Local and holistic electromagnetic therapies

Based on decades of experimental evidence an excellent argument can be made for the existence of a fundamental functional relationship between living systems and electromagnetic fields. We have previously hypothesized that this relationship can be expressed in terms of a field vector whose source is the distribution of electric polarization within the system and which has both a phylogenetic and ontogenetic time dependence. Ion cyclotron resonance (ICR)-like magnetic signals have resulted in physiologic changes in many in vitro and in vivo model systems and have been applied medically with success to bone repair and spinal fusion. This type of local ICR-like therapy has recently been broadened into a holistic application following the remarkable discovery that the whole-body bioimpedance is sharply dependent on ICR signals. We relate this observation to the integrated electric polarization vector, in turn a measure of the double layer charge distribution at the cell membrane. This discovery, already being applied to a number of clinical problems, lends strong support to the concept of an overarching electromagnetic framework for living systems.     

Power frequency fields promote cell differentiation coincident with an increase in transforming growth factor-beta(1) expression.

Recent information from several laboratories suggest that power frequency fields may stimulate cell differentiation in a number of model systems. In this way, they may be similar to pulsed electromagnetic fields, which have been used therapeutically. However, the effects of power frequency fields on phenotypic or genotypic expression have not been explained. This study describes the ability of power frequency fields to accelerate cell differentiation in vivo and describes dose relationships in terms of both amplitude and exposure duration. No change in proliferation or cell content were observed. A clear dose relationship, in terms of both amplitude and duration of exposure, was determined with the maximal biological response occurring at 0.1 mT and 7-9 h/day. Because this study was designed to explore biological activity at environmental exposure levels, this exposure range does not necessarily define optimal dosing conditions from the therapeutic point of view. This study reports the stimulation by power frequency fields of transforming growth factor-beta, an important signalling cytokine known to regulate cell differentiation. The hypothesis is raised that the stimulation of regulatory cytokines by electromagnetic fields may be an intermediary mechanism by which these fields have their biological activity.     

On the mechanisms of stimulation and inhibition during germination of wheat seeds in extremely low frequency electromagnetic fields

It has been shown that the effects of stimulation of germination of wheat seeds by electromagnetic field depend on the degree of membrane tension during imbibition of seeds in sucrose solutions. This provides further confirmation of the influence of electromagnetic fields on the release of proteins from the bound state on the membranes. The prolonged treatment with electromagnetic fields during the imbibition of seeds leads not only to the inhibition of germination of sprouts but also to a decrease in their germinability, which can be as strong as twofold for seeds with the initial low germinability. This is related to the desynchronization of germination processes, caused by the stimulation of the release of proteins and inhibition of another stage during the cell division, the assembly of complex structures. It is noted that the activation of the release of proteins and inhibition of their binding by the action of electromagnetic fields must elevate the cell excitability. The presumably, the excitability of cells determines the effects of magnetic storms and high solar activity on the physiological state of organisms.     

Bio-soliton model that predicts non-thermal electromagnetic frequency bands,that either stabilize or destabilize living cells

Solitons, as self-reinforcing solitary waves, interact with complex biological phenomena such as cellular self-organization. A soliton model is able to describe a spectrum of electromagnetism modalities that can be applied to understand the physical principles of biological effects in living cells, as caused by endogenous and exogenous electromagnetic fields and is compatible with quantum coherence. A bio-soliton model is proposed, that enables to predict which eigen-frequencies of non-thermal electromagnetic waves are life-sustaining and which are, in contrast, detrimental for living cells. The particular effects are exerted by a range of electromagnetic wave eigen-frequencies of one-tenth of a Hertz till Peta Hertz that show a pattern of 12 bands, and can be positioned on an acoustic reference frequency scale. The model was substantiated by a meta-analysis of 240 published articles of biological electromagnetic experiments, in which a spectrum of non-thermal electromagnetic waves were exposed to living cells and intact organisms. These data support the concept of coherent quantized electromagnetic states in living organisms and the theories of Fröhlich, Davydov and Pang. It is envisioned that a rational control of shape by soliton-waves and related to a morphogenetic field and parametric resonance provides positional information and cues to regulate organism-wide systems properties like anatomy, control of reproduction and repair.     

