Comparative Analysis of Stress-Protective Activity and Prevention of Fatigue during Physical Load of Standardized Humic Acids from Peat and Officinal Preparations of Succinic Acid in Experiment.

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.

[Speciality of restoring the psychophysiological parameters of laboratory rats with the help of balneological procedures during the periods of equinox]. / Osobennosti vosstanovleniya psikhofiziologicheskikh pokazatelei laboratornykh krys s pomoshch'yu bal'neologicheskikh protsedur v periody ravnodenstviya.

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 «Pantovanna¼ (groups 5 and 8). After the completion of exposures, the animals were tested in the «open field¼ 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.

[Comparison of neurotropic and antioxidant activity of Cytoflavin and etilmetilgydroxypiridine succinat in patients with chronic brain ischemia]. / Sravnitel'naya kharakteristika neirotropnoi i antioksidantnoi aktivnosti Tsitoflavina i etilmetilgidroksipiridina suktsinata u patsientov s khronicheskoi ishemiei golovnogo mozga.

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.

[Experimental study of the features of post-stress recovery of psychophysiological functions using balneological treatments during the solstice]. / Eksperimental'noe issledovanie osobennostei poststressornogo vosstanovleniya psikhofiziologicheskikh funktsii s pomoshch'yu bal'neoprotsedur v period solntsestoyanii.

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 «Pantovanna¼ (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.

[Effectiveness and safety of mexidol forte 250 in the sequential therapy in patients with chronic ischemia]. / Effektivnost' i bezopasnost' preparata Meksidol FORTE 250 pri posledovatel'noi terapii patsientov s khronicheskoi ishemiei mozga.

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.

[An effect of mexidol on the level of corsticosteron in the blood serum and beam zone cells in rats with light desynhronizes and physical loads]. / Vliyanie meksidola na uroven' kortikosterona v syvorotke krovi i kletki puchkovoi zony kory nadpochechnikov u krys pri svetovykh desinkhronozakh i fizicheskikh nagruzkakh.

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 Microscopy¼, 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.

Effect of Humic Acids from Lowland Peat on Endurance of Rats in Forced Swim Test in Relation to Serum Lactate and Corticosterone.

The study substantiated the possibility of using peat humic acids for improving endurance during extreme physical exertion. The mature outbred Wistar rats weighing 200-250 g (n=40) were subjected to forced swim test until complete exhaustion. The humic acids (1%) were administered intragastrically (0.5 ml/100 g body weight) 30 min prior to the test. Chronic administration of peat humic acids for 5 days increased physical capacity and endurance of rats in exhaustive forced swim test without the changes in serum lactate and corticosterone.

[Effect of mexidol on physical working capacity and level of lactate in the blood of rats in conditions of light deprivation]. / Vliianie meksidola na fizicheskuiu rabotosposobnost' i uroven' laktata v krovi krys v usloviiakh svetovykh desinkhronozov.

AIM: To 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 METHODS: The 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 CONCLUSION: Mexidol 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.

[SEASONAL FEATURES OF SEROTONIN IN BLOOD SERUM OF RATS AFTER PHYSICAL OVERWORK UNDER DESYNCHRONOSIS].

The content of serotonin in the blood serum of rats with light desynchronizes and physical fatigue in different seasons was investigated ву enzyme immunoassay. It was found that long-term light deprivation and exercise to complete depletion lowered levels of serotonin in the blood serum of rats in the winter and increased that of the spring season. At the same time, a dark deprivation and physical activity had no effect on this indicator.

[CHRONOBIOLOGICAL ACTIVITY OF AQUEOUS EXTRACTS OF THE ABOVE-GROUND PART OF AGRIMONIA PILOSA L. IN RATS.]

