Multiple Sclerosis

Neural Regen Res. 2016 Dec; 11(12): 1888–1895. doi: 10.4103/1673-5374.195277 PMCID: PMC5270416

Extremely low frequency electromagnetic fields stimulation modulates autoimmunity and immune responses: a possible immuno-modulatory therapeutic effect in neurodegenerative diseases

Fabio Guerriero, M.D., Ph.D.^1,^2,^* and Giovanni Ricevuti^1,²¹Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, Pavia, Italy ²Azienda di Servizi alla Persona, Istituto di Cura Santa Margherita of Pavia, Pavia, Italy ^*Correspondence to: Fabio Guerriero, ti.aivapidatisrevinu@10oreirreug.oibaf.

Author contributions: All authors contributed to developing the concepts, designing the structure, and writing/revising the manuscript, and approved the final version before submission and agree to be accountable. Author information ? Article notes ? Copyright and License information ? Accepted 2016 Nov 25. Copyright : © Neural Regeneration Research This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Abstract

Increasing evidence shows that extremely low frequency electromagnetic fields (ELF-EMFs) stimulation is able to exert a certain action on autoimmunity and immune cells. In the past, the efficacy of pulsed ELF-EMFs in alleviating the symptoms and the progression of multiple sclerosis has been supported through their action on neurotransmission and on the autoimmune mechanisms responsible for demyelination. Regarding the immune system, ELF-EMF exposure contributes to a general activation of macrophages, resulting in changes of autoimmunity and several immunological reactions, such as increased reactive oxygen species-formation, enhanced phagocytic activity and increased production of chemokines. Transcranial electromagnetic brain stimulation is a non-invasive novel technique used recently to treat different neurodegenerative disorders, in particular Alzheimer’s disease. Despite its proven value, the mechanisms through which EMF brain-stimulation exerts its beneficial action on neuronal function remains unclear. Recent studies have shown that its beneficial effects may be due to a neuroprotective effect on oxidative cell damage. On the basis of in vitro and clinical studies on brain activity, modulation by ELF-EMFs could possibly counteract the aberrant pro-inflammatory responses present in neurodegenerative disorders reducing their severity and their onset. The objective of this review is to provide a systematic overview of the published literature on EMFs and outline the most promising effects of ELF-EMFs in developing treatments of neurodegenerative disorders. In this regard, we review data supporting the role of ELF-EMF in generating immune-modulatory responses, neuromodulation, and potential neuroprotective benefits. Nonetheless, we reckon that the underlying mechanisms of interaction between EMF and the immune system are still to be completely understood and need further studies at a molecular level.Keywords: electromagnetic fields, Alzheimer’s disease, transcranial magnetic stimulation, autoimmunity, immunomodulation

Introduction

The etiology of neurodegenerative diseases is multifactorial. Genetic polymorphisms, increasing age and environmental cues are recognized to be primary risk factors. Although different neuronal cell populations are affected across diverse neurodegenerative disorders, hallmark protein modifications is a common feature that supports the differential disease diagnosis and provides a mechanistic basis to gauge disease progression (Bossy-Wetzel et al., 2004).

It is becoming increasingly clear that, particularly for chronic neurodegenerative disorders occurring late in life, a complex combination of risk factors can initiate disease development and modify proteins that have a physiological function into ones with pathological roles via a number of defined mechanisms (Moreno-Gonzalez and Soto, 2011).

Amyloid-beta plaques and tau protein tangles – hallmarks of the pathology – are most likely a non-specific result of the disease process, rather than a cause (Lee et al., 2007). A large body of evidence supports the direct contribution of inflammation in the development and progression of neurodegeneration (Tweedie et al., 2007). A common denominator in the occurrence of different pathogenic mechanisms is oxidative stress accompanied by redox dysregulation, which have a role in mitochondrial dysfunction, toxicity, missignalling by calcium, glial cell dysfunction and neuroinflammation itself. Each of these can influence one another at multiple different levels, and hence oxidative stress can both be secondary to them as well as have a primary part in their initiation (von Bernhardi and Eugenin, 2012).

In the last years, evidence are remarkably revealing that Alzheimer’s disease (AD) has an autoimmune component (D’Andrea, 2005). In older patients the presence of anti-neuronal autoantibodies in the serum frequently occurs; if blood-brain barrier (BBB) dysfunction comes up, these autoantibodies are able to reach their targets and determine deleterious effect (D’Andrea, 2003). In fact, a profound change in BBB permeability has been observed in AD. In these patients amyloid deposits have been observed in microvessels and this overload is associated with degenerating endothelium (decreased mitochondrial content, increased pinocytotic vesicles), damaged smooth muscle cells and pericytes, and basement membrane changes (focal necrosis, reduplication, increased collagen content, disintegrating) (Thomas et al., 1996; Wardlaw et al., 2003). All these components strengthen the possibility that the ‘major pathological role of amyloid in AD may be to inflict vascular damage’ and hence, impair BBB function (Franzblau et al., 2013; Attems and Jellinger, 2014).

Immunoglobulins (IGs) have been detected in serum, cerebrospinal fluid and amyloid plaques of patients with AD. IGs are associated with vessel-associated amyloid, which has been linked to a faulty BBB (Franzblau et al., 2013). As a consequence, the presence of neuronal autoantibodies associated with a BBB dysfunction seems to be a relevant part of AD neuropathology (Attems and Jellinger, 2014).

Additional data about relationship between autoimmune diseases (e.g., thyroid dysfunction, diabetes) and AD has been proven. In fact, patients with AD have a significant increase in the values of anti-thyroglobulin and anti-microsomial autoantibodies compared to healthy controls (Genovesi et al., 1996).

Moreover, typical features of autoimmunity have been associated with both AD and diabetes (e.g., high levels of advanced glycation end products and their receptor have been detected in tissues and in the circulation in both disease) (Mruthinti et al., 2006).

In summary, these data in the context of the underlying mechanisms of many autoimmune diseases indicated that AD has proven autoimmune mechanisms, which provide a link between vascular pathology (altered BBB function) and neuronal cell death. Furthermore, according to these data, BBB dysfunction precedes neuronal degeneration and dementia (Rhodin and Thomas, 2001).

Electromagnetic Brain Stimulation and Immunomodulation in Neurodegenerative Diseases

Over the past decades, neuroscientists and clinicians have been exploring the properties of the brain’s electromagnetic activity for both diagnostic and therapeutic purposes. In the 1990s, research on electromagnetic radiation was motivated by the need to better understand the potential harmful effects of environmental magnetic fields (Bennett, 1995; Bracken and Patterson, 1996); actually, it is becoming increasingly clear that interactions between magnetic fields and biological systems deserve to be studied in their own right because these interactions appear to be fundamental to life processes and could represent a therapeutic agent in several diseases.

In our opinion, one of the more striking observations related to the effects of EMFs on biological systems concerns the presence of a “window effect,” showing that biological effects occur only at particular combinations of frequency and field intensity (Panagopoulos and Margaritis, 2010). These effects have been reported especially for changes in calcium ion flux in cells and tissues. Related window effects are reports of signal-specific quantitative and qualitative response to EMFs in several different tissues (Azanza and del Moral, 1994).

ELF-EMFs interact readily with the central nervous system (CNS). While the high-frequency EMFs encountered in industry can expose workers to an increased risk of AD (Hakansson et al., 2003), amyotrophic lateral sclerosis and multiple sclerosis (MS) (Johansen, 2004), EMFs of weak and very weak intensity can exert interesting and proven therapeutic effects on the CNS (Sandyk, 1992; Sandyk and Iacono, 1994; Boggio et al., 2012). The level of radiation is typically in the range of 1 millitesla (mT) in most studies.

Transcranial magnetic brain stimulation (TMS) is a commonly-used neurostimulation and a neuromodulation technique, based on the principle of electromagnetic induction of an electrical field in the brain. This field can be of sufficient magnitude and density to depolarize neurons, and when TMS pulses are applied repetitively they can modulate cortical excitability, decreasing or increasing it, depending on the parameters of stimulation, even beyond the duration of the train of stimulation (Fregni and Pascual-Leone, 2007; Ridding and Rothwell, 2007).

The last decade has seen a rapid increase in the applications of TMS to study cognition, neurobehavioral relations and the pathophysiology of several neurologic and psychiatric disorders. Evidence has accumulated that demonstrates that TMS provides a valuable tool for modulating brain activity in a specific, distributed, cortico-subcortical network through control and manipulation of cognition, neuromotoricity and behavior (George et al., 2007; Guerriero et al., 2015).

Since the immune system plays a primary role in the control of many diseases and tumor growth, many laboratories have investigated the influence of ELF-EMF stimulation on blood mononuclear cells, various cellular components and cellular processes; other studies have examined electromagnetic effects on specific genes expressions and signal transduction pathways, but the experimental data obtained are currently controversial (Cossarizza et al., 1993; Onodera et al., 2003).

The mechanisms by which ELF-EMFs elicit cellular responses are somewhat still unknown, and it is still unclear which cellular components mediate these fields’ effects. However, there are several hypotheses to explain EMF interaction with the living matter.

It is assumed that some type of initial interaction occurs at the level of the cell membrane and that specific signal amplification processes carry the membrane-mediated effect into the cell (Frey, 1993). Molecular studies of the membrane signaling processes have shown, for example, that the involved cells can use mechanisms such as intracellular second-messenger (e.g., Ca²⁺, cyclic adenosine monophosphate [cAMP], cyclic guanosine monophosphate [cGMP]) cascades, positive feedback, and linear membrane channel-gating (Grundler et al., 1992). Some of the most important calcium-related processes such as synaptic neurotransmitter and synthesis and release and levels of cAMP (Matthews and Gersdorff, 1996), essential for the functioning of the neurons that are influenced by EMFs (Rosen, 1992). In addition, amplification via calcium flux could also provide the means by which the membrane-mediated effects of EMFs could be carried into the cell (Karabakhtsian et al., 1994).

As described below, EMFs proved to exert a certain immune function modulation. Modulation of neural activity by ELF-EMFs could possibly counteract the aberrant pro-inflammatory responses present in neurodegenerative and neuropsychiatric disorders reducing their severity and, possibly, their onset.

Thus, in the next sections we will address the influence of ELF-EMFs on autoimmunity and immune cells, supposing that ELF-EMF may act on the basis of mechanisms centered on immunomodulation. This could have particular relevance for the treatment of neurodegenerative disorders, such as AD.

Low-frequency Electromagnetic Fields Stimulation and Autoimmunity

Regarding a possible relationship between EMF and autoimmunity, the researches conducted by Sandyk and colleagues deserve great interest. In the 1990s, Sandyk amply demonstrated the efficacy of pulsed ELF-EMFs of a few mT in alleviating the symptoms of MS through their action on axonal and synaptic neurotransmission (Sandyk and Iacono, 1993; Sandyk and Dann, 1995). Weekly treatment administered for years with very weak ELF-EMFs can alter the clinical course of chronic progressive MS, arresting progression of the disease for as long as four years (Sandyk, 1995a, 1997). This observation prompts the hypothesis that, in addition to effects on axonal and synaptic neurotransmission, effects may also be exerted on the autoimmune mechanisms responsible for demyelination.

Other proposals that to use pulsed ELF-EMFs of a few mT aims to modify the autoimmune pathology of the disease by eliciting profound membrane changes (Bistolfi, 2002) (the so-called Marinozzi effect) (Marinozzi et al., 1982) in the MS plaque cells.

While the action of ELF fields of a few pT is characterized by an improvement in neurotransmission, the use of ELF fields of a few mT aims to exert an action of local immunomodulation on the cells of the MS plaque through the induction of the Marinozzi effect. It therefore follows that the targets of ELF fields in the mT range will be the plaque cells (T-lymphocytes, macrophagic monocytes, microglia cells and dendritic cells), those cells disseminated in the seemingly normal nervous tissue (macrophages and microglia cells) (Bistolfi, 2007).

More specifically, the target should be the plasma membrane of these cells, which is almost always carpeted with microvilli and protrusions of various types. Since the plasma membrane is central to the relationships among immune cells (Lassmann et al., 2007) and since the plasma membrane itself is the elective target of ELF-EMF, a possible induction of the Marinozzi effect could slow down the activity of autoimmune cells in the plaque. It may determine an effect of local (on the brain) or regional immunomodulation (on the entire CNS) (Baureus Koch et al., 2003).

In far 1998, Richards et al. (1998) expressed the hope that electromagnetic fields might find application in the therapy of MS, both to manage symptoms and to achieve long-term effects by eliciting beneficial changes in the immune system and in nerve regeneration.

Our personal hypothesis is that – as observed in MS – similar effects could be present and relevant during EMF brain stimulation in patients with other CNS neurodegenerative disorders and be responsible for their therapeutic effect.

Low-frequency Electromagnetic Fields Stimulation and Immunomodulation

ELF-EMF effects on macrophages, nitric oxide and heat shock proteins

Macrophages are responsible for eliminating infectious agents and other cellular debris (Tintut et al., 2002). The recruitment of monocytes/macrophages to inflammatory sites and neoplastic tissues and their activation therein is crucial to the success of an immune reaction, in part because further cell migration is intimately related to leukocyte function. Resting macrophages have low levels of phagocytic activity and become fully active through the binding of pathogens or by local cytokine release. Once activated, macrophages exhibit an increased level of phagocytic activity and an increased production of reactive oxygen species (ROS) enabling the killing of microbes within phagosomes. The first step is the phagocytosis of the infectious agent, which is then transferred to the phagosome where it is killed by ROS and reactive nitrogen oxide species. The main protagonist of this process is nitric oxide (NO), which in turn induces the formation of cGMP, which in turn triggers a cascade of intracellular signaling. In the other hand, ROS also act as a signaling molecule and targets a wide range of physiological pathways. Activation of these cellular pathways also causes the secretion of inflammatory cytokines including IL-1b and TNF-alpha (Laskin and Laskin, 2001). Therefore when stimulated with bacterial toxins, NO and ROS stimulate cells to synthesize heat shock proteins (HSPs) (Polla et al., 1996).

Several studies have shown the effect of ELF-EMFs on macrophages. Kawczyk-Krupka and colleagues aimed to determine the effect of ELF-EMFs on the physiological response of phagocytes to an infectious agent. Human monocytic leukemia cell lines were cultured and 50 Hz, 1 mT EMF was applied for 4–6 hours to cells induced with Staphylococcus aureus. The growth curve of exposed bacteria was lower than the control, while field application increased NO levels. The increase was more prominent for Staphylococcus aureus-induced cells and appeared earlier than the increase in cells without field application (Kawczyk-Krupka et al., 2002). Increased cGMP levels in response to field application were closely correlated with increased NO levels (Azanza and del Moral, 1994).

Another study on mouse macrophages after short-term (45 minutes) exposure to 50 Hz EMF at 1.0 mT showed a significant uptake of carboxylated latex beads in macrophages, suggesting EMFs stimulate the phagocytic activity of their macrophages (Frahm et al., 2006). Tetradecanoylphorbol acetate (TPA) was used as positive control to prove the activating capacity of cells, as TPA is known to activate the protein kinase C and induce cellular processes including pinocytosis and phagocytosis (Laskin et al., 1980). On the basis of these data, ELF-EMF seems to potentially play a role in decreasing the growth rate of bacteria and other pathogens eliminated by phagocytosis.

A significant increase of free radical production has been observed after exposure to 50 Hz electromagnetic fields at a flux density of 1 mT to mouse macrophages (Aktan, 2004). To elucidate whether NADPH- or NADH-oxidase functions are influenced by EMF interaction, the flavoprotein inhibitor diphenyleneiodonium chloride (DPI) was used. EMF-induced free radical production was not inhibited by DPI, whereas TPA-induced free radical production was diminished by approximately 70%. Since DPI lacks an inhibitory effect in EMF-exposed cells, 50 Hz EMF stimulates the NADH-oxidase pathway to produce superoxide anion radicals, but not the NADPH pathway. Furthermore, the oscillation in superoxide anion radical release in mouse macrophages suggests a cyclic pattern of NADH-oxidase activity (Rollwitz et al., 2004).

An important aspect of these phagocytic cells is that they produce high levels of free radicals in response to infection, and the effect of ELF-EMF on free radicals has been widely proposed as a probable direct mechanism for the action of ELF-EMF on the living systems (Simko and Mattsson, 2004).

NO, a free radical, is an intra-cellular and inter-cellular signaling molecule and it constitutes an important host defense effector for the phagocytic cells of the immune system. It is synthesized by NO synthase, which has two major types: “constitutive” and “inducible”. Inducible nitric oxide synthase (iNOS) is particularly expressed in macrophages and other phagocytic cells that are stimulated during an immune response to infection (Aktan, 2004). Although high concentration of NO can be beneficial as an antibacterial and antitumor agent, an excess of NO can be fatal and can lead to cell injury. For example the excessive activity of iNOS has detrimental effects on oligodendrocytes, cells responsible for the myelination of neuron in the CNS (Klostergaard et al., 1991). The roles of NO in the pathophysiology of disease are still being defined, but there is a growing body of evidence that the neutralization of iNOS activity may have a therapeutic value (Parmentier et al., 1999).

Some studies have focused on the potential toxicity of the ensuing high-output NO-synthesis serving as a mean to eliminate pathogens or tumor cells, but the expression of iNOS, contributes to local tissue destruction during chronic inflammation. NO increases the ability of monocytes to respond to chemotactic agents more effectively, and it is considered to be one of the principal effector molecules involved in macrophage-mediated cytotoxicity (Desai et al., 2003).

It has been observed that exposure to ELF-EMFs modifies both NOS and MCP-1 chemokine expression and that these modifications are related to each other and are furthermore mediated by increased NF-?B protein expression (Goodman et al., 1994). EMF represents a non-pharmacological inhibitor of NO and an inducer of MCP-1, the latter of which activates one of these molecules and leads to inhibition of the former and vice versa, establishing a mechanism that protects cells from excess stimulation and contributes to the regulation of cellular homeostasis (Biswas et al., 2001). Moreover in vitro study observed a slight decrease was observed in iNOS levels was observed in cells induced with Staphlococcus aureus after ELF-EMF stimulation (Azanza and del Moral, 1994).

