8. Mechanisms of Action of EHF EMR on Biological Objects
The current state of research on use of EHF EMR of non-thermal intensity in medicine and experimental biology is characterized by an increasing volume of theoretical research and practical utilization, with wide introduction into clinical practice. This is very significant, considering that to this day there is not yet a consistent general conception of a mechanism for the effects of EHF EMR on the human organism, although a few concepts have gained curency in Russia and Ukraine. In the west, research on this theme is carried forward basically in an applied nature.
Historically, the first hypothesis was put forward by the Moscow school of radiophysicists, the basis of which was an assertion of the coherent nature of interaction of external EHF EMR with the cells' own EMF. The Pushchino school of cellular biophysicists, N.K. Chemeris et al., insist that stochastic resonance plays a dominant role, in other words, it is a question of the energetically dominant action in the bioenergetic informational field. Here, though, we have already stressed the role of modulating frequencies. The concepts of the Tula school of field, radiation and bioinformatics biophysics stresses the role of the frequencies of physiological rhythms of the body. However, in view of the relatively recent beginning of mass utilization of EHF therapy procedures, the question of genetic factors in the consequences of EHF irradiation remains open.
As early as 1968, [A.S. Presman] noted that in any living organism there exists a reliable protection against external natural and artificial electromagnetic noise disturbances (signals not coherent with any of the signals used by the system), and against other incommensurate external influences. Apparently, it is the action of this multi-stage (passive or active) protection in the organism that is connected with the experimentally detected biphasic dependency of the bioeffects of electromagnetic fields on their intensity, i.e., initiation of opposite physiological changes under the influence of EMF of low and high intensities. By way of illustration in experiments on dogs, the following results were obtained: 100-200 mW/cm2--suppression of conditioned reflexes; 5-10 mW/cm2--stimulation; 0.2-2 mW/cm2--suppression.
On the basis of experimental data in the work of [I.V. Rodshtadt], an attempt was made to calculate the reflex arc under the influence of EHF EMR. According to all the calculated data, EHF radiation of low intensity significantly modulates the frequency of spontaneous discharges of Ruffini's corpuscles. But Ruffini's corpuscles are generally concentrated in the region of the large joints and on the hairy part of the head. The region of the shoulder joints was selected as the zone for therapeutic irradiation. Firstly, the skin in the region of large joints (in this case, the shoulders) is strongly hydrated because of folds of collagen, great content of proteoglycans, significant movement of biologically active substances, including histamine and proteinase and their inhibitors, and excess concentrations of fat cells. Excessively hydrated tissues, as is known, absorb extremely high frequency electromagnetic waves especially strongly. Secondly, the regions of the large joints coincide in a number of cases with the zones of Zakharyin-Ged and segmentary acupuncture points, which ensure adequate targeting of the therapeutic effects to the corresponding ailing organ. With regard to the reflex arc of therapeutic action, a few key elements can be described. The information from EHF oscillations of low intensity is transmitted from Ruffini's corpuscles by the so-called LIF (low-intensity fluorescing) neurons. They enter into the structure of the vegetative ganglia, secreting into their vascular channels and synaptic fissures adrenaline and noradrenaline in the course of their rhythmic activity. This rhythmic activity has a latent period of 30 seconds and is revealed in the modulating effect of fluorophor (dopamine) on the slow excitatory, acetylcholine-dependent post-synaptic potential. A further reference point for calculating the reflex arc is provided by data from N.P. Zalyubovskaya on increased levels of adrenaline and noradrenaline in the blood, and also adrenaline in the hypothalamus, in experimental animals under the influence of EHF EMR of low intensity. That is, the humoral part of the reflex arc begins with the LIF-neurons. Noradrenaline, reaching the vessels of the brain via blood flow, crosses the blood-brain barrier in the region of the pituitary gland, inducing a small spasm of the brain arterioles. The sensory reception of EHF EMR waves of low intensity is completed with optimization of the activity of the brain owing to adequate correlation of its microcirculation and metabolism. Unlike noradrenaline, adrenaline does not cross the blood-brain barrier. Therefore, the origin of the increased level of adrenaline in the hypothalamus during EHF exposure is not fully clear. Apparently, having overcome the blood-brain barrier in the region of the pituitary, noradrenaline gives a signal for the secretion of adrenaline by the chromaffinocytes and glial cells of the hypothalamus. This has been confirmed in experiments. In turn, adrenaline, as is well known, is a