На крысах линии Вистар изучено влияние 5-дневного введения физиологического раствора внутримышечно или внутрижелудочно на динамику физической работоспособности животных в плавательном тесте с грузом, поведение животных в тесте «Открытое поле», а также уровень кортикостерона, лактата, активность аланинаминотранс- феразы (АлТ) и аспартатаминотрансферазы (АсТ) в сыворотке крови. Оба способа введения физиологического раствора перед плавательным тестом сопровождались повышением работоспособности крыс: в среднем на 73 % (p = 0,013) при внутримышечном введении и на 70 % (p = 0,002) при внутрижелудочном, относительно аналогичного показателя у крыс, которых подвергали только плавательному тесту. Тренировочный процесс при внутримышечном введении существенно ускорялся, а при внутрижелудочном – тормозился, по сравнению с контролем. После 5-дневного плавания с совместным введением физиологического раствора, как внутримышечно, так и внутрь, поведение животных в тесте «Открытое поле» существенно не отличалось от поведения животных, не получавших никаких раздражителей и нагрузок. У животных, получавших физиологический раствор внутримышечно перед плаванием, сывороточные уровни кортикостерона и активность АлТ не изменялись, а уровень лактата и активность АсТ — увеличивались на 35 % (p = 0,002) и 48 % (p = 0,001) соответственно по сравнению с интактной группой. У крыс с внутрижелудочным введением физиологического раствора перед физической нагрузкой, уровень кортикостерона и активность АлТ понижались на 350 % (p = 0,04) и 63 % (p = 0,003) соответственно по сравнению с интактной группой. Уровень лактата и активность АсТ в этой группе животных оставались неизменными, относительно аналогичных показателей крыс, не получавших никаких воздействий. Полученные результаты говорят о необходимости параллельного и последовательного контроля способов введения лекарственных веществ и их растворителей, в том числе физиологического раствора в экспериментальных исследованиях. Также стоит учитывать сезонность и время суток введения.

An assessment was made of hematological parameters of peripheral blood and structural and functional changes in the adrenal glands in stress-unresistant rats (passive-defensive type of behavior in the open field test) after exposure to light deprivation and physical activity during the spring equinox. The experiment showed that light deprivation for 10 days reduces the total number of leukocytes, the absolute content of monocytes, granulocytes, lymphocytes and the level of corticosterone in the peripheral blood compared to the intact group, that was on a natural lighting regime. Histological analysis of the adrenal glands of this group showed, that in the zona fasciculata under such conditions there was nuclear hypertrophy, an increase in the nuclear-cytoplasmic ratio of adrenocorticocytes and a decrease in the size of the zona glomerulosa of the adrenal cortex of rats in relation to the intact group. Physical activity in the form of forced swimming until complete fatigue for 5 days in a row in natural light in stress-unresistant rats did not change the parameters of the peripheral blood of animals, however it led to an increase in the area of the cytoplasm, the nuclear-cytoplasmic ratio, as well as the formation of nuclear hypertrophy of adrenocorticocytes in the fascicle adrenal zones, which indicated the preparation of cells for increased synthetic activity. Keeping rats for 10 days in complete darkness before forced swimming every day for 5 days, on the one hand, formed a hypoxic state and exhaustion of the adrenal glands, on the other hand, stabilized the leukocyte pool of peripheral blood compared to similar indicators in intact rats.

The effect of humic acids and substances with similar action - derivatives of succinic acid (ethylmethylhydroxypyridine succinate) and combined agent consisting of succinic acid, nicotinamide, riboflavin, and riboxin on the performance and stress resistance of experimental rats was studied. Performance was assessed in the test of exhaustive forced swimming with a load, stress resistance was evaluated by the serum level of corticosterone and open field behavior, and the state of anaerobic metabolism was estimated by the serum level of lactate after swimming test. Humic acids from peat showed anti-stress activity comparable to that of the officinal preparation and preventive effect on fatigue during physical exercise. They can be recommended as a component for the development of drugs that increase human performance and stress resistance.

