1. ARTICLE TITLE: Effects of magnetic fields on soliton mediated charge transport in biological systems
   REFERENCE: Journal of Advances In Physics, Vol. 6, No. 2, 26 November 2014, 1191.
   AUTHORS: L. Brizhik
   TOPIC: Review of literature about the interaction of PEMF with biological tissues
   ABSTRACT: In this paper, we analyze biological effects produced by magnetic fields in order to elucidate the physical mechanisms, which can produce them. We show that there is a hierarchy of such mechanisms and that the mutual interplay between them can result in the synergetic outcome. In particular, we analyze the biological effects of magnetic fields on soliton mediated charge transport in the redox processes in living organisms. Such solitons are described by nonlinear systems of equations and represent electrons that are self-trapped in alpha-helical polypeptides due to the moderately strong electron-lattice interaction. They represent a particular type of disssipativeless large polarons in low-dimensional systems. We show that the effective mass of solitons is different from the mass of free electrons, and that there is a resonant effect of the magnetic fields on the dynamics of solitons, and, hence, on charge transport that accompanies photosynthesis and respiration. These effects can result in non-thermal resonant effects of magnetic fields on redox processes in particular, and on the metabolism of the organism in general. This can explain physical mechanisms of therapies based on applying magnetic fields.
2. ARTICLE TITLE: Safety and Effectiveness of Therapeutic Magnetic Resonance in the Management of Postsurgical Lesion of the Diabetic Foot.
   REFERENCE: International Journal of Lower Extremity Wounds March 2015 14: 4-10
   AUTHORS: Lorenza Abbruzzese, DPM, Elisabetta Iacopi, MD, Alberto Coppelli, MD, Giovanni Bonino, DPM, Chiara Goretti, MD, and Alberto Piaggesi, MD
   TOPIC: Clinical trail on TMR® application on patients with Diabetic Foot Ulcers
   ABSTRACT: To evaluate the safety and effectiveness of therapeutic magnetic resonance (TMR) in the management of the diabetic foot (DF), we treated a group of consecutive type 2 diabetic inpatients with wide postsurgical lesions (Group A: N = 10; age 67.7 ± 18.9 years, duration of diabetes 22.3 ± 6.6 years, 8.1 ± 1.1%, body mass index 29.4 ± 2.1 kg/m2), for 2 consecutive weeks, while admitted, with a low-intensity magnetic resonance equipment, in addition to standard treatment. Patients, compared with a matched control group with the same clinical characteristics (Group B), were then followed monthly for 6 months to evaluate healing rate (HR), healing time (HT), rate of granulation tissue (GT) at 3 months, and adverse events. HR was of 90% in Group A and 30% in Group B (P < .05); GT was 73.7 ± 13.2% in Group A versus 51.84 ± 18.77% in Group B (P < .05). HT in Group A was 84.46 ± 54.38 days versus 148.54 ± 78.96 days in Group B (P < .01). No difference in adverse events (5 in Group A and 6 in Group B) was observed throughout the study period. In this pilot study, the use of TMR at this dose and duration was safe. The results also permit the observation that TMR plus standard care offered a faster healing rate compared with standard care alone.
3. ARTICLE TITLE: Treatment by Therapeutic Magnetic Resonance (TMR™) increases fibroblastic activity and keratinocyte differentiation in an in vitro model of 3D artificial skin.
   REFERENCE: Journal of Tissue Engineering and Regenerative Medicine (2015) Published online in Wiley Online Library DOI: 10.1002/term.2031
   AUTHORS: Letizia Ferroni, Gloria Bellin, Valeria Emer, Rosario Rizzuto, Maurizio Isola, Chiara Gardin and Barbara Zavan
   TOPIC: In vitro study on TMR® stimulation on the cells involved in wound healing processes (fibroblasts, endothelial cells, keratinocytes)
   ABSTRACT: This study investigated the effect of extremely low-frequency pulsed electromagnetic fields (PEMFs) on skin wound healing in an in vitro dermal-like tissue. In this study, fibroblast and endothelial cells were utilized for the in vitro reconstruction of dermal-like tissues treated for various times up to 21 days with PEMFs. The effects of PEMFs on cell proliferation (MTT test), cell ageing (β-galactosidase test, ROS production), gene expression, the quality of the extracellular matrix and the amount of fibroblast growth factors were analysed. The high quality of the dermis products in the presence of PEMFs at the end of the study was confirmed through the high degree of organization of keratinocytes, which were subsequently seeded on the aforementioned in vitro reconstructed dermis. The cells organized themselves in well-defined multi-layers and were better organized compared with the epidermis present on the dermis that was obtained without PEMF treatment.
