BACKGROUND: The need to increase the tolerance of various extreme effects is associated not only with the expansion of human professional activity regions but also with the need to assist victims of natural and man-made disasters. The use of pharmacological agents for individual adverse effects is a well-known method; however, considering the combined effects of several physical or chemical factors, only a few references are found in the literature. AIM: This preclinical study aimed to examine the effectiveness of a new derivative of aminoethanol and intermediates of the Krebs cycle in relation to the isolated and combined effects of hypoxia and temperature (hyperthermia and hypothermia). MATERIALS AND METHODS: The fumaric salt of the amber ether of diethylaminoethanol was synthesized at St. Petersburg State University of Chemistry and Pharmacy, Department of Organic Chemistry (Head Professor I.P. Yakovlev). The study was conducted on small laboratory animals. Resistance to hypoxia was assessed by the dynamics of the altitude threshold of animals, tolerance to hyperthermia by survival in a thermal chamber at 40°C, and tolerance to hypothermia by the time of maximum swimming in water at 10–12°C. Under combined exposure, the condition of the animals was assessed by the dynamics of physical performance, hypoxia was induced by preliminary administration of the methemoglobin former sodium nitrite at a dose of 50 mg/kg, and thermal exposure was induced by placing the animal in water at 40°C (hyperthermia) or 9–11°C (hypothermia). RESULTS: After a single intragastric administration in a wide range of doses, the test compound stimulated the physical performance of animals and exhibited a protective effect under the isolated effects of hypobaric hypoxia, hyperthermia, and hypothermia. With combined exposure to hemic hypoxia and hyperthermia, the compound was effective at a dose of 250 mg/kg. With combined exposure to hemic hypoxia and hypothermia, efficiency was also noted at lower doses (25 and 50 mg/kg). CONCLUSION: Fumaric salt of dimethylaminoethanol amber ether, a new derivative of dimethylaminoethanol, butenedioic, and trans-butenedioic acids, is promising for further study as a means of increasing the body’s resistance to extreme influences.

This study revealed the pathogenetic patterns of the development of hypoxic and ischemic disorders in various pathological conditions and substantiated approaches to the use of drugs with antihypoxic activity. The role of the receptor interaction of succinic acid in the composition of succinate-containing antihypoxants with succinate receptor SUCNR1 has been demonstrated. The pharmacodynamic properties of the combined preparation of succinic acid that also contains vitamin precursors of the cofactors of Krebs cycle dehydrogenases nicotinamide (precursor of NAD) and riboflavin mononucleotide (precursor of FAD) and precursor of purine nucleotides (inosine) (cytoflavin) for intravenous drip and oral administration were analyzed. Literature data were also analyzed to evaluate the effectiveness of the use of the metabolic corrector of energy-dependent and hypoxic conditions (cytoflavin) in various central nervous system and cardiovascular diseases. In the case of ischemic disorders of cerebral and coronary blood flow, the effects of the drug are concentrated on the penumbra zone (ischemic penumbra), which is associated with the intravenous administration of the drug to its metabolic activity by influencing endothelial cells, restoring microcirculation, and enhancing the oxygen transport function of the blood. Among the new areas of drug use, the use of cytoflavin in the complex therapy of traumatic brain injuries, traumatic shock, acute respiratory distress syndrome, toxic lesions of the central nervous system, multiple organ failure syndrome, and post-COVID syndrome is promising.

A new derivative of dimethylaminoethanol, butanedioic and trans-butenedioic acids (laboratory code ADK-17) was synthesized at the Department of Organic Chemistry (Professor I.P. Yakovlev is the Head of the Department) of St. Petersburg State Chemical and Pharmaceutical University (SPCPU). This is a promising compound planned for use as an oral dosage form. In this work, we aim to evaluate manifestations of the general and specific toxicity of the new drug. Laboratory animals (white mice, rats, rabbits, guinea pigs) were used as test systems for the preclinical safety study of the new compound. Manifestations of general toxicity (acute and chronic), local irritant action, allergenic properties, immunotoxic action were studied. The reproductive toxicity of the ADK-17 drug when administered intragastrically was studied. The studied drug was found to exhibit low toxicity, cause no changes in the biochemical and morphological parameters of rats and rabbits under the conditions of course use, and have no negative effects on internal organs. When administered intragastrically in maximum doses, the drug causes no irritating effects. The use of the drug did not lead to the development of a local allergic reaction of an immediate type. Carrying out sensitization in the DTH reaction showed the absence of a sensitizing effect. The study of the immunotoxic effect of the ADK-17 drug showed that its prolonged intragastric administration for 30 days at doses of 93 and 930 mg/kg did not lead to a violation of the humoral immune response and a decrease in antibody production. Setting a delayed-type hypersensitivity reaction also confirms that the drug does not affect the development of cellular immunity. The conducted experimental studies of the drug’s reproductive toxicity in rats showed that its repeated intragastric administration at doses of 50 and 250 mg/kg to pregnant females did not have a negative effect on the reproductive system of laboratory animals, embryo- and fetotoxic, as well as teratogenic effects, having no effect on the antenatal and postnatal development of offspring.