Currently methods development for restoring physiological functions and increasing the adaptive capabilities of the body after prolonged stress exposure of various genesis is an urgent problem in the field of balneology and physiotherapy. It is known that the adaptive potential of the organism is not the same in different seasons of the year. In this regard, it becomes necessary to take into account the seasonality factor when carrying out recreational activities.PURPOSE OF THE STUDY:To perform a comparative study of balneotherapeutic procedures effectiveness in the form of water and antler baths in relation to the restoration of the psychophysiological parameters of laboratory rats after a consistent stressful effect of light desynchronosis and physical activity to a state of complete fatigue during autumn and spring equinoxes.MATERIAL AND METHODS:The experiment was carried out during the periods of the spring and autumn equinoxes on 160 male Wistar rats weighing 220-250 g. In each season, the animals were divided into 8 groups of 10 individuals. Two groups were in natural lighting conditions. Animals of the 1st group (intact) were not exposed to experimental influences; rats of the 2nd group were exposed to physical activity in the form of a swimming test until complete fatigue for 5 days in a row in the morning; animals of groups 3-8 were exposed to stress loads in the form of 10-day light desynchronosis (light or dark deprivation) followed by physical activity. In the 4-th, 5-th, 7-th and 8-th groups, post-experimental post-stress recovery programs were carried out using water baths (groups 4 and 7) and baths with drug «Pantovanna» (groups 5 and 8). After the completion of exposures, the animals were tested in the «open field» according to the standard method. The level of corticosterone in the blood serum was determined by ELISA.RESULTS:It was found that in laboratory rats sensitivity to stressful influences - light desynchronosis followed by physical activity to the point of fatigue, as well as active post-stress recovery were determined by the nature of desynchronosis and the season of the year. The stress load was accompanied by a phase of exhaustion during the spring equinox and by a phase of anxiety during the autumn equinox. In the spring, antler baths as a procedure for active post-stress recovery were ineffective; in autumn, they had a normalizing effect on the level of corticosterone and behavior only after dark deprivation.CONCLUSION:The conducted experiment indicates the need to take into account the season of the year and the direction of the transmeridian flight to sanatorium-and-spa treatment with balneotherapy procedures. Using the example of equinoxes under experimental conditions on laboratory rats, it has been shown that balneological procedures will more effectively perform rehabilitative functions when the light phase of the day expands as a result of such a shift, but not the dark one.

OBJECTIVE:Determination of the total antioxidant activity of blood serum (AOA) of patients with chronic cerebral ischemia (CCI) I-II st. against the background of treatment with Cytoflavin or ethylmethylhydroxypyridine succinate (EMGPS) and evaluation of the effect of drugs on the state of cognitive functions and emotional sphere of patients.MATERIAL AND METHODS:The main group consisted of 12 women with CCI I-II st., treated on an outpatient basis with Cytoflavin 1 tablet 2 times/day as part of complex therapy for 1 month; 12 patients with CCI I-II st., treated as part of complex therapy with EMGPS 125 mg 2 times/day for 1 month we made a comparison group. The groups are comparable in age, gender, the nature of risk factors, the severity of neurological manifestations, and the nature of basic therapy. The state of AOA, the severity and nature of cognitive and emotional disorders were assessed.RESULTS:It was found that the inclusion of Cytoflavin or EMGPS in complex therapy equally increased the AOA of patients. The decrease in the severity of neurological deficit during treatment consisted in improving spatio-temporal gnosis by improving the relationships in the cortex and synchronizing the activity of its different departments with the rate of nervous activity and neurophysiological characteristics different for each drug. The use of both drugs led to a decrease in the selection reaction time and the number of errors in recognizing the angular velocity of movement. Cytoflavin increased the selectivity of perception and attention in patients, while EMGPS did not affect this indicator.CONCLUSION:The use of Cytoflavin and EMGPS leads to an increase in AOA, has various effects on the cognitive functions of patients with CCI.

