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Dzhuliia Sh Dzhalilova,1 Anna M Kosyreva,1 Mikhail E Diatroptov,1 Elena A Ponomarenko,1 Ivan S Tsvetkov,1 Natalia A Zolotova,1 Vladimir A Mkhitarov,2 Dmitry N Khochanskiy,1 Olga V Makarova1 1Department of Immunomorphology of Inflammation, Federal State Budgetary Institution “Science Research Institute of Human Morphology”, Moscow, Russia; 2Department of Informatics and Morphometry, Federal State Budgetary Institution “Science Research Institute of Human Morphology”, Moscow, Russia Purpose: The aim of the study was to characterize the severity of the systemic inflammatory response induced by lipopolysaccharide (LPS) in animals with different resistance levels to hypoxia. Materials and methods: Two to three months old male Wistar rats (220–240 g) were divided according to hypoxia tolerance in a hypobaric chamber. After a month, they were injected intraperitoneally with Escherichia coli LPS at a dose of 1.5 mg/kg. After 3, 6 and 24 hours of LPS injection, we studied the levels of IL-1β, C-reactive protein (CRP) and TGF-β in the serum, the expression of Hif-1α and Nf-kb in the liver, morphological disorders in the lung and ex vivo production of IL-10 by splenic cells activated by ConA. Results: In the early periods after the injection of LPS, increase in Nf-kb expression in the liver was observed only in the rats susceptible to hypoxia. After 6 hours of LPS injection, the number of neutrophils in the interalveolar septa of the lungs of rats susceptible to hypoxia was higher than in tolerant rats. This points to the development of more pronounced LPS-induced inflammation in the rats susceptible to hypoxia and is accompanied by increased expression of Hif-1α in the liver after 6 hours of LPS administration, serum IL-1β level after 3 hours and CRP level after 24 hours. The production of the anti-inflammatory cytokine IL-10 by the spleen was significantly decreased after 6 hours of LPS injection only in the animals tolerant to hypoxia. After 24 hours of LPS injection, a significant decrease in serum TGF-β level occurred in the rats tolerant to hypoxia in comparison with the control group, which improved the survival rates of the animals. Conclusion: We have demonstrated the differences in the severity of the LPS-induced inflammatory response in male Wistar rats with different resistance levels to hypoxia. Rats susceptible to hypoxia are characterized by a more pronounced inflammatory response induced by LPS. Keywords: tolerant, susceptible, hypoxia, inflammation, SIRS, lipopolysaccharide, Hif-1α, Nf-kb

A positive correlation was found between the level of global seismic activity and dynamics of cortisol concentration in blood serum of male rabbits (r=0.33, p=0.01) and Campbell's dwarf hamsters (r=0.38, p=0.04). For a small group of healthy volunteers (n=5), we also found a positive correlation between cortisol levels and the number of major earthquakes, excluding aftershocks (r=0.36, p=0.009) and a negative correlation with IL-18 levels (r=-0.28, p=0.04). The body response to earthquakes is not delayed, and the numerous aftershocks do not seem to affect the biological indicators under study. These facts showed that the earthquakes themselves do not affect the cortisol level via the changes of the environmental parameters. In contrast, the underlying biotropic factor is an unknown trigger responsible for an increase in the number of potent earthquakes. Evidently, it is important to take into account the level of global seismicity as a marker of this trigger provoking the rise of glucocorticoid hormones., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

It has been found that the intraday dynamics of body temperature in small mammal and bird species on the adjacent day are similar. Therefore, by focusing on the body temperature dynamics of the previous day, it is possible to predict with a high degree of accuracy the periods of increase and decrease in body temperature for the current day. This phenomenon was observed when animals were kept under natural illumination and under artificial illumination when the phase of the intrinsic circadian rhythm shifted by 1-2 h every day. When analyzing this phenomenon in birds, it has been shown that the best match for body temperature dynamics occurs when comparing adjacent days based on sidereal days (a period of 23 h and 56 min). Over time, after several days, the daily patterns of body temperature fluctuation take on a completely different form and frequency. These facts suggest a connection between ultradian rhythms and the rotation of the Earth around its axis, and consequently, the position of animals on the surface of the planet relative to space objects., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