limiting factor in the secretion of corticotropin-releasing hormone by neurons of the hypothalamus, which determines the production of adrenocorticotropic hormone (ACTH) by the adeno-pituitary cells. According to the data of various authors, the time from the moment adrenaline and noradrenaline appear in the blood to when ACTH also appears in the blood is 10-30 seconds. Thus, in calculating the reflex arc of the therapeutic effects, good correspondence is obtained between the sum of the latent periods of its nervous and humoral parts (40-60 seconds), and the time for indication of sensory feeling during EHF exposure at low intensity of the skin of basically healthy volunteers (40-50 seconds). The experimental data of N.P. Zalyubovskaya say that an increase in the level of ACTH under the influence of EHF exposure of low intensities actually occurs. In particular, she noted an increase in the amount of 17-OCS in the blood against a background of decreased ascorbic acid content in the adrenal cortex.
Crossing over to the questions of biochemical reception of EHF exposure at low intensities, we must keep in mind that the effects occur at the transduction stage, when the natural humoral signals penetrating into the cells are modulated. This type of physiological effect is realized through the phospholipids of the cells' plasma membranes, and in our case, apparently, is achieved through some acceleration of their peroxide oxidation. The described effects of EHF exposure at low intensities occurs through a change in the rate of diffusion of the substrates and products of peroxide oxidation of lipids. This situation is fully possible at the level of capillary vessels, i.e., in the microcirculatory system, where, for example, in the case of functional hyperemia, and consequently against a background of stronger processes of filtration-absorption, there occurs facilitation of diffusion in the interstitial canaliculi. The temperature threshold for dilation of skin vessels is quite low, only 0.06_C, i.e. is on the border of millimeter radiowave heating of tissue. Apparently, this effect happens to the venous walls, leukocytes and fibroblasts, inasmuch as they belong to type-B tissue according to Labori, which is equipped with metabolic blocks of the pentose-phosphate cycle, and is therefore sensitive, according to the data of N.P. Zalyubovskaya, to EHF EMR waves of low intensity. We must bear in mind that millimeter waves penetrate irradiated skin to a depth of 1 mm, but the microcirculatory system of the skin begins to function at a depth of 150 microns, i.e., is fully accessible to direct EHF exposure. Reception of EHF EMR of low intensity by the intradermal venous network, apparently, is accompanied by intensification of the pentose-phosphate cycle, which according to all physiological canons, should lead to change in the concentration of potassium ions. In turn, the potassium, or more accurately, its physiologically high concentration, in the presence of calcium ions, is an adequate stimulus for nerve fibers secreting neuropeptides. Biochemical reception of EHF EMR of low intensity is thus accompanied by release of physiologically active substances, which often play the role of endogenous medicines. Moreover, the therapeutic effect in this case does not depend on localization of the EHF exposure, because the microcirculatory channels are distributed throughout the surface of the skin sufficiently evenly.
We introduce detailed data from I.V. Rodshtadt on differences in therapeutic effects from EHF therapy during irradiation of the right and left halves of the body, which have a direct bearing on the theme of our review. Irradiation of the left half of the body by millimeter waves of low intensity is targeted primarily to the right hemisphere in healthy volunteers and stroke patients, and in experimental animals is accompanied by increases in the population of long-lived lymphocytes in the lymph nodes on the irradiated side. An increase in the total phosphatase activity in the mitochondria of these recirculating small lymphocytes (irrespective of EHF exposure) is a hopeful prognostic feature for stroke patients in terminal conditions. Apparently, an increase in antigen-specific T-cell activity occurs in parallel, especially in cases of damage to the right hemisphere. The effect observed during irradiation by millimeter waves of low intensity of the right half of the body in experimental animals consists of an increase in the population of short-lived lymphocytes and lymphocytes normally found in the lymphoid organs and, taking into account clinical observations as well as research on healthy volunteers, is explained by more equal targeting of the effects to both hemispheres of the brain. As a result it can be proposed that EHF modulation of the activity of the brain during irradiation of the left half of the body is accomplished via both nervous and humoral mechanisms. In the first case, the effect is addressed primarily to the right hemisphere, and in the second, i.e., during use of humoral mechanisms, the effect is addressed to the hypothalamus. EHF modulation of the activity of the brain during irradiation of the right half of the body is accomplished mainly through nervous mechanisms, and the effect is more equally addressed to both hemispheres.