4. ARTICLE TITLE: Calcium cyclotron resonance and diatiom mobility.
   REFERENCE: Bioelecromagnetics, 1987; 8(3) PMID 3663247
   AUTHORS: Smith SD, Mcleod BR, Liboff AR, Cooksey K.
   TOPIC: Biophysical model of PEMF influence in biological tissues
   ABSTRACT: Cyclotron resonance theory is applied to movement of biological ions through cell membranes: Ca ion is moved across membranes in response to AC e DC values of magnetic flux density at frequency derived from cyclotron resonance theory and a clear resonance is shown.
5. ARTICLE TITLE: A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial.
   REFERENCE: British Journal of Dermatology, 1992 Aug; 127(2) PMID 1390143
   AUTHORS: Stiller MJ, Pak GH, Shupack JL, Thaler S, Kenny C, Jondreau L.
   TOPIC: Clinical study on the application of PEMF in recalcitrant venous leg ulcers
   ABSTRACT: Prospective, randomized, double-blind, placebo controlled on PELUT (pulsed electromagnetic limb ulcer therapy) clinical study on patients treated at home for recalcitrant venous leg ulcers, for 3 h daily treatment for 8 weeks. Results show high efficacy: 50% of ulcers healed or improved versus 0% in the control, while 0% worsened versus 50% in the control.
6. ARTICLE TITLE: Mechanisms of electromagnetic interaction with cellular system.
   REFERENCE: Naturwissenschaften, 1992 Dec; 79(12) PMID 1480219
   AUTHORS: Grundler W, Kaiser F, Keilmann F, Walleczek J.
   TOPIC: Biophysical model of PEMF influence in biological tissues
   ABSTRACT: Review of interaction between electromagnetic field and biological systems: emphasis on occurrence of non-thermal interactions.
7. ARTICLE TITLE: Empirical test of an ion parametric resonance model for magnetic field interactions with PC-12 cells.
   REFERENCE: Bioelecromagnetics, 1995; 16(2) PMID 8074739
   AUTHORS: Blackman CF, Blanchard JP, Benane SG, House DE
   TOPIC: Biophysical model of PEMF influence in biological tissues
   ABSTRACT: Experimental confirmation of the Ion Parametric Resonance (IPR) model, examining the response of PC-12 cells: interactions between magnetic field and biological systems is based on a selective between the ratio of the static field to the AC field and the charge –to-mass ratio of ions of biological relevance.
8. ARTICLE TITLE: Clarification and applications of an ion parametric resonance model for magnetic field interactions with biological systems.
   REFERENCE: Bioelecromagnetics, 1994; 15(3) PMID 8074738
   AUTHORS: Blackman CF, Blanchard JP
   TOPIC: Biophysical model of PEMF influence in biological tissues
   ABSTRACT: It proposes an Ion Parametric Resonance (IPR) model improved with respect to that proposed by Lednev on the basis of the atomic spectroscopy theory described by Podgoretskii and Khrustalev: parameters controlled are densities of the AC and DC magnetic fields, AC frequency and charge to mass ratio of target ions. The IPR model is considered heuristic when applied to biological systems.
9. ARTICLE TITLE: Do electromagnetic fields interact directly with DNA.
   REFERENCE: Bioelecromagnetics, 1997; 18(2) PMID 9084861
   AUTHORS: Blank M,Goodman R.
   TOPIC: Biophysical model of PEMF influence in biological tissues, in particular with cell’s DNA
   ABSTRACT: Gene activation by magnetic fields can be due to direct interactions with moving electrons within DNA: magnetic fields stimulate transcription and can interact directly with DNA. The stimulus to changes in biosysnthesis in cells therefore can occur not only through the well documented cell membranes pathway.
10. ARTICLE TITLE: Mechanism of action of weak electromagnetic field on ionic currents in aqueous solutions of amino acids.
    REFERENCE: Bioelecromagnetics, 1997; 18(1) PMID 9125229
    AUTHORS: Novikov VV, Karnaukhov AV
    TOPIC: Biophysical model of PEMF influence in biological tissues
    ABSTRACT: It describes collective interaction of large ensambles of ions in solution with weak magnetic fields.
