav.mx</a></span> </p>
<p><strong>Abstract</strong> </p>
<p>BACKGROUND: Recently, extremely low frequency electromagnetic fields (ELF-EMF) have been studied with great interest due to their possible effects on human health. In this study, we evaluated the effect of 4.5 mT-120 Hz ELF-EMF on the development of preneoplastic lesions in experimental hepatocarcinogenesis. </p>
<p>METHODS: Male Fischer-344 rats were subjected to the modified resistant hepatocyte model and were exposed to 4.5 mT &#8211; 120 Hz ELF-EMF. The effects of the ELF-EMF on hepatocarcinogenesis, apoptosis, proliferation and cell cycle progression were evaluated by histochemical, TUNEL assay, caspase 3 levels, immunohistochemical and western blot analyses. </p>
<p>RESULTS: The application of the ELF-EMF resulted in a decrease of more than 50% of the number and the area of gamma-glutamyl transpeptidase-positive preneoplastic lesions (P = 0.01 and P = 0.03, respectively) and glutathione S-transferase placental expression (P = 0.01). The number of TUNEL-positive cells and the cleaved caspase 3 levels were unaffected; however, the proliferating cell nuclear antigen, Ki-67, and cyclin D1 expression decreased significantly (P &lt; or = 0.03), as compared to the sham-exposure group. </p>
<p>CONCLUSION: The application of 4.5 mT-120 Hz ELF-EMF inhibits preneoplastic lesions chemically induced in the rat liver through the reduction of cell proliferation, without altering the apoptosis process. </p>
<p>Cell Biochem Biophys. 2009;55(1):25-32. Epub 2009 Jun 18. </p>
<h1>Evaluation of the potential in vitro antiproliferative effects of millimeter waves at some therapeutic frequencies on RPMI 7932 human skin malignant melanoma cells.</h1>
<p>Beneduci A. </p>
<p>Department of Chemistry, University of Calabria, Via P. Bucci, Cubo 17/D, Arcavacata di Rende (CS), Italy.<a href="mailto:beneduci@unical.it">beneduci@unical.it</a> </p>
<p>Abstract </p>
<p>The potential antiproliferative effects of low power millimeter waves (MMWs) at 42.20 and 53.57 GHz on RPMI 7932 human skin melanoma cells were evaluated in vitro in order to ascertain if these two frequencies, comprised in the range of frequency used in millimeter wave therapy, would have a similar effect when applied in vivo to malignant melanoma tumours. Cells were exposed for 1 h exposure/day and to repeated exposure up to a total of four treatments. Plane wave incident power densities &lt;1 mW/cm(2) were used in the MMWs-exposure experiments so that the radiations did not cause significant thermal effects. Numerical simulations of Petri dish reflectivity were made using the equations for the reflection coefficient of a multilayered system. Such analysis showed that the power densities transmitted into the aqueous samples were &lt; or = 0.3 mW/cm(2). Two very important and general biological endpoints were evaluated in order to study the response of melanoma cells to these radiations, i.e. cell proliferation and cell cycle. Herein, we show that neither cell doubling time nor the cell cycle of RPMI 7932 cells was affected by the frequency of the GHz radiation and duration of the exposure, in the conditions above reported. </p>
<p>&#8211; &#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212;&#8212; </p>
<p>Bioelectrochemistry. 2010 Oct;79(2):257-60. Epub 2010 Mar 10. </p>
<h1>Electroporation and alternating current cause membrane permeation of photodynamic cytotoxins yielding necrosis and apoptosis of cancer cells.</h1>
<p>Traitcheva N, Berg H. </p>
<p>Institute of Plant Physiology &#8220;M. Popov,&#8221; Bulgarian Acad. of Sciences, Sofia, Bulgaria. </p>
<p>Abstract </p>
<p>In order to increase the permeability of cell membranes for low doses of cytostatic drugs, two bioelectrochemical methods have been compared: (a) electric pore formation in the plasma membranes by single electric impulses (electroporation), and (b) reordering of membrane structure by alternating currents (capacitively coupled). These treatments were applied to human leukemic K-562 cells and human lymphoma U-937 cells, yielding apoptotic and necrotic effects, determined by flow cytometry. Additional cell death occurs after exposure to light irradiation at wavelengths lambda &gt; 600 nm, of cells which were electroporated and had incorporated actinomycin-C or daunomycin (daunorubicin). It is observed that drug uptake after an exponentially decaying electroporation pulse of the initial field strength Eo=1.4 kV/cm and pulse time constants in the time range 0.5-3 ms is faster than during PEMF-treatment, i.e., application of an alternating current of 16 kHz, voltage U&lt;100 V, I=55 mA, and exposure time 20 min. However, at the low a.c. voltage of this treatment, more apoptotic and necrotic cells are produced as compared to the electroporation treatment with one exponentially decaying voltage pulse. Thus, additional photodynamic action appears to be more effective than solely drugs and electroporation as applied in clinical electrochemotherapy, and more effective than the noninvasive pulsed electromagnetic fields (PEMFs), for cancer cells in general and animals bearing tumors in particular. </p>
<p>Arch Biochem Biophys. 2010 May;497(1-2):82-9. Epub 2010 Mar 24. </p>
<h1>Nanosecond pulsed electric fields stimulate apoptosis without release of pro-apoptotic factors from mitochondria in B16f10 melanoma.</h1>
<p>Ford WE, Ren W, Blackmore PF, Schoenbach KH, Beebe SJ. </p>
<p>Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA. </p>
<p>Abstract </p>
<p>Nanosecond pulsed electric fields (nsPEFs) eliminates B16f10 melanoma in mice, but cell death mechanisms and kinetics of molecular events of cell death are not fully characterized. Treatment of B16f10 cells in vitro resulted in coordinate increases in active caspases with YO-PRO-1 uptake, calcium mobilization, decreases in mitochondria membrane potential with decreases in forward light scatter (cell size), increases in ADP/ATP ratio, degradation of actin cytoskeleton and membrane blebbing. However, there was no mitochondrial release of cytochrome c, AIF or Smac/DIABLO or generation of reactive oxygen species. Phosphatidylserine externalization was absent and propidium iodide uptake was delayed in small populations of cells. The results indicate that nsPEFs rapidly recruit apoptosis-like mechanisms through the plasma membrane, mimicking the extrinsic apoptosis pathway without mitochondrial amplification yet include activation of initiator and executioner caspases. nsPEFs provide a new cancer therapy that can bypass cancer-associated deregulation of mitochondria-mediated apoptosis in B16f10 melanoma. </p>
<p>J Physiol Pharmacol. 2010 Apr;61(2):201-5. </p>
<h1>Pulsating electromagnetic field stimulation prevents cell death of puromycin treated U937 cell line.</h1>
<p>Kaszuba-Zwoinska J, Wojcik K, Bereta M, Ziomber A, Pierzchalski P, Rokita E, Marcinkiewicz J, Zaraska W, Thor P. </p>
<p>Department of Pathophysiology, Jagiellonian University Medical College, Cracow, Poland. <a href="mailto:jkaszuba@cm-uj.krakow.pl">jkaszuba@cm-uj.krakow.pl</a> </p>
<h3>Abstract</h3>
<p>Aim of study was to verify whether pulsating electromagnetic field (PEMF) can affect cancer cells proliferation and death. U937 human lymphoid cell line at densities starting from 1 x 10(6) cells/ml to 0.0625 x 10(6) cells/ml, were exposed to a pulsating magnetic field 50 Hz, 45+/-5 mT three times for 3 h per each stimulation with 24 h intervals. Proliferation has been studied by counting number of cells stimulated and non-stimulated by PEMF during four days of cultivation. Viability of cells was analyzed by APC labeled Annexin V and 7-AAD (7-amino-actinomycin D) dye binding and flow cytometry. Growing densities of cells increase cell death in cultures of U937 cells. PEMF exposition decreased amount of cells only in higher densities. Measurement of Annexin V binding and 7-AAD dye incorporation has shown that density-induced cell death corresponds with decrease of proliferation activity. PEMF potentiated density-induced death both apoptosis and necrosis. The strongest influence of PEMF has been found for 1 x 10(6)cells/ml and 0.5 x 10(6) cells/ml density. To eliminate density effect on cell death, for further studies density 0.25 x 10(6) cells/ml was chosen. Puromycin, a telomerase inhibitor, was used as a cell death inducer at concentration 100 microg/ml. Combined interaction of three doses of puromycin and three fold PEMF interaction resulted in a reduced of apoptosis by 24,7% and necrosis by 13%. PEMF protects U937 cells against puromycin- induced cell death. PEMF effects on the human lymphoid cell line depends upon cell density. Increased density induced cells death and on the other hand prevented cells death induced by puromycin. </p>
<p>Int J Radiat Biol. 2010 Feb;86(2):79-88. </p>
<h1>Growth of injected melanoma cells is suppressed by whole body exposure to specific spatial-temporal configurations of weak intensity magnetic fields.</h1>
<p>Hu JH, St-Pierre LS, Buckner CA, Lafrenie RM, Persinger MA. </p>
<p>Department of Biology, Laurentian University, Sudbury, Ontario, Canada. </p>
<p>Abstract </p>
<p>PURPOSE: To measure the effect of exposure to a specific spatial-temporal, hysiologically-patterned electromagnetic field presented using different geometric configurations on the growth of experimental tumours in mice. </p>
<p>METHODS: C57b male mice were inoculated subcutaneously with B16-BL6 melanoma cells in two blocks of experiments separated by six months (to control for the effects of geomagnetic field). The mice were exposed to the same time-varying electromagnetic field nightly for 3 h in one of six spatial configurations or two control conditions and tumour growth assessed. </p>
<p>RESULTS: Mice exposed to the field that was rotated through the three spatial dimensions and through all three planes every 2 sec did not grow tumours after 38 days. However, the mice in the sham-field and reference controls showed massive tumours after 38 days. Tumour growth was also affected by the intensity of the field, with mice exposed to a weak intensity field (1-5 nT) forming smaller tumours than mice exposed to sham or stronger, high intensity (2-5 microT) fields. Immunochemistry of tumours from those mice exposed to the different intensity fields suggested that alterations in leukocyte infiltration or vascularisation could contribute to the differences in tumour growth. </p>
<p>CONCLUSIONS: Exposure to specific spatial-temporal regulated electromagnetic field configurations had potent effects on the growth of experimental tumours in mice. </p>
<p>Melanoma Res. 2009 Aug 26. [Epub ahead of print] </p>
<h1>Histopathology of normal skin and melanomas after nanosecond pulsed electric field treatment.</h1>
<p>Chen X, James Swanson R, Kolb JF, Nuccitelli R, Schoenbach KH. </p>
<p>Department of Hepatobiliary Surgery, the First Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China bFrank Reidy Research Center for Bioelectrics cDepartment of Biological Sciences, Old Dominion University, Norfolk, Virginia, USA. </p>
<p>Abstract </p>
<p>Nanosecond pulsed electric fields (nsPEFs) can affect the intracellular structures of cells in vitro. This study shows the direct effects of nsPEFs on tumor growth, tumor volume, and histological characteristics of normal skin and B16-F10 melanoma in SKH-1 mice. A melanoma model was set up by injecting B16-F10 into female SKH-1 mice. After a 100-pulse treatment with an nsPEF (40-kV/cm field strength; 300-ns duration; 30-ns rise time; 2-Hz repetition rate), tumor growth and histology were studied using transillumination, light microscopy with hematoxylin and eosin stain and transmission electron microscopy. Melanin and iron within the melanoma tumor were also detected with specific stains. After nsPEF treatment, tumor development was inhibited with decreased volumes post-nsPEF treatment compared with control tumors (P&lt;0.05). The nsPEF-treated tumor volume was reduced significantly compared with the control group (P&lt;0.01). Hematoxylin and eosin stain and transmission electron microscopy showed morphological changes and nuclear shrinkage in the tumor. Fontana-Masson stain indicates that nsPEF can externalize the melanin. Iron stain suggested nsPEF caused slight hemorrhage in the treated tissue. Histology confirmed that repeated applications of nsPEF disrupted the vascular network. nsPEF treatment can significantly disrupt the vasculature, reduce subcutaneous murine melanoma development, and produce tumor cell contraction and nuclear shrinkage while concurrently, but not permanently, damaging peripheral healthy skin tissue in the treated area, which we attribute to the highly localized electric fields surrounding the needle electrodes. </p>
<p>Cancer Biol Ther. 2009 Sep;8(18):1756-62. Epub 2009 Sep 17. </p>
<h1>Static magnetic fields impair angiogenesis and growth of solid tumors in vivo.</h1>
<p>Strelczyk D, Eichhorn ME, Luedemann S, Brix G, Dellian M, Berghaus A, Strieth S. </p>
<p>Walter-Brendel-Center for Experimental Medicine (WBex), Campus Grosshadern, University of Munich (LMU), Munich, Germany. </p>
<p>Abstract </p>
<p>Exposure to static magnetic fields (SMFs) results in a reduced blood flow in tumor vessels as well as in activation and adherence of platelets. Whether this phenomenon may have a significant functional impact on tumors has not been investigated as yet. The aim of our study was to evaluate the effects of prolonged exposure to SMFs on tumor angiogenesis and growth. Experiments were performed in dorsal skinfold chamber preparations of Syrian Golden hamsters bearing syngenic A-Mel-3 melanomas. On 3 d following tumor cell implantation one group of animals was immobilized and exposed to a SMF of 586 mT for three h. Control animals were immobilized for the same duration without SMF exposure. Using in vivo-fluorescence microscopy the field effects on tumor angiogenesis and microcirculation were analyzed for seven days. Tumor growth was assessed by repeated planimetry of the tumor area during the observation period. Exposure to SMFs resulted in a significant retardation of tumor growth ( approximately 30%). Furthermore, histological analysis showed an increased peri- and intratumoral edema in tumors exposed to SMFs. Analysis of microcirculatory parameters revealed a significant reduction of functional vessel density, vessel diameters and red blood cell velocity in tumors after exposure to SMFs compared to control tumors. These changes reflect retarded vessel maturation by antiangiogenesis. The increased edema after SMF exposure indicates an increased tumor microvessel leakiness possibly enhancing drug-uptake. Hence, SMF therapy appears as a promising new anticancer strategy-as an inhibitor of tumor growth and angiogenesis and as a potential sensitizer to </p>
<p>J Exp Clin Cancer Res. 2009 Apr 14;28:51. </p>
<div>
<h1>Amplitude-modulated electromagnetic fields for the treatment of cancer: discovery of tumor-specific frequencies and assessment of a novel therapeutic approach.</h1>
<p><strong> </strong>Barbault A, Costa FP, Bottger B, Munden RF, Bomholt F, Kuster N, Pasche B. </p>
<div>Cabinet Médical, Avenue de la Gare 6, Lausanne, Switzerland. <a href="mailto:alexandre.barbault@gmail.com">alexandre.barbault@gmail.com</a></div>
<p>Abstract </p>
<div>PURPOSE:<strong> </strong>Because in vitro studies suggest that low levels of electromagnetic fields may modify cancer cell growth, we hypothesized that systemic delivery of a combination of tumor-specific frequencies may have a therapeutic effect. We undertook this study to identify tumor-specific frequencies and test the feasibility of administering such frequencies to patients with advanced cancer.</div>
<div>PATIENTS AND METHODS:<strong> </strong>We examined patients with various types of cancer using a noninvasive biofeedback method to identify tumor-specific frequencies. We offered compassionate treatment to some patients with advanced cancer and limited therapeutic options.</div>
<div>RESULTS:<strong> </strong>We examined a total of 163 patients with a diagnosis of cancer and identified a total of 1524 frequencies ranging from 0.1 Hz to 114 kHz. Most frequencies (57-92%) were specific for a single tumor type. Compassionate treatment with tumor-specific frequencies was offered to 28 patients. Three patients experienced grade 1 fatigue during or immediately after treatment. There were no NCI grade 2, 3 or 4 toxicities. Thirteen patients were evaluable for response. One patient with hormone-refractory breast cancer metastatic to the adrenal gland and bones had a complete response lasting 11 months. One patient with hormone-refractory breast cancer metastatic to liver and bones had a partial response lasting 13.5 months. Four patients had stable disease lasting for +34.1 months (thyroid cancer metastatic to lung), 5.1 months (non-small cell lung cancer), 4.1 months (pancreatic cancer metastatic to liver) and 4.0 months (leiomyosarcoma metastatic to liver).</div>
<div>CONCLUSION: Cancer-related frequencies appear to be tumor-specific and treatment with tumor-specific frequencies is feasible, well tolerated and may have biological efficacy in patients with advanced cancer.</div>
<div><strong> </strong></div>
<div>J Ethnopharmacol. 2009 Jun 22;123(2):293-301. Epub 2009 Mar 24.</div>
<h1>Induction of apoptosis in human hepatocarcinoma SMMC-7721 cells in vitro by flavonoids from Astragalus complanatus.</h1>
<p>Hu YW, Liu CY, Du CM, Zhang J, Wu WQ, Gu ZL. </p>
<p>Department of Pharmacology, Medical College of Soochow University, 199 RenAi Road, Suzhou 215123, PR China. </p>
<h3>Abstract</h3>
<p>AIM OF THE STUDY: Flavonoids extracted from the seeds of Astragalus complanatus R.Br. reduce the proliferation of many cancer cells. The present study was carried out to evaluate the effects of these flavonoids from Astragalus complanatus (FAC) on human hepatocarcinoma cell viability and apoptosis and to investigate its mechanisms of action in SMMC-7721 cells. </p>
<p>MATERIALS AND METHODS: Cell viability was measured using the MTT assay. To detect apoptotic cells, SMMC-7721 cells treated with FAC were stained with Hoechst 33258 and subjected to agarose gel electrophoresis. Quantitative detection of apoptotic cells was performed by flow cytometry. The effects of FAC on apoptosis and cell cycle regulatory genes and proteins in SMMC-7721 cells were examined using an S series apoptosis and cell cycle gene array and Western blot analysis. </p>
<p>RESULTS: The growth of SMMC-7721 and HepG2 cells was inhibited by treatment with FAC. Cell death induced by FAC was characterized by nuclear condensation and DNA fragmentation. Moreover, the cell cycle was arrested in the G0/G1 and S phases in FAC-treated SMMC-7721 cells. A sub-G1 peak with reduced DNA content was also formed. The activity of caspase-3 was significantly increased following FAC treatment. Microarray data indicated that the expression levels of 76 genes were changed in SMMC-7721 cells treated with FAC: 35 genes were up-regulated and 41 were down-regulated. Western blot analysis showed that caspase-3, caspase-8, Bax, P21, and P27 protein levels in SMMC-7721 cells were increased after 48 h of FAC treatment, while cyclinB1, cyclinD1, CDK1, and CDK4 protein levels were decreased. </p>
<p>CONCLUSIONS: These results suggest that FAC may play an important role in tumor growth suppression by inducing apoptosis in human hepatocarcinoma cells via mitochondria-dependent and death receptor-dependent apoptotic pathways. </p>
<p>Anticancer Res. 2008 Jul-Aug;28(4B):2245-51. </p>
<h1>Effect of steep pulsed electric field on proliferation, viscoelasticity and adhesion of human hepatoma SMMC-7721 cells.</h1>
<p>Song G, Qin J, Yao C, Ju Y. </p>
<p>Department of Bioengineering, College of Bioengineering, Ministry of Education of China, Chongqing University, Chongqing, PR China. </p>
<p><a href="mailto:song@cqu.edu.cn">song@cqu.edu.cn</a> </p>
<p>Abstract </p>
<p>It has been proven that steep pulsed electric field (SPEF) can directly kill tumor cells and plays an important role in anticancer treatment. The biorheological mechanisms, however, that destroy tumor cells are almost unknown. To resolve this issue, here, an SPEF generator was used to assess the effects of high- and low-dose SPEF on the proliferation of human hepatoma SMMC-7721 cells by MTT assay, and on the viscoelasticity, adhesion of SMMC-7721 cells to endothelial cells by micropipette aspiration technique. Viability and proliferation of SPEF-treated SMMC-7721 cells were significantly inhibited. Cell cycle analysis indicated that SPEF arrested the cell cycle progression of SMMC-7721 cells at the G0/G1 transition to the S-phase. Viscoelastic data fitted by a standard linear solid model showed that viscoelasticity of SMMC-7721 cells changed after treatment with SPEF. Moreover, the adhesive force of low-dose SPEF-treated SMMC-7721 cells to endothelial cells markedly decreased compared to that of control cells. These results suggest that the suppressant effects of SPEF on the proliferation of SMMC-7721 cells appeared to be mediated, at least in part, through arresting cell cycle progression and altering the viscoelastic and adhesive properties of the cells, which provides a novel biorheological mechanism for the antitumor therapy of SPEF.</p>
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<h1>The Effect of Intense Subnanosecond Electrical Pulses on Biological Cells</h1>
<p><strong> </strong>Schoenbach, K.H. Shu Xiao Joshi, R.P. Camp, J.T. Heeren, T. Kolb, J.F. Beebe, S.J.<br />
Old Dominion Univ., Norfolk; </p>
<p>This paper appears in: Plasma Science, IEEE Transactions on<br />
Publication Date: April 2008<br />
Volume: 36, Issue: 2, Part 1<br />
On page(s): 414-422<br />
Location: Eindhoven, Netherlands,<br />
ISSN: 0093-3813<br />
INSPEC Accession Number: 9921271<br />
Digital Object Identifier: 10.1109/TPS.2008.918786<br />
Current Version Published: 2008-04-08 </td>
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<td width="738"><strong>Abstract</strong>Nanosecond electrical pulses have been successfully used to treat melanoma tumors by using needle arrays as pulse delivery systems. Reducing the pulse duration of intense electric field pulses from nanoseconds into the subnanosecond range will allow us to use wideband antennas to deliver the electromagnetic fields into tissue with a spatial resolution in the centimeter range. To explore the biological effect of intense subnanosecond pulses, we have developed a generator that provides voltage pulses of 160 kV amplitude, 200 ps rise time, and 800 ps pulse width. The pulses are delivered to a cylindrical Teflon chamber with polished flat electrodes at either end. The distance between the electrodes is variable and allows us to generate electric fields of up to 1 MV/cm in cell suspensions. The pulses have been applied to B16 (murine melanoma) cells, and the plasma membrane integrity was studied by means of trypan blue exclusion. For pulse amplitudes of 550 kV/cm, approximately 50% of the cells took up trypan blue right after pulsing, whereas only 20% were taking it up after 1 h. This indicates that the plasma membrane in a majority of the cells affected by the pulses recovers with a time constant of about 1 h. The cells that show trypan blue uptake after this time suffer cell death through apoptosis. Evaluation of the experimental results and molecular dynamics modeling results indicate that with a pulse duration of 800 ps, membrane charging and nanopore formation are the dominant bioelectric effects on B16 cells. This information has been used in a continuum model to estimate the increase in membrane permeability and, consequently, the increase in pore size caused by repetitive pulsing.</td>
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<p>Conf Proc IEEE Eng Med Biol Soc. 2008;2008:1044-7. </p>
<h1>Experiment and mechanism research of SKOV3 cancer cell apoptosis induced by nanosecond pulsed electric field.</h1>
<p>Yao C, Mi Y, Hu X, Li C, Sun C, Tang J, Wu X. </p>
<p>State Key Laboratory of Power Transmission Equipment &amp; System Security and New Technology, Chongqing University, Chongqing 400044, China. </p>
<p>Abstract </p>
<p>This paper studies the apoptosis of human ovarian carcinoma cell Line (SKOV3) induced by the nanosecond pulsed electric field (10kV/cm, 100ns, 1 Hz) and its effect on intracellular calcium concentration ([Ca2+]i). These cells were doubly marked by Annexin V-FITC/PI, and the apoptosis rate was analyzed with flow cytometry. After AO/EB staining the morphological changes were observed under fluorescent microscope, and their ultrastructural changes were observed under scanning electron microscope (SEM). With Fluo-3/AM as calcium fluorescent marker, laser scanning confocal microscope (LSCM) was used to detect the effect of nsPEF on [Ca2+]i and the source of Ca2+. The results showed that the early apoptosis rate of the treatment group was (22.21+/-2.71)%, significantly higher than that of the control group (3.04+/-0.44)% (P&lt;0.01). The typical features of apoptotic cell have been observed by fluorescent microscope and SEM. It is proved that nsPEF can induce apoptosis of SKOV3 cells and result in distinct increase in [Ca2+]i (P0.01), which was independent of extracellular calcium concentration (P&gt;0.05). Since nsPEF can penetrate cell membrane due to its high frequency components, one of the mechanisms of nsPEF-induced apoptosis may be that activating intracellular calcium stores can increase the [Ca2+]i, and consequently, the apoptotic signal pathway can be induced. </p>
<p>Apoptosis. 2007 Sep;12(9):1721-31. </p>
<h1>Nanosecond pulsed electric fields induce apoptosis in p53-wildtype and p53-null HCT116 colon carcinoma cells.</h1>
<p>Hall EH, Schoenbach KH, Beebe SJ. </p>
<p>Center for Pediatric Research, Children&#8217;s Hospital of the King&#8217;s Daughters, Department of Physiological Sciences, Eastern Virginia Medical School, PO Box 1980, Norfolk, VA 23501-1980, USA. </p>
<p>Abstract </p>
<p>Non-ionizing radiation produced by nanosecond pulsed electric fields (nsPEFs) is an alternative to ionizing radiation for cancer treatment. NsPEFs are high power, low energy (non-thermal) pulses that, unlike plasma membrane electroporation, modulate intracellular structures and functions. To determine functions for p53 in nsPEF-induced apoptosis, HCT116p53(+/+) and HCT116p53(-/-) colon carcinoma cells were exposed to multiple pulses of 60 kV/cm with either 60 ns or 300 ns durations and analyzed for apoptotic markers. Several apoptosis markers were observed including cell shrinkage and increased percentages of cells positive for cytochrome c, active caspases, fragmented DNA, and Bax, but not Bcl-2. Unlike nsPEF-induced apoptosis in Jurkat cells (Beebe et al. 2003a) active caspases were observed before increases in cytochrome c, which occurred in the presence and absence of Bax. Cell shrinkage occurred only in cells with increased levels of Bax or cytochrome c. NsPEFs induced apoptosis equally in HCT116p53(+/+) and HCT116p53(-/-) cells. These results demonstrate that non-ionizing radiation produced by nsPEFs can act as a non-ligand agonist with therapeutic potential to induce apoptosis utilizing mitochondrial-independent mechanisms in HCT116 cells that lead to caspase activation and cell death in the presence or absence of p-53 and Bax. </p>
<div>Hell J Nucl Med. 2007 May-Aug;10(2):95-101.</div>
<h1>Anticancer effects on leiomyosarcoma-bearing Wistar rats after electromagnetic radiation of resonant radiofrequencies.</h1>
<p>Avdikos A, Karkabounas S, Metsios A, Kostoula O, Havelas K, Binolis J, Verginadis I, Hatziaivazis G, Simos I, Evangelou A. </p>
<p>Source </p>
<p>Laboratory of Physiology, Unit of Environmental Physiology, Faculty of Medicine, University of Ioannina, Greece. </p>
<div>
<p><strong>Abstract</strong> </p>
<p>In the present study, the effects of a resonant low intensity static electromagnetic field (EMF), causing no thermal effects, on Wistar rats have been investigated. Sarcoma cell lines were isolated from leiomyosarcoma tumors induced in Wistar rats by the subcutaneous (s.c) injection of 3,4-benzopyrene. Furthermore, smooth muscle cells (SMC) were isolated from the aorta of Wistar rats and cultivated. Either leiomyosarcoma cells (LSC) or SMC were used to record a number of characteristic resonant radiofrequencies, in order to determine the specific electromagnetic fingerprint spectrum for each cell line. These spectra were used to compose an appropriate algorithm, which transforms the recorded radiofrequencies to emitted ones. The isolated LSC were cultured and then exposed to a resonant low intensity radiofrequency EMF (RF-EMF), at frequencies between 10 kHz to 120 kHz of the radiowave spectrum. The exposure lasted 45 consecutive minutes daily, for two consecutive days. Three months old female Wistar rats were inoculated with exposed and non-exposed to EMF LSC (4 x 10(6) LCS for animal). Inoculated with non-exposed to EMF cells animals were then randomly separated into three Groups. The first Group was sham exposed to the resonant EMF (control Group-CG), the second Group after the inoculation of LSC and appearance of a palpable tumor mass, was exposed to a non-resonant EMF radiation pattern, for 5 h per day till death of all animals (experimental control Group-ECG). The third Group of animals after inoculation of LSC and the appearance of a palpable tumor mass, was exposed to the resonant EMF radiation for 5 h per day, for a maximum of 60 days (experimental Group-I, EG-I). A fourth Group of animals was inoculated with LSC exposed to EMF irradiation and were not further exposed to irradiation (experimental Group-II, EG-II). Tumor induction was 100% in all Groups studied and all tumors were histologically identified as leiomyosarcomas. In the case of the EG-I, a number of tumors were completely regretted (final tumor induction: 66%). Both Groups of animals inoculated with exposed or non-exposed to the EMF LSC, (EG-I and EG-II, respectively) demonstrated a significant prolongation of the survival time and a lower tumor growth rate, in comparison to the control Group (CG) and the experimental control Group (ECG). However, the survival time of EG-I animals was found to be significantly longer and tumor growth rate significantly lower compared to EG-II animals. In conclusion, our results indicate a specific anticancer effect of resonant EMF irradiation. These results may possibly be attributed to (a) the duration of exposure of LSC and (b) the exposure of the entire animal to this irradiation. </p>
<p>Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2007 Feb;24(1):230-4. </p>
<h1>Biological effects and their applications in medicine of pulsed electric fields.</h1>
<p>[Article in Chinese] </p>
<p>Huang H, Song G, Wang G, Sun C. </p>
<p>Key Laboratory for Biomnechanics &amp; Tissue Engineering of the State Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China. </p>
<h3>Abstract</h3>
<p>Pulsed electric fields can induce various kinds of biological effects that are essentially different from the normal electric fields, especially the interactions of Nanosecond Pulsed electric field (nsPEF) with cells. The biological effects of different pulsed electric fields on cell membranes, cytoplasmic matrixes, cell growth are introduced in this paper. Based on these effects, some applications of pulsed electric fields in cancer therapy, gene therapy, and delivery of drugs are reviewed in details. </p>
<p>Biochem Biophys Res Commun. 2006 May 5;343(2):351-60. Epub 2006 Mar 10. </p>
<h1>Nanosecond pulsed electric fields cause melanomas to self-destruct.</h1>
<p>Nuccitelli R, Pliquett U, Chen X, Ford W, James Swanson R, Beebe SJ, Kolb JF, Schoenbach KH. </p>
<p>Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA. <a href="mailto:yaochenguo@cqu.edu.cn">yaochenguo@cqu.edu.cn</a> </p>
<h3>Abstract</h3>
<p>We have discovered a new, drug-free therapy for treating solid skin tumors. Pulsed electric fields greater than 20 kV/cm with rise times of 30 ns and durations of 300 ns penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. Melanomas shrink by 90% within two weeks following a cumulative field exposure time of 120 micros. A second treatment at this time can result in complete remission. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin. Each pulse deposits 0.2 J and 100 pulses increase the temperature of the treated region by only 3 degrees C, ten degrees lower than the minimum temperature for hyperthermia effects. </p>
<p>Bioelectromagnetics. 2006 May;27(4):258-64. </p>
<h1>Effect of millimeter wave irradiation on tumor metastasis.</h1>
<p>Logani MK, Szabo I, Makar V, Bhanushali A, Alekseev S, Ziskin MC. </p>
<p>Richard J. Fox Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, PA 19140, USA. <a href="mailto:mlogani@temple.edu">mlogani@temple.edu</a> </p>
<h3>Abstract</h3>
<p>One of the major side effects of chemotherapy in cancer treatment is that it can enhance tumor metastasis due to suppression of natural killer (NK) cell activity. The present study was undertaken to examine whether millimeter electromagnetic waves (MMWs) irradiation (42.2 GHz) can inhibit tumor metastasis enhanced by cyclophosphamide (CPA), an anticancer drug. MMWs were produced with a Russian-made YAV-1 generator. Peak SAR and incident power density were measured as 730 +/- 100 W/kg and 36.5 +/- 5 mW/cm(2), respectively. Tumor metastasis was evaluated in C57BL/6 mice, an experimental murine model commonly used for metastatic melanoma. The animals were divided into 5 groups, 10 animals per group. The first group was not given any treatment. The second group was irradiated on the nasal area with MMWs for 30 min. The third group served as a sham control for group 2. The fourth group was given CPA (150 mg/kg body weight, ip) before irradiation. The fifth group served as a sham control for group 4. On day 2, all animals were injected, through a tail vein, with B16F10 melanoma cells, a tumor cell line syngeneic to C57BL/6 mice. Tumor colonies in lungs were counted 2 weeks following inoculation. CPA caused a marked enhancement in tumor metastases (fivefold), which was significantly reduced when CPA-treated animals were irradiated with MMWs. Millimeter waves also increased NK cell activity suppressed by CPA, suggesting that a reduction in tumor metastasis by MMWs is mediated through activation of NK cells. </p>
<p>Bioelectromagnetics. 2006 Apr;27(3):226-32. </p>
<h1>Effect of extremely low frequency electromagnetic fields (ELF-EMF) on Kaposi&#8217;s sarcoma-associated herpes virus in BCBL-1 cells.</h1>
<p>Pica F, Serafino A, Divizia M, Donia D, Fraschetti M, Sinibaldi-Salimei P, Giganti MG, Volpi A. </p>
<p>Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy. </p>
<p><a href="mailto:pica@uniroma2.it">pica@uniroma2.it</a> </p>
<h3>Abstract</h3>
<p>Association between extremely low frequency electromagnetic fields (ELF-EMF) and human cancers is controversial, and few studies have been conducted on their influence on oncogenic viruses. We studied the effects of 1 mT, 50 Hz sine waves, applied for 24-72 h, on Kaposi&#8217;s sarcoma (KS)-associated herpesvirus (KSHV or HHV-8) in BCBL-1, a latently infected primary effusion lymphoma (PEL) cell line. ELF-EMF exposure did not affect the growth and viability of BCBL-1 cells, either stimulated or not with TPA. The total amount of KSHV DNA detected in ELF-EMF exposed cultures not stimulated with TPA did not differ from that of the unexposed controls (P = ns). However, in the presence of TPA stimulation, total KSHV DNA content was found higher in ELF-EMF exposed than in control BCBL-1 cultures (P = .024) at 72 h exposure, but not earlier. Viral DNA increase significantly correlated with increased mean fluorescence intensity/cell for the lytic antigen gp K8.1A/B (P &lt; .01), but not with percentage of gp K8.1A/B-positive cells or of cells containing virions. Viral progeny produced under ELF-EMF exposure consisted mainly of defective viral particles. </p>
<p>Conf Proc IEEE Eng Med Biol Soc. 2006;1:6370-2. </p>
<h1>Outlook for the use of focused shock waves and pulsed electric fields in the complex treatment of malignant neoplasms.</h1>
<p>Garilevich BA, Andrianov YV, Olefir YV, Zubkov AD, Rotov AE. </p>
<p>Central Air Force Clinical Hosp., Moscow, Russia. </p>
<p><a href="mailto:medic-air@mtu-net.ru">medic-air@mtu-net.ru</a> </p>
<h3>Abstract</h3>
<p>The experimental studies the synchronous action of electric field microsecond range with amplitude within the range of 1-7 kV/sm and shock waves with pressure before 100 MPa on cells membrane permeability of the mouse&#8217;s ascitic tumors in vitro have shown the intensification the efficiency of the forming the irreversible pores under synchronous action. Thereby, enabling the electric field in the compression phase of shock wave pulse which can essentially reduce the electric field intensity required for breakdown cell membrane. In usual condition at amplitude of electric field, specified above, electric breakdown membrane carries basically reversible nature. At the same time in the pressure field tension phase of shock-wave pulse reversible pores, created by electric field, can grow before sizes, under which wholeness membrane is not restored. Under simultaneous action on cellular suspension the shock wave and electric field with moderate intensity cells survival is reduced in 5 once in contrast with occuring at different time&#8217;s action, and in 10 once in contrast with checking. The most sensitive to influence by under study fields are cells in phase of the syntheses DNA, preparation to fission and in phase of the mitosis. Thereby, continuation of the studies on use synchronous action shock waves and pulsed electric fields in complex treatment of the tumors introduces perspectiv </p>