In modern times, one may consider the concept of proteins as dynamic systems to be fully confirmed [Demchenko, 1986; and Demchenko, 1988]. Efforts by researchers should be directed toward analysis of specific types of movement and location in connection with function. The frequencies of oscillation of groups of atoms in the active center of an enzyme are located in the range of 10-100 GHz. The approximate resonant frequencies in Hz have been determined experimentally for a few structures in living cells: somatic cell--2.39 x 1012; somatic cell nucleus--9.55 x 1012; mitochondria from liver cells--3.18 x 1013; human cell genome--2.5 x 1013; interphase chromosome--7.5 x 1011; metaphase chromosome--1.5 x 1013; DNA--(2-9) x 109; nucleosome--4.5 x 1015; ribosome--2.65 x 1015; cellular membrane--5 x 1010; cytoskeleton--108; erythrocyte (3.5-4.0) x 1010 [Illarionov].
Application of the information theory to biology [Presman], showed that along with energetic interactions in biological processes, a significant (if not main) role is played by informational interactions. These are characterized by transformation of information and its transmission, codification and storage. Biological effects associated with these interactions, depend not on the strength of the energy carried into one or another system, but on the information carried into it. A signal carrying information only induces redistribution of energy in the system itself and directs the processes happening in the system. If the sensitivity of the perceiving systems is sufficiently high, the transmission of information may occur with the help of very little energy. Information may accumulate in the system with the help of small signals [Nefedov, Protopopov, Khadartsev and Yashin]. In living organisms, systems for perceiving information transmitted with the help of EMF are reliably shielded from natural electromagnetic interference, but when there are pathological conditions in the organism, spontaneous changes in EMF (from solar eruptions or lightning) disturb the regulation of physiological processes. Whole organisms have maximal sensitivity to EMF, and isolated organs and cells lesser sensitivity, solutions of macromolecules even lesser. Significant differences are observed in reactions to EMF in one and the same biological system (molecular, cellular, organ or systemic) depending on whether it is located in an intact organism or in an isolated condition. Differences are noted in these two cases even in the nature of dependency of the reaction of the system on EMF parameters.
All this indicates that systems especially sensitive to EMF were apparently formed in the process of evolution only at the macroscopic level. In other words, the perception of weak natural EMF occurs only on the level of sufficiently complex biological systems, and is fully developed only in intact organisms. As mentioned above, one of the first hypotheses was that put forward by the biophysical school of academician N.D. Devyatkov (Institute of Radio Engineering and Electronics, Russian Academy of Sciences) on the coherent nature of activation of the cells of an organism [Devyatkov, Golant and Betskiy]. According to this hypothesis, the microstructure of the cell membrane (the aggregate of mitochondrial membranes) ensures the formation of the dipolar component of the cell. This oscillating electrical dipole, combined with acoustical vibration of the membrane, is the cellular generator of the cell's own EHF EMF. In a healthy cell, the nature of the vibrations is stochastic (especially considering the interaction of the EMF of the ensemble of cells), and the spectral nature of the field is near to noise at some intermediate intensity. During pathological changes in the cell, the reaction of the cell is expressed in growth in intensity of generation in relatively narrow bands of the spectrum. It can be proposed that, when considering one or another form of disturbance of metabolic processes in the cell, an increase in the intensity of generation is connected with the redistribution of free energy and its influx into the part producing the spectrum characteristic of the disturbance (the simplest, most understandable analog at the macro-organism level is an increase in body temperature during inflammatory illness). According to the hypothesis of coherent resonance, strictly speaking, the process is bioinformational [Afromeev, Subbotina and Yashin], insofar as the intensity of external EMF plays no particular role in the occurrence of a chain reaction in the cell; what is important is its information content (frequency, modulation, polarization, etc.). A weak point of this concept is the absence of the proven selection of discrete frequencies of external EMF used widely in therapeutic practice: 3-4 therapeutic monochromatic frequencies in the range from 2 to 8 mm. A possible variant (particularly subjective) selection of these frequencies is considered by [Khadartsev and Yashin].