11. ARTICLE TITLE: Combined action of static and alternating magnetic fields on ionic currents in aqueous glutamic acid solution.
    REFERENCE: Bioelecromagnetics, 1998; 19(1) PMID 9453705
    AUTHORS: Zhadin MN, Novikov VV, Barnes FS, Pergola NF.
    TOPIC: Biophysical model of PEMF influence in biological tissues
    ABSTRACT: Combined parallel static and alternating magnetic field cause a rapid change in the ionic current flowing through a solution when the alternating field frequency is equal to the cyclotron frequency, with one peak of resonance between 1 and 10 Hz., at the very small amplitude of 0.02 to 0.08 microT.
12. ARTICLE TITLE: Fifty-hertz magnetic fields induce free radical formation in mouse bone marrow-derived promonocytes and macrophages.
    REFERENCE: Biochim Biophys Acta. 2004 Nov 1
    AUTHORS: Rollwitz J, Lupke M, Simkó M
    TOPIC: In vitro study on PEMF effect ion macrophages and its precusrors. In particular effects on free radical production.
    ABSTRACT: Our findings show a significant increase of free radical production after exposure to 50 Hz electromagnetic fields at a flux density of 1 mT to mouse bone marrow-derived (MBM) promonocytes and macrophages, indicating the cell-activating capacity of extremely low frequency magnetic fields (ELF-MF). We demonstrate that after exposure to ELF-MF mainly superoxide anion radicals were produced, both in MBM macrophages (33%) and also in their precursor cells (24%). To elucidate whether NADPH- or NADH-oxidase functions are target proteins for MF interaction, the flavoprotein inhibitor diphenyleneiodonium chloride (DPI) was used. MF-induced free radical production was not inhibited by DPI, whereas tetradecanoylphorbolacetate (TPA)-induced free radical production was diminished by about 70%. TPA is known to induce a direct activation of NADPH-oxidase through the PKC pathway. Since DPI lacks an inhibitory effect in MF-exposed MBM cells, we suggest that 50 Hz MF stimulates the NADH-oxidase pathway to produce superoxide anion radicals, but not the NADPH pathway. Furthermore, we showed an oscillation (1-10 days) in superoxide anion radical release in mouse macrophages, indicating a cyclic pattern of NADH-oxidase activity.
13. ARTICLE TITLE: Extremely low frequency electromagnetic fields as effectors of cellular responses in vitro: possible immune cell activation.
    REFERENCE: J Cell Biochem. 2004 Sep 1
    AUTHORS: Simkó M, Mattsson MO.
    TOPIC: Biophysical model of PEMF influence in biological tissues, in particular with cell’s DNA and immune response
    ABSTRACT: There is presently an intense discussion if electromagnetic field (EMF) exposure has consequences for human health. This include exposure to structures and appliances that emit in the extremely low frequency (ELF) range of the electromagnetic spectrum, as well as emission coming from communication devices using the radiofrequency part of the spectrum. Biological effects of such exposures have been noted frequently, although the implication for specific health effects is not that clear. The basic interaction mechanism(s) between such fields and living matter is unknown. Numerous hypotheses have been suggested, although none is convincingly supported by experimental data. Various cellular components, processes, and systems can be affected by EMF exposure. Since it is unlikely that EMF can induce DNA damage directly, most studies have examined EMF effects on the cell membrane level, general and specific gene expression, and signal transduction pathways. In addition, a large number of studies have been performed regarding cell proliferation, cell cycle regulation, cell differentiation, metabolism, and various physiological characteristics of cells. Although 50/60 Hz EMF do not directly lead to genotoxic effects, it is possible that certain cellular processes altered by exposure to EMF indirectly affect the structure of DNA causing strand breaks and other chromosomal aberrations. The aim of this article is to present a hypothesis of a possible initial cellular event affected by exposure to ELF EMF, an event which is compatible with the multitude of effects observed after exposure. Based on an extensive literature review, we suggest that ELF EMF exposure is able to perform such activation by means of increasing levels of free radicals. Such a general activation is compatible with the diverse nature of observed effects. Free radicals are intermediates in natural processes like mitochondrial metabolism and are also a key feature of phagocytosis. Free radical release is inducible by ionizing radiation or phorbol ester treatment, both leading to genomic instability. EMF might be a stimulus to induce an “activated state” of the cell such as phagocytosis, which then enhances the release of free radicals, in turn leading to genotoxic events. We envisage that EMF exposure can cause both acute and chronic effects that are mediated by increased free radical levels: (1) Direct activation of, for example macrophages (or other cells) by short-term exposure to EMF leads to phagocytosis (or other cell specific responses) and consequently, free radical production. This pathway may be utilized to positively influence certain aspects of the immune response, and could be useful for specific therapeutic applications. (2) EMF-induced macrophage (cell) activation includes direct stimulation of free radical production. (3) An increase in the lifetime of free radicals by EMF leads to persistently elevated free radical concentrations. In general, reactions in which radicals are involved become more frequent, increasing the possibility of DNA damage. (4) Long-term EMF exposure leads to a chronically increased level of free radicals, subsequently causing an inhibition of the effects of the pineal gland hormone melatonin. Taken together, these EMF induced reactions could lead to a higher incidence of DNA damage and therefore, to an increased risk of tumour development. While the effects on melatonin and the extension of the lifetime of radicals can explain the link between EMF exposure and the incidence of for example leukaemia, the two additional mechanisms described here specifically for mouse macrophages, can explain the possible correlation between immune cell system stimulation and EMF exposure.