HSPs are evolutionarily conserved proteins known to play a key role in cellular defense against the effect of stressors and their function in modulating apoptosis has been well assessed (Beere, 2004). Concerning the relationship between EMF stimulus and HSPs expressions, Goodman et al. (1994) first demonstrated that HSP expression was enhanced by exposure to electromagnetic fields. Tokalov and Gutzeit (2004) showed the effect of ELF-EMF on heat shock genes and demonstrated that even a low dose of ELF-EMF (10 mT) caused an increase in HSPs, especially hsp70, implying that the cell senses ELF-EMF as a physical stressor.

ELF-EMF stimulation and oxidative stress

Oxidative stress derives from two primary sources: 1) chronic ROS creation that is generated from the mitochondrial electron transport chain during normal cellular function; 2) high levels of acute ROS generation resulting from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, particularly associated with the activation of the CNS immune system (Barja, 1998). In both circumstances, oxidative stress comes up when an imbalance between ROS production and clearance of radical species occurs.

ROS have been implicated as second messengers that activate protein kinase cascades, although the means by which ROS regulate signal transduction remains unclear. ROS release and cytokine production, such as IL-1?, are common cell activation markers in immune relevant cells. ROS is involved in the activation of IL-1? signal transduction pathway (Li and Engelhardt, 2006). To neutralize the detrimental effects of ROS, cells have evolved a hierarchy of sophisticated antioxidant response mechanisms regulated by NF-E2-related factor 2 (Nrf2) transcription factor (Tasset et al., 2010).

Environmental factors including EMFs, stressors or diseases that augment the former or lower the latter can amplify and drive the process. Thus, in practical terms, oxidative stress is determined by excessive exposure to oxidant molecules when there is insufficient availability of antioxidant mechanisms, with the resulting free ROS oxidizing vulnerable cellular constituents, including proteins, nucleic acids and lipids, inducing microglial activation, inducing pro-inflammatory and suppressing anti-inflammatory cytokines and related signaling pathways and ultimately causing both synaptic and neuronal damage and dysfunction (Bonda et al., 2010). Whereas most environmental electromagnetic radiations cause oxidative stress in the brain (Sahin and Gumuslu, 2007), ELF-EMF seems to have an antioxidant and neuroprotective effect (Medina and Tunez, 2010).

As shown by Tunez et al. (2006), ELF-EMF induces the antioxidant pathway Nrf2, which is closely associated with its protective effect against neurotoxicity induced by 3-nitropropionic acid (3-NP) (Tunez et al., 2006). This effect may be due to the induction of Nrf2, increasing its concentration in the nucleus as a result, at least in part, on its translocation from the cytoplasm to the nucleus. These changes in antioxidant systems were associated with a reduction of cell and oxidative damage biomarkers. In fact given that Nrf2 regulates the expression of antioxidant protein systems, its decrease may plausibly be related to a reduction in antioxidant system levels. Thus, the depletion of Nrf2 showed that 3-NP induced a significant decrease in antioxidant enzyme activity in the striatum and an intense depletion of glutathione levels. This was accompanied by clear and intense oxidative damage characterized by lipid and protein oxidation, an increase in cell death and damage markers and neuronal loss. Thus, the reduction in Nrf2 in both cytoplasm and nucleus may have been due to significant cell loss induced by 3-NP (Tunez et al., 2006).

Animal studies have demonstrated that ELF-EMF exposure, in the form of TMS (60 Hz, 0.7 mT) applied to rats for 2 hours twice daily, can be neuroprotective (Tunez et al., 2006; Tasset et al., 2012). Administered prior to and after a toxic insult to the brain, for example in the systemic injection of 3-nitropropionic acid to induce an animal model of Huntington’s disease (Tunez and Santamaria, 2009), ELF-EMF can mitigate oxidative damage, elevate neurotrophic protein levels in brain and potentially augment neurogenesis (Arias-Carrion et al., 2004).

EMF 1.0 mT exposure of mouse macrophages showed a significant increase in extracellular IL-1b release after only 4 hours of exposure, which was continuously increased after 12–24 hours of exposure. This data suggests that EMF stimulation is able to increase cytokines in murine macrophages. Cossarizza and colleagues described the increased release of IL-2, IL-1, and IL-6 in peritoneal lymphocytes after long-term exposure to ELF-EMF (Cossarizza et al., 1989). On the other hand, investigation on cytokine production by Pessina et al. showed no effects after EMF on peritoneal blood cells (Pessina and Aldinucci, 1998).

Beyond these results, such studies reiterate the importance that the cellular effects of ELF-EMFs depend, in a large part, on their intensity and exposure time, as well as on the phenotype of the cellular target and interactions with intracellular structures. The level and timing of exposure can potentially be scheduled to optimize endogenous compensatory mechanisms following an adverse reaction.

ELF-EMF effects on pro-inflammatory chemokines

Chemokines are produced by a variety of cells including monocytes, T lymphocytes, neutrophils, fibroblasts, endothelial cells and epithelial cells (Murdoch and Finn, 2000). Chemokines play a relevant role in inflammatory events, such as trans-endothelial migration and accumulation of leucocytes at the site of damage. In addition, they modulate a number of biological responses, including enzyme secretion, cellular adhesion, cytotoxicity, T-cell activation and tissue regeneration (Zlotnik and Yoshie, 2000).

Since their discovery, chemokines have emerged as important regulators of leukocyte trafficking, and MCP-1, one of the best-studied chemokines, is known to exert multiple effects on target cells, such as increased cytosolic calcium levels, superoxide anion production, lysosomal enzyme release, production of anti-inflammatory cytokines and adhesion molecules in monocytes. MCP-1 is involved in the induction of polarized type Th2 responses and in the enhancement of IL-4 production. A possible feedback loop for Th2 activation would be the production of IL-4 and IL-13 by Th2, which stimulates MCP-1 production and leads to further recruitment of Th2 cells (Moser and Loetscher, 2001).

The fine control of inflammatory mediator levels is critical to neuronal homeostasis and health. For example, a deficiency in neuronal TGF-? signaling promotes neurodegeneration and AD, whereas augmented TGF-? can act as an anti-inflammatory cytokine and has potential neuroprotective action in AD and following other insults to the central nervous system (Ren et al., 1997).

Studies have shown the anti-inflammatory effects of ELF-EMF in vivo; for instance, Selvam used a coil system emitting a 5 Hz frequency to treat rats with rheumatoid arthritis for 90 minutes, producing significant anti-exhudative effects and resulting in the restoration of normal functional parameters (Vianale et al., 2008). This anti-inflammatory effect was reported to be partially mediated through the stabilizing action of ELF-EMF on cell membranes, reflected the restoration of intracellular C^a2+ levels in plasma lymphocytes (Selvam et al., 2007). Other investigators have suggested that ELF-EMF can interact with cells through mechanisms that involve extracellular calcium channels (Cho et al., 1999).

Moreover, incubating mononuclear cells with an iNOS inhibitor showed a significant reduction of iNOS and an increase of MCP-1 levels, and these effects are consistent with iNOS and MCP-1 level modifications observed in mononuclear cells exposed to ELF-EMF. Selective inhibition of the NF-?B signaling pathway by ELF-EMF may be involved in the decrease of chemokine production. If so, ELF-EMF exposure, interfering with many cellular processes, may be included in the plethora of stimuli that modulate NF-?B activation (including pro-inflammatory cytokines such as tumor necrosis factor-? and IL-1?, chemokines, phorbol 12-myristate 13-acetate, growth factors, lipopolysaccharide, ultraviolet irradiation, viral infection, as well as various chemical and physical stresses) (Vianale et al., 2008).

Lymphocyte activity and electrotaxis: a possible link to ELF-EMF stimulation

Recent studies have shown that cells can directionally respond to applied electric fields, in both in vitro and in vivo settings, a phenomenon called electrotaxis. However, the exact cellular mechanisms for sensing electrical signals are still not fully well understood, and it is thus far unknown how cells recognize and respond to electric fields, although some studies have suggested that electro-migration of some cell surface receptors and ion channels in cells could be involved (Cortese et al., 2014). Directed cell migration is essential to numerous physiological processes including immune responses, wound healing, cancer metastasis and neuron guidance (Kubes, 2002). Normal blood lymphocytes and monocytes respond to a steady electric field in Transwell assays. All lymphocyte subsets, including naive and memory CD4⁺, CD8⁺ T cells and B cells migrated toward the cathode. Electrotaxisis highly directional and the uniform migration of circulating lymphocytes suggests that other leukocyte subsets (e.g., tissue memory cells) may undergo electrotaxis as well.

Lymphocytes respond to electric fields with activation of Erk-kinases and Akt, which are involved in chemo-attractant receptor signaling and in electrotactic signaling in other cells (Sotsios et al., 1999; Zhao et al., 2006). Activation of these pathways suggests that electrotaxis and chemotaxis engage common intracellular cell motility programs in responding lymphocytes. In fact, electric field exposure induces Erk1/2 and Akt activation in lymphocytes, consistent with the activation of the MAPK and PI3K signaling pathways implicated in coordinated cell motility. Furthermore, it has been proven that an applied electric field induced the electrotactic migration of endogenous lymphocytes to mouse skin (Lin et al., 2008). These data thus define electrotaxis andpotentially present an additional mechanism for the control of lymphocyte and monocyte migration.

ELF-EMFs can either inhibit or stimulate lymphocyte activity as a function not only of the exposure (Petrini et al., 1990), but also of the biological conditions to the cells are exposed, with mitogen-activated cells being more responsive than resting cells (Conti et al., 1986). To explain this ambivalence of the effects of ELF magnetic fields on the immune system, Marino and colleagues have presented the hypothesis that the biological effects of ELF magnetic fields are governed by non-linear laws, and that deterministic responses may therefore occur that are both real and inconsistent, thereby yielding two conflicting types of results (Marino et al., 2000). A particular role in the interaction of ELF-EMFs with lymphocytes seems to be played by the mobilization of intracellular Ca²⁺from the calciosomes and of extracellular Ca²⁺ through the membrane channels (Conti et al., 1985). The action of ELF-EMFs on lymphoid cells, however, can also be exerted on the functions of the plasma membrane: the duration of the ligand-receptor bond (Chiabrera et al., 1984), the clustering of membrane proteins (Bersani et al., 1997), the activity of enzymatic macro-molecules (Lindstrom et al., 2001), and the active ion pumps (Ca²⁺ ATPase and Na⁺ K⁺ATPase).

Conclusions

Several studies have shown that ELF-EMF exposure is able to activate primary monocytes and macrophages from different species and also in cell lines. This activation potential is comparable to the activation by certain chemicals resulting in physiologically relevant cellular responses.

In the past, several findings have demonstrated the efficacy of pulsed ELF-EMFs of a few mT in alleviating the symptoms of MS through their action on synaptic neurotransmission and autoimmunity (by determining cell membrane changes in plaques).

Moreover, ELF-EMF exposure contributes to a general activation of macrophages, resulting in changes of numerous immunological reactions, such as increased ROS formation, in an enhanced phagocytic activity, and in an increased IL-1? release. Therefore, we can deduce that EMFs activate physiological functions of immune cells. However, the underlying mechanisms of interaction between EMF and immune system are still to be completely understood and need further studies at the molecular level.

Animal studies have demonstrated that ELF-EMF exposure, in the form of transcranial magnetic stimulation (60 Hz, 0.7 mT) applied to rats for 2 hours twice daily, has been seen to be neuroprotective (Sahin and Gumuslu, 2007; Medina and Tunez, 2010).

The effects of low flux density magnetic fields are exerted on altered functional states, in the sense of hyper- or hypo-function, rather than on normal functional states. The neurophysiological interpretation is that neurotransmission is favored at various sites: partially synapses, the cerebellum, and interhemisphere transcallosal connections, an idea which is strongly supported by the rapid regression seen in certain symptoms in patients with MS (Sandyk, 1995b). Based on all these evidences such effect could be attributed to the correction of perturbations of synaptic conductivity and immunomodulation (Bistolfi, 2007), resulting in clinical therapeutic effect as observed in neurodegenerative disorders such as AD (Mruthinti et al., 2006; Attems and Jellinger, 2014).

However, so far there is still no general agreement on the exact biological effect elicited by EMFs on the physical mechanisms that may be behind their interaction with biological systems. Of course the biological effects of EMFs are dependent on frequency, amplitude, timing and length of exposure, but are also related to intrinsic susceptibility and responsiveness of different cell types (Tenuzzo et al., 2006). Level and timing of exposure can be potentially scheduled to optimize endogenous compensatory mechanisms following an adverse challenge.

In the light of results reviewed here, we conclude that there is growing evidence of the potential role of EMFs in biological modulation of autoimmunity, immune functions and oxidative stress. As a consequence, the hypothesis that ELF-EMFs explicit their therapeutic effect through modulation of immune relevant cells is of clear interest, in particular in neurodegenerative diseases.

It is notable to underline that the effects of ELF-EMFs are not unique as they depend on their intensity, exposure time and cellular targets; further efforts towards more scheduled and well defined level and timing of exposure should be warranted.

Hence, it is necessary to proceed with substantial research on this issue, paying particular attention to the choice of the appropriate biological model and controlled experimental conditions.

Footnotes

Conflicts of interest: The authors report no conflicts of interest in this work. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Articles from Neural Regeneration Research are provided here courtesy of Medknow Publications Altern Ther Health Med. 2011 Nov-Dec;17(6):22-8.

Long-term Effects of Bio-electromagnetic-energy regulation 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 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.

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.

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.

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. J Altern Complement Med. 2009 May;15(5):507-11.

Effect of BEMER magnetic field therapy on the level of fatigue in patients with multiple sclerosis: a randomized, double-blind controlled trial.

Piatkowski J, Kern S, Ziemssen T.

Source

Neurological Outpatient Center Reichenbachstrasse, Dresden, Germany.

Abstract

OBJECTIVES:

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.

DESIGN:

This was a monocenter, patient- and rater-blinded, placebo-controlled trial.

PATIENTS:

There were 37 relapsing-remitting patients with MS with significant fatigue in the study.

INTERVENTION:

The intervention consisted of BEMER magnetic field treatment for 8 minutes twice daily in comparison to placebo for 12 weeks.

OUTCOME MEASURES:

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).

RESULTS:

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’ 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.

DISCUSSION:

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.

Electromagn Biol Med. 2007;26(4):311-3.

Utilization of extremely low frequency (ELF) magnetic fields in chronic disease; five years experience: three case reports.

Mancuso M, Ghezzi V, Di Fede G.

Institute of Biological Medicine, Milano, Italy.

Abstract

We present three examples of the use of ELF magnetic therapy, two cases of multiple sclerosis and one of chronic pulmonary disease. In each of the two MS cases the Seqex device was applied as an adjunct to antioxidant medication two times a week for six weeks. Radiological and MRI examination indicated improvement in the two MS patients and stabilization in the patient with obstructive pulmonary disease following merely five treatments.

Altern Ther Health Med. 2003 Jul-Aug;9(4):38-48.

Effects of a pulsed electromagnetic therapy on multiple sclerosis fatigue and quality of life: a double-blind, placebo controlled trial.

Lappin MS, Lawrie FW, Richards TL, Kramer ED.

Energy Medicine Developments, (North America), Inc., Burke, Va., USA.

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.

OBJECTIVE: To evaluate the effects of a pulsed electromagnetic therapy on MS related fatigue, spasticity, bladder control, and overall quality of life.

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.

SUBJECTS: 117 patients with clinically definite MS.

INTERVENTION: Daily exposure to a small, portable pulsing electromagnetic field generator.

Sandyk R.

NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.

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’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.

Int J Neurosci. 1994 Dec;79(3-4):199-212.

Weak electromagnetic fields attenuate tremor in multiple sclerosis.

Sandyk R, Dann LC.

NeuroCommunication Research Laboratories, Danbury, CT 06811, USA.

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 (‘kinetic tremor’) although postural tremor (‘static tremor’) 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.

Therapeutic effects of alternating current pulsed electromagnetic fields in multiple sclerosis

Sandyk R. Dep. of Neuroscience, Institute for Biomedical Engineering and Rehab Services of Touro College, Dix Hills, New York.

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.

Double-blind study of pulsing magnetic field effects on multiple sclerosis.

Richards T. et.al. Dep. Radiology, University of Washington

We performed a double-blind study to measure the clinical and sub-clinical effects of an alternative medicine electromagnetic device on disease activity in multiple sclerosis (MS). The MS patients were exposed to a magnetic pulsing device where the frequency of the magnetic pulse was in the 4-13 Hz range. A total of 30 MS patients wore the device on pre-selected sites between 10 and 24 hours a day for 2 months. Half of the patients (15) randomly received a device that was magnetically inactive and the other half received an active device. Each MS patient received a set of tests to evaluate MS disease status before and after wearing the device. The tests included (1) a clinical rating (Kurtzke, EDSS), (2) patient-reported performance scales, and (3) quantitative electro-encephalography (QEEG) during a language task. Although there was no significant change between pretreatment and post-treatment in the EDSS scale, there was a significant improvement in the performance scale (PS) combined rating for bladder control, cognitive function, fatigue level, mobility, spasticity, and vision (active group -3.83 +/- 1.08, p < 0.005; placebo group -0.17 +/- 1.07, change in PS scale). There was also a significant change between pre-treatment and post-treatment in alpha EEG magnitude during the language task recorded at various electrode sites on the left side. In this double-blind, placebo-controlled study, we have demonstrated a statistically significant effect of themagnetic pulsing device on patient performance scales and on alpha EEG magnitude during a language task.
J In Biologic Effects of Light 1998 Symposium

Pulsing magnetic field effects on brain electrical activity in multiple sclerosis.