The development of new programs and methods of rehabilitation after the action of various stress factors on the body continues to be an actual problem. There are post-stress recovery programs include both standard pharmacotherapy and physical therapies. However, when prescribing certain types of physiotherapy procedures, the season of the year is not taken into account.OBJECTIVE:During the summer and winter solstices to study the features of post-stress recovery of psychophysiological functions of laboratory rats after light or dark deprivation, followed by physical exertion and rehabilitation procedures in the form of water and antler baths.MATERIAL AND METHODS:The experiment was carried out on 160 male Wistar rats. The animals were divided into 8 groups of 10 individuals at each solstice period (winter, summer). Group 1 was not exposed to any impact. Group 2 was presented with physical activity (swimming test). These two groups were in natural light conditions. Groups 3-8 underwent light desynchronosis (light or dark deprivation) followed by physical activity. After the above-mentioned influences, procedures were carried out in the form of water baths (groups 4 and 7) and baths with a preparation based on pantogematogen «Pantovanna» (groups 5 and 8). Behavioral responses were assessed using the open field test. The content of corticosterone was determined by enzyme immunoassay.RESULTS:During the periods of the winter solstice, dark or light deprivation increased the resistance of animals to the stress of subsequent physical activity, i.e. showed a training effect, while during the summer solstice the studied stress factors led to depletion of serum corticosterone levels, although the structure of behavior did not undergo significant changes. Post-stress recovery in the form of water and antler baths for 10 days was determined by the nature of desynchronosis and the solstice period. Pantobaths were effective in summer and winter only under TT conditions. However, in winter, after the CC-regime, the antlers intensified the stressful effect of physical activity on the animals' organism.CONCLUSION:The experiment carried out indicates the need to take into account the season of the year and the direction of the transmeridian flight to balneological resorts. Using the example of solstices in experimental conditions on rats, we have shown that balneological procedures will perform best the restorative functions when expanding as a result of such a movement of the light phase of the day, but not the dark one. It is possible that this feature can also persist for a person, since a more rapid adaptation to new light-dark conditions has been established also with the expansion of the light phase, but not the dark one.

OBJECTIVE:To study of efficacy and safety of mexidol used as intravenous infusion for 14 days, followed by per os treatment with mexidol FORTE 250 for 60 days in patients with chronic brain ischemia (CHM) complicated with arterial hypertension and atherosclerosis.MATERIAL AND METHODS:The mexidol group included 27 patients (24 women and 3 men) with CHM I-II gr and the combination of arterial hypertension and atherosclerosis who received intravenous infusions of mexidol (500 mg once daily) within 14 days, with the subsequent per os treatment with mexidol FORTE 250 in a daily dose of 750 mg (1 tablet 3 times a day) for 60 days. The comparison group consisted of 30 patients (22 women and 8 men) with CHM I-II gr, comparable in age, nature of risk factors and expression of neurological manifestations. Patients in both groups received basic medications to treat their risk factors. Motor activity (Tinetti test), cognitive functions (MoCa test), anxiety and depression (Hamilton anxiety and depression scale), clinical condition (General Clinical Impression scale) were assessed.RESULTS AND CONCLUSION:Inclusion of mexidol (500 mg iv infusion once a day within 14 days with the subsequent oral administration of 750 mg (1 tablet 3 times a day) for 60 days) in standard therapy of arterial hypertension with atherosclerosis and chronic brain ischemia is expedient. The results show greater clinical efficacy and sufficient safety of such combination therapy. By the end of therapy (day 74), patients in the mexidol group have a reliable improvement in motor activity, cognitive function and psychoemotional sphere, as well as a decrease in fatigue and neurological manifestations compared with the comparison group.