14. ARTICLE TITLE: Alteration in cellular functions in mouse macrophages after exposure to 50 Hz magnetic fields.
    REFERENCE: J Cell Biochem. 2006 Sep 1
    AUTHORS: Frahm J, Lantow M, Lupke M, Weiss DG, Simkó M
    TOPIC: In vitro study on PEMF effects on macrophages
    ABSTRACT: In this study, the influence of 50 Hz magnetic fields (MF) at 1.0 mT was investigated on the phagocytic activity and on the interleukin-1beta (IL-1beta) production in differentiated macrophages. MF-exposure led to an increased phagocytic activity after 45 min, shown as a 1.6-fold increased uptake of latex beads in MF-exposed cells compared to controls. We also demonstrate an increased IL-1beta release in macrophages after 24 h exposure (1.0 mT MF). Time-dependent IL-1beta formation was significantly increased already after 4 h and reached a maximum of 12.3-fold increase after 24 h compared to controls. Another aspect of this study was to examine the genotoxic capacity of 1.0 mT MF by analyzing the micronucleus (MN) formation in long-term (12, 24, and 48 h) exposed macrophages. Our data show no significant differences in MN formation or irregular mitotic activities in exposed cells. Furthermore, the effects of different flux densities (ranging from 0.05 up to 1.0 mT for 45 min) of 50 Hz MF was tested on free radical formation as an endpoint of cell activation in mouse macrophage precursor cells. All tested flux densities significantly stimulated the formation of free radicals. Here, we demonstrate the capacity of ELF-EMF to stimulate physiological cell functions in mouse macrophages shown by the significantly elevated phagocytic activity, free radical release, and IL-1beta production suggesting the cell activation capacity of ELF-EMF in the absence of any genotoxic effects.
15. ARTICLE TITLE: Extremely low frequency electromagnetic field enhances human keratinocyte cell growth and decreases proinflammatory chemokine production.
    REFERENCE: The British Journal of Dermatology 2008 Jun;158(6)
    AUTHORS: Vianale G, Reale M, Amerio P, Stefanachi M, Di Luzio S, Muraro R
    TOPIC: In vitro study of PEMF effects on different tissue models in cell growth and inflammation inhibition
    ABSTRACT: Proliferation and differentiation of keratinocytes are central processes in tissue regeneration after injury. Chemokines, produced by a wide range of cell types including keratinocytes, play a regulatory role in inflammatory skin diseases. Several studies have shown that an electromagnetic field (EMF) can influence both inflammatory processes and repair mechanisms including wound healing on different tissue models. Our results show that ELF-EMF modulates chemokine production and keratinocyte growth through inhibition of the NF-kappaB signalling pathway and thus may inhibit inflammatory processes. ELF-EMF could represent an additional therapeutic approach in the treatment of skin injury.
16. ARTICLE TITLE: Effects of extremely low frequency magnetic field on the parameters of oxidative stress in heart.
    REFERENCE: Journal of physiology and pharmacology 2010 Jun
    AUTHORS: Goraca A, Ciejka E, Piechota A.
