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The study examined association between oscillations of body temperature of laboratory Wistar rats maintained under constant illumination with the amplitude of fluctuations of secondary cosmic rays reported by neutron count rate provided by neutron monitors and geomagnetic undulations. In contrast to geomagnetic undulations, neutron count rate variations and body temperature oscillations in rats assessed by spectrum analysis of the corresponding step functions at 1-min intervals demonstrated almost permanent variations with the periods ranging from 100 to 400 min. Under conditions of constant illumination inducing changes in the period of circadian rhythm and predominance of the ultradian rhythms, an association between neutron count rate fluctuations and body temperature oscillations was observed perpetually during the day- and nighttime.

The study examined the effect of passive magnetic shielding on the magnitude of rhythmic oscillations of body temperature (BT) with 4-20 min periods in mice and their correlation with similar oscillations in unshielded control group. A magnetic permalloy screen that 35-fold attenuates the total geomagnetic field and decreased the undulations of magnetic field with the periods of few minutes by 5 times, produced no effect on the mean amplitude of BT oscillations within the same period range, their spectral power, and the cross-spectral density of examined rhythms in comparison with the control (unshielded) mice. Thus, either the mice possess a very sensitive magnetic sensory system or there exists an external non-magnetic factor affecting rhythmicity of BT. The study advanced intensity of thermal neutron radiation near the Earth’s surface known to reflect the flow of accelerated particles generated by the secondary cosmic rays as the external factor, which strongly correlates with BT rhythms revealed by cross-spectrum analysis.

There are individual differences in the tolerance to hypoxia and stress. Stress can contribute to the development of various diseases, including inflammatory bowel disease. It was found that inflammatory bowel diseases in animals susceptible to hypoxia runs more severe course than in tolerant animals. We studied morphofunctional changes in the colon under conditions of modeled cold stress in male C57BL/6 mice susceptible and tolerant to hypoxia. The animals were daily subjected to cold stress (20 min at -20°C) for 2 weeks. Cold stress was followed by an increase in the volume fraction of goblet cells in the colon and production of mucins by these cells in mice tolerant to hypoxia and an increase in cell content in the lamina propria of the colon mucous membrane in animals susceptible to hypoxia. The number of serotoninproducing endocrine cells increased in both groups, but these changes were more pronounced in mice susceptible to hypoxia.

We studied the dynamic of proliferative activity of cultured mouse transformed fibroblast-like L-929 cells in the logarithmic growth phase. During a long period (December 5-23, 2020), we revealed a 4-day rhythm of daily increase in the number of L-929 cells with an amplitude not lower than in a culture of embryonic fibroblast-like cells. Hence, the formation of the 4-day rhythm is not associated with the molecular mechanisms of inhibition of proliferation, which are absent in transformed cells. Daily thawing of samples of one culture over 17 days showed the presence of a 4-day rhythm synchronous between all thawed samples and the control cell culture. As deep freezing leads to the cessation of all life processes in cells, the formation of a 4-day rhythm of proliferative activity of cell culture is determined by an exogenous mechanism.

We have studied body temperature dynamics of mature male Wistar rats maintained under constant illumination after surgical removal of the testicles and adrenal glands. In gonadectomized animals, pronounced increases in body temperature (>0.9°C) were observed every 4-6 h; during the periods 03.35-04.30, 07.35-08.30, 11.35-12.30, 15.35-16.30, 19.35-20.30, and 23.35-00.30, they were recorded 1.5-fold more often than during the rest periods. These results do not significantly differ from the parameters of the control group. Combined removal of the testicles and adrenal glands led to shortening of main period of temperature oscillations to 4-4.5 h and a decrease in its amplitude; pronounced increase in body temperature (>0.5°C) was observed 2.1 times more often during the periods 03.35-04.30, 07.35-08.30, 11.35-12.30, 15.35-16.30, 19.35-20.30, and 23.35-00.30 than in other time intervals. Thus, the removal of the testicles and adrenal glands does not violate the 4-h intraday rhythm of body temperature.

The study analyzed the dynamics of intraperitoneal body temperature in C57BL/6 mice during 39 days of uninterrupted measurements. When mice were exposed to constant illumination, the ultradian oscillations of body temperature demonstrated the rhythms with periods of 2 h, 60 min, and 12 min, which were the higher harmonics of the circadian temperature oscillations. In two mutually isolated groups exposed to constant illumination, the phases of revealed biorhythms coincided. When the mice maintained under natural illumination, the body temperature demonstrated the ultradian rhythms with the same periods, which indicated that constant illumination did not distort the parameters of ultradian biorhythms. Probably, there is an external biotropic factor with similar harmonic spectrum, which synchronizes these biorhythms.