<p>Bioelectromagnetics. 2006 Jan;27(1):64-72. </p>
<h1>Effects of pulsed magnetic stimulation on tumor development and immune functions in mice.</h1>
<p>Yamaguchi S, Ogiue-Ikeda M, Sekino M, Ueno S. </p>
<p>Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, Japan. </p>
<p><a href="mailto:chikko@medes.m.u-tokyo.ac.jp">chikko@medes.m.u-tokyo.ac.jp</a> </p>
<h3>Abstract</h3>
<p>We investigated the effects of pulsed magnetic stimulation on tumor development processes and immune functions in mice. A circular coil (inner diameter = 15 mm, outer diameter = 75 mm) was used in the experiments. Stimulus conditions were pulse width = 238 micros, peak magnetic field = 0.25 T (at the center of the coil), frequency = 25 pulses/s, 1,000 pulses/sample/day and magnetically induced eddy currents in mice = 0.79-1.54 A/m(2). In an animal study, B16-BL6 melanoma model mice were exposed to the pulsed magnetic stimulation for 16 days from the day of injection of cancer cells. A tumor growth study revealed a significant tumor weight decrease in the stimulated group (54% of the sham group). In a cellular study, B16-BL6 cells were also exposed to the magnetic field (1,000 pulses/sample, and eddy currents at the bottom of the dish = 2.36-2.90 A/m(2)); however, the magnetically induced eddy currents had no effect on cell viabilities. Cytokine production in mouse spleens was measured to analyze the immunomodulatory effect after the pulsed magnetic stimulation. tumor necrosis factor (TNF-alpha) production in mouse spleens was significantly activated after the exposure of the stimulus condition described above. These results showed the first evidence of the anti-tumor effect and immunomodulatory effects brought about by the application of repetitive magnetic stimulation and also suggested the possible relationship between anti-tumor effects and the increase of TNF-alpha levels caused by pulsed magnetic stimulation. </p>
<p>Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7093s-7103s. </p>
<h1>Application of high amplitude alternating magnetic fields for heat induction of nanoparticles localized in cancer.</h1>
<p>Ivkov R, DeNardo SJ, Daum W, Foreman AR, Goldstein RC, Nemkov VS, DeNardo GL. </p>
<p>Triton BioSystems, Inc., Chelmsford, Massachusetts 01824, USA. <a href="mailto:rivkov@tritonbiosystems.com">rivkov@tritonbiosystems.com</a> </p>
<h3>Abstract</h3>
<p>OBJECTIVE: Magnetic nanoparticles conjugated to a monoclonal antibody can be i.v. injected to target cancer tissue and will rapidly heat when activated by an external alternating magnetic field (AMF). The result is necrosis of the microenvironment provided the concentration of particles and AMF amplitude are sufficient. High-amplitude AMF causes nonspecific heating in tissues through induced eddy currents, which must be minimized. In this study, application of high-amplitude, confined, pulsed AMF to a mouse model is explored with the goal to provide data for a concomitant efficacy study of heating i.v. injected magnetic nanoparticles. </p>
<p>METHODS: Thirty-seven female BALB/c athymic nude mice (5-8 weeks) were exposed to an AMF with frequency of 153 kHz, and amplitude (400-1,300 Oe), duration (1-20 minutes), duty (15-100%), and pulse ON time (2-1,200 seconds). Mice were placed in a water-cooled four-turn helical induction coil. Two additional mice, used as controls, were placed in the coil but received no AMF exposure. Tissue and core temperatures as the response were measured in situ and recorded at 1-second intervals. </p>
<p>RESULTS: No adverse effects were observed for AMF amplitudes of &lt; or = 700 Oe, even at continuous power application (100% duty) for up to 20 minutes. Mice exposed to AMF amplitudes in excess of 950 Oe experienced morbidity and injury when the duty exceeded 50%. </p>
<p>CONCLUSION: High-amplitude AMF (up to 1,300 Oe) was well tolerated provided the duty was adjusted to dissipate heat. Results presented suggest that further tissue temperature regulation can be achieved with suitable variations of pulse width for a given amplitude and duty combination. These results suggest that it is possible to apply high-amplitude AMF (&gt; 500 Oe) with pulsing for a time sufficient to treat cancer tissue in which magnetic nanoparticles have been embedded. </p>
<p>Anticancer Res. 2005 Mar-Apr;25(2A):1023-8. </p>
<h1>Frequency and irradiation time-dependant antiproliferative effect of low-power millimeter waves on RPMI 7932 human melanoma cell line.</h1>
<p>Beneduci A, Chidichimo G, De Rose R, Filippelli L, Straface SV, Venuta S. </p>
<p>Department of Chemistry, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. <a href="mailto:beneduci@unical.it">beneduci@unical.it</a> </p>
<h3>Abstract</h3>
<p>The biological effects produced by low power millimeter waves (MMW) were studied on the RPMI 7932 human melanoma cell line. Three different frequency-type irradiation modes were used: the 53.57-78.33 GHz wide-band frequency range, the 51.05 GHz and the 65.00 GHz monochromatic frequencies. In all three irradiation conditions, the radiation energy was low enough not to increase the temperature of the cellular samples. Three hours of radiation treatment, applied every day to the melanoma cell samples, were performed at each frequency exposure condition. The wide-band irradiation treatment effectively inhibited cell growth, while both the monochromatic irradiation treatments did not affect the growth trend of RPMI 7932 cells. A light microscopy analysis revealed that the low-intensity wide-band millimeter radiation induced significant morphological alterations on these cells. Furthermore, a histochemical study revealed the low proliferative state of the irradiated cells. This work provides further evidence of the antiproliferative effects on tumor cells induced by low power MMW in the 50-80 GHz frequency range of the electromagnetic spectrum. </p>
<p>Bioelectromagnetics. 2005 Jan;26(1):10-9. </p>
<h1>Effect of millimeter waves on natural killer cell activation.</h1>
<p>Makar VR, Logani MK, Bhanushali A, Kataoka M, Ziskin MC. </p>
<p>Richard J Fox Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, PA 19140, USA. </p>
<h3>Abstract</h3>
<p>Millimeter wave therapy (MMWT) is being widely used for the treatment of many diseases in Russia and other East European countries. MMWT has been reported to reduce the toxic effects of chemotherapy on the immune system. The present study was undertaken to investigate whether millimeter waves (MMWs) can modulate the effect of cyclophosphamide (CPA), an anticancer drug, on natural killer (NK) cell activity. NK cells play an important role in the antitumor response. MMWs were produced with a Russian-made YAV-1 generator. The device produced modulated 42.2 +/- 0.2 GHz radiation through a 10 x 20 mm rectangular output horn. Mice, restrained in plastic tubes, were irradiated on the nasal area. Peak SAR at the skin surface and peak incident power density were measured as 622 +/- 100 W/kg and 31 +/- 5 mW/cm2, respectively. The maximum temperature elevation, measured at the end of 30 min, was 1 degrees C. The animals, restrained in plastic tubes, were irradiated on the nasal area. CPA injection (100 mg/kg) was given intraperitoneally on the second day of 3-days exposure to MMWs. All the irradiation procedures were performed in a blinded manner. NK cell activation and cytotoxicity were measured after 2, 5, and 7 days following CPA injection. Flow cytometry of NK cells showed that CPA treatment caused a marked enhancement in NK cell activation. The level of CD69 expression, which represents a functional triggering molecule on activated NK cells, was increased in the CPA group at all the time points tested as compared to untreated mice. However, the most enhancement in CD69 expression was observed on day 7. A significant increase in TNF-alpha level was also observed on day 7 following CPA administration. On the other hand, CPA caused a suppression of the cytolytic activity of NK cells. MMW irradiation of the CPA treated groups resulted in further enhancement of CD69 expression on NK cells, as well as in production of TNF-alpha. Furthermore, MMW irradiation restored CPA induced suppression of the cytolytic activity of NK cells. Our results show that MMW irradiation at 42.2 GHz can up-regulate NK cell functions. </p>
<p>Bioelectromagnetics. 2004 Oct;25(7):516-23. </p>
<h1>Combined millimeter wave and cyclophosphamide therapy of an experimental murine melanoma.</h1>
<p>Logani MK, Bhanushali A, Anga A, Majmundar A, Szabo I, Ziskin MC. </p>
<p>Richard J. Fox Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. </p>
<p><a href="mailto:mlogani@temple.edu">mlogani@temple.edu</a> </p>
<h3>Abstract</h3>
<p>The objective of the present studies was to investigate whether millimeter wave (MMW) therapy can increase the efficacy of cyclophosphamide (CPA), a commonly used anti-cancer drug. The effect of combined MMW-CPA treatment on melanoma growth was compared to CPA treatment alone in a murine model. MMWs were produced with a Russian made YAV-1 generator. The device produced 42.2 +/- 0.2 GHz modulated wave radiation through a 10 x 20 mm rectangular output horn. The animals, SKH-1 hairless female mice, were irradiated on the nasal area. Peak SAR and incident power density were measured as 730 +/- 100 W/kg and 36.5 +/- 5 mW/cm2, respectively. The maximum skin surface temperature elevation measured at the end of 30 min irradiation was 1.5 degrees C. B16F10 melanoma cells (0.2 x 10(6)) were implanted subcutaneously into the left flank of mice on day 1 of the experiment. On days 4-8, CPA was administered intraperitoneally (30 mg/kg/day). MMW irradiation was applied concurrently with, prior to or following CPA administration. A significant reduction (P &lt; .05) in tumor growth was observed with CPA treatment, but MMW irradiation did not provide additional therapeutic benefit as compared to CPA alone. Similar results were obtained when MMW irradiation was applied both prior to and following CPA treatment. </p>
<p>Biofizika. 2004 May-Jun;49(3):545-50. </p>
<h1>A comparison of the effects of millimeter and centimeter waves on tumor necrosis factor production in mouse cells.</h1>
<p>[Article in Russian] </p>
<p>Sinotova OA, Novoselova EG, Glushkova OV, Fesenko EE. </p>
<h3>Abstract</h3>
<p>The effects of millimeter (40 GHz) and centimeter (8.15-18.00 GHz) low-intensity waves on the production of tumor necrosis factor (TNE) in macrophages and lymphocytes from exposed mice as well as in exposed isolated cells were compared. It was found that the dynamics of TNF secretory activity of cells varies depending on the frequency and duration of exposure. The application of millimeter waves induced a nonmonotonous course of the dose-effect curve for TNF changes in macrophages and splenocytes. Alternately, a stimulation and a decrease in TNF production were observed following the application of millimeter waves. On the contrary, centimeter waves provoked an activation in cytokine production. It is proposed that, in contrast to millimeter waves, the single application of centimeter waves to animals (within 2 to 96 h) or isolated cells (within 0.5 to 2.5 h) induced a much more substantial stimulation of immunity. </p>
<p>Bioelectromagnetics. 2004 Oct;25(7):503-7. </p>
<h1>Differences in lethality between cancer cells and human lymphocytes caused by LF-electromagnetic fields.</h1>
<p>Radeva M, Berg H. </p>
<p>Labor Bioelectrochemistry (Campus Beutenberg, Jena) of the Saxonian Academy of Sciences, Leipzig, Germany. </p>
<h3>Abstract</h3>
<p>The lethal response of cultured cancer cells lines K-562, U-937, DG-75, and HL-60 were measured directly after a 4 h exposure to a pulsating electromagnetic field (PEMF, sinusoidal wave form, 35 mT peak, 50 Hz) [Traitcheva et al. (2003): Bioelectromagnetics 24:148-158] and 24 h later, to determine the post-exposure effect. The results were found to depend on the medium, pH value, conductivity, and temperature. From these experiments, suitable conditions were chosen to compare the vitality between K-562 cells and normal human lymphocytes after PEMF treatment and photodynamic action. Both agents enhance necrosis synergistically for diseased as well as for healthy cells, but the lymphocytes are more resistant. The efficacy of PEMF on the destruction of cancer cells is further increased by heating (hyperthermia) of the suspension up to 44 degrees C or by lowering the pH-value (hyperacidity) to pH 6.4. Similar apoptosis and necrosis can be obtained using moderate magnetic fields (B &lt; or = 15 mT 50/60 Hz), but this requires longer treatment of at least over a week. PEMF application combined with anticancer drugs and photodynamic therapy will be very effective. </p>
<p>Bioelectromagnetics. 2004 Sep;25(6):466-73. </p>
<h1>Millimeter wave-induced suppression of B16 F10 melanoma growth in mice: involvement of endogenous opioids.</h1>
<p>Radzievsky AA, Gordiienko OV, Szabo I, Alekseev SI, Ziskin MC. </p>
<p>Center for Biomedical Physics, Temple University Medical School, Philadelphia, Pennsylvania 19140, USA. <a href="mailto:aradziev@temple.edu">aradziev@temple.edu</a> </p>
<h3>Abstract</h3>
<p>Millimeter wave treatment (MMWT) is widely used in Eastern European countries, but is virtually unknown in Western medicine. Among reported MMWT effects is suppression of tumor growth. The main aim of the present &#8220;blind&#8221; and dosimetrically controlled experiments was to evaluate quantitatively the ability of MMWT to influence tumor growth and to assess whether endogenous opioids are involved. The murine experimental model of B16 F10 melanoma subcutaneous growth was used. MMWT characteristics were: frequency, 61.22 GHz; average incident power density, 13.3 x 10(-3) W/cm2; single exposure duration, 15 min; and exposure area, nose. Naloxone (1 mg/kg, intraperitoneally, 30 min prior to MMWT) was used as a nonspecific blocker of opioid receptors. Five daily MMW exposures, if applied starting at the fifth day following B16 melanoma cell injection, suppressed subcutaneous tumor growth. Pretreatment with naloxone completely abolished the MMWT-induced suppression of melanoma growth. The same course of 5 MMW treatments, if started on day 1 or day 10 following tumor inoculations, was ineffective. We concluded that MMWT has an anticancer therapeutic potential and that endogenous opioids are involved in MMWT-induced suppression of melanoma growth in mice. However, appropriate indications and contraindications have to be developed experimentally before recommending MMWT for clinical usage. </p>
<p>Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2004 Aug;21(4):546-8. </p>
<h1>Effects of steep pulsed electric fields on cancer cell proliferation and cell cycle.</h1>
<p lang="fr-FR">[Article in Chinese] </p>
<p>Yao C, Sun C, Mi Y, Xiong L, Hu L, Hu Y. </p>
<p>Key Lab of High Voltage Engineering and Electrical New Technology, Ministry of Education, Chongqing University, Chongqing 400044, China. </p>
<h3>Abstract</h3>
<p>To assess study the cytocidal and inhibitory effects of steep pulsed electric fields (SPEFs) on ovarian cancer cell line SKOV3, the cancer cell suspension was treated by SPEFs with different parameters (frequency, pulse duration, peak value of voltage). Viability rate and growth curves of two test groups (high dosage and low dosage of SPEFs) and one control group were also measured. The DNA contents and cell cycle were analyzed by flow cytometry (FCM). Different dosing levels of SPEFs exerted obviously different effects on cancer cell viability. With the enhancement of each pulse parameter, the viability rate was promoted and the inhibitory effect on the proliferation of treated cells was more evident. The cells exposed to SPEFs grew slower than the control. The ratio of S+G2/M phase cells was decreased, which restrained the DNA synthesis and division, but the ratio of G0/G1 phase cells was increased in the treated groups. It was also indicated that the SPEFs blocked the cell transition from G0/G1 phase to S+G2/M phase. There was a significant difference in cell cycle between treated group and control group (P&lt;0.01). Lethal effects of SPEFs were represented by inhibiting the cancer cell proliferation at the cell level and by influencing the cell cycle at the DNA level.</p>
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<td width="573">Physiol Meas. 2004 Aug;25(4):1077-93.</td>
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<h1>Nanosecond pulsed electric fields modulate cell function through intracellular signal transduction mechanisms.</h1>
<p><strong> </strong>Beebe SJ, Blackmore PF, White J, Joshi RP, Schoenbach KH. </p>
<p>Center for Pediatric Research, Eastern Virginia Medical School, Children&#8217;s Hospital for The King&#8217;s Daughters, Norfolk, VA, USA. <a href="mailto:sbeebe@chkd.com">sbeebe@chkd.com</a> </p>
<p>These studies describe the effects of nanosecond (10-300 ns) pulsed electric fields (nsPEF) on mammalian cell structure and function. As the pulse durations decrease, effects on the plasma membrane (PM) decrease and effects on intracellular signal transduction mechanisms increase. When nsPEF-induced PM electroporation effects occur, they are distinct from classical PM electroporation effects, suggesting unique, nsPEF-induced PM modulations. In HL-60 cells, nsPEF that are well below the threshold for PM electroporation and apoptosis induction induce effects that are similar to purinergic agonistmediated calcium release from intracellular stores, which secondarily initiate capacitive calcium influx through store-operated calcium channels in the PM. NsPEF with durations and electric field intensities that do or do not cause PM electroporation, induce apoptosis in mammalian cells with a well-characterized phenotype typified by externalization of phosphatidylserine on the outer PM and activation of caspase proteases. Treatment of mouse fibrosarcoma tumors with nsPEF also results in apoptosis induction. When Jurkat cells were transfected by electroporation and then treated with nsPEF, green fluorescent protein expression was enhanced compared to electroporation alone. The results indicate that nsPEF activate intracellular mechanisms that can determine cell function and fate, providing an important new tool for probing signal transduction mechanisms that modulate cell structure and function and for potential therapeutic applications for cancer and gene therapy.</p>
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<td width="574">Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2004 Jun;21(3):433-5.</td>
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<h1>Effect of steep pulsed electric fields on survival of tumour-bearing mice.</h1>
<p>[Article in Chinese] </p>
<p>Yao C, Sun C, Xiong L, Mi Y, Liao R, Hu L, Hu Y. </p>
<p>College of Electrical Engineering, Chongqing University, Chongqing, 400044, China. </p>
<p>To investigate the lethal effect of steep pulsed electric fields (SPEFs) on cancer cells and the life-prolonging effect of SPEFs on the survival of tumour-bearing mice, this study was carried out with the use of SPEFs to treat 40 BALB/C mice inoculated by cervical cancer. The lethal effect on cancer cells and the life-prolonging effect on tumour-bearing mice were examined and compared between the experiment group and control group. The survival periods of the experiment group and control group were 52.05 days and 33.03 days, respectively. There was a significant difference in survival curve between the two groups. The results confirmed the inhibitiory effect and lethal effect of SPEFs on cancer cells. SPEFs can prolong the survival period of tumour-bearing mice.</p>
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<td width="573">Ann Biomed Eng. 2003 Jan;31(1):80-90.</td>
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<h1>Viability of cancer cells exposed to pulsed electric fields: the role of pulse charge.</h1>
<p>Krassowska W, Nanda GS, Austin MB, Dev SB, Rabussay DP. </p>
<p>Department of Biomedical Engineering, Duke University, Durham, NC 27708-0281, USA. <a href="mailto:wanda.krassowska@duke.edu">wanda.krassowska@duke.edu</a> </p>
<p>The goal of this study was to collect a comprehensive set of data that related lethal effects of electric fields to the duration of the pulse. Electric pulses of different strengths and durations were applied to a suspension of HEp-2 cells (epidermoid carcinoma of the human larynx) using a six-needle electrode array connected through an autoswitcher to a square wave generator. Pulse durations varied from 50 micros to 16 ms and the ranges of electric field were adjusted for each duration to capture cell viabilities between 0% and 100%. After pulsation, cells were incubated for 44 h at 37 degrees C, and their viability was measured spectrophotometrically using an XTT assay. For each pulse duration (d), viability data were used to determine the electric field that killed half of the cells (E50). When plotted on logarithmic axes, E50 vs. d was a straight line, leading to a hyperbolic relationship: E50=const/d. This relationship suggests that the total charge delivered by the pulse is the decisive factor in killing HEp-2 cells.</p>
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<td width="573"><span style="text-decoration: underline;">Vopr Onkol.</span> 2003;49(6):748-51.</td>
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<h1>Experience with turbulent magnetic field as a component of breast cancer therapy.</h1>
<p>[Article in Russian] </p>
<p>Letiagin VP, Protchenko NV, Rybakov IuL, Dobrynin IaV. </p>
<p>N.N. Blokhin Center for Oncology Research, Russian Academy of Medical Sciences, Zdorovje Research Center, Moscow. </p>
<p>No adverse side-effects were reported in an investigation of the antitumor effect of turbulent magnetic field (TMF) carried out as a component of preoperative chemoradiotherapy for breast cancer at the Center&#8217;s Clinic. The study group included 114 patients with locally advanced tumors(T3, N1-N3, M0). According to the clinical, roentgenological and histological evidence on the end-results, the procedure was highly effective. Also, it was followed by shorter and less extensive postoperative lymphorrhea. </p>
<p>Bioelectromagnetics. 2003 Feb;24(2):148-50. </p>
<h1>ELF fields and photooxidation yielding lethal effects on cancer cells.</h1>
<p>Traitcheva N, Angelova P, Radeva M, Berg H. </p>
<p>Laboratory of Bioelectrochemistry, Institute of Virology, FSU, Jena, Germany. </p>
<h3>Abstract</h3>
<p>The lethal effect on human cancer cells was studied under three types of treatment: A) an ELF pulsed sinusoidal of 50 Hz electromagnetic field (PEMF) with amplitudes between 10 and 55 mT; B) the field and a cytostatic agent (actinomycin-C); and C) the field, the cytostatic agent, which has a photodynamic effect, and exposure to a halogen lamp. The results show a decreasing vitality of human K-562 and U-937 cancer cells in suspension with each additional treatment. Combination with other parameters as hyperthermia and/or hyperacidity could yield high killing rates by this noninvasive method. </p>
<p>Technol Cancer Res Treat. 2002 Feb;1(1):71-82. </p>
<h1>Enhancing the effectiveness of drug-based cancer therapy by electroporation (electropermeabilization).</h1>
<p>Rabussay DP, Nanda GS, Goldfarb PM. </p>
<p>Genetronics, Inc., 11199 Sorrento Valley Road, San Diego CA 92121, USA. <a href="mailto:dietmarr@genetronics.com">dietmarr@genetronics.com</a> </p>
<h3>Abstract</h3>
<p>Many conventional chemotherapeutic drugs, as well as DNA for cancer gene therapy, require efficient access to the cell interior to be effective. The cell membrane is a formidable barrier to many of these drugs, including therapeutic DNA constructs. Electropermeabilization (EP, often used synonymously with &#8220;electroporation&#8221;) has become a useful method to temporarily increase the permeability of the cell membrane, allowing a broad variety of molecules efficient access to the cell interior. EP is achieved by the application of short electrical pulses of relatively high local field strength to the target tissue of choice. In cancer therapy, EP can be applied in vivo directly to the tumor to be treated, in order to enhance intracellular uptake of drugs or DNA. Alternatively, EP can be used to deliver DNA into cells of healthy tissue to achieve longer-lasting expression of cancer-suppressing genes. In addition, EP has been used in ex vivo therapeutic approaches for the transfection of a variety of cells in suspension. In this paper, we communicate results related to the development of a treatment for squamous cell carcinomas of the head and neck, using electropermeabilization to deliver the drug bleomycin in vivo directly into the tumor cells. This drug, which is not particularly effective as a conventional therapeutic, becomes highly potent when the intracellular concentration is enhanced by EP treatment. In animal model experiments we found a drug dose of 1 U/cm(3) tumor tissue (delivered in 0.25 mL of an aqueous solution/cm3 tumor tissue) and an electrical field strength of 750 V/cm or higher to be optimal for the treatment of human squamous cell tumors grown subcutaneously in mice. Within 24-48 hours, the majority of tumor cells are rapidly destroyed by this bleomycin-electroporation therapy (B-EPT). This raises the concern that healthy tissue may be similarly affected. In studies with large animals we showed that normal muscle and skin tissue, normal tissue surrounding major blood vessels and nerves, as well as healthy blood vessels and nerves themselves, are much less affected than tumor tissue. Normal tissues did show acute, focal, and transitory effects after treatment, but these effects are relatively minor under standard treatment conditions. The severity of these effects increases with the number of electric pulse cycles and applied voltage. The observed histological changes resolved 20 to 40 days after treatment or sooner, even after excessive EP treatment. Thus, B-EPT is distinct from other ablative therapies, such as thermal, cryo, or photodynamic ablation, which equally affect healthy and tumor tissue. In comparison to surgical or radiation therapy, B-EPT also has potential as a tissue-sparing and function-preserving therapy. In clinical studies with over 50 late stage head and neck cancer patients, objective tumor response rates of 55-58%, and complete tumor response rates of 19-30% have been achieved. </p>
<p>Bioelectromagnetics. 2002 Dec;23(8):578-85. </p>
<h1>Influence of 1 and 25 Hz, 1.5 mT magnetic fields on antitumor drug potency in a human adenocarcinoma cell line.</h1>
<p>Ruiz-Gómez MJ, de la Peña L, Prieto-Barcia MI, Pastor JM, Gil L, Martínez-Morillo M. </p>
<p>Laboratory of Radiobiology, Department of Radiology and Physical Medicine, Faculty of Medicine, University of Málaga, Teatinos, Málaga, Spain. </p>
<h3>Abstract</h3>
<p>The resistance of tumor cells to antineoplastic agents is a major obstacle during cancer chemotherapy. Many authors have observed that some exposure protocols to pulsed electromagnetic fields (PEMF) can alter the efficacy of anticancer drugs; nevertheless, the observations are not clear. We have evaluated whether a group of PEMF pulses (1.5 mT peak, repeated at 1 and 25 Hz) produces alterations of drug potency on a multidrug resistant human colon adenocarcinoma (HCA) cell line, HCA-2/1(cch). The experiments were performed including (a) exposures to drug and PEMF exposure for 1 h at the same time, (b) drug exposure for 1 h, and then exposure to PEMF for the next 2 days (2 h/day). Drugs used were vincristine (VCR), mitomycin C (MMC), and cisplatin. Cell viability was measured by the neutral red stain cytotoxicity test. The results obtained were: (a) The 1 Hz PEMF increased VCR cytotoxicity (P &lt; 0.01), exhibiting 6.1% of survival at 47.5 microg/ml, the highest dose for which sham exposed groups showed a 19.8% of survival. For MMC at 47.5 microg/ml, the % of survival changed significantly from 19.2% in sham exposed groups to 5.3% using 25 Hz (P &lt; 0.001). Cisplatin showed a significant reduction in the % of survival (44.2-39.1%, P &lt; 0.05) at 25 Hz and 47.5 microg/ml, and (b) Minor significant alterations were observed after nonsimultaneous exposure of cells to PEMF and drug. The data indicate that PEMF can induce modulation of cytostatic agents in HCA-2/1(cch), with an increased effect when PEMF was applied at the same time as the drug. The type of drug, dose, frequency, and duration of PEMF exposure could influence this modulation. </p>
<p>Biofizika. 2002 Mar-Apr;47(2):376-81. </p>
<h1>Immunomodulating effect of electromagnetic waves on production of tumor necrosis factor in mice with various rates of neoplasm growth.</h1>
<p>[Article in Russian] </p>
<p>Glushkova OV, Novoselova EG, Sinotova OA, Vrublevskaia VV, Fesenko EE. </p>
<p>Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia. </p>
<h3>Abstract</h3>
<p>The effects of low-density centimeter waves (8.15-18 GHz, 1 microW/cm2, 1 h daily for 14 days; MW) on tumor necrosis factor production in macrophages of mice with different growth rate of a cancer solid model produced after hypodermic injection of Ehrlich carcinoma ascites cells into hind legs were studied. After irradiation, an increase in the concentration of tumor necrosis factor in immunocompetent cells of healthy and, specially, of tumor-bearing animals was observed; and the effect of stimulation was higher upon exposure of mice carrying rapidly growing tumors. We suggest that the significant immunomodulating effect of low-density microwaves can be utilized for tumor growth suppression. </p>
<p>Biofizika. 2001 Jan-Feb;46(1):131-5. </p>
<h1>Effect of centimeter m</h1>
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<div>Cell Biol. Int. 2002;26(7):599-603.</div>
<h1>Extremely low frequency (ELF) pulsed-gradient magnetic fields inhibit malignant tumour growth at different biological levels.</h1>
<div>Zhang X, Zhang H, Zheng C, Li C, Zhang X, Xiong W.</div>
<div>
<p>Source </p>
<p>Biomedical Physics Unit, Department of Physics, Wuhan University, Wuhan, 430072, China. </p>
<div>
<p>Abstract </p>
<p>Extremely low frequency (ELF) pulsed-gradient magnetic field (with the maximum intensity of 0.6-2.0 T, gradient of 10-100 T.M(-1), pulse width of 20-200 ms and frequency of 0.16-1.34 Hz treatment of mice can inhibit murine malignant tumour growth, as seen from analyses at different hierarchical levels, from organism, organ, to tissue, and down to cell and macromolecules. Such magnetic fields induce apoptosis of cancer cells, and arrest neoangiogenesis, preventing a supply developing to the tumour. The growth of sarcomas might be amenable to such new method of treatment. </p>
</div>
<h1>icrowaves and the combined magnetic field on the tumor necrosis factor production in cells of mice with experimental tumors.</h1>
<p>[Article in Russian] </p>
<p>Novoselova EG, Oga? VB, Sorokina OV, Novikov VV, Fesenko EE. </p>
<p>Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia. </p>
<h3>Abstract</h3>
<p>The effect of fractionated exposure to low-intensity microwaves (8.15-18 GHz, 1 microW/cm2, 1.5 h daily for 7 days) and combined weak magnetic field (constant 65 1 microT; alternating&#8211;100 nT, 3-10 Hz) on the production of tumor necrosis factor in macrophages of mice with experimental solid tumors produced by transplantation of Ehrlich ascites carcinoma was studied. It was found that exposure of mice to both microwaves and magnetic field enhanced the adaptive response of the organism to the onset of tumor growth: the production of tumor necrosis factor in peritoneal macrophages of tumor-bearing mice was higher than in unexposed mice.</p>
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<td width="574">J Photochem Photobiol B. 2001 Nov 1;64(1):21-6.</td>
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<h1>Photodynamic effect on cancer cells influenced by electromagnetic fields.</h1>
<p>Pang L, Baciu C, Traitcheva N, Berg H. </p>
<p>Institute of Physics, Nankai University, Nankai, PR China. </p>
<p>The synergism of low-frequency electromagnetic field treatment and photodynamic effect on killing of human cancer cells is presented. The weak pulsating electromagnetic field (PEMF) generated by Helmholtz coils in the mT range influences the permeability of cell membranes for photosensitizers. Several types of sensitizers were excited by visible light during incorporation without and with two kinds of PEMF treatment. In the first part suitable photosensitizers were selected in the absorption range between 400 and 700 nm against human myeloid leukaemia K562 and human histiocytic lymphoma U937 cells by treatment of PEMF consisting of rectangular pulse groups. In the second part amplitude and frequency dependencies were measured using sinuous PEMF and white light with the result that after 12 min the PEMF treatment enhanced photodynamic effectivity by more than 40% over the control value. Taking into account the influence of many parameters, an additional optimization will be possible by photodynamic PEMF synergism for an increased drug delivery in general. </p>
<p>Bioelectromagnetics. 2001 Oct;22(7):503-10. </p>
<h1>Pulsed electromagnetic fields affect the intracellular calcium concentrations in human astrocytoma cells.</h1>
<p>Pessina GP, Aldinucci C, Palmi M, Sgaragli G, Benocci A, Meini A, Pessina F. </p>
<p>Institute of General Physiology and Nutritional Science, University of Siena, Italy. <a href="mailto:pessina@unisi.it">pessina@unisi.it</a> </p>
<h3>Abstract</h3>
<p>Experiments assessed whether long term exposure to 50 Hz pulsed electromagnetic fields with a peak magnetic field of 3 mT can alter the dynamics of intracellular calcium in human astrocytoma U-373 MG cells. Pretreatment of cells with 1.2 microM substance P significantly increased the [Ca(2+)](i). The same effect was also observed when [Ca(2+)](i) was evaluated in the presence of 20 mM caffeine. After exposure to electromagnetic fields the basal [Ca(2+)](i) levels increased significantly from 143 +/- 46 nM to 278 +/- 125 nM. The increase was also evident after caffeine addition, but in cells treated with substance P and substance P + caffeine we observed a [Ca(2+)](i) decrease after exposure. When we substituted calcium-free medium for normal medium immediately before the [Ca(2+)](i) measurements, the [Ca(2+)](i) was similar to that measured in the presence of Ca(2+). In this case, after EMFs exposure of cells treated with substance P, the [Ca(2+)](i), measured without and with addition of caffeine, declined from 824 +/- 425 to 38 +/- 13 nM and from 1369 +/- 700 to 11 +/- 4 nM, respectively, indicating that electromagnetic fields act either on intracellular Ca(2+) stores or on the plasma membrane. Moreover the electromagnetic fields that affected [Ca(2+)](i) did not cause cell proliferation or cell death and the proliferation indexes remained unchanged after exposure. </p>
<p id="sendto">Cell Biol Int. 2002;26(7):599-603.</p>
<div>
<div>
<h1>Extremely low frequency (ELF) pulsed-gradient magnetic fields inhibit malignant tumour growth at different biological levels.</h1>
<div>Zhang X, Zhang H, Zheng C, Li C, Zhang X, Xiong W.</div>
<div>
<p><strong>Source</strong></p>
<p>Biomedical Physics Unit, Department of Physics, Wuhan University, Wuhan, 430072, China.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p>Extremely low frequency (ELF) pulsed-gradient magnetic field (with the maximum intensity of 0.6-2.0 T, gradient of 10-100 T.M(-1), pulse width of 20-200 ms and frequency of 0.16-1.34 Hz treatment of mice can inhibit murine malignant tumour growth, as seen from analyses at different hierarchical levels, from organism, organ, to tissue, and down to cell and macromolecules. Such magnetic fields induce apoptosis of cancer cells, and arrest neoangiogenesis, preventing a supply developing to the tumour. The growth of sarcomas might be amenable to such new method of treatment.</p>
</div>
</div>
</div>
<p>Cell Mol Biol (Noisy-le-grand). 2001;47 Online Pub:OL115-7. </p>
<h1>Inhibition of proliferation of human lymphoma cells U937 by a 50 Hz electromagnetic field.</h1>
<p>Glück B, Güntzschel V, Berg H. </p>
<p>Laboratory Cell Culture, Institute of Virology, Friedrich-Schiller-University Jena, Germany. <a href="mailto:i6glbr@rz.uni-jena.de">i6glbr@rz.uni-jena.de</a> </p>
<h3>Abstract</h3>
<p>Weak pulsating electromagnetically induced fields (PEMF) by Helmholtz coils changes cell metabolism, if cells are treated with a certain range of frequency and amplitude. The influence on proliferation of human histiocytic lymphoma cells U937 has been studied applying a sinusoidal 50 Hz field with amplitudes of the flux density B = 0.3 to 4.7 mT for 4 days. No difference between experiment and control was found in the region 0.3 and 2 mT. However, stronger fields (&gt; or =2.5 mT) inhibit cell division. Fields &gt; or =3.5 mT treatment kill &gt; or =80% of the cell number at the beginning (1.5 x 10(5)/ml). This effect may be an electromagnetocally induced cell death as the first step for a non-invasive application on cell proliferation process. </p>
