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Bidirectional effect of electromagnetic fields on ketanserin-induced yawning in patients with multiple sclerosis: the role of melatonin.

5-HT2 receptors regulate sleep including yawning behavior. Ritanserin, a selective 5-HT2A receptor antagonist, increases the duration of slow wave in rats and humans. This effect is more pronounced during the light period when melatonin plasma levels are low; melatonin inhibits the sleep effects of ritanserin. These findings indicate that melatonin co-determines the effects of ritanserin on sleep. In a cohort of multiple sclerosis (MS) patients ketanserin, a selective 5-HT2A receptor antagonist, induces recurrent yawning particularly when administered in daytime. The frequency of yawning induced by the drug was modified by AC pulsed picotesla flux electromagnetic fields (EMFs) which affect melatonin secretion. Two MS patients are presented in whom the frequency of ketanserin-induced yawning was altered in opposite directions by these EMFs. The first patient, a 50 year old woman with a remitting-relapsing course, developed recurrent yawning and sleepiness after administration of ketanserin (10 mg, PO). Yawning was decreased dramatically during application of EMFs but was unaffected by a placebo EMFs treatment. The second patient, a 35 year old man with a chronic progressive course, manifested a single and brief yawn after administration of an equal dose of ketanserin. Yawning was increased dramatically during application of EMFs while remaining unchanged during a placebo EMFs treatment. These observations demonstrate a bidirectional effect of picotesla flux EMFs on ketanserin-induced yawning which may be related to differences in daytime melatonin plasma levels among MS patients. If validated by estimations of melatonin plasma levels in a larger cohort of patients the information derived from the effects of picotesla EMFs on ketanserin-induced yawning could be used to: (a) assess pineal melatonin functions in patients with MS; (b) indicate differences in pineal functions between male and female MS patients; and (c) indicate a relationship between plasma melatonin levels and the fatigue of MS.

Adult↗

Power line frequency electromagnetic fields do not increase the rate of protein synthesis in human skin fibroblasts as previously reported.

Rodemann et al. [Rodemann et al. (1987): Biochem Biophys Res Commun 145:1-9] reported that human skin fibroblasts increase their rate of protein synthesis by as much as over ninefold in response to long term exposure to 20 Hz, 8.4 mT (84 G) magnetic fields. Here we report studies of protein synthesis using an identical cell type, exposure conditions, and the same means of measuring protein synthetic rates. Our initial goal was to determine if the earlier results could be replicated, but we found an inconsistency in the earlier protocol. It exposed cells to [(3)H]leucine for 6 h prior to measuring incorporation into protein. We found, however, that 24 h is required for [(3)H]leucine to reach a steady state distribution across the cells' plasma membranes. In addition, we typically measured 100-200 cpm/thousand cells. This is four- to eightfold higher than the 19-28 cpm/1000 cells previously reported. Using these conditions, we could find no significant difference in protein synthesis rates between control cells and cells exposed for up to three weeks in an identical electromagnetic field. In addition, we investigated the effects of a 60 Hz field since that is the frequency used for electric power distribution in the United States. Again, we could find no significant effect of this field on rates of protein synthesis, even after 21 days of exposure.

Cells, Cultured↗

[Effect of pulsed electromagnetic fields (PEMF) on human periodontal ligament in vitro. Alterations of intracellular Ca2+].

The concept of orthodontic tooth movement is based on the hypothesis that teeth move as a result of the biological response of periodontal tissues to the mechanical forces applied. There is a widely held hypothesis that mechanical stress generates an electrical signal which sets in motion the subsequent events, as in bone exposed to mechanical forces electrical currents are produced affect bone growth and remodeling. This implies a transduction mechanism which translates the electrical signal into a biochemical message, recognizable by the cellular machine. This study is aimed at the identification of the message and the investigation of its control. In fact, the effect of Pulsed Electromagnetic Fields (PEMF) on the intracellular second messenger, cytoplasmic Ca2+ in Human Periodontal Ligament Fibroblasts (HPLF) was investigated. The resting intracellular ionized calcium concentration ([Ca+2]i) of HPLF cells was 232.7 +/- 25.0 nM, and with PEMF [Ca2+]i increased from 12 hrs to 499.0 +/- 115.5 nM up to 12 hrs, then reached to a steady level through 24 hrs. The PEMF were also found to decrease the responses towards epidermal growth factor (EGF) and serum, when the degree of response was based on the intracellular Ca2+ transient. These effects of PEMF were mimicked by 12-0-tetradecanoyl phorbol 13-acetate (TPA), a potent activator of protein kinase C. Some reports have suggested that fibroblasts of the periodontal ligament contain high alkaline phosphatase (ALPase) activity as much as osteoblast. Since similar results concerning the [Ca2+]i were obtained in osteoblast (OB)-like cells, this experiment also supports the hypothesis that fibroblasts of periodontal ligament have osteoblastic features.