The objective of this study was to assess the level of antibodies to carbamylated proteins and analyze the clinical and immunological associations in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis., Materials and Methods: . The study involved 150 patients with a reliable diagnosis of rheumatoid arthritis and 25 patients as healthy controls. Depending on ACPA values, two groups of patients were recruited: ACPA-positive (n = 75) and ACPA-negative (n = 75). RA activity was assessed by the DAS28 index. Determination of antibodies to carbamylated proteins was performed by enzyme-linked immunosorbent assay (BlueGene Biotech, China). Quantitative determination of ACPA in serum was performed by enzyme immunoassay using a commercial reagent kit (AxisShield, UK; upper limit of normal 5.0 U/mL; Orgentec, Germany; upper limit of normal 20.0 U/mL)., Results and Discussion: . Median anti-CarP in patients with RA was 126.2 [100.83; 157.41] ng/mL and was statistically significantly higher (p < 0.001) than in healthy controls (88.89 [70.53; 107.75] ng/mL). Among all patients with RA, 50 (33.3%) were anti-Carp-positive (22 (29.3%) in the ACPA(+) group and 28 (37.3%) in the ACPA(-) group), and one (2%) volunteer from healthy controls was anti-CarP(+) (p = 0.002). In ROC analysis performed to assess the diagnostic significance of anti-CarP for RA for all patients with RA, the area under the curve was 0.783 ± 0.047 with 95% CI: 0.691-0.874 (p < 0.001), with a cut-off point of 143 ng/mL, specificity 96%, sensitivity 36.7%. In the ACPA(+) RA group, the erosion count was statistically significantly higher (p = 0.044) in anti-CarP(+) patients than in anti-CarP(-) patients. A weak direct correlation between anti-CarP and DAS28 was found in the ACPA(-) RA group., Conclusions: . We studied the predictive value of anti-CarP as an auxiliary biomarker in ACPA(+) and ACPA(-) subtypes of RA. ACPA(+) anti-CarP(+) patients have a more "erosive" subtype of the disease than ACPA(+) anti-CarP(-) patients. In ACPA(-) patients, anti-CarP helps to identify a more erosive subtype of the disease, and among ACPA(-) patients it helps to reduce the proportion of seronegative patients. Further studies are required to determine the optimal standards for the laboratory diagnosis of anti-CarP and to clarify the diagnostic potential of these ABs as part of the differential diagnosis of arthritis in other rheumatic diseases., (© 2024. Pleiades Publishing, Ltd.)

Aim: To study the association of bone mineral density (BMD) with serum biochemical and immunological markers in postmenopausal women with rheumatoid arthritis (RA)., Materials and Methods: The study included 173 women with RA (age 61.0 [56.0; 66.0] years). A survey, dual-energy X-ray absorptiometry to measure the BMD of the lumbar spine (L I -L IV ), femoral neck (FN) and total hip (TH), routine blood chemistry, measurement of C-reactive protein (CRP), rheumatoid factor, cyclic citrullinated peptide antibodies (CCPA), parathyroid hormone (PTH), vitamin D 3 , myostatin, follistatin, interleukin-6 (IL-6), IL-6 receptors, insulin-like growth factor 1, adiponectin, leptin, fibroblast growth factor 23, and tumor necrosis factor SF12 were performed., Results: PTH (β=-0.22, -0.35 and -0.30 for L I -L IV , FN and TH, respectively), CRP (β=-0.18, 0.23 and -0.22 for L I -L IV , FN and TH, respectively) and leptin (β=0.35, 0.32 and 0.42 for L I -L IV , FN and TH, respectively) were shown a significant association with BMD in all sites of measurement. It was independent of age, body mass index and postmenopause duration. Associations were also found between adiponectin and BMD of L I -L IV and TH (β=-0.36 and -0.28, respectively), CCPA and BMD of FN and TH (β=-0.21, -0.24, respectively) and IL-6 and BMD of FN (β=0.37)., Conclusion: The study of biochemical and immunological markers in women with RA demonstrated that CRP, CCPA, PTH, IL-6, adiponectin, and leptin influenced BMD.