<p>Laryngoscope. 2001 Jan;111(1):52-6. </p>
<h1>Electroporation therapy for head and neck cancer including carotid artery involvement.</h1>
<p>Allegretti JP, Panje WR. </p>
<p>Department of Otolaryngology, Rush-Presbyterian-St Luke&#8217;s Medical Center, Rush Medical College, Chicago, Illinois 60612, USA. </p>
<h3>Abstract</h3>
<p>OBJECTIVES: Electroporation therapy with intralesional bleomycin (EPT) is a novel, technically simple outpatient technique in which high-voltage electric impulses delivered into a neoplasm transiently increase cell membrane permeability to large molecules, including cytotoxic agents, causing localized progressive necrosis. Unlike many laser ablation methods, EPT can treat bulky tumors (&gt;2 cm) with complete penetration. Our recent publication confirms an excellent response rate in the use of EPT in a clinical trial. STUDY </p>
<p>DESIGN, PATIENTS, AND METHODS: Following our initial prospective study report in 1998, we have followed our entire initial cohort (10 patients) of patients with head and neck cancer beyond 24-months follow-up. Additionally, we have used this approach to treat four additional patients (total: 9 males/5 females) with upper aerodigestive tract squamous cell carcinoma, including three with internal carotid artery (ICA) involvement up to or within the skull base. Two patients underwent preoperative balloon test occlusion with cerebral perfusion studies followed by carotid embolization. EPT was then done safely at least 2 weeks later to avoid the temporary hypercoagulable state. </p>
<p>RESULTS: Within the overall cohort (14 patients) 6 patients had a complete response, 6 had a partial response, and 2 did not respond (overall 85.7% response rate). Both patients with ICA involvement had a partial or complete response to treatment; neither patient had a hemorrhagic or neurologic complication. Overall, 13 of the 14 patients were treated for persistent or recurrent head and neck cancer. Two of the four patients with early recurrent stage tumors had no evidence of recurrence after EPT with an average follow-up of 31.5 months. The overall early stage tumor group had four complete responders out of five (80%). On the contrary, only 2 of 9 patients with advanced recurrent stage tumors were disease-free at 18 months. Morbidity was low for early stage tumors, but higher for advanced tumors with complications, including poor wound healing, dysphagia, and osteomyelitis. There were no treatment-related deaths. </p>
<p>CONCLUSION: We found EPT to be safe and efficacious in patients with head and neck cancer, even with internal carotid artery involvement. Patients with early stage recurrences have the potential for prolonged survival beyond 2 years without the morbidity of surgery and radiation or toxicity of systemic chemotherapy. Because of its superb access qualities even for bulky tumors, EPT is a potential method of delivery for other tumoricidal agents such as in genetic-altering schemes.</p>
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<td width="573"><span style="text-decoration: underline;">Vopr Onkol.</span> 2000;46(4):469-72.</td>
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<h1>Use of artificial magnetic field for rehabilitation of children with malignant tumors.</h1>
<p>[Article in Russian] </p>
<p>Kiselev AV, Grushina TI. </p>
<p>N.N. Blokhin Center for Oncology Research, Russian Academy of Medical Sciences, Moscow. </p>
<p>Local complications of standard intravenous injections for chemotherapy and due to error of administration were compared in 400 patients (200 of them children) and general wound pathologies described. Treatment for wounds included two modalities: standard medication and alternating or pulsating magnetic field. Magnetic therapy proved highly effective: wound healing was 3-3.5 times faster while duration of treatment&#8211;2-3 times shorter than in standard procedure. Clinically-verified partial adhesion-related intestinal obstruction was eliminated by magnetic procedure in 18 children after combined treatment for lymphosarcoma involving the ileum. </p>
<p>Bioelectromagnetics. 2000 Feb;21(2):112-21. </p>
<h1>Effects of PEMF on a murine osteosarcoma cell line: drug-resistant (P-glycoprotein-positive) and non-resistant cells.</h1>
<p>Miyagi N, Sato K, Rong Y, Yamamura S, Katagiri H, Kobayashi K, Iwata H. </p>
<p>Department of Orthopaedic Surgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan. </p>
<p>Abstract </p>
<p>After pulsed exposure of Dunn osteosarcoma cells (nonresistant cells) to Adriamycin (ADR) at increasing concentrations and single-cell cloning of surviving cells, ADR-resistant cells were obtained. These resistant cells expressed P-glycoprotein and had resistance more than 10 times that of their nonresistant parent cells. Compared to the nonresistant cells not exposed to pulsing electromagnetic fields (PEMF) in ADR-free medium, their growth rates at ADR concentrations of 0.01 and 0.02 micrograms/ml, which were below IC50, were 83.0% and 61.8%, respectively. On the other hand, in the nonresistant cells exposed to PEMF (repetition frequency, 10 Hz; rise time, 25 microsec, peak magnetic field intensity, 0.4-0.8 mT), the growth rate was 111.9% in ADR-free medium, 95.5% at an ADR concentration of 0.01 micrograms/ml, and 92.2% at an ADR concentration of 0.02 micrograms/ml. This promotion of growth by PEMF is considered to be a result of mobilization of cells in the non-proliferative period of the cell cycle due to exposure to PEMF. However, at ADR concentrations above the IC50, the growth rate tended to decrease in the cells not exposed to PEMF. This may be caused by an increase in cells sensitive to ADR resulting from mobilization of cells in the non-proliferative period to the cell cycle. The growth rate in the resistant cells exposed to PEMF was significantly lower than that in the non-exposed resistant cells at all ADR concentrations, including ADR-free culture (P&lt;/=0.0114). Therefore, this study suggests that PEMF promotes the growth of undifferentiated cells but progressively suppresses the growth of more differentiated cells, i.e., PEMF controls cell growth depending on the degree of cell differentiation. This study also shows the potentiality of PEMF as an adjunctive treatment method for malignant tumors </p>
<p>J Physiol Biochem. 1999 Jun;55(2):79-83. </p>
<h1>Growth modification of human colon adenocarcinoma cells exposed to a low-frequency electromagnetic field.</h1>
<p>Ruiz Gómez MJ, Pastor Vega JM, de la Peña L, Gil Carmona L, Martínez Morillo M. </p>
<p>Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Málaga, Teatinos, Spain. <a href="mailto:mjrg@uma.es">mjrg@uma.es</a> </p>
<h3>Abstract</h3>
<p>The influence of variable low-intensity, low-frequency electromagnetic fields on culture cells is investigated. Human colon adenocarcinoma cells were exposed to a rectangular and variable magnetic field (1 and 25 Hz; 1.5 mT peak). Cultures were exposed to a dose for 15 and 360 minutes, and after 24 hours incubation, cell viability was measured with neutral red stain. The group treated for 15 minutes showed a statistically significant increase in cell growth with 1 Hz (p &lt; 0.002) and 25 Hz (p &lt; 0.003). In contrast, a significant decrease in cell growth was found in those cultures treated with 1 Hz for 360 minutes (p &lt; 0.02). The effects reported could be influenced by the magnetic field frequency and the exposure time.</p>
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<td width="574">Am J Physiol. 1997 May;272(5 Pt 2):R1677-83.</td>
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<h1>Electrical fields enhance growth of cancer spheroids by reactive oxygen species and intracellular Ca2+.</h1>
<p>Wartenberg M, Hescheler J, Sauer H. </p>
<p>Institute for Neurophysiology, University of Cologne, Germany. </p>
<p>A single electrical field pulse (500 V/m) with a duration of 60 s increased tumor outgrowth over a postpulse period of 24 h. RNA staining with acridine orange showed a rise in RNA content in pulsed spheroids, indicating stimulation of cell cycle activity. The electropulse induced an intracellular Ca2+ concentration ([Ca2+]i) transient that started approximately 40 s after the onset of the electrical field. Neither the presence of extracellular Ni2+ (0.5 mM) nor the absence of extracellular Ca2+ impeded the [Ca2+]i rise. It was, however, totally blocked by thapsigargin (1 microM), indicating that the initial Ca2+ response is due to Ca2+ release from intracellular stores. The [Ca2+]i transient was paralleled by an increase in reactive oxygen species (ROS), as revealed using 2&#8242;,7&#8242;-dichlorofluorescein diacetate as an indicator. The radical scavengers N-acetyl-L-cysteine (NAC)(20 mM) and dehydroascorbate (5 mM) inhibited both ROS production and the [Ca2+]i transient during electrical field treatment. The mitogenic activation was dependent on the rise in [Ca2+]i because inhibition of Ca2+ release during electrical field treatment by addition of either thapsigargin or NAC to the incubation medium abolished the observed effect. We conclude that a single, direct current electrical field pulse induces production of ROS, which in turn mediate Ca2+ release from intracellular stores and activate cell cycle activity in multicellular spheroids. </p>
<p>Anticancer Res. 1997 May-Jun;17(3C):2083-8. </p>
<h1>Enhanced potency of daunorubicin against multidrug resistant subline KB-ChR-8-5-11 by a pulsed magnetic field.</h1>
<p>Liang Y, Hannan CJ Jr, Chang BK, Schoenlein PV. </p>
<p>Department of Radiology, Research and Nuclear Medicine, Medical College of Georgia, Augusta 30912, USA. </p>
<h3>Abstract</h3>
<p>Tumor cell resistance to many unrelated anticancer drugs is a major obstacle during cancer chemotherapy. One mechanism of drug resistance is thought to be due to the efflux of anticancer drugs caused by P-glycoprotein. In recent years, magnetic fields have been found to enhance the potency of anticancer drugs, with favorable modulation of cancer therapy. In this study, KB-ChR-8-5-11, a multidrug resistant (MDR) human carcinoma subline, was used as a model to evaluate the ability of pulsed magnetic fields (PMF) to modulate the potency of daunorubicin (DNR) in vivo and to determine the appropriate order of exposure to drugs and PMF using an in vitro cytotoxicity assay. Solenoid coils with a ramped pulse current source were used at 250 pulses per second for both in vivo and in vitro experiments. For the in vivo study, KB-ChR-8-5-11 cells were inoculated into thymic Balbc-nu/nu female mice. Treatment was begun when the average tumor volume reached 250-450 mm3. Treatment consisted of whole body exposure to PMF for one hour, followed immediately by intravenous (i.v.) injection of 8 mg/kg DNR designated as day 0, and repeated on days 7 and 14. Among the various groups, significant differences in the tumor volume were found between PMF + saline and PMF + DNR groups (p = 0.0107) at 39 days and 42 days (p = 0.0101). No mice died in the PMF alone group, and no toxicity attributable to PMF was found during the experimental period. For the in vitro studies, the sulforhodamine blue (SRB) cytotoxicity assay was used to determine the effect of the sequence which cells are exposed to PMF and/or DNR. Cells were exposed to PMF either before (pre-PMF) or after (post-PMF) drug was added. Results showed that the IC50 was significantly different between controls and pre-PMF + DNR groups (P = 0.0096, P = 0.0088). The IC50 of the post-PMF + DNR group was not found to be significantly different from control groups. Thus, the data in this report demonstrates that PMF enhanced the potency of DNR against KB-ChR-8-5-11 xenograft in vivo, while the efficacy of DNR was potentiated in vitro by PMF exposure only when PMF exposure occurred in the presence of drug. The data in vitro suggest that the mechanism by which PMFs modulate DNR&#8217;s potency may be by inhibition of the efflux pump, P-glycoprotein. Further work to determine conditions for maximum modulation of drug potency by PMFs is warranted. </p>
<p>Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997 May;17(5):286-8. </p>
<h1>Effect of acupoint irradiation with Q-wave millimeter microwave on peripheral white blood cells in post-operational treatment with chemotherapy in stomach and colorectal cancer patients.</h1>
<p>[Article in Chinese] </p>
<p>Wu JG, Huang WZ, Wu BY. </p>
<p>Oncology Department of Second Ningde District Hospital, Fujian. </p>
<h3>Abstract</h3>
<p>OBJECTIVE: To explore the biological effect of Q-wave millimeter microwave (QWMM). </p>
<p>METHODS: The QWMM was used to irradiate the acupoints Xuehai (Sp10) and Geshu (B17) in treating post-operational and chemotherapy treated stomach cancer and colorectal cancer patients. The effect of irradiation on chemotherapy affected peripheral white blood cells was observed. 62 cases (stomach cancer 42, colorectal cancer 20) in total were divided into two groups: group A, 21 cases (stomach cancer 15, colorectal cancer 6) the irradiation began 10 days after operation, and on the 16th day the chemotherapy combined with irradiation started. Group B had 41 cases (stomach cancer 27, colorectal cancer 14), in which the irradiation began immediately after the occurrence of chemotherapy induced peripheral WBC reduction, which persisted for at least 12 days. </p>
<p>RESULTS: The effective rate for the group A and B was 85.7% (18/21) and 73.2% (30/41) respectively. The total effective rate of the two groups was 77.4% (48/62). The effective rate of group A was significantly higher than that of group B, P &lt; 0.01. </p>
<p>CONCLUSION: GWMM irradiation at acupoints could promote the hematopoietic function of bone marrow, and the irradiation performed 1 week before chemotherapy yielded even better protection on bone marrow.</p>
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<td width="573">Bioelectromagnetics 1996;17(5):358-63.</td>
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<h1>Exposure to strong static magnetic field slows the growth of human cancer cells in vitro.</h1>
<p>Raylman RR, Clavo AC, Wahl RL. </p>
<p>University of Michigan Medical Center, Department of Internal Medicine, Ann Arbor, USA. </p>
<p>Proposals to enhance the amount of radiation dose delivered to small tumors with radioimmunotherapy by constraining emitted electrons with very strong homogeneous static magnetic fields has renewed interest in the cellular effects of prolonged exposures to such fields. Past investigations have not studied the effects on tumor cell growth of lengthy exposures to very high magnetic fields. Three malignant human cell lines, HTB 63 (melanoma), HTB 77 IP3 (ovarian carcinoma), and CCL 86 (lymphoma: Raji cells), were exposed to a 7 Tesla uniform static magnetic field for 64 hours. Following exposure, the number of viable cells in each group was determined. In addition, multicycle flow cytometry was performed on all cell lines, and pulsed-field electrophoresis was performed solely on Raji cells to investigate changes in cell cycle patterns and the possibility of DNA fragmentation induced by the magnetic field. A 64 h exposure to the magnetic field produced a reduction in viable cell number in each of the three cell lines. Reductions of 19.04 +/- 7.32%, 22.06 +/- 6.19%, and 40.68 +/- 8.31% were measured for the melanoma, ovarian carcinoma, and lymphoma cell lines, respectively, vs. control groups not exposed to the magnetic field. Multicycle flow cytometry revealed that the cell cycle was largely unaltered. Pulsed-field electrophoresis analysis revealed no increase in DNA breaks related to magnetic field exposure. In conclusion, prolonged exposure to a very strong magnetic field appeared to inhibit the growth of three human tumor cell lines in vitro. The mechanism underlying this effect has not, as yet, been identified, although alteration of cell growth cycle and gross fragmentation of DNA have been excluded as possible contributory factors. Future investigations of this phenomenon may have a significant impact on the future understanding and treatment of cancer.</p>
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<td colspan="2" width="573">J Cell Biochem. 1993 Apr;51(4):387-93.</td>
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<h1>Beneficial effects of electromagnetic fields.</h1>
<p><strong> </strong>Bassett CA. </p>
<p>Bioelectric Research Center, Columbia University, Riverdale, New York 10463. </p>
<p>Selective control of cell function by applying specifically configured, weak, time-varying magnetic fields has added a new, exciting dimension to biology and medicine. Field parameters for therapeutic, pulsed electromagnetic field (PEMFs) were designed to induce voltages similar to those produced, normally, during dynamic mechanical deformation of connective tissues. As a result, a wide variety of challenging musculoskeletal disorders have been treated successfully over the past two decades. More than a quarter million patients with chronically ununited fractures have benefitted, worldwide, from this surgically non-invasive method, without risk, discomfort, or the high costs of operative repair. Many of the athermal bioresponses, at the cellular and subcellular levels, have been identified and found appropriate to correct or modify the pathologic processes for which PEMFs have been used. Not only is efficacy supported by these basic studies but by a number of double-blind trials. As understanding of mechanisms expands, specific requirements for field energetics are being defined and the range of treatable ills broadened. These include nerve regeneration, wound healing, graft behavior, diabetes, and myocardial and cerebral ischemia (heart attack and stroke), among other conditions. Preliminary data even suggest possible benefits in controlling malignancy.</p>
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<td width="573">In Vivo. 1991 Jan-Feb;5(1):39-40.</td>
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<h1>Effect of a 9 mT pulsed magnetic field on C3H/Bi female mice with mammary carcinoma. A comparison between the 12 Hz and 460 Hz frequencies.</h1>
<p>Bellossi A, Desplaces A. </p>
<p>Laboratoire de Biophysique, Faculte de Medecine, Rennes, France. </p>
<p>In a previous experiment, the exposure of tumoral C3H/Bi female mice to a 9 mT, 460 Hz pulsed magnetic field led to an increase in the length of survival in the late period of the disease; this might be due to a hampered metastatic process. In the present study 27 controls and 52 exposed mice were treated with the same protocol (a 10-minute exposure, 3 non-consecutive days a week, from 2-3 weeks after the tumors appeared until death) but with a 12 Hz PMF. In this experiment the 12 Hz PMF appeared to increase length of survival times in the early period of the disease.</p>
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<td width="572">Sov Med. 1991;(7):25-7.</td>
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<h1>The assessment of the efficacy of the effect of a rotational magnetic field on the course of the tumor process in patients with generalized breast cancer.</h1>
<p>[Article in Russian] </p>
<p>Bakhmutskii NG, Pyleva TA, Frolov VE, Sinitskii DA, Ripa IM. </p>
<p>The efficacy of rotational magnetic field generated by a &#8220;Magnitoturbotron&#8221; unit was evaluated in 51 women with advanced breast cancer. The effect resulted from an action on the patient&#8217;s body by modulated rotational magnetic field changing in cycles according to induction. A significant response was achieved in 27 of 51 patients. There was no hemopoiesis suppression, negative functional shifts. The unit is recommended for introduction in a combined treatment of breast cancer.</p>
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<td width="573">Jpn J Cancer Res. 1990 Sep;81(9):956-61.</td>
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<h1>Treatment of experimental tumors with a combination of a pulsing magnetic field and an antitumor drug.</h1>
<p>Omote Y, Hosokawa M, Komatsumoto M, Namieno T, Nakajima S, Kubo Y, Kobayashi H. </p>
<p>Laboratory of Pathology, Hokkaido University School of Medicine, Sapporo. </p>
<p>We investigated the effects of a combination treatment involving a pulsing magnetic field (PMF) and an antitumor drug, mitomycin C (MMC), on two experimental tumors (fibrosarcoma KMT-17 and hepatocellular carcinoma KDH-8) in WKA rats, paying attention to possible potentiation of the therapeutic effect of the antitumor drug. PMF was obtained using a system generating a pulsed current in a solenoid coil. On day 7 after tumor implantation into the right thighs of rats, the region of the tumor was exposed to PMF (frequency 200 Hz, mean magnetic flux density 40 gauss) for 1 h immediately after iv injection of MMC at a dose of 1 mg/kg. Survival rates at day 90 of KMT-17 implanted rats were 0% (0/10) in the non-treated group, 34% (4/12) in the MMC-treated group, 47% (6/13) in the PMF-treated group and 77% (10/13) in the MMC/PMF combination group. The increase of life span (ILS) of KDH-8-implanted rats in the combination therapy group was significantly prolonged (%ILS 17.6%) compared with that in the MMC-treated (%ILS 3.4%) and PMF-treated (%ILS 7.6%) groups. By using cultured cells of the above two lines of tumor, the therapeutic effects of MMC and PMF were also determined from the cell colony-forming efficiency in soft agar. The colony-forming efficiencies of both cell lines were significantly suppressed in the combination therapy group compared with those in the other single therapy groups. The present results indicate that PMF exhibited a potentiation of the antitumor effect of mitomycin C.</p>
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<p lang="fr-FR">Nippon Geka Gakkai Zasshi. 1988 Aug;89(8):1155-66. </p>
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<h1>An experimental attempt ot potentiate therapeutic effects of combined use of pulsing magnetic fields and antitumor agents.</h1>
<p>[Article in Japanese] </p>
<p>Omote Y. </p>
<p>First Department of Surgery, Asahikawa Medical College, Japan. </p>
<p>With a view to examining the possible clinical applicability of pulsing magnetic fields (PMF), we investigated the effects of weak, non-heat inducing, PMF on DNA synthesis and sensitivity of cancer cells to antitumor agents. Leukemic T-cells (Molt-4) and a pancreatic ductal adenocarcinoma (solid tumor) transplanted in a Syrian golden hamster were used for the in vitro experiment and in vivo experiment respectively. In order to evaluate the effects of PMF on the DNA synthesis of cancer cells and the incorporation of antitumor agent into cancer cells, cultured cells or solid tumor were exposed to PMF generated by a solenoid coil immediately after 3H-or 14C-thymidine and 3H-methotrexate administration respectively. Thymidine uptake was found to increase by exposure to PMF, as did also 3H-methotrexate uptake by leukemic T-cells. Following exposure to PMF immediately after administration of methotrexate or mitomycin C, antitumor activity in both cells was increased. From these results it appears that the incorporation of antitumor agents into the cells increases by eddy current stimulation induced by PMF, and that the cell cycle shifts from the non-proliferative to proliferative phase, resulting in increased antitumor activity.</p>
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<td width="574">Anticancer Res. 1987 May-Jun;7(3 Pt B):391-3.</td>
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<h1>Tumoricidal cells increased by pulsating magnetic field.</h1>
<p>Malter M, Schriever G, Kuhnlein R, Suss R. </p>
<p>Repeated applications of pulsed magnetic fields (right-angle waves, 50 Hz = 135 Gauss, 2 Hz = 262 Gauss) significantly enhanced the number and the tumoricidal activity of nonparenchymal liver cells. The transplantable mouse leukemia L1210 used as a tumor model was not significantly influenced, either directly or during Cyclophosphamide treatment</p>
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<td width="572">Vopr Onkol. 1980;26(1):28-34.</td>
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<h1>Morphological criteria of lung cancer regression under the effect of magnetotherapy.</h1>
<p>[Article in Russian] </p>
<p>Ogorodnikova LS, Gairabed&#8217;iants NG, Ratner ON, Chirvina ED, Sem LD. </p>
<p>The complex investigation (histological, histochemical, morphological, electrone microscopy) of lung cancerous tumors from 20 patients, subjected preoperatively to the action of magnetic fields enhancing the antitumor resistance by developing general nonspecific adaptation reactions: activation and training, has revealed a number of morphological changes which indicate a marked antitumor effect of magnetic fields. These changes were maximum manifest after 20-30 sessions. High-differentiated adenocarcinoma proved to be mostly sensitive to the magnetic field action. </p>
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		<title>Arterial Dilation by Phototherapy</title>
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		<pubDate>Sun, 04 Mar 2012 17:47:24 +0000</pubDate>
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		<description><![CDATA[Cardiovasc Res.  2009 Sep 1;83(4):785-92. Epub 2009 May 14. Low-level laser irradiation inhibits abdominal aortic aneurysm progression in apolipoprotein E-deficient mice. Gavish L, Rubinstein C, Bulut A, Berlatzky Y, Beeri R, Gilon D, Gavish L, Harlev M, Reissman P, Gertz SD. Source Department of Anatomy, The Hebrew University-Hadassah Medical School, PO Box 12272, Jerusalem 91120, [...]]]></description>
			<content:encoded><![CDATA[<div>
<div>Cardiovasc Res.  2009 Sep 1;83(4):785-92. Epub  2009 May 14.</div>
<h1>Low-level laser irradiation inhibits abdominal aortic aneurysm progression in apolipoprotein E-deficient mice.</h1>
<div>Gavish L, Rubinstein C, Bulut A, Berlatzky Y, Beeri R, Gilon D, Gavish L, Harlev M, Reissman P, Gertz SD.</div>
<div>
<p><strong>Source</strong></p>
<p>Department of Anatomy, The Hebrew University-Hadassah Medical School, PO Box 12272, Jerusalem 91120, Israel.</p>
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<div>
<p><strong>Abstract</strong></p>
<p><strong>AIMS:</strong></p>
<p>Increased early detection of abdominal aortic aneurysm (AAA) and the severe complications of its current treatment have emphasized the need for alternative therapeutic strategies that target pathogenetic mechanisms of progression and rupture. Recent in vitro studies from our laboratory have shown that low-level laser irradiation (LLLI) (780 nm) modifies cellular processes fundamental to aneurysm progression. The present study was designed to determine whether LLLI retards the progression of suprarenal AAA in vivo.</p>
<p><strong>METHODS AND RESULTS:</strong></p>
<p>High-frequency ultrasonography (0.01 mm resolution) was used to quantify the effect of LLLI on aneurysmatic aortic dilatation from baseline to 4 weeks after subcutaneous infusion of angiotensin II by osmotic minipumps in the apolipoprotein E-deficient mouse. At 4 weeks, seven of 15 non-irradiated, but none of the 13 LLLI, mice had aneurysmal dilatation in the suprarenal aneurysm-prone segments that had progressed to &gt;or=50% increase in maximal cross-sectional diameter (CSD) over baseline (P = 0.005 by Fisher&#8217;s exact test). The mean CSD of the suprarenal segments (normalized individually to inter-renal control segments) was also significantly lower in irradiated animals (LLLI vs. non-irradiated: 1.32 +/- 0.14 vs. 1.82 +/- 0.39, P = 0.0002 by unpaired, two-tailed t-test) with a 94% reduction in CSD at 4 weeks compared with baseline. M-mode ultrasound data showed that reduced radial wall velocity seen in non-treated was significantly attenuated in the LLLI mice, suggesting a substantial effect on arterial wall elasticity.</p>
<p><strong>CONCLUSION:</strong></p>
<p>These in vivo studies, together with previous in vitro studies from this laboratory, appear to provide strong evidence in support of a role for LLLI in the attenuation of aneurysm progression. Further studies in large animals would appear to be the next step towards testing the applicability of this technology to the human interventional setting.</p>
</div>
<p>J Hypertens.  2009 Aug;27(8):1631-40.</p>
</div>
<h1>Light-induced vs. bradykinin-induced relaxation of coronary arteries: do S-nitrosothiols act as endothelium-derived hyperpolarizing factors?</h1>
<div>Batenburg WW, Kappers MH, Eikmann MJ, Ramzan SN, de Vries R, Danser AH.</div>
<div>
<p><strong>Source</strong></p>
<p>Department of Internal Medicine, Division of Pharmacology, Vascular and Metabolic Diseases, Erasmus Medical Center, Rotterdam 3015 GE, The Netherlands.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p><strong>BACKGROUND:</strong></p>
<p>Light-induced relaxation depends on S-nitrosothiols. S-Nitrosothiols may also serve as endothelium-derived hyperpolarizing factors, mediating the relaxant response of porcine coronary arteries (PCAs) to bradykinin. Here we compared the mechanism of light-induced and bradykinin-induced PCA relaxation.</p>
<p><strong>METHODS:</strong></p>
<p>PCAs were mounted in organ baths in the dark, preconstricted and exposed to polychromatic light (5 min) or 100 nmol/l bradykinin.</p>
<p><strong>RESULTS:</strong></p>
<p>Light relaxed PCAs by maximally 71 +/- 1%. S-Nitrosothiol depletion abolished this relaxation. Relaxations diminished following repetitive light exposures, particularly if the dark periods between the light exposures were less than 10 min, and increased following endothelium removal or nitric oxide synthase blockade with N(omega)-nitro-L-arginine methyl ester (L-NAME), despite the prevention of guanosine-3&#8242;,5&#8242;-cyclic monophosphate generation by the latter two procedures. Thus, reloading of the storage pools occurs in the dark, endothelial nitric oxide inhibits this process and photorelaxation does not depend on guanosine-3&#8242;,5&#8242;-cyclic monophosphate. Bradykinin relaxed PCAs by 69 +/- 3%. The nitric oxide scavenger hydroxocobalamin and the Na+-K+ ATPase inhibitor ouabain abolished the responses to bradykinin and light. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one abolished the response to light, and, like L-NAME, blocked the response to bradykinin by more than 50%. On top of L-NAME, intermediate and small conductance Ca2+-dependent K+ channel (IKCa/SKCa) blockade further reduced the response to bradykinin and enhanced photorelaxation.</p>
<p><strong>CONCLUSION:</strong></p>
<p>Photorelaxation depends on stored S-nitrosothiols and their release/synthesis is negatively affected by endothelial nitric oxide and IKCa/SKCa. S-Nitrosothiols activate endothelial IKCa/SKCa and, via guanylyl cyclase, smooth muscle Na+-K+ ATPase. Thus, they possess all properties of a bradykinin-induced endothelium-derived hyperpolarizing factor.</p>
<div>Br J Pharmacol.  2003 Mar;138(5):932-40.</div>
<h1>A photosensitive vascular smooth muscle store of nitric oxide in mouse aorta: no dependence on expression of endothelial nitric oxide synthase.</h1>
<div>Andrews KL, McGuire JJ, Triggle CR.</div>
<div>
<p><strong>Source</strong></p>
<p>Smooth Muscle Research Group, 3330 Hospital Dve, NW, University of Calgary, Calgary, Alberta, Canada, T2N 4N1.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p>(1) Photorelaxation is the reversible relaxation of vascular smooth muscle (VSM) when irradiated with ultraviolet (UV) light resulting from the release of nitric oxide (NO). In this study we characterize the involvement of endothelial nitric oxide synthase (eNOS) in the photorelaxation response of thoracic aorta from endothelial NOS deficient (-/-) and control (C57BL/6j) mice. (2) Cirazoline contracted aortae were repeatedly exposed to 30 s of UV light every 3-4 min. Equal levels of photorelaxation (45+/-2%; n=34) was observed in both strains. (3) 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), K(+), 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), 4-aminopyridine (4-AP) and ethacrynic acid significantly reduced the photorelaxation response. In C57BL/6j mice diethyldithiocarbamate (DETCA) also reduced photorelaxation. (4) Control endothelium-intact and -denuded aorta and L-NAME (100 micro M) treated and untreated eNOS (-/-) aortae were repeatedly exposed to UV light for 5 min every 10 min until no photorelaxation response was observed. After 1 h of rest in the dark the vessels showed between 30-70% recovery of the photorelaxation response indicating regeneration of the store in the absence of the endothelium and eNOS. (5) The results of this study suggest that photorelaxation in mouse aorta VSM results from the release of NO from a stable store of RSNOs, which activates soluble guanylate cyclase (sGC), leading to cGMP-dependent relaxation that is partially mediated by an increase in K(V) channel activation and hyperpolarization. In addition, the eNOS isoform is not essential for the formation of the photorelaxation store and a non-NOS source of NO may be involved in the maintenance of this store.</p>
<div>Lasers Surg Med.  2000;27(5):427-37.</div>
<h1>Effects of near-infrared low-level laser irradiation on microcirculation.</h1>
<div>Maegawa Y, Itoh T, Hosokawa T, Yaegashi K, Nishi M.</div>
<div>
<p><strong>Source</strong></p>
<p>Department of Anesthesiology, Kyoto Prefectural University of Medicine, Japan.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p><strong>BACKGROUND AND OBJECTIVE:</strong></p>
<p>Recently, there has been an increase in the clinical application of low-level laser irradiation (LLLI) in various fields. The present study was conducted to explore the effects of LLLI on microcirculation.</p>
<p><strong>STUDY DESIGN/MATERIAL AND METHODS: </strong></p>
<p>We investigated the effects of LLLI on rat mesenteric microcirculation in vivo, and on cytosolic calcium concentration ([Ca2+]i) in rat vascular smooth muscle cells (VSMCs) in vitro.</p>
<p><strong>RESULTS:</strong></p>
<p>LLLI caused potent dilation in the laser-irradiated arteriole, which led to marked increases in the arteriolar blood flow. The changes were partly attenuated in the initial phase by the superfusion of 15 microM L-NAME, but they were not affected by local denervation. Furthermore, LLLI caused a power-dependent decrease in [Ca2+]i in VSMCs.</p>
<p><strong>CONCLUSION:</strong></p>
<p>The circulatory changes observed seemed to be mediated largely by LLLI-induced reduction of [Ca2+]i in VSMCs, in addition to the involvement of NO in the initial phase.</p>
</div>
</div>
</div>
]]></content:encoded>
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		</item>
		<item>
		<title>Aquired Immune Deficiency Syndrome (AIDS)</title>
		<link>http://www.healinglightseminars.com/bioelectromagnetic-research-library/aquired-immune-deficiency-syndrome-aids/</link>
		<comments>http://www.healinglightseminars.com/bioelectromagnetic-research-library/aquired-immune-deficiency-syndrome-aids/#comments</comments>
		<pubDate>Sat, 25 Feb 2012 20:50:06 +0000</pubDate>
		<dc:creator>Hldavid</dc:creator>
				<category><![CDATA[Bioelectromagnetic Research Library]]></category>

		<guid isPermaLink="false">http://www.healinglightseminars.com/?p=9001</guid>
		<description><![CDATA[Recent Pat Antiinfect Drug Discov. 2012 Feb 17. [Epub ahead of print] Safety and Efficacy of Setarud (IMOD(TM)) Among People Living with HIV/AIDS: A Review. Paydary K, Emamzadeh-Fard S, Khorshid HR, Kamali K, Seyed Alinaghi S, Mohraz M. Source IRCHA, Imam Khomeini Hospital, Keshavarz Blvd., Tehran, Iran. s_a_alinaghi@yahoo.com Abstract The broad use of highly active [...]]]></description>
			<content:encoded><![CDATA[<div>Recent Pat Antiinfect Drug Discov. 2012 Feb 17. [Epub ahead of print]</div>
<h1>Safety and Efficacy of Setarud (IMOD(TM)) Among People Living with HIV/AIDS: A Review.</h1>
<div>Paydary K, Emamzadeh-Fard S, Khorshid HR, Kamali K, Seyed Alinaghi S, Mohraz M.</div>
<div>
<p><strong>Source</strong></p>
<p>IRCHA, Imam Khomeini Hospital, Keshavarz Blvd., Tehran, Iran. <a href="mailto:s_a_alinaghi@yahoo.com">s_a_alinaghi@yahoo.com</a></p>
<p><strong>Abstract</strong></p>
</div>
<div>
<p>The broad use of highly active anti-retroviral therapy (HAART), especially in developing world, has been associated with several problems such as<br />
lactic acidosis, lipodistrophy, pancreatitis, hyperlipidemia, insulin resistance and hepatotoxicity. Extensive use of HAART has also resulted<br />
in emergence of resistant HIV variants. Thereby, a pressing need for development of novel and cost-effective agents arises from these<br />
limitations. Setarud (IMOD(TM)) is a safe, naturally-derived immunomodulator that was introduced for treatment of HIV patients in<br />
Iran. It is prepared as a mixture of herbal extracts including Tanacetum vulgare (tansy), Rosa canina and Urtica dioica (nettle) in addition to<br />
selenium, flavonoids and carotenes. Tanacetum vulgare may relieve anti-inflammatory symptoms and Rosa canina defers blood glucose and<br />
cholesterol elevation. Extracts from Urtica dioica may prevent maturation of myeloid dendritic cells and reduce T cell responses. A<br />
