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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.

1,4-Pyrazine-3-carboxamide-based antiviral compounds have been under intensive study for the last 20 years. One of these compounds, favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, T-705), is approved for use against the influenza infection in a number of countries. Now, favipiravir is being actively used against COVID-19. This review describes the in vivo metabolism of favipiravir, the mechanism of its antiviral activity, clinical findings, toxic properties, and the chemical synthesis routes for its production. We provide data on the synthesis and antiviral activity of structural analogs of favipiravir, including nucleosides and nucleotides based on them.

Introduction. From 1960 to 2018, 282 people were enrolled in cosmonaut groups in the USSR and Russia. Extreme special training and working conditions could lead to health disorders, which may be reflected in the causes and rates of mortality in the future. The goal of this work is to study the causes and rates of mortality in two cohorts of cosmonauts: those with and without spaceflight experience. The study aim is to research the causes and mortality rates of astronauts who have made and did not fly into space. Methods. A cohort study of mortality of 263 male cosmonauts was conducted, 118 cosmonauts with spaceflight experience formed cohort 1, 145 cosmonauts without it - cohort 2. The follow-up period was 59 yrs. (01.01.1960-31.12.2018) with 8351,4 person-years obtained. The reference group for both cohorts was the male population of Russia, cohort 2 was also the reference group for the cohort 1. Mortality risk was assessed using standardized mortality ratio (SMR) with 95% confidence interval (95% CI). Results. Death risk from all causes (A00-Y98) for each cohort was significantly lower than that for the male population (SMR=0,39, 95% CI 0,28-0,54 for cohort 1; SMR=0,53, 95% CI 0,41-0,69 for cohort 2). Moreover, the risk of death for cosmonauts with spaceflight experience is also lower than for cosmonauts without it (SMR=0,66, 95% CI 0,46-0,91). The most common causes of death in both cohorts were circulatory system diseases, and cosmonauts without spaceflight experience died at a younger age. Conclusion. Further research is required to understand the true influence of extreme working conditions on cosmonauts’ health, especially in the long-term period.

Two recombinant purine nucleoside phosphorylases from thermophilic bacterium Thermus thermophilus HB27 encoded by genes TT_C1070 (TthPNPI) and TT_C0194 (TthPNPII) were purified and characterized. T...

1-(2′-Deoxy-2′-fluoro-β- d -arabinofuranosyl)benzimidazoles containing 4,6-difluoro-, 4,5,6-trifluoro-, 5-fluoro-6-methoxy-, and 5-methoxy-4,6-difluorobenzimidazole fragments were synthesized by using purine nucleoside phosphorylase-catalyzed chemoenzymatic approach. As expected, enzymatic synthesis of nucleosides proceeds in lower yields of target compounds in comparison with the synthesis of ribo- and 2′-deoxyribobenzimidazoles (40–55% vs 60–90%). The compounds obtained were tested against the herpes simplex virus type 1, by using the Vero E6 cells. 5-Methoxy-4,6-difluoro-1-β- d -(2′-deoxy-2′-fluoroarabinofuranosyl)benzimidazole did not show any antiviral activity, when used in nontoxic concentration. All other nucleosides proved to exhibit a selective antiherpes activity. In contrast, it was shown that benzimidazole-β- d -arabinofuranosides of both di- and trisubstituted derivatives, having substituents in positions 4–6 of the benzene ring, as well as unsubstituted compounds, cannot be synthesized by enzymatic transglycosylation. 1-(β- d -Arabinofuranosyl)benzimidazole was obtained through glycosylation of N -trimethylsilylbenzimidazole with 1-chloro-2,3,5- O -methoxymethyl- d -arabinose. The behavior of this compound, as inhibitor of purine nucleoside phosphorylase (PNP) E. сoli , was investigated . 1-(β- d -Arabinofuranosyl)benzimidazole was found to belong to a mixed type of inhibitors of PNP. This fact explains why all attempts to perform enzymatic arabinosylation of 4,6-di-, 5,6-di-, and 4,5,6-trisubstituted benzimidazoles failed.

Two genes of T. thermophilus HB27, TT_C1184 and TT_C1274, encoding proteins with phosphoribosyl pyrophosphate synthetase activity were cloned in an expressing vector pET23d+. Escherichia coli strains overproducing two relevant proteins in soluble forms were obtained. The methods of isolation of thermophilic phosphoribosyl pyrophosphate synthetases Tth PRPPS1 and Tth PRPPS2 were developed. The activities of these enzymes were determined as a function of concentration of metal ions, inorganic phosphate, and temperature. The kinetic parameters for basic natural substrates were calculated; the substrate specificity for different carbohydrate 5-phosphates of D-series was studied. It was shown that the two proteins differ significantly in these characteristics. According to the results and comparison of amino acid sequences of new proteins with those of other phosphoribosyl pyrophosphate synthetases, both enzymes belong to class I PRPPS.

We found a unique property of E. coli purine nucleoside phosphorylases to selectively perform the arsenolysis reaction of ribonucleosides in their active site without affecting β-D-arabinonucleosides. In the synthesis of modified β-D-arabinonucleosides from the corresponding ribonucleosides, the catalytical amount of sodium arsenate in the transglycosylation reaction provided a 95 to 98% conversion rate. Such an approach was shown to simplify the composition of the reaction mixtures and facilitate the isolation of the target nucleosides, particularly, vidarabine, fludarabine, and nelarabine.