    TOPIC: In vivo (animals) study on PEMF effect in heart tissue’s ROS production
    ABSTRACT: Increasing production of free radicals in organisms is one of the putative mechanisms by which a extremely low frequency magnetic field (ELF-MF) may affect biological systems. The present study was designated to assess if ELF-MF applied in the magnetotherapy, affects generation of reactive oxygen species (ROS) in heart tissue and antioxidant capacity of plasma according to its working time. The experiments were performed on 3 groups of animals: group I – control; group II – exposed to 40 Hz, 7 mT, 30 min/day for 14 days (this field is commonly applied in magnetotherapy); group III – exposed to 40 Hz, 7 mT, 60 min/day for 14 days. Control rats were housed in a separate room without exposure to ELF-MF. Immediately after the last exposure, blood was taken from the tail vein and hearts were removed under anesthesia. The effect of the exposure to ELF-MF on oxidative stress was assessed on the basis of the measurements of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), total free sulphydryl groups (-SH groups) and reduced glutathione (GSH) concentrations in heart homogenates. The total antioxidant capacity of plasma was measured using ferric reducing ability method (FRAP). Exposure to ELF-MF (40 Hz, 7 mT, 30 min/day for 2 weeks) did not significantly alter tissue TBARS, H(2)O(2), total free -SH groups, reduced glutathione (GSH) and total antioxidant capacity of plasma. By contrast, ELF-MF with the same frequency and induction but used for 60 min/day for 14 days caused significant increase in TBARS and H(2)O(2) concentration (P<0.01) and decrease in the concentration of GSH (P<0.05) and total free -SH groups in heart homogenates. Moreover, exposure of rats to ELF-MF (40 Hz, 7 mT, 60 min/day for 2 weeks) resulted in the decrease of plasma antioxidant capacity. Our results indicate that effects of ELF-MF on ROS generation in the heart tissue and antioxidant capacity of plasma depend on its working time.
17. ARTICLE TITLE: Extremely low frequency electromagnetic fields modulate expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and cyclooxygenase-2 in the human keratinocyte cell line HaCat: potential therapeutic effects in wound healing.
    REFERENCE: The British Journal of Dermatology, 2010 Feb 1;162(2)
    AUTHORS: Patruno A, Amerio P, Pesce M, Vianale G, Di Luzio S, Tulli A, Franceschelli S, Grilli A, Muraro R, Reale M
    TOPIC: Biological basis of the effect of PEMF in wound healing
    ABSTRACT: Extremely low frequency (ELF) electromagnetic fields (EMF) are known to produce a variety of biological effects. Clinical studies are ongoing using EMF in healing of bone fractures and skin wounds. However, little is known about the mechanisms of action of ELF-EMF. Several studies have demonstrated that expression and regulation of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) are vital for wound healing; however, no reports have demonstrated a direct action of ELF-EMF in the modulation of these inflammatory molecules in human keratinocytes. Mediators of inflammation, such as reactive nitrogen and PGE(2), and keratinocyte proliferation are critical for the tissue regenerative processes. The ability of ELF-EMF to upmodulate NOS activities, thus nitrogen intermediates, as well as cell proliferation, and to downregulate COX-2 expression and the downstream intermediate PGE(2), highlights the potential therapeutic role of ELF-EMF in wound healing processes.
18. ARTICLE TITLE: Trends in Wound Repair: Cellular and Molecular Basis of Regenerative Therapy Using Electromagnetic Fields.
    REFERENCE: Current Molecular Medicine 2012, 12, 14-26
    AUTHORS: G.-E. Costin, S.A. Birlea and D.A. Norris
    TOPIC: Biological basis of the effect of PEMF in wound healing
    ABSTRACT: The data analysis supports three main effects of electromagnetic fields on the wound healing pathways: 1) an anti-inflammatory effect, by modulation of cytokine profile that induces the transition of the healing process from a chronic pro-inflammatory to an anti-inflammatory state; 2) a neo-angiogenic effect, by increased endothelial cells proliferation and tubulization and production of fibroblast growth factor (FGF)-2; and 3) a reepithelialization effect, by stimulation of collagen formation. We believe that utilization of ELF-EMF in larger clinical trials designed to optimize these functional parameters would facilitate a better understanding of ELFEMF-induced healing mechanisms and lead to improved therapeutic outcomes for this disabling condition which is often totally resistant to treatment.
