[Study of some pharmacological properties of a new adenine derivative].

It is established that the new compound, 9-[2-(4-isopropylphenoxy)ethyl]adenine (9-IPE-adenine) in a dose of 10 mg/kg per day produces neuroprotective effect in rats with brain ischemia model. 9-IPE-adenine decreased the neurologic deficiency 1.2 times more effectively (p < 0.05) than the reference drug mexidol in analogous dose, and had equal effect with this drug at 25 mg/kg per day on the neurologic deficiency and survival of animals. Electrophysiological studies in hippocampal slices in rats showed that 9-IPE-adenine depressed orthodromic population spikes in CA1 area by 42 ± 4%. Non-competitive antagonist of NMDA receptor complex MK-801, in contrast to D-AP5 (competitive NMDA receptor antagonist) and CNQX (competitive AMPA receptor antagonist), enhanced the depressive effect of the new drug more than two times. These ese results are indicative of the ability of 9-IPE-adenine to modulate the ion channel of NMDA receptor complex.

[Investigation into the vestibular protective properties of melatoninergic agents].

Experiments with rats showed that melatonin (2.5 mg/kg) produces a distinct vestibular protective effect excelling promethazine (50 mg/kg) as a reference agent, and also antidepressant agomelatine (5 mg/kg) as another melatoninergic agent. Lusindol, a blocker of MT1/MT2-receptors (2.5 mg/kg), and bicuculline (1.5 mg/kg), a specific GABA-receptors antagonist, weakened the melatonin effect significantly. The results testify mediation of the melatonin action by these receptors. Whole-cell patch clamp in an experiment with convoluted oblongata sections from white nonlinear infant male rats (14-d old) disclosed that melatonin (2 mM) inhibited drastically (29 +/- 3%) the excitatory postsynaptic current caused by depolarization step in neurons of the medial vestibular nucleus. Lusindol (0.1 mM) inhibited the effect of melatonin (2 mM) significantly (71 +/- 6%) which suggests involvement of melatonin MT1/MT2-receptors.

[On the mechanism of ikaron-1 anti-naupathia action].

Pneumomicroinjection of vestibuloprotector ikaron-1 (Russia) in specific neurons of the medial vestibular nucleus (MVN) was studied in cats immobilized by muscle relaxants using microelectrode devices. The original preparation had a direct effect on the majority of MVN neurons (95 %). Thirty four neurons of 37 cells (92 %) developed an inhibitory response, only one cell (3 %) was activated and 2 neurons (5 %) were areactive. Therefore, the inhibitory reaction to the preparation was 34 times more often than excitatory. An investigation of the MVN neurons activity evoked by adequate stimulation of the vestibular apparatus showed that ikaron-1 attenuates the evoked response in 92 % cells. This phenomenon could be behind the ikaron-lantinaupathia action.

[Analgesic effect of succinate-containing preparations].

It was established that mexidol (100 mg/kg, i.v.) in contrast to cytoflavin (1 ml/kg, i.v.) and reamberin (100 mg/kg, i.v.) produced analgesic effect in rabbits by raising pain threshold under electric stimulation of dental pulp. Mexidol (200 mg/kg, i.p.) also raised the nociceptive threshold of the same tail stimulation by in rats (vocalization test). Non-competitive antagonist of NMDA receptor complex, MK-801 (0.1 mg/kg, i.p.), and selective GABAA receptor antagonist bicuculline (1.5 mg/kg, i.p.) decrease the effect of mexidol. Therefore, the antinociceptive effect of mexidol in rats is mediated by the NMDA receptor complex and GABAA receptors. It was also found that mexidol (microiontophoretic application) produced inhibiting effect on spontaneous and evoked (caused by nociceptive electric stimulation of hind paw) activity of neurons (major part) of sensorimotor cortex and ventral posterior thalamic nucleus in rabbits. On the background of MK-801 and GABA blockers (bicuculline and picrotoxin), this action of mexidol was completely prevented or considerably decreased (by almost 80 and 60% of cells, respectively). Therefore, the effect of mexidol on these neurons is realized by inhibiting ion currents through NMDA receptor complex and via GABAA/benzodiazepine receptor complex.

[Radiation lesion formation and character of repair processes in the hematopoietic system of primates exposed to continuous and fractionated gamma-irradiation by equally effective doses].