Richards TL, Acosta-Urquidi,

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 “Bio-electromagnetic applications for multiple sclerosis,” 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<.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.

Treatment with weak electromagnetic fields improves fatigue associated with multiple sclerosis.

Sandyk R. NeuroCommunication Research Laboratories, Danbury, CT, USA

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.

Int J Neurosci. 1998 Jul;95(1-2):107-13.

Yawning and stretching–a behavioral syndrome associated with transcranial application of electromagnetic fields in multiple sclerosis.

Sandyk R.

Department of Neuroscience at the Institute for Biomedical Engineering and Rehabilitation Services of Touro College, Dix Hills, NY 11746, USA.

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.

Int J Neurosci. 1997 Jan;89(1-2):39-51.

Progressive cognitive improvement in multiple sclerosis from treatment with electromagnetic fields.

Sandyk R.

Department of Neuroscience, Touro College, Dix Hills, NY 11746, USA.

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 “subcortical dementia” 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’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.

Wiad Lek. 2003;56(9-10):434-41.

Application of variable magnetic fields in medicine–15 years experience.

[Article in Polish]

Sieron A, Cieslar G.

Katedra i Klinika Chorob Wewnetrznych, Angiologii i Medycyny Fizykalnej SAM, ul. Batorego 15, 41-902 Bytom. sieron@mediclub.pl

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’s disease, spastic paresis, diabetic polyneuropathy and retinopathy, vegetative neurosis, peptic ulcers, colon irritable and trophic ulcers was confirmed.

January 31, 2019January 31, 2019

Millimeter Waves – EHF

Adv Gerontol. 2015;28(1):68-71.

INFLUENCE OF MILLIMETER-WAVE ELECTROMAGNETIC EMISSION ON NITRIC OXIDE SYNTHESIS DURING VESSEL ENDOTHELIUM AGING IN VITRO.

[Article in Russian] Molodtsova ID, Medvedev DS, Poliakova VO, Lin’kova NS, Gurko GI. Abstract
The applying of millimeter-wave electromagnetic emission (EHF-therapy) is an effective method for various age-related pathologies treatment, among other cardio-vascular diseases. During the EHF-emission of aging human endothelial cell cultures it was obtained changing of NO-synthase (eNOS), endothelin-1, angiotensin-2 and vasopressin expression dependence of irradiation exposition. These data have shown that EHF-emission has activated endothelium functional activity, which can play the important role to search for approaches to treatment of arterial hypertension and atherosclerosis. Bull Exp Biol Med. 2014 Sep;157(5):574-6. doi: 10.1007/s10517-014-2618-6. Epub 2014 Sep 27.

Effects of millimeter-wave electromagnetic exposure on the morphology and function of human cryopreserved spermatozoa.

Volkova NA¹, Pavlovich EV, Gapon AA, Nikolov OT.

Author information

¹Institute of Cryobiology and Cryomedicine Problems, National Academy of Sciences of Ukraine, Kharkov, Ukraine, volkovanatali2006@yandex.ru.

Abstract

Exposure of human cryopreserved spermatozoa to millimeter-wave electromagnetic radiation of 0.03 mW/cm2 density for 5 min in normozoospermia and for 15 min in asthenozoospermia lead to increase of the fraction of mobile spermatozoa without impairing the membrane integrity and nuclear chromatin status and without apoptosis generation.

Int J Mol Med. 2012 May;29(5):823-31. doi: 10.3892/ijmm.2012.919. Epub 2012 Feb 16.

Millimeter wave treatment promotes chondrocyte proliferation via G1/S cell cycle transition.

Li X, Ye H, Yu F, Cai L, Li H, Chen J, Wu M, Chen W, Lin R, Li Z, Zheng C, Xu H, Wu G, Liu X.

Source

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, P.R. China.

Abstract

Millimeter waves, high-frequency electromagnetic waves, can effectively alleviate the clinical symptoms in osteoarthritis patients, as a non-pharmaceutical and non-invasive physical therapy regimen. However, the molecular mechanisms of the therapeutic effects of millimeter wave treatment are not well understood. In the present study, the effect of millimeter waves on the G1/S cell cycle progression in chondrocytes and the underlying mechanism was investigated. Chondrocytes isolated from the knee of SD rats were cultured and identified using toluidine blue staining. The second generation chondrocytes were collected and stimulated with or without millimeter waves for 48 h. Chondrocyte viability was analyzed using the MTT assay. The cell cycle distribution of chondrocytes was analyzed by flow cytometry. mRNA and protein expression levels of cyclin D1, cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) and p21 were detected using real-time PCR and western blotting, respectively. Millimeter wave stimulation was found to significantly enhance chondrocyte viability. Moreover, the percentage of chondrocytes in the G0/G1 phase was significantly decreased, whereas that in the S phase was significantly increased. In addition, following millimeter wave treatment, cyclin D1, CDK4 and CDK6 expression was significantly upregulated, whereas p21 expression was significantly downregulated. The results indicate that millimeter wave treatment promotes chondrocyte proliferation via cell cycle progression. Int J Mol Med. 2010 Jul;26(1):77-84.

Millimeter wave treatment promotes chondrocyte proliferation by upregulating the expression of cyclin-dependent kinase 2 and cyclin A.

Li X, Du M, Liu X, Chen W, Wu M, Lin J, Wu G.

Source

Fujian University of Traditional Chinese Medicine, University Town, Minhou Shangjie, Fujian 350108, PR China.

Abstract

We investigated the effects of millimeter wave treatment on the expression of the cell cycle regulating proteins cyclin-dependent kinase 2 (CDK2) and cyclin A in chondrocytes. Knee articular cartilage from SD rats was used to establish cultured primary chondrocytes. After identification using toluidine blue staining, passage 2 chondrocytes were randomly divided into different groups and treated with nocodazole or millimeter wave. The RNA expression of CDK2 and cyclin A was measured using RT-PCR, and their protein levels were detected by Western blotting. Cell cycle analysis showed that nocodazole treatment significantly increased the number of G0/G1 and G2/M stage chondrocytes and decreased the amount of S phase cells. In contrast, millimeter wave treatment significantly decreased the number of G0/G1 and G2/M chondrocytes and increased the number of S phase cells. The mRNA and protein levels of CDK2 and cyclin A consistently demonstrated a reverse trend, with the lowest levels in the chondrocytes treated with nocodazole. The expression of CDK2 and cyclin A was higher in chondrocytes receiving millimeter wave treatment than in untreated cells. In conclusion, millimeter wave treatment induces CDK2 and cyclin A expression, accelerates S-phase entry and G2/M transition and promotes chondrocyte cell cycle progression.

Int J Mol Med. 2012 May;29(5):823-31. doi: 10.3892/ijmm.2012.919. Epub 2012 Feb 16.

Millimeter wave treatment promotes chondrocyte proliferation via G1/S cell cycle transition.

Li X, Ye H, Yu F, Cai L, Li H, Chen J, Wu M, Chen W, Lin R, Li Z, Zheng C, Xu H, Wu G, Liu X.

Source

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, P.R. China.

Abstract

The effect of rehabilitation with therapeutic Akhtala muds and electromagnetic radiation of millimeter range on biochemical indices in patients with post discectomy syndrome.

[Article in Russian] Dokhnadze TD.

Abstract

Noise EHF radiation under low-frequency (10 Hz) modulation both in monovariant and in combination with spinal tractions promotes regression of neuro-orthopedic disorders. Good effects were achieved due to improvement of zonal hemodynamics, conditions of functioning of the neuromuscular and locomotor system of the spine and limbs, favourable shifts in biochemical and autonomic status of patients with lumbar osteochondrosis and osteoarthrosis.

Evid Based Complement Alternat Med. 2006 Jun;3(2):201-7. Epub 2006 Apr 24.

Makar VR, Logani MK, Bhanushali A, Kataoka M, Ziskin MC.

Richard J Fox Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, PA 19140, USA.

BACKGROUND: Pain relief is reported to be the most common clinical application of electromagnetic millimetre waves.

AIM: To evaluate safety and pain relief effect of millimetre wave therapy (MWT) for treatment of chronic joint pain in a group of patients with diffuse connective tissue diseases.

METHODS: Twelve patients with diffuse connective tissue diseases received MWT in addition to their analgesic medication with non-steroidal anti-inflammatory drugs. MWT procedure included the exposure of tender points around the painful joints to electromagnetic waves with frequency 54-78GHz and power density of 2.5mW/cm(2). The time of exposure was 35 +/-5 min and the total number of sessions ranged from 5 to 10 (median 6). Intensity of pain, medication requirement, joint stiffness and subjective assessment of therapy success were measured before, during and immediately after the treatment, and after a 6-months follow-up.

RESULTS: No adverse effects of MWT were noted. Pain intensity and required medication decreased significantly after the treatment (p<0.05) and remained at the same level throughout the follow-up period. The joint stiffness decreased and the subjective assessment of the treatment success after 6 month did not change except in only one patient.

CONCLUSION: MWT applied to tender points around the affected joints was safe under the conditions of our study and after an appropriate full-scale double-blind clinical study, may be recommended as an effective adjunct therapy for chronic pain treatment in patients with diffuse connective tissue diseases.