Association was assessed between the data harvested by a long-baseline laser interference deformograph and the dynamics of body temperature (BT) in hamsters deprived of natural daily light-darkness changes. The power spectral data revealed the positive correlation between simultaneous time series of hamster BT and the Earth's crust deformation (ECD). The superposed epoch analysis established an association between abrupt upstrokes of hamster BT and ECD increments. Thus, the direct relationships between BT dynamics (reflecting predominance of sympathetic part of autonomic nervous system) and ECD (according to long-baseline laser interference deformography) were established. The study observed synchronization of the free-running circadian rhythm of hamster BT with the tidal stress in Earth's lithosphere. Further studies are needed to find the physical factor underlying the revealed relationships., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Background:  It has been suggested that the presence of chronic immunoinflammatory rheumatic disease (CIRD) may be a factor that increases the likelihood of developing hypogonadism syndrome, and conversely, the presence of uncompensated testosterone deficiency may predispose to a greater risk of developing or more severe course of ICRD., Aim:  To study the incidence of hypogonadism in men with rheumatoid arthritis (RA) and evaluate its impact on the course of RA and concomitant diseases., Materials and Methods:  A one-time continuous study included 170 men with RA who were undergoing inpatient treatment at the Federal State Budgetary Institution NIIR named after. V.A. Nasonova. Patients were assessed for total testosterone levels and subsequently divided into subgroups with normal (&gt;12 nmol/l) and reduced levels. An intergroup comparison was carried out on the main indicators used in clinical rheumatological practice to assess the stage, activity and other medical and demographic characteristics of RA, as well as the state of purine and carbohydrate metabolism. A correlation analysis was performed between the level of total testosterone and some clinical and laboratory parameters., Results:  The frequency of detected testosterone deficiency in the study group was 24.1%. Significant correlations were noted between the level of total testosterone and body mass index (r=-0.29), the level of blood uric acid (r=-0.19) and C-reactive protein (r=-0.18). Patients with hypogonadism compared to the group with normal testosterone levels were characterized by higher body mass index (29.3±5.6 vs 26.3±4.0 kg/m2; p&lt;0.001), glucose levels (6.95±7 .85 mmol/l vs 5.42±1.13 mmol/l; p=0.034) and uric acid (354.6±110.7 vs 317.5±84.8 µmol/l; p=0.03) blood. In addition, patients with hypogonadism were more likely to suffer from obesity (41.6% vs 15.7%; p=0.001) and diabetes mellitus (21.6% vs 10.2%; p=0.075) without a statistically significant difference, and also had higher ESR (46.5±42.2 vs 31.0±30.9 mm/h; p=0.012). A more frequent occurrence of anemia was noted in hypogonadism (32.4% vs 16.7%; p=0.041)., Conclusion:  Testosterone levels and the presence of hypogonadism were not associated with the stage and activity of RA, however, testosterone deficiency was accompanied by a more frequent development of overweight and obesity, and a deterioration in purine and carbohydrate metabolism.

We studied the influence of epiphysectomy and administration of melatonin to epiphysectomized outbred white rats on the level and daily dynamics of damage to the genetic material of developing male germ cells. Epiphysectomy leads to an increase in the level of damage in the DNA structure and the disappearance of the circadian rhythm of the activity of repair enzyme PARP-1 and the apoptosis-inducing enzyme caspase-3. The administration of melatonin to animals after epiphysectomy reduces the level of DNA damage, restores the circadian rhythm of activity of PARP-1 and caspase-3. These fundings suggest that melatonin can indirectly protect DNA of maturing male gametes., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

The multi-day dynamics of the intensity of 40 K decay fluctuations was compared with motor activity of laboratory mice, circulating cortisol in rabbits, and proliferation of fibroblast-like cultured cells L-929. A positive correlation was established between the intensity of decay fluctuations on the one hand, and total daily motor activity in mice and plasma cortisol level in rabbits, on the other hand. In addition, a negative correlation was observed between 40 K decay fluctuations and proliferative activity of the cultured cells. Interestingly, these close correlations were observed not only against the background 4-day rhythm, but also in the time when any rhythmicity was absent. Thus, the intensity of 40 K decay fluctuations is an indicator of a biotropic environmental factor that augments motor activity and raises the circulating cortisol in animals and down-regulates proliferation of cultured cells., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

In a long-term (8 months) study, we examined the degree of synchronization of ultradian body temperature oscillations of two isolated groups of mice kept under constant dim illumination. In most cases, the periods of increased activity accompanied by rapid elevation of body temperature coincided in these groups of mice, but in some days, no significant synchronization between the examined parameters was observed. Analysis of the effects of environmental factors on the degree of synchronization of ultradian rhythms in mice revealed association of this parameter with the dynamics of atmospheric pressure (AtmP) and to a lesser extent with the vertical component of interplanetary magnetic field Bz. The loss in synchronicity of ultradian rhythms of mouse activity occurred after a rapid drop of AtmP or during pronounced negative Bz. Therefore, these factors can be viewed as desynchronizers of the biological ultradian rhythms., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