Endothelial cell response to pulsed electromagnetic fields: stimulation of growth rate and angiogenesis in vitro

The effects of pulsed electromagnetic fields on the repopulation rate of denuded regions of endothelial cell monolayers and on endothelial cell reorganization into complex vessellike structures was monitored in vitro by using human umbilical vein and bovine aortic endothelial cells. A small (20-40%) but statistically significant enhancement in growth rate of partially denuded endothelial cell monolayers as determined by tritiated thymidine incorporation was observed in the presence of pulsed electromagnetic fields. Morphologically, endothelial cells entering the denuded regions were observed to be elongated, often connecting end to end to form a mycelial or "sprouting" pattern when exposed to pulsed electromagnetic fields. This was in contrast to cells outside of the field which had a more cuboidal morphology. Complete disruption of the endothelial cell monolayer by passaging the cells with EDTA-trypsin resulted in reorganization of some of the cells into three-dimensional vessellike structures after as little as 5-8 hours in the presence of the pulsed electromagnetic field. This reorganization occurred in the presence of heparin, endothelial cell growth factor, and a competent fibronectin matrix. Vascularization for comparable cultures outside of the field did not occur during the time-course of the experiments. Discrete stages of neovascularization were observed in the presence of the field that were qualitatively similar to stages of angiogenesis observed in vivo.     

Involvement of ERK and protein tyrosine phosphatase signaling pathways in EGCG-induced cyclooxygenase-2 expression in Raw 264.7 cells

The cellular stress response which can be elicited by a variety of physical or chemical stressors challenges the homeostatic mechanisms of the cells. Two stressors may interact such that, for example, in the presence of a defined thermal stress ("costress") a second weak stressor like electromagnetic fields (50 MHz, 100 microT) produces strong biological effects. Based on the apparent interaction of these stressors a concept is suggested that explains the observed effects and defines the limits of cellular homeostasis in general terms. The homeostatic potential of a cell and hence the ability to cope with stressors can be altered by eliciting or depressing the heat shock response. This manipulation has several promising medical applications.     

Radiofrequency and extremely low-frequency electromagnetic field effects on the blood-brain barrier

During the last century, mankind has introduced electricity and during the very last decades, the microwaves of the modern communication society have spread a totally new entity--the radiofrequency fields--around the world. How does this affect biology on Earth? The mammalian brain is protected by the blood-brain barrier, which prevents harmful substances from reaching the brain tissue. There is evidence that exposure to electromagnetic fields at non thermal levels disrupts this barrier. In this review, the scientific findings in this field are presented. The result is a complex picture, where some studies show effects on the blood-brain barrier, whereas others do not. Possible mechanisms for the interactions between electromagnetic fields and the living organisms are discussed. Demonstrated effects on the blood-brain barrier, as well as a series of other effects upon biology, have caused societal anxiety. Continued research is needed to come to an understanding of how these possible effects can be neutralized, or at least reduced. Furthermore, it should be kept in mind that proven effects on biology also should have positive potentials, e.g., for medical use.     

Stochastic resonance as a possible mechanism of amplification of weak electric signals in living cells

The most important but still unresolved problem in bioelectromagnetics is the interaction of weak electromagnetic fields (EMFs) with living cells. Thermal and other types of noise pose restrictions in cell detection of weak signals. As a consequence, some extant experimental results that indicate low-intensity field effects cannot be accounted for, and this renders the results themselves questionable. One way out of this dead end is to search for possible mechanisms of signal amplification. In this paper, we discuss a general mechanism in which a weak signal is amplified by system noise itself. This mechanism was discovered several years ago in physics and is known, in its simplest form, as a stochastic resonance. It was shown that signal amplification may exceed a factor of 1000, which renders existing estimations of EMF thresholds highly speculative. The applicability of the stochastic resonance concept to cells is discussed particularly with respect to the possible role of the cell membrane in the amplification process. © 1994 Wiley-Liss, Inc.     