Bioelectromagnetics. 2003 Jul;24(5):356-65.

Effect of millimeter waves on cyclophosphamide induced suppression of T cell functions.

Makar V, Logani M, Szabo I, Ziskin M.

Richard J. Fox Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.

Abstract

The effects of low power electromagnetic millimeter waves (MWs) on T cell activation, proliferation, and effector functions were studied in BALB/c mice. These functions are important in T-lymphocyte mediated immune responses. The MW exposure characteristics were: frequency = 42.2 GHz; peak incident power density = 31 +/- 5 mW/cm(2), peak specific absorption rate (SAR) at the skin surface = 622 +/- 100 W/kg; duration 30 min daily for 3 days. MW treatment was applied to the nasal area. The mice were additionally treated with cyclophosphamide (CPA), 100 mg/kg, a commonly used immunosuppressant and anticancer drug. Four groups of animals were used in each experiment: naive control (Naive), CPA treated (CPA), CPA treated and sham exposed (CPA + Sham), and CPA treated and MW exposed (CPA + MW). MW irradiation of CPA treated mice significantly augmented the proliferation recovery process of T cells (splenocytes). A statistically significant difference (P <.05) between CPA and CPA + MW groups was observed when cells were stimulated with an antigen. On the other hand, no statistically significant difference between CPA and CPA-Sham groups was observed. Based on flow cytometry of CD4(+) and CD8(+) T cells, two major classes of T cells, we show that CD4(+) T cells play an important role in the proliferation recovery process. MW exposure restored the CD25 surface activation marker expression in CD4(+) T cells. We next examined the effector function of purified CD4(+) T cells by measuring their cytokine profile. No changes were observed after MW irradiation in interleukin-10 (IL-10) level, a Th2 type cytokine, while the level of interferon-gamma (IFN-gamma), a Th1 type cytokine was increased twofold. Our results indicate that MWs enhance the effector function of CD4(+) T cells preferentially, through initiating a Th1 type of immune response. This was further supported by our observation of a significant enhancement of tumor necrosis factor-alpha (TNF-alpha) production by peritoneal macrophage’s in CPA treated mice. The present study shows MWs ameliorate the immunosuppressive effects of CPA by augmenting the proliferation of splenocytes, and altering the activation and effector functions of CD4(+) T cells.

Radiats Biol Radioecol. 2003 Sep-Oct;43(5):531-4.

Activity of natural killer cells of the spleen of mice exposed to low-intensity of extremely high frequency electromagnetic radiation.

[Article in Russian]

Oga? VB, Novoselova EG, Cherenkov DA, Fesenko EE.

Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, 142290 Russia. ogay@mail.icb.psn.ru

Abstract

The dose dependence of natural killer (NK) cell activity from mouse spleen upon action of low-intensity millimeter waves in the exposure range from 5 to 96 hours was studied. It has found an increase of NK activity by 24 hours posttreatment that returned to normal level in a day after the cessation of the irradiation. Also the stimulation of isolated NK cell activity after millimeter waves treatment within 1 hour was revealed.

Acupunct Electrother Res. 2003;28(1-2):11-8.

Treatment of rheumatoid arthritis with electromagnetic millimeter waves applied to acupuncture points–a randomized double blind clinical study.

Usichenko TI, Ivashkivsky OI, Gizhko VV.

Anesthesiology & Intensive Care Medicine Department, University of Greifswald, Germany. taras@uni-greifswald.de

Abstract

The aim of the study was to evaluate the efficacy and safety of electromagnetic millimeter waves (MW) applied to acupuncture points in patients with rheumatoid arthritis (RA). Twelve patients with RA were exposed to MW with power 2.5 mW and band frequency 54-64 GHz. MW were applied to the acupuncture points of the affected joints in a double blind manner. At least 2 and maximum 4 points were consecutively exposed to MW during one session. Total exposure time consisted of 40 minutes. According to the study design, group I received only real millimeter wave therapy (MWT) sessions, group II only sham sessions. Group III was exposed to MW in a random cross-over manner. Pain intensity, joint stiffness and laboratory parameters were recorded before, during and immediately after the treatment. The study was discontinued because of beneficial therapeutic effects of MWT. Patients from group I (n=4) reported significant pain relief and reduced joint stiffness during and after the course of therapy. Patients from group II (n=4) revealed no improvement during the study. Patients from group III reported the changes of pain and joint stiffness only after real MW sessions. After further large-scale clinical investigations MWT may become a non-invasive adjunct in therapy of patients with RA.

Zhonghua Kou Qiang Yi Xue Za Zhi. 2003 Mar;38(2):89-92.

Effect of millimeter therapy in burning mouth syndrome,

[Article in Chinese]

He Y, Lin M, Li BQ, Xia J, Zeng GM.

Department of Oral Medicine, West China College of Stomatology, Sichuan University, Chengdu 610041, China.

Abstract

OBJECTIVE: To observe the millimeter wave therapy responses in patients with burning mouth syndrome.

METHODS: Eighty patients were randomized divided into 4 groups. The first group was treated with both millimeter wave irradiation and routine medication, the second group with millimeter wave irradiation, the third with pretending millimeter wave irradiation and routine medication and the fourth with routine medication. Pain, extravasated blood level and autonomic nerve system condition were double-blindly evaluated either before or after the treatment.

RESULTS: Statistically significant difference (P < 0.05) was found as the degree of pain was compared before and after treatment of all the 4 groups. The first and second group, which were affected by the millimeter wave irradiation, had obvious improvements in the extravasated blood level and autonomic nerve system condition (P < 0.05). When the 4 groups were compared with each other, there were significant differences (P < 0.05) between the first and the fourth groups, and the second and the fourth groups regarding the reduction of pain. According to extravasated blood level, significant differences (P < 0.05) were found in the first and third or fourth groups, the second and third or fourth groups.

CONCLUSIONS: The irradiation of holographic point by millimeter wave can improve the patients’ pain, extravasated blood level and autonomic nerve system condition. It might provide a new treatment method for burning mouth syndrome.

Hua Xi Kou Qiang Yi Xue Za Zhi. 2001 Dec;19(6):366-8.

A study of millimeter wave’s clinical and immunological effects on oral lichen planus patients.

[Article in Chinese]

BALB/c mice were injected i.p. with either ketamine 80 mg/kg or chloral hydrate 450 mg/kg. Anaesthetized mice were exposed to unmodulated electromagnetic millimeter waves at the frequency of 61.22 GHz with a peak specific absorption rate of 420 W/kg and corresponding incident power density of 15 mW/cm2 for 15 min or sham-exposed. In combination with either of the anaesthetics used, mm waves increased the duration of anaesthesia by approximately 50% (p < 0.05) in a dose (power)-dependent manner. Sham exposure to mm waves did not affect the sleeping time of mice. Pretreatment of mice with naloxone, an opioid antagonist, did not change the duration of anaesthesia caused by the corresponding chemical agent, but completely blocked or decreased the additional effect of mm waves. The data in this study indicates that exposure of mice to mm waves in vivo releases endogenous opioids or enhances the activity of opioid signalling pathway.

Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997 May;17(5):286-8.

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.

[Article in Chinese]

Richard A. Sherman, PhD; Nancy M. Acosta, BS; Linda Robson, BA

The effect of exposure to pulsing electromagnetic fields on migraine activity was evaluated by having 42 subjects (34 women and 8 men), who met the International Headache Society’s criteria for migraine, participate in a double-blind, placebo-controlled study. Each subject kept a 1-month, pretreatment, baseline log of headache activity prior to being randomized to having either actual or placebo pulsing electromagnetic fields applied to their inner thighs for 1 hour per day, 5 days per week, for 2 weeks.After exposure, all subjects kept the log for at least 1 follow-up month. During the first month of follow-up, 73% of those receiving actual exposure reported decreased headaches (45% good decrease, 14% excellent decrease) compared to half of those receiving the placebo (15% worse, 20% good, 0% excellent). Ten of the 22 subjects who had actual exposure received 2 additional weeks of actual exposure after their initial 1-month follow-up. All showed decreased headache activity (50% good, 38% excellent). Thirteen subjects from the actual exposure group elected not to receive additional exposure. Twelve of them showed decreased headache activity by the second month (29% good, 43% excellent). Eight of the subjects in the placebo group elected to receive 2 weeks of actual exposure after the initial 1-month follow-up with 75% showing decreased headache activity (38% good, 38% excellent).In conclusion, exposure of the inner thighs to pulsing electromagnetic fields for at least 3 weeks is an effective, short-term intervention for migraine, but not tension headaches. Curr Rev Pain. 1999;3(5):342-347. Sphenopalatine Ganglion Analgesia. Day M. Texas Tech University Health Sciences Center, Department of Anesthesiology, 3601 4th Street, Room 1C282, Lubbock, TX 79430, USA. The sphenopalatine ganglion and its involvement in the pathogenesis of pain has been the subject of debate for the last 90 years. The ganglion is a complex neural center composed of sensory, motor, and autonomic nerves, which makes it difficult to determine its pathophysiology. Current indications for blockade of the sphenopalatine ganglion include sphenopalatine and trigeminal neuralgia, migraine and cluster headaches, and atypical facial pain. Methods of blockade use local anesthetics, steroids, phenol, and conventional radiofrequency and electromagnetic field- pulsed radiofrequency lesioning. The techniques for blockade range from superficial to highly invasive. Efficacy studies, though few and small, show promise in patients who have failed pharmacologic or surgical therapies. Anesth Pain Control Dent. 1992 Spring;1(2):85-9.