The study monitored the long-term body temperature (BT) oscillations of C57BL/6 mice and outbred starlings (Sturnus vulgaris) to compare them with fluctuation in decay rate of radioactive natural 40 K isotope. The spectrum analysis revealed simultaneous changes of the predominant periods in BT spectra of the animals and those in fluctuation in 40 K decay rate. A positive correlation was established between BT dynamics and fluctuation in decay rate. The superposed epoch analysis revealed predominant coincidence of the moments of BT and fluctuation in 40 K decay rate. The novel data indicate association between BT ultradian rhythms with quasirhythmic variations of fluctuation in 40 K decay rate., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Body temperature rhythms of C57Bl/6 laboratory mice and common greenfinches (Chloris chloris) and feeding periods of common starlings (Sturnus vulgaris) were compared with the intensity of fluctuations in 40 К radioactive decay. Body temperature changes in greenfinches and mice were found to positively correlate with the intensity of fluctuations in 40 K radioactive decay. Superposed epoch analysis showed that an increase in mouse body temperature, which reflects the start of the active phase in the sleep-wake cycle, and food intake in starlings coincide with an increase in the intensity of 40 K radioactive decay. Thus, animal activity in the ultradian range of periods may be related to external quasi-rhythmic physical influences, rather than being determined only by endogenous processes. Given the extremely low dose of natural 40 К exposure, a factor responsible for radioactivity fluctuations may act as a biotropic factor., (© 2023. Pleiades Publishing, Ltd.)

A study of the 4-day rhythm of the proliferative activity of the embryonic fibroblast-like cells in the logarithmic growth phase was carried out. It was shown that in cell cultures obtained on different days from embryos of different ages, the phase of the 4-day rhythm coincides. In vitro the maxima of the proliferative activity were consistent with the minima of the motor activity of mice. Freezing the culture for 2 or 6 days does not cause a shift in the phase of the 4-day rhythm of cell proliferative activity compare with the unfreezing culture. That indicates the existence of an external synchronizer, which determines the 4-day infradian rhythm of the proliferative activity of embryonic cells. Then we daily thawed samples of single L929 culture of mice fibroblast-like cells for 22 and 17 days and researched the dynamics of its proliferative activity. We also showed 4-day rhythm of the simultaneous increase in the number of cells for all thawed samples. Taking into account that deep freezing of a culture leads to the cessation of all life processes, the fact we obtained indicates an exogenous mechanism of the formation of about a 4-day rhythm of the proliferative activity of cell culture. Variations of the Earth's magnetic field could be one of the external synchronizers of the infradian rhythm. We studied the increase in number of L929 cell in conditions of a magnetic permalloy screen and showed that the magnetic shielding no affect the parameters of the infradian rhythm of L929 cell proliferative activity. So further searches of the external synchronizers are need., (© 2022. The Author(s).)