The article explores the potential of using peptide bioregulators-cytomedins to enhance the bodys resistance against adverse environmental influences. The study examines scientific literature on the general mechanisms of action of peptide bioregulators, their main clinical effects, and applications. Furthermore, it analyzes the results of research on their activity in individuals with signs of asthenia and reduced immunoreactivity under various adverse conditions, such as hypoxia, hyperthermia, and exposure to aviation and space flight factors, deep-sea diving, and the challenging environment of the Arctic zone. The research indicates that a single intranasal administration of cortexin, epithalamin, thymogen, and prostatilen in low doses contributes to an increase in the tolerance of adverse effects. Additionally, their short-term use shows delayed positive effects, reflecting their impact on the level of nonspecific resistance of the organism. The specific effects of these drugs depend on the type of adverse effect and the organ tropism of each drug.

The essence of the preconditioning effect is the activation of urgent defense mechanisms of adaptation as a result of a short episode of weak, non-damaging hypoxic or ischemic exposure, which contributes to an increase in the tolerance of the subsequent delayed, more severe exposure to hypoxia or ischemia. Aim of the study was to assess the literature data on the possibility of using the method of remote ischemic preconditioning (RIP) as a non-pharmacological method for correcting physical performance. Material and methods. In the Scopus, PubMed and eLibrary databases, a selection and analysis of modern literature sources devoted to the issues of increasing human performance, especially by nonpharmacological methods, as well as the use of distant preconditioning to increase physical performance and the mechanisms for implementing this effect, were carried out. Results. Since the discovery of the phenomenon until now, researchers have considered RIP, mainly as a way to protect organs and cells from ischemic damage in clinical practice. The article presents the literature data on the use of RIP as a non-drug method for improving physical performance with single and course use cases. In addition, the article focuses on the mobilization of the body’s own resources through the mechanisms of adaptation to hypoxia developing during RIP. Conclusions. Among the non-pharmacological methods of increasing physical performance, one of the most promising, in our opinion, is RIP that mobilizes the body’s own resources through the mechanisms of adaptation to hypoxia. The advantage of the method based on short-term cessation of blood circulation in the lower extremities and subsequent reperfusion does not apply to the ways prohibited in sports, does not require the use of drugs and the availability of special equipment, signifcant costs of economic and organizational resources.

BACKGROUND: One of the key transcriptional regulators that determine the bodys resistance to hypoxia is the hypoxia-inducible factor HIF-1, the study of the role of which in the bodys resistance to extreme influences can justify new directions in medical technologies for its increase. The bodys resistance to hypoxia largely determines the resistance to other critically significant influences (hyperthermia, hypothermia, hyperbaria, ionizing radiation, chemicals, etc.). However, it was not possible to find a quantitative assessment of this effect in the literature studied by us, which served as the basis for this study. AIM: To assess the role of the level of expression of the hypoxia-inducible factor HIF-1 in various tissues of laboratory animals in increasing the resistance of animals to the effects of extreme hyperthermia. MATERIALS AND METHODS: The study was carried out on outbred white laboratory rats obtained from the Rappolovo nursery weighing 180220 g. For the study, preliminary laboratory animals were tested for an individual level of resistance to hyperthermia (40 animals), which made it possible to form experimental groups from highly resistant and low resistant to extreme animal influences. The definition of resistance to hyperthermia was carried out by the rate of increase in rectal temperature in animals during 20-minute air hyperthermia (40C). 4 groups of laboratory animals were formed (2 each with high and low resistance), half of which were exposed to a pronounced adverse effect of hyperthermia. Biological material was taken from all animals (whole blood, plasma, tissues of the heart, liver, kidneys, brain), in which the expression of the HIF-1 and TSPO genes (housekeeping gene) was determined by the Real-Time-PCR method. Statistical processing of the obtained data was carried out using the ANOVA analysis of variance. RESULTS: It has been established that the level of resistance of animals to hyperthermia is largely determined by their genetic characteristics. Even under thermocomfort conditions, the expression of the TSPO housekeeping gene in animals with a high level of resistance to hyperthermia differed with a high degree of reliability from low-resistant animals (in the kidneys, liver, and brain, on average, by 4060%; in the heart, by 25%). The expression values of this gene, determined in whole blood or plasma, make it possible to differentiate groups of animals according to the level of resistance to hyperthermia. A similar relationship between animals with high and low resistance is also observed in tissues obtained immediately after thermal exposure. CONCLUSIONS: The main organ that provides a high level of resistance to both hypoxia and hyperthermia associated with the basic (under thermal comfort conditions) expression of HIF-1 is the brain. The expression of the hypoxia-inducible factor in it is more than 300 times higher than the expression of the housekeeping genes. The second most important organ is the liver, in which HIF-1 expression activity is more than 15 times higher than the expression of housekeeping genes. Under conditions of hyperthermia, low-resistant animals show a compensatory-adaptive reaction associated with the activation of hypoxic defense mechanisms in blood cells, kidneys, and liver, in the absence of such a reaction in the tissues of the heart and brain. Animals highly resistant to hyperthermia were characterized by a significant (30 times) increase in the relative activity of HIF-1 expression mechanisms in blood cells, 2.5 times in liver cells, and a decrease in expression by 25% in the kidneys and almost 2 times in brain tissues. A high level of basal expression of the transcription factor HIF-1 under everyday (thermocomfortable) conditions may be a predictor of a high level of resistance to hyperthermia in a given animal. Probably, to increase the bodys resistance to extreme impacts, it is advisable to use medical technologies that increase the level of HIF-1 expression in everyday (thermocomfortable) conditions in key tissues the brain, liver, and myocardium.