significant rise of CD4 count was observed in HIV patients treated by IMOD(TM) in clinical trial phases, which could be explained by its<br />
immunomodulatory effects. Anti-oxidative activity of compounds in IMOD(TM) might play a role in the clinical outcomes of patients treated<br />
with this drug. Moreover, IMOD(TM) may show improving activity upon lipid profile and liver metabolism. According to studies on IMOD(TM), it<br />
seems that IMOD(TM) has minor side effects. IMOD(TM) with international publication number WO 2007/087825 A1 is an herbal extract which<br />
includes Rosa canina, Urtica dioica, Tanacetum vulgare, and selenium comprising a treatment by pulsed electromagnetic field of high frequency<br />
and is useful in treatment of HIV infection and AIDS.</p>
<div>Int J Nanomedicine. 2010 Apr 7;5:157-66.</div>
<div>
<div>
<h1>Magnetic nanoformulation of azidothymidine 5&#8242;-triphosphate for targeted delivery across the blood-brain barrier.</h1>
<div>Saiyed ZM, Gandhi NH, Nair MP.</div>
<div>
<p><strong>Source</strong></p>
<p>Department of Immunology, College of Medicine, Florida International University, Miami, FL, USA.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p>Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood-brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5&#8242;-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS.</p>
<div>J Neurovirol. 2009 Jul;15(4):343-7.</div>
<h1>AZT 5&#8242;-triphosphate nanoformulation suppresses human immunodeficiency virus type 1 replication in peripheral blood mononuclear cells.</h1>
<div>Saiyed ZM, Gandhi NH, Nair MP.</div>
<div>
<p><strong>Source</strong></p>
<p>Department of Immunology, College of Medicine, Florida International University, Miami, Florida 33199, USA.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p>Inefficient cellular phosphorylation of nucleoside and nucleotide analog reverse transcriptase inhibitors (NRTIs) to their active nucleoside 5&#8242;-triphosphate (NTPs) form is one of the limitations for human immunodeficiency virus (HIV) therapy. We report herein direct binding of 3&#8242;-azido-3&#8242;-deoxythymidine-5&#8242;-triphosphate (AZTTP) onto magnetic nanoparticles (Fe(3)O(4); magnetite) due to ionic interaction. This magnetic nanoparticle bound AZTTP (MP-AZTTP) completely retained its biological activity as assessed by suppression of HIV-1 replication in peripheral blood mononuclear cells. The developed MP-AZTTP nanoformulation can be used for targeting active NRTIs to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat NeuroAIDs.</p>
<p>Int J Pharm. 2008 Mar 3;351(1-2):271-81. Epub 2007 Sep 22.</p>
<h1>Electromagnetic interference in the permeability of saquinavir across the blood-brain barrier using nanoparticulate carriers.</h1>
<div>Kuo YC, Kuo CY.</div>
<div>
<p><strong>Source</strong></p>
<p>Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102, Republic of China. <a href="mailto:chmyck@ccu.edu.tw">chmyck@ccu.edu.tw</a></p>
<p><strong>Abstract</strong></p>
</div>
<div>
<p>Transport of antiretroviral agents across the blood-brain barrier (BBB) is of key importance to the treatment for the acquired immunodeficiency syndrome (AIDS). In this study, impact of exposure to electromagnetic field (EMF) on the permeability of saquinavir (SQV) across BBB was investigated. The in vitro BBB model was based on human brain-microvascular endothelial cells (HBMEC), and the concentration of SQV in receiver chamber of the transport system was evaluated. Polybutylcyanoacrylate (PBCA), methylmethacrylate-sulfopropylmethacrylate (MMA-SPM), and solid lipid nanoparticle (SLN) were employed as carriers for the delivery systems. Cytotoxicity of SLN decreased as content of cacao butter increased. Power of 5mV was apposite for the study on HBMEC without obvious apoptosis. Square wave produced greater permeability than sine and triangle waves. The carrier order on permeability of SQV across HBMEC monolayer under exposure to EMF was SLN&gt;PBCA&gt;MMA-SPM. Also, a larger frequency, modulation or depth of amplitude modulation (AM), or modulation or deviation of frequency modulation (FM) yielded a greater permeability. Besides, enhancement of permeability by AM wave was more significant than that by FM wave. Transport behavior of SQV across BBB was strongly influenced by the combination of nanoparticulate PBCA, MMA-SPM, and SLN with EMF exposure. This combination would be beneficial to the clinical application to the therapy of AIDS and other brain-related diseases.</p>
<div>Panminerva Med.  1995 Mar;37(1):22-7.</div>
<h1>A magnetic approach to AIDS.</h1>
<div>Jacobson JI</div>
<div><strong>Source</strong></div>
<div>
<p>Institute of Theoretical Physics and Advanced Studies for Biophysical Res, Jupiter, FL 334377-1418, USA.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p>Jacobson Resonance is the unified field equation yielding a frontier vision in magnetotherapy. The possible application to AIDS is considered.</p>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
]]></content:encoded>
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		<slash:comments>0</slash:comments>
		</item>
		<item>
		<title>HIV / AIDs</title>
		<link>http://www.healinglightseminars.com/bioelectromagnetic-research-library/hiv-aids/</link>
		<comments>http://www.healinglightseminars.com/bioelectromagnetic-research-library/hiv-aids/#comments</comments>
		<pubDate>Sat, 25 Feb 2012 14:52:53 +0000</pubDate>
		<dc:creator>Hldavid</dc:creator>
				<category><![CDATA[Bioelectromagnetic Research Library]]></category>

		<guid isPermaLink="false">http://www.healinglightseminars.com/?p=8991</guid>
		<description><![CDATA[Recent Pat Antiinfect Drug Discov.   2012 Feb 17. [Epub ahead of print] Safety and Efficacy of Setarud (IMOD(TM)) Among People Living with HIV/AIDS: A Review. Paydary K, Emamzadeh-Fard S, Khorshid HR, Kamali K, Seyed Alinaghi S, Mohraz M. Source IRCHA, Imam Khomeini Hospital, Keshavarz Blvd., Tehran, Iran. s_a_alinaghi@yahoo.com Abstract The broad use of highly active [...]]]></description>
			<content:encoded><![CDATA[<div class="cit">Recent Pat Antiinfect Drug Discov.   2012 Feb 17. [Epub ahead of print]</div>
<h1>Safety and Efficacy of Setarud (IMOD(TM)) Among People Living with HIV/AIDS: A Review.</h1>
<div class="auths">Paydary K, Emamzadeh-Fard S, Khorshid HR, Kamali K, Seyed Alinaghi S, Mohraz M.</div>
<div class="aff">
<p class="label"><strong>Source</strong></p>
<p>IRCHA, Imam Khomeini Hospital, Keshavarz Blvd., Tehran, Iran. <a href="mailto:s_a_alinaghi@yahoo.com">s_a_alinaghi@yahoo.com</a></p>
<p><strong>Abstract</strong></p>
</div>
<div class="abstr">
<p>The broad use of highly active anti-retroviral therapy (HAART), especially in developing world, has been associated with several problems such as<br />
lactic acidosis, lipodistrophy, pancreatitis, hyperlipidemia, insulin resistance and hepatotoxicity. Extensive use of HAART has also resulted<br />
in emergence of resistant HIV variants. Thereby, a pressing need for development of novel and cost-effective agents arises from these<br />
limitations. Setarud (IMOD(TM)) is a safe, naturally-derived immunomodulator that was introduced for treatment of HIV patients in<br />
Iran. It is prepared as a mixture of herbal extracts including Tanacetum vulgare (tansy), Rosa canina and Urtica dioica (nettle) in addition to<br />
selenium, flavonoids and carotenes. Tanacetum vulgare may relieve anti-inflammatory symptoms and Rosa canina defers blood glucose and<br />
cholesterol elevation. Extracts from Urtica dioica may prevent maturation of myeloid dendritic cells and reduce T cell responses. A<br />
significant rise of CD4 count was observed in HIV patients treated by IMOD(TM) in clinical trial phases, which could be explained by its<br />
immunomodulatory effects. Anti-oxidative activity of compounds in IMOD(TM) might play a role in the clinical outcomes of patients treated<br />
with this drug. Moreover, IMOD(TM) may show improving activity upon lipid profile and liver metabolism. According to studies on IMOD(TM), it<br />
seems that IMOD(TM) has minor side effects. IMOD(TM) with international publication number WO 2007/087825 A1 is an herbal extract which<br />
includes Rosa canina, Urtica dioica, Tanacetum vulgare, and selenium comprising a treatment by pulsed electromagnetic field of high frequency<br />
and is useful in treatment of HIV infection and AIDS.</p>
<div>Int J Nanomedicine.  2010 Apr 7;5:157-66.</div>
<div>
<div>
<h1>Magnetic nanoformulation of azidothymidine 5&#8242;-triphosphate for targeted delivery across the blood-brain barrier.</h1>
<div>Saiyed ZM, Gandhi NH, Nair MP.</div>
<div>
<p><strong>Source</strong></p>
<p>Department of Immunology, College of Medicine, Florida International University, Miami, FL, USA.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p>Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood-brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5&#8242;-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS.</p>
<div>J Neurovirol.  2009 Jul;15(4):343-7.</div>
<h1>AZT 5&#8242;-triphosphate nanoformulation suppresses human immunodeficiency virus type 1 replication in peripheral blood mononuclear cells.</h1>
<div>Saiyed ZM, Gandhi NH, Nair MP.</div>
<div>
<p><strong>Source</strong></p>
<p>Department of Immunology, College of Medicine, Florida International University, Miami, Florida 33199, USA.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p>Inefficient cellular phosphorylation of nucleoside and nucleotide analog reverse transcriptase inhibitors (NRTIs) to their active nucleoside 5&#8242;-triphosphate (NTPs) form is one of the limitations for human immunodeficiency virus (HIV) therapy. We report herein direct binding of 3&#8242;-azido-3&#8242;-deoxythymidine-5&#8242;-triphosphate (AZTTP) onto magnetic nanoparticles (Fe(3)O(4); magnetite) due to ionic interaction. This magnetic nanoparticle bound AZTTP (MP-AZTTP) completely retained its biological activity as assessed by suppression of HIV-1 replication in peripheral blood mononuclear cells. The developed MP-AZTTP nanoformulation can be used for targeting active NRTIs to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat NeuroAIDs.</p>
<p>Int J Pharm.  2008 Mar 3;351(1-2):271-81. Epub 2007 Sep 22.</p>
<h1>Electromagnetic interference in the permeability of saquinavir across the blood-brain barrier using nanoparticulate carriers.</h1>
<div>Kuo YC, Kuo CY.</div>
<div>
<p><strong>Source</strong></p>
<p>Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102, Republic of China. <a href="mailto:chmyck@ccu.edu.tw">chmyck@ccu.edu.tw</a></p>
<p><strong>Abstract</strong></p>
</div>
<div>
<p>Transport of antiretroviral agents across the blood-brain barrier (BBB) is of key importance to the treatment for the acquired immunodeficiency syndrome (AIDS). In this study, impact of exposure to electromagnetic field (EMF) on the permeability of saquinavir (SQV) across BBB was investigated. The in vitro BBB model was based on human brain-microvascular endothelial cells (HBMEC), and the concentration of SQV in receiver chamber of the transport system was evaluated. Polybutylcyanoacrylate (PBCA), methylmethacrylate-sulfopropylmethacrylate (MMA-SPM), and solid lipid nanoparticle (SLN) were employed as carriers for the delivery systems. Cytotoxicity of SLN decreased as content of cacao butter increased. Power of 5mV was apposite for the study on HBMEC without obvious apoptosis. Square wave produced greater permeability than sine and triangle waves. The carrier order on permeability of SQV across HBMEC monolayer under exposure to EMF was SLN&gt;PBCA&gt;MMA-SPM. Also, a larger frequency, modulation or depth of amplitude modulation (AM), or modulation or deviation of frequency modulation (FM) yielded a greater permeability. Besides, enhancement of permeability by AM wave was more significant than that by FM wave. Transport behavior of SQV across BBB was strongly influenced by the combination of nanoparticulate PBCA, MMA-SPM, and SLN with EMF exposure. This combination would be beneficial to the clinical application to the therapy of AIDS and other brain-related diseases.</p>
<div>
<div>Panminerva Med. 1995 Mar;37(1):22-7.</div>
<h1>A magnetic approach to AIDS.</h1>
<div>Jacobson JI</div>
<div><strong>Source</strong></div>
<div>
<p>Institute of Theoretical Physics and Advanced Studies for Biophysical Res, Jupiter, FL 334377-1418, USA.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p>Jacobson Resonance is the unified field equation yielding a frontier vision in magnetotherapy. The possible application to AIDS is considered.</p>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
]]></content:encoded>
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		<slash:comments>0</slash:comments>
		</item>
		<item>
		<title>Central Nervous System Disorders</title>
		<link>http://www.healinglightseminars.com/bioelectromagnetic-research-library/central-nervous-system-disorders-2/</link>
		<comments>http://www.healinglightseminars.com/bioelectromagnetic-research-library/central-nervous-system-disorders-2/#comments</comments>
		<pubDate>Sat, 11 Feb 2012 14:31:48 +0000</pubDate>
		<dc:creator>Hldavid</dc:creator>
				<category><![CDATA[Bioelectromagnetic Research Library]]></category>

		<guid isPermaLink="false">http://www.healinglightseminars.com/?p=8977</guid>
		<description><![CDATA[Altern Ther Health Med.  2011 Nov-Dec;17(6):22-8. Long-term Effects of Bio-electromagnetic-energyregulation Therapy on Fatigue in Patients With Multiple Sclerosis. Ziemssen T, Piatkowski J, Haase R. Abstract Background Electromagnetic-field therapy has beneficial short-term effects in multiple sclerosis (MS) patients with major fatigue, but long-term data are lacking. Primary Study Objectives To evaluate the long-term effects of a [...]]]></description>
			<content:encoded><![CDATA[<table style="height: 1px;" border="0" cellspacing="0" cellpadding="0">
<tbody>
<tr>
<td width="573">
<div>Altern Ther Health Med.  2011 Nov-Dec;17(6):22-8.</div>
<h1>Long-term Effects of Bio-electromagnetic-energyregulation Therapy on Fatigue in Patients With Multiple Sclerosis.</h1>
<div>Ziemssen T, Piatkowski J, Haase R.</div>
<div>
<p><strong>Abstract</strong></p>
<p>Background Electromagnetic-field therapy has beneficial short-term effects in multiple sclerosis (MS) patients with major fatigue, but long-term data are lacking.</p>
<p>Primary Study Objectives To evaluate the long-term effects of a specific electromagnetic therapy device (Bio-Electromagnetic- Energy-Regulation [BEMER]) on MS-related fatigue, we designed a crossover control of a previously performed randomized controlled trial and a long-term open-label follow-up trial.</p>
<p>Design and Setting: Crossover and open-label follow-up trials at a single neurological outpatient center. Participants Patients with relapsing-remitting MS who had major fatigue (N = 37 patients). Intervention After a previous randomized controlled trial (exposure to low-frequency pulsed magnetic fields for 8 min twice daily or to placebo treatment for 12 wk), a crossover from control to treatment for another 12 weeks, followed by an openlabel follow-up trial to 3 years, were done.</p>
<p>Primary Outcome Measures The outcome criteria were the Modified Fatigue Impact Scale (MFIS), Fatigue Severity Scale (FSS), German long version of the Center for Epidemiologic Studies Depression Scale (CES-D), Multiple Sclerosis Functional Scale (MSFC), and Expanded Disability Status Scale (EDSS). Results Patients previously on placebo during the randomized controlled trial experienced significant reductions in fatigue after crossing over to treatment. The MFIS and FSS scores were significantly lower in the open-label group than in the control subjects after follow-up. Participation in the open-label treatment was the strongest predictor of low fatigue outcome after followup. Electromagnetic-field therapy was well tolerated.</p>
<p>Conclusions In this long-term study, a beneficial effect of long-term BEMER therapy on MS fatigue was demonstrated. Electromagnetic-field therapy may be a useful therapeutic modality in MS patients with severe fatigue.</p>
</div>
<div> J Recept Signal Transduct Res. 2010 Aug;30(4):214-26.</div>
<h1>Electromagnetic fields: mechanism, cell signaling, other bioprocesses, toxicity, radicals, antioxidants and beneficial effects.</h1>
<p>Kovacic P, Somanathan R.</p>
<p>Department of Chemistry, San Diego State University, San Diego, California, USA. <a href="mailto:pkovacic@sundown.sdsu.edu">pkovacic@sundown.sdsu.edu</a></p>
<h3>Abstract</h3>
<p>Electromagnetic fields (EMFs) played a role in the initiation of living systems, as well as subsequent evolution. The more recent literature on electrochemistry is documented, as well as magnetism. The large numbers of reports on interaction with living systems and the consequences are presented. An important aspect is involvement with cell signaling and resultant effects in which numerous signaling pathways participate. Much research has been devoted to the influence of man-made EMFs, e.g., from cell phones and electrical lines, on human health. The degree of seriousness is unresolved at present. The relationship of EMFs to reactive oxygen species (ROS) and oxidative stress (OS) is discussed. There is evidence that indicates a relationship involving EMFs, ROS, and OS with toxic effects. Various articles deal with the beneficial aspects of antioxidants (AOs) in countering the harmful influence from ROS-OS associated with EMFs. EMFs are useful in medicine, as indicated by healing bone fractures. Beneficial effects are recorded from electrical treatment of patients with Parkinson&#8217;s disease, depression, and cancer.</p>
<p>J Altern Complement Med.  2009 May;15(5):507-11.</p>
<h1>Effect of BEMER magnetic field therapy on the level of fatigue in patients with multiple sclerosis: a randomized, double-blind controlled trial.</h1>
<div>Piatkowski J, Kern S, Ziemssen T.</div>
<div>
<p><strong>Source</strong></p>
<p>Neurological Outpatient Center Reichenbachstrasse, Dresden, Germany.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p><strong>OBJECTIVES:</strong></p>
<p>Electromagnetic field therapy has been reported to be beneficial in patients with multiple sclerosis (MS) with significant fatigue. This study was designed to evaluate the long-term effects of Bio-Electro-Magnetic-Energy-Regulation (BEMER) on MS-related fatigue.</p>
<p><strong>DESIGN:</strong></p>
<p>This was a monocenter, patient- and rater-blinded, placebo-controlled trial.</p>
<p><strong>PATIENTS:</strong></p>
<p>There were 37 relapsing-remitting patients with MS with significant fatigue in the study.</p>
<p><strong>INTERVENTION:</strong></p>
<p>The intervention consisted of BEMER magnetic field treatment for 8 minutes twice daily in comparison to placebo for 12 weeks.</p>
<p><strong>OUTCOME MEASURES:</strong></p>
<p>The primary outcome criterion was change in the Modified Fatigue Impact Scale (MFIS) between baseline and 12 weeks. The secondary outcome criteria were changes of the Fatigue Severity Scale (FSS), a general depression scale-long version (ADS-L), Multiple Sclerosis Functional Scale (MSFC), and the Expanded Disability Status Scale (EDSS).</p>
<p><strong>RESULTS:</strong></p>
<p>There was evidence of a significant difference of MFIS value (primary outcome criterion) after 12 weeks in favor of the verum group (26.84 versus 36.67; p = 0.024). In addition, FSS values were significantly lower in the verum group after 12 weeks (3.5 versus 4.7; p = 0.016). After 6 weeks&#8217; follow-up, verum and placebo groups did not differ in experienced fatigue (MFIS, FSS). Regarding the subscales of the MFIS, there was a significant decrease in physical (p = 0.018) and cognitive (p = 0.041), but not in psychologic subscales only in the verum group regarding the timepoints baseline and 12 weeks. BEMER therapy was well tolerated.</p>
<p><strong>DISCUSSION:</strong></p>
<p>In this pilot study, we were able to demonstrate a beneficial effect of BEMER intervention on MS fatigue. As this was only a pilot study, trials with more patients and longer duration are mandatory to describe long-term effects.</p>
</div>
<p>Biolectromagn Biol Med. 2007;26(4):305-9.</p>
<h1>The autistic syndrome and endogenous ion cyclotron resonance: state of the art.</h1>
<p>Crescentini F.</p>
<p>Department of Bioelectromagnetic Research, I.R.P. L&#8217;Aquila, Pescara, Italy.</p>
<p>The autistic syndrome is a multigenic disease whose expression is different according to the level of involvement of different structures in the central nervous system. The pathogenesis is unknown. No completely effective medical therapy has yet been demonstrated. Accepting the request of the families of eight autistic children in Lomazzo, Milan and Naples, we used ion cyclotron resonance (Seqex(R) therapy) therapeutic support after many other therapies had been already carried out on these patients. After regimens consisting of 20-30 treatments with ICR, improvements were noted in all cases.</p>
<p>Int J Neurosci. 2006 Jul;116(7):775-826.</p>
<h1>Serotonergic mechanisms in amyotrophic lateral sclerosis.</h1>
<p>Sandyk R.</p>
<p>The Carrick Institute for Clinical Ergonomics Rehabilitation, and Applied Neurosciences, School of Engineering Technologies State University of New York at Farmingdale, Farmingdale, New York 11735, USA. rsandyk@optonline.net</p>
<p>Serotonin (5-HT) has been intimately linked with global regulation of motor behavior, local control of motoneuron excitability, functional recovery of spinal motoneurons as well as neuronal maturation and aging. Selective degeneration of motoneurons is the pathological hallmark of amyotrophic lateral sclerosis (ALS). Motoneurons that are preferentially affected in ALS are also densely innervated by 5-HT neurons (e.g., trigeminal, facial, ambiguus, and hypoglossal brainstem nuclei as well as ventral horn and motor cortex). Conversely, motoneuron groups that appear more resistant to the process of neurodegeneration in ALS (e.g., oculomotor, trochlear, and abducens nuclei) as well as the cerebellum receive only sparse 5-HT input. The glutamate excitotoxicity theory maintains that in ALS degeneration of motoneurons is caused by excessive glutamate neurotransmission, which is neurotoxic. Because of its facilitatory effects on glutaminergic motoneuron excitation, 5-HT may be pivotal to the pathogenesis and therapy of ALS. 5-HT levels as well as the concentrations 5-hydroxyindole acetic acid (5-HIAA), the major metabolite of 5-HT, are reduced in postmortem spinal cord tissue of ALS patients indicating decreased 5-HT release. Furthermore, cerebrospinal fluid levels of tryptophan, a precursor of 5-HT, are decreased in patients with ALS and plasma concentrations of tryptophan are also decreased with the lowest levels found in the most severely affected patients. In ALS progressive degeneration of 5-HT neurons would result in a compensatory increase in glutamate excitation of motoneurons. Additionally, because 5-HT, acting through presynaptic 5-HT1B receptors, inhibits glutamatergic synaptic transmission, lowered 5-HT activity would lead to increased synaptic glutamate release. Furthermore, 5-HT is a precursor of melatonin, which inhibits glutamate release and glutamate-induced neurotoxicity. Thus, progressive degeneration of 5-HT neurons affecting motoneuron activity constitutes the prime mover of the disease and its progression and treatment of ALS needs to be focused primarily on boosting 5-HT functions (e.g., pharmacologically via its precursors, reuptake inhibitors, selective 5-HT1A receptor agonists/5-HT2 receptor antagonists, and electrically through transcranial administration of AC pulsed picotesla electromagnetic fields) to prevent excessive glutamate activity in the motoneurons. In fact, 5HT1A and 5HT2 receptor agonists have been shown to prevent glutamate-induced neurotoxicity in primary cortical cell cultures and the 5-HT precursor 5-hydroxytryptophan (5-HTP) improved locomotor function and survival of transgenic SOD1 G93A mice, an animal model of ALS.</p>
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<p>Neuron. 2005 Jan 20;45(2):181-3.</td>
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<h1>Toward establishing a therapeutic window for rTMS by theta burst stimulation.</h1>
<p>Paulus W.</p>
<p>Department of Clinical Neurophysiology, University of Goettingen, D-37075 Goettingen, Germany.</p>
<p>In this issue of Neuron, Huang et al. show that a version of the classic theta burst stimulation protocol used to induce LTP/LTD in brain slices can be adapted to a transcranial magnetic stimulation (TMS) protocol to rapidly produce long lasting (up to an hour), reversible effects on motor cortex physiology and behavior. These results may have important implications for the development of clinical applications of rTMS in the treatment of depression, epilepsy, Parkinson&#8217;s, and other diseases.</p>
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<td width="573">Wiad Lek. 2003;56(9-10):434-41.</td>
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<h1>Application of variable magnetic fields in medicine-15 years experience.</h1>
<p>[Article in Polish]</p>
<p>Sieron A, Cieslar G.</p>
<p>Katedra i Klinika Chorob Wewnetrznych, Angiologii i Medycyny Fizykalnej SAM, ul. Batorego 15, 41-902 Bytom. sieron@mediclub.pl</p>
<p>The results of 15-year own experimental and clinical research on application of variable magnetic fields in medicine were presented. In experimental studies analgesic effect (related to endogenous opioid system and nitrogen oxide activity) and regenerative effect of variable magnetic fields with therapeutical parameters was observed. The influence of this fields on enzymatic and hormonal activity, free oxygen radicals, carbohydrates, protein and lipid metabolism, dielectric and rheological properties of blood as well as behavioural reactions and activity of central dopamine receptor in experimental animals was proved. In clinical studies high therapeutic efficacy of magnetotherapy and magnetostimulation in the treatment of osteoarthrosis, abnormal ossification, osteoporosis, nasosinusitis, multiple sclerosis, Parkinson&#8217;s disease, spastic paresis, diabetic polyneuropathy and retinopathy, vegetative neurosis, peptic ulcers, colon irritable and trophic ulcers was confirmed.</p>
<p>Adv Anat Embryol Cell Biol. 2003;173:III-IX, 1-77.</p>
<h1>Electric field-induced effects on neuronal cell biology accompanying dielectrophoretic trapping.</h1>
<p>Heida T.</p>
<p>University of Twente, Faculty of Electrical Engineering, Mathematics and Computer Science, Laboratory of Measurement and Instrumentation, Laboratory of Biomedical Engineering, P.O. Box 217, 7500 AE Enschede, The Netherlands. t.heida@el.utwente.nl</p>
<h3>Abstract</h3>
<p>Trapping neuronal cells may aid in the creation of the cultured neuron probe. The aim of the development of this probe is the creation of the interface between neuronal cells or tissue in a (human) body and electrodes that can be used to stimulate nerves in the body by an external electrical signal in a very selective way. In this way, functions that were (partially) lost due to nervous system injury or disease may be restored. First, a direct contact between cultured neurons and electrodes is created. This is realized using a microelectrode array (MEA) which can be fabricated using standard photolithographic and etching methods. Section 1 gives an overview of the human nervous system, methods for functional recovery focused on the cultured neuron probe, and the prerequisites for culturing neurons on a microelectrode array. An important aspect in the selective stimulation of neuronal cells is the positioning of cells or a small group of cells on top of each of the electrode sites of the MEA. One of the most efficient methods for trapping neuronal cells is to make use of di-electrophoresis (DEP). Dielectrophoretic forces are created when (polarizable) cells are located in nonuniform electric fields. Depending on the electrical properties of the cells and the suspending medium, the DEP force directs the cells towards the regions of high field strength (positive dielectrophoresis; PDEP) or towards regions of minimal field intensities (negative dielectrophoresis; NDEP). Since neurons require a physiological medium with a sufficient concentration of Na+, the medium conductivity is rather high (~ 1.6 S/m). The result is that negative dielectrophoretic forces are created over the entire frequency range. With the use of a planar quadrupole electrode sturcture negative forces are directed so that in the center of this structure cell can be collected. The process of trapping cortical rat neurons is described in Sect. 2 theoretically and experimentally. Medium and cell properties are frequency-dependent due to relaxation processes, which have a direct influence on the strength of the dielectrophorectic force. On the other hand, the nonideal material properties of the gold electrodes and glass substrate largely determine the electric field strength created inside the medium. Especially, the electrode-medium interface results in a significant loss of the imput signal at lower frequencies (&lt; 1 MHz), and thus a reduction of the electric field strength inside the medium. Furthermore, due to the high medium conductivity, the electric field causes Joule heating. Local temperature rises result in local gradients in fluid density, which induces fluid flow. The electrode-medium interface and induced fluid flow are theoretically investigated with the use of modeling techniques such as finite elements modeling. Experimental and theoretical results agreed with each other on the occurrence of the effects described in this section. For the creation of the cultured neuron probe, preservation of cell viability during the trapping process is a prerequisite. Cell viability of dielectrophoretically trapped neurons has to be investigated. The membrane potential induced by the external field plays a crucial role in preservation of cell viability. The membrane can effectively be represented by a capaticance in parallel woth a low conductance; with increasing frequency and /or decreasing field strength the induced membrane potential decreases. At high induced membrane potentials ths representation for the membrane is no longer valid. At this point membrane breakdown occurs and the normally insulating membrane becomes conductive and permeable. The creation of electropores has been proposed in literature to be the cause of this high permeability state. Pores may grow or many small pores may be created which eventually may lead to membrane rupture, and thus cell death. Membrane breakdown may be reversible, but a chemical imbalance created during the high permeability state may still exist after the resealing of the membrane. This may cause cell death after several hours or even days after field application. Section 3 gives a detailed description of membrane breakdown. Since many investigations on electroporation of lipid bilayers and cell membranes are based on uniform electric fields, a finite element model is used to investigate induced membrane potentials in the nonuniform field created by the quadropole electrode structure. Modeling results are presented in cmbination with the results of breakdown experiments using four frequencies in the range from 100 kHz to 1MHz. Radomly positioned neuronals cells were exposed to stepwise increasing electric field strengths. The field strength at which membrane rupture occurred gives an indication of the maximum induced membrane potential. Due to the nonuniformity of the electric field, cell collapse was expected to be position-dependent. However, at 100 kHz cells collapsed at a break down level of about 0.4 V, in contradistinction to findings at higher frequencies where more variation in breakdown levels were found. Model simulations were able to explain the experimental results. For examining whether the neuronal cells trapped by dielectrophoresis were still viable after the trapping process, the frequency range was divided into two ranges. First, a high frequency (14 MHz) and a rather low signal amplitude (3 Vpp) were used to trap cells. At this high frequency the field-induced membrane potential is small according to the theoretical model, and therefore no real damage is expected. The experimental analysis included the investigation of the growth of the neurons, number and length of the processes (dendrites and axons), and the number of outgrowing (~ viable) versus nonoutgrowing (~ nonviable) neural cells. The experimental results agreed with the expectation. The effect of the use of driving signals with lower frequencies and/or higher amplitudes on cell viability was investigated using a staining method as described in the second part of Sect. 4. Survival chances are not directly linked to the estimated maximum induced membrane potential. The frequency of the dield plays an important role, decreasing frequency lowering the chance of survival. A lower frequency limit of 100 kHz is preferable at field strengths less than 80 k V/m, while with increasing field strength this limit shifts towards higher frequencies. The theoretical and experimental results presented in this review form the inception of the development of new electrode structures for trapping neuronal cells on top of each of the electrodes of the MEA. New ways to investigate cell properties and the phenomenon of electroporation using electrokinetic methods were developed that can be exploited in future research linking cell biology to technology.</p>
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<td width="574">Curr Opin Neurol. 2000 Aug;13(4):397-405.</td>
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<h1>Recent advances in amotrophic lateral sclerosis.</h1>
<p>Al-Chalabi A, Leigh PN.</p>
<p>Department of Neurology, Guy&#8217;s King&#8217;s and St Thomas&#8217; School of Medicine and Institute of Psychiatry, De Crespigny Park, London, UK.</p>
<p>The mechanisms by which mutations of the SOD1 gene cause selective motor neuron death remain uncertain, although interest continues to focus on the role of peroxynitrite, altered peroxidase activity of mutant SOD1, changes in intracellular copper homeostasis, protein aggregation, and changes in the function of glutamate transporters leading to excitotoxicity. Neurofilaments and peripherin appear to play some part in motor neuron degeneration, and amyotrophic lateral sclerosis is occasionally associated with mutations of the neurofilament heavy chain gene. Linkage to several chromosomal loci has been established for other forms of familial amyotrophic lateral sclerosis, but no new genes have been identified. In the clinical field, interest has been shown in the population incidence and prevalence of amyotrophic lateral sclerosis and the clinical variants that cause diagnostic confusion. Transcranial magnetic stimulation has been used to detect upper motor neuron damage and to explore cortical excitability in amyotrophic lateral sclerosis, and magnetic resonance imaging including proton magnetic resonance spectroscopy and diffusion weighted imaging also provide useful information on the upper motor neuron lesion. Aspects of care including assisted ventilation, nutrition, and patient autonomy are addressed, and underlying these themes is the requirement to measure quality of life with a new disease-specific instrument. Progress has been made in developing practice parameters. Riluzole remains the only drug to slow disease progression, although interventions such as non-invasive ventilation and gastrostomy also extend survival.</p>
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<td width="573">Int J Neurosci. 1994 Jun;76(3-4):185-225.</td>
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<h1>Alzheimer&#8217;s disease: improvement of visual memory and visuoconstructive performance by treatment with picotesla magnetic fields.</h1>
<p>Sandyk R.</p>
<p>NeuroCommunication Research Laboratories, Danbury, CT 06811.</p>
<p>Impairments in visual memory and visuoconstructive functions commonly occur in patients with Alzheimer&#8217;s disease (AD). Recently, I reported that external application of electromagnetic fields (EMF) of extremely low intensity (in the picotesla range) and of low frequency (in the range of 5Hz-8Hz) improved visual memory and visuoperceptive functions in patients with Parkinson&#8217;s disease. Since a subgroup of Parkinsonian patients, specifically those with dementia, have coexisting pathological and clinical features of AD, I investigated in two AD patients the effects of these extremely weak EMF on visual memory and visuoconstructive performance. The Rey-Osterrieth Complex Figure Test as well as sequential drawings from memory of a house, a bicycle, and a man were employed to evaluate the effects of EMF on visual memory and visuoconstructive functions, respectively. In both patients treatment with EMF resulted in a dramatic improvement in visual memory and enhancement of visuoconstructive performance which was associated clinically with improvement in other cognitive functions such as short term memory, calculations, spatial orientation, judgement and reasoning as well as level of energy, social interactions, and mood. The report demonstrates, for the first time, that specific cognitive symptoms of AD are improved by treatment with EMF of a specific intensity and frequency. The rapid improvement in cognitive functions in response to EMF suggests that some of the mental deficits of AD are reversible being caused by a functional (i.e., synaptic transmission) rather than a structural (i.e., neuritic plaques) disruption of neuronal communication in the central nervous system.</p>
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<td width="574">Acupunct Electrother Res. 1992;17(2):107-48.</td>
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<h1>Common factors contributing to intractable pain and medical problems with insufficient drug intake in areas to be treated, and their pathogenesis and treatment: Part I. Combined use of medication with acupuncture, (+) Qi gong energy-stored material, soft laser or electrical stimulation.</h1>
<p><strong> </strong>Omura Y, Losco BM, Omura AK, Takeshige C, Hisamitsu T, Shimotsuura Y, Yamamoto S, Ishikawa H, Muteki T, Nakajima H, et al.</p>
<p>Heart Disease Research Foundation, New York.</p>
<p>Most frequently encountered causes of intractable pain and intractable medical problems, including headache, post-herpetic neuralgia, tinnitus with hearing difficulty, brachial essential hypertension, cephalic hypertension and hypotension, arrhythmia, stroke, osteo-arthritis, Minamata disease, Alzheimer&#8217;s disease and neuromuscular problems, such as Amyotrophic Lateral Sclerosis, and cancer are often found to be due to co-existence of 1) viral or bacterial infection, 2) localized microcirculatory disturbances, 3) localized deposits of heavy metals, such as lead or mercury, in affected areas of the body, 4) with or without additional harmful environmental electro-magnetic or electric fields from household electrical devices in close vicinity, which create microcirculatory disturbances and reduced acetylcholine. The main reason why medications known to be effective prove ineffective with intractable medical problems, the authors found, is that even effective medications often cannot reach these affected areas in sufficient therapeutic doses, even though the medications can reach the normal parts of the body and result in side effects when doses are excessive. These conditions are often difficult to treat or may be considered incurable in both Western and Oriental medicine. As solutions to these problems, the authors found some of the following methods can improve circulation and selectively enhance drug uptake: 1) Acupuncture, 2) Low pulse repetition rate electrical stimulation (1-2 pulses/second), 3) (+) Qi Gong energy, 4) Soft lasers using Ga-As diode laser or He-Ne gas laser, 5) Certain electro-magnetic fields or rapidly changing or moving electric or magnetic fields, 6) Heat or moxibustion, 7) Individually selected Calcium Channel Blockers, 8) Individually selected Oriental herb medicines known to reduce or eliminate circulatory disturbances. Each method has advantages and limitations and therefore the individually optimal method has to be selected. Applications of (+) Qi Gong energy stored paper or cloth every 4 hours, along with effective medications, were often found to be effective, as Qigongnized materials can often be used repeatedly, as long as they are not exposed to rapidly changing electric, magnetic or electro-magnetic fields. Application of (+) Qi Gong energy-stored paper or cloth, soft laser or changing electric field for 30-60 seconds on the area above the medulla oblongata, vertebral arteries or endocrine representation area at the tail of pancreas reduced or eliminated microcirculatory disturbances and enhanced drug uptake.(ABSTRACT TRUNCATED AT 400 WORDS)</p>
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<td width="573">Int J Neurosci. 1991 Aug;59(4):259-62.</td>
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<h1>Age-related disruption of circadian rhythms: possible relationship to memory impairment and implications for therapy with magnetic fields.</h1>
<p>Sandyk R, Anninos PA, Tsagas N.</p>
<p>Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461.</p>
<p>Disorganization of circadian rhythms, a hallmark of aging, may be related causally to the progressive deterioration of memory functions in senescence and possibly Alzheimer&#8217;s disease (AD). In experimental animals, disruption of circadian rhythms produces retrograde amnesia by interfering with the circadian organization of memory processes. The circadian system is known to be synchronized to external 24 h periodicities of ambient light by a neural pathway extending from the retina to the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. There is also evidence that the earth&#8217;s magnetic field is a time cue (&#8220;Zeitgeber&#8221;) of circadian organization and that shielding of the ambient magnetic field leads to disorganization of the circadian rhythms in humans. Since aging is associated with a delay of the circadian rhythm phase, and since light, which phase advances circadian rhythms, mimics the effects of magnetic fields on melatonin secretion, we postulate that application of magnetic fields might improve memory functions in the elderly as a result of resynchronization of the circadian rhythms. Moreover, since the circadian rhythm organization is more severely disrupted in patients with AD, it is possible that magnetic treatment might prove useful also in improving memory functions in these patients. If successful, application of magnetic fields might open new avenues in the management of memory disturbances in the elderly and possibly in AD.</p>
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<td width="574">Zh Nevropatol Psikhiatr Im S S Korsakova. 1990;90(7):108-12.</td>
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<h1>Regional cerebral angiodystonia in the practice of a neuropathologist and therapist.</h1>
<p>[Article in Russian]</p>
<p>Pokalev GM, Raspopina LA.</p>
<p>Altogether 108 patients with regional cerebral angiodystonia were examined using rheoencephalography, measurements of temporal and venous pressure and functional tests (nitroglycerin and bicycle ergometry). Three variants of abnormalities connected with regional cerebral angiodystonia were distinguished: dysfunction of the inflow, derangement of the venous outflow, and initial functional venous hypertonia. The patients were treated with nonmedicamentous therapy (electroanalgesia, magnetotherapy, iontotherapy).</p>
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<td width="573">Rev Neurol. 2004 Feb 16-29;38(4):374-80.</td>
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<h1>Transcranial magnetic stimulation. Applications in cognitive neuroscience.</h1>
<p>[Article in Spanish]</p>
<p>Calvo-Merino B, Haggard P.</p>
<p>Institute of Movement Neuroscience, University College, Londres, UK. b.calvo@ion.ucl.ac.uk</p>
<p>OBJECTIVE: In this review we trace some of the mayor developments in the use of transcranial magnetic stimulation (TMS) as a technique for the investigation of cognitive neuroscience. Technical aspects of the magnetic stimulation are also reviewed.</p>
<p>DEVELOPMENT: Among the many methods now available for studying activity of the human brain, magnetic stimulation is the only technique that allows us to interfere actively with human brain function. At the same time it provides a high degree of spatial and temporal resolution. Standard TMS applications (central motor conduction time, threshold and amplitude of motor evoked potentials) allow the evaluation of the motor conduction in the central nervous system and more complex TMS applications (paired pulse stimulation, silent period) permit study the mechanisms of diseases causing changes in the excitability of cortical areas. These techniques also allow investigation into motor disorder, epilepsy, cognitive function and psychiatric disorders.</p>
<p>CONCLUSIONS: Transcranial magnetic stimulation applications have an important place among the investigative tools to study cognitive functions and neurological and psychiatric disorders. Even so, despite the many published research and clinical studies, a systematic study about the possible diagnostic value and role in neurocognitive rehabilitation of TMS testing need to be realized to offer new possibilities of future applications.</p>
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<td width="574">Neuroreport. 2005 Nov 7;16(16):1849-1852.</td>
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<h1>Repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex affects strategic decision-making.</h1>
<p>Wout MV, Kahn RS, Sanfey AG, Aleman A.</p>
<p>aDepartment of Psychonomics, Helmholtz Research Institute, University of Utrecht bDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht cBCN NeuroImaging Center, Groningen, The Netherlands dDepartment of Psychology, University of Arizona, Tucson, Arizona, USA.</p>
<p>Although decision-making is typically seen as a rational process, emotions play a role in tasks that include unfairness. Recently, activation in the right dorsolateral prefrontal cortex during offers experienced as unfair in the Ultimatum Game was suggested to subserve goal maintenance in this task. This is restricted to correlational evidence, however, and it remains unclear whether the dorsolateral prefrontal cortex is crucial for strategic decision-making. The present study used repetitive transcranial magnetic stimulation in order to investigate the causal role of the dorsolateral prefrontal cortex in strategic decision-making in the Ultimatum Game. The results showed that repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex resulted in an altered decision-making strategy compared with sham stimulation. We conclude that the dorsolateral prefrontal cortex is causally implicated in strategic decision-making in healthy human study participants.</p>
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<td width="574">Trends Cogn Sci. 2005 Nov;9(11):503-5. Epub 2005 Sep 21.</td>
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<h1>Recharging cognition with DC brain polarization.</h1>
<p>Wassermann EM, Grafman J.</p>
<p>Brain Stimulation Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.</p>
<p>Electrical direct current (DC) has been applied to the human head throughout history for various reasons and with claims of behavioral effects and clinical benefits. This technique has recently been rediscovered and its effects validated with modern quantitative techniques and experimental designs. Despite the very weak current used, DC polarization applied to specific brain areas can alter verbal fluency, motor learning and perceptual thresholds, and can be used in conjunction with transcranial magnetic stimulation. Compact and safe, this old technique seems poised to allow major advances cognitive science and therapy.</p>
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<td width="572"><span style="text-decoration: underline;">J ECT.</span> 2005 Jun;21(2):88-95.</td>
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<h1>Transcranial magnetic stimulation in persons younger than the age of 18.</h1>
<p>Quintana H.</p>
<p>Department of Psychiatry, Division of Child and Adolescent Psychiatry, Louisiana State University Health Science Center, School of Medicine, New Orleans, Louisiana 70112-2822, USA. Hquint@lsuhsc.edu</p>
<p>OBJECTIVES: To review the use of transcranial magnetic stimulation (single-pulse TMS, paired TMS, and repetitive TMS [rTMS]) in persons younger than the age of 18 years. I discuss the technical differences, as well as the diagnostic, therapeutic, and psychiatric uses of TMS/rTMS in this age group.</p>
<p>METHODS: I evaluated English-language studies from 1993 to August 2004 on nonconvulsive single-pulse, paired, and rTMS that supported a possible role for the use of TMS in persons younger than 18. Articles reviewed were retrieved from the MEDLINE database and Clinical Scientific index.</p>
<p>RESULTS: The 48 studies reviewed involved a total of 1034 children ages 2 weeks to 18 years; 35 of the studies used single-pulse TMS (980 children), 3 studies used paired TMS (20 children), and 7 studies used rTMS (34 children). Three studies used both single and rTMS. However, the number of subjects involved was not reported.</p>
<p>CONCLUSIONS: Single-pulse TMS, paired TMS, and rTMS in persons younger than 18 has been used to examine the maturation/activity of the neurons of various central nervous system tracts, plasticity of neurons in epilepsy, other aspects of epilepsy, multiple sclerosis, myoclonus, transcallosal inhibition, and motor cortex functioning with no reported seizure risk. rTMS has been applied to psychiatric disorders such as ADHD, ADHD with Tourette&#8217;s, and depression. Adult studies support an antidepressant effect from repetitive TMS, but there is only one study that has been reported on 7 patients that used rTMS to the left dorsal prefrontal cortex on children/adolescents with depression (5 of the 7 subjects treated responded). Although there are limited studies using rTMS (in 34 children), these studies did not report significant adverse effects or seizures. Repetitive TMS safety, ethical, and neurotoxicity concerns also are discussed.</p>
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<td width="574">Biol Psychiatry. 2005 Jun 15;57(12):1597-600.</td>
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<h1>Transcranial magnetic stimulation-evoked cortical inhibition: a consistent marker of attention-deficit/hyperactivity disorder scores in tourette syndrome.</h1>
<p>Gilbert DL, Sallee FR, Zhang J, Lipps TD, Wassermann EM.</p>
<p>Division of Neurology, Cincinnati Children&#8217;s Hospital Medical Center and University of Cincinnati, OH 45229-3039, USA. d.gilbert@cchmc.org</p>
<p>BACKGROUND: Prior case-control studies using Transcranial Magnetic Stimulation (TMS) to probe the neural inhibitory circuitry of Attention Deficit Hyperactivity Disorder (ADHD), Tourette Syndrome (TS), and Obsessive Compulsive Disorder (OCD), have yielded conflicting results. Using regression analysis in TS patients with tics, ADHD, and/or OCD symptoms, all ranging from none to severe, we previously found that TMS-evoked short interval intracortical inhibition (SICI) correlated inversely with ADHD scores. We sought to validate this observation.</p>
<p>METHODS: We used regression to estimate the consistency of the association between ADHD symptom scores and TMS-evoked SICI at two separate visits in 28 children and adults with TS.</p>
<p>RESULTS: ADHD scores correlated significantly and consistently with SICI, particularly in patients not taking dopamine receptor blockers (r=.60 and r=.58). Hyperactivity, not inattention, scores accounted for ADHD-related variance in SICI.</p>
<p>CONCLUSIONS: SICI reliably reflects the severity of hyperactivity in children and adults with TS.</p>
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<td width="574">Child Adolesc Psychiatr Clin N Am. 2005 Jan;14(1):1-19, v.</td>
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<h1>Emerging brain-based interventions for children and adolescents: overview and clinical perspective.</h1>
<p>Hirshberg LM, Chiu S, Frazier JA.</p>
<p>The NeuroDevelopment Center, 260 West Exchange Street, Suite 302, Providence, RI 02903, USA. lhirshberg@neruodevelopmentcenter.com</p>
<p>Electroencephalogram biofeedback (EBF), repetitive transcranial magnetic stimulation (rTMS), and vagal nerve stimulation (VNS) are emerging interventions that attempt to directly impact brain function through neurostimulation and neurofeedback mechanisms. This article provides a brief overview of each of these techniques, summarizes the relevant research findings, and examines the implications of this research for practice standards based on the guidelines for recommending evidence based treatments as developed by the American Academy of Child and Adolescent Psychiatry for attention deficit hyperactivity disorder (ADHD). EBF meets the &#8220;Clinical Guidelines&#8221; standard for ADHD, seizure disorders, anxiety, depression, and traumatic brain injury. VNS meets this same standard for treatment of refractory epilepsy and meets the lower &#8220;Options&#8221; standard for several other disorders. rTMS meets the standard for &#8220;Clinical Guidelines&#8221; for bipolar disorder, unipolar disorder, and schizophrenia. Several conditions are discussed regarding the use of evidence based thinking related to these emerging interventions and future directions.</p>
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<td width="573"><span style="text-decoration: underline;">Curr Med Res Opin.</span> 2003;19(2):125-30.</td>
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<h1>Repetitive transcranial magnetic stimulation (rTMS): new tool, new therapy and new hope for ADHD.</h1>
<p>Acosta MT, Leon-Sarmiento FE.</p>
<p>Department of Neurology, Children&#8217;s National Medical Center, Washington, DC, USA.</p>
<p>Attention-deficit hyperactivity disorder (ADHD) is the most common developmental disorder that is associated with environmental and genetic factors. Neurobiological evidence suggests that fronto-striatum-cerebellum circuit abnormalities, mainly in the right hemisphere, are responsible for most of the disturbed sensorimotor integration; dopamine seems to be the main neurochemical alteration underlying these morphological abnormalities. Different conventional treatments have been employed on ADHD; however, repetitive transcranial magnetic stimulation (rTMS), a new and useful option for the clinical/research investigation of several neuropsychiatric disorders involving dopamine circuits, has yet to be considered as a therapeutic tool and possible drug-free option for ADHD. Here the authors explore the available evidence that makes this tool a rational therapeutic possibility for patients with ADHD, calling attention to safety issues, while highlighting the potentials of such an approach and the new hope it may bring for patients, parents, researchers and clinicians. The authors advocate carefully conducted clinical trials to investigate efficacy, safety, cost-effectiveness and clinical utility of rTMS for ADHD patients &#8211; in comparison to both placebo and standard treatments.</p>
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<td width="574">Clin Neurophysiol. 2003 Nov;114(11):2036-42.</td>
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<h1>Disturbed transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD).</h1>
<p>Buchmann J, Wolters A, Haessler F, Bohne S, Nordbeck R, Kunesch E.</p>
<p>Department of Child and Adolescence Neuropsychiatry, Centre of Nerve Disease, University of Rostock, Gehlsdorfer Strasse 20, 18147 Rostock, Germany.</p>
<p>OBJECTIVE: The aim of this study was to investigate mechanisms of motor-cortical excitability and inhibition which may contribute to motor hyperactivity in children with attention deficit hyperactivity disorder (ADHD).</p>
<p>METHODS: Using transcranial magnetic stimulation (TMS), involvement of the motor cortex and the corpus callosum was analysed in 13 children with ADHD and 13 sex- and age-matched controls. Contralateral silent period (cSP) and transcallosally mediated ipsilateral silent period (iSP) were investigated.</p>
<p>RESULTS: Resting motor threshold (RMT), amplitudes of motor evoked potentials (MEP) and cSP were similar in both groups whereas iSP-latencies were significantly longer (p&lt;0.05) and their duration shorter (p&lt;0.01) in the ADHD group. For the ADHD group iSP duration tended to increase and iSP latency to decrease with age (n.s.). Conners-Scores did neither correlate with iSP-latencies and -duration nor with children&#8217;s age.</p>
<p>CONCLUSIONS: The shortened duration of iSP in ADHD children could be explained by an imbalance of inhibitory and excitatory drive on the neuronal network between cortex layer III-the projection site of transcallosal motor-cortical fibers-and layer V, the origin of the pyramidal tract. The longer iSP-latencies might be the result of defective myelination of fast conducting transcallosal fibers in ADHD. iSP may be a useful supplementary diagnostic tool to discriminate between ADHD and normal children.</p>
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<td width="573">J Child Neurol. 2001 Dec;16(12):891-4.</td>
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<h1>Subjective reactions of children to single-pulse transcranial magnetic stimulation.</h1>
<p>Garvey MA, Kaczynski KJ, Becker DA, Bartko JJ.</p>
<p>Pediatric Movement Disorders Unit, Pediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1255, USA. garveym@intra.nimh.nih.gov</p>
<p>Single-pulse transcranial magnetic stimulation is a useful tool to investigate cortical function in childhood neuropsychiatric disorders. Magnetic stimulation is associated with a shock-like sensation that is considered painless in adults. Little is known about how children perceive the procedure. We used a self-report questionnaire to assess children&#8217;s subjective experience with transcranial magnetic stimulation. Normal children and children with attention-deficit hyperactivity disorder (ADHD) underwent transcranial magnetic stimulation in a study of cortical function in ADHD. Subjects were asked to rate transcranial magnetic stimulation on a 1 to 10 scale (most disagreeable = 1, most enjoyable = 10) and to rank it among common childhood events. Thirty-eight subjects completed transcranial magnetic stimulation; 34 said that they would repeat it. The overall rating for transcranial magnetic stimulation was 6.13, and transcranial magnetic stimulation was ranked fourth highest among the common childhood events. These results suggest that although a few children find transcranial magnetic stimulation uncomfortable, most consider transcranial magnetic stimulation painless. Further studies are necessary to confirm these findings.</p>
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<td width="573">Int J Neurosci. 1994 Jun;76(3-4):185-225.</td>
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<h1>Alzheimer&#8217;s disease: improvement of visual memory and visuoconstructive performance by treatment with picotesla range magnetic fields.</h1>
<p>Sandyk R.</p>
<p>NeuroCommunication Research Laboratories, Danbury, CT 06811.</p>
<p>Impairments in visual memory and visuoconstructive functions commonly occur in patients with Alzheimer&#8217;s disease (AD). Recently, I reported that external application of electromagnetic fields (EMF) of extremely low intensity (in the picotesla range) and of low frequency (in the range of 5Hz-8Hz) improved visual memory and visuoperceptive functions in patients with Parkinson&#8217;s disease. Since a subgroup of Parkinsonian patients, specifically those with dementia, have coexisting pathological and clinical features of AD, I investigated in two AD patients the effects of these extremely weak EMF on visual memory and visuoconstructive performance. The Rey-Osterrieth Complex Figure Test as well as sequential drawings from memory of a house, a bicycle, and a man were employed to evaluate the effects of EMF on visual memory and visuoconstructive functions, respectively. In both patients treatment with EMF resulted in a dramatic improvement in visual memory and enhancement of visuoconstructive performance which was associated clinically with improvement in other cognitive functions such as short term memory, calculations, spatial orientation, judgement and reasoning as well as level of energy, social interactions, and mood. The report demonstrates, for the first time, that specific cognitive symptoms of AD are improved by treatment with EMF of a specific intensity and frequency. The rapid improvement in cognitive functions in response to EMF suggests that some of the mental deficits of AD are reversible being caused by a functional (i.e., synaptic transmission) rather than a structural (i.e., neuritic plaques) disruption of neuronal communication in the central nervous system.</p>
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<td width="573">Int J Neurosci. 1991 Aug;59(4):259-62.</td>
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<h1>Age-related disruption of circadian rhythms: possible relationship to memory impairment and implications for therapy with magnetic fields.</h1>
<p>Sandyk R, Anninos PA, Tsagas N.</p>
<p>Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461.</p>
<p>Disorganization of circadian rhythms, a hallmark of aging, may be related causally to the progressive deterioration of memory functions in senescence and possibly Alzheimer&#8217;s disease (AD). In experimental animals, disruption of circadian rhythms produces retrograde amnesia by interfering with the circadian organization of memory processes. The circadian system is known to be synchronized to external 24 h periodicities of ambient light by a neural pathway extending from the retina to the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. There is also evidence that the earth&#8217;s magnetic field is a time cue (&#8220;Zeitgeber&#8221;) of circadian organization and that shielding of the ambient magnetic field leads to disorganization of the circadian rhythms in humans. Since aging is associated with a delay of the circadian rhythm phase, and since light, which phase advances circadian rhythms, mimics the effects of magnetic fields on melatonin secretion, we postulate that application of magnetic fields might improve memory functions in the elderly as a result of resynchronization of the circadian rhythms. Moreover, since the circadian rhythm organization is more severely disrupted in patients with AD, it is possible that magnetic treatment might prove useful also in improving memory functions in these patients. If successful, application of magnetic fields might open new avenues in the management of memory disturbances in the elderly and possibly in AD.</p>
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<td width="573">Clin EEG Neurosci. 2004 Jan;35(1):4-13.</td>
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<h1>Current status of the utilization of antileptic treatments in mood, anxiety and aggression: drugs and devices.</h1>
<p>Barry JJ, Lembke A, Bullock KD.</p>
<p>Department of Psychiatry, Stanford University Medical Center, 401 Quarry Road MC 5723, Stanford, CA 94305, USA. jbarry@leland.stanford.edu</p>
<p>Interventions that have been utilized to control seizures in people with epilepsy have been employed by the psychiatric community to treat a variety of disorders. The purpose of this review will be to give an overview of the most prominent uses of antiepileptic drugs (AEDs) and devices like the Vagus Nerve Stimulator (VNS) and Transcranial Magnetic Stimulation (TMS) in the treatment of psychiatric disease states. By far, the most prevalent use of these interventions is in the treatment of mood disorders. AEDs have become a mainstay in the effective treatment of Bipolar Affective Disorder (BAD). The U.S. Food and Drug Administration has approved the use of valproic acid for acute mania, and lamotrigine for BAD maintenance therapy. AEDs are also effectively employed in the treatment of anxiety and aggressive disorders. Finally, VNS and TMS are emerging as possibly useful tools in the treatment of more refractory depressive illness.</p>
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<td width="573">Am J Psychiatry. 2004 Jan;161(1):93-8.</td>
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<h1>Low-field magnetic stimulation in bipolar depression using an MRI-based stimulator.</h1>
<p>Rohan M, Parow A, Stoll AL, Demopulos C, Friedman S, Dager S, Hennen J, Cohen BM, Renshaw PF.</p>
<p>Brain Imaging Center, McLean Hospital, Belmont, MA 02478, USA. mrohan@mclean.harvard.edu</p>
<p>OBJECTIVE: Anecdotal reports have suggested mood improvement in patients with bipolar disorder immediately after they underwent an echo-planar magnetic resonance spectroscopic imaging (EP-MRSI) procedure that can be performed within clinical MR system limits. This study evaluated possible mood improvement associated with this procedure.</p>
<p>METHOD: The mood states of subjects in an ongoing EP-MRSI study of bipolar disorder were assessed by using the Brief Affect Scale, a structured mood rating scale, immediately before and after an EP-MRSI session. Sham EP-MRSI was administered to a comparison group of subjects with bipolar disorder, and actual EP-MRSI was administered to a comparison group of healthy subjects. The characteristics of the electric fields generated by the EP-MRSI scan were analyzed.</p>
<p>RESULTS: Mood improvement was reported by 23 of 30 bipolar disorder subjects who received the actual EP-MRSI examination, by three of 10 bipolar disorder subjects who received sham EP-MRSI, and by four of 14 healthy comparison subjects who received actual EP-MRSI. Significant differences in mood improvement were found between the bipolar disorder subjects who received actual EP-MRSI and those who received sham EP-MRSI, and, among subjects who received actual EP-MRSI, between the healthy subjects and the bipolar disorder subjects and to a lesser extent between the unmedicated bipolar disorder subjects and the bipolar disorder subjects who were taking medication. The electric fields generated by the EP-MRSI scan were smaller (0.7 V/m) than fields used in repetitive transcranial magnetic stimulation (rTMS) treatment of depression (1-500 V/m) and also extended uniformly throughout the head, unlike the highly nonuniform fields used in rTMS. The EP-MRSI waveform, a 1-kHz train of monophasic trapezoidal gradient pulses, differed from that used in rTMS.</p>
<p>CONCLUSIONS: These preliminary data suggest that the EP-MRSI scan induces electric fields that are associated with reported mood improvement in subjects with bipolar disorder. The findings are similar to those for rTMS depression treatments, although the waveform used in EP-MRSI differs from that used in rTMS. Further investigation of the mechanism of EP-MRSI is warranted.</p>
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<td width="574">Psychiatry Res. 2004 Sep 30;128(2):199-202.</td>
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<h1>Repetitive transcranial magnetic stimulation as an add-on therapy in the treatment of mania: a case series of eight patients.</h1>
<p>Saba G, Rocamora JF, Kalalou K, Benadhira R, Plaze M, Lipski H, Januel D.</p>
<p>Unite de recherche clinique, secteur III de Ville Evrard, 5, Rue du Dr Delafontaine, Saint-Denis, 93200 France. urcve@free.fr</p>
<p>The aim of this study is to assess the efficacy of repetitive transcranial magnetic stimulation (rTMS) as an add-on therapy in the treatment of manic bipolar patients. Eight patients were enrolled in an open trial. They received fast rTMS (five trains of 15 s, 80% of the motor threshold, 10 Hz) over the right dorsolateral prefrontal cortex (DLPFC). They were evaluated using the Mania Assessment Scale (MAS) and the Clinical Global Impression (CGI) at baseline and at day 14. All patients were taking medication during the treatment trial. There was a significant improvement of manic symptoms at the end of the trial. No side effects were reported. The results show a significant improvement of mania when patients are treated with fast rTMS over the right DLPFC. However, these results have to be interpreted with caution since they derive from an open case series and all the subjects were taking psychotropic medication during rTMS treatment. Double-blind controlled studies with a sham comparison condition should be conducted to investigate the efficiency of this treatment in manic bipolar disorders.</p>
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<td width="573">J Affect Disord. 2004 Mar;78(3):253-7.</td>
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<h1>Treatment of bipolar mania with right prefrontal rapid transcranial magnetic stimulation.</h1>
<p>Michael N, Erfurth A.</p>
<p>Mood Disorders Unit, Department of Psychiatry, University of Muenster, Albert-Schweitzer-Str. 11, 48129 Muenster, Germany.</p>
<p>BACKGROUND: Transcranial magnetic stimulation (TMS) has been suggested for the treatment of a variety of CNS disorders including depression and mania.</p>
<p>METHODS: Nine bipolar (I) in-patients diagnosed with mania were treated with right prefrontal rapid TMS in an open and prospective study. Eight of nine patients received TMS as add-on treatment to an insufficient or only partially effective drug therapy.</p>
<p>RESULTS: During the 4 weeks of TMS treatment a sustained reduction of manic symptoms as measured by the Bech-Rafaelsen mania scale (BRMAS) was observed in all patients.</p>
<p>LIMITATIONS: Due to the open and add-on design of the study, a clear causal relationship between TMS treatment and reduction of manic symptoms cannot be established.</p>
<p>CONCLUSIONS: Our data suggest that right prefrontal rapid TMS is safe and efficacious in the add-on treatment of bipolar mania showing laterality opposed to the proposed effect of rapid TMS in depression.</p>
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<td width="573">Bipolar Disord. 2003 Feb;5(1):40-7.</td>
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<h1>Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy.</h1>
<p>Nahas Z, Kozel FA, Li X, Anderson B, George MS.</p>
<p>Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston 29425, USA.</p>
<p>OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve depressive symptoms. We designed and carried out the following left prefrontal rTMS study to determine the safety, feasibility, and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder (BPAD).</p>
<p>METHODS: We recruited and enrolled 23 depressed BPAD patients (12 BPI depressed state, nine BPII depressed state, two BPI mixed state). Patients were randomly assigned to receive either daily left prefrontal rTMS (5 Hz, 110% motor threshold, 8 sec on, 22 sec off, over 20 min) or placebo each weekday morning for 2 weeks. Motor threshold and subjective rating scales were obtained daily, and blinded Hamilton Rating Scale for Depression (HRSD) and Young Mania Rating Scales (YMRS) were obtained weekly.</p>
<p>RESULTS: Stimulation was well tolerated with no significant adverse events and with no induction of mania. We failed to find a statistically significant difference between the two groups in the number of antidepressant responders (&gt;50% decline in HRSD or HRSD &lt;10 &#8211; 4 active and 4 sham) or the mean HRSD change from baseline over the 2 weeks (t = -0.22, p = 0.83). Active rTMS, compared with sham rTMS, produced a trend but not statistically significant greater improvement in daily subjective mood ratings post-treatment (t = 1.58, p = 0.13). The motor threshold did not significantly change after 2 weeks of active treatment (t = 1.11, p = 0.28).</p>
<p>CONCLUSIONS: Daily left prefrontal rTMS appears safe in depressed BPAD subjects, and the risk of inducing mania in BPAD subjects on medications is small. We failed to find statistically significant TMS clinical antidepressant effects greater than sham. Further studies are needed to fully investigate the potential role, if any, of TMS in BPAD depression.</p>
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<td width="572">CNS Drugs.<span style="text-decoration: underline;"> </span>2002;16(1):47-63.</td>
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<h1>The Bech-Rafaelsen Mania Scale in clinical trials of therapies for bipolar disorder: a 20-year review of its use as an outcome measure.</h1>
<p>Bech P.</p>
<p>Psychiatric Research Unit, WHO Collaborating Centre for Mental Health, Frederiksborg General Hospital, Hillerod, Denmark. pebe@fa.dk</p>
<p>Over the last two decades the Bech-Rafaelsen Mania Scale (MAS) has been used extensively in trials that have assessed the efficacy of treatments for bipolar disorder. The extent of its use makes it possible to evaluate the psychometric properties of the scale according to the principles of internal validity, reliability, and external validity. Studies of the internal validity of the MAS have demonstrated that the simple sum of the 11 items of the scale is a sufficient statistic for the assessment of the severity of manic states. Both factor analysis and latent structure analysis (the Rasch analysis) have been used to demonstrate this. The total score of the MAS has been standardised such that scores below 15 indicate hypomania, scores around 20 indicate moderate mania, and scores around 28 indicate severe mania. The inter-observer reliability has been found to be high in a number of studies conducted in various countries. The MAS has shown an acceptable external validity, in terms of both sensitivity and responsiveness. Thus, the MAS was found to be superior to the Clinical Global Impression scale with regard to responsiveness, and sensitivity has been found to be adequate, with the MAS able to demonstrate large drug-placebo differences. Based on pretreatment scores, trials of antimanic therapies can be classified into: (i) ultrashort (1 week) therapy of severe mania; (ii) short-term therapy (3 to 8 weeks) of moderate mania; (iii) short-term therapy of hypomanic or mixed bipolar states; and (iv) long-term (12 months) therapy of bipolar states. The responsiveness of MAS is such that the scale has been able to demonstrated that typical antipsychotics are effective as an ultrashort therapy of severe mania; that lithium and anticonvulsants are effective in the short-term therapy of moderate mania; and that atypical antipsychotics, electroconvulsive therapy (ECT) and transcranial magnetic stimulation seem to have promising effects in the short-term therapy of moderate mania. In contrast, the scale has been used to demonstrate that calcium antagonists (e.g. verapamil) are ineffective in the treatment of mania. MAS has also been used to add to the literature on the evidence-based effect of lithium as a short-term therapy for hypomania or mixed bipolar states and as a long-term therapy of bipolar states.</p>