The study collated oscillations of body temperature of С57BL/6 mice and Roborovski hamsters (Phodopus roborovskii) in the period range of 100-240 min and fluctuations of the secondary cosmic rays reflected by neutron count rate of a neutron monitor at the Earth's surface. Cross-correlation of body temperature and neutron count rate data revealed their strong association only for simultaneous measurements. Collation of the phase of neutron count rate fluctuations with maxima of body temperature oscillations revealed the coincidence of the phases of both processes. There was a temporary connection between the periods of body temperature elevation and neutron count rate rise. Thus, not only the spectral parameters of biological and physical processes, but also their phases coincided, which corroborates the hypothesis on stimulating effect of increasing neutron count rate on activity of the animals.

The study compared the daily mean intensity of one-minute-step fluctuations in intensity of the secondary cosmic rays reflected by neutron count rate and dynamics of body temperature, motor activity, as well as concentration of glucocorticoid hormones in birds and rodents. A positive correlation was established between body temperature oscillations and neutron count rate fluctuations. A similar correlation was observed between physical parameter (neutron count rate), on the one hand, and daily mean motor activity and concentration of glucocorticoid hormones in the animals. The periods and phases of these processes presented in synchronous time series coincided. The facts of simultaneous variations or disturbances of the periods in dynamics of biological and physical parameters attest to their relationships. The study concluded that the infradian rhythms with the periods of 3-5 days depend on some external environmental factor related to fluctuations in intensity of secondary cosmic rays.

The dynamics of proliferative activity of the L-929 cell culture of mouse fibroblast-like cells in the phase of logarithmic growth was compared with some heliogeophysical parameters (Ap and ULF indexes of geomagnetic activity, vertical component of the interplanetary magnetic field, and intensity of fluctuations of secondary cosmic radiation estimated by the neutron monitoring near the Earth's surface). Among the considered heliogeophysical parameters, only the magnitude of fluctuations of minute-to-minute changes in the neutron monitor indicator reliably and negatively correlates with the rate of cell culture reproduction. Considering that the amplitude of secondary cosmic fluctuations is about 5%, which is 0.1% of the total ray flux, and proliferative activity varies in the range of 30-50%, the probability of a direct biotrophic effect of this physical factor is extremely low. It seems likely that proliferative activity of L-929 cell culture is directly affected by another environmental factor, the marker of which is the intensity of neutron counting rate fluctuations.

We studied the dynamics of the body temperature in mature male Wistar rats maintained under condition of constant illumination. It was shown that body temperature under these conditions varied with a 3-5-h period. The daily dynamics of body temperature summed up over 20-23-day intervals showed a 4-h ultradian rhythm with maxima at 3.35-4.30, 7.35-8.30, 11.35-12.30, 15.35-16.30, 19.35-20.30, and 23.35-00.30 h. During these hours, pronounced (>0.9°C) increase in body temperature was observed by 1.6 times more often than in other eriods. Thus, there are periods during the day when the increase in body temperature in rats in the absence of light cues occurs more often than in other periods of the day. Hence, about 4-h ultradian rhythm of body temperature has an external synchronizer that differs from lighting conditions.

There are individual differences in the tolerance to hypoxia and stress. Stress can contribute to the development of various diseases, including inflammatory bowel disease. It was found that inflammatory bowel diseases in animals susceptible to hypoxia runs more severe course than in tolerant animals. We studied morphofunctional changes in the colon under conditions of modeled cold stress in male C57BL/6 mice susceptible and tolerant to hypoxia. The animals were daily subjected to cold stress (20 min at -20°C) for 2 weeks. Cold stress was followed by an increase in the volume fraction of goblet cells in the colon and production of mucins by these cells in mice tolerant to hypoxia and an increase in cell content in the lamina propria of the colon mucous membrane in animals susceptible to hypoxia. The number of serotoninproducing endocrine cells increased in both groups, but these changes were more pronounced in mice susceptible to hypoxia.