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., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The study examined the rhythmic oscillations of body temperature with the period ranging 100-400 min in three groups of laboratory mice maintained under persistent artificial illumination in Moscow and Ulyanovsk. The difference in the moments of sunrise or sunset in these towns is about 1 h. The greatest rhythmic oscillations of body temperature in examined mice had the periods of 100-400 min. The phase analysis of 100-200-min rhythms revealed their synchronicity with local but not universal time despite the mice had no photic signs indicating alternation of day and night. Of them, the most pronounced were the rhythms with the periods of 121, 143, 151, and 186 min. The present data suggest existence of an external environmental synchronizer of body temperature ultradian rhythms related to local solar time., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The rhythmic variations of body temperature in two groups of mice located in Moscow and Novosibirsk were compared with geomagnetic undulations within Pc5/Pi3 (1-5 mHz) range measured in Borok and Novosibirsk middle-latitude geophysical observatories located at the same longitudes as the examined mice. The spectral maxima of geomagnetic undulations and body temperature variations were observed with greatest probability at the frequencies of 1.6, 2.3, and 3.1 mHz. At this, the mean square of the distance between the frequencies of spectral maxima of simultaneous oscillations was smaller than that of random intervals favoring the hypothesis on geomagnetic undulations as the synchronizer of biorhythms. In both groups of mice, the share of intervals with a high spectral coherency between geomagnetic undulations and body temperature variations had common maximum in the pre-midnight sector of local time and it was higher for the large-scale geomagnetic undulations. Dependence of geomagnetic undulations on spatial scale suggests that body temperature is affected by electrotelluric field., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The study examined the changes in intraperitoneal body temperature of laboratory mice, Jungar hamsters, European greenfinch Chloris chloris, and starlings. In a few minutes range, these changes significantly correlated not only between the animals of the same species, but also between the different classes such as birds and mammals, which were isolated from each other and maintained under different illumination regimen. This phenomenon indicates some external influence(s) on the central mechanisms of the thermal control system not related to illumination regiment. In 80% cases, the phases of most pronounced rhythms of body temperature oscillating with the periods of 8-9 and 12-13 min coincided with those of geomagnetic field within the accuracy of ±1 min. However, the amplitude of body temperature oscillations did not depend on the amplitude of geomagnetic field (GMF) oscillations. Synchronicity of the changes in body temperature and GMF was observed at the amplitude of GMF oscillation of 0.4 nT, which is extremely low value. In contrast, there was no reaction of body temperature to greater (6-10 nT) but irregular and abrupt perturbations of GMF., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Previously, in male Greenfinch, we have described ultradian rhythms of body temperature with periods of 3-6, 8-10, 12-20, and 40-60 min. There are individual variations in this rhythmicity. Rhythms with a period of 3-7 min are more characteristic of some males but not for the others. These males had small values of the ratio of the harmonic spectral density in the range of 12-20 min to the harmonic spectral density in the range of 3-7 min. In this study, we hypothesized that ultradian rhythmicity of body temperature fluctuations is related to the nervous system activity in general and to temperament in particular. We have conducted two sets of experiments for estimating the aggression level (n = 12 males) and reaction to novelty (n = 17). Individuals with predominant rhythms with a period of 3-7 min are less aggressive and more slowly adapt to new conditions. Thus, the ultradian body temperature rhythmicity in Greenfinch is related to their behavioral features and temperament., (© 2021. Pleiades Publishing, Ltd.)

The study examined the infradian rhythms in total motor activity and the periods of "freerunning" circadian rhythm in male C57BL/6 mice and European greenfinch Chloris chloris exposed to constant light. In birds and mice, the motor activity was characterized with inphase 4-day-long rhythm. The periods of free-running circadian rhythms in birds and mice were 23 and 25 h, respectively, and they were modulated with 4-day-long periodicity. The maximal deviations in the period of free-running circadian rhythm from the individual mean levels coincided with the acrophase of 4-day-long rhythm of motor activity in both species.

We have studied the dynamics of the singing of garden bunting (Emberiza hortulana) and the dispersal of a flock of starlings (Sturnus vulgaris) for the night rest. The results were compared with the body temperature fluctuations measured in parallel in a group of laboratory mice. The validity of such comparisons was determined by the presence of a stable correlation between the indicators of minutely changes in body temperature in mice and greenfinches (Chloris chloris). The increase in the frequency of chanting of garden buntings was observed simultaneously with the increase in body temperature in mice. Moreover, the exact moments of the flights into the birdhouse for the night in starlings coincided with the maximums in the dynamics of minutely changes in body temperature of mice. These facts suggest an external synchronizer of "spontaneous" fluctuations of the activity and associated changes in body temperature, which are probably determined by the tone of the sympathetic nervous system.

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.

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.

The time course of intraperitoneal body temperature has been analyzed in two species of mammals (laboratory C57Bl/6 mice and white-breasted hedgehogs (Erinaceus roumanicus) and in two species of passerine birds (common greenfinch Chloris chloris and Japanese quail Coturnix japonica) with different body weights. Similar sets of basic harmonics appearing synchronously in different individuals have been found in the body temperature spectra of the species studied. The level of basal metabolism in those animal species considerably vary; therefore, the period of fluctuations of body temperature in the range of 10-120 min is not determined by the internal characteristics of the body and, presumably, reflects the influence of an external biotropic environmental factor.

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 dynamics of body temperature was used to determine the food intake synchronization in starlings located at a distance of 105 km from each other. Thermal accumulators were implanted intraperitoneally to the birds; the birds had free access to food or were kept under the conditions of food deprivation. It was found that food intake moments significantly more often coincided with an accuracy of up to a minute even in the birds separated by a considerable distance. The difference in time of sunrise of a few minutes, as well as the conditions of constant lighting did not affect the synchronism of food intake. On the basis of the data obtained, it can be assumed that there is a certain external factor, probably of an electromagnetic nature, which synchronizes the functional activity of the body, including food intake.