<p>Altern Ther Health Med. 2006 Sep-Oct;12(5):42-9</p>
<h1>Regenerative effects of pulsed magnetic field on injured peripheral nerves.</h1>
<ul>
<li>Mert T,</li>
<li>Gunay I,</li>
<li>Gocmen C,</li>
<li>Kaya M,</li>
<li>Polat S.</li>
</ul>
<p>Department of Biophysics, University of Cukurova School of Medicine, Adana, Turkey.</p>
<p>Previous studies confirm that pulsed magnetic field (PMF) accelerates functional recovery after a nerve crush lesion. The contention that PMF enhances the regeneration is still controversial, however. The influence of a new PMF application protocol (trained PMF) on nerve regeneration was studied in a model of crush injury of the sciatic nerve of rats. To determine if exposure to PMF influences regeneration, we used electrophysiological recordings and ultrastructural examinations. After the measurements of conduction velocity, the sucrose-gap method was used to record compound action potentials (CAPs) from sciatic nerves. PMF treatment during the 38 days following the crush injury enhanced the regeneration. Although the axonal ultrastructures were generally normal, slight to moderate myelin sheath degeneration was noted at the lesion site. PMF application for 38 days accelerated nerve conduction velocity, increased CAP amplitude and decreased the time to peak of the CAP. Furthermore, corrective effects of PMF on. the abnormal characteristics of sensory nerve fibers were determined. Consequently, long-periodic trained-PMF may promote both morphological and electrophysiological properties of the injured nerves. In addition, corrective effects of PMF on sensory fibers may be considered an important finding for neuropathic pain therapy.</p>
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<td width="573">Bioelectromagnetics. 2005 Jan;26(1):20-7.</td>
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<h1>Pulsed electromagnetic fields induce peripheral nerve regeneration and endplate enzymatic changes.</h1>
<p>De Pedro JA, Perez-Caballer AJ, Dominguez J, Collia F, Blanco J, Salvado M.</p>
<p>Department of Orthopaedics, University Hospital of Salamanca, Salamanca, Spain. jpedrom@usal.es</p>
<p>An experimental study was carried out in rats with the purpose of demonstrating the capacity of pulsed electromagnetic fields (PEMFs) to stimulate regeneration of the peripheral nervous system (PNS). Wistar and Brown Norway (BN) rats were used. Direct sciatic nerve anastomoses were performed after section or allograft interposition. Treatment groups then received 4 weeks of PEMFs. Control groups received no stimulation. The evaluation of the results was carried out by quantitative morphometric analysis, demonstrating a statistically significant increase in regeneration indices (P &lt; 0.05) in the stimulated groups (9000 +/- 5000 and 4000 +/- 6000) compared to the non-stimulated groups (2000 +/- 4000 and 700 +/- 200). An increase of NAD specific isocitrate dehydrogenase (IDH) activity was found along with an increase in the activity of acetyl cholinesterase at the motor plate. The present study might lead to the search for new alternatives in the stimulation of axonal regenerative processes in the PNS and other possible clinical applications. 2004 Wiley-Liss, Inc.</p>
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<td width="573">Spine. 2003 Dec 15;28(24):2660-6.</td>
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<h1>Exposure to pulsed magnetic field enhances motor recovery in cats after spinal cord injury.</h1>
<p>Crowe MJ, Sun ZP, Battocletti JH, Macias MY, Pintar FA, Maiman DJ.</p>
<p>Neuroscience Research Laboratories, The Clement J. Zablocki VA Medical Center, Milwaukee, WI 53295, USA. mcrowe@mcw.edu</p>
<p>STUDY DESIGN: Animal model study of eight healthy commercial cats was conducted.</p>
<p>OBJECTIVE: To determine whether pulsed electromagnetic field (PMF) stimulation results in improvement of function after contusive spinal cord injury in cats. SUMMARY OF</p>
<p>BACKGROUND DATA: PMF stimulation has been shown to enhance nerve growth, regeneration, and functional recovery of peripheral nerves. Little research has been performed examining the effects of PMF stimulation on the central nervous system and no studies of PMF effects on in vivo spinal cord injury (SCI) models have been reported.</p>
<p>MATERIALS AND METHODS: PMF stimulation was noninvasively applied for up to 12 weeks to the midthoracic spine of cats with acute contusive spinal cord injury. The injury was produced using a weight-drop apparatus. Motor functions were evaluated with the modified Tarlov assessment scale. Morphologic analyses of the injury sites and somatosensory-evoked potential measurements were conducted to compare results between PMF-stimulated and control groups.</p>
<p>RESULTS: There was a significant difference in locomotor recovery between the PMF-stimulated and control groups. Although not statistically significant, PMF-stimulated spinal cords demonstrated greater sparing of peripheral white matter and smaller lesion volumes compared to controls. Somatosensory-evoked potential measurements indicated that the PMF-stimulated group had better recovery of preinjury waveforms than the control group; however, this observation also was not statistically significant because of the small sample size.</p>
<p>CONCLUSIONS: This preliminary study indicates that pulsed magnetic fields may have beneficial effects on motor function recovery and lesion volume size after acute spinal cord injury.</p>
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<td width="573">J Neurosci Res. 1999 Jan 15;55(2):230-7.</td>
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<h1>Electromagnetic fields influence NGF activity and levels following sciatic nerve transection.</h1>
<p>Longo FM, Yang T, Hamilton S, Hyde JF, Walker J, Jennes L, Stach R, Sisken BF.</p>
<p>Department of Neurology, UCSF/VAMC, San Francisco, California, USA. LFM@itsa.UCSF.edu</p>
<p>Pulsed electromagnetic fields (PEMF) have been shown to increase the rate of nerve regeneration. Transient post-transection loss of target-derived nerve growth factor (NGF) is one mechanism proposed to signal induction of early nerve regenerative events. We tested the hypothesis that PEMF alter levels of NGF activity and protein in injured nerve and/or dorsal root ganglia (DRG) during the first stages of regeneration (6-72 hr). Rats with a transection injury to the midthigh portion of the sciatic nerve on one side were exposed to PEMF or sham control PEMF for 4 hr/day for different time periods. NGF-like activity was determined in DRG, in 5-mm nerve segments proximal and distal to the transection site and in a corresponding 5-mm segment of the contralateral nonoperated nerve. NGF-like activity of coded tissue samples was measured in a blinded fashion using the chick DRG sensory neuron bioassay. Overall, PEMF caused a significant decrease in NGF-like activity in nerve tissue (P &lt; 0.02, repeated measures analysis of variance, ANOVA) with decreases evident in proximal, distal, and contralateral nonoperated nerve. Unexpectedly, transection was also found to cause a significant (P=0.001) 2-fold increase in DRG NGF-like activity between 6 and 24 hr postinjury in contralateral but not ipsilateral DRG. PEMF also reduced NGF-like activity in DRG, although this decrease did not reach statistical significance. Assessment of the same nerve and DRG samples using ELISA and NGF-specific antibodies confirmed an overall significant (P &lt; 0.001) decrease in NGF levels in PEMF-treated nerve tissue, while no decrease was detected in DRG or in nerve samples harvested from PEMF-treated uninjured rats. These findings demonstrate that PEMF can affect growth factor activity and levels, and raise the possibility that PEMF might promote nerve regeneration by amplifying the early postinjury decline in NGF activity.</p>
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<td width="574">Neurosci Behav Physiol. 1998 Sep-Oct;28(5):594-7.</td>
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<h1>Magnetic and electrical stimulation in the rehabilitative treatment of patients with organic lesions of the nervous system.</h1>
<p>Tyshkevich TG, Nikitina VV.</p>
<p>A. L. Polenov Russian Science Research Neurosurgical Institute, St. Petersburg.</p>
<p>Studies were performed on 89 patients with organic lesions of the nervous system in which the leading clinical symptoms consisted of paralysis and pareses. Patients received complex treatment, including pulsed magnetic fields and an electrical stimulation regime producing multilevel stimulation. A control group of 49 patients with similar conditions was included, and these patients received only sinusoidal currents. Combined treatment with magnetic and electrical stimulation was more effective, as indicated by radiographic and electromyographic investigations.</p>
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<td width="574">Arch Otolaryngol Head Neck Surg. 1998 Apr;124(4):383-9.</td>
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<h1>Effect of pulsed electromagnetic stimulation on facial nerve regeneration.</h1>
<p>Byers JM, Clark KF, Thompson GC.</p>
<p>Department of Otorhinolaryngology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.</p>
<p>OBJECTIVE: To determine if exposure to electromagnetic fields influences regeneration of the transected facial nerve in the rat.</p>
<p>DESIGN AND METHODS: The left facial nerve was transected in the tympanic section of the fallopian canal in 24 rats randomly assigned to 2 groups. The cut ends of the facial nerve were reapproximated without sutures within the fallopian canal to maximize the potential for regeneration. Rats in the experimental group (n= 12) were then exposed to pulsed electromagnetic stimulation (0.4 millitesla at 120 Hz) for 4 hours per day, 5 days per week, for 8 weeks. Rats in the control group (n=12) were handled in an identical manner without pulsed electromagnetic stimulation. Four other rats were given sham operations in which all surgical procedures were carried out except for the actual nerve transection. Two of these rats were placed in each group. Nerve regeneration was evaluated using electroneurography (compound action potentials), force of whisker and eyelid movements, and voluntary facial movements before and at 2-week intervals after transection. Histological evaluation was performed at 10 weeks after transection. Each dependent variable was analyzed using a 2-way analysis of variance with 1 between variable (groups) and 1 within repeated measures variable (days after transection).</p>
<p>RESULTS: Statistical analysis indicated that N1 (the negative deflection of depolarization phase of the muscle and/or nerve fibers) area, N1 amplitude, and N1 duration, as well as absolute amplitude of the compound action potentials, were all significantly greater 2 weeks after transection in the experimental than in the control group of rats. The force of eye and whisker movements after electrical stimulation was statistically greater in the experimental group of rats 4 weeks after transection. Voluntary eye movements in the experimental group were significantly better at 5 and 10 weeks, while whisker movements were better at 3 and 10 weeks. There was no statistical difference between the 2 groups for any histological variable.</p>
<p>CONCLUSION: Results of this study indicate that pulsed electromagnetic stimulation enhances early regeneration of the transected facial nerve in rats.</p>
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<td width="573">J Cell Biochem. 1993 Apr;51(4):387-93.</td>
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<h1>Beneficial effects of electromagnetic fields.</h1>
<p>Bassett CA.</p>
<p>Bioelectric Research Center, Columbia University, Riverdale, New York 10463.</p>
<p>Selective control of cell function by applying specifically configured, weak, time-varying magnetic fields has added a new, exciting dimension to biology and medicine. Field parameters for therapeutic, pulsed electromagnetic field (PEMFs) were designed to induce voltages similar to those produced, normally, during dynamic mechanical deformation of connective tissues. As a result, a wide variety of challenging musculoskeletal disorders have been treated successfully over the past two decades. More than a quarter million patients with chronically ununited fractures have benefitted, worldwide, from this surgically non-invasive method, without risk, discomfort, or the high costs of operative repair. Many of the athermal bioresponses, at the cellular and subcellular levels, have been identified and found appropriate to correct or modify the pathologic processes for which PEMFs have been used. Not only is efficacy supported by these basic studies but by a number of double-blind trials. As understanding of mechanisms expands, specific requirements for field energetics are being defined and the range of treatable ills broadened. These include nerve regeneration, wound healing, graft behavior, diabetes, and myocardial and cerebral ischemia (heart attack and stroke), among other conditions. Preliminary data even suggest possible benefits in controlling malignancy.</p>
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<td width="573">Bioelectromagnetics. 1993;14(4):353-9.</td>
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<h1>Pretreatment of rats with pulsed electromagnetic field enhances regeneration of the sciatic nerve.</h1>
<p>Kanje M, Rusovan A, Sisken B, Lundborg G.</p>
<p>Department of Animal Physiology, University of Lund, Sweden.</p>
<p>Regeneration of the sciatic nerve was studied in rats pretreated in a pulsed electromagnetic field (PEMF). The rats were exposed between a pair of Helmholtz coils at a pulse repetition rate of 2 pps at a field density of 60 or 300 microT. The PEMF treatment was then discontinued. After an interval of recovery, regeneration of the sciatic nerve was initiated by a crush lesion. Regeneration of sensory fibers was measured by the &#8220;pinch test&#8221; after an additional 3-6 days. A variety of PEMF pretreatments including 4 h/day for 1-4 days or exposure for 15 min/day during 2 days resulted in an increased regeneration distance, measured 3 days after the crush lesion. This effect could be demonstrated even after a 14-day recovery period. In contrast, pretreatment for 4 h/day for 2 days at 60 microT did not affect the regeneration distance. The results showed that PEMF pretreatment conditioned the rat sciatic nerve in a manner similar to that which occurs after a crush lesion, which indicates that PEMF affects the neuronal cell body. However, the mechanism of this effect remains obscure.</p>
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<td width="573">Brain Res. 1989 Apr 24;485(2):309-16.</td>
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<h1>Stimulation of rat sciatic nerve regeneration with pulsed electromagnetic fields.</h1>
<p>Sisken BF, Kanje M, Lundborg G, Herbst E, Kurtz W.</p>
<p>Center for Biomedical Engineering, University of Kentucky, Lexington 40506.</p>
<p>The effects of pulsed electromagnetic fields (PEMF) on rat sciatic nerve regeneration after a crush lesion were determined. The rats were placed between a pair of Helmholtz coils and exposed to PEMF of frequency 2 Hz and magnetic flux density of 0.3 mT. A 4 h/day treatment for 3-6 days increased the rate of nerve regeneration by 22%. This stimulatory effect was independent of the orientation of the coils. Exposure times of 1 h/day-10 h/day were equally effective in stimulating nerve regeneration. Rats exposed to PEMF for 4 h/day for 7 days before crush, followed by 3 days after crush without PEMF, also showed significantly increased regeneration. This pre-exposure &#8216;conditioning&#8217; effect suggests that PEMF influences regeneration indirectly.</p>
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<td width="573">J Hand Surg [Br]. 1984 Jun;9(2):105-12.</td>
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<h1>An experimental study of the effects of pulsed electromagnetic field (Diapulse) on nerve repair.</h1>
<p>Raji AM.</p>
<p>This study investigates the effects of a pulsed electromagnetic field (PEMF) (Diapulse) on experimentally divided and sutured common peroneal nerves in rats. Evidence is presented to show that PEMF accelerates recovery of use of the injured limb and enhances regeneration of damaged nerves.</p>
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<td width="574">Clin Orthop Relat Res. 1983 Dec;(181):283-90.</td>
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<h1>Effect of weak, pulsing electromagnetic fields on neural regeneration in the rat.</h1>
<p>Ito H, Bassett CA.</p>
<p>The short- and long-term effects of pulsed electromagnetic fields (PEMFs) on the rate and quality of peripheral nerve regeneration were studied. High bilateral transections of rat sciatic nerves were surgically approximated (a 1-mm gap was left) and shielded with a Silastic sleeve. Animals were exposed to PEMFs for two to 14 weeks after operation. Three groups of 20 rats each (control rats and rats undergoing 12- and 24-hour/day PEMF exposure) were killed at two weeks. Histologically, regenerating axons had penetrated the distal stump nearly twice as far in the PEMF-exposed animals as in the control animals. Return of motor function was judged two to 14 weeks after operation by the load cell-measured, plantar-flexion force produced by neural stimulation proximal to the transection site. Motor function returned earlier in experimental rats and to significantly higher load levels than in control rats. Nerves from animals functioning 12-14 weeks after operation had less interaxonal collagen, more fiber-containing axis cylinders, and larger fiber diameters in the PEMF-exposed group than in the control rats. Histologic and functional data indicate that PEMFs improve the rate and quality of peripheral nerve regeneration in the severed rat sciatic nerve by a factor of approximately two.</p>
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<td width="573">Paraplegia. 1976 May;14(1):12-20.</td>
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<h1>Experimental regeneration in peripheral nerves and the spinal cord in laboratory animals exposed to a pulsed electromagnetic field.</h1>
<p>Wilson DH, Jagadeesh P.</p>
<p>Peripheral nerve section and suture was performed in 132 rats. Postoperatively half the animals were exposed to a pulsed electromagnetic field each day and half were kept as controls. Nerve conduction studies, histology and nerve fibre counts all indicated an increased rate of regeneration in the treated animals. A similar controlled study of spinal cord regeneration following hemicordotomy in cats has been started, and preliminary results indicate that when the animals are sacrificed three months after the hemicordotomy, the pulsed electromagnetic therapy has induced nerve fibre regeneration across the region of the scar.</p>
<p>Altern Ther Health Med. 2006 Sep-Oct;12(5):42-9</p>
<h1>Regenerative effects of pulsed magnetic field on injured peripheral nerves.</h1>
<p>Mert T, Gunay I, Gocmen C, Kaya M, Polat S.</p>
<p>Department of Biophysics, University of Cukurova School of Medicine, Adana, Turkey.</p>
<p>Previous studies confirm that pulsed magnetic field (PMF) accelerates functional recovery after a nerve crush lesion. The contention that PMF enhances the regeneration is still controversial, however. The influence of a new PMF application protocol (trained PMF) on nerve regeneration was studied in a model of crush injury of the sciatic nerve of rats. To determine if exposure to PMF influences regeneration, we used electrophysiological recordings and ultrastructural examinations. After the measurements of conduction velocity, the sucrose-gap method was used to record compound action potentials (CAPs) from sciatic nerves. PMF treatment during the 38 days following the crush injury enhanced the regeneration. Although the axonal ultrastructures were generally normal, slight to moderate myelin sheath degeneration was noted at the lesion site. PMF application for 38 days accelerated nerve conduction velocity, increased CAP amplitude and decreased the time to peak of the CAP. Furthermore, corrective effects of PMF on. the abnormal characteristics of sensory nerve fibers were determined. Consequently, long-periodic trained-PMF may promote both morphological and electrophysiological properties of the injured nerves. In addition, corrective effects of PMF on sensory fibers may be considered an important finding for neuropathic pain therapy.</p>
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<td width="574">Neurorehabil Neural Repair. 2004 Mar;18(1):42-6.</td>
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<h1>Pulsed magnetic field therapy in refractory neuropathic pain secondary to peripheral neuropathy: electrodiagnostic parameters&#8211;pilot study.</h1>
<p>Weintraub MI, Cole SP.</p>
<p>New York Medical College, Briarcliff Manor, New York 10510, USA.</p>
<p>CONTEXT: Neuropathic pain (NP) from peripheral neuropathy (PN) arises from ectopic firing of unmyelinated C-fibers with accumulation of sodium and calcium channels. Because pulsed electromagnetic fields (PEMF) safely induce extremely low frequency (ELF) quasirectangular currents that can depolarize, repolarize, and hyperpolarize neurons, it was hypothesized that directing this energy into the sole of one foot could potentially modulate neuropathic pain.</p>
<p>OBJECTIVE: To determine if 9 consecutive 1-h treatments in physician&#8217;s office (excluding weekends) of a pulsed signal therapy can reduce NP scores in refractory feet with PN.</p>
<p>DESIGN/SETTING/PATIENTS: 24 consecutive patients with refractory and symptomatic PN from diabetes, chronic inflammatory demyelinating polyneuropathy (CIDP), pernicious anemia, mercury poisoning, paraneoplastic syndrome, tarsal tunnel, and idiopathic sensory neuropathy were enrolled in this nonplacebo pilot study. The most symptomatic foot received therapy. Primary endpoints were comparison of VAS scores at the end of 9 days and the end of 30 days follow-up compared to baseline pain scores. Additionally, Patients&#8217; Global Impression of Change (PGIC) questionnaire was tabulated describing response to treatment. Subgroup analysis of nerve conduction scores, quantified sensory testing (QST), and serial examination changes were also tabulated. Subgroup classification of pain (Serlin) was utilized to determine if there were disproportionate responses.</p>
<p>INTERVENTION: Noninvasive pulsed signal therapy generates a unidirectional quasirectangular waveform with strength about 20 gauss and a frequency about 30 Hz into the soles of the feet for 9 consecutive 1-h treatments (excluding weekends). The most symptomatic foot of each patient was treated.</p>
<p>RESULTS: All 24 feet completed 9 days of treatment. 15/24 completed follow-up (62%) with mean pain scores decreasing 21% from baseline to end of treatment (P=0.19) but with 49% reduction of pain scores from baseline to end of follow-up (P&lt;0.01). Of this group, self-reported PGIC was improved 67% (n=10) and no change was 33% (n=5). An intent-to-treat analysis based on all 24 feet demonstrated a 19% reduction in pain scores from baseline to end of treatment (P=0.10) and a 37% decrease from baseline to end of follow-up (P&lt;0.01). Subgroup analysis revealed 5 patients with mild pain with nonsignificant reduction at end of follow-up. Of the 19 feet with moderate to severe pain, there was a 28% reduction from baseline to end of treatment (P&lt;0.05) and a 39% decrease from baseline to end of follow-up (P&lt;0.01). Benefit was better in those patients with axonal changes and advanced CPT baseline scores. The clinical examination did not change. There were no adverse events or safety issues.</p>
<p>CONCLUSIONS: These pilot data demonstrate that directing PEMF to refractory feet can provide unexpected short term analgesic effects in more than 50% of individuals. The role of placebo is not known and was not tested. The precise mechanism is unclear yet suggests that severe and advanced cases are more magnetically sensitive. Future studies are needed with randomized placebo-controlled design and longer treatment periods.</p>
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<td width="574">Arch Phys Med Rehabil. 2003 May;84(5):736-46.</td>
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<h1>Static magnetic field therapy for symptomatic diabetic neuropathy: a randomized double-blind, placebo-controlled trial.</h1>
<p>Weintraub MI, Wolfe GI, Barohn RA, Cole SP, Parry GJ, Hayat G, Cohen JA, Page JC, Bromberg MB, Schwartz SL; Magnetic Research Group.</p>
<p>Department of Neurology, New York Medical College, Valhalla, NY, USA. miwneuro@pol.net</p>
<p>OBJECTIVE: To determine if constant wearing of multipolar, static magnetic (450G) shoe insoles can reduce neuropathic pain and quality of life (QOL) scores in symptomatic diabetic peripheral neuropathy (DPN).</p>
<p>DESIGN: Randomized, placebo-control, parallel study.</p>
<p>SETTING: Forty-eight centers in 27 states.</p>
<p>PARTICIPANTS: Three hundred seventy-five subjects with DPN stage II or III were randomly assigned to wear constantly magnetized insoles for 4 months; the placebo group wore similar, unmagnetized device.</p>
<p>INTERVENTION: Nerve conduction and/or quantified sensory testing were performed serially.</p>
<p>MAIN OUTCOME MEASURES: Daily visual analog scale scores for numbness or tingling and burning and QOL issues were tabulated over 4 months. Secondary measures included nerve conduction changes, role of placebo, and safety issues. Analysis of variance (ANOVA), analysis of covariance (ANCOVA), and chi-square analysis were performed.</p>
<p>RESULTS: There were statistically significant reductions during the third and fourth months in burning (mean change for magnet treatment, -12%; for sham, -3%; P&lt;.05, ANCOVA), numbness and tingling (magnet, -10%; sham, +1%; P&lt;.05, ANCOVA), and exercise-induced foot pain (magnet, -12%; sham, -4%; P&lt;.05, ANCOVA). For a subset of patients with baseline severe pain, statistically significant reductions occurred from baseline through the fourth month in numbness and tingling (magnet, -32%; sham, -14%; P&lt;.01, ANOVA) and foot pain (magnet, -41%; sham, -21%; P&lt;.01, ANOVA).</p>
<p>CONCLUSIONS: Static magnetic fields can penetrate up to 20mm and appear to target the ectopic firing nociceptors in the epidermis and dermis. Analgesic benefits were achieved over time.</p>
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<td width="574">Neurosci Behav Physiol. 2003 Oct;33(8):745-52.</td>
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<h1>The use of pulsed electromagnetic fields with complex modulation in the treatment of patients with diabetic polyneuropathy.</h1>
<p>Musaev AV, Guseinova SG, Imamverdieva SS.</p>
<p>Science Research Institute of Medical Rehabilitation, Baku, Azerbaidzhan.</p>
<p>Clinical and electroneuromyographic studies were performed in 121 patients with diabetic polyneuropathy (DPN) before and after courses of treatment with pulsed electromagnetic fields with complex modulation (PEMF-CM) at different frequencies (100 and 10 Hz). Testing of patients using the TSS and NIS LL scales demonstrated a correlation between the severity and frequency of the main subjective and objective effects of disease and the stage of DPN. The severity of changes in the segmental-peripheral neuromotor apparatus&#8211;decreases in muscle bioelectrical activity, the impulse conduction rate along efferent fibers of peripheral nerves, and the amplitude of the maximum M response&#8211;depended on the stage of DPN and the duration of diabetes mellitus. The earliest and most significant electroneuromyographic signs of DPN were found to be decreases in the amplitude of the H reflex and the Hmax/Mmax ratio in the muscles of the lower leg. Application of PEMF-CM facilitated regression of the main clinical symptoms of DPN, improved the conductive function of peripheral nerves, improved the state of la afferents, and improved the reflex excitability of functionally diverse motoneurons in the spinal cord. PEMF-CM at 10 Hz was found to have therapeutic efficacy, especially in the initial stages of DPN and in patients with diabetes mellitus for up to 10 years.</p>
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<td width="574">Vopr Kurortol Fizioter Lech Fiz Kult. 1993 Sep-Oct;(5):38-41.</td>
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<h1>The use of combined methods of magnetoelectrotherapy in treating polyneuropathies.</h1>
<p>[Article in Russian]</p>
<p>A comparative evaluation by such parameters as alleviation of pain syndrome, improvement of peripheral resistance and vegetotrophic processes, a decline in pareses and sensory disorders has been performed in 3 groups of patients: group 1 underwent benzohexonium electrophoresis, group 2 benzohexonium electrophoresis in the magnetic field produced by the unit &#8220;Polyus-I&#8221; followed by low-frequency electrotherapy with bipolar impulse current, group 3 benzohexonium electrophoresis in the magnetic field from the unit &#8220;ADMT-Magnipuls&#8221; followed by low-frequency electrotherapy with bipolar impulse current. The best clinical and physiological results were reported in group 3 patients.</p>
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<td width="573">Wiad Lek. 2003;56(9-10):434-41.</td>
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<h1>Application of variable magnetic fields in medicine&#8211;15 years experience.</h1>
<p>[Article in Polish]</p>
<p>Sieron A, Cieslar G.</p>
<p>Katedra i Klinika Chorob Wewnetrznych, Angiologii i Medycyny Fizykalnej SAM, ul. Batorego 15, 41-902 Bytom. sieron@mediclub.pl</p>
<p>The results of 15-year own experimental and clinical research on application of variable magnetic fields in medicine were presented. In experimental studies analgesic effect (related to endogenous opioid system and nitrogen oxide activity) and regenerative effect of variable magnetic fields with therapeutical parameters was observed. The influence of this fields on enzymatic and hormonal activity, free oxygen radicals, carbohydrates, protein and lipid metabolism, dielectric and rheological properties of blood as well as behavioural reactions and activity of central dopamine receptor in experimental animals was proved. In clinical studies high therapeutic efficacy of magnetotherapy and magnetostimulation in the treatment of osteoarthrosis, abnormal ossification, osteoporosis, nasosinusitis, multiple sclerosis, Parkinson&#8217;s disease, spastic paresis, diabetic polyneuropathy and retinopathy, vegetative neurosis, peptic ulcers, colon irritable and trophic ulcers was confirmed.</p>
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<td width="573">Klin Med (Mosk). 1996;74(5):39-41.</td>
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<h1>Magentotherapy in the comprehensive treatment of vascular complications of diabetes mellitus.</h1>
<p>[Article in Russian]</p>
<p>Kirillov IB, Suchkova ZV, Lastushkin AV, Sigaev AA, Nekhaeva TI.</p>
<p>320 diabetes mellitus (DM) patients were exposed to impulsed magnetic field, 100 control DM patients received conservative therapy alone. 270 patients had microangiopathy, macroangiopathy was diagnosed in 50 patients. Good and satisfactory results of magnetotherapy in combination with conservative methods were achieved in 74% of patients versus 28% in control group. Metabolism stabilization resulted in some patients in reduced blood sugar. Use of magnetic field produced faster and longer response than conservative therapy.</p>
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<td width="573">Vestn Oftalmol. 1990 Sep-Oct;106(5):54-7.</td>
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<h1>Effectiveness of magnetotherapy in optic nerve atrophy.  A preliminary study.</h1>
<p>[Article in Russian]</p>
<p>Zobina LV, Orlovskaia LS, Sokov SL, Sabaeva GF, Konde LA, Iakovlev AA.</p>
<p>Magnetotherapy effects on visual functions (vision acuity and field), on retinal bioelectric activity, on conductive vision system, and on intraocular circulation were studied in 88 patients (160 eyes) with optic nerve atrophy. A Soviet Polyus-1 low-frequency magnetotherapy apparatus was employed with magnetic induction of about 10 mT, exposure 7-10 min, 10-15 sessions per course. Vision acuity of patients with its low (below 0.04 diopters) values improved in 50 percent of cases. The number of patients with vision acuity of 0.2 diopters has increased from 46 before treatment to 75. Magnetotherapy improved ocular hemodynamics in patients with optic nerve atrophy, it reduced the time of stimulation conduction along the vision routes and stimulated the retinal ganglia cells. The maximal effect was achieved after 10 magnetotherapy sessions. A repeated course carried out in 6-8 months promoted a stabilization of the process.</p>
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<td width="573"><span style="text-decoration: underline;">I</span>nt J Neurosci. 1998 Apr;93(3-4):239-50.</td>
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<h1>Treatment with AC pulsed electromagnetic fields normalizes the latency of the visual evoked response in a multiple sclerosis patient with optic atrophy.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience at the Institute for Biomedical Engineering and Rehabilitation Services of Touro College, Dix Hills, NY 11746, USA.</p>
<p>Visual evoked response (VER) studies have been utilized as supportive information for the diagnosis of multiple sclerosis (MS) and may be useful in objectively monitoring the effects of various therapeutic modalities. Delayed latency of the VER, which reflects slowed impulse transmission in the optic pathways, is the most characteristic abnormality associated with the disease. Brief transcranial applications of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density are efficacious in the symptomatic treatment of MS and may also reestablish impulse transmission in the optic pathways. A 36 year old man developed an attack of right sided optic neuritis at the age of 30. On presentation he had blurring of vision with reduced acuity on the right and fundoscopic examination revealed pallor of the optic disc. A checkerboard pattern reversal VER showed a delayed latency to right eye stimulation (P100 = 132 ms; normal range: 95-115 ms). After he received two successive applications of AC pulsed EMFs of 7.5 picotesla flux density each of 20 minutes duration administered transcranially, there was a dramatic improvement in vision and the VER latency reverted to normal (P100= 107 ms). The rapid improvement in vision coupled with the normalization of the VER latency despite the presence of optic atrophy, which reflects chronic demyelination of the optic nerve, cannot be explained on the basis of partial or full reformation of myelin. It is proposed that in MS synaptic neurotransmitter deficiency is associated with the visual impairment and delayed VER latency following optic neuritis and that the recovery of the VER latency by treatment with pulsed EMFs is related to enhancement of synaptic neurotransmitter functions in the retina and central optic pathways. Recovery of the VER latency in MS patients may have important implications with respect to the treatment of visual impairment and prevention of visual loss. Specifically, repeated pulsed applications of EMFs may maintain impulse transmission in the optic nerve and thus potentially sustain its viability.</p>
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<td width="574">Altern Ther Health Med. 2003 Jul-Aug;9(4):38-48.</td>
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<h1>Effects of a pulsed electromagnetic therapy on multiple sclerosis fatigue and quality of life: a double-blind, placebo-controlled trial.</h1>
<p>Lappin MS, Lawrie FW, Richards TL, Kramer ED.</p>
<p>Energy Medicine Developments, (North America), Inc., Burke, Va., USA.</p>
<p>CONTEXT: There is a growing literature on the biological and clinical effects of pulsed electromagnetic fields. Some studies suggest that electromagnetic therapies may be useful in the treatment of chronic illnesses. This study is a follow-up to a placebo controlled pilot study in which multiple sclerosis (MS) patients exposed to weak, extremely low frequency pulsed electromagnetic fields showed significant improvements on a composite symptom measure.</p>
<p>OBJECTIVE: To evaluate the effects of a pulsed electromagnetic therapy on MS related fatigue, spasticity, bladder control, and overall quality of life.</p>