Headache: The Journal of Head and Face Pain

Volume 38 Issue 3 Page 208 – March 1998
doi:10.1046/j.1526-4610.1998.3803208.x

Initial Exploration of Pulsing Electromagnetic Fields for Treatment of Migraine

Richard A. Sherman, PhD; Linda Robson, BA; Linda A. Marden, MD

Two studies were conducted during which 23 patients with chronic migraine were exposed to pulsing electromagnetic fields over the inner thigh. In an open study, 11 subjects kept a 2-week headache log before and after 2 to 3 weeks of exposure to pulsing electromagnetic fields for 1 hour per day, 5 days per week. The number of headaches per week decreased from 4.03 during the baseline period to 0.43 during the initial 2-week follow-up period and to 0.14 during the extended follow-up which averaged 8.1 months. In a double-blind study, 9 subjects kept a 3-week log of headache activity and were randomly assigned to receive 2 weeks of real or placebo pulsing elactromagnetic field exposures as described above. They were subsequently switched to 2 weeks of the other mode, after which they kept a final 3-week log. Three additional subjects in the blind study inadvertently received half-power pulsing electromagnetic field exposures. The 6 subjects exposed to the actual device first showed a change in headache activity from 3.32 per week to 0.58 per week. The 3 subjects exposed to only half the dose showed no change in headache activity. Large controlled studies should be performed to determine whether this intervention is actually effective

The management of craniofacial pain in a pain relief unit.

Hillman L, Burns MT, Chander A, Tai YM.

Russells Hall Hospital, Dudley, United Kingdom.

This paper reports the results of 34 craniofacial pain sufferers who were treated at the Dudley Pain Relief Unit over a 1-year period. Most of the patients were referred by their general medical practitioners. They were adults representing all age groups, with a female-male ratio of 4:1. The average history of pain was 5.5 years. Neuralgic pain (as distinct from temporomandibular joint dysfunction syndrome, migrainous disorders, and pain of iatrogenic origin) was most frequently seen. Oral drug therapy, local injection of corticosteroids and analgesics, peripheral neurolysis, magnetotherapy, hypnotherapy, and acupuncture were the lines of management available. By the end of this study period, pain had been relieved or eliminated in 30 of the patients (88%).

January 31, 2019January 31, 2019

Our specific aim was to investigate whether a local static magnetic field of a permanent magnet, of either pole, affects resting skin blood perfusion. This was done by measuring skin blood perfusion (SBF) by laser-Doppler in dorsum skin of 2nd and 4th fingers of the nondominant hands of 12 volunteers. Both fingers were first exposed to sham magnets, and then the 2nd finger was exposed alternately to north and south poles of a neodymium magnet that produced a field of 4024 G at the palmar part of the finger and a field of 879 +/- 52 G at the site of finger dorsum SBF measurement. Each of the three exposure intervals was 15 min. SBF values were analyzed by first computing the average SBF during the last 5 min of each of the three 15-min exposure intervals. These SBF averages were initially tested for magnet or magnet-pole effects by analysis of variance for repeated measures with finger as a factor, using SBF values for each finger as the test variable. Results of this analysis revealed a large variability in finger SBF among subjects and no significant difference in SBF between exposure conditions (P = 0.705) or any significant interaction between SBF and finger (P = 0.396). However, when intersubject variability was reduced by using the flow difference between treated and nontreated fingers in each exposure interval as the test variable, a statistically significant effect (P = 0.016) attributable to magnet exposure was uncovered. This effect was a reduction in resting SBF in the magnet-exposed fingers that was similar for north and south pole magnet exposure. The present findings are the first to demonstrate a direct effect of locally applied magnets on human skin blood perfusion.

J Orthop Res. 2004 Jan;22(1):80-4.

Microcirculatory effects of pulsed electromagnetic fields.

Smith TL, Wong-Gibbons D, Maultsby J.

Department of Orthopaedic Surgery, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1070, USA.tsmith@wfubmc.edu

PURPOSE: Pulsed electromagnetic fields (PEMF) are used clinically to expedite healing of fracture non-unions, however, the mechanism of action by which PEMF stimulation is effective is unknown. The current study examined the acute effects of PEMF stimulation on arteriolar microvessel diameters in the rat cremaster muscle. The study hypothesis was that PEMF would increase arteriolar diameters, a potential mechanism involved in the healing process.

METHODS: Local PEMF stimulation/sham stimulation of 2 or 60 min duration was delivered to the cremaster muscle of anesthetized rats. Arteriolar diameters were measured before and after stimulation/sham stimulation using intravital microscopy. Systemic hemodynamics also were monitored during PEMF stimulation.

RESULTS: Local PEMF stimulation produced significant (p<0.001) vasodilation, compared to pre-stimulation values, in cremasteric arterioles in anesthetized rats (n=24). This dilation occurred after 2 min of stimulation (9% diameter increase) and after 1 h of stimulation (8.7% diameter increase). Rats receiving “sham” stimulation (n=15) demonstrated no statistically significant change in arteriolar diameter following either “sham” stimulation period. PEMF stimulation of the cremaster (n=4 rats) did not affect systemic arterial pressure or heart rate, nor was it associated with a change in tissue environmental temperature.

CONCLUSIONS: These results support the hypothesis that local application of a specific PEMF waveform can elicit significant arteriolar vasodilation. Systemic hemodynamics and environmental temperature could not account for the observed microvascular responses.

Neurosci Lett. 2002 Nov 22;333(2):136-40.

Vasodilitation of muscle microvessels induced by somatic afferent stimulation is mediated by calcitonin gene-related peptide release in the rat.

Loaiza LA, Yamaguchi S, Ito M, Ohshima N.

Department of Biomedical Engineering, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba Science City, Ibaraki 305-8575, Japan.

In anesthesized rats, the effects of electrical stimulation (ES) to the saphenous nerve on the microcirculation of the gracilis muscle were assessed through the measurement of two different hemodynamic parameters: (a). the muscle blood flow (MBF) using a laser Doppler flowmeter; and (b). the changes in diameter of the muscle arterioles observed directly using an intravital microscope system. Ipsilateral ES (5 V, 20 Hz, for 30 s) produced increases in MBF and mean arterial pressure (47+/-10% and 18+/-5%) over the baseline, while no significant changes in MBF were observed in the contralateral muscle. Neither selective nor simultaneous alpha- and beta-adrenergic blockade altered the increases in MBF induced by ipsilateral ES. The arteriolar diameter was found to increase by 38.9+/-5% following ipsilateral ES. This response in diameter was abolished after the topical application of a calcitonin gene-related peptide receptor antagonist (CGRP(8-37)). Contralateral ES produced a decrease in arteriolar diameter by 26+/-14%. Thus, ipsilateral nerve ES produced vasodilative responses in the muscle accompanied by increases in MBF independently of the sympathetic activity. Furthermore, CGRP was found directly involved in the reflex neural regulation of the muscle microcirculation, which suggests the participation of an axon reflex mechanism.

J Orthop Res. 1992 Mar;10(2):256-62.

The effects of pulsed electromagnetic fields on blood vessel growth in the rabbit ear chamber.

Greenough CG.

Department of Orthopaedics, Middlesbrough General Hospital, Cleveland, U.K.

A double-blind, controlled trial of the effects of pulsed electromagnetic fields on capillary growth in the rabbit ear chamber in adult New Zealand white rabbits has been performed. Three waveforms have been investigated. The first, a pulse burst waveform, produced a significant increase in the rate of growth of the vascular tissue within the chamber, but had no effect on macroscopic tissue maturation. The second and third, two different single pulse waveforms, had, in contrast, no significant effect on the rate of vascular growth and only an effect on vessel characteristics, with increased maturation of vessels using the second waveform. It is concluded that some of the observed effects of pulsed electromagnetic fields on tissue healing may be mediated through a primary effect on vascular growth.

January 31, 2019January 31, 2019

Melanoma

Otsuka Pharmaceutical Factory, Inc., Muya-cho, Naruto, Tokushima 772-8601, Japan. oharams@otsukakj.co.jp

Abstract

The effects of blue light on B16 melanoma cells and on the metastasis of these cells to the lungs were investigated in mice. The exposure of B16 melanoma cells to blue light in two 20-min sessions resulted in marked suppression of cell growth measured at 7 days after exposure. When these cells were harvested, re-inoculated into medium and incubated for a further 7 days, their growth activity returned to almost the same level as that of cultured cells from the non-exposure control group. The melanoma cells harvested after 7 days of incubation were injected intravenously into mice. In the non-exposure group, black nodules developed on the lung surface and the nodules increased in size over time. In the blue-light-exposure group, the development of such black nodules on the lung surface was delayed, and the nodules were smaller. Histopathological examination revealed that blue light suppressed the growth of metastatic tumor cells, and no increase in the number of melanin-containing cells or atypical cells was induced in the metastatic lesions. These results suggest that blue light suppresses the metastasis of B16 melanoma cells.

