N. K. Chemeris

Inhibition of the production of reactive oxygen species in mouse peritoneal neutrophils by millimeter wave radiation in the near and far field zones of the radiator

Abstract Using the luminol-dependent chemiluminescence technique effects of a low-intensity electromagnetic field (EMF) of extremely high frequency of the production of reactive oxygen species (ROS) by mouse peritoneal neutrophils was studied. The neutrophils were activated by opsonized zymosan. It was found that the EMF inhibits the ROS production by the neutrophils. However, in the near field zone of the channel radiator a quasi-resonance inhibition of the ROS production was observed in a narrow band of frequencies (41.8–42.05 GHz). On the other hand, no frequency dependence of the EMF effect in the far field zone of the radiator was found. The data suggest that the quasi-resonance dependence of the ROS inhibition of the EMF frequency in the near field zone of the radiator could be conditioned by some peculiarities of the structure and nature of the EMF in this zone.

Age-related changes of skin blood flow during postocclusive reactive hyperemia in human

The objective was to study age‐related alterations in the time‐amplitude characteristics of the oscillatory components of peripheral blood flow in healthy humans during postocclusive reactive hyperemia.

Modification of production of reactive oxygen species in mouse peritoneal neutrophils on exposure to low-intensity modulated millimeter wave radiation

Abstract The effect of low-intensity modulated electromagnetic radiation of extremely high frequencies (EHF EMR) on the production of reactive oxygen species by mouse peritoneal neutrophils was investigated. The neutrophil activity in synergistic reaction of calcium ionophore A23187 and phorbol ester PMA was estimated by luminol-dependent chemiluminescence technique. The cells were irradiated for 20 min in the far-field zone of the channel radiator in the presence of A23187 and then were activated by PMA. It was shown, that continuous EHF EMR (50 μW cm −2 ) inhibited quasi-resonantly the synergistic reaction. The maximum effect was about 25% at carrier frequency of 41.95 GHz. The effect had S-like dependence on an absorbed energy flux density, and in a range from 20 to 150 μW cm −2 varied slightly and on the average was about 24%. The modulated radiation with carrier frequency of 41.95 GHz and modulation frequency of 1 Hz activated the synergistic reaction, but at modulation frequencies of 0.1, 16 and 50 Hz inhibited one. At fixed modulation frequency of 1 Hz the nonlinear dependence of the effect on the carrier frequency was found. The synergistic reaction was activated in the frequency range of 41.95–42.05 GHz and was inhibited at the frequencies of 41.8–41.9 GHz. The effect was observed only at high A23187 concentrations used. The obtained results prove the opportunity of control over neutrophil functioning by low-intensity modulated EHF EMR, presumably manipulating by coupled systems of enzyme reactions.

The role of fatty acids in anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation

The effects of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR; 42.2 GHz, 0.1 mW/cm(2) , exposure duration 20 min) on the fatty acid (FA) composition of thymic cells and blood plasma in normal mice and in mice with peritoneal inflammation were studied. It was found that the exposure of normal mice to EHF EMR increased the content of polyunsaturated FAs (PUFAs) (eicosapentaenoic and docosapentaenoic) in thymic cells. Using a model of zymosan-induced peritoneal inflammation, it was shown that the exposure of mice to EHF EMR significantly increased the content of PUFAs (dihomo-γ-linolenic, arachidonic, eicosapentaenoic, docosapentaenoic, and docosahexaenoic) and reduced the content of monounsaturated FAs (MUFAs) (palmitoleic and oleic) in thymic cells. Changes in the FA composition in the blood plasma were less pronounced and manifested themselves as an increase in the level of saturated FAs during the inflammation. The data obtained support the notion that MUFAs are replaced by PUFAs that can enter into the thymic cells from the external media. Taking into account the fact that the metabolites of PUFAs are lipid messengers actively involved in inflammatory and immune reactions, we assume that the increase in the content of n-3 and n-6 PUFAs in phospholipids of cellular membranes facilitates the realization of anti-inflammatory effects of EHF EMR.

Changes in the chromatin structure of lymphoid cells under the influence of low-intensity extremely high-frequency electromagnetic radiation against the background of inflammatory process

Using the alkaline single cell gel electrophoresis technique (comet assay), changes in chromatin structure of peripheral blood leukocytes and peritoneal neutrophils have been studied in mice exposed to low-intensity extremely high-frequency electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, 20 min at 1 h after induction of inflammation) against the background of the systemic inflammatory process. It was revealed that the exposure of mice with the developing inflammation leads to a pronounced decrease in the level of DNA damage to peripheral blood leukocytes and peritoneal neutrophils. It is supposed that the changes in the chromatin structure of lymphoid cells have a genoprotective character in the inflammatory process and can underlie the mechanisms of realization of antiinflammatory effects of the electromagnetic radiation.