BACKGROUND:One of the key transcriptional regulators that determine the bodys resistance to hypoxia is the hypoxia-inducible factorHIF-1, the study of the role of which in the bodys resistance to extreme influences can justify new directions in medical technologies for its increase. AIM:To evaluate the quantitative contribution of the level of expression of the hypoxia-inducible factorHIF-1in various tissues of laboratory animals to the increase in the resistance of animals to the effects of hypoxic hypoxia. MATERIALS AND METHODS:The study was carried out on outbred white laboratory rats obtained from the Rappolovo nursery weighing 180220 g. To conduct the study, animals were previously tested for an individual level of resistance to hypoxia, which made it possible to form experimental groups from highly resistant and low resistant animals. Biological material was taken from all animals (whole blood, plasma, tissues of the heart, liver, kidneys, brain), in which the expression of theHIF-1andTSPOgenes (housekeeping gene) was determined by the Real-Time-PCR method. Total RNA was isolated from the test material by affinity sorption,synthesis of the first strand of cDNA, amplification, followed by determination of the expression level of theHIF-1gene in rats was carried out according to the instructions and the manufacturers protocol by PCR with detection of the accumulation of reaction products in real time (Real-Time PCR) using a CFX-96 detecting amplifier (Bio-Rad, USA) and specific primers and probes for theHIF-1gene in rats (DNK-Sintez, Russia). Statistical processing of the obtained data was carried out using the ANOVA analysis of variance. RESULTS:It has been established that the level of resistance of animals to hypoxia is largely determined by their genetic characteristics. Even under normoxic conditions, the expression of theTSPOhousekeeping gene in animals with a high level of resistance to hypoxia differed with a high degree of reliability from low-resistance animals (in the kidneys, liver, and brain, on average, by 4060%; in the heart, by 25%). The values of the expression of this gene, determined in whole blood or plasma, make it possible to differentiate groups of animals according to the level of resistance to hypoxia. A similar ratio between animals with high and low resistance is also observed in tissues obtained immediately after hypoxic exposure. An analysis of the reaction of the genomic regulation system to extreme exposure showed that it increased the expression of the TSPO gene by 1.62 times equally in all tissues, regardless of the level of animal resistance. For theHIF-1gene, similar patterns were found, but the severity of their manifestations is more and significant. CONCLUSIONS:The main organ that provides a high level of resistance to hypoxia associated with the basic (under normoxic conditions) expression ofHIF-1is the brain. The expression of the hypoxia-inducible factor in it is more than 300 times higher than the expression of the housekeeping genes. The second most important organ is the liver, in whichHIF-1expression activity is more than 15 times higher than the expression of housekeeping genes. Under conditions of moderate hypoxia, a compensatory-adaptive reaction is noted, associated with the activation of hypoxic defense mechanisms in blood and liver cells, and in low-resistant animals, also in the brain tissue. In the myocardium, such a compensatory-adaptive reaction is activated only in the group of highly resistant animals. A high level of basal expression of theHIF-1transcription factor under daily (normoxic) conditions may be a predictor of a high level of resistance to hypoxia in a given animal.