The aim of the study was to identify ultradian (intraday) and infradian (multi-day) rhythms in the dynamics of testosterone concentration in the blood serum of white-breasted hedgehogs. Blood sampling was performed from the femoral veins of 12 male hedgehogs. We found ultradian rhythms of testosterone on both sampling dates-March 7-8 (a day length of 11 hours and 15 minutes) and May 10-11 (a day length of 16 hours). An 8-hour rhythm of testosterone concentration has been established. The acrophases were at the same times in both photoperiods and thus independent of sunset times. The study of the infradian rhythms of testosterone was daily carried out on May 22-June 3, at 07:40 to 08:50 and from June 27 to July 7, at 16:15-16:50. It revealed an infradian rhythm of the testosterone concentration with a period of 4-days in both the morning and the evening sampling. According to our previous investigation, the infradian rhythms of testosterone among individual hedgehogs, rodents and primates have the same period. That indicates the common mechanisms for their formation. In case of experimental studies, the phase of ultradian and infradian biorhythms will need to be taken into account because the testosterone concentration in acrophase is 2-4 times higher than in bathyphase.

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.

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.

On the model of the systemic inflammatory response (SIRS), induced by lipopolysaccharide (LPS), the morphological and functional changes in the thymus and spleen and the subpopulation composition of peripheral blood lymphocytes of rats differing in resistance to hypoxia were studied. It was demonstrated that the level of endotoxin in blood serum after 3 hours of LPS administration in susceptible-to-hypoxia rats was 64 times higher than in the control group, while in tolerant-to-hypoxia animals it was only 8 times higher in 6 hours. After 24 hours of LPS injection, only in susceptible-to-hypoxia rats did the level of C-reactive protein in blood serum increase. There is a difference in the dynamics of morphological changes of lymphoid organs after LPS injection in tolerant- and susceptible-to-hypoxia animals. After 3 hours of LPS administration, the tolerant-to-hypoxia rats showed no changes in the thymus, spleen, and subpopulation composition of lymphocytes in peripheral blood. After 6 hours there was only a decrease in B-lymphocytes and increase in cytotoxic T-lymphocytes and NK cells. After 1 day of LPS injection, the tolerant-to-hypoxia rats had devastation in PALS of the spleen. After 3 hours of LPS injection the susceptible-to-hypoxia animals had reactive changes in the lymphoid organs: decrease of the thymus cortex, narrowing of the marginal zones of spleen lymphoid follicles, widening of their germinal centers, and a decrease in the absolute number of cytotoxic T-lymphocytes, NK cells, and B-lymphocytes. After 24 hours of LPS injection the tolerant-to-hypoxia animals had a greater absolute number of T-lymphocytes and NK cells in comparison with the susceptible rats. Thus, in animals with different resistance to hypoxia the LPS-induced SIRS is characterized by different dynamics of morphological and functional changes of the thymus and spleen. The obtained data will serve as a basis for the development of new individual approaches to the prevention and treatment of infectious and inflammatory diseases.

Hypoxia tolerance and the intensity of systemic inflammatory response during endotoxemia were examined in newborn, prepubertal, and mature Wistar rats. To assess the sensitivity to hypoxia, the rats were placed into a pressure chamber simulating an altitude of 11,500 m. The systemic inflammatory response was provoked by intraperitoneal injection of LPS from E. coli O26:B6. Serum concentrations of HIF-1α, neopterin, C-reactive protein, and endotoxin were measured. In histological sections of the liver, the area of necrosis was assessed. The smallest tolerance of the prepubertal males to hypoxia correlated with the greatest manifestations of hepatic inflammation and elevated endotoxin, neopterin, and C-reactive protein. Elevation of serum HIF-1α in 3 h after LPC injection was observed in only prepubertal rats. The data obtained should be taken into account during the development of therapeutic strategy for prepubertal children with infectious and inflammatory diseases.

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.

We studied the expression of Hif-1α, Nf-κb, and Vegf genes in the liver and serum levels of HIF-1α, erythropoietin, VEGF, TGF-β, 8-isoprostane, and corticosterone in Wistar rats with different resistance to hypoxia in 5 and 90 min after acute exposure to hypobaric hypoxia. In 5 min after hypoxic exposure, Hif-1α expression in the liver and serum levels of erythropoietin, VEGF, and TGF-β in high-resistant rats were higher than in low-resistant animals. In highresistant rats, the increment in expression of Nf-κb gene responsible for the control over the inflammatory processes was more pronounced than in low-resistant animals. In 90 min after hypoxic exposure, the serum levels of HIF-1α, erythropoietin, VEGF, and TGF-β returned to normal in high-resistant rats, while in low-resistant animals, an increase in 8-isoprostane and TGF-β concentrations was observed. The rats with different resistance to hypoxia were characterized by different changes in biomolecular parameters determining predilection to inflammatory diseases.