The article is dedicated to comparison of the biological effectiveness of continuous and fractionated gamma-irradiation of rhesus macaques by equally effective doses. These radiation conditions are broadly used in radiobiological experiments. Specifically, they are applied in modeling radiation effects on cosmonauts during extended exploration mission. A model of radiation damage and repair on the cell, tissue and organism levels, i.e., a model of effective residual dose responsible for change in mammals' resistance to irradiation of varying duration was used to calculate equally effective doses in the experiment with primates subject to continuous and fractionated exposure. The authors publish data related to formation of radiation lesion and rate of ensuing hemopoiesis reparation. Two groups of animals were compared in resistance modification followed after testing by acute irradiation. The test was to reproduce a radiation situation for cosmonauts in the event of a cannonade of powerful solar proton events resulting in an effective residual dose of 1 Sv total The experiment evidenced close resemblance of the hemopoietic effects in primates exposed to the compared radiation conditions.

[Investigation of anti-hypoxic action of 3-hydroxypyridine derivatives in animals with some types of experimental pathology].

Experiments with occlusion of the common carotid artery in mice demonstrated that, unlike mexidol and SK-170, single injection of new derivatives of 3-hydroxypyridine (3-HP) SK-100 and IBKhF-2, and semax have an anti-hypoxic action on the model of acute normobaric hypoxia with hypercapnia. In analogous experiments with rats the distinct anti-hypoxic action was produced by 4 new 3-HP derivatives (SK-100, SK-170, IBKhF-22 at the dose of 100 mg/kg and IBKhF-2 at the doses of 10 and 30 mg/kg--extension of life span by 25-39%), mexidol (100 mg/kg) and reference-class antihypoxant amtisol (30 mg/kg, life span expansion by 19 and 27%, respectively). A series of experiments with rats with acute pancreatitis, a distinct anti-hypoxic action was shown by SK-100, SK-170 at 100 mg/kg and IBKhF at 10 and 30 mg/kg (life span extension by 26-40%), mexidol (100 mg/kg) and amtisol (30 mg/kg) which extended life span by 17 and 22%, respectively. Therefore, SK-100 and IBKhF-2 are potent to prolong life span of equally mice and rats; SK-170 and mexidol were effective only in experiments with rats.

[Effect of intermittent hypergravity on cerebellum Purkinje's cells in suspended rats].

The quantitative cytochemical and morphometrical techniques applied in the experiment with 24-d tail-suspension of rats demonstrated a decrease of cytochrome oxidase activity and downsizing of Purkinje's cell bodies in the proprioceptive cerebellum (cerebellar vermis upper central lobule), as well as a decrease of cytochrome oxidase activity in Purkinje's cells in the vestibular cerebellum (nodulus). The observed suppression of the Purkinje's cells functional activity indicates reductions in the proprioceptive and vestibular afferent inputs to these cells during simulation of the microgravity effects in rats. Intermittent exposure to hypergravity (2 G, one hour a day) prevented the decreases in cytochome oxidase activity in Purkinje's cells of both the proprioceptive and vestibular cerebella of tail-suspended rats suggesting a nearly same level of functioning as in the vivarium controls.

[Reaction of the neuronal population of rat's L5 spinal ganglia to primary and repeated modeling of microgravity effects].

Cytochrome oxidase activity as well as neurons' body and nuclei sizes were measured in the spinal L5 ganglia receiving the hindlimb afferent input during primary and repeated 14-d tail-suspension of rats. The measurements were performed using the quantitative cytochemical and morphometric techniques. The animals were suspended 30 days and returned to vivarium. Thirty day later, they were suspended again, together with a group of intact rats, this time for 14 days. Primary 14-day suspension reduced significantly the cytochrome oxidase activity in small, middle and large neurons (cross-section area of bodies less than 800, 800-2000 microm2 and more than 2000 microm2, respectively) and yielded a trend-like diminution of the nerve cells bodies and nuclei. The postponed repeated suspension, unlike the primary 14-d one, resulted in a substantial downsizing of bodies and nuclei of middle neurons suggesting a more dramatic hypofunction and a more dramatic decrease of afferent input. However, the cytochrome oxidase activity was not suppressed considerably in small and middle neurons which might be explained by initiation of the afferent input recovery.