BACKGROUND: Despite the abundance of research in the field of high-altitude physiology and medicine, the problem of resistance to moderate hypoxia has not been practically studied. This is partly due to methodological difficulties: the studies were conducted on healthy people and climbers who tolerated the effects of moderate hypoxia well. Such studies have become necessary in connection with the development of hypoxic therapy. AIM: To search for indicators of the functional state of a person that are highly sensitive to the effects of moderate hypobaric hypoxia. MATERIAL AND METHODS: The examined group consisted of 65 practically healthy men aged 1925 years who were selected for work in high mountains. The main indicators characterizing the state of the central nervous system, cardiovascular and respiratory systems were studied in a state of relative rest and when performing a dosed two-stage bicycle ergometric test, in normoxia conditions (altitude 0) and during a pressure chamber rise in the TABAY climate complex (Japan) to altitudes of 3500 and 4500 m Statistically analyzed were the characteristics of the dynamics of indicators during the transition from normoxia to states of moderate hypoxia, correlations between indicators, their sensitivity to hypoxic effects, the significance of reactivity to hypoxic effects and mobilization of the bodys functional reserves in resistance to hypoxia. RESULTS: It has been shown that the key pathophysiological markers of reduced body resistance to moderate hypoxic exposure are a rapid decrease in the level of peripheral blood saturation, high reactivity of the cardiovascular and respiratory systems to hypoxic exposure, as well as excessive mobilization of the bodys functional reserves in response to additional physical activity. CONCLUSION: The presented materials confirm that the functional state of a healthy person under conditions of moderate hypoxia at rest is determined by the level of saturation of his peripheral blood. Maintaining saturation at a higher level ensures the maintenance of an optimal level of functional state, physical and operator performance, a lower degree of stress on the respiratory and cardiovascular systems.

BACKGROUND: The proportion of the golden section, discovered by Pythagoras, is of great importance in the organization of wildlife. Since the golden proportion is one of the criteria for self-organization in living nature, it is natural to assume that this criterion can also be manifested in the work of the heart. The organization of the cardiac cycle is the result of a long evolution of a living organism in the direction of optimizing the structure and functions, ensuring life with minimal energy consumption. However, in clinical medicine and physiological research, until recently, this approach has hardly been used, and there are only a few reports in the literature on the effectiveness of this method. AIM: To study the sensitivity of indicators of the symmetry analysis of the cardiocycle in accordance with the methodology of the golden section to physical exertion, hypoxic and temperature effects for an integral assessment of the functional state of the heart. For the geometric analysis of the ECG, the ratios of the main parameters were used to assess their compliance with the criteria of the golden section. MATERIALS AND METHODS: Geometric analysis of ECG interval intervals according to the principles of the golden section in healthy individuals exposed to debilitating physical activity, hypoxia, combined hyperthermia or low temperatures. In the course of the work, the results of a study of 252 male volunteers aged 2035 years were analyzed, of which 46 people underwent an exhaustive exercise test, 113 a hypoxic test, 34 a combined hyperthermia tolerance test, and 69 a moderate cooling tolerance test. RESULTS: the use of a geometric analysis of cardiocycles at rest, during exercise, as well as moderate exposure to typical adverse environmental factors (hypoxia, high or low temperatures) showed the fundamental possibility of assessing the dynamics of the functional state in young practically healthy individuals. The indicators characterizing the activity of the processes of regulation of myocardial work at the extracardiac and intracardiac levels were more dynamic. The indicator of symmetry analysis, which characterizes the level of myocardial homeostasis, energy processes and contractility, to a greater extent reflects unfavorable prognostic characteristics in terms of failure of myocardial adaptation. It has been established that for practically healthy individuals (in the normal state of activity, without external influences), the 1st class of the functional state occurs in 83% of cases, hemodynamic stress is noted in 16% of the subjects, hemodynamic inadequacy in 1%. CONCLUSIONS: The deviations from the ideal proportion of the golden section identified as a result of adverse external influences remained within acceptable fluctuations, which indicated a fairly perfect functioning of the heart and the cardiovascular system as a whole in the surveyed contingent of young, practically healthy individuals. Proposed by N.V. Dmitrieva (1989) the classification of functional states, based on the assessment of the degree of deviation of the calculated coefficients from the optimal value corresponding to the golden section, is not optimal for healthy young men, which include athletes without signs of sports heart and other myocardial pathology. It does not take into account the sign of the deviation, as a result, for the state of rest, with the predominance of bradycardia, typical for athletes, there is an overdiagnosis of tense hemodynamics. At the same time, the work of the heart during short-term intense physical exertion, which naturally causes pronounced sympathicotonia, can be unreasonably characterized as a premorbid or pathological condition.