January 31, 2019January 31, 2019

Maxillofacial

Vopr Kurortol Fizioter Lech Fiz Kult. 2000 Nov-Dec;(6):27-9.

New aspects of rehabilitating patients with post-traumatic defects and deformation of the maxillofacial regions.

[Article in Russian]

Gerasimenko MIu, Filatova EV, Nikitin AA, Stuchilov VA, Kosiakov MN, Grishina NV.

Efficacy was compared of local magnetotherapy and electrostimulation in rehabilitation of patients with posttraumatic maxillofacial defects and deformities. A multidirectional mechanism of the two complexes on peripheral and central structures of the maxillofacial region was discovered.

Stomatologiia (Mosk). 1999;78(5):35-8. Low-frequency pulsed magnetotherapy combined with electrostimulation of biologically active points in the combined treatment of traumatic mandibular osteomyelitis. [Article in Russian] Korotkikh NG, Oreshkin AV. The results of treatment are analyzed in 51 patients (35 with exacerbation of chronic traumatic mandibular osteomyelitis and 16 with chronic traumatic mandibular osteomyelitis). Low-intensity pulsed magnetic therapy of the focus in combination with electric stimulation of segmentary bioactive points, synchronized by the patient’s pulse, are proposed to be added to the therapeutic complex. Such a modality improved the regional hemodynamics, promoted liquidation of the postoperative edema on days 1-2 after intervention, and sooner than after traditional therapy repaired the energy of the patient’s organism.

Anesth Pain Control Dent. 1992 Spring;1(2):85-9.

The management of craniofacial pain in a pain relief unit.

Hillman L, Burns MT, Chander A, Tai YM.

Russells Hall Hospital, Dudley, United Kingdom.

January 31, 2019January 31, 2019

Mandibular Osteomyelitis

Stomatologiia (Mosk). 1999;78(5):35-8.

Low-frequency pulsed magnetotherapy combined with electrostimulation of biologically active points in the combined treatment of traumatic mandibular osteomyelitis.

[Article in Russian]

Korotkikh NG, Oreshkin AV.

The results of treatment are analyzed in 51 patients (35 with exacerbation of chronic traumatic mandibular osteomyelitis and 16 with chronic traumatic mandibular osteomyelitis). Low-intensity pulsed magnetic therapy of the focus in combination with electric stimulation of segmentary bioactive points, synchronized by the patient’s pulse, are proposed to be added to the therapeutic complex. Such a modality improved the regional hemodynamics, promoted liquidation of the postoperative edema on days 1-2 after intervention, and sooner than after traditional therapy repaired the energy of the patient’s organism.

January 31, 2019January 31, 2019

Lymphadenitis

Stomatologiia (Mosk). 1999;78(2):28-30.

Low-intensity infrared laser radiation in the diagnosis and combined treatment of acute nonspecific lymphadenitis of the face and neck in children.

[Article in Russian]

Oasevich IA, Shargorodskii AG.

Clinical course of acute nonspecific lymphadenitis of the face and neck is studied in 241 patients aged 1-14 years in order to improve the diagnosis and therapy of this condition. General clinical examinations were supplemented by laser biophotometry and assessment of the activities of some local defense factors (lysozyme, beta-lysine, secretory and serum IgA). Multiple-modality treatment for the first time included magnetic laser therapy (MLT), and its efficacy is assessed. Results of biophotometry helped define objective criteria for the diagnosis and evaluation of treatment efficacy in children with acute lymphadenitis of the face and neck. MLT proved to be a highly effective treatment modality, decreasing the inflammation and correcting local (oral) defense factors. Use of MLT accelerated all phases of the inflammatory process, promoted its regression at the serous stage, and decreased the incidence of suppurative forms of acute lymphadenitis by 40%.

January 31, 2019January 31, 2019

Lupus Erythematosus

Ter Arkh. 1995;67(10):84-7.

The use of a pulsed magnetic field in the treatment of lupus erythematosus.

[Article in Russian]

Khamaganova IV, Berlin IuV, Volkov VE, Voinich ZV, Arutiunova ES.

The authors review literature data on application of impulsed magnetic field (IMF) in clinical practice. IMF introduction in LE treatment is thought beneficial because IMF antiinflammatory, analgetic effects, positive action on microcirculation, immunological reactivity, the ability to upgrade the effect of combined therapy. The trends observed in the clinical and laboratory indices allowed the authors to recommend IMF for wide application in LE.

January 31, 2019January 31, 2019

Longevity – Aging

Vopr Kurortol Fizioter Lech Fiz Kult. 1999 Sep-Oct;(5):7-9.

The characteristics of the geroprotective action of magnetotherapy in elderly patients with combined cardiovascular pathology.

[Article in Russian]

Abramovich SG, Fedotchenko AA, Koriakina AV, Pogodin KV, Smirnov SN.

Central hemodynamics, diastolic and pumping functions of the heart, myocardial reactivity, microcirculation and biological age of cardiovascular system were studied in 66 elderly patients suffering from hypertension and ischemic heart disease. The patients received systemic magnetotherapy which produced a geroprotective effect as shown by improved microcirculation, myocardial reactivity, central hemodynamics reducing biological age of cardiovascular system and inhibiting its ageing.

Naturforsch [C]. 2000 Mar-Apr;55(3-4):267-70.

Effect of a pulsed magnetic field and of first cold-pressure sunflower oil on mice.

Bellossi A, Rocher C, Ruelloux M.

Laboratoire de Biophysique, Faculte de Medecine, Rennes, France. bellossi@univ-rennes1.fr

In previous studies it has been shown that exposure of mice to a 12-Hz 6 mT unipolar square pulsed magnetic field (PMF) suppressed the excess of weight due to application of 1st cold-pressure sunflower oil. This time we considered the effect of oil and/or PMF on the growing curves lifespans of mice. The exposure took place for 30 min 5 days a week, from the 7th week of life to death. The results are 1) a broken slope in the growing curves from the 125th day of aging: the exposed mice were lighter than the controls, keeping the differences between the growing curves needed a repeated exposure all life long; 2) a significant increase in the lifespan of the controls which received oil versus the controls which received water; 3) an increase in the lifespan of the exposed mice versus the non-exposed control batches. On one hand it has been reported that essential polyunsaturated fatty acids found in first cold-pressure sunflower oil played a prominent role in membrane structures and in immune equilibrium. On the other hand, it was shown that oscillating electric fields could activate Na+K+-ATPase.

Aging (Milano). 1991 Sep;3(3):241-6.

Exposure to low-frequency pulsed electromagnetic fields increases mitogen-induced lymphocyte proliferation in Down’s syndrome.

Cossarizza A, Monti D, Bersani F, Scarfi MR, Zanotti M, Cadossi R, Franceschi C.

Institute of General Pathology, University of Modena School of Medicine, Italy.

We previously reported that exposure of human mitogen-stimulated peripheral blood lymphocytes (PBL) to extremely low frequency pulsed electromagnetic fields (PEMFs) could restore the defective proliferative capability of PBL from aged subjects. The effects of exposure to PEMFs were studied in PBL from 25 patients with Down’s syndrome (DS), a syndrome of premature aging characterized by precocious immune system derangement, including age-related defective PBL proliferative capability. PBL were stimulated with different doses of phytohemagglutinin, and cell proliferation was assessed by measuring the incorporation of tritiated thymidine. After PEMF-exposure, a significant increase in cell proliferation was observed in cells from DS children and young adults, but it was much more evident in PBL from relatively aged DS patients. The age-related effect of PEMFs on DS lymphocytes demonstrates that age must be considered a major variable when studies on DS are performed, and confirms that DS must be regarded as a syndrome of accelerated aging.

FEBS Lett. 1989 May 8;248(1-2):141-4.

Extremely low frequency pulsed electromagnetic fields increase interleukin-2 (IL-2) utilization and IL-2 receptor expression in mitogen-stimulated human lymphocytes from old subjects.

Cossarizza A, Monti D, Bersani F, Paganelli R, Montagnani G, Cadossi R, Cantini M, Franceschi C.

Institute of General Pathology, University of Modena, Italy.

The effects of the exposure of mitogen-stimulated human lymphocytes from aged subjects to low-frequency pulsed electromagnetic fields (PEMFs) were studied by measuring the production of interleukin-2 (IL-2) and the expression of IL-2 receptor. PEMF-exposed cultures that presented increased [3H]thymidine incorporation showed lower amounts of IL-2 in their supernatants, but higher percentages of IL-2 receptor-positive cells and of T-activated lymphocytes. Taken together, these data suggest that PEMFs were able to modulate mitogen-induced lymphocyte proliferation by provoking an increase in utilization of IL-2, most likely acting on the expression of its receptor on the plasma membrane.