The relationship between the phase of 4-day serum corticosteroid biorhythm and resistance to acute hypobaric hypoxia was studied in male rats. Single evaluations of hypoxic resistance of Wistar rats during the same time of the day have shown that the lifespan of animals is significantly longer during the 4-day biorhythm acrophase than during the bathyphase. Daily testing for 12 days has detected a 4-day rhythm of hypoxic resistance, synphasic with corticosterone biorhythm, irrespective of the wave-like course of the adaptation process phase from the beginning of daily testing and hypoxic resistance. Experiments on Sprague-Dawley rats have shown that animals highly resistant and medium resistant to hypoxia during the infradian biorhythm acrophase become medium resistant and poorly resistant during the bathyphase. In order to detect the animals with the least hypoxic resistance in the population, the studies should be carried out during the 4-day infradian biorhythm acrophase, while detection of the most resistant animals should be carried out during the bathyphase.

We studied the effect of pinealectomy on the parameters of 4-day infradian biorhythms in mature male Wistar rats. It was shown that pinealectomy did not change the period and phase of infradian biorhythm of total locomotor activity, serum concentrations corticosterone and testosterone, and mitotic index of esophageal epithelium. No significant changes in the number of nucleated cells in the spleen of pinealectomized animals in comparison with intact animals were found. The amplitude of biorhythms of locomotor activity and corticosterone and testosterone concentrations did not significantly change in pinealectomized animals. Despite the important role of the epiphysis in the regulation of circadian biorhythms in mammals, this organ is not the main synchronizer of infradian biorhythms of glucocorticoid and sex hormones in male Wistar rats.

Infradian rhythms of esophageal epithelium mitotic activity were studied in male Wistar rats of two age groups: 35-45 days (prepubertal) and 3-4 months (adults). Studies of the time course of esophageal epithelium mitotic indexes in adult males showed 4- and 12-day biorhythms, while prepubertal rats exhibited only 4-day infradian biorhythms of this parameter. Studies of the mitotic activity over long periods (3 years) showed 4.058- and 12.175-day periodicity of infradian biorhythms for this parameter, presumably due to external exposures synchronizing the biorhythms. Studies of the mean daily values of the Bz component of interplanetary magnetic field during the period of our research (2012-2013) showed rhythmicities analogous to changes in the mitotic activity of the epithelium. The minimum mitotic indexes were detected on the days of the most pronounced negative values of the interplanetary magnetic field Bz component.

In the course of 15 days, the thyroxine and corticosterone level was measured daily in blood serum of molting starlings, Sturnus vulgaris, by use of enzyme immunodetection method. Revealed are three-day rhythm in changes of thyroxine level and four-day one in changes of corticosterone level, both rhythms being synchronized in different birds. A beginning of growth of new oar feathers coincides with maximum thyroxine concentration in blood serum and also demonstrates a three-day period. In free-living passerine birds (Passer montamus, Parus major, Chloris chloris) a three-day rhythm is found in the dynamics of feather replacement. This rhythm is manifested synchronously in the studied species that differ in timing of post-nuptial molting. Established is the synchronous manifestation of three-day rhythm in changes of thyroxine level and feather replacement during molting in different passerine species and different birds of the same species.

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.

We carried out a prolonged investigation of thymic cells, melatonin and corticosterone biorhythms in male Wistar rats. The total number ofthymic cells, lymphocyte numbers in the peripheral blood and percentrage of CD3+ lymphocyte had a 6-days period of fluctuation. The other period of fluctuation in 4 days was found in the dynamics width of subcapsular layer of the thymus and inclusion of the thymidine label. Biorhythms of the melatonin and corticosterone levels were in on antiphase and had a 4-days period.

Four psychotypes differing by cognitive activity and psychoemotional reactions were distinguished in a population of orchiectomied Wistar rats and in a population of intact animals on the model of a complex cognitive test combined with the free choice method. With similar parameters of cognitive activity, the psychotypes of castrated rats were inferior to those of intact animals by the number of psychoemotional reactions and levels of locomotor activity. Infradian rhythms of spontaneous locomotor activity with a 4-day period were detected in intact and castrated rats. These rhythms did not change under the effect of mental stress, associated with food-getting behavior training, and did not depend on testosterone level.