В статье представлен анализ направлений повышения жизнеспособности тканей в условиях критической гипоксии, связанных со снижением потребности клеток в кислороде. Реализация этих направлений гипобиоза сопряжена либо со снижением температуры органов и тканей, либо с индукцией механизмов торможения метаболизма и энергетического обмена, усиливающих эффекты управляемой гипотермии. Представлены основные биологические и патофизиологические закономерности, характеризующие состояния тканевой гипотермии различной степени выраженности. Приведены основные научные и технические решения, направленные на формирование у людей состояния управляемой гипотермии (искусственной гибернации) при критических состояниях, включая способы и устройства охлаждения организма, составы и перспективные направления развития фармакологической группы перфузирующих гипотермических растворов, средств индукции гибернации, устройств и способов криоконсервации органов и тканей для трансплантологии.

Введение. Статья посвящена решению задачи количественной оценки взаимодействия двух неблагоприятных факторов - гипоксического и температурного, при их сочетанном действии на организм лабораторных животных. Исследовали эффекты нормобарической и гемической гипоксии, воздействия высоких и низких температур. цель работы - количественная оценка взаимодействия гипоксии и температурных факторов при их сочетанном действии на организм лабораторных животных. методика. Состояние нормобарической гипоксии моделировали с использованием мембранного гипоксикатора. Установка обеспечивала плавную регулировку концентрации кислорода от 2 до 10% в гипоксической газовой смеси. Гипертермию моделировали путем термостатического поддержания температуры воздуха +40 °С и влажности 30-60%. Гипотермия формировалась в условиях воздушного охлаждения (в холодовой камере при температуре воздуха 5±1 °С и влажности 75-80%). Для оценки функционального состояния проводили тестирование физической работоспособности методом вынужденного плавания с грузом 5% от массы тела в воде различной температуры. Оценка взаимодействия факторов проводилась методом двухфакторного дисперсионного анализа с тремя уровнями выраженности каждого фактора. результаты. Установлено, что гипоксический и тепловой фактор оказывают влияние независимо друг от друга, при превалировании воздействия гипоксии. Взаимодействие между факторами cинергидное умеренное по выраженности, протекает по типу дополняющего эффекта, и может служить основой развития синдрома взаимного отягощения. Воздушная гипотермия слабо влияет на переносимость гипоксического воздействия, влияние иммерсионной гипотермии проявляется более существенно. Заключение. Критическое ухудшение функционального состояния при действии гипоксии и экстремальных температурсопряжено с активацией гипоталамо-гипофизарно-надпочечниковой системы, интенсификацией катаболизма белков, жиров и углеводов, развитием вторичной тканевой гипоксии и формированием митохондриальных дисфункций. Наиболее вероятным механизмом развития синдрома взаимного отягощения при сочетанном воздействии гипоксии и гипертермии является нарушение генерации АТФ в процессе фосфорилирующего митохондриального окисления, который является общим звеном патогенеза различных экстремальных состояний. Introduction. The article focuses on quantitative assessment of the interaction of two unfavorable factors, hypoxia and temperature, during their combined effect on the body of laboratory animals. The effects of normobaric and hemic hypoxia and of high and low temperatures were studied. the aim of the study was to quantify the interaction between hypoxia and temperature factors during their combined effect on the body of laboratory animals.methods. Normobaric hypoxia was produced in a membrane hypoxicator. The oxygen concentration in the hypoxic gas mixture was smoothly adjustable from 2 to 10%. Hyperthermia was modeled by thermostatic maintenance of the air temperature at +40°C and the humidity at 30-60%. Hypothermia was produced in a cold chamber at the air temperature of 5±1°C and the air humidity of 75-80%. Physical performance was tested using forced swimming with a load of 5% of body weight at various water temperatures. The interaction of the factors was assessed by a two-factor analysis of variance for three levels of severity of each factor. results. The hypoxic and thermal factors exerted independent effects, with hypoxia effects prevailing. The factor interaction was synergistic, moderately severe, complementary, and could underlie the mutual aggravation syndrome. Air hypothermia had a slight effect on the tolerance to hypoxic exposure; the effect of immersion hypothermia was more pronounced.conclusion. The critical impairment of the functional state under the action of hypoxia and extreme temperature is associated with the activation of the hypothalamic-pituitary-adrenal system, intensification of protein, lipid and carbohydrate catabolism, development of secondary tissue hypoxia, and the formation of mitochondrial dysfunction. The most likely mechanism for the development of mutual aggravation syndrome under the combined action of hypoxia and hyperthermia is impairment of ATP generation in the process of phosphorylating mitochondrial oxidation, which is a common stage in the pathogenesis of various extreme conditions.