Bone Remodeling↗

Chronic relapsing multiple sclerosis: a case of rapid recovery by application of weak electromagnetic fields.

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.

Antineoplastic Agents↗

Immediate recovery of cognitive functions and resolution of fatigue by treatment with weak electromagnetic fields in a patient with multiple sclerosis.

Cognitive deficits are common among patients with multiple sclerosis (MS). The pathogenetic mechanisms underlying the cognitive impairment in MS are unknown and there is presently no effective therapeutic modality which has shown efficacy in improving cognitive deficits in MS. A 53 year old college professor with a long history of secondary progressive MS experienced, over the preceding year, noticeable deterioration in cognitive functions with difficulties in short and long term memory, word finding in spontaneous speech, attention and concentration span. Unable to pursue his academic activities, he was considering early retirement. Mental examination disclosed features of subcortical and cortical dementia involving frontal lobe, left hemispheric and right hemispheric dysfunction. Almost immediately following the extracerebral application of AC pulsed electromagnetic fields (EMFs) of 7.5 picotesla intensity and a 4-Hz sinusoidal wave, the patient experienced a heightend sense of well being, which he defined as enhancement of cognitive functions with a feeling "like a cloud lifted off my head." He reported heightend clarity of thinking and during the application of EMFs he felt that words were formed faster and he experienced no difficulty finding the appropriate words. His speech was stronger and well modulated and he felt "energized" with resolution of his fatigue. There was improvement in manual dexterity and handwriting and testing of constructional praxis demonstrated improvement in visuospatial, visuoperceptive and visuomotor functions. It is suggested that some of the cognitive deficits associated with MS, which are caused by synaptic disruption of neurotransmitter functions, may be reversed through pulsed applications of picotesla range EMFs.

Cognition Disorders↗

Improvement in word-fluency performance in Parkinson's disease by administration of electromagnetic fields.

The association between degeneration of the nigrostriatal dopamine (DA) system and the motor manifestations of Parkinson's disease (PD) provided the impetus for the development of DA replacement therapy. However, clinical experience has demonstrated that DA-ergic drugs, while attenuating the motor symptoms of PD, have little or no consistent effect on the mental and cognitive symptoms of the disease which are thought to be related partly to degeneration of the meso-cortico-limbic DA system. Thus, failure of DA-ergic drugs to improve the mental and cognitive deficits of PD indicates that these agents cannot fully restore DA functions in the meso-cortico-limbic circuits. The present communication concerns five fully medicated Parkinsonian patients in whom application of a series of treatments with electromagnetic fields (EMF) of extremely low intensity (in the picotesla range) and frequency (5-8Hz) produced a dramatic improvement in performance on Thurstone's World-Fluency Test, a sensitive marker of frontal lobe functions. These findings suggest that in contrast to DA replacement therapy application of low intensity EMF may improve frontal lobe functions in patients with PD presumably by augmenting DA activity in the mesocortical system. As deficiency of the frontal DA system has been implicated also in the development of akinesia and freezing in PD these observations may explain the beneficial effects of EMF on the motor manifestations of the disease.

Aged↗

Nitric oxide mediates the effects of pulsed electromagnetic field stimulation on the osteoblast proliferation and differentiation.

The purpose of this research was to investigate whether the effects of pulsed electromagnetic field (PEMF) stimulation on the osteoblast proliferation and differentiation are mediated by the increase in the nitric oxide (NO, nitrogen monoxide) synthesis. The osteoblasts (MC3T3-E1 cell line) were cultured in the absence (-NMMA group) or in the presence (+NMMA group) of the NO synthase inhibitor L-NMMA. First, osteoblasts were subjected to PEMF stimulation (15 Hz and 0.6 mT) up to 15 days. The DNA content and the NO concentration in the conditioned medium were determined on the 3rd, 7th, and 15th days of culture. Following, osteoblasts were stimulated in the proliferation (P-NMMA and P+NMMA groups) or in the differentiation (D-NMMA and D+NMMA groups) stages of maturation, and the alkaline phosphatase (AlPase) activity was determined on the 15th day of culture for all groups. PEMF stimulation increased significantly the nitrite concentration in the -NMMA group on the 3rd, 7th, and 15th days of culture. However, this effect was partially blocked in the +NMMA group. The DNA content in the -NMMA group, but not in the +NMMA group, increased significantly on the 3rd and 7th days of culture. The AlPase activity in the P-NMMA and D-NMMA groups, but not in the P+NMMA and D+NMMA groups, also increased significantly. In conclusion, the PEMF stimulatory effects on the osteoblasts proliferation and differentiation were mediated by the increase in the NO synthesis.

