Most clinically used magnetotherapies are supported by "black box" experimental and clinical data. On May 19, 2000, a meeting of the Working Group 'Electrophysiology of Bone' of the German Society of Osteology was held in Berlin to discuss the basic mechanisms of pathophysiological regulation to explain the therapeutic significance of various modes of clinical magnetotherapies.This short paper outlines the discussion held at that meeting, which searched for a rational scientific understanding or basis for the use of various clinical magnetotherapies.
This paper describes the effect of weak microwave fields on the amounts of heat-shock proteins in cell cultures at various temperatures.The field was generated by signal simulation of the Global System for Mobile communications (GSM) of 950 Mhz, used in portable phones. Transformed human epithelial amnion (AMA) cells, growing on glass coverslips, were exposed in a transverse electromagnetic (TEM) cell to a microwave field, generating a specific absorption rate (SAR) of 2.1 mW.kg(-1) in the cells. Exposure temperatures were 35, 37, and 40 +/-0.1 degreesC, respectively, and the exposure time was 20 min.The heat-shock proteins Hsp-70 and Hsp-27 were detected by immunofluorescence. Higher amounts of Hsp-70 were present in the cells exposed at 35 and 37 degreesC than in the sham-exposed cells.These effects can be considered to be athermal, since the field strength was much lower than the safety standard for absence of heat generation by microwave fields.There was no significant response in the case of Hsp-27.
Glass microelectrodes were inserted into the growing zone of sporangiophores of Phycomyces blakesleeanus that had been submersed in artificial pond water. The membrane potential (inside negative) increased with increasing pH of the bathing solution from an average of -98 mV at pH 5 up to -131 mV at pH 7. Removal of Ca2+ from the medium hyperpolarized the membrane potential in the wild type, but caused a significant depolarization in the blue-light-insensitive madC mutant. KCN, diethylstilbestrol, and N,N'-dicyclohexylcarbodiimide depolarized the membrane potential in both the wild type and the madC mutant, while fusicoccin had no effect. Endogenous ion current of up to 2 muA cm(-2) was measured in the growing zone of sporangiophores with an extracellular vibrating electrode. The current density and current pattern varied with the pH of the medium. At pH 5 most sporangiophores had weak inward current along the growing zone, whereas at pH 7 most sporangiophores had strong outward current. The response of the membrane potential to specific inhibitors and the presence of an endogenous ion current indicate an electrogenic H+-ATPase in the plasma membrane. The results show a negative correlation between growth rate of sporangiophores growing in buffered aqueous medium and magnitude of membrane potential, as well as density of outward current. They also indicate an important role of protons in controlling the growth of Phycomyces sporangiophores.
The purpose of the work was to further investigate the effect of zero magnetic field (ZMF) on the concentration of ions in the human blood compared to the effect of the normal geomagnetic field (GMF). We have investigated the total Zn and Cu concentrations in the blood serum during in vitro aging of blood. The investigation was carried out both on blood from healthy donors as well as from chronic bronchial asthma (BA) patients. Blood samples were kept for 48 hours in a Helmholtz coil compensating system to remove the static component of the geomagnetic field, at room temperature. We found that zinc concentrations in the plasma were not significantly influenced by the exposure to ZMF compared to GMF for both healthy and pathological samples. In contrast, copper concentration was found to be significantly sensitive to the magnetic environment. Healthy blood showed a slight loss of copper from the blood serum in GMF, which further increased in ZMF. BA pathology is characterized by four distinct types of disease, which showed both qualitative and quantitative distinctive sensitivity to the magnetic environment, as compared to healthy blood. The aging effect appeared to be slowed down for most of the BA types of pathologies. These results point to the sensitivity of ion binding to serum proteins and/or transport through cell membranes in the magnetic environment, in our case in the absence of the normal geomagnetic field.
The microtubules in the cellular cytoskeleton have a fundamental role in the living processes of biological cells. They are hollow cylinders which resemble circular waveguides or cylindrical resonators. The cutoff and resonant frequencies of the transverse magnetic and transverse electric modes of the microtubule cavities are in the band of soft x-rays. This suggests the possibility of interaction of electromagnetic cavity modes with inner electrons in atoms (e.g., in carbon, nitrogen, and oxygen). Biological cells (e.g., the yeast cells of spherical shape) may also represent cavity resonators. In this case, the resonant frequencies may be in the infrared region.
Pink (1/f-) noise is one of the most common behaviors of biosystems. This paper is devoted to clarifying the stochastic answer given to white-noise excitation of bio-systems.It is assumed that a living system in general is a bifurcative self-organizing system, and has cyclic symmetry with infinite degrees of freedom, and stationary random stochastic processes characterize their dynamism.We show that this bifurcation characterizes all levels of bioactivity, and the white-noise excited biosystem has a filter function, and generates a pink-noise spectrum.Environmental white-noise electromagnetic excitation (like 'electrosmog' in general) is filtered by the biosystem, and it gives a characteristic pink-noise answer-signal to this excitation.
Electroporative drug delivery (electroloading of cells) takes place effectively by inserting electrodes mediating strong electric pulses. Another possibility is the disturbance of lipid bilayer structures by weak pulsating electromagnetically induced currents (PEMIC) produced by Helmholtz coils. In yeast cells (Saccharomyces cerevisiae) the enhancement of drug (sensitizer) transport through cell membranes by PEMIC results in an increased photodynamic cell killing. Depending on the magnetic flux, a window of 25% killing rate, caused by the photodynamic effect, could be observed at approximately 8 mT with a frequency of 50 Hz.
A controlled pilot study was performed to examine the possibility of finding a specific electromagnetic field signal to inhibit angiogenesis during tumor growth. A 120 Hz pulsating magnetic field of 4 and 5 mT was applied to female mice which had been inoculated with murine 16/C mammary adenocarcinoma. After 11 consecutive sessions of 10 min/day exposure to the magnetic field, the animals were sacrificed and an immunohistochemistry analysis of the tumors was performed. CD31 staining indicated that both magnetic fields significantly reduced the vasculature in the tumors: 39% at 4 mT magnetic flux density and 53% at 5 mT. The positive implications for impeding tumor growth and metastasis warrant further studies.
It is well known that weak, about 1 G and less, magnetic fields (MFs) cause a biological response. Processes of different hierarchic levels of a living organism, from molecular (bio)physical to complex adaptive biological processes, contribute essentially to the effect of MFs on biology. In biophysics, separate magnetosensitive processes at the fundamental level of interaction of fields and substance are studied. It is exactly at this level that complex spectral or “window” modes of the relation between biophysical processes and biologically significant MF parameters originate. A review is given of the present situation. The paper concentrates on models that deal with extremely low frequency (ELF) MFs. Theoretical amplitude–frequency limits are considered that constrain possible physical mechanisms underlying biological effects.
Laboratory studies of the biological effects of low-frequency electromagnetic fields (EMFs) have demonstrated that the fields can produce or alter a wide range of phenomena. Explaining the diversity of the reported effects is a central problem. Our basic hypothesis is that the effects are generally indirect, and arise as a consequence of sensory transduction of the fields. In this view, EMF detection and its biological consequences occur in different types of cells. Experimental verification of the hypothesis will ultimately require data showing that the interaction of EMFs with tissue results in biological changes that are the same as or similar to changes that occur during sensory transduction. The goal was to identify the specific phenomena that would be expected to occur if the hypothesis were true. We therefore analyzed the presently accepted models of sensory transduction in the somatic and special senses. Many kinds of processes were identified in connection with transduction of different kinds of stimuli, but we found that a change in the conductance of a membrane ion channel in a neuron or a neuroepithelial cell was the earliest process that occurred in all forms of sensory transduction. Evidence from an appropriate model excitable cell or tissue that EMFs affect membrane currents or membrane potential would therefore support the hypothesis that EMF transduction is a species of sensory transduction.
Electromagnetic activity around yeast mitotic cells (Saccharomyces cerevisiae) was measured in the frequency range 8–9 MHz and special care was taken to extract reliable information from the raw signals. The characteristic of cold-sensitive tubulin mutants tub2-401 and tub2-406, which come to arrest before mitosis at a restrictive temperature (14°C) and which re-enter mitosis upon a shift back to a permissive temperature (28°C), was used to prepare synchronized mitotic cells. Immunofluorescence microscopy using an antitubulin antibody was used to analyze microtubular structures. The arrested tub2-401 mutant that had back-shifted to permissive temperature displayed no microtubules and no electromagnetic activity around the cells. In contrast, the arrested cells of the mutant tub2-406 displayed developed, but aberrant, nonfunctional microtubules and a high electromagnetic activity around the cells. The electromagnetic activity around the arrested mutant tub2-401 back-shifted to permissive temperature peaks at four time points which may coincide with (i) formation of the mitotic spindle, (ii) binding of chromatids to kinetochore microtubules, (iii) elongation of the spindle in anaphase A, and (iv) elongation of the spindle in anaphase B. The profile of the electromagnetic activity around the synchronized mutant tub2-406 at permissive temperature seems to be delayed by the time required for aberrant nonfunctional microtubules to be depolymerized. Experimental results presented in this paper support Pohl's idea of existence of the electromagnetic field around yeast cells.