19. ARTICLE TITLE: Pulsed Electromagnetic Fields Reduce Postoperative Interleukin-1β, Pain, and Inflammation: A Double-Blind, Placebo-Controlled Study in TRAM Flap Breast Reconstruction Patients.
    REFERENCE: Plastic and Reconstructive Surgery 2015 May;135(5):808e-817e.
    AUTHORS: Rohde CH, Taylor EM, Alonso A, Ascherman JA, Hardy KL, Pilla AA.
    TOPIC: Clinical study on the effect of PEMF treatment in surgical patients (breast reduction and augmentation)
    ABSTRACT: Background: Pulsed electromagnetic fields have been shown to reduce postoperative pain, inflammation, and narcotic requirements after breast reduction and augmentation surgical procedures. This study examined whether pulsed electromagnetic field therapy could produce similar results in patients undergoing unilateral transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction, a significantly more complex and painful surgical procedure.Methods: In this double-blind, placebo-controlled, randomized study, 32 patients undergoing unilateral TRAM flap breast reconstruction received active or sham pulsed electromagnetic field therapy. Pain levels were measured by using a visual analogue scale; narcotic use and wound exudate volume were recorded starting 1 hour postoperatively. Wound exudates were analyzed for interleukin-1β.Results: Mean visual analogue scale pain scores were 2-fold higher in the sham cohort at 5 hours and 4-fold higher at 72 hours (p < 0.01), along with a concomitant 2-fold increase in narcotic use in sham patients (p < 0.01). Wound exudate volume was 2-fold higher in the sham cohort at 24 hours (p < 0.01), and mean interleukin-1β concentration in wound exudates of sham patients was 5-fold higher at 24 hours (p < 0.001). Conclusions: Pulsed electromagnetic field therapy significantly reduced postoperative pain, inflammation, and narcotic use following TRAM flap breast reconstruction, paralleling its effect in breast reduction patients. Both studies also report a significant reduction of interleukin-1β in the wound exudate, supporting a mechanism involving a pulsed electromagnetic field effect on nitric oxide/cyclic guanosine monophosphate signaling, which modulates the body’s antiinflammatory pathways. Adjunctive pulsed electromagnetic field therapy could impact the speed and quality of wound repair in many surgical procedures.
20. ARTICLE TITLE: Pulsed electromagnetic field therapy promotes healing and microcirculation of chronic diabetic foot ulcers: a pilot study.
    REFERENCE: Adv Skin Wound Care. 2015 May;28(5):212-9. AUTHORS: Kwan RL, Wong WC, Yip SL, Chan KL, Zheng YP, Cheing GL.
    TOPIC: Biological basis of the effect of PEMF in wound healing
    ABSTRACT: Objective: To examine the effects of pulsed electromagnetic field (PEMF) therapy on promoting the healing and microcirculation of chronic diabetic foot ulcers. Design: A randomized, double-blind, placebo-controlled clinical trial on a homogenous subset of chronic diabetic foot ulcers. Setting: Hospital and university. Patients: Thirteen subjects (7 in the PEMF group and 6 in the control group) diagnosed with type 2 diabetes and had unsatisfactory healing of ulcer(s) in the preceding 4 weeks were recruited. Interventions: Subjects were randomly allocated to receive either active PEMF therapy (duration: 60 minutes; frequency: 12 Hz; intensity: 12 Gauss) or nonactive PEMF for 14 sessions within 3 weeks. Main outcome measures: Assessment on wound closure, wound depth, and microcirculation were performed at the baseline, end of the treatment period, and 1-month follow-up. Main results: By the end of the treatment period, there was an 18% decrease in wound size in the active PEMF group as compared with a 10% decrease in the control group. The PEMF group demonstrated significant cumulative increase in cutaneous capillary blood velocity (by 28%) and 14% increase in capillary diameter. In contrast, the control group showed a decrease in both capillary blood velocity and diameter. Conclusion: In this study, PEMF therapy seemed to accelerate wound healing and improve microcirculation.
21. ARTICLE TITLE: Pulsed electromagnetic field (PEMF) promotes collagen fibre deposition associated with increased myofibroblast population in the early healing phase of diabetic wound.
    REFERENCE: Arch Dermatol Res. 2016 Jan;308(1):21-9
    AUTHORS: Choi MC, Cheung KK, Li X, Cheing GL
    TOPIC: In vivo (44 rats) study on PEMF application in diabetic ulcers.