Functional tension of the immune system was considered as depending on the level of physical activity in young people. The subjects were 77 healthy men aged 18–20 years, who were junior students of Yaroslavl universities. The subjects were grouped by physical activity level. The state of the immune system was judged from the lymphocytes phenotype, serum immunoglobulin levels, phagocytic indicators, oxygen-dependent metabolism of neutrophils, and plasma levels of lactoferrin and ferritin. The tension level of specific humoral immunity was inferred from the titers of antibodies to a wide group of bacterial pathogens. The overall tension level of the immune system in subject groups with different levels of physical activity was assessed by the index of conjugation of paired correlation coefficients of immunity indicators. The significance of the controlled factors was assessed by one-way ANOVA in terms of the coefficient of determination; the reliability of the dispersion model was assessed by Fisher’s F -test. The significance of differences between the groups was evaluated by the nonparametric Wilcoxon–Mann–Whitney test. The baseline level of physical activity was not found to act as an activating factor for the immune system. Almost all indicators were within reference ranges optimal for healthy people. At the systemic level, the variability of indicators of various immune processes was determined by stochastic processes without compensatory mechanisms being triggered at the cell and humoral levels. The involvement in regular exercise at a moderate level was a factor that caused not only activation of some mechanisms of the immune response, but also tension in coordinated activity of various mechanisms of immunity as a functional system. Phagocytosis-related mechanisms of immunity and ferritin-dependent reactions were more sensitive in this case. In subjects who had a high level of physical activity and had been involved in regular physical activity for a long period of time, processes of body adaptation to the physical activity regime started to form, being accompanied by a partial decrease in the tension of immunity at the systemic level. Particular indicators of the immune system had higher values (compared to the baseline), while not leaving the reference ranges characteristic of healthy people. Along with the activation of humoral immunity, stimulation of functional activity of cell immunity was observed in subjects with a higher level of fitness. Methodologically importantly, the season did not significantly influence the main immunity indicators with the exception of spontaneous and induced chemiluminescence indicators, whose autumn values significantly differed from the annual average.

В статье представлен анализ направлений повышения жизнеспособности тканей в условиях критической гипоксии, связанных со снижением потребности клеток в кислороде. Реализация этих направлений гипобиоза сопряжена либо со снижением температуры органов и тканей, либо с индукцией механизмов торможения метаболизма и энергетического обмена, усиливающих эффекты управляемой гипотермии. Представлены основные биологические и патофизиологические закономерности, характеризующие состояния тканевой гипотермии различной степени выраженности. Приведены основные научные и технические решения, направленные на формирование у людей состояния управляемой гипотермии (искусственной гибернации) при критических состояниях, включая способы и устройства охлаждения организма, составы и перспективные направления развития фармакологической группы перфузирующих гипотермических растворов, средств индукции гибернации, устройств и способов криоконсервации органов и тканей для трансплантологии. The article presents an analysis of ways to increase the viability of tissues under conditions of critical hypoxia, associated with a decrease in the oxygen demand of cells. The implementation of these directions of hypobiosis is associated either with a decrease in the temperature of organs and tissues, or with the induction of mechanisms of inhibition of metabolism and energy metabolism, which enhance the effects of controlled hypothermia. The main biological and pathophysiological patterns that characterize the state of tissue hypothermia of varying severity are presented. The main scientific and technical solutions aimed at creating a state of controlled hypothermia (artificial hibernation) in people under critical conditions are given, including methods and devices for cooling the body, compositions and promising directions for the development of a pharmacological group of perfusing hypothermic solutions, means of hibernation induction, devices and methods for cryopreservation of organs. and tissues for transplantation.

Background. A typical extreme factor is hypoxia, which significantly affects the ability to perform tasks of professional activity, in particular, physical activity of various intensity. Physical and neuro-emotional stress under conditions of hypoxia can cause the breakdown of compensatory and adaptive mechanisms with the development of extreme and critical conditions.The aim of the study. Quantitative assessment of the effect of hypoxia on the physical performance of laboratory animals at different levels of their natural resistance.Research methods. Modeling of hypoxia was carried out by the methods of pressure chamber rise of laboratory animals and the administration of a methemoglobin former. Resistance to hypoxic hypoxia was assessed by the criterion of the threshold elevation, to hemic hypoxia – by the lifetime. The criterion for the functional state of laboratory animals was their ability to perform physical activity, which was created by treadmill run or swimming with a load.Results of the study. An altitude of 3500 m causes a decrease in the physical performance of male rats by a third of normoxia level; an altitude of 5000 m – decrease by two times; an altitude of 6500 m – decrease by four times, and at an altitude of 8000 m makes running physical activity by rats impossible. A mild degree of hemic hypoxia causes a decrease in swimming time by almost 2 times, which corresponds to the effect of an altitude of 5000 m on the working capacity; and a moderate degree of hemic hypoxia causes a decrease in swimming time by more than 3 times, which approximately corresponds to the effect of an altitude of 6000 m. The level of resistance to hypoxia has a moderate effect on physical performance, and the factor of a low level of physical performance has almost no effect on the resistance to hypoxia (28 % and 7 % of the trait variability respectively). In animals with an initially low level of resistance to hypoxia, there is also a decrease in working capacity by an average of 20 %.Conclusion. Hemic hypoxia is an adequate model in studies with a complex effect of various extreme factors. Simulation of mild hypoxia caused by the administration of 30 mg/kg of sodium nitrite is an optimal method.

The pathophysiological features of the development of maladjustment under mountain-cold conditions as a manifestation of the syndrome of mutual burdening are considered. In this study, contents of various literary sources, characterizing a persons resistance to the effects of a complex of factors under high mountains and polar zones conditions, were analyzed. With the simultaneous exposure to hypoxia and hypothermia from a pathophysiological point of view, intersecting links of terminological paths, often having diametrically opposite dynamics of changes in the characterized concepts, will be significant. Thus, in the terminological mitochondrial pathway of energy metabolism, uncoupling proteins are present, which, to increase the resistance to hypothermia, should be activated to switch the energy metabolism to predominantly use fatty acids. However, hypoxic conditions should be suppressed to maintain the level of adenosine triphosphate acid available for cells. In the terminological tract of compensatory reactions in response to hypoxemia, the volume of pulmonary ventilation is released, which must increase to improve tolerance to hypoxia, which, under mountain-cold conditions, increased heat loss and promote the deterioration of the condition, i.e., tolerance to low temperatures. Under hypoxic and hypothermic conditions, a synergistic interaction can form, which can be manifested by the development of a syndrome of mutual burdening, which will result in a significant decrease in the functional capabilities of the body, result, and productivity. Maladjustment to mountain cold, with maximum probability, will manifest as disorders of the central nervous system, decreased physical performance, depletion of the functional and regulatory reserves of the body, functional immunodeficiency, decreased regenerative potential, and development of endogenous intoxication. With a high degree of probability, a significant synergistic interaction of hypoxia and hypothermia can be found in relation to the indicators of pulmonary ventilation, blood gases (hypercapnia), acidbase balance (gas alkalosis and lactic acidosis), heart rate (tachycardia), blood pressure (hypotension), central venous pressure (increase), blood viscosity (increase) and its coagulability (hypercoagulation), peroxide and free radical oxidation (activation), and protein catabolism (increase). These changes will negatively affect the functional state of specialists performing complex professional tasks in polar latitudes.

Purpose of the study: to study the effect of Vitrum in combination with adaptogens on immunological reactivity and physical performance in athletes under conditions of intense training.Materials and methods: 4 groups of athletes, 10 people in each, went through a cycle of intensive training according to a specially developed methodology. Group I took Vitrum, group II — Vitrum + Eleutherococcus extract, group III — Vitrum + ginseng tincture. Group IV — ascorbic acid and was used as a control. Blood for analysis was taken from the cubital vein before and after 28 days of drug administration. Indicators of immunological reactivity were determined by modern laboratory methods. Physical performance was determined by the index of the Harvard step test (IHST) and the PWC170 test.Results: the use of Vitrum in combination with adaptogens promotes a significant increase in the parameters of humoral (increase in IgA by 32–40 %, IgM by 28–43 %, IgG by 9–14 %) and cellular (increasing the completeness of phagocytosis by 9–37 % immunity.Conclusion: intake of Vitrum in combination with adaptogens was accompanied by a significant increase in nonspecific immunity and increased the level of fitness.

In a study on healthy athletes of the track and field profile, it was shown that the hypoxia of physical activity is most fully reflected by the indicator of specific oxygen debt (maximum oxygen debt divided by 1000 J of work performed). When simulating load hypoxia in laboratory animals, direct registration of the arising oxygen debt is technically difficult to implement, and its indirect signs may be a decrease in peripheral blood saturation, excessive tachycardia, and hyperlactatemia of the post-load period. Key words: hypoxia of physical activity, oxygen debt, athletes, laboratory animals, blood lactate, physical activity.