Electromagnetic field effects on cells of the immune system: the role of calcium signaling.

During the past decade considerable evidence has accumulated demonstrating that nonthermal exposures of cells of the immune system to extremely low-frequency (ELF) electromagnetic fields (< 300 Hz) can elicit cellular changes that might be relevant to in vivo immune activity. A similar responsiveness to nonionizing electromagnetic energy in this frequency range has also been documented for tissues of the neuroendocrine and musculoskeletal system. However, knowledge about the underlying biological mechanisms by which such fields can induce cellular changes is still very limited. It is generally believed that the cell membrane and Ca(2+)-regulated activity is involved in bioactive ELF field coupling to living systems. This article begins with a short review of the current state of knowledge concerning the effects of nonthermal levels of ELF electromagnetic fields on the biochemistry and activity of immune cells and then closely examines new results that suggest a role for Ca2+ in the induction of these cellular field effects. Based on these findings it is proposed that membrane-mediated Ca2+ signaling processes are involved in the mediation of field effects on the immune system.     

Extremely low frequency 7 Hz 100 microT electromagnetic radiation promotes differentiation in the human epithelial cell line HaCaT

Electromagnetic therapy is a treatment method in which an electromagnetic or magnetic stimulus is used to achieve physiological changes in the body. The specific aim of the present work concerns the effectiveness of low frequency electromagnetic fields to modify the biochemical properties of human keratinocytes (HaCaT). Cells exposed to a 7 Hz 100 microT electromagnetic field for one hour (twice daily), indicated modification in shape and morphology. These modifications were also associated with different actin distribution as revealed by phalloidin fluorescence analysis. Indirect immunofluorescence with fluorescent antibodies against involucrin and beta-Catenin, both differentiation and adhesion markers, revealed an increase in involucrin and beta-Catenin expression, supporting the conclusion that exposure to electromagnetic field carries keratinocytes to an upper differentiation level. This study confirms our previous observation and supports the hypothesis that 7 Hz electromagnetic field, may modify cell biochemistry interfering in the differentiation and cellular adhesion of normal keratinocytes.     

Pulsed Low-Frequency Magnetic Fields Induce Tumor Membrane Disruption and Altered Cell Viability

Tumor cells express a unique cell surface glycocalyx with upregulation of sulfated glycosaminoglycans and charged glycoproteins. Little is known about how electromagnetic fields interact with this layer, particularly with regard to harnessing unique properties for therapeutic benefit. We applied a pulsed 20-millitesla (mT) magnetic field with rate of rise (dB/dt) in the msec range to cultured tumor cells to assess whether this affects membrane integrity as measured using cytolytic assays. A 10-min exposure of A549 human lung cancer cells to sequential 50- and 385-Hz oscillating magnetic fields was sufficient to induce intracellular protease release, suggesting altered membrane integrity after the field exposure. Heparinase treatment, which digests anionic sulfated glycan polymers, before exposure rendered cells insensitive to this effect. We further examined a non-neoplastic human primary cell line (lung lymphatic endothelial cells) as a typical normal host cell from the lung cancer microenvironment and found no effect of field exposure on membrane integrity. The field exposure was also sufficient to alter proliferation of tumor cells in culture, but not that of normal lymphatic cells. Pulsed magnetic field exposure of human breast cancer cells that express a sialic-acid rich glycocalyx also induced protease release, and this was partially abrogated by sialidase pretreatment, which removes cell surface anionic sialic acid. Scanning electron microscopy showed that field exposure may induce unique membrane “rippling” along with nanoscale pores on A549 cells. These effects were caused by a short exposure to pulsed 20-mT magnetic fields, and future work may examine greater magnitude effects. The proof of concept herein points to a mechanistic basis for possible applications of pulsed magnetic fields in novel anticancer strategies.     