Regarding this question, one may also note the research being conducted under the leadership of N.K. Chemeris at the Institute of Cellular Biophysics, Russian Academy of Sciences, in the city of Pushchino-na-Oke. The results of theoretical and experimental research by [Gapeev and Chemeris] led to the concept of stochastic resonance with a special role played by double resonance at EHF frequencies carrying a low-frequency modulated signal; the latter, by all appearances, is located in a region of frequencies of the basic physiological rhythms of the body. Redistribution of the free energy of cellular metabolism takes place not in the form of frequency resonance, but resonance which is energetic in a quite wide frequency spectrum. Therefore, one of the preliminary conclusions is not about the bioinformational, but the bioenergetic nature of activation of cellular generation by external EMF. At the same time, it follows simply from experiment that the energetics of external electromagnetic exposure plays no role; even relatively low (threshold) levels suffice. In principle, this is in complete agreement with the biological mechanism of the chain reaction of free energy formation in cellular metabolism, but in order to reject the informational component, it would be necessary to undertake a large series of experiments at all EMF ranges which play a vitally important role in cell functioning. The most attractive aspect of this concept is the expressly experimental approach.
It is obvious that it is meaningless to argue over the primacy (or dominance) of biochemical or biophysical processes in the creation of a cell's own EMF. It is clear that the free energy, needed by the cell for processes including generation of EHF EMF, is produced through biological oxidation in the mitochondria. The most important role here is played by adenosine triphosphate (ATP). And this energy is transferred further in the cell by chemical means.
The natural biological field of a living organism is EMF in the ranges from infrared to ultraviolet, and possibly, even shorter waves. A second, also natural field for an organism is the field which depends upon physiological rhythms. These are the low-frequency oscillations from fractions of a Hertz to hundreds (or thousands) of Hertz, physically realized as acoustical-electrical oscillations. Here arises, from the point of view of radiophysics, a very significant question: within the boundaries of the organism, all fields should be simultaneously tied together as (we repeat) biocybernetic and biophysical systems; in this case, this correlational bond occurs only as modulation (in the model, amplitudinal, but in reality, carried in a very complex, combined manner). Therefore, and only for this reason (rather than because of the response to external, natural EMF) there exist oscillations within an organism, part of whose spectra most likely coincides with both the long-wave and EHF ranges. Their function in the natural biophysical process is correlational-connecting; median-modulating. In other words, the EHF range is a medium frequency between low and high ranges, allowing the correlation of fields within an organism and the transfer of information by modulation [Afromeev, Subbotina and Yashin].
[Khar'kyanen] came to the conclusion in his research that a cooperative system of a large number (105-1010) of molecular centers transmitting energy to some collective, distributed level of freedom should serve in the capacity of an effective primary target of weak-intensity EHF EMR. It was shown that such a collective degree mode is achievable for a system with a large number of cooperatively functioning channel-receptors on a membrane or a large number of molecular reagents, the state of which is fixed near a critical point.
The search for effective molecular mechanisms of EHF bioeffects has led to the necessity of clear accounting of the dynamics of active biomolecular structures participating in a complex system of chemical chain reactions, as a rule, of a catalytic nature. In most cases the question may be about the processes of synthesis and breakdown of the same biopolymers, about conformational transitions and about the dynamics of hydrated membranes [Serikov].