Alkaline Phosphatase↗

Cellular effects of electromagnetic fields.

Studies at the cellular level are needed to reveal the cellular and molecular biological mechanisms underlying the biological effects and possible health implications of non-ionising radiation, such as extremely low frequency (ELF) magnetic fields (MFs) and radiofrequency (RF) fields. Our research group has studied the effects of 50 Hz ELF MFs (caused by power lines and electric devices) and 872 MHz or 900 MHz RFs (emitted by mobile phones and their base stations) on cellular ornithine decarboxylase activity, cell cycle kinetics, cell proliferation, and necrotic or apoptotic cell death. For RFs, pulse-modulated (217 Hz modulation frequency corresponding a global system for mobile communication-type signal) or continuous wave (unmodulated) signals were used. To expose the cell cultures to MFs or RFs, specially developed exposure systems were used, where levels of electromagnetic field exposure and the conditions of cell culture could be precisely controlled. A coexposure approach was used in many studies, i.e. the cell cultures were exposed to other stressors in addition to MFs or RFs. Ultraviolet radiation, serum deprivation, or fresh medium addition, were used as co-exposures. The results presented in this short review show that the effects of mere MFs or RF on cell culture models are quite minor, but that various co-exposure approaches warrant additional study.

Animal Testing Alternatives↗

Growth assessment of children exposed to low frequency electromagnetic fields at the Abu Sultan area in Ismailia (Egypt).

UNLABELLED: A cross-sectional study was carried out to assess the growth of 780 children of both sexes, aged between 0-12 years, and living at two different areas in Ismailia, Egypt, with approximately similar socioeconomic standards. Based on a designed questionaire, the exposed group was formed of 390 children from the Abu Sultan area. They were chosen from families living within 50 meters nearby high voltage electric power lines. Another 390 children from the El-Sheikh Zayed area were chosen as the control group. Standard anthropometric measurements were carried out for each child. Plain X-ray was done on the hands of 200 randomly selected children from both groups (100 each) to assess their bone maturation. In the exposed group the weight was significantly decreased only at birth, while the circumferences of the head and chest as well as the height were significantly reduced at all studied ages. The radiological study revealed a significant delay in carpal bone ossification of the exposed children. IN CONCLUSION: Exposure to low frequency electromagnetic fields emerged from high voltage electric power lines increases the incidence of growth retardation of children. Isolating these power lines in a scientific way in order to shield both the magnetic and electric fields or removing them far away from the inhabitant areas is recommended.

Bone Development↗

[Treatment of subjective noise in the ear by impulse low-frequency electromagnetic field (preliminary results)].

25 patients with subjective noise in the ears, primarily in neurosensory hypoacusis, were exposed to pulse low-frequency electromagnetic field (PLFEMF) generated by INFITA unit with attached device ELEMAGS. The noise complaints began 1 to 10 years before. The previous conservative therapy failed. PLFEMF eliminated the noise in 2 patients, reduced it noticeably (by 60%) or changed its tone in 19 patients. At 6-12-month follow-up positive effect persisted. The results of the study allow the authors to recommend PLFEMF for wide clinical practice.

Adolescent↗

Reversal of a visuoconstructional disorder by weak electromagnetic fields in a child with Tourette's syndrome.

Tourette's syndrome (TS), a chronic familial neuropsychiatric disorder of unknown etiology, is characterized clinically by the occurrence of motor and vocal tics and by the presence of a variety of neurobehavioral and neurocognitive abnormalities including hyperactivity, self-mutilatory behavior, obsessive-compulsive behavior, learning disabilities, and conduct disorder. Cognitive deficits related to right hemispheric dysfunction are common in TS patients accounting for decrements in visuospatial, visuoconstructional and visuomotor skills. An 11 year old boy with a 5 years history of TS exhibited during a routine neuropsychological assessment an unusual visuoconstructional disorder which previously has been observed in dyslexic children. Specifically, when instructed to draw a bicycle from memory, he drew spontaneously a design executed from the perspective of a bird's eye view. After receiving a 20 minute treatment session with picotesla range electromagnetic fields (EMFs) applied extracranially, this visuocontructional disorder was spontaneously reversed and he drew an elaborate and detailed bicycle positioned in profile. A placebo EMF treatment, which was administered prior to magnetic therapy, had no effect on this child's visuoconstructional disorder. During the ensuing week there was a marked reduction in the child's hyperactive behavior with attentuation of motor tics. Spontaneous drawing of a bicycle a week after the administration of magnetic therapy was executed in profile although some elements were presented from a bird's eye view. This case demonstrates the potential impact of treatment with picotesla EMFs in reversing specific cognitive deficits in TS related to right posterior hemispheric dysfunction.