The theoretical analysis of responses of calcium-dependent membrane-associated signaling systems to weak extremely low-frequency periodic signals with different waveform parameters was performed on a model suggested recently (Gapeyev and Chemeris, Electro- and Magnetobiology 19, 21-42, 2000). Calcium channels of the plasma membrane were chosen as the target for the influence of external periodic signals. The effect of external signals was manifested as an increase in average [Ca2+](i) at certain parameters of the signals. The effect had a threshold dependence on the relative amplitude of the external signal. The effect character was shown to depend strongly on a sequence of delivery of the external stimuli. The effect also depended on the phase of the influencing signal with respect to the moment of the chemical stimulation of the cell. Under the influence of sine-wave, rectangular, and sawtooth external signals, amplitude- and phase-frequency "windows" of the rise in average [Ca2+](i) were revealed. Locations of amplitude-frequency "windows" and phase-frequency characteristics of the effect were determined by "the width of effective range of the signal," that is, the time during which the signal amplitude exceeded a certain threshold value. The presence of negative amplitudes, i.e., variation of the rate of calcium signaling process around an inherent value, played an important role for the effect characteristics. To ensure a regimen for the optimal effect, it is necessary for the external signal parameters to be interrelated with characteristics of transient processes during the system's response to an intensive chemical stimulus. Results of theoretical analysis led us to the conclusion that the signal waveform parameters, which are determined not only by frequency spectrum, but also by initial phase of each frequency component, play a major role in the revelation and development of the biological system response to an external electromagnetic signal.
The importance of cellular electrical phenomena is well known.Most investigations have been limited to static and quasi-static effects.Very few studies deal with the occurrence of RF fields, which can be expected for theoretical reasons. Indirect evidence arises from microdielectrophoretic work that delivers information about the spatial distribution and temporal development of AC electric fields around biological cells. A more detailed investigation is possible by an electronic detection of these fields. A survey of both microdielectrophoretic and electronic work is given, together with some principles that are crucial for the design and interpretation of experiments.We present a multichannel frequency analysis system that for the first time allows the continuous monitoring of cellular RF activities over a wide frequency range. For the fission yeast Schizosaccharomyces pomberhythmic signal changes with period lengths of about 400 s have been found that could be reproduced in a number of experiments.
The purpose of this study was to investigate the effects of 9450-MHz microwaves and extremely low frequency magnetic fields (ELFMF) on the phagocytic activity of rat macrophages in control rats and those treated with vitamins C and E. In the microwave group, 24 albino Wistar rats were exposed to microwaves (2.65 mW/cm(2), specific absorption rate [SAR]: 1.80 W/kg) for 1 h/day for 21 days. Thirty-two albino Wistar rats were divided into four groups (one control, three experimental) (n = 8). The rats in the first exposure group were only exposed to microwaves for 1 h per day for 21 days. In addition to exposure with microwaves as in the first experimental group, vitamins E and C (150 mg/kg/day) were injected intraperitoneally into the rats in the second and third exposure groups, respectively. In the magnetic field exposure group, 26 albino Wistar rats were divided into two groups: the sham (n = 12) and exposed groups (n = 14). The rats in the experimental group were exposed to ELFMF (50 Hz, 0.75 mT) for 3 h/day for 3 weeks. After completing the exposure period, the rats were sacrificed under ketalar anesthesia. The viability of isolated alveolar macrophages of rats in the microwave and ELF groups was determined and compared to sham groups. The results were analyzed with the Mann-Whitney U test. In the microwave group, the phagocytic activity in the experimental groups was found to be higher than the sham groups. However, with phagocytic activity in rats treated with both microwaves and vitamins, only the vitamin C group was significant (p < 0.05). In the magnetic field group, the phagocytic activity of rats exposed to ELFMF was lower than that of the sham group, but the results were not significant (p > 0.05). Rectal temperatures of microwave-exposed groups were found to be significantly higher compared to the control group (p < 0.05).
Non-ionizing physical field interactions with cells, both in situ and in vitro, is of current interest globally. This is from various directions—starting from their abilities to induce permanent modifications in cell behavior in situ, through carcinogenesis and mutagenesis, to utilizing field effects for possibly enhancing the viable cell population in vitro. This results in parallel increase in some high-value, low-volume biochemical production. In the present study, screening experiments were carried out with a unique cell line—hybridoma (OKT3) (secreting monoclonal antibodies [MAbs] against T3 surface antigens of human peripheral CD4+ cells)—for a possible enhancement in the yield of extremely high value product (MAb). Overall, in the absence of any such data globally, there is apparently an urgent need for screening of such “field effects” on various other cell types in vitro for various reasons; e.g., low cost of manipulation, nonpolluting nature of interactions, distinct possibility of enhancement of produced biochemical titers, etc. In the present study, we observed various responses of the cell population both to magnetic fields alone and in combination with other known chemical stimulants of viable biomass (mono- and poly-lysine). Fifty hertz, 0.8 mT magnetic field and below, in conjunction with bulkier poly-lysine molecules, needs to be investigated further for a possible resonance-induced anti-interaction between these known mitogens and their cell surface receptors, which possibly could be extrapolated to other growth factor-receptor interactions in magnetic field environments, in situ.
