Detailed post-marketing studies of phenosanoic acid, the active ingredient of the original domestic medicinal product Dibufelon®, approved for human medical use as an antiepileptic agent, are aimed at improving its clinical use.

Objective - analysis of toxic properties, immunotoxicity, toxicokinetics and elements of drug dependence development, assessment of possible carcinogenic properties of phenosanoic acid in sexually mature beagle dogs with repeated oral administration with a period of delayed observation.

Materials and methods. Phenosanoic acid was administered orally to dogs (control group of animals, 2 males and 2 females and 3 experimental groups of animals of 5 males and 5 females) for 270 days at doses of 24, 60 and 120 mg/kg (1; 2.5 and 5 higher therapeutic doses (VTD), respectively). The general toxic properties, local irritating effect, effect on immunocompetent organs, elements of drug dependence development, possible carcinogenic properties, as well as basic pharmacococcinetic parameters (C_max, T_max, AUC_0-24, MRT, T_1/2) were evaluated.

Results. the drug phenosanoic acid did not have a locally irritating, immunotoxic and carcinogenic effect, did not cause withdrawal syndrome. Neurological and behavioral abnormalities (tremors, isolated cases of slight depression of behavior and refusal of feed) were detected when the drug was administered mainly at medium and maximum doses. No dose of no apparent adverse effect (NOAEL) was established (less than 24 mg/kg). Toxicokinetic analysis showed no cumulation of the active ingredient after repeated oral administration.

Conclusion. the use of phenosanoic acid should take into account possible side effects (neurological and behavioral) that are associated with the direct pharmacological profile of the drug. Keywords: phenosanic acid; safety; toxicokinetics; preclinical studies.

Objective - histological examination of the structure and cellular composition of the colon wall in rats after administration of the peptide Thr-Lys-Pro-Arg-Pro-Gly-Pro under chronic immobilization stress.

Material and methods. The experiments were carried out on 45 male Wistar rats. All animals were divided into 5 groups of 9 animals each. In group 1 group, non-stressed animals received 0.9% NaCl solution; in group 2, animals were stressed and NaCl solution was administered; in groups 3, 4 and 5, stressed animals were administered tuftsin-PGP at doses of 80, 250 and 750 µg/kg, respectively. The animals were stressed for 28 consecutive days, the peptide was administered from the 15th to 28th experimental day. Histological examination of rat colon was performed, the depth of intestinal crypts and the number of goblet cells in them were determined. The number of granulocytes, plasma cells, lymphocytes, macrophages and mast cells in the lamina propria of the mucous layer was counted.

Results. Chronic stress in experimental animals (for 28 days) caused structural shifts and changes in the cellular composition of the colon wall with the development of signs of chronic inflammation in it. Application of the peptide tuftsin-PGP from day 15 to day 28 of the experiment contributed to a significant reduction in the severity of stress-induced changes in the parameters studied, with the greatest effect at a dose of 750 µg/kg.

Conclusion. Administration of taftsin-PGP peptide at doses of 250 and 750 µg/kg on the background of stressing promotes the correction of inflammatory stress-induced morphofunctional changes in the colon wall.

Objective - to evaluate vitamin D and myostatin serum levels in postmenopausal women, and their associations with age, postmenopausal duration (PMD), and clinical severity of stress urinary incontinence (SUI).

Materials and methods. 150 postmenopausal women suffering from SUI were examined. Patients were interviewed using The Overactive Bladder Questionnaire. Serum concentrations of vitamin D and myostatin were studied.

Results. The subjective frequency of SUI symptoms in postmenopausal women increases with age and PMD (p=0,001 - p=0,045). Serum vitamin D concentrations decrease with age (p=0,004) and PMD (p=0,023). Serum myostatin levels increase with age (p=0,038). An increase in the age and PMD (p<0,0001), as well as reduced serum vitamin D concentrations (p<0,0001) and elevated myostatin levels (p=0,0004), are associated with a statistically significant decrease in the life quality of female patients with SUI.

Conclusions. The data obtained allow us to consider indicators of age and PMD, as well as serum concentrations of vitamin D and myostatin, as personalized predictors of deterioration in the life quality of women with SUI in the postmenopausal period.

Objective - to evaluate the dynamics of changes in the level of the biomarker of acute kidney injury - cystatin C in blood serum and urine in patients with thermal skin burns.

Materials and methods. The study included 74 patients with thermal skin burns of I-III degree with a skin lesion area of more than 25%, of which at least 15% are deep burns. Serum creatinine levels were determined using the kinetic Jaffe method. The concentration of cystatin C was studied by multiplex analysis on a flow cytofluorimeter.

Results. It was found that the concentration of cystatin C in the blood serum during burn shock increases by 1.9 times, with burn toxemia and septicotoxemia - by 1.5 times in relation to the control group. In urine, this indicator increases 17.4 times during burn shock, 17.1 times with burn toxemia and 15.8 times with septicotoxemia relative to the control group.

Conclusion. Cystatin C in serum and urine can be considered as an early biomarker of acute kidney injury in patients with thermal skin burns.

Objective - study of the antibacterial activity of extracts from leaves and fruits of staghorn sumac.

Materials and methods. Extraction of leaves and fruits of staghorn sumac harvested in the Botanical Garden of the Pyatigorsk Medical and Pharmaceutical Institute, leaves - June 2023; fruits - end of October 2022. Determination of the main groups of biologically active compounds was carried out: tannins by the Folin-Chocalteu method, flavonoids and anthocyanins by spectrophotometry, organic acids and ascorbic acid by titration. To establish the antimicrobial activity of the studied extracts, eight clinical test strains were used. Antimicrobial activity was carried out by diffusion into agar. Determination of the sensitivity of microorganisms to the extractions under study using the "well" method.

Results. For staghorn sumac leaves, the dominant groups of bioactive compounds are tannins and flavonoids. The fruit has a lower content of tannins, but there is a high content of organic acids and anthocyanins. Screening studies have shown that extracts from the leaves and fruits of staghorn sumac have a pronounced antibacterial activity. Growth inhibition zones for all studied strains were more than 10 mm (from 13 mm to 30 mm), which characterizes their activity as high.

Conclusion. Antimicrobial activity against the most common pathogens of infectious diseases has been established: Escherichia coli, Salmonella enterica, Proteus mirabilis, Klebsiella pneumoniae, Shigella flexneri, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes. The obtained chemical, analytical and biological data allow us to consider extracts from the leaves and fruits of staghorn sumac (Rhus typhina L.) as potential antimicrobial agents.

Tetraethylthiuram disulfide or antabuse (1,1',1'',1'''-[disulfanedylbis-(carbonothioylnitrilo)]tetratane) is a biologically active substance that can be used to treat alcohol and cocaine addiction, a number of infections, cataracts, and some neurological and oncological diseases.

Objective - development of a method for determining tetraethylthiuram disulfide in a substance and a model biological object (liver tissue) using the derivative spectrophotometry method.

Materials and methods. The object of the study is tetraethylthiuram disulfide (1,1',1'',1'''-[disulfanedylbis-(carbonothioylnitrilo)]tetratane). The applied chemical-analytical method of research is second-order derivative electron spectrophotometry. Liver tissue was used as a model of a biological matrix.

Results. A method for studying biomaterial for the presence of tetraethylthiuram disulfide has been developed, based on isolation with toluene, purification by changing the solvent and sorption in a thin layer of silica gel, detection by TLC with subsequent identification and assessment of the quantitative content by spectrophotometry in the UV region based on the calculation of second-order derivatives. The position of the maxima of the pronounced and hidden absorption bands of the analyte in the electronic spectrum has been clarified. The presence of a linear dependence of the intensity of light absorption of tetraethylthiuram disulfide in the acetonitrile medium on the concentration of the analyte in the photometric solution (range 1.0-24.0 μg/ml) has been shown. It has been established that the developed method allows determining (61.42-63.11) ± (2.66-4.21)% tetraethylthiuram disulfide in model mixtures with liver tissue containing 0.005-0.2% of the analyte. The values of the standard deviation S and the relative standard deviation Sr, % are 2.14-3.39 and 3.39-5.51, respectively.

Conclusion. Using the method of derivative spectrophotometry, a reproducible and correct method for assessing the qualitative and quantitative content of tetraethylthiuram disulfide in the substance and model biomatrix (liver tissue) has been developed.