Brain Diseases↗

Effects of picotesla flux electromagnetic fields on dopaminergic transmission in Tourette's syndrome.

Tourette's syndrome (TS), a chronic familial neuropsychiatric disorder of unknown etiology, is characterized clinically by the presence of motor and vocal tics that wax and wane in severity over the time and by the occurrence of a variety of neurobehavioral disorders. It is believed that the tics of TS result from increased dopamine (DA) activity caused by postsynaptic DA receptor supersensitivity. The synthesis and release of DA is regulated presynaptically by a specific class of DA D2 receptors, termed autoreceptors activation of which causes inhibition of DA synthesis and release. In experimental animals and humans administration of small doses of apomorphine, a DA D2 autoreceptor agonist, produces yawning. Recurrent episodes of yawning followed by increased motor tic activity was observed in two patients with TS during exposure to brief, extracranial applications of picotesla flux electromagnetic fields (EMFs). On the basis of these observations it is suggested that recurrent episodes of yawning in response to application of EMFs was induced by activation of presynaptic DA D2 autoreceptors while further exposure to these EMFs caused excessive stimulation of postsynaptic DA D2 receptors resulting in exacerbation of the tics. Thus, the dual effects of picotesla flux EMFs on the DA D2 autoreceptor and the postsynaptic receptor resemble the biphasic pharmacological and behavioral properties of apomorphine, a DA agonist which activates the autoreceptors in low doses while in higher doses causes stimulation of the postsynaptic receptors producing exacerbation of symptoms of TS. These findings demonstrate that picotesla flux EMFs applied extracerebrally may influence nigrostriatal DA transmission at pre- and postsynaptic DA D2 receptor sites.

Dopamine↗

Reversal of a body image disorder (macrosomatognosia) in Parkinson's disease by treatment with AC pulsed electromagnetic fields.

Macrosomatognosia refers to a disorder of the body image in which the patient perceives a part or parts of his body as disproportionately large. Macrosomatognosia has been associated with lesions in the parietal lobe, particularly the right parietal lobe, which integrates perceptual-sensorimotor functions concerned with the body image. It has been observed most commonly in patients with paroxysmal cerebral disorders such as epilepsy and migraine. The Draw-a-Person-Test has been employed in neuropsychological testing to identify disorders of the body image. Three fully medicated elderly Parkinsonian patients who exhibited, on the Draw-a-Person Test, macrosomatognosia involving the upper limbs are presented. In these patients spontaneous drawing of the figure of a man demonstrated disproportionately large arms. Furthermore, it was observed that the arm affected by tremor or, in the case of bilateral tremor, the arm showing the most severe tremor showed the greatest abnormality. This association implies that dopaminergic mechanisms influence neuronal systems in the nondominant right parietal lobe which construct the body image. After receiving a course of treatments with AC pulsed electromagnetic fields (EMFs) in the picotesla flux density applied transcranially, these patients' drawings showed reversal of the macrosomatognosia. These findings demonstrate that transcranial applications of AC pulsed EMFs affect the neuronal systems involved in the construction of the human body image and additionally reverse disorders of the body image in Parkinsonism which are related to right parietal lobe dysfunction.

Aged↗

Electromagnetic fields induced by Helmholtz aiding coils inside saline-filled boundaries.

The use of Helmholtz aiding coils to induce small electromagnetic (EM) fields in living tissue for both medical and research purposes has become quite common. While much progress has been made in showing that these induced EM signals can cause a variety of effects in tissues and individual cells, a satisfactory explanation of how the effects occur or how the EM signals couple to the tissue has not yet emerged. To address the latter problem adequately, it becomes necessary to know the spatial distribution of the induced fields inside a given set of boundaries. This paper examines the situation used for much in vitro research where a cylindrical culture dish is filled with a conducting solution and placed between the Helmholtz coils. Two cases are considered. The first assumes that the coils are above and below the culture dish (the planes of the coils are parallel with the top and bottom of the dish); the second assumes that the planes of the coils are parallel with the sides of the dish. A closed form solution is obtained for both cases, and it is shown that the induced EM field distribution is markedly different for the two cases.