It is established that lithium is accumulated in the above-ground part of agrimony (Agrimoniapilosa L.), the aqueous extract of which exhibits lithium-specific chronobiological activity in rats. The chronobiological study was carried out during the winter solstice on 40 adult male rats divided into three groups: control (intact animals treated with purified water and the extract purified from lithium) and two test groups. Animals in the test groups were administered the aqueous extract of A. pilosa in the morning (8.00 am) and evening (19.00 pm) in amount corresponding to receiving lithium hydroxybutyrate in a dose of 10 mg/kg (p.o.). From the sixth to seventh day of experiment, without canceling this treatment, pilot testing (open field test, rectal temperature measurement) was started at 9 am and continued every 4 h over a period of 48 hours. The primary chronograms were statistically processing by analysis of variance, spectral analysis, and cosinor analysis. The quantitative determination of lithium in the above-ground part of A. pilosa L., its extract and brain of animals was carried out by flame photometry on a SOLAAR Series S spectrometer (Thermo Scientific Co., United States) equipped with a flaming atomizer operating in increased deuterium background correction emission mode. It was found that aqueous extract of the above-ground part of A. pilosa L. contained up to 8.5 ± 0.4 µg/g lithium; in the extract purified by ion-exchange chromatography, this amount was reduced to 1.4 ± 0.2 pg/g. All control animals exhibited external and internal desynchronism. Under the action of herbal extract, the daily dynamics of behavioral activity and rectal temperature in animals acquired a rhythmic character and became consistent with the external day-night cycle.

[Reactivity of the central nervous system influences the sensitivity of secretory cells of the stomach to carbacholine and glycyl-proline (Gly-Pro)].

In experiments using cluster analysis of the behavioral activity of rats in the "open field" test, the animals were divided into three groups with different types of behavior and response to the first presentation of the test: (i) active-search (all the studied reactions are expressed), (ii) intermediate, and (iii) passive-defensive (lowest level of activity). Differences in the indices of carbacholine-stimulated gastric secretion in rats of different groups were manifested by greater secretion of the stomach and lower digestive capacity of gastric juice observed in rats with active-search and intermediate types of behavior in the "open field" test in contrast to rats with passive-defensive type. Combined administration of cholinomimetic and glycyl-proline (Gly-Pro) lead to decreased proteolytic activity of gastric juice in rats with active-search behavior in the "open field" test, decreased volume of gastric secretion in rats with an intermediate type of behavior, and increased volume of juice and its decreased digestive ability in rats with passive-defensive behavior.

Mechanisms of psychopharmacological effects of alkaloid Z77 under conditions of brain ischemia.

We studied the psychopharmacological effects of atisine-type diterpene alkaloid Z77 in a rat model of brain ischemia in the morning and at night. The type of developing locomotor disorders in animals was shown to depend on circadian rhythms. Administration of Z77 substantially corrected manifestations of psychoneurological symptoms. The parameters of orientation and exploratory behavior and conditioned reflex activity were normalized. The key role of receptors of neural stem cells to fibroblast growth factor in the realization of their growth potential under the influence of the alkaloid was demonstrated. Under in vitro conditions, antibodies to fibroblast growth factor receptor abolished the increase in the number of neural CFU caused by Z77 in the culture of intact cells from the paraventricular region of the brain.

[The chronobiological peculiarities of the hepatobiliary system function in chronic cholecystitis with dysfunction of the gallbladder].

Study of biological cycles in chronic cholecystitis with dysfunction of gallbladder has a great practical importance. The results of chronoanalysis testify a dominance of 24-hours cycle in structure of cycles of functional activity of organs of hepatobiliary system. The comparative analysis of trust intervals reveals the intensification of internal connections, expressed intensification of synchronization of cycles of functional activity of system and a breach of synchronism of central regulation and self-regulation, testifying overstrain of proper adaptive possibilities and unconcordance in system of regulation. This manifestations of desynchronization provokes development and progress of dysfunction of gallbladder and dysbalance of vegetative nervous system, that make worse the present disturbances.

[Influence of simulated hypomagnetic environment in a far space flight on the rhythmic structure of rat's behavior].

