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Introduction. The naïve Bayes classifier combined with principal component analysis allows to distinguish the effects of antipsychotic agents effectively as well as evaluate their dose-dependency based on their impact on electroencephalogram parameters in rats. Further development of this method requires its validation as an instrument for the screening of new understudied molecules. Valproic acid derivatives appear to be a promising neuropharmacological group as they exhibit not only antiepileptic activity but also mood-stabilizing, antimigraine, neuroprotective and analgesic effects.Aim. This work was carried out to perform the pharmacological screening of a valproic acid aminoester (AVA) that exhibits antidote properties in case of poisoning with anticholinesterase agents.Materials and methods. The experiments were conducted in white outbred rats with chronically implanted electrocorticographic electrodes. AVA was administered at doses of 0,5, 5 and 30 mg/kg. The training set, used as a reference to determine the pharmacological effects of each dose of the investigated substance, included matrixes of effects of 7 drugs: the antiepileptic agent sodium valproate, the D2-dopamine receptor blocker haloperidol, the M-cholinergic receptor blocker tropicamide, the H1-histamine receptor blocker chloropyramine, the acetylcholinesterase inhibitor galantamine, the sedative dexmedetomidine, and the anxiolytic phenazepam.Results and discussion. AVA at the dose of 0,5 mg/kg showed effects similar to those of sodium valproate, while a tenfold dose increase led to the predominance of an atropine-like effect. When administered at the dose of 30 mg/kg, the compound exhibited dexmedetomidine-like action. The central M-anticholinergic effect of AVA was confirmed by an arecoline test in mice, in which the substance at a dose of 88 mg/kg completely abolished the onset of tremor. Dexmedetomidine-like action was cancelled by the administration of atipamezole in equimolar quantities, which may indicate the potential сapability of AVA to activate α2-adrenergic receptors at a high dose. The results of molecular docking suggest that this effect is related specifically to the original aminoester molecule and not to its presumable active metabolites.Сonclusion. The obtained results confirm the effectiveness of the naïve Bayes classifier as an instrument for the prediction of the pharmacological activity of compounds based on their impact on electroencephalogram parameters in rats. Identification of new pharmacological effects of understudied compounds may widen the potential range of their clinical application as well as reveal probable adverse effects.

BACKGROUND: Half of all patients with chronic heart failure (CHF) have preserved ejection fraction (CHF-nEF). The drug’s use effective for treatment of CHF with reduced ejection fraction (CHF-nFV) reduces the hospitalization incidence but does not affect the cardiovascular incidence or overall mortality in patients with CHF-nFV. Finding differences between CSN-SFV and CSN-nFV biomarkers is a pressing scientific problem.AIM: To study the metabolic disorders biomarkers intergenic relationships, myocardial damage, and to evaluate their role in the CHF development in patients with DM2.MATERIALS AND METHODS: We studied the lipid and carbohydrate metabolism disorder genes polymorphisms frequencies in patients with CHF-CFV and DM2 (48 patients), CHF-NFV and DM2 (46) and patients with metabolic syndrome (MS) without CHF (68), mean age of patients was 69,7±5,3 yo. DNA was isolated from venous blood according to the manufacturer’s methodology. Gene polymorphisms were determined by real time PCR. The studied polymorphisms correlations with clinical and laboratory data and associations between clinical and laboratory tests were identified by regression analysis.RESULTS: In the control group, PPARG, APOC3 C3238G rs5128, LIPC -250 G>A rs2070895, APOA1 G-75A rs670, FABP2 Ala54Thr G>A rs1799883, ADRB2 5318 C>G rs1042714 genes polymorphisms, along with co-dependent ADRB3, FTO, FABP2 genes polymorphic form a gene network regulating plasma concentrations of LDL, uric acid and CAD. Gene polymorphisms have been found to be associated with clinical and/or laboratory parameters in patients with CHF-CFV: PPARGC1AGly482Ser G>A rs8192678 with CAD; PPARGT-2821C rs12497191 with glycated hemoglobin level; FTO A>T rs9939609 (α-ketoglutarate dependent dioxygenase gene) with waist circumference; LEPR A>G rs1137101 (leptin receptor gene) with MAP. The following polymorphisms were found to be associated in patients with CHF-nFV: LIPC-250 G>A rs2070895 (liver triglyceride lipase gene) with MAP; PPARGC1A Gly482Ser G>A rs8192678 with MAP; FTO A>T rs9939609 with waist volume.CONCLUSIONS: From the study results, it is evident that patients with DM2 having CHF with different PV differ significantly among themselves by the presence of polymorphic genes prone to network interactions. The greatest number of such interactions is observed in the group of CHF-sFV, which determines a more complex course of this variant of CHF than in patients with CHF-nFV.