Culture Techniques↗

Lack of effect of extremely low frequency electromagnetic fields on cyclin-dependent kinase 4 inhibitor gene p18(INK4C) in electric energy workers.

BACKGROUND: Long-term exposure to extremely low frequency magnetic fields (ELF-MFs) may be a risk factor for human cancer. One mechanism through which ELF-MFs could influence neoplastic development is the deletion/mutation of cancer-related genes. Cellular proliferation follows an orderly progression through the cell cycle, which is governed by different cyclins and cyclin-dependent kinase inhibitors (CDKIs). The putative tumor suppressor gene p18(INK4C) encodes a specific inhibitor of cyclin D-cyclin-dependent kinase 4 inhibitor complexes having an important role in cell-cyclin regulation. It has been found to be deleted/mutated in a variety of human cancers. Therefore, this study is to investigate whether or not long-term extremely low frequency electromagnetic field exposure may be a risk factor for human cancer due to the gene p18(INK4C) deletion/mutation. METHODS: The study was carried out on 31 male electric workers and 30 healthy males between 30 and 40 years of age from the same geographic area and with similar lifestyles. We studied both groups by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). RESULTS: In comparison to the controls, band migration of exon 1 was found to be indifferent in all the subjects tested. However, only exon 2 of two electric workers was slow in migration with respect to both control and other subjects in the same class. This slow migration suggests that point mutations or polymorphisms may exist in this region of the p18(INK4C) gene. The relative risk (RR) for the unmatched analysis was 1,069 (95% confidence interval [CI] 0.975-1.172). CONCLUSIONS: The results suggest that long-term ELF-MFs exposure does not significantly increase the risk of cancer.

Adult↗

Application of weak electromagnetic fields facilitates sensory-motor integration in patients with multiple sclerosis.

Electrophysiological studies in behaving animals have shown the function of cerebral serotonin (5-HT) neurons to be altered in association with motor output in both the tonic and repetitive modes and also in relation to an orienting response. Brainstem 5-HT neurons increase their firing rate two to five-fold during repetitive motor activity to facilitate motor output while simultaneously suppressing transmission in sensory pathways. Reciprocally, during an orienting response motor activity is suppressed and 5-HT neuronal activity is inhibited to facilitate transmission of sensory information. These reciprocal changes in 5-HT neuronal activity serve to facilitate brainstem reticular sensory-motor integration which, due to 5-HT neurotransmission deficiency, may be disrupted in patients with multiple sclerosis (MS). For instance, MS patients are unable to process auditory information in the presence of competing ambient stimuli, while under a controlled laboratory environment they demonstrate unimpaired verbal information processing. This report concerns three MS patients who experienced rapid deterioration in balance resulting in falling when subjected, during ambulation, to distracting external auditory stimuli. After receiving a series of treatments with low frequency picotesla range intensity electromagnetic fields (EMFs), which were applied extracranially for brief periods, these patients experienced resolution of these symptoms with ambulation being unaffected by auditory stimuli. It is suggested that application of picotesla EMFs may restore abnormal reticular sensory-motor integration in MS patients with the effect being related to facilitation of 5-HT neurotransmission at both junctional (synaptic) and nonjunctional neuronal target sites.

Acoustic Stimulation↗

Weak electromagnetic fields restore dream recall in patients with multiple sclerosis.

It is now well established that dreaming is a phenomenon associated with REM sleep and that we dream far more than we can recall. Loss of dream recall has been reported in association with cerebral lesions of different sites with predilection to the posterior cerebral hemispheres. Multiple sclerosis (MS) is a chronic neurological disorder characterised by the presence of diffuse pathological lesions affecting cortical, subcortical, and brainstem areas which are implicated in the generation and maintenance of REM sleep as well as dream recall. Although MS is associated with a high incidence of sleep disturbances, little is known about the frequency of dreaming and particularly dream recall in these patients and their association with such features as the course of the disease, extent of neurological deficits, rate of progression, sites of demyelinating plaques on MRI scan, and recovery. In my experience morning dream recall and probably dreaming activity become infrequent with the onset and/or during periods of exacerbation of the disease. The present communication concerns four selected MS patients who experienced alterations in dream content and loss of morning dream recall during the course of the disease. In all patients dream recall was restored, along with improvement in neurological symptoms, following the external application of a series of treatments with weak electromagnetic fields (EMFs). These findings suggest that in MS morning dream recall may decline and cease to occur during the course of the disease. Recurrence of dream recall may be a marker of clinical recovery which can be used to assess neurologic improvement in patients undergoing treatment with experimental treatment modalities.

Adult↗