[Influences of primary and repeated modeling of microgravity effects on spinal motoneurons l5 in rats: cytological analysis].

The cytochrome oxidase activity, sizes of bodies, nuclei, and nucleoli of alpha-motoneurons from the L5 anterior horns were investigated in rats once or repeatedly suspended by tails to model the effects of microgravity. Rats were suspended 30 days, then held in vivarium 30 days w/o any behavior restriction and suspended once again 14 days simultaneously with rats that had not been suspended before. The first-time 14-d suspension reduced the cytochrome oxidase activity as well as sizes of bodies and nuclei in alpha-motoneurons which pointed to hypofunctioning of these nervous cells. Repeated (14-d) suspension after the 30-day maintenance in vivarium decreased the alpha-motoneurons parameters much less significantly implying mild hypofunction and a faster adaptation of L5 alpha-motoneurons to microgravity modeled again after a long period of recess.

[Reproductive function and viability of progeny in female rats under unfavourable influences in run up to puberty].

Wistar female rats were subjected to a 3.5-day water deprivation once a week in the period of 1.5 to 3 months of age. Their progeny was subjected to the same influences during the same period of life. A week later, reproductive function of female rats was evaluated by mating them with normal males. In the experimental groups of both generations, no significant changes were found in number of neonates and their body mass, in maternal behaviour during the lactation period, in postnatal mortality of pups, in their growth and development, in motor activity, physical endurance and behaviour.

[Intermittent exposure to hypergravity of rats deprived of support to the hind limbs. analysis of the somatosensory cortex ultrastructure].

Intermittent hypergravity was evaluated as a method to prevent the unfavorable nervous effects of microgravity. It was shown that intermittent exposure to hypergravity (2 G, 1 h. a day) of rats during 24-d tail-suspension put a barrier to changes in the ultrastructure of the brain somatosensory cortex associated with a reduction in the afferent input to the somatosensory cortex from the hind limbs.

[Functioning of the brain vessels in rats after repeated simulation of some effects of microgravity (histological analysis)].

Histological methods were employed to investigate brain vessels of rats subjected to 30-d tail-suspension and 30-d readaptation in the horizontal position afterwards, and suspended again for 14 days simultaneously with other rats that had no such experience in the past. Repeated suspension produced, although there was blood redistribution to the cranial end, much less profound changes in brain vessels as compared with the previous 30-d suspension and the first-time suspended mates. This suggests an unknown arterial mechanism triggered in the region forward of the extracerebral arteries of the brain surface which hampered an excess blood flow to the brain during repeated suspension.

[Blood plasma volume dynamics in monkeys during immersion]. / Dinamika ob"ema plazmy u obez'ian v usloviiakh immersii.

Dynamics of blood plasma volume (PV) was studied with indirect methods (hematocrit count, hemoglobin, total protein and high-molecular protein) during 9-d immersion of monkeys Macaca mulatta. The animals were donned in waterproof suits, motor restrained in space seat liners and immersed down to the xiphisternum. Two monkeys were immersed in the bath at one time. The suits were changed every day under ketamine (10 mg/kg of body mass). There were two groups with 12 animals in each. The first group was kept in the bath 3 days and the second--9 days. Prior to the experiment, the animals had been trained to stay in the seat liner put down into the dry bath. It was shown that already two days of exposure to the hydrostatic forces (approximately 15 mm Hg) and absence of negative pressure breathing reduced PV by 18-20% on the average in all animals. Subsequent PV dynamics was individual by character; however, PV deficit persisted during 4 days of immersion in the whole group. In this period, albumin filtration was increased significantly, whereas high-molecular protein filtration was increased to a less degree. During the remaining days in immersion PV regained normal values. Ten days of readaptation (reclined positioning of monkeys brought back into cage) raised VP beyond baseline values. This phenomenon can be attributed to the necessity to provide appropriate venous return and sufficient blood supply of organs and tissues following extension of blood vessels capacity.

[The influence of hypokinesia on the mother-fetus system]. / Vliianie gipokinezii na sistemy "mat'-plod".