Currently, there are no reliable universal dependencies of the Poisson’s ratio on the geomechanical and geophysical characteristics of productive objects. This study aims to investigate the influence of geophysical parameters on the Poisson’s ratio for oilfield productive objects using machine learning methods. The analysis is based on data from several oil and gas fields, presenting results of dependencies between the Poisson’s ratio and parameters such as natural radioactivity of rocks and P-wave velocity. The elastic parameters were identified through triaxial tests of rock samples under reservoir conditions conducted on the PIK-UIDK/PL triaxial system at Perm National Research Polytechnic University. A brief overview of existing standards for conducting triaxial tests is also provided. The importance of standardizing methods for determining the Poisson’s ratio and other elastic parameters of rocks is emphasized to ensure comparability of research results from different fields and their applicability in various geological conditions. The proposed data analysis method relies on linear regression and machine learning methods to establish stable relationships between the Poisson’s ratio and geophysical parameters obtained from various well logging studies. These dependencies allow for more accurate estimation of the Poisson’s ratio for different types of rocks and fields, representing a significant step in developing methods for assessing elastic properties of rocks in oil fields. The obtained results can be used for more precise modeling and forecasting of oil field development processes, contributing to increased efficiency in hydrocarbon extraction and optimization of production processes in the oil industry.

Introduction. Modern chemotherapy widely considers the role of antioxidant and pro-oxidant methods in the treatment of oncologic pathologies. The use of agents that cause an increase of ROS is a relevant way to destroy tumors. At the same time, there is evidence of the ability of some antioxidants to lead to the cancer cells apoptosis through the generation of free radical forms of oxygen due to disruption of cellular homeostasis. The combination of the «Ecolum» biosensor using technique, antiradical activity data, and information about the cytotoxicity of compounds used in the study allows us to consistently conduct low-cost screening of as antioxidant, as antiradical activities and potentially reduce the required number of expensive cytotoxicity determinations using tumor cells.Aim. The main target of our work is the evaluation of antioxidant and cytotoxic activities of 1,3-dioxolane derivatives of imidazole using antioxidant, antiradical and cytotoxicity tests in vitro.Materials and methods. To carry out this study, 1,3-dioxolane derivatives of imidazole were obtained. The antiradical tests was performed using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method. Antioxidant properties were assessed within the Ecolum biosensor in the state of oxidative stress. Cytotoxic activity was assessed in GIST-T1 cell culture using the MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide).Results and discussion. Data from studies of the antioxidant activity of substances using the «Ecolum» biosensor showed varying degrees of damage to the biosensor in the absence of antioxidant action. The antiradical potential, initially used to reveal a possible mechanism of antioxidant action, actually demonstrated a possible mechanism of toxic action of substance 2c due to its antiradical effect comparable to the standard (Trolox), but the substance has the highest cytotoxicity. However, the properties of substance 2a shows that the direct correlation discussed earlier is not found in all cases.Conclusion. The asessment of the antioxidant properties and cytotoxic activity of 1,3-dioxolane derivatives of imidazole demonstrated the relevance of further searching for connections between the results of substances binding with the Ecolum biosensor under conditions of oxidative stress, their antiradical potential and cytotoxic properties. This combination of tests will potentially reduce the cost of screening through the use of an available biosensor, establish a possible mechanism of action aimed at redox balance, and confirm previously obtained data through the use of tumor cell culture.