Behavior of a group of rats was observed visually and tape recorded continuously from day 19 till the end of 25-d hypomagnetic experiments. Results were statistically processed with the help of Statistica 6.0, time series spectral analysis, and cosinor analysis. The 25-d HM exposure was shown to suppress food-motivated behavior in the mornings on the background of step-up in serotoninergic processes in the brain, and exaggerate the intraspecific violent conduct at night. The hypogeomagnetic environment impacted diurnal system adaptability to the seasonal light period drifting and produced exo- and endogenous desynchronosis.

[The rhythm-modulant effect of lithium hydroxybutyrate on the background of electrolytic lesion of the right suprachiasmatic nucleus of hypothalamus].

Experimental lesion of the right suprachiasmatic nucleus of hypothalamus in rats facilitates manifestations of the free-running locomotor rhythm in winter solstice, but decreases the entrainment of the light cycle of this rhythm in the period of summer solstice. The administration of lithium hydroxybutyrate in both illumination regimes compensates the influence of lesion of the right suprachiasmatic nucleus. Features of the observed effect depend on the circadian phase of drug administration.

[Effect of lithium hydroxybutyrate on the circadian dynamics of the urinary excretion of Li(+), Na(+), K(+), and Ca(2+) in rats depending on the circadian phase of the drug administration]. / Vliianie litiia oksibutirata na sutochnuiu dinamiku pochechnoi ékskretsii Li(+), Na(+), K(+) i Ca(2+) u krys v zavisimosti ot tsirkadiannoi fazy naznacheniia preparata.

In winter solstice, the urinary excretion of Li+ and Na+ in intact rats has a uniform circadian profile, while K+ and Ca2+ exhibit a 23-h and 24-h rhythm, respectively. The administration of lithium hydroxybutyrate (10 mg/kg, 6 days) at 8 a.m. forms the 24-h Li+ and Na+ excretion rhythm, while not significantly affecting the circadian profiles of K+ and Ca2+. The lithium loading at 8 p.m. made the circadian urinary excretion profiles of Ca2+ and Na+ uniform, while the excretion of Li+ and K+ acquired a 24-h rhythm. Irrespective of the circadian phase, the administration of lithium hydroxybutyrate decreased the average daily concentration of Na+ in the urine, while the average concentration of Ca2+ remains unchanged; the concentration of K+ decreases after lithium hydroxybutyrate injections in the morning. Upon the morning treatment, lithium cations are excreted faster than after the evening injections.

[Lithium oxybutyrate and the rhythmic structure of the actively exploratory behavior and body temperature in rats under constant illumination conditions]. / Litiia oksibutirat i ritmicheskaia struktura aktivno-poiskovogo povedeniia i temperatury tela krys v postoiannykh usloviiakh osveshcheniia.

Under constant illumination (LL 24) conditions, lithium hydroxybutyrate (LHB, daily dose 10 mg/kg, 10 days) facilitated the formation of synchronized 24-h rhythms in the active-search (open-field) behavior and body temperature variation in rats, independently of the objective drug administration time. In the dark (DD 24), LHB increased the free-running rhythms and facilitated synchronization of the internal harmonics, especially upon the drug administration in the objective p.m. phase.

[The effect of damage to the locus coeruleus or the raphe nuclei on circadian rhythms in rats in open-field testing]. / Vliianie povrezhdeniia golubogo piatna ili iader shva na tsirkadnye ritmy krys, testirovannykh v "otkrytom pole".

The electrolytic lesions of raphe or locus coeruleus (I = 1-1.5 mA, 20 sec, with a change in polarity) produce a destabilization in the circadian rhythms of the active searching behaviour (tested in the "open field") in rats kept under conditions of natural illumination in the period of the winter or summer solstice. The daily or circadian components are substituted, respectively, for the ultra- or infradian rhythms. If the animals are kept for 10 days under 24-h light or dark conditions, the serotoninergic or noradrenergic deficit delays the formation of free-running rhythms.