The efficiency of weak ELF (extremely low frequency) EMF on living systems can be explained by taking into account the nonstationary processes that arise when ions pass part of the intermembrane distance during the EMF period. The periodic movement of ions in the heterogeneous medium would result in the nonlinear effects influencing the ionic strength and pH near the membrane and the release of some peripheral proteins to the water phase. Based on this notion, we studied the effects of EMF treatment (30 or 50 Hz, 30 mT) at different stages of imbibition of wheat seeds. The treatment at the stage of activation of esterases increased the leakage of the products of esterase reaction with its following retardation, which contrasts with the linear kinetics for untreated seeds and for seeds treated at earlier stages. The treatment also led to a reliable increase in pH near the embryo surface. When the wheat seeds with germinability of 50% were treated at the stage of root formation, a significant increase in the number of seeds with roots was observed. The sprout length reliably increased after this treatment with respect to seeds treated later and untreated seeds. In the latter case, only the number of seeds with sprouts increased. Long treatment of seeds during the second day of imbibition reduced the length of sprouts. The observed effects are discussed on the basis of this proposed mechanism.
Response of leukocytes to exposure to an external magnetic field with frequency 50 Hz and sinusoidal waveform was investigated in vitro using the leukocyte adherence inhibition (LAI) assay developed as a measure of cell-mediated immunity. Leukocytes taken from healthy humans adhere, but their adherence decreases after 1 hr of exposure to the magnetic field with magnetic induction of 1 and 10 mT. The majority of leukocytes taken from cancer patients before any medical treatment do not adhere, and exposure to the magnetic field increases adherence. Correlation between the LAI assay results and the cell-mediated immunity suggests an effect of magnetic fields on leukocyte immune function in humans.
The aim of this study was to investigate the induction of genotoxic and cytotoxic effects in cultured human lymphocytes from healthy donors following combined exposure to a 50 Hz sinusoidal magnetic field (1 mT field intensity) and a chemical mutagen: mitomycin-C or hydroquinone. The induced effects were evaluated by applying the cytokinesis-block technique, because it offers the advantage of providing simultaneously information on both cell cycle progression (cytokinesis block proliferation index) and chromosomal damage (micronucleus frequency). The results obtained indicate that magnetic field exposure does not affect spontaneous micronucleus frequency, although a slight increase in cell proliferation was observed (p = 0.031). Both mutagens induce a statistically significant increase in micronucleus frequency (p = 0.0 and p = 0.015 for mitomycin-C and hydroquinone, respectively). Moreover, the combined exposure to both magnetic field and chemicals does not increase the damage due to the chemical treatments alone, both in terms of genotoxicity and cell proliferation (p > 0.05 in all cases), suggesting that, in the experimental condition adopted, no cooperative effects are induced.
We have computationally explored the effect of quantitative variations in the extent of cell-to-cell electrical coupling on the synaptic potentials generated in smooth muscle. Neuronally produced spontaneous excitatory junction potentials (SEJPs) generated in a cubical "bidomain" model of syncytial tissue were simulated computationally. It was found that SEJP properties vary conspicuously as the principal parameter of interest, the cell-to-cell coupling resistance, Ri, is altered. For example, on increasing Ri, SEJP peak amplitudes at node zero (the node of generation) increase dramatically, while amplitudes at nodes 1 and 2 (which are passively depolarized) become progressively lower fractions of the amplitude of the zeroeth-node SEJP. The time to peak of the SEJPs also increases concomitantly when R-i is elevated. These observations indicate the nature of variations in synaptic potentials that would be expected under conditions of altered intercellular electrical coupling in smooth muscle. We discuss their implications in relation to the physiology of syncytial tissue, and in the context of recent experimental observations made in the presence of a putative inhibitor of cell-to-cell electrical coupling, 1-heptanol.
In this work we have studied some hematological and biochemical parameters of peripheral blood, as well as some histological aspects of liver and spleen during chronic exposure (1, 6, and 8 months) to extremely low-frequency magnetic fields (ELF-MF). Balb/C mice were exposed to an experimental sinusoidal magnetic wavefield of 60 Hz with a 0.11-mT intensity, generated in a system of Helmholtz coils. The results have shown no ELF-MF–cancer relationship during our experimental exposure time. However, leukopenia, hemoglobin decrease, and liver and spleen weight increase were observed. The bioeffects described could be correlated with spleen hyperfunction, which could have been produced by chronic exposure to this ELF-MF.