    ABSTRACT: The present study evaluated the effects of PEMF on collagen fibre deposition, collagen fibril alignment and collagen fibre orientation. The potential relationships between collagen fibre deposition and myofibroblast population in diabetic wound healing were also examined. Forty young male streptozotocin-induced diabetic Sprague-Dawley rats were randomly assigned to PEMF group or control group. 2 cm × 2 cm square wounds were made at their back. The PEMF group received daily exposure of PEMF to the wounds, while control group was handled in the same manner except that the PEMF device was not activated. Wound tissues harvested on post-wounding day 7, 10 and 14 were fixed, processed and sectioned. The abundance, fibril alignment and fibre orientation of type I collagen were quantified with picro-sirius polarization method and image analysis software (Nikon NIS Element AR). Myofibroblast population data were adopted from our previous study. Correlation between myofibroblast population and collagen fibre deposition was examined. There was significantly greater abundance of type I collagen fibre in the PEMF group than in the control on day 7 (P = .013), but not on day 10 or 14. No significant between-group differences were found in collagen fibril alignment and collagen fibre orientation at any measured time points. Positive correlation was found between collagen fibre deposition and myofibroblast population only on day 7 (r = .729, P = .007). In conclusion, PEMF can significantly increase collagen fibre in the early phase of diabetic wound healing, which is associated with the enhancement of myofibroblast population.
22. ARTICLE TITLE: Treatment of chronic varicose ulcers with pulsed electromagnetic fields: a controlled pilot study.
    REFERENCE: Ir Med J. 1991 Jun;84(2):54-5.
    AUTHORS: Todd DJ, Heylings DJ, Allen GE, McMillin WP
    TOPIC: Clinical trial on 19 patients with chronic varicose ulcers treated PEMF therapy
    ABSTRACT: To evaluate the efficacy of pulsed electromagnetic fields (PEMF) in healing of chronic varicose ulcers, 19 patients with this condition were included in a double-blind controlled clinical trial. All patients received standard ulcer therapy throughout the duration of the study and were randomly divided into two groups to receive either active or inactive PEMF therapy. Active therapy was provided by the use of a pait of helmholtz coils on a twice weekly basis over a five week period and inactive therapy was provided on an identical regimen with identical coils wound so that no magnetic field was produced when an electric current was passed through them. The clinician and patients were unable to distinguish the active or inactive coils. No statistically relevant difference was noted between the two groups in the healing rates of the ulcer, change in the lower leg girth, pain or infection rates. However there was a trend in favour of a decrease in ulcer size and lower leg girth in the group treated with active PEMF. As PEMF is a novel treatment for chronic varicose ulcers, more work needs to be done to establish treatment parameters and its usefulness in the treatment of this condition.
23. ARTICLE TITLE: Trends in wound repair: cellular and molecular basis of regenerative therapy using electromagnetic fields.
    REFERENCE: Curr Mol Med. 2012 Jan;12(1):14-26
    AUTHORS: Costin GE, Birlea SA, Norris DA
    TOPIC: Basis for PEMF application in chronic ulcers ABSTRACT: Chronic ulceration of the leg represents a major, underestimated problem of modern health care, involving physical and cosmetic impairment and social stigma along with high community costs for patients’ treatment. The increasing prevalence of chronic ulcers, currently reported to be as much as 0.3% in the general population, should stimulate identification of more efficacious therapeutic approaches to achieve complete healing. The strategies of regenerative medicine based on small molecules, biomimetic scaffolds, gene or cell therapy, and electromagnetic field manipulation represent some of the modern therapeutic alternatives for wound healing. Here we review in an integrated, interdisciplinary approach the modern cellular and molecular mechanistic concepts regarding the involvement of extremely low frequency electromagnetic fields (ELF-EMF) in the complex process of tissue repair, with particular focus on chronic wounds. The data analysis supports three main effects of electromagnetic fields on the wound healing pathways: 1) an antiinflammatory effect, by modulation of cytokine profile that induces the transition of the healing process from a chronic pro-inflammatory to an anti-inflammatory state; 2) a neo-angiogenic effect, by increased endothelial cells proliferation and tubulization and production of fibroblast growth factor (FGF)-2; and 3) a reepithelialization effect, by stimulation of collagen formation. We believe that utilization of ELF-EMF in larger clinical trials designed to optimize these functional parameters would facilitate a better understanding of ELFEMF- induced healing mechanisms and lead to improved therapeutic outcomes for this disabling condition which is often totally resistant to treatment.