A Theoretical Analysis of the Effects of Tumor-Treating Electric Fields on Single Cells

Tumor-treating fields (TTFields) are low-intensity and intermediate-frequency alternating electric fields that have been found to inhibit tumor cell growth. While effective, the mechanism by which TTFields affect cell growth is not yet clearly understood. Although numerous mathematical studies on the effects of electromagnetic fields on single cells exist, the effect of TTFields on single cells have been analyzed less frequently. The goal of this study is to explore through a mathematical analysis the effects of TTFields on single cells, with particular emphasis on the thermal effect. We examine herein two single-cell models, a simplified spheroidal model and a simulation of a U-87 MG glioblastoma cell model obtained from microscopic images. A finite element method is used to analyze the electric field distribution, electromagnetic loss, and thermal field distribution. The results further prove that the electric field in the cytoplasm is too weak and its thermal damage can be excluded as a mechanism for cell death in TTFields. Bioelectromagnetics. 2020;41:438–446. © 2020 Bioelectromagnetics Society.     

Perception of Risks from Electromagnetic Fields: Lessons for the Future

Technologies based on extremely highfrequency electromagnetic fields, inparticular in the terahertz region, arequite recent and new to the public. While anumber of advantages have been shown,especially in the biomedical area,biological effects and possible healthimplications have not been fullyinvestigated. The experience gained withelectromagnetic fields of lowerfrequencies, from ELF to microwaves,suggests that innovating technologies maycreate concern, or even fear, among thepublic for hypothetical health risks.Social research has shown that worries arerelated to the perception of risks by thepublic more than to their actual existence.Risk perception depends on several factors,many of which are relevant forelectromagnetic fields. They include lackof familiarity with the agent, difficultyin understanding interaction mechanisms,and uncertainty in scientific knowledge.Lessons learnt from the past lead torecommend that specific research onbiological effects of terahertz radiationbe started from the very beginning of thedevelopment of technological applicationsand that a continuous and effectivedialogue be established between thescientific community and the public.     

Calcium protects differentiating neuroblastoma cells during 50 Hz electromagnetic radiation

Despite growing concern about electromagnetic radiation, the interaction between 50- to 60-Hz fields and biological structures remains obscure. Epidemiological studies have failed to prove a significantly correlation between exposure to radiation fields and particular pathologies. We demonstrate that a 50- to 60-Hz magnetic field interacts with cell differentiation through two opposing mechanisms: it antagonizes the shift in cell membrane surface charges that occur during the early phases of differentiation and it modulates hyperpolarizing K channels by increasing intracellular Ca. The simultaneous onset of both mechanisms prevents alterations in cell differentiation. We propose that cells are normally protected against electromagnetic insult. Pathologies may arise, however, if intracellular Ca regulation or K channel activation malfunctions.     

Detection and processing of electromagnetic and near-field acoustic signals in elasmobranch fishes

The acoustic near field of quietly moving underwater objects and the bio-electric field of aquatic animals exhibit great similarity, as both are predominantly governed by Laplace's equation. The acoustic and electrical sensory modalities thus may, in directing fishes to their prey, employ analogous processing algorithms, suggesting a common evolutionary design, founded on the salient physical features shared by the respective stimulus fields. Sharks and rays are capable of orientating to the earth's magnetic field and, hence, have a magnetic sense. The electromagnetic theory of orientation offers strong arguments for the animals using the electric fields induced by ocean currents and by their own motions in the earth's magnetic field. In the animal's frame of reference, in which the sense organs are at rest, the classical concept of motional electricity must be interpreted in relativistic terms. In the ampullae of Lorenzini, weak electric fields cause the ciliated apical receptor-cell membranes to produce graded, negative receptor currents opposite in direction to the fields applied. The observed currents form part of a positive-feedback mechanism, supporting the generation of receptor potentials much larger than the input signal. Acting across the basal cell membranes, the receptor potentials control the process of synaptic transmission.     