OBJECTIVE:In order to develop methods and means of maintaining normal human functioning under conditions of desynchronizes, the effect of mexidol on the level of corticosterone in the blood serum and the state of the cells of the beam zone of the adrenal cortex of rats after light or dark deprivation and physical activity to a state of fatigue.MATERIALS AND METHODS:The experiments were performed on 7 groups of rats (10 animals each) in the spring. The model of physical activity is the method of forced swimming of rats until exhaustion in its own modification. For the induction of experimental desynchronizes, the animals of the experimental groups were kept around the clock for 10 days with artificial bright light of 150 LX or a complete darkening of 2-3 LX. Mexidol was administered intramuscularly at a dose of 10 mg/kg animal 30 minutes before the swimming test. Control animals under similar conditions were administered 0.9% sodium chloride solution. The level of corticosterone in the serum was determined using enzyme immunoassay. The measurements were carried out on a programmable photometer for STAR FAX 303 PLUS microsamples (USA). Histological analysis of the adrenal glands was carried out according to standard methods. Microscopy of preparations, imaging and measurements were carried out using an Axio Lab A1 microscope, an AxioCamERc 5s camera and ZEN 2012 software («Carl Zeiss Microscopy», Germany). Statistical processing of the results was carried out using standard parametric and non-parametric methods, depending on the nature of the distributions.RESULTS AND CONCLUSION:Mexidol under combined successive stress loads - desynchronizes and physical activity - demonstrated anti-stress properties not only at the level of corticosterone in the blood serum of rats, but also at the level of adrenal glands. The severity of this effect of the drug depended on the number of stress loads (isolated physical or shown in conditions of desynchronizes), the phase of stress and the nature of deprivation. Under natural lighting conditions and after light deprivation, when animals were in the anxiety phase of varying severity, the drug worked more reliably than after dark deprivation in conditions of developing depletion. Nevertheless, even in the latter case, he showed himself as a means of preventing exhaustion in animals and the breakdown of adaptation.

Here, we studied the effect of the Gly-Pro peptide on the reactivity and adaptive potential during the stimulation of the parasympathetic nervous system by carbachol under the conditions of successive combined effects of three stressors: immobilization, surgical intervention, and the injection procedure. Consistent combined effect of the surgical intervention in the form of the ligature application to the pyloric stomach, the immobilization, and the saline injection procedure under the carbachol allowed to identify 4 typer of responses. These types were characterized by different combinations of corticosterone contents, and separate leukocyte subpopulations. All responses were accompanied by the stress development, as indicated by the adaptation intensity index. The most prominent stress reactions were observed in animals after the immobilization and surgery, and the combined effects of saline and carbachol injections. Through the modulation of the parasympathetic link of the autonomic nervous system, and probably the direct effect on the adrenal glands, Gly-Pro changed the corticosterone levels, individual leukocyte subpopulations, and the adaptation intensity index under multicomponent stress. In the case of the simultaneous peptide and carbachol administration, it apparently activated the resistant (resistance, counteraction) pathway of adaptation, and in the case when it was administered before carbachol, – the tolerance (endurance, patience) pathway.

The available evidence on seasonal changes in work capacity and anaerobic metabolism is very heterogeneous. Animal studies contribute to better understanding of adaptive reactions of the body to various influences and can serve as a basis for the development of physiotherapeutic, pharmacological and other methods to increase adaptive capabilities of the human body to hard working conditions and environmental situations. The aim was to study the characteristics of the five-days working capacity dynamics serum lactate concentration in laboratory rats across seasons. Methods. Eighty male Wistar rats (220-250g) comprised the sample. Measurements were taken in the middle of each season. The working capacity of animals until complete fatigue was assessed in a swimming test at the same time of a day. Results. Working capacity in rats in the swimming test had the highest values in the summer (75.4 s) and in the spring (78 s), while it was the lowest in the autumn (47.8 s). The highest concentrations of lactate we, on the contrary, observed in the in the autumn. Conclusions. Our results suggest that the working capacity in rats is the best in the spring and in the summer, worse in the winter and the worst in the autumn. One may speculate that the genetically determined seasonal pattern of metabolic processes in the skeletal muscle of rats may determines seasonality in their working capacity.