В статье на основе анализа материалов изучения открытых баз генетических данных, сведений о генетической предрасположенности к формированию и тяжести течения ряда психических заболеваний (шизофрения, депрессия, циклотимия) и состояний зависимости от этилового спирта и опиатов выявлены перспективные макромолекулярные мишени, воздействие на которые может быть перспективным для разработки фармакологических средств генной терапии. Продемонстрировано, что полигенный характер предрасположенности к шизофрении делает нереальным решение задачи по генной диагностике и терапии этого заболевания. Генным маркером клинически значимой депрессии была статистически достоверно повышенная экспрессия гена рецептора 1 запуска естественной цитотоксичности (NCR1). Для клинически близкого состояния циклотимии генным маркером может быть гипоэкспрессия А3-аденозинового рецептора. К числу генов, являющихся маркерами предрасположенности к алкоголизму, могут быть отнесены как неспецифические для нервной системы гены (главного комплекса гистосовместимости, универсального ГТФ-связывающего рецепторного белка, мембранные транспортеры растворимых веществ), так и специфические для ЦНС гены (опиоидного рецептора, кислого лейцин-насыщенного ядерный протеина, РНК-связывающего протеина, транскрипционного фактора семейства LIM), а тяжесть токсического действия этанола в большей степени связана с полиморфизмами гена ГАМК-А рецептора. Наибольшая дифференцирующая зависимость от алкоголя способность характерна для генов H2-D1, Anp32a, Gnb1, Rbm45. Анализ геномных баз данных показал, что с предрасположенностью к опийной наркомании наиболее тесно связаны гены, кодирующие синтез рецепторных белков дельта1-опиатного рецептора. Выявленные генные маркеры имеют популяционные полиморфизмы, влияющие на психическое состояние жителей определенных этнических категорий, проживающих преимущественно в азиатской части территории РФ, что необходимо учитывать в решении задач персонифицированной и популяционной психофармакологии и фармакоэкономики. В соответствии с общими принципами генной терапии, воздействие на гиперэкс-прессированный ген может осуществляться специфическими к нему рибозимами или антисмысловыми интерферирующими микроРНК. На современном уровне развития средств генной терапии для гипоэкспрессивного состояния рецептор-зависимых процессов фармакологические подходы к их коррекции до настоящего времени не разработаны. Having analyzed genetic databases, information about genetic predisposition to development and severe course of certain mental diseases (schizophrenia, depression, cyclothymia) and states of dependence on ethanol and opiates, we distinguish prospective macromolecular targets, the impact on the targets in question may turn out to be promising for the development of pharmacological agents for gene therapy. We demonstrate that the polygenic nature of the predisposition to schizophrenia makes it impossible to solve the problem of gene diagnosis and therapy of this disease. The statistically proved increased expression of the gene-receptor of natural cytotoxicity (NCR1) was the gene marker of clinically significant depression. For a clinically similar state of cyclothymia, hypo-expression of the A3-adenosine receptor may be the gene marker. Non-specific genes for the nervous system (the main histocompatibility complex, universal GTP-binding receptor protein, membrane transporters of soluble substances) as well as CNS-specific genes (opioid receptor, acidic leucine-saturated nuclear protein, RNA-binding protein, transcription factor of the LIM family) can be attributed to the gene markers of predisposition to alcoholism, and the severity of the toxic effect of ethanol is mostly associated with the polymorphisms of the GABA-A receptor gene. The greatest differentiating alcohol addiction is characteristic of the genes H2-D1, Anp32a, Gnb1, Rbm45. The analysis of genomic databases showed that the genes encoding the synthesis of delta1-opiate receptor proteins are most closely associated with predisposition to opiate addiction. The identified gene markers have population polymorphisms affecting the mental state of residents of certain ethnic categories living mainly in the Asian part of the territory of the Russian Federation, which must be taken into account when solving the problems of personalized and population psychopharmacology and pharmacoeconomy. In accordance with the general principles of gene therapy, the impact on the overexpressed gene can be carried out by specific ribozymes or antisense interfering microRNAs. At the current level of the development of gene therapy tools for the hypo-expressive state of receptor-dependent processes, pharmacological approaches to their correction have not been developed yet.

The results of content analysis of the role of polymorphism of the ACE gene genotype (RS4646994) in persons employed in the Arctic region are presented. It has been shown that it can be recommended as a universal marker in the diagnosis of not only essential hypertension, but other diseases of the cardiovascular system. In order to reduce the risk of developing pathological conditions, when planning official activities in the Arctic region, it is advisable to build professional selection, taking into account not only their genetic predisposition, but also the body's ability to maintain homeostasis. Key words: Arctic, polymorphism, ACE gene (RS4646994), arterial hypertension, homeostasis.