Leonid Vasilyevich Sobolev is an outstanding pathologist, whose name definitely should occupy an honorable place in the galaxy of great scientists of Russia. However, his name was undeservedly forgotten, and the role of his work was underestimated. This Russian scientist made the most important discovery: he proved in an experiment that it is the islets of Langerhans in the pancreas that secrete a humoral regulator, "factor X", the deficiency of which leads to diabetes mellitus. This mysterious islet factor will be isolated from the pancreas of dogs in 1921 by the future Nobel laureate Frederick G. Banting and will become part of the medicine as insulin. However, there is every reason to believe that the discovery of F. G. Banting, who repeated a series of experiments by Leonid Vasilyevich Sobolev, is, in fact, secondary, which is the research subject in this paper.

Background. It is important to note a close comorbidity of type 2 diabetes mellitus (DM2) and cardiovascular issues, in particular, chronic heart failure (CHF) among the elderly patients. Research of predisposing genes’ polymorphisms allows to connect genotype particularities with the development of such conditions. Aim. Identify genetic polymorphisms in patients with DM2 and CHF with preserved ejection fraction. Materials and methods. Polymorphisms of genes of folate cycle, metabolism, hemostasis, neurohumoral status were studied in 106 patients (age 69.7±10.1 years) with DM2 and hypertension with and without CHF. Results. In patients with DM2 without CHF, the frequency of polymorphisms of these genes is comparable to the population. There are MTHFR: 677 CT, MTR: A2756G, ITGB3: T1565C, PAI-1: -675 5G4G, NOS3: -786 TC, PPARG: C1431T was found in patients with DM2 and CHF, a statistically significant increase in the frequency of gene polymorphisms was found, compared with patients with DM2 without CHF. Conclusion. The identified polymorphisms in patients with type 2 diabetes and CHF with preserved LV ejection fraction are associated with such phenotypic manifestations as: a tendency to thrombophilia, realized through a violation of homocysteine, vascular tone and trophism, immune response, as well as the oxidation of free fatty acids and the activation of the inflammation process.

BACKGROUND. Patients with type 2 diabetes mellitus (DM2) have disorders of cellular and plasma hemostasis independent of the level of glycemia, increased platelet activation, combined with microvascular angiopathy. The study of the role of genetic markers of hemostasis disorders in the formation and progression of chronic heart failure (CHF) in patients with type 2 diabetes will allow for prevention, possibly optimize treatment and improve prognosis.AIM. To reveal polymorphisms of genes of the hemostasis system in patients with type 2 diabetes mellitus and chronic heart failure with preserved ejection fraction.MATERIALS AND METHODS. The frequency of coagulation factor genetic polymorphisms was studied in patients with CHF-pEF and DM2 (52 people), CHF with reduced ejection fraction (CHF-rEF) and DM2 (49) and healthy volunteers (66), mean age 69.9±10.1 years old. DNA was isolated from venous blood according to the method of the manufacturer. Genetic polymorphisms were determined by real-time polymerase chain reaction.RESULTS. The frequencies of polymorphisms rs1799963 and rs6025 of the genes of blood coagulation factors F2 (prothrombin) and F5 (factor V of blood coagulation) in all three groups were insignificant and comparable in magnitude. In patients with CHF and DM2, the frequencies of the rs6046 polymorphism of the factor F7 gene in the heterozygous form were slightly higher (by 2.6 and 1.7 times, respectively) than in the control group, but the result was not statistically significant. The CHF-pEF and CHF-rEF groups differ in the frequencies of F13 (rs5985) and fibrinogen (rs1800790) genetic polymorphisms, but are more common in patients with CHF-rEF and DM2.CONCLUSION. Based on the results of the study, it follows that the groups of CHF-pEF and CHF-rEF differ significantly in the frequencies of polymorphisms of the studied genes, both among themselves and with the control group. The highest frequency of polymorphisms of genes, the products of which are involved in the coagulation and cellular components of hemostasis, is observed in the group of patients with DM2 and CHF-rEF.