Humic acids (HAs) positively affect many body systems: excretory, digestive, nervous. In a few studies, the effect of HAs on the activity of the cardiovascular system is proved [Zykova, 2017; Lasukova, 2018]. With pathology of the heart and blood vessels, which annually take the lives of about 17 million people, there is a decrease in exercise tolerance due to the development of hypoxia. Due to the high mortality from cardiovascular disease, it is important to investigate the actoprotective activity of HAs. Materials and methods. HAs were isolated by alkaline extraction from sample of lowland wood-grass peats collected from «Tagan» deposit of Tomsk region [Zykova, 2013]. Physicochemical study of HAs carried out [Zykova, 2013]. Bioactivity of HAs was tested on 40 utbred male rats “Wistar” 250-300 g in autumn. The animals were divided on 4 groups of 10 animals each (Table 1). Solution of NaCl and HAs was administered intragastrically to experimental animals before 30 min swimming at the rate of 0.5 ml per 100 g of mass. As forced exercise used a forced swimming test [Pat. 2617206]. Upon completion of the five-day testing, all animals were withdrawn from the experiment by simultaneous decapitation under CO2-anesthesia. Decapitated animals collected blood to obtain serum. To assess the level of glycolytic processes during exercise, the rat serum lactate content was determined [Brancaccio, 2010; Brooks, 1999]. The concentration of lactate in the serum of the experimental and intact groups was determined by the colorimetric method [Dolgova, 2012; Kamyshnikov, 2000].

AIMTo study an effect of mexidol on the performance of rats after light or dark deprivations in the swimming test with a load and to evaluate the state of glycolytic processes under these conditions.MATERIAL AND METHODSThe experiment was carried out in the spring on 70 Wistar male rats. Three groups (30 animals) were in natural light conditions. One of them was not affected. The other two groups were subjected to exercise and 30 minutes before it either saline or mexidol was administered intramuscularly. Four other groups (40 animals) for 10 days were under conditions of dark or light deprivation prior to the presentation of physical activity and received either saline or mexidol before the test after deprivation was canceled. A forced swimming test with an additional load, which was presented to animals every day at 10-11 am for five days in a row, was used as a model of physical activity. The level of lactate was determined by colorimetric method.RESULTS AND CONCLUSIONMexidol increased the performance of rats in the swimming test, both under natural lighting conditions and with light desynchronization, contributed to the formation of cross adaptation to physical activity under natural lighting conditions and prolonged this state under conditions of light deprivation, did not change the content of lactate in the blood of rats after exercise in natural lighting conditions and dark deprivation and prevented its rise after light deprivation.

It is known that desynchronosis and physical stress to the point of fatigue are powerful stressors for the body. Studies indicate a depleting effect of the combined stress factors on the adaptive reserves of the organism, especially when the joint exposure is prolonged. However, the adaptive value of the training process in various activities is also well known. In this regard, it seems important to study these two aspects of adaptation when combined effects of light desynchronosis and physical overwork on the body. Р urpose of this study was to study the features of adaptive reactions of rats under conditions of light desynchronosis and physical overwork. Materials and methods . An experimental study was performed on 60 mature male rats of the Wistar breed. For the induction of experimental desynchronosis, the animals of the experimental groups were kept for 10 days in artificial bright illumination (150 LX) or full darkening (2-3 LX). The model of physical overfatigue used the method of forced swimming of rats to complete fatigue in their own modification. At the end of the swim test, all the animals were withdrawn from the experiment and underwent one-step-long decapitation under CO2 with anesthesia. In decapitated animals, to collect serum, the blood was collected in a clean, dry vial. In the blood serum of rats, the biochemical standard method was used to determine the level of lactate. Using the ELISA method and the reagent kit “IBL” (Germany), the concentrations of corticosterone and serotonin were determined. The histological analysis of the stress-realizing organs was carried out according to a standard procedure using light microscopy using the Axioskop 40 microscope from CarlZeiss (Germany). Results. It was found that physical fatigue in rats after daily swimming activities (5 days) was accompanied by a decrease in the level of corticosterone in the blood serum and destructive changes in the adrenal and femoral muscles in comparison with intact animals. In comparison with the intact group, dark deprivation and physical activity did not alter the content of corticosterone, serotonin, and lactate in the blood and caused minor destructive processes in the adrenal glands. Light deprivation and fatigue lowered the level of corticosterone in the blood, caused destructive changes in the adrenal glands and muscles, and increased serotonin levels in serum, but did not change the level of lactate. Conclusions. The features of adaptive reactions of rats under conditions of light desynchronosis and physical overfatigue are determined by the nature of deprivation or the direction of the phase shift (deprivation of light or darkness). Dark deprivation followed by physical overfatigue causes the development of the resistance phase of the general adaptation syndrome, and light deprivation followed by physical overwork is the phase of exhaustion.