<p>DESIGN: A multi-site, double-blind, placebo controlled, crossover trial. Each subject received 4 weeks of the active and placebo treatments separated by a 2-week washout period. SETTING: The University of Washington Medical Center in Seattle Wash, the Neurology Center of Fairfax in Fairfax, Va, and the headquarters of the Multiple Sclerosis Association of America in Cherry Hill, NJ.</p>
<p>SUBJECTS: 117 patients with clinically definite MS.</p>
<p>INTERVENTION: Daily exposure to a small, portable pulsing electromagnetic field generator.</p>
<p>MAIN OUTCOME: The MS Quality of Life Inventory (MSQLI) was used to assess changes in fatigue, bladder control, spasticity, and a quality of life composite.</p>
<p>RESULTS: Paired t-tests were used to assess treatment differences in the 117 subjects (81% of the initial sample) who completed both treatment sessions. Improvements in fatigue and overall quality of life were significantly greater on the active device. There were no treatment effects for bladder control and a disability composite, and mixed results for spasticity.</p>
<p>CONCLUSIONS: Evidence from this randomized, double-bind, placebo controlled trial is consistent with results from smaller studies suggesting that exposure to pulsing, weak electromagnetic fields can alleviate symptoms of MS. The clinical effects were small, however, and need to be replicated. Additional research is also needed to examine the possibility that ambulatory patients and patients taking interferons for their MS may be most responsive to this kind of treatment.</p>
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<td width="574">Phys Med Rehabil Clin N Am. 1998 Aug;9(3):659-74.</td>
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<h1>Bioelectromagnetic applications for multiple sclerosis.</h1>
<p>Richards TL, Lappin MS, Lawrie FW, Stegbauer KC.</p>
<p>Department of Radiology, University of Washington, Seattle, USA.</p>
<p>There are EM effects on biology that are potentially both harmful and beneficial. We have reviewed applications of EM fields that are relevant to MS. It is possible that EM fields could be developed into a reproducible therapy for both symptom management and long-term care for MS. The long-term care for MS would have to include beneficial changes in the immune system and in nerve regeneration.</p>
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<td width="573">Mult Scler. 2005 Jun;11(3):302-5.</td>
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<h1>Effect of pulsed magnetic field therapy on the level of fatigue in patients with multiple sclerosis&#8211;a randomized controlled trial.</h1>
<p>Mostert S, Kesselring J.</p>
<p>Department of Neurology, Rehabilitation Centre, CH 7317 Valens, Switzerland.</p>
<p>Twenty-five multiple sclerosis patients, taking part in a rehabilitation program, were randomly assigned to treatment with pulsed magnetic field therapy (PMFT) or to sham therapy in order to study the additional effect of PMFT as part of a multimodal neurological rehabilitation program on fatigue. Patients demographic and disease specific characteristics were recorded. Level of fatigue was measured by fatigue severity scale (FSS) at entrance and discharge and with a visual analog scale (VAS) immediate before and after a single treatment session. The &#8216;Magnetic Cell Regeneration&#8217; system by Santerra was used for PMFT. A single treatment lasted 16 minutes twice daily over 3-4 weeks and consisted of relaxed lying on a PMF mattress. Sham intervention was conducted in an identical manner with the PMF-device off. Patients and statistics were blinded. Level of fatigue measured by FSS was high at entrance in both treatment group (TG) and control group (CG) (5.6 versus 5.5). Over time of rehabilitation fatigue was reduced by 18% in TG and 7% in CG which was statistically not significant. There was a statistically significant immediate effect of the single treatment session which 18% reduction of fatigue measured by VAS in TG versus 11% in CG. Because of a high &#8216;placebo effect&#8217; of simple bed rest, a only small and short lasting additional effect of PMFT and high costs of a PMF-device, we cannot recommend PMFT as an additional feature of a multimodal neurological rehabilitation program in order to reduce fatigue level of MS-patients.</p>
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<td width="573">Int J Neurosci. 1997 Nov;92(1-2):95-102.</td>
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<h1>Treatment with electromagnetic fields improves dual-task performance (talking while walking) in multiple sclerosis.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.</p>
<p>Multiple sclerosis (MS) is associated with an increased risk of falling resulting from visual disturbances, difficulties with gait and balance, apraxia of gait and peripheral neuropathy. These factors often interact synergistically to compromise the patient&#8217;s gait stability. It has long been recognized that walking involves a cognitive component and that simultaneous cognitive and motor operations (dual-task) such as talking while walking may interfere with normal ambulation. Talking while walking reflects an example of a dual-task which is frequently impaired in MS patients. Impaired dual-task performance during walking may compromise the patient&#8217;s gait and explain why in some circumstances, MS patients unexpectedly lose their balance and fall. Frontal lobe dysfunction, which commonly occurs in MS patients, may disrupt dual-task performance and increase the risk of falling in these patients. This report concerns a 36 old man with remitting-progressive MS with an EDSS score of 5.5 who experienced marked increase in spasticity in the legs and trunk and worsening of his gait and balance, occasionally resulting in falling, when talking while walking. His gait and balance improved dramatically after he received two successive transcranial treatments, each of 45 minutes, with AC pulsed electromagnetic fields (EMFs) of 7.5 picotesla flux density. Simultaneously, there was improvement in dual-task performance to the extent that talking while walking did not adversely affect his ambulation. In addition, neuropsychological testing revealed an almost 5-fold increase in word output on the Thurstone&#8217;s Word-Fluency Test, which is sensitive to frontal lobe dysfunction. It is suggested that facilitation of dual-task performance during ambulation contributes to the overall improvement of gait and balance observed in MS patients receiving transcranial treatment with AC pulsed EMFs.</p>
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<td width="573">Int J Neurosci. 1997 Aug;90(3-4):177-85.</td>
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<h1>Treatment with electromagnetic fields reverses the long-term clinical course of a patient with chronic progressive multiple sclerosis.</h1>
<p><strong></strong>Sandyk R.</p>
<p>Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.</p>
<p>It is estimated that 10-20% of patients with multiple sclerosis (MS) have a chronic progressive (CP) course characterized by an insidious onset of neurological deficits followed by steady progression of disability in the absence of symptomatic remission. To date no therapeutic modality has proven effective in reversing the clinical course of CP MS although there are indications that prolonged treatment with picotesla electromagnetic fields (EMFs) alters the clinical course of patients with CP MS. A 40 year-old woman presented in December of 1992 with CP MS with symptoms of spastic paraplegia, loss of trunk control, marked weakness of the upper limbs with loss of fine and gross motor hand functions, severe fatigue, cognitive deficits, mental depression, and autonomic dysfunction with neurogenic bladder and bowel incontinence. Her symptoms began at the age of 18 with weakness of the right leg and fatigue with long distance walking and over the ensuing years she experienced steady deterioration of functions. In 1985 she became wheelchair dependent and it was anticipated that within 1-2 years she would become functionally quadriplegic. In December of 1992 she began experimental treatment with EMFs. While receiving regularly weekly transcortical treatments with AC pulsed EMFs in the picotesla range intensity she experienced during the first year improvement in mental functions, return of strength in the upper extremities, and recovery of trunk control. During the second year she experienced the return of more hip functions and recovery of motor functions began in her legs. For the first time in years she can now initiate dorsiflexion of her ankles and actively extend her knees voluntarily. Over the past year she started to show signs of redevelopment of reciprocal gait. Presently, with enough function restored in her legs, she is learning to walk with a walker and is able to stand unassisted and maintain her balance for a few minutes. She also regained about 80% of functions in the upper limbs and hands. Most remarkably, there was no further progression of the disease during the 4 years course of magnetic therapy. This patient&#8217;s clinical recovery cannot be explained on the basis of a spontaneous remission. It is suggested that pulsed applications of picotesla EMFs affect the neurobiological and immunological mechanisms underlying the pathogenesis of CP MS.</p>
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<td width="573">Int J Neurosci. 1997 Aug;90(3-4):145-57.</td>
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<h1>Resolution of sleep paralysis by weak electromagnetic fields in a patient with multiple sclerosis.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.</p>
<p>Sleep paralysis refers to episodes of inability to move during the onset of sleep or more commonly upon awakening. Patients often describe the sensation of struggling to move and may experience simultaneous frightening vivid hallucinations and dreams. Sleep paralysis and other manifestations of dissociated states of wakefulness and sleep, which reflect deficient monoaminergic regulation of neural modulators of REM sleep, have been reported in patients with multiple sclerosis (MS). A 40 year old woman with remitting-progressive multiple sclerosis (MS) experienced episodes of sleep paralysis since the age of 16, four years prior to the onset of her neurological symptoms. Episodes of sleep paralysis, which manifested at a frequency of about once a week, occurred only upon awakening in the morning and were considered by the patient as a most terrifying experience. Periods of mental stress, sleep deprivation, physical fatigue and exacerbation of MS symptoms appeared to enhance the occurrence of sleep paralysis. In July of 1992 the patient began experimental treatment with AC pulsed applications of picotesla intensity electromagnetic fields (EMFs) of 5Hz frequency which were applied extracerebrally 1-2 times per week. During the course of treatment with EMFs the patient made a dramatic recovery of symptoms with improvement in vision, mobility, balance, bladder control, fatigue and short term memory. In addition, her baseline pattern reversal visual evoked potential studies, which showed abnormally prolonged latencies in both eyes, normalized 3 weeks after the initiation of magnetic therapy and remained normal more than 2.5 years later. Since the introduction of magnetic therapy episodes of sleep paralysis gradually diminished and abated completely over the past 3 years. This report suggests that MS may be associated with deficient REM sleep inhibitory neural mechanisms leading to sleep paralysis secondary to the intrusion of REM sleep atonia and dream imagery into the waking state. Pineal melatonin and monoaminergic neurons have been implicated in the induction and maintenance of REM sleep and the pathogenesis of sleep paralysis and it is suggested that resolution of sleep paralysis in this patient by AC pulsed applications of EMFs was related to enhancement of melatonin circadian rhythms and cerebral serotoninergic neurotransmission.</p>
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<td width="573">Int J Neurosci. 1997 Jun;90(1-2):59-74.</td>
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<h1>Immediate recovery of cognitive functions and resolution of fatigue by treatment with weak electromagnetic fields in a patient with multiple sclerosis.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience, Institute for Biomedical Engineering, Dix Hills, NY, USA.</p>
<p>Cognitive deficits are common among patients with multiple sclerosis (MS). The pathogenetic mechanisms underlying the cognitive impairment in MS are unknown and there is presently no effective therapeutic modality which has shown efficacy in improving cognitive deficits in MS. A 53 year old college professor with a long history of secondary progressive MS experienced, over the preceding year, noticeable deterioration in cognitive functions with difficulties in short and long term memory, word finding in spontaneous speech, attention and concentration span. Unable to pursue his academic activities, he was considering early retirement. Mental examination disclosed features of subcortical and cortical dementia involving frontal lobe, left hemispheric and right hemispheric dysfunction. Almost immediately following the extracerebral application of AC pulsed electromagnetic fields (EMFs) of 7.5 picotesla intensity and a 4-Hz sinusoidal wave, the patient experienced a heightend sense of well being, which he defined as enhancement of cognitive functions with a feeling &#8220;like a cloud lifted off my head.&#8221; He reported heightend clarity of thinking and during the application of EMFs he felt that words were formed faster and he experienced no difficulty finding the appropriate words. His speech was stronger and well modulated and he felt &#8220;energized&#8221; with resolution of his fatigue. There was improvement in manual dexterity and handwriting and testing of constructional praxis demonstrated improvement in visuospatial, visuoperceptive and visuomotor functions. It is suggested that some of the cognitive deficits associated with MS, which are caused by synaptic disruption of neurotransmitter functions, may be reversed through pulsed applications of picotesla range EMFs.</p>
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<td width="573">Int J Neurosci. 1996 Oct;87(1-2):5-15.</td>
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<h1>Suicidal behavior is attenuated in patients with multiple sclerosis by treatment with electromagnetic fields.</h1>
<p>Sandyk R.</p>
<p>NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.</p>
<p>A marked decrease in the levels of serotonin (5-HT) and its metabolite (5-HIAA) has been demonstrated in postmortem studies of suicide victims with various psychiatric disorders. Depression is the most common mental manifestation of multiple sclerosis (MS) which accounts for the high incidence of suicide in this disease. CSF 5-HIAA concentrations are reduced in MS patients and nocturnal plasma melatonin levels were found to be lower in suicidal than in nonsuicidal patients. These findings suggest that the increased risk of suicide in MS patients may be related to decreased 5-HT functions and blunted circadian melatonin secretion. Previous studies have demonstrated that extracerebral applications of pulsed electromagnetic fields (EMFs) in the picotesla range rapidly improved motor, sensory, affective and cognitive deficits in MS. Augmentation of cerebral 5-HT synthesis and resynchronization of circadian melatonin secretion has been suggested as a key mechanism by which these EMFs improved symptoms of the disease. Therefore, the prediction was made that this treatment modality would result in attenuation of suicidal behavior in MS patients. The present report concerns three women with remitting-progressive MS who exhibited suicidal behavior during the course of their illness. All patients had frequent suicidal thoughts over several years and experienced resolution of suicidal behavior within several weeks after introduction of EMFs treatment with no recurrence of symptoms during a follow-up of months to 3.5 years. These findings demonstrate that in MS pulsed applications of picotesla level EMFs improve mental depression and may reduce the risk of suicide by a mechanism involving the augmentation of 5-HT neurotransmission and resynchronization of circadian melatonin secretion.</p>
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<td width="573">Int J Neurosci. 1996 Jul;86(1-2):79-85.</td>
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<h1>Effect of weak electromagnetic fields on body image perception in patients with multiple sclerosis.</h1>
<p>Sandyk R.</p>
<p>NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.</p>
<p>Cerebellar ataxia is one of the most disabling symptoms of multiple sclerosis (MS) and also one of the least responsive to pharmacotherapy. However, cerebellar symptoms often improve dramatically in MS patients by brief, extracerebral applications of picotesla flux electromagnetic fields (EMFs). This report concerns two MS patients with chronic disabling ataxia who experienced rapid improvement in gait and balance after receiving a series of treatments with EMFs. To assess whether improvement in cerebellar gait is accompanied by changes in body image perception, a parietal lobe function, both patients were administered the Human Figure Drawing Test before and after a series of brief treatments with EMFs. Prior to application of EMFs these patients&#8217; free drawings of a person showed a figure with a wide-based stance characteristic of cerebellar ataxia. After receiving a series of EMFs treatments both patients demonstrated a change in body image perception with the drawings of the human figure showing a normal stance. These findings demonstrate that in MS improvement in cerebellar symptoms by pulsed applications of picotesla EMFs is associated with changes in the body image.</p>
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<td width="573">Int J Neurosci. 1996 Jul;86(1-2):67-77.</td>
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<h1>Treatment with weak electromagnetic fields attenuates carbohydrate cravings in a patients with multiple sclerosis.</h1>
<p>Sandyk R.</p>
<p>NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.</p>
<p>Pharmacological studies have implicated serotonergic (5-HT) neurons in the regulation of food intake and food preference. It has been shown that the urge to consume carbohydrate rich foods is regulated by 5-HT activity and that carbohydrate craving is triggered by 5-HT deficiency in the medical hypothalamus. Ingestion of carbohydrate foods stimulates insulin secretion which accelerates the uptake of tryptophan, the precursor of 5-HT and melatonin, into the brain and pineal gland, respectively. Thus, carbohydrate craving might be considered a form of &#8220;self medication&#8221; aimed at correcting an underlying dysfunction of cerebral 5-HT and pineal melatonin functions. A 51 year old woman with remitting-progressive MS experienced carbohydrate craving during childhood and adolescence and again in temporal association with the onset of her first neurological symptoms at the age of 45. Carbohydrate craving, which resembled the pattern observed in patients with seasonal affective disorder (SAD), was attenuated by a series of extracranial AC pulsed applications of picotesla (10(-12) Tesla) flux intensity electromagnetic fields (EMFs). It is suggested that AC pulsed EMFs applications activated retinal mechanisms which, through functional interactions with the medial hypothalamus, initiated an increased release of 5-HT and resynchronization of melatonin secretion ultimately leading to a decrease in carbohydrate craving. The occurrence of carbohydrate craving in early life may have increased the patient&#8217;s vulnerability to viral infection given the importance of 5-HT and melatonin in immunomodulation and the regulation of the integrity of the blood brain barrier. The recurrence of this craving in temporal relation to the onset of neurological symptoms suggests that 5-HT deficiency and impaired pineal melatonin functions are linked to the timing of onset of the clinical symptoms of the disease. The report supports the role of experimental factors in the pathophysiology of MS.</p>
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<td width="573">Int J Neurosci. 1995 Nov;83(1-2):81-92.</td>
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<h1>Resolution of dysarthria in multiple sclerosis by treatment with weak electromagnetic fields.</h1>
<p>Sandyk R.</p>
<p>NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.</p>
<p>It has been reported that 50% or more of patients diagnosed with multiple sclerosis (MS) exhibit speech impairment (dysarthria) which in some cases can be exceedingly disabling. Currently there is no effective medical treatment for the dysarthria of MS which occurs as a result of lesions to the cerebellum and its outflow tracts. It was reported recently that extracranial application of brief AC pulsed electromagnetic fields (EMFs) in the picotesla (pT) range intensity produced in patients with MS sustained improvement in motor functions including cerebellar symptomatology. This communication concerns two MS patients with a chronic progressive course who exhibited severe dysarthria which improved already during the initial treatment with pulsed EMFs and which resolved completely 3-4 weeks later. Since application of EMFs has been shown to alter: (a) the resting membrane potential and synaptic neurotransmitter release through an effect involving changes in transmembrane calcium flux; and (b) the secretion of pineal melatonin which in turn influences the synthesis and release of serotonin (5-HT) and gamma-amino butyric acid (GABA) in the cerebellum, it is suggested that the immediate improvement of the dysarthria occurred as a result of changes in cerebellar neurotransmitter functions particularly 5-HT and GABA rather than from remyelination.</p>
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<td width="573">Int J Neurosci. 1995 Jun;82(3-4):223-42.</td>
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<h1>Chronic relapsing multiple sclerosis: a case of rapid recovery by application of weak electromagnetic fields.</h1>
<p>Sandyk R.</p>
<p>NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.</p>
<p>A 54 year-old woman was diagnosed with multiple sclerosis (MS) in 1985 at the age of 45 after she developed diplopia, slurred speech, and weakness in the right leg. A Magnetic Resonance Imaging (MRI) scan obtained in 1985 showed several areas of plaque formation distributed in the periventricular white matter and centrum semiovale bilaterally. Coincident with slow deterioration in her condition since 1990 a second MRI scan was obtained in 1991 which showed a considerable increase in the number and size of plaques throughout both cerebral hemispheres, subcortical white matter, periventricularly and brainstem. In 1994, the patient received treatment with Interferon beta- 1b (Betaseron) for 6 months with no improvement in symptoms. However, following two successive extracranial applications of pulsed electromagnetic fields (EMFs) in the picotesla (pT) range each of 20 minutes duration the patient experienced an immediate improvement in symptoms most dramatically in gait, balance, speech, level of energy, swallowing, mood, and vision. On a maintenance program of 3 treatments per month the patient&#8217;s only symptom is mild right foot and leg weakness. The report points to the unique efficacy of externally applied pT range EMFs in the symptomatic treatment of MS, indicates a lack of an association between the extent of demyelinating plaques on MRI scan and rate and extent of recovery in response to EMFs, and supports the notion that dysfunction of synaptic conductivity due to neurotransmitter deficiency particularly of serotonin (5-HT) contributes more significantly to the development of MS symptoms than the process of demyelination which clinically seems to represent an epiphenomenon of the disease.</p>
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<td width="573">Int J Neurosci. 1994 Dec;79(3-4):199-212.</td>
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<h1>Weak electromagnetic fields attenuate tremor in multiple sclerosis.</h1>
<p>Sandyk R, Dann LC.</p>
<p>NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.</p>
<p>It has been estimated that about 75% of patients diagnosed with multiple sclerosis (MS) have tremor which can be exceedingly disabling. The most common tremor observed in patients with MS is a cerebellar intention tremor (&#8216;kinetic tremor&#8217;) although postural tremor (&#8216;static tremor&#8217;) is also common and often extremely incapacitating. Currently there is no effective medical treatment for the tremor of MS which, in some severe cases, may be abolished by stereotactic thalamotomy. It was reported recently that extracranial application of brief AC pulsed electromagnetic fields (EMFs) in the picotesla (pT) range produced improvement in motor and cognitive functions in patients with MS. The present communication concerns three MS patients with a chronic progressive course of the disease (mean age: 39.3 +/- 8.3 years; mean duration of illness: 11.3 +/- 3.2 years) in whom brief external applications of pulsed EMFs of 7.5 pT intensity reduced intention and postural tremors resulting in significant functional improvement. The report suggests that these extremely low intensity EMFs are beneficial also in the treatment of tremors in MS and that this treatment may serve as an alternative method to stereotactic thalamotomy in the management of tremor in MS. The mechanisms by which EMFs attenuate the tremors of MS are complex and are thought to involve augmentation of GABA and serotonin (5-HT) neurotransmission in the cerebellum and its outflow tracts.</p>
<h1>Therapeutic effects of alternating current pulsed electromagnetic fields in multiple sclerosis.</h1>
<p>Sandyk R. Dep. of Neuroscience, Institute for Biomedical Engineering and Rehab Services of Touro College, Dix Hills, New York.</p>
<p>Multiple sclerosis is the third most common cause of severe disability in patients between the ages of 15 and 50 years. The cause of the disease and its pathogenesis remain unknown. The last 20 years have seen only meager advances in the development of effective treatments for the disease. No specific treatment modality can cure the disease or alter its long-term course and eventual outcome. Moreover, there are no agents or treatments that will restore premorbid neuronal function. A host of biological phenomena associated with the disease involving interactions among genetic, environmental, immunologic, and hormonal factors, cannot be explained on the basis of demyelination alone and therefore require refocusing attention on alternative explanations, one of which implicates the pineal gland as pivotal. The pineal gland functions as a magnetoreceptor organ. This biological property of the gland provided the impetus for the development of a novel and highly effective therapeutic modality, which involves transcranial applications of alternating current (AC) pulsed electromagnetic fields flux density. This review summarizes recent clinical work on the effects of transcranially applied pulsed electromagnetic fields for the symptomatic treatment of the disease.</p>
<p>J In Biologic Effects of Light 1998 Symposium<strong> </strong></p>
<h1>Pulsing magnetic field effects on brain electrical activity in multiple sclerosis.</h1>
<p><strong></strong>Richards TL, Acosta-Urquidi,</p>
<p>Multiple sclerosis (MS) is a disease of the central nervous system. Clinical symptoms include central fatigue, impaired bladder control, muscle weakness, sensory deficits, impaired cognition, and others. The cause of MS is unknown, but from histologic, immunologic, and radiologic studies, we know that there are demyelinated brain lesions (visible on magnetic resonance images) that contain immune cells such as macrophages and T-cells (visible on microscopic analysis of brain sections). Recently, a histologic study has also shown that widespread axonal damage occurs in MS along with demyelination. What is the possible connection between MS and bio-electromagnetic fields? We recently published a review entitled &#8220;Bio-electromagnetic applications for multiple sclerosis,&#8221; which examined several scientific studies that demonstrated the effects of electromagnetic fields on nerve regeneration, brain electrical activity (electro-encephalography), neurochemistry, and immune system components. All of these effects are important for disease pathology and clinical symptoms in multiple sclerosis (MS). EEG was measured in this study in order to test our hypothesis that the pulsing magnetic device affects the brain electrical activity, and that this may be a mechanism for the effect we have observed on patient-reported symptoms. The EEG data reported previously were measured only during resting and language conditions. The purpose of the current study was to measure the effect of the electromagnetic device on EEG activity during and after photic stimulation with flashing lights. After photic stimulation, there was a statistically significant increase in alpha EEG magnitude that was greater in the active group compared to the placebo group in electrode positions P3, T5, and O1 (analysis of variance p&lt;.001, F=14, DF = 1,16). In the comparison between active versus placebo, changes measured from three electrode positions were statistically significantly even after multiple comparison correction.</p>
<h1>Treatment with weak electromagnetic fiels improves fatigue associated with multiple sclerosis.</h1>
<p>Sandyk R. NeuroCommunication Research Laboratories, Danbury, CT, USA</p>
<p>It is estimated that 75-90% of patients with multiple sclerosis (MS) experience fatigue at some point during the course of the disease and that in about half of these patients, subjective fatigue is a primary complaint. In the majority of patients fatigue is present throughout the course of the day being most prominent in the mid to late afternoon. Sleepiness is not prominent, but patients report that rest may attenuate fatigability. The pathophysiology of the fatigue of MS remains unknown. Delayed impulse conduction in demyelinated zones may render transmission in the brainstem reticular formation less effective. In addition, the observation that rest may restore energy and that administration of pemoline and amantadine, which increase the synthesis and release of monoamines, often improve the fatigue of MS suggest that depletion of neurotransmitter stores in damaged neurons may contribute significantly to the development of fatigue in these patients. The present report concerns three MS patients who experienced over several years continuous and debilitating fatigue throughout the course of the day. Fatigue was exacerbated by increased physical activity and was not improved by rest. After receiving a course of treatments with picotesla flux electromagnetic fields (EMFs), which were applied extracranially, all patients experienced improvement in fatigue. Remarkably, patients noted that several months after initiation of treatment with EMFs they were able to recover, after a short period of rest, from fatigue which followed increased physical activity. These observations suggest that replenishment of monoamine stores in neurons damaged by demyelination in the brainstem reticular formation by periodic applications of picotesla flux intensity EMFs may lead to more effective impulse conduction and thus to improvement in fatigue including rapid recovery of fatigue after rest.</p>
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<td width="573">Int J Neurosci. 1998 Jul;95(1-2):107-13.</td>
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<h1>Yawning and stretching&#8211;a behavioral syndrome associated with transcranial application of electromagnetic fields in multiple sclerosis.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience at the Institute for Biomedical Engineering and Rehabilitation Services of Touro College, Dix Hills, NY 11746, USA.</p>
<p>Intracerebral administration of adrenocorticotropic hormone (ACTH) elicits in experimental animals a yawning stretching behavior which is believed to reflect an arousal response mediated through the septohippocampal cholinergic neurons. A surge in plasma ACTH levels at night and just prior to awakening from sleep is also associated in humans with yawning and stretching behavior. Recurrent episodes of uncontrollable yawning and body stretching, identical to those observed upon awakening from physiological sleep, occur in a subset of patients with multiple sclerosis (MS) during transcranial therapeutic application of AC pulsed electromagnetic fields of picotesla flux density. This behavioral response has been observed exclusively in young female patients who are fully ambulatory with a relapsing remitting course of the disease who also demonstrate a distinctly favorable therapeutic response to magnetic stimulation. ACTH is employed for the treatment of MS due to its immunomodulatory effects and a surge in its release in response to AC pulsed magnetic stimulation could explain some of the mechanism by which these fields improve symptoms of the disease.</p>
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<td width="573">Int J Neurosci. 1997 Jan;89(1-2):39-51.</td>
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<h1>Progressive cognitive improvement in multiple sclerosis from treatment with electromagnetic fields.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.</p>
<p>It has long been recognized that cognitive impairment occurs in patients with multiple sclerosis (MS) particularly among patients with a chronic progressive course. MS is considered a type of &#8220;subcortical dementia&#8221; in which cognitive and behavioral abnormalities resemble those observed in patients with a frontal lobe syndrome. The Bicycle Drawing Test is employed for the neuropsychological assessment of cognitive impairment specifically that of mechanical reasoning and visuographic functioning. It also provides clues concerning the patient&#8217;s organizational skills which are subserved by the frontal lobes. Extracerebral pulsed applications of picotesla flux intensity electromagnetic fields (EMFs) have been shown to improve cognitive functions in patients with MS. I present three patients with long standing symptoms of MS who, on the initial baseline, pretreatment Bicycle Drawing Test, exhibited cognitive impairment manifested by omissions of essential details and deficient organizational skills. All patients demonstrated progressive improvement in their performance during treatment with EMFs lasting from 6-18 months. The improvement in cognitive functions, which occurred during the initial phases of the treatment, was striking for the changes in organizational skills reflecting frontal lobe functions. These findings demonstrate that progressive recovery of cognitive functions in MS patients are observed over time through continued administration of picotesla flux intensity EMFs. It is believed that the beneficial cognitive effects of these EMFs are related to increased synaptic neurotransmission and that the progressive cognitive improvement noted in these patients is associated with slow recovery of synaptic functions in monoaminergic neurons of the frontal lobe or its projections from subcortical areas.</p>
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<td width="573">Wiad Lek. 2003;56(9-10):434-41.</td>
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<h1>Application of variable magnetic fields in medicine&#8211;15 years experience.</h1>
<p>[Article in Polish]</p>
<p>Sieron A, Cieslar G.</p>
<p>Katedra i Klinika Chorob Wewnetrznych, Angiologii i Medycyny Fizykalnej SAM, ul. Batorego 15, 41-902 Bytom. sieron@mediclub.pl</p>
<p>The results of 15-year own experimental and clinical research on application of variable magnetic fields in medicine were presented. In experimental studies analgesic effect (related to endogenous opioid system and nitrogen oxide activity) and regenerative effect of variable magnetic fields with therapeutical parameters was observed. The influence of this fields on enzymatic and hormonal activity, free oxygen radicals, carbohydrates, protein and lipid metabolism, dielectric and rheological properties of blood as well as behavioural reactions and activity of central dopamine receptor in experimental animals was proved. In clinical studies high therapeutic efficacy of magnetotherapy and magnetostimulation in the treatment of osteoarthrosis, abnormal ossification, osteoporosis, nasosinusitis, multiple sclerosis, Parkinson&#8217;s disease, spastic paresis, diabetic polyneuropathy and retinopathy, vegetative neurosis, peptic ulcers, colon irritable and trophic ulcers was confirmed.</p>
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<td width="574">Ann Neurol. 2005 Oct 20; [Epub ahead of print]</td>
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<h1>Altered plasticity of the human motor cortex in Parkinson&#8217;s disease.</h1>