On the basis of the magnetic-resonance mechanism of action of EMR of low (non-thermal) intensities on biological objects, [Dmitrievskiy] found a highly effective action of circular-polarized radiation on the permeability of biological membranes, experimentally determined over the range of visible light as well as across the entire range of EHF frequencies. There is also polarization of radiation in the Zeeman effect (and in NMR, and EPR, and in chemical polarization of ions and free radicals in the constant magnetic field of the Earth or separate parts of the organism). Excitation of the corresponding levels may be caused by EMR from external sources or arising due to internal biochemical processes.
[Subbotina and Yashin] proposed in their research the task of determining the basic mechanisms of action of EHF EMR on separate human systems and organs. According to modern concepts, the effect of irradiating the human body with EHF EMR lies in activation of the biologically active points (BAPs), the signals from which are transmitted along the main acupuncture channels (meridians) to the responding organs or systems and act further at the cellular level. The biophysical mechanism of action should occur on the level of normal functioning of the whole body. At the same time, low-level action of EHF EMR on isolated biological tissue should not create a characteristic effect which can be detected in preparations taken from biopsies. Research conducted on EHF EMR irradiation of biopsied and intact livers of experimental animals showed that morphological changes are characteristic only of irradiation of the intact animal. This confirms the bioinformational nature of low-level, non-thermal exposure, derived from the concept of the body as a complex self-organizing system. From the informational effect of MMW we may anticipate mobilization of the reserve potentialities of an organism in anomalous conditions.
Thus, to this day there is no precise concept of the physical-chemical mechanisms of action of EHF irradiation on biological systems, and there is likewise no precise clarity on the nature of sensation of extremely high frequencies in living objects. Regarding this there exist only a number of hypotheses: the hypothesis of coherent excitement and interaction [Devyatkov, Golant and Betskiy], the information hypothesis [Nefedov, Protopopov, Sementsov and Yashin], the hypothesis on the soliton mechanism of energy transmission [Davydov] and a few others connected with effective absorption of energy from EHF EMR by water molecules [Gapeev, Safronova, Chemeris and Fesenko].
We will consider the hypothesis of the Kiev school (Prof. S.P. Sit'ko in Ukraine), which has been developed in considerable detail and confirmed experimentally. Living things are considered as a fourth quantum level (after nuclear, atomic and molecular levels) of structural organization of nature. In this way, the physics of the alive, as opposed to biophysics, is arrived at from a definition of life in terms of fundamental natural science: any independent living thing is a quantum-mechanical whole, the self-coordinated, non-local potential of which is formed through a type of laser-coherence in the mm wavelength range [Sit'ko and Mkrtchyan]. A number of facts support the possibility of the existence of such a coherent field in an organism in the mm range:
-intensity of the electrical field in the protoplasmic membranes of each cell of a living organism (10-5V/m);
-frequency of vibration of its membranes, 1010-1011 Hz;
-the density of EHF EMR inside the body maintained beyond a threshold of non-equilibrium phase transition becauset of the mechanism of full internal reflection by the skin;
-the genomes of all somatic cells of any organism are identical, and this means that these cella may be regarded as active centers of the system in a regime of multi-modal coherence.
In his articles, S.P. Sit'ko has reported the direct detection of a non-equilibrium component of EMR from the human body in the mm range. This, he says, is a decisive experiment which converts the working hypothesis into the scientific trend "Physics of the Alive" [Sit'ko and Yanenko].
The results of clinical and experimental research on the effect of super-low levels of EMR in the mm range on biological objects of various levels of complexity are the basis for ideas about the means of expression of genetic information at the macroscopic level of the whole organism. An important test of the new concepts is the possibility of restoring the functional state of the body with only a few quanta of EMR (10-20 W/Hz cm2). Quantum medicine has now demonstrated this with a few thousand patients [Sit'ko and Mkrtchyan].