The threedimensional structures of thymidine phosphorylase from E. coli containing the bound sulfate ion in the phosphatebinding site and of the co mplex of thymidine phosphorylase with sulfate in the phosphatebinding site and the inhibitor 3'�azido�2'�fluoro�2',3'�dideoxyuridine ( N3FddU ) in the nucleo� sidebinding site were determined at 1.55 and 1.50 A resolution, respectively. The aminoacid residues involved in the ligand binding and the hydrogenbond network in the active site occupied by a large number of bound water molecules are described. A comparison of the structure of thymidine phosphorylase in com� plex with N3 FddU with the structure of pyrimidine nucleoside phosphorylase from St. Aureus in complex with the natural substrate thymidine (PDB_ID: 3H5Q) shows that the substrate and the inhibitor in the nucleosidebinding pocket have different orientations. It is suggested that the position of N3FddU can be influenced by the presence of the azido group, which prefers a hydrophobic environment. In both structures, the active sites of the subunits are in the open conformation.

Possibilities and limitations of chemoenzymatic synthesis of novel structural analogues of an antiviral preparation of Ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) were established. A synthesis of various amides of 1H-1,2,4-triazole-3-carboxylic acid and its 5-substituted analogues—potential substrates of purine nucleoside phosphorylase—has been described. Comparative efficiency of preparation methods of these amides, as well as the methods of introduction of functional groups to the C5 position of heterocyclic system, were investigated. Novel analogues of Ribavirin containing various substitutes in the carboxamide group were synthesized. A biotechnological method was developed for the preparation of 1-β-D-ribofuranozyl-1,2,4-triazole-3-carbonitryl, an intermediate in the synthesis of Viramidine, the modern analogue of Ribavirin.

A model of brain ischemia induced by staged ligation of the left and right common carotid arteries has been developed in experiments on rats. The use to this model led to reduction of animal mortality. On days 2-5 after the second ligature, the animals lost weight, the level of their CNS vulnerability increased, the volume of perceived information reduced, adaptation to environmental conditions and reproduction of conditioned reflexes were disordered. Focal and diffuse destructive changes in the nerve and glia cells were found in the cerebral cortex, hippocampus, and thalamic nuclei. The severity of disorders in the blood supply to the brain depended on the interval between ligation of the carotid arteries. This recommends this model for evaluation of the efficiency of drugs of various pharmacological groups.

The paper suggest the methodology of virtual laboratory works for Hydraulics, hydromachines and hydraulic transmissions. Similar laboratory systems are needed for further progress of distance learning system in Russian Federation.

The article is dedicated to the description of calculation algorithm for hydraulic drives of any configuration. The solution is received in the form of transient process of key parameters of drive: pressure, consumption, velocities, loads, etc. There are mentioned some differential equations for primary elements of hydrostatic drive system, the fundamentals for building of a computer program, which enable to modify it.

The tolerance of five central muscarinic receptor antagonists has been studied in experimental animals. According to the effect on orientation-exploratory reaction, drugs were arranged in the following order of increasing toxicity: procyclidinetrihexiphenidylbenactizineatropinescopolamine. For the same therapeutic index, trihexiphenidyl and benactizine were characterized by the maximum tolerance (TD50/ED5010) in mice. Scopolamine and atropine exhibited anticonvulsant activity at doses exceeding the threshold values by a factor of 6.3 and 3.9, respectively. For procyclidine, the average anticonvulsant dose was threefold lower than the threshold value. Benactizine and procyclidine had maximum tolerance levels in rats. The TD50/ED50 ratio for these drugs was greater than 3 (against 0.5 - 0.7 in groups treated with trihexiphenidyl, atropine and scopolamine).

The potentialities and restrictions of chemoenzymatic approach to the synthesis of new structural analogues of antiviral drug Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) have been determined. Syntheses of various amides of 1H-1,2,4-triazole-3-carboxylic acid and its 5-substituted analogues, prospective substrates of purine nucleoside phosphorylase (PNP), have been reported. The comparative effectiveness of the methods for obtaining amides aforementioned and also the methods for introducing functional groups to the C5 position of the heterocyclic system has been studied. New Ribavirin analogues bearing various substituents in the carboxamide group have been synthesized. The biotechnological method for the preparation of 1-beta-D-ribofuranosyl- 1,2,4-triazole-3-carbonitrile used as the intermediate in the synthesis of Viramidine, a contemporary Ribavirin analogue, has been developed.

We studied the effects of 2-(hexyl(methyl)amino)methyl)pyridyl-3-dimethyl carbamate (OPDC), a structural analogue of aminostigmine oxalate, on memory formation in rats with toxic scopolamine-induced amnesia. It was shown that OPDC in non-toxic doses ((1)/215 LD50) has significant anti-amnesic action. Ipidacrine and galantamine in the doses similar to toxic doses ((1)/17 and (1)/6 of LD50, respectively) induced the retention of memory trace. Administration of aminostigmine ((1)/11 of LD50) induced unstable anti-amnesic effect in the model of scopolamine-induced amnesia.