<p>Ueki Y, Mima T, Ali Kotb M, Sawada H, Saiki H, Ikeda A, Begum T, Reza F, Nagamine T, Fukuyama H.</p>
<p>Human Brain Research Center, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan.</p>
<p>Interventional paired associative stimulation (IPAS) to the contralateral peripheral nerve and cerebral cortex can enhance the primary motor cortex (M1) excitability with two synchronously arriving inputs. This study investigated whether dopamine contributed to the associative long-term potentiation-like effect in the M1 in Parkinson&#8217;s disease (PD) patients. Eighteen right-handed PD patients and 11 right-handed age-matched healthy volunteers were studied. All patients were studied after 12 hours off medication with levodopa replacement (PD-off). Ten patients were also evaluated after medication (PD-on). The IPAS comprised a single electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1 with an interstimulus interval of 25 milliseconds (240 paired stimuli every 5 seconds for 20 minutes). The motor-evoked potential amplitude in the right abductor pollicis brevis muscle was increased by IPAS in healthy volunteers, but not in PD patients. IPAS did not affect the motor-evoked potential amplitude in the left abductor pollicis brevis. The ratio of the motor-evoked potential amplitude before and after IPAS in PD-off patients increased after dopamine replacement. Thus, dopamine might modulate cortical plasticity in the human M1, which could be related to higher order motor control, including motor learning. Ann Neurol 2006.</p>
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<td width="573">Int J Neurosci. 1999 Aug;99(1-4):139-49.</td>
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<h1>AC pulsed electromagnetic fields-induced sexual arousal and penile erections in Parkinson&#8217;s disease.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience at the Institute for Biomedical Engineering and Rehabilitation Services, Touro College, Bay Shore, NY 11706, USA.</p>
<p>Sexual dysfunction is common in patients with Parkinson&#8217;s disease (PD) since brain dopaminergic mechanisms are involved in the regulation of sexual behavior. Activation of dopamine D2 receptor sites, with resultant release of oxytocin from the paraventricular nucleus (PVN) of the hypothalamus, induces sexual arousal and erectile responses in experimental animals and humans. In Parkinsonian patients subcutaneous administration of apomorphine, a dopamine D2 receptor agonist, induces sexual arousal and penile erections. It has been suggested that the therapeutic efficacy of transcranial administration of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density in PD involves the activation of dopamine D2 receptor sites which are the principal site of action of dopaminergic pharmacotherapy in PD. Here, 1 report 2 elderly male PD patients who experienced sexual dysfunction which was recalcitrant to treatment with anti Parkinsonian agents including selegiline, levodopa and tolcapone. However, brief transcranial administrations of AC pulsed EMFs in the picotesla flux density induced in these patients sexual arousal and spontaneous nocturnal erections. These findings support the notion that central activation of dopamine D2 receptor sites is associated with the therapeutic efficacy of AC pulsed EMFs in PD. In addition, since the right hemisphere is dominant for sexual activity, partly because of a dopaminergic bias of this hemisphere, these findings suggest that right hemispheric activation in response to administration of AC pulsed EMFs was associated in these patient with improved sexual functions</p>
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<td width="573">Int J Neurosci. 1999 Apr;97(3-4):225-33.</td>
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<h1>Treatment with AC pulsed electromagnetic fields improves olfactory function in Parkinson&#8217;s disease.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience at the Institute for Biomedical Engineering and Rehabilitation Services of Touro College, Dix Hills, NY 11746, USA.</p>
<p>Olfactory dysfunction is a common symptom of Parkinson&#8217;s disease (PD). It may manifest in the early stages of the disease and infrequently may even antedate the onset of motor symptoms. The cause of olfactory dysfunction in PD remains unknown. Pathological changes characteristic of PD (i.e., Lewy bodies) have been demonstrated in the olfactory bulb which contains a large population of dopaminergic neurons involved in olfactory information processing. Since dopaminergic drugs do not affect olfactory threshold in PD patients, it has been suggested that olfactory dysfunction in these patients is not dependent on dopamine deficiency. I present two fully medicated Parkinsonian patients with long standing history of olfactory dysfunction in whom recovery of smell occurred during therapeutic transcranial application of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density. In both patients improvement of smell during administration of EMFs occurred in conjunction with recurrent episodes of yawning. The temporal association between recovery of smell and yawning behavior is remarkable since yawning is mediated by activation of a subpopulation of striatal and limbic postsynaptic dopamine D2 receptors induced by increased synaptic dopamine release. A high density of dopamine D2 receptors is present in the olfactory bulb and tract. Degeneration of olfactory dopaminergic neurons may lead to upregulation (i.e., supersensitivity) of postsynaptic dopamine D2 receptors. Presumably, small amounts of dopamine released into the synapses of the olfactory bulb during magnetic stimulation may cause activation of these supersensitive receptors resulting in enhanced sense of smell. Interestingly, in both patients enhancement of smell perception occurred only during administration of EMFs of 7 Hz frequency implying that the release of dopamine and activation of dopamine D2 receptors in the olfactory bulb was partly frequency dependent. In fact, weak magnetic fields have been found to cause interaction with biological systems only within narrow frequency ranges (i.e., frequency windows) and the existence of such frequency ranges has been explained on the basis of the cyclotron resonance model.</p>
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<td width="573">Int J Neurosci. 1998 Sep;95(3-4):255-69.</td>
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<h1>Reversal of the bicycle drawing direction in Parkinson&#8217;s disease by AC pulsed electromagnetic fields.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.</p>
<p>The Draw-a-Bicycle Test is employed in neuropsychological testing of cognitive skills since the bicycle design is widely known and also because of its complex structure. The Draw-a-Bicycle Test has been administered routinely to patients with Parkinson&#8217;s disease (PD) and other neurodegenerative disorders to evaluate the effect of transcranial applications of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density on visuoconstructional skills. A seminal observation is reported in 5 medicated PD patients who demonstrated reversal of spontaneous drawing direction of the bicycle after they received a series of transcranial treatments with AC pulsed EMFs. In 3 patients reversal of the bicycle drawing direction was observed shortly after the administration of pulsed EMFs while in 2 patients these changes were observed within a time lag ranging from several weeks to months. All patients also demonstrated a dramatic clinical response to the administration of EMFs. These findings are intriguing because changes in drawing direction do not occur spontaneously in normal individuals as a result of relateralization of cognitive functions. This report suggests that administration of AC pulsed EMFs may induce in some PD patients changes in hemispheric dominance during processing of a visuoconstructional task and that these changes may be predictive of a particularly favourable response to AC pulsed EMFs therapy.</p>
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<td width="573">Int J Neurosci. 1998 May;94(1-2):41-54.</td>
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<h1>Transcranial AC pulsed applications of weak electromagnetic fields reduces freezing and falling in progressive supranuclear palsy: a case report.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience, Institute for Biomedical Engineering and Rehabilitation Services, Touro College, Dix Hills, NY 11746, USA.</p>
<p>Freezing is a common and disabling symptom in patients with Parkinsonism. It affects most commonly the gait in the form of start hesitation and sudden immobility often resulting in falling. A higher incidence of freezing occurs in patients with progressive supranuclear palsy (PSP) which is characterized clinically by a constellation of symptoms including supranuclear ophthalmoplegia, postural instability, axial rigidity, dysarthria, Parkinsonism, and pseudobulbar palsy. Pharmacologic therapy of PSP is currently disappointing and the disease progresses relentlessly to a fatal outcome within the first decade after onset. This report concerns a 67 year old woman with a diagnosis of PSP in whom freezing and frequent falling were the most disabling symptoms of the disease at the time of presentation. Both symptoms, which were rated 4 on the Unified Parkinson Rating Scale (UPRS) which grades Parkinsonian symptoms and signs from 0 to 4, with 0 being normal and 4 being severe symptoms, were resistant to treatment with dopaminergic drugs such as levodopa, amantadine, selegiline and pergolide mesylate as well as with the potent and highly selective noradrenergic reuptake inhibitor nortriptyline. Weekly transcranial applications of AC pulsed electromagnetic fields (EMFs) of picotesla flux density was associated with approximately 50% reduction in the frequency of freezing and about 80-90% reduction in frequency of falling after a 6 months follow-up period. At this point freezing was rated 2 while falling received a score of 1 on the UPRS. In addition, this treatment was associated with an improvement in Parkinsonian and pseudobulbar symptoms with the difference between the pre-and post EMF treatment across 13 measures being highly significant (p &lt; .005; Sign test). These results suggest that transcranial administration AC pulsed EMFs in the picotesla flux density is efficacious in the treatment of PSP.</p>
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<td width="573">J Neurosci. 1998 Feb;93(1-2):43-54.</td>
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<h1>Reversal of a body image disorder (macrosomatognosia) in Parkinson&#8217;s disease by treatment with AC pulsed electromagnetic fields.</h1>
<p><strong></strong>Sandyk R.</p>
<p>Department of Neuroscience, Institute for Biomedical Engineering and Rehabilitation Services of Touro College, Dix Hills, NY 11746, USA.</p>
<p>Macrosomatognosia refers to a disorder of the body image in which the patient perceives a part or parts of his body as disproportionately large. Macrosomatognosia has been associated with lesions in the parietal lobe, particularly the right parietal lobe, which integrates perceptual-sensorimotor functions concerned with the body image. It has been observed most commonly in patients with paroxysmal cerebral disorders such as epilepsy and migraine. The Draw-a-Person-Test has been employed in neuropsychological testing to identify disorders of the body image. Three fully medicated elderly Parkinsonian patients who exhibited, on the Draw-a-Person Test, macrosomatognosia involving the upper limbs are presented. In these patients spontaneous drawing of the figure of a man demonstrated disproportionately large arms. Furthermore, it was observed that the arm affected by tremor or, in the case of bilateral tremor, the arm showing the most severe tremor showed the greatest abnormality. This association implies that dopaminergic mechanisms influence neuronal systems in the nondominant right parietal lobe which construct the body image. After receiving a course of treatments with AC pulsed electromagnetic fields (EMFs) in the picotesla flux density applied transcranially, these patients&#8217; drawings showed reversal of the macrosomatognosia. These findings demonstrate that transcranial applications of AC pulsed EMFs affect the neuronal systems involved in the construction of the human body image and additionally reverse disorders of the body image in Parkinsonism which are related to right parietal lobe dysfunction.</p>
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<td width="573">Int J Neurosci. 1997 Nov;92(1-2):63-72.</td>
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<h1>Speech impairment in Parkinson&#8217;s disease is improved by transcranial application of electromagnetic fields.</h1>
<p><strong></strong>Sandyk R.</p>
<p>Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.</p>
<p>A 52 year old fully medicated physician with juvenile onset Parkinsonism experienced 4 years ago severe &#8220;on-off&#8221; fluctuations in motor disability and debilitating speech impairment with severe stuttering which occurred predominantly during &#8220;on-off&#8221; periods. His speech impairment improved 20%-30% when sertraline (75 mg/day), a serotonin reuptake inhibitor, was added to his dopaminergic medications which included levodopa, amantadine, selegiline and pergolide mesylate. A more dramatic and consistent improvement in his speech occurred over the past 4 years during which time the patient received, on a fairly regular basis, weekly transcranial treatments with AC pulsed electromagnetic fields (EMFs) of picotesla flux density. Recurrence of speech impairment was observed on several occasions when regular treatments with EMFs were temporarily discontinued. These findings demonstrate that AC pulsed applications of picotesla flux density EMFs may offer a nonpharmacologic approach to the management of speech disturbances in Parkinsonism. Furthermore, this case implicates cerebral serotonergic deficiency in the pathogenesis of Parkinsonian speech impairment which affects more than 50% of patients. It is believed that pulsed applications of EMFs improved this patient&#8217;s speech impairment through the facilitation of serotonergic transmission which may have occurred in part through a synergistic interaction with sertraline.</p>
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<td width="573">Int J Neurosci. 1997 Oct;91(3-4):189-97.</td>
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<h1>Treatment with AC pulsed electromagnetic fields improves the response to levodopa in Parkinson&#8217;s disease.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.</p>
<p>A 52 year old fully medicated Parkinsonian patient with severe disability (stage 4 on the Hoehn &amp; Yahr disability scale) became asymptomatic 10 weeks after he received twice weekly transcranial treatments with AC pulsed electromagnetic fields (EMFs) of picotesla flux density. Prior to treatment with EMFs, his medication (Sinemet CR) was about 50% effective and he experienced end-of-dose deterioration and diurnal-related decline in the drug&#8217;s efficacy. For instance, while his morning medication was 90% effective, his afternoon medication was only 50% effective and his evening dose was only 30% effective. Ten weeks after introduction of treatment with EMFs, there was 40% improvement in his response to standard Sinemet medication with minimal change in its efficacy during the course of the day or evening. These findings demonstrate that intermittent, AC pulsed applications of picotesla flux density EMFs improve Parkinsonian symptoms in part by enhancing the patient&#8217;s response to levodopa. This effect may be related to an increase in the capacity of striatal DA neurons to synthesize, store and release DA derived from exogenously supplied levodopa as well as to increased serotonin (5-HT) transmission which has been shown to enhance the response of PD patients to levodopa. Since decline in the response to levodopa is a phenomenon associated with progression of the disease, this case suggests that intermittent applications of AC pulsed EMFs of picotesla flux density reverse the course of chronic progressive PD.</p>
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<td width="573">Int J Neurosci. 1997 Sep;91(1-2):57-68.</td>
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<h1>Reversal of cognitive impairment in an elderly parkinsonian patient by transcranial application of picotesla electromagnetic fields.</h1>
<p><strong></strong>Sandyk R.</p>
<p>Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.</p>
<p>A 74 year old retired building inspector with a 15 year history of Parkinson&#8217;s disease (PD) presented with severe resting tremor in the right hand, generalized bradykinesia, difficulties with the initiation of gait with freezing, mental depression and generalized cognitive impairment despite being fully medicated. Testing of constructional abilities employing various drawing tasks demonstrated drawing impairment compatible with severe left hemispheric dysfunction. After receiving two successive transcranial applications, each of 20 minutes duration, with AC pulsed electromagnetic fields (EMFs) of 7.5 picotesla flux density and frequencies of 5Hz and 7Hz respectively, his tremor remitted and there was dramatic improvement in his drawing performance. Additional striking improvements in his drawing performance occurred over the following two days after he continued to receive daily treatments with EMFs. The patient&#8217;s drawings were subjected to a Reliability Test in which 10 raters reported 100% correct assessment of pre- and post drawings with all possible comparisons (mean 2 = 5.0; p &lt; .05). This case demonstrates in PD rapid reversal of drawing impairment related to left hemispheric dysfunction by brief transcranial applications of AC pulsed picotesla flux density EMFs and suggests that cognitive deficits associated with Parkinsonism, which usually are progressive and unaffected by dopamine replacement therapy, may be partly reversed by administration of these EMFs. Treatment with picotesla EMFs reflects a &#8220;cutting edge&#8221; approach to the management of cognitive impairment in Parkinsonism.</p>
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<td width="573">Int J Neurosci. 1997 Jun;90(1-2):75-86.</td>
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<h1>Treatment with weak electromagnetic fields restores dream recall in a parkinsonian patient.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience, Institute for Biomedical Engineering and Rehabilitation Services, Touro College, Dix Hills, NY 11746, USA.</p>
<p>Absent or markedly reduced REM sleep with cessation of dream recall has been documented in numerous neurological disorders associated with subcortical dementia including Parkinson&#8217;s disease, progressive supranuclear palsy and Huntington&#8217;s chorea. This report concerns a 69 year old Parkinsonian patient who experienced complete cessation of dreaming since the onset of motor disability 13 years ago. Long term treatment with levodopa and dopamine (DA) receptor agonists (bromocriptine and pergolide mesylate) did not affect dream recall. However, dreaming was restored after the patient received three treatment sessions with AC pulsed picotesla range electromagnetic fields (EMFs) applied extracranially over three successive days. Six months later, during which time the patient received 3 additional treatment sessions with EMFs, he reported dreaming vividly with intense colored visual imagery almost every night with some of the dreams having sexual content. In addition, he began to experience hypnagogic imagery prior to the onset of sleep. Cessation of dream recall has been associated with right hemispheric dysfunction and its restoration by treatment with EMFs points to right hemispheric activation, which is supported by improvement in this patient&#8217;s visual memory known to be subserved by the right temporal lobe. Moreover, since DA neurons activate REM sleep mechanisms and facilitate dream recall, it appears that application of EMFs enhanced DA activity in the mesolimbic system which has been implicated in dream recall. Also, since administration of pineal melatonin has been reported to induce vivid dreams with intense colored visual imagery in normal subjects and narcoleptic patients, it is suggested that enhanced nocturnal melatonin secretion was associated with restoration of dream recall in this patient. These findings demonstrate that unlike chronic levodopa therapy, intermittent pulsed applications of AC picotesla EMFs may induce in Parkinsonism reactivation of reticular-limbic-pineal systems involved in the generation of dreaming.</p>
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<td width="573">Int J Neurosci. 1996 Nov;87(3-4):209-17.</td>
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<h1>Brief communication: electromagnetic fields improve visuospatial performance and reverse agraphia in a parkinsonian patient.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.</p>
<p>A 73 year old right-handed man, diagnosed with Parkinson&#8217;s disease (PD) in 1982, presented with chief complaints of disabling resting and postural tremors in the right hand, generalized bradykinesia and rigidity, difficulties with the initiation of gait, freezing of gait, and mild dementia despite being fully medicated. On neuropsychological testing the Bicycle Drawing Test showed cognitive impairment compatible with bitemporal and frontal lobe dysfunction and on attempts to sign his name he exhibited agraphia. After receiving two successive treatments, each of 20 minutes duration, with AC pulsed electromagnetic fields (EMFs) of 7.5 picotesla intensity and 5 Hz frequency sinusoidal wave, his drawing to command showed improvement in visuospatial performance and his signature became legible. One week later, after receiving two additional successive treatments with these EMFs each of 20 minutes duration with a 7 Hz frequency sinusoidal wave, he drew a much larger, detailed and visuospatially organized bicycle and his signature had normalized. Simultaneously, there was marked improvement in Parkinsonian motor symptoms with almost complete resolution of the tremors, start hesitation and freezing of gait. This case demonstrates the dramatic beneficial effects of AC pulsed picotesla EMFs on neurocognitive processes subserved by the temporal and frontal lobes in Parkinsonism and suggest that the dementia of Parkinsonism may be partly reversible.</p>
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<td width="573">Int J Neurosci. 1996 Mar;85(1-2):111-24.</td>
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<h1>Freezing of gait in Parkinson&#8217;s disease is improved by treatment with weak electromagnetic fields.</h1>
<p>Sandyk R.</p>
<p>NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.</p>
<p>Freezing, a symptom characterized by difficulty in the initiation and smooth pursuit of repetitive movements, is a unique and well known clinical feature of Parkinson&#8217;s disease (PD). It usually occurs in patients with long duration and advanced stage of the disease and is a major cause of disability often resulting in falling. In PD patients freezing manifests most commonly as a sudden attack of immobility usually experienced during walking, attempts to turn while walking, or while approaching a destination. Less commonly it is expressed as arrest of speech or handwriting. The pathophysiology of Parkinsonian freezing, which is considered a distinct clinical feature independent of akinesia, is poorly understood and is believed to involve abnormalities in dopamine and norepinephrine neurotransmission in critical motor control areas including the frontal lobe, basal ganglia, locus coeruleus and spinal cord. In general, freezing is resistant to pharmacological therapy although in some patients reduction or increase in levodopa dose may improve this symptom. Three medicated PD patients exhibiting disabling episodes of freezing of gait are presented in whom brief, extracerebral applications of pulsed electromagnetic fields (EMFs) in the picotesla range improved freezing. Two patients had freezing both during &#8220;on&#8221; and &#8220;off&#8221; periods while the third patient experienced random episodes of freezing throughout the course of the day. The effect of each EMFs treatment lasted several days after which time freezing gradually reappeared, initially in association with &#8220;off&#8221; periods. These findings suggest that the neurochemical mechanisms underlying the development of freezing are sensitive to the effects of EMFs, which are believed to improve freezing primarily through the facilitation of serotonin (5-HT) neurotransmission at both junctional (synaptic) and nonjunctional neuronal target sites.</p>
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<td width="573">Int J Neurosci. 1998 Apr;93(3-4):239-50.</td>
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<h1>Treatment with AC pulsed electromagnetic fields normalizes the latency of the visual evoked response in a multiple sclerosis patient with optic atrophy.</h1>
<p>Sandyk R.</p>
<p>Department of Neuroscience at the Institute for Biomedical Engineering and Rehabilitation Services of Touro College, Dix Hills, NY 11746, USA.</p>
<p>Visual evoked response (VER) studies have been utilized as supportive information for the diagnosis of multiple sclerosis (MS) and may be useful in objectively monitoring the effects of various therapeutic modalities. Delayed latency of the VER, which reflects slowed impulse transmission in the optic pathways, is the most characteristic abnormality associated with the disease. Brief transcranial applications of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density are efficacious in the symptomatic treatment of MS and may also reestablish impulse transmission in the optic pathways. A 36 year old man developed an attack of right sided optic neuritis at the age of 30. On presentation he had blurring of vision with reduced acuity on the right and fundoscopic examination revealed pallor of the optic disc. A checkerboard pattern reversal VER showed a delayed latency to right eye stimulation (P100 = 132 ms; normal range: 95-115 ms). After he received two successive applications of AC pulsed EMFs of 7.5 picotesla flux density each of 20 minutes duration administered transcranially, there was a dramatic improvement in vision and the VER latency reverted to normal (P100= 107 ms). The rapid improvement in vision coupled with the normalization of the VER latency despite the presence of optic atrophy, which reflects chronic demyelination of the optic nerve, cannot be explained on the basis of partial or full reformation of myelin. It is proposed that in MS synaptic neurotransmitter deficiency is associated with the visual impairment and delayed VER latency following optic neuritis and that the recovery of the VER latency by treatment with pulsed EMFs is related to enhancement of synaptic neurotransmitter functions in the retina and central optic pathways. Recovery of the VER latency in MS patients may have important implications with respect to the treatment of visual impairment and prevention of visual loss. Specifically, repeated pulsed applications of EMFs may maintain impulse transmission in the optic nerve and thus potentially sustain its viability.</p>
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<p>Int J Neurosci, 66(3-4):209-35 1992 Oct</p>
<h1>Magnetic fields in the therapy of parkinsonism.</h1>
<p>Sandyk R NeuroCommunication Research Laboratories, Danbury, CT 06811.</p>
<p>In a recent Editorial published in this Journal, I presented a new and revolutionary method for the treatment of Parkinson&#8217;s disease (PD). I reported that extracranial treatment with picoTesla magnetic fields (MF) is a highly effective, safe, and revolutionary modality in the symptomatic management of PD. My conclusion was based on experience gained following the successful treatment of over 20 Parkinsonian patients, two of whom had levodopa-induced dyskinesias. None of the patients developed side effects during a several month period of follow-up. In the present communication, I present two reports. The first concerns four Parkinsonian patients in whom picoTesla MF produced a remarkable and sustained improvement in disability. Three of the patients had idiopathic PD and the fourth patient developed a Parkinsonian syndrome following an anoxic episode. In all patients, treatment with MF was applied as an adjunct to antiParkinsonian medication. The improvement noted in these patients attests to the efficacy of picoTesla MF as an additional, noninvasive modality in the therapy of the disease. The second report concerns two demented Parkinsonian patients in whom treatment with picoTesla MF rapidly reversed visuospatial impairment as demonstrated by the Clock Drawing Test. These findings demonstrate, for the first time, the efficacy of these MF in the amelioration of cognitive deficits in Parkinson&#8217;s disease. Since Alzheimer&#8217;s pathology frequently coexists with the dementia of Parkinsonism, these observations underscore the potential efficacy of picoTesla MF in the treatment of dementias of various etiologies.</p>
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		<title>Curriculum Vitae</title>
		<link>http://www.healinglightseminars.com/uncategorized/curriculum-vitae-david-rindge/</link>
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		<pubDate>Tue, 07 Feb 2012 02:44:38 +0000</pubDate>
		<dc:creator>Hldavid</dc:creator>
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		<description><![CDATA[David Rindge, DOM, LAc, RN Healing Light Seminars, Inc Center for Cooperative Medicine, PA 1601 Airport Blvd, Suite 1 Melbourne, FL 32901 (321) 751-7001 More than 37 years experience as a registered nurse, perfusionist, respiratory therapist, clinical lab technologist, doctor of oriental medicine, author and educator. Committed to advancing energy-based treatments and working with those [...]]]></description>
			<content:encoded><![CDATA[<p>David Rindge, DOM, LAc, RN<br />
Healing Light Seminars, Inc<br />
Center for Cooperative Medicine, PA<br />
1601 Airport Blvd, Suite 1<br />
Melbourne, FL 32901<br />
(321) 751-7001</p>
<p>More than 37 years experience as a registered nurse, perfusionist, respiratory therapist, clinical lab technologist, doctor of oriental medicine, author and educator. Committed to advancing energy-based treatments and working with those seeking to bring about kind, cost-effective health care.</p>
<p>Professional Experience</p>
<ul>
<li>Secretary – North American Association for Laser Therapy 2008 – 2010.</li>
<li>Presenter, Society of Photo-Optical Instrumentation Engineers, 2009.</li>
<li>Member, Scientific Advisory Board of the Research Center for Traditional Chinese Medicine, Medical University of Graz, Austria, 2009 – present.</li>
<li>Presenter, European Society for Biological Laser Therapy and Acupuncture, 2008.</li>
<li>Presenter, North American Association for Laser Therapy, 2009, 2008, 2006, 2002.</li>
<li>Presenter, European Medical Laser Association, 2007.</li>
<li>Membership Secretary – North American Association for Laser Therapy, 2005 – 2007.</li>
<li>President Emeritus, Florida State Oriental Medical Association, 2002 – 2004.</li>
<li>Co-author, Laser Therapy A Clinical Manual, 2003.</li>
<li>Founded the Florida Independent Investigational Review Board for LASER Acupuncture Research in 2001 to oversee clinical research with laser therapy.</li>
<li>Columnist, Acupuncture Today, June 2002 – Present.</li>
<li>Presenter, Laser Therapy Certification Seminar, American Association of Oriental Medicine, 2003.</li>
<li>Recipient, Conscious Living Partnerships’ Leader of Innovative Medicine Award, 2005.</li>
<li>Lecturer, New England School of Acupuncture, 2002.</li>
<li>President, Center for Cooperative Medicine, Melbourne, FL, 1999 – present.</li>
<li>President and lecturer, Healing Light Seminars, Melbourne, FL, 2001 – present.</li>
</ul>
<p>Education</p>
<ul>
<li>Diplomate in Acupuncture,  National Certification Commitssion for Acupuncture and Oriental Medicine.  1999.</li>
<li>Diploma, Acupuncture with concentration in oriental body work, acupuncture, Chinese herbology and homeopathy, Acupressure-Acupuncture Institute, Miami , FL 1997.</li>
<li>AS, Accelerated Option, RN, Miami Dade College, Miami, FL 1994<br />
Anna Brenner Myers Scholarship recipient.</li>
<li>Certification, American Board of Cardiovascular Perfusion, 1990</li>
<li>Certificate Extracorporeal Circulation, Northeastern University, 1988</li>
<li>BS, Cardiopulmonary Sciences, University of Central Florida , 1986</li>
<li>BA, Liberal Arts, University of Central Florida , 1986</li>
<li>Certificate, Respiratory Therapy, Miami Dade College, Miami, FL 1976, Summa cum Laude and Class Vice-President.</li>
</ul>
<p>Professional Memberships</p>
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<li>North American Association for Laser Therapy</li>
<li>World Association for Laser Therapy</li>
<li>European Medical Laser Association</li>
<li>Bioelectromagnetics Society</li>
<li>American Association of Acupuncture and Oriental Medicine</li>
<li>Florida State Oriental Medical Association</li>
<li>Alliance for Holistic Healing</li>
<li>Melbourne Palm Bay Area Chamber of Commerce</li>
</ul>
</div>
</div>
</div>
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		<pubDate>Tue, 07 Feb 2012 02:22:10 +0000</pubDate>
		<dc:creator>Hldavid</dc:creator>
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		<title>Osteonecrosis &#8211; Prevention of</title>
		<link>http://www.healinglightseminars.com/bioelectromagnetic-research-library/osteonecrosis-prevention-of/</link>
		<comments>http://www.healinglightseminars.com/bioelectromagnetic-research-library/osteonecrosis-prevention-of/#comments</comments>
		<pubDate>Sat, 04 Feb 2012 19:57:57 +0000</pubDate>
		<dc:creator>Hldavid</dc:creator>
				<category><![CDATA[Bioelectromagnetic Research Library]]></category>

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		<description><![CDATA[BMC Musculoskeletal Disord.  2011 Sep 29;12:215. Pulsed electromagnetic fields stimulation prevents steroid-induced osteonecrosis in rats. Ding S, Peng H, Fang HS, Zhou JL, Wang Z. Source Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People&#8217;s Republic of China. Abstract BACKGROUND: Pulsed electromagnetic fields (PEMF) stimulation has been used successfully to treat nonunion [...]]]></description>
			<content:encoded><![CDATA[<div>BMC Musculoskeletal Disord.  2011 Sep 29;12:215.</div>
<h1>Pulsed electromagnetic fields stimulation prevents steroid-induced osteonecrosis in rats.</h1>
<div>Ding S, Peng H, Fang HS, Zhou JL, Wang Z.</div>
<div>
<p><strong>Source</strong></p>
<p>Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People&#8217;s Republic of China.</p>
</div>
<div>
<p><strong>Abstract</strong></p>
<p><strong>BACKGROUND:</strong></p>
<p>Pulsed  electromagnetic fields (PEMF) stimulation has been used  successfully to  treat nonunion fractures and femoral head  osteonecrosis, but relatively  little is known about its effects on  preventing steroid-induced  osteonecrosis. The purpose of the study was  to investigate the effects  of PEMF stimulation on the prevention of  steroid-induced osteonecrosis  in rats and explore the underlying  mechanisms.</p>
<p><strong>METHODS:</strong></p>
<p>Seventy-two  male adult Wistar rats were divided into three groups  and treated as  follows. (1) PEMF stimulation group (PEMF group, n =  24): intravenously  injected with lipopolysaccharide (LPS, 10 g/kg) on  day 0 and  intramuscularly injected with methylprednisolone acetate  (MPSL, 20  mg/kg) on days 1, 2 and 3, then subjected to PEMF stimulation  4 h per  day for 1 to 8 weeks. (2) Methylprednisolone-treated group  (MPSL group, n  = 24): injected the same dose of LPS and MPSL as the  PEMF group but  without exposure to PEMF. (3) Control group (PS group, n  = 24): injected  0.9% saline in the same mode at the same time points.  The incidence of  osteonecrosis, serum lipid levels and the mRNA and  protein expression of  transforming growth factor ?1 (TGF-?1) in the  proximal femur were  measured 1, 2, 4 and 8 weeks after the last MPSL  (or saline) injection.</p>
<p><strong>RESULTS:</strong></p>
<p>The  incidence of osteonecrosis in the PEMF group (29%) was  significantly  lower than that observed in the MPSL group (75%), while  no osteonecrosis  was observed in the PS group. The serum lipid levels  were significantly  lower in the PEMF and PS groups than in the MPSL  group. Compared with  the MPSL and PS groups, the mRNA expression of  TGF-B1 increased,  reaching a peak 1 week after PEMF treatment, and  remained high for 4  weeks, then declined at 8 weeks, whereas the  protein expression of  TGF-B1 increased, reaching a peak at 2 weeks  after PEMF treatment, and  remained high for 8 weeks.</p>
<p><strong>CONCLUSIONS:</strong></p>
<p>PEMF stimulation  can prevent steroid-induced osteonecrosis in rats,  and the underlying  mechanisms involve decreased serum lipid levels and  increased expression  of TGF-B1.</p>
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