Generic UMTS test signal for RF bioelectromagnetic studies

This report outlines the characteristics of universal mobile telecommunications system (UMTS) signals and discusses the signal parameters with respect to their possible biological relevance in order to define a generic UMTS test signal (GUS) for experiments aiming at the investigation of biological effects of weak electromagnetic fields. The GUS includes features of a real UMTS signal and especially the characteristics of UMTS, which differ from those of already applied second generation mobile communication systems (GSM 900, DCS1800, PCS1900, IS-95). It has been specified on the basis of the recommendations of a working group of the German Forschungsgemeinschaft Funk (FGF) with a focus on the mechanisms of UMTS which are responsible for slow term signal contributions, i.e., low frequency variations of the radio frequency (RF) envelope, since the hypothetical possibility of biological relevance of weak electromagnetic fields is often attributed to time variations of the RF envelope with frequencies close to those of natural processes. In this respect, it is also shown that the mandatory power control loop in UMTS gives rise to very strong 1.5 kHz variations on the air interface. Based upon the concept of the GUS, a UMTS test signal generator (GUS6960S) is described.     

Antenna impedance matching with neural networks

Impedance matching between transmission lines and antennas is an important and fundamental concept in electromagnetic theory. One definition of antenna impedance is the resistance and reactance seen at the antenna terminals or the ratio of electric to magnetic fields at the input. The primary intent of this paper is real-time compensation for changes in the driving point impedance of an antenna due to frequency deviations. In general, the driving point impedance of an antenna or antenna array is computed by numerical methods such as the method of moments or similar techniques. Some configurations do lend themselves to analytical solutions, which will be the primary focus of this work. This paper employs a neural control system to match antenna feed lines to two common antennas during frequency sweeps. In practice, impedance matching is performed off-line with Smith charts or relatively complex formulas but they rarely perform optimally over a large bandwidth. There have been very few attempts to compensate for matching errors while the transmission system is in operation and most techniques have been targeted to a relatively small range of frequencies. The approach proposed here employs three small neural networks to perform real-time impedance matching over a broad range of frequencies during transmitter operation. Double stub tuners are being explored in this paper but the approach can certainly be applied to other methodologies. The ultimate purpose of this work is the development of an inexpensive microcontroller-based system.     

Spatial Distribution of Optical Near-Fields in Plasmonic Gold Sphere Segment Voids

We present a comprehensive experimental and computational study on the electromagnetic field distribution in sphere segment void arrays. Surface plasmon polaritons can be excited in these void arrays, resulting in greatly enhanced electromagnetic fields. With the scanning near-field optical microscope (SNOM) we are able to measure the electromagnetic field distribution at the sample surface. For this purpose, an array of relatively large voids with a sphere diameter of 900 nm was fabricated, allowing for an easy access of the scanning glass-fibre tip and yielding very detailed scans. Complementary, finite-difference time-domain (FDTD) calculations on a complete void array have been performed and compared with the SNOM intensity maps and experimental reflectivity data. We show in a direct way both the existence of extended and localised modes in the Au void array for three different void depths. We also show and discuss the changes that the modes undergo for the different void depths and excitation wavelengths. Moreover, since the simulations were performed for two different void geometries, one containing perfectly spherical void surfaces and another more realistic one, which considers the presence of interstitial wall holes and other imperfections, as observed in scanning electron micrographs, we were able to determine by comparison with the experiment under which conditions an array of idealised sphere segment voids is a meaningful model. This demonstrates that both SNOM and FDTD simulations are powerful tools for understanding the plasmonic response of metallic nanostructures, thus enabling, for instance, a design for applications in ultra-sensitive optical detection.