It is a common fact, that the content of sex hormones in humans and animals varies in different age periods. The functional state of the immune system also changes with age. However, sex differences studies of inflammatory and immune responses during puberty prevail in literature. Investigation of immune responses to LPS peculiarities in prepubertal females and males may contribute to the development of more effective immunotherapy and minimize side effects of children vaccination. Therefore, the aim of this work was to investigate the LPS-induced SIRS sex differences in prepubertal Wistar rats. Despite the absence of sex differences in estradiol and testosterone levels, LPS-induced inflammatory changes in liver and lungs are more pronounced among males. Males demonstrate the increasing neopterin, corticosterone levels and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. Not less important is that in females, demonstrating less morphological changes in liver and lungs, endotoxin level is tenfold higher, and corticosterone level decreases. Thus, endotoxin cannot be used as a marker of the severity of multiple organ failure in prepubertal period. The LPS-induced immune reactions in females and males are similar and are characterized by immunosuppression. Both females and males have decreased production of cytokines (IL-2, IL-4, TNF-α, TGF-β) and the absolute number of CD3 + and CD3 + CD8 + lymphocytes in blood. The acute atrophy of thymus and apoptosis of thymic cells are revealed in animals of both sexes. However, the number of CD3 + CD4 + T-helpers and CD4 + CD25 + Foxp3 + T-cells decreases only in females with SIRS, and in males there was a decrease of CD45R + B-cells. The least expressed sex differences in immune responses in the prepubertal period can be determined by the low levels of sex steroids and the absence of their immunomodulatory effect. Further studies require the identification of mechanisms, determining the sex differences in the inflammatory and immune responses in prepubertal animals.

We studied daily dynamics of proliferative activity of embryonic fibroblast-like cells in culture during the logarithmic growth phase. Daily increase in cell count in the culture showed a 4-day rhythm that persisted over 3 weeks of culturing. In cultures from different animals, the phase of this rhythm was synchronous and did not depend on the moment of cell isolation. It can be hypothesized that the 4-day biorhythm of proliferative activity of embryonic fibroblast-like cells in culture is determined by external environmental factors, probably of electromagnetic nature.

Studies of the dynamics of thyroid hormone concentrations in the blood revealed a 3-day rhythm that significantly manifested in male Wistar rats and Chinchilla rabbits during intensive growth and in common starlings (Sturnus vulgaris) during moult. Synphasic 3-day biorhythms of thyroid hormonal activities were found in these animals, which attested to an external synchronizer of this biorhythm common for mammals and birds. The maximum level of thyroid hormones coincided with the extrema of daily fluctuations of the Earth rotation velocity, as a result of which this external factor or another factor closely related to it seemed to be involved in synchronization of the 3-day infradian biorhythm of thyroid hormones in mammals and birds.

The rhythms of short-term arousal episodes, associated with normalization of low body temperature, were studied in hibernating Erinaceus roumanicus. The episodes of body temperature recovery during hibernation were 1.7 times more incident during the acrophase of 4.058-day rhythm of glucocorticoid hormones, detected previously, than during the batiphase of this rhythm. Ultradian rhythm of arousal episodes conformed to a 4-h biorhythm: the maximum number of body temperature resumption episodes was recorded at 00.00-01.00, 04.00-05.00, 08.00-09.00, 12.00-13.00, 16.00-17.00, and 20.00-21.00. These data indicated that in mammals the mechanisms of infradian and ultradian rhythm maintenance were stable and did not depend on body temperature or were determined by external factors with periods of 4.058 days and 4 h.

Daily dynamics of changes in the latency of a response to dissociative anesthetic tiletamine (time from injection to ataxia) was studied in mature Wistar rats. Both intramuscular and intravenous administration of the anesthetic was associated with 4-day oscillations of the latent period synchronous with the dynamics of changes in the concentration of glucocorticoid hormones. The period and phases of the infradian rhythm of resistance to the anesthetic remained unchanged after removal of both adrenal glands and testes and administration of corticosterone synthesis blocker trilostane diminishing the 4-day cycle of changes in corticosterone level. Therefore, hormones of the adrenal glands and testes do not play the key role in the mechanisms of formation of the 4-day infradian rhythm.

The levels of cortisol, free and total thyroxin in the serum of the 6 th woman of 23-33 aged old in the follicular phase of menstrual cycle was studied by ELISA method. The cortisol level was fluctuated during the 4-day period. The levels of free and total thyroxin were changed in the 3-day period. Both fluctuations were synchronous in all studied woman. Revealed biological rhythms of glucocorticoids and thyroid hormones should be taken into account when hormonal and immunologic status of healthy woman is researched and corrective methods of pathologic states are developed.

Many-day rhythms of proliferative activity of the corneal and esophageal epithelium and serum corticosterone levels were studied in adult male Wistar rats. We detected a 4-day rhythm of proliferative activity of esophageal epithelium negatively correlating with corticosterone level. A more pronounced decrease in the number of mitoses in the esophageal and corneal epithelium was recorded every 12 days. Analysis of the rhythm of mitotic activity in different experimental series carried out over 9 months showed that the acrophase of the detected 4- and 12-day periods is shifted 1 day forward every 69-73 days. The detected infradian constituents of the circadian rhythms of epithelial proliferative activity should be taken into consideration in experimental studies and in development of chronobiological approaches to the treatment of diseases caused by disorders of the proliferative activity of the epithelium.