24. ARTICLE TITLE: Pulsedelectromagnetic fields accelerate normal and diabetic wound healing by increasing endogenous FGF-2 release.
    REFERENCE: Plast Reconstr Surg. 2008 Jan;121(1):130-41.
    AUTHORS: Callaghan MJ, Chang EI, Seiser N, Aarabi S, Ghali S, Kinnucan ER, Simon BJ, Gurtner GC
    TOPIC: Basis for PEMF application in chronic ulcers
    ABSTRACT: Background: Chronic wounds, particularly in diabetics, result in significant morbidity and mortality and have a profound economic impact. The authors demonstrate that pulsed electromagnetic fields significantly improve both diabetic and normal wound healing in 66 mice through up-regulation of fibroblast growth factor (FGF)-2 and are able to prevent tissue necrosis in diabetic tissue after an ischemic insult. Methods: Db/db and C57BL6 mice were wounded and exposed to pulsed electromagnetic fields. Gross closure, cell proliferation, and vascularity were assessed. Cultured medium from human umbilical vein endothelial cells exposed to pulsed electromagnetic fields was analyzed for FGF-2 and applied topically to wounds. Skin flaps were created on streptozocin-induced diabetic mice and exposed to pulsed electromagnetic fields. Percentage necrosis, oxygen tension, and vascularity were determined. Results: Pulsed electromagnetic fields accelerated wound closure in diabetic and normal mice. Cell proliferation and CD31 density were significantly increased in pulsed electromagnetic field-treated groups. Cultured medium from human umbilical vein endothelial cells in pulsed electromagnetic fields exhibited a three-fold increase in FGF-2, which facilitated healing when applied to wounds. Skin on diabetic mice exposed to pulsed electromagnetic fields did not exhibit tissue necrosis and demonstrated oxygen tensions and vascularity comparable to those in normal animals. Conclusions: This study demonstrates that pulsed electromagnetic fields are able to accelerate wound healing under diabetic and normal conditions by up-regulation of FGF-2-mediated angiogenesis. They also prevented tissue necrosis in response to a standardized ischemic insult, suggesting that noninvasive angiogenic stimulation by pulsed electromagnetic fields may be useful to prevent ulcer formation, necrosis, and amputation in diabetic patients.
25. ARTICLE TITLE: Healing of chronic arterial and venous leg ulcers through systemic effects of electromagnetic fields.
    REFERENCE: Arch Med Res. 2002 May-Jun;33(3):281-9.
    AUTHORS: Cañedo-Dorantes L, García-Cantú R, Barrera R, Méndez-Ramírez I, Navarro VH, Serrano G
    TOPIC: Clinical trail on 26 patients with chronic leg ulcers treated with PEMF therapyABSTRACT: Background: Mitogen-activated autologous peripheral blood mononuclear cells applied locally on the ulcer surface promote healing of chronic arterial and venous leg ulcers. In vitro, extremely low frequency electromagnetic fields (ELF) interact with peripheral blood mononuclear cells (PBMC) via Ca++ channels, activating signal transduction cascades, promoting cytokine synthesis, and changing cell proliferation patterns. Methods: ELF frequencies were configured to interact in vitro with the proliferation patterns of PBMC obtained from normal human volunteers. These ELF were then applied peripherally as the sole treatment to 26 patients with 42 chronic leg ulcers of predominantly arterial or venous etiology unresponsive to previous medical and/or surgical treatments in a phase I before-after design. Results: At admission, age of ulcers had a skewed distribution with a median of 639 days. Wound healing or deleterious effects began in all patients during the first 2 weeks after ELF exposure, permitting their previously unresponsive ulcers to function as internal controls. After ELF exposure, 69% of all lesions were cured or healed >50% in a period <4 months. Defective wound healing was observed in lesions associated with important arterial occlusion, uncontrolled arterial hypertension, severe lipodermatosclerosis, non-pitting edema, and obesity (body mass index >30). Lesions worsened in patients with autoimmune diseases

Conclusions: Systemic effects are hypothetically explained by ELF activation of PBMC and their subsequent transportation to the ulcer site via humoral route. This therapy is effective in selected patients with chronic arterial and venous leg ulcers.

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