An everyday investigation of the dynamics of the blood serum corticosterone and thyroxin levels, as well as the esophageal epithelium proliferation activity of male Japanese quails has been conducted over the period of 16 days. A 4-day rhythm of the corticosterone serum level occurring synchronically in the bodies of different individuals was discovered. A 3-day biorhythm of the thyroxin level was shown. The mitotic index figures in the esophageal epithelium negatively correlated with the corticosterone level. The revealed infradian rhythms of the thyroxin corticosterone and thyroxin levels as well as those of the esophageal epithelium mitotic index should not be overlooked white planning and carrying out the experiments concerning the determination of the level of these hormones and the mitotic activity of epithelial tissues.

Chronic endotoxicosis was modeled by subcutaneous injection of the sepharose in complex with LPS. In these conditions we have studied morphofunctional changes of the immune system of BALB/c and C57Bl/6 mice, which are characterized by the different types of the immune response (Th2 type is predominant in BALB/c, Th1--in C57Bl/6). In the 1st-7th day t in the serum of BALB/c mice the endotoxin level increased in 21.3 times, in C57Bl/6--in 20.6 times. The endotoxin antibodies significantly decreased in 1th-7th days, on the 14th day it increased in the serum of both mice's strains. Morphofunctional changes of the immune system after chronic endotoxicosis were different in BALB/c and C57BI/6 mice. On the 1th day after injection of LPS and sepharose, in the thymus of C57Bl/6 mice the cortex layer was exhausted because of cell death, in the thymus of BALB/c mice II-III stages of accidental involution were developed. On the 7-14th day after injection of LPS and sepharose in the spleen of C57Bl/6 mice T- and B-zones were hyperplastic, however in spleen of BALB/c mice only T-zone were enlarged. After LPS and sepharose injection changes of cytokine production synthesized by KonA activated splenic cells were found out. In both strains the level of proinflammatory cytokines--TNFalpha and IL-1beta decreased, as well the Th1-cytokine IL-2. The production o fTh2-cytokine - IL-4, significantly decreased only in C57BI/6 mice. We suggest that damaging effect of LPS injection is determined by predominant Th2 or Th2 types of the immune response.

Several-day rhythmic changes in the lymphocyte subpopulation composition and peripheral blood levels of IL-2 and hydrocortisone were studied in healthy men. The samples were collected daily at 8.00. A 4-day rhythm of hydrocortisone secretion manifested synchronously in different individuals. Rhythmic changes in IL-2 level, T-helper/T-suppressor cytotoxic lymphocyte index, and percentage of NK cells in the peripheral blood related to the hormone levels were detected. Rhythmic changes in these parameters should be taken into consideration when evaluating the hormonal profiles and immunological status of healthy subjects and development of methods for correction of abnormalities.

This work presents the results of the amplitude-phase structure of the physiological rhythms (locomotor activity) and steroid hormones production (common testosterone and cortisole) in gelded and intact Wistar male rats as well as rats exposed to an information load. The markers have been shown to depend on the social state of the animal. It was proved that there was a phase coincidence of the periods of the biological rhythms of common testosterone (intact rats), cortisole and locomotor activity for animals with different individualand typological features. It was shown that the oscillation period of infradian rhythms of the measured markers of physiologic and metabolic processes in the animals of all groups amounted to 4 days. It was found that infradian rhythms were not sensitive to factors of various genesis.

The dynamics of serum testosterone was studied in laboratory male rats kept separately from females. Infradian rhythm of changes in testosterone level equal to 4 days and ultradian (within 24 h) periods equal to 160 and 480 min were detected. The maximum serum level of testosterone in male rats was synchronized with the greatest number of estrous females.

Inbred animals serve as an adequate model to study the role of genetic factors in adaptive, disadaptive, and pathological processes. Morphofunctional study of the immune system was performed on intact BALB/c and C57Bl/6 mice. The structural and functional parameters of the immune system in BALB/c and C57Bl/6 mice differ under physiological conditions. In BALB/c mice, volume density of T zone in the spleen and production of IL-2, IL-3, IL-4, IL-10, and TNF-α were much higher than in C57Bl/6 mice. However, IL-12 production in BALB/c mice was lower than in C57Bl/6 mice. C57Bl/6 mice were characterized by higher cytostatic activity of splenic NK cells. The observed interstrain differences are genetically determined and contribute to the type of adaptive processes and different sensitivity of these mice to pathogenic agents.