Age-related differences in the dynamics of the skin blood flow oscillations during postocclusive reactive hyperemia

Age-related changes in peripheral microcirculation were studied using laser Doppler flowmetry in 60 apparently healthy subjects. The response of microcirculation to short-term ischemia was studied using the occlusion test. Changes in the amplitude of the peripheral blood flow oscillations were determined using time-amplitude analysis based on continuous adaptive wavelet filtration. The oscillation amplitude in the frequency range of the heart rate was found to reach the maximum with a delay after the removal of the occlusion, whereas in the range of the respiratory rhythm, no delay was observed. The hyperemic response to short-term ischemia is assumed to develop under the predominant influence of the arterial-arteriolar component, whereas the dynamics of amplitude oscillations in the range of the respiratory rhythm is a result of the devastation of the venular component after removal of occlusion. In response to short-term ischemia, the maximum oscillation amplitudes of myogenic, neurogenic, and endothelial rhythms decreased with age, which demonstrates the restriction of the regulatory control of the peripheral blood flow by the corresponding systems.

Application of vasoactive and matrix-modifying drugs can improve polyplex delivery to tumors upon intravenous administration

Low efficacy of cationic polymer-based formulations (polyplexes) for systemic gene delivery to tumors remains the crucial concern for their clinical translation. Here we show that modulating the physiological state of a tumor using clinically approved pharmaceuticals can improve delivery of intravenously injected polyplexes to murine melanoma tumors with different characteristics. Direct comparison of drugs with different mechanisms of action has shown that application of nitroglycerin or losartan improved extravasation and tumor uptake of polyplex nanoparticles, whereas angiotensin II had almost no effect on polyplex accumulation and microdistribution in the tumor tissue. Application of nitroglycerin and losartan caused from 2- to 6-fold enhanced efficacy of polyplex-mediated gene delivery depending on the tumor model. The results obtained on polyplex behavior in tumor tissues depending on physiological state of the tumor can be relevant to optimize delivery of polyplexes and other nanomedicines with similar physicochemical properties.

NONLINEAR PROCESSES OF INTRACELLULAR CALCIUM SIGNALING AS A TARGET FOR THE INFLUENCE OF EXTREMELY LOW-FREQUENCY FIELDS

Theoretical analysis of peculiarities of reception of weak extremely low-frequency periodic signals by calcium-dependent intracellular regulatory systems was performed on the reduced “minimal” model for calcium oscillations suggested by Goldbeter et al. (Proc. Natl. Acad. Sci. USA 87, 1461–1465, 1990). The model considered the following calcium-dependent processes: the rise in intracellular free calcium concentration ([Ca2+]i) due to calcium ionophore A23187 action on a cell, activation of the Ca2+ entry through calcium channels in the plasma membrane by the initial rise in [Ca2+]i, and the Ca2+ release from intracellular stores by the calcium-induced calcium release mechanism. Calcium channels of plasma membrane were chosen as a target for the modulating signal and an additive noise influence in the model. An increase in [Ca2+]i under the influence of the modulating signal was demonstrated to depend not only on the amplitude and frequency of this signal, but also on the phase of the signal with respect to a momentary chemical stimulation of the cell. Such an effect was found only at high strengths of chemical stimulation and with a particular sequence of delivery of the chemical and electromagnetic stimuli. An increase in noise intensity led to magnification of the mean level of [Ca2+]i in a narrow frequency range by the mechanism of stochastic resonance. Under the influence of a modulating periodic signal, the gradual increase in strength of chemical stimulation induced a system transition from regular to chaotic behavior, and then to induced periodic oscillations. A boundary of the transition from chaotic to periodic oscillations corresponded to a “threshold” of sensitivity of calcium-dependent intracellular signaling systems on [Ca2+]i to the influence of the modulating signal. Results of the theoretical analysis led us to conclude that the narrow-band response of a system to an external electromagnetic signal is determined purely by nonlinear properties of the system.

Involvement of the sympatho-vagal balance in the formation of respiration-dependent oscillations in the human cardiovascular system

The effect of deep breathing controlled in both rate and amplitude on the heart rate variability (HRV) and respiration-dependent blood flow oscillations was studied in the forearm and finger-pad skin of healthy 18- to 25-year-old volunteers. In order to reveal the effects of the divisions of the autonomic nervous system on the amplitudes of respiratory sinus arrhythmia (RSA) and skin blood flow oscillations, we studied the indices of the cardiovascular system in two groups of subjects with respectively lower and higher values of the sympatho-vagal balance. This index was calculated as a ratio of low frequency and high frequency HRV spectral power (LF/HF) under the conditions of spontaneous breathing. It was found that, in subjects with a predominant parasympathetic tone, the amplitudes of RSA and the rate of blood flow in the finger-pad skin were higher compared to subjects with a predominant sympathetic tone during respiration with the frequency lower than 4 cycle/min. In the forearm skin, where sympathetic innervation is weaker compared to the finger-pad skin, there were no significant differences in respiration-dependent oscillations of the rate of blood flow in two groups of subjects.

Role of additive stochastic modulation of the heart activity in the formation of 0.1-Hz blood flow oscillations in the human cardiovascular system

In the framework of our previous hypothesis about the participation of structural and hydrodynamic properties of the vascular bed in the formation of the 0.1-Hz component of blood flow oscillations in the human cardiovascular system and on the basis of the reduced hydrodynamic model, the role of additive stochastic perturbations of the operation of the single-chamber pump that simulates the heart was investigated. It was shown that aperiodic noise modulation of the rigidity of the walls of the pump or its valves generates low-frequency oscillations of pressure and blood flow velocity of arterial vascular bed with the maximum amplitude at a frequency close to 0.1 Hz.