In experiments with rats effects of hypokinesia on the course of pregnancy and the mother-fetus system were investigated. Immobilization in penal-type cages of female rats on days 8 through to 19 of pregnancy gave rise to significant shifts in mother's organism, i.e. retarded body mass gain, mass reductions in thymus, spleen, liver, some other organs, and adipose tissue. Rates of prenatal fatality in the experimental group were not changed; yet, fetuses were behind the control by the values of body mass, ossification ranges, development of analyzers and other parameters. Quantities of liquid, sodium, magnesium and calcium per one gram of dry tissue were equal in the experimental and control fetuses. Comparison of the data with results of the embryological experiment with rats aboard the space "shuttle" suggests that immobilization is more baneful for the mother-fetus system than microgravity of the same length.

[Repeated hypergravity: morphologic investigations of pituitary, thyroid, blood and bone marrow in rats]. / Povtornoe vozdeistvie gipergravitatsii: morfologicheskoe issledovanie gipofiza, shchitovidnoi zhelezy, krovi i kostnogo mozga krys.

To elicit the mechanism of facilitating the mammals' adaptation to repeated changed gravity influence, the pituitary, thyroid, blood and bone marrow were investigated morphologically in rats exposed to single and repeated hypergravity (2 g) and Coriolis accelerations for 5 days during rotation on centrifuge. No distinct difference in blood and bone marrow cytology was determined after single and repeated exposure to 2 g and the Coriolis accelerations. Compared to single and in contrast to single and repeated exposures to the Coriolis accelerations, a repeated 2 g influence produced some structural changes in somatotropic cells of the pituitary and thyroid parenchyma of the thyroid. These changes were indicative of a significant intensification of synthesis and secretion of somatotropic and thyroid hormones. Elevated functional activity of the somatotropic cells and thyroid parenchyma during repeated exposure to 2 g appears to be a part of mechanism that makes adaptation to repeated hypergravity easier and points to the ability of mammals "to remember" changed gravity. It also advocates for the potentiality of intermittent centrifugation as a means of generating artificial gravity forces in space flight.

[The effect of weightlessness on erythrocyte resistance in vivo and in vitro]. / Vliianie nevesomosti na rezistentnost' éritrotsitov in vivo i in vitro.

One of the significant changes developing in animals and humans in the space mission environments is a decreased volume of red blood mass. For the analysis of causes of this phenomenon it is reasonable to compare the data on erythrocyte resistance to hemolysis in vivo and in vitro obtained in the rat experiments on Cosmos biosatellites. After 18 to 22-day space missions, the osmotic resistance of erythrocytes in vitro in animal blood samples and the level of spontaneous hemolysis in vivo directly in the vascular bed of rat have been determined. To this end, an original method based on a quantitative determination of 14Co in the expired air following previous (prior to space mission) 2(14)C glycine labeling in vivo of erythrocyte 2 group has been utilized. In both cases there were a decreased erythrocyte resistance and an increased hemolysis level. During the studies in vivo these changes were significantly great. Inflight application of artificial gravity of 1 G prevented microgravity-induced changes in the characteristics of the erythrocyte life cycle. The changes in erythrocyte shape and membrane properties as well as the factors affecting the cells in vascular bed (altered concentration of fatty acids in blood plasma and others) are discussed as possible causes of the above alterations.

[General characteristics of an experiment to study the ontogeny of rats on board the Kosmos-1514 biosatellite]. / Obshchaia kharakteristika éksperimenta po izucheniiu ontogeneza krys na biosputnike "Kosmos-1514".

Ten female Wistar rats were exposed to zero-g during 5 days, i. e., from gestation day 13 to day 18. After recovery the flight animals showed a significant delay in weight gain, thymus involution, decreased liver weight, hemoglobin concentration. Nevertheless, their reproductive function did not differ from that of the controls: the rate of preimplantation and total fetal mortality as well as the number of live fetuses were very similar in the experimental and control animals. The flight group showed a slight decline of fetal weight and water content. The size of the litters produced by the flight and control rats was identical but the mortality rate of those former during the first 7 days after birth was significantly higher. This experiment has demonstrated that the mammalian fetus exposed to zero-g during the last term of pregnancy, i. e., at the stage of active organogenesis, can grow and develop in the normal way. A large body of biological material has been obtained for biochemical and histological examinations that will help evaluate the condition of dams, fetuses, and newborns.