9. Standards and Normalization of HF EMR
In the USSR, wide research into electromagnetic fields was begun in the 1960s. Much clinical material accumulated on undesirable effects of magnetic and electromagnetic fields, and it was proposed to introduce a new nosological illness "radiowave sickness" or "chronic injury from microwaves." Thenceforth work by scholars in Russia established that, firstly, the human nervous system, especially higher nervous activity, is sensitive to EMF, and, secondly, that EMF possesses a so-called informational action in its effects on humans at intensities below the threshold values of thermal effects. The results of this work were used in the development of normative documents in Russia. As a result, the norms established in Russiawere very strict and differed from those in Americaand Europe by a few orders of magnitude (for example, in Russia,the maximum permissible level for workers is 0.01 mW/cm2; in the USA, 5 mW/cm2). It is mentioned that subsequently a Soviet-American group was formed with scholars from the USSR and America, which acted from 1975 to 1985. This group organized joint biological research, which confirmed the correctness of the concepts of the Soviet scholars.
All norms and standards constitute a compromise between the advantages afforded by using new technology and possible risks connected with their use. Therefore, the maximum permissible levels of exposure to any factor depend on the degree of knowledge about health damage, on criteria of risk adopted in this regard, and established capacity for endurance. Taking this into account, permissible (operational) levels, cumulative (daily) exposure limits and maximum endurable levels (for emergency procedures) were established [Dumanskiy and Prokhvatilo, All-Union Standards]. Permissible operational levels for an 8-hour workday were:
30-300 kHz 20 V/m none
0.3-3 MHz 10 V/m 614 V/m
3-30 MHz 4 V/m 614-61.4 V/m
30-300 MHz 3 V/m 61.4 V/m
0.3-300 GHz 5 _W/cm2 1-5 _W/cm2
According to OST 11.2.004-84 "Radiofrequency electromagnetic fields of 300 MHz-300 GHz," maximum endurable levels are 1000 _W/ cm2 = 1 mW/ cm2, and the allowable energy load during a working day is 200 _W-hour/ cm2. Maximum permissible exposure is calculated as (allowable energy load)/(time of exposure (hours)).
In [Pyasetskiy and Pisanko, 1991], on the basis of much clinical and experimental material, the following were noted:
1) EHF EMR of low intensity (less than 10 mW/cm2) is capable of changing the functional condition of living organisms of different levels of organization. The acting and initiating factor is the power and duration of exposure.
2) Physiological reactions resulting from exposure to EHF EMR at non-thermal levels of power lie within the limits of normal and may be registered by length of time of reordering the functions of the pathological system or organ subjected to EHF exposure.
3) During prolonged exposure of a living organism, low-intensity EHF EMR may change from a normalizing, stimulating factor into a factor able to induce bioeffects uncharacteristic of the functioning of the affected organ or system as a whole. Negative effects and their strength depend on the time of exposure to EHF radiation and the level of development and differentiation of the living organism.
4) When creating devices which generate low-intensity EHF EMR, it is essential to foresee the technical development of the instruments and devices for medical-biological research and therapeutic use.
Medical-biological instruments should be retuned in terms of frequency, power and time of exposure, to the guiding informational signals from the biosystem which is undergoing EHF exposure. Therapeutic instruments should possess stable power of EMR, not induce negative bioeffects, and limit the time of exposure to 15-30 minutes. In this connection, the Ukrainian government published a "Resolution of the Necessity of Testing and Certifying EHF Instruments Used in Medical-Biological Practice." A laboratory was established in the Ministry of Public Health of Ukraine for monitoring and certifying EHF instruments.
As was noted in A Brief Ecological Encyclopedia, [Person in Electromagnetic Fields], issued by the Center for Electromagnetic Safety, Institute of Biophysics, the systems most sensitive to EMF are the central nervous, hormonal or cardiovascular systems. Groups requiring closer attention are children, pregnant women, people with illnesses of the central nervous, hormonal or cardiovascular systems or with weakened immunity or allergies. They should carefully observe rules of electromagnetic safety in their lifestyles and protect themselves from the effects of EMF.
It is considered that under Russian Sanitary Norms such values of EMF have been adopted as maximum permissible levels for irradiation of the population that in everyday irradiation under conditions characteristic of the given source do not induce illness or divergence from health detectable by modern research methods during the period of irradiation or for periods of time after its cessation in the population, regardless of sex or age.
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