The accident at the Fukushima NPP has revealed a certain drawback of traditional methods of registration of ionizing radiation by means of the automated radiation monitoring system, because in the conditions of the accident at the NPP the monitoring posts of the system were damaged as a result of the tsunami (23 of 24), which did not allow to evaluate the degree of radioactive contamination of the area in the early stages. In such conditions the most promising method of radiation control carried out on the potentially hazardous area is a non-contact method using an unmanned dosimetry complex (UDC), the application of which would reduce the risk of exposure to additional dose loads of personnel carrying out search and reconnaissance work and, additionally, provide management not only with information regarding radioactive contamination of the environment, but also directly provide the results of the search and reconnaissance. However, apart from the equipment used to determine the radiation background (detectors, spectrometers, radiometers, etc.) an important part of the UDC is the organization of the dosimetry complex and the way of information transfer.A possible variant of data transmission channel from the dosimetry complex installed on the UDC to the operator's personal computer is presented using NRF radio modules as an example.

Aim to determine the optimal tactics for the examination and treatment of patients with macronadular bilateral adrenal hyperplasia. Material and methods. The study included 11 patients with macronodular bilateral adrenal hyperplasia (main group). To compare biochemical parameters, the results of 26 healthy people were studied (control group). Results. The patients with macronodular bilateral adrenal hyperplasia were characterized by deficiency of 11-hydroxylase, 21-hydroxylase, 11-hydroxysteroid dehydrogenase type 2 and increased activity of 5-reductase compared with the control group. The optimal treatment for these patients is unilateral adrenalectomy. A comparative selective blood sampling from the central veins of the adrenals is necessary to select the side of intervention in patients with bilateral macronodular adrenal hyperplasia with ACTH-independent Cushing's syndrome. Conclusion. The first step in the treatment of patients with bilateral macronodular adrenal hyperplasia with ACTH-independent Cushing's syndrome is unilateral adrenalectomy, which reduces the risk of developing adrenal insufficiency and subsequent hormone replacement therapy.

Introduction. Modern therapy defines oxidative stress as one of the key links in the pathogenesis of different diseases, which makes the search for new low molecular weight antioxidants actual [1]. The widely used methods are imperfect, since they reflects reactivity of the sample under artificial conditions [2–4]. The proposed technique of using the "Ecolum" biosensor makes it possible to preserve the advantages of in vitro methods and improve the accuracy of determination through the use of biological reactions of cells [5, 6].Aim. Studying of the antiradical and antioxidant activity of 2-aminopyrroles, using in vitro methods and quantum-chemical calculations. Materials and methods. Earlier, derivatives of 2-aminopyrroles were obtained. Antiradical activity of the compounds was studied using the DPPH test (2,2-diphenyl-1-picrylhydrazyl). Antioxidant activity was evaluated on the model of oxidative stress using the «Ecolum» biosensor. The calculation data of the indices of reactivity in the approximation of the gas phase were obtained using quantum-chemical methods.Results and discussion. The antioxidant activity test indicated a higher antioxidant potential of 2a, compared to 2b. Antiradical activity test revealed a greater antiradical potential of 2b. Quantum-chemical calculations showed that 2b is characterized by a higher ionization potential, which may indicate its greater resistance to oxidation compared to 2a.Conclusion. The study of the antiradical and antioxidant activity of 2-aminopyrroles showed the importance of developing a methodology for the search for new antioxidants, because of antiradical activity test deviations, compared to living cell reactions.

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.