Introduction. The requirements of modern clinical guidelines for the treatment of respiratory viral infections suggest the possibility of identifying a specific viral pathogen. In this regard, the search for drugs with selective activity against respiratory syncytial virus and parainfluenza virus is relevant. The purpose of the work is to study the antiviral activity of the drug Cytovir®-3 in vitro in relation to the cytopathogenic effect of respiratory viruses (parainfluenza virus and respiratory syncytial virus). Material and methods. The antiviral effect of Cytovir®-3 in comparison with Umifenovir against parainfluenza virus and respiratory syncytial virus was studied on Vero cell culture. Drugs were administered 1 hour before (prophylactic regimen) and 1 hour after (treatment regimen) infection of the cell culture with respiratory viruses. The working range of concentrations of the studied drugs was calculated based on the values of 50% cytotoxic concentration calculated based on the results of a quantitative microtetrazole test. Results and discussion. The drug Cytovir®-3 in two schemes of application (therapeutic or prophylactic) showed its antiviral efficacy in vitro against respiratory syncytial virus and parainfluenza virus due in the non-toxic range (0–794 µg/ml). At the same time, the suppressive effect of the drug Cytovir®-3 against the parainfluenza virus begins at lower concentrations of the drug with its early (preventive) introduction into cell culture (250 mcg/ml). Conclusion. Antiviral activity of Cytovir®-3 has been proven in vitro against parainfluenza virus and respiratory syncytial virus. At the same time, in all series of experiments, Cytovir®-3 had a higher index of selectivity of antiviral action than that of the comparison drug Umifenovir.

Due to the emergence of antibiotic resistance in pathogenic microorganisms, it is urgent to search for producers of new antimicrobial metabolites. Actinomycetes are gram-positive mycelial bacteria that produce a large number of antibiotics used in medicine and the agro-industrial complex. Currently, researchers are focused on the search for actinomycetes in ecological niches such as freshwater and marine reservoirs, zones with extreme natural conditions (permafrost soils, glaciers, desert, saline soils, etc.). In this study, cultures of marine actinomycetes were restored after 15 years of storage under vaseline oil. It was shown that all strains retained viability and antibiotic activity at a high level. Based on the results of 16S rRNA gene sequence analysis, the species were identified as: Streptomyces sampsonii 6N, Streptomyces sampsonii 8N, Streptomyces sampsonii 521N, Streptomyces halstedii 22N, Streptomyces brevispora 12N, Streptomyces hirsutus 23N, Streptomyces niveus 14N, Nocardiopsis alba 24N, Nocardiopsis alba 73N, Nocardiopsis alba 85N, Nocardiopsis alba 106N, Nocardiopsis alborubida 722N, Nocardiopsis umidischolae 755N, Nocardiopsis umidischolae 763N. These strains of actinobacteria possessed significant antibiotic activity against the following pathogens: Micrococcus luteus ATCC 9341, Staphylococcus aureus INA 00985, Bacillus subtilis ATCC 6633, Staphylococcus aureus INA 00761 (MRSA — Staphylococcus aureus), Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Pectobacterium carotovorum VKM-B1247, Saccharomyces cerevisiae INA 01042, Candida albicans ATCC 14053, Aspergillus niger ATCC 16404, Aspergillus fumigatus CPB F -37, Fusarium solani VKPM F-890, Fusarium oxysporum VKPM F-148. Therefore, this study evaluated the marine actinomycetes can be potential producers of the novel antibiotics.

Background. Antibiotic resistance of bacteria is a serious concern for modern medicine. The search for new compounds with a pronounced antibacterial effect is an urgent task of pharmaceutical chemistry. The aim of the study was to assess nfluence of the structure of benzimidazole and its derivatives the ability to inhibit the growth of gram-positive bacteria Bacillus subtilis. Materials and methods. Antibacterial activity of diazaheterocycles was evaluated by the method of serial dilutions. Сoncentrations from 0,06 to 1000 µg/l were used. Тhe minimum inhibitory concentration (MIC) of benzimidazole derivatives against Bacillus subtilis BKM B-407 was determined. The antibacterial effect of the studied halogen- and nitrobenzimidazoles was compared with the antimicrobial activity of benzimidazole. Results. The antimicrobial activity of the 12 benzimidazole derivatives was established. 2-trifluoromethylbenzimidazoles containing halogen atoms in the phenylene fragment had the most pronounced inhibitory effect. The dihalogenated derivatives exhibited greater antibacterial activity than the compounds with one halogen atom in the benzene ring. 5,6-dibromo-2-(trifluoromethyl)benzimidazole was the most active compound with an MIC of 0.49 µg/mL, comparable to the commercial antibiotic tetracycline. The antibacterial activity of erythromycin is a half that of this substance. Conclusions. Polyhalogen derivatives of benzimidazole are promising compounds for the development of new antimicrobial drugs against Gram-positive bacteria.

Objectives. No sulfated polysaccharides (fucoidans) has been declared as the pharmaceutical substances, adjuvants, etc., which is associated with the problems of obtaining the structurally characterized and homogeneous samples or their oligomeric fractions that retain high biological activity. The highly purified fucoidan with regular reproducible structural characteristics (F1) was obtained by enzymatic hydrolysis of native fucoidan (F2). Aim. The comparative study of fucoidans from the brown alga Fucus evanescens (F1 and F2) effects on the effector functions of innate and adaptive immunity cells loaded with ovalbumin (OVA) in vitro and in vivo. Material and methods. Fucoidan F1 — the enzymatically modified product of native fucoidan; F2 — the native fucoidan. The fucoidans effects on the expression level of the main immunophenotypic markers of innate and adaptive immunity (neutrophils, monocytes, natural killers, lymphocytes) cells in vitro were studied by methods of flow cytometry. The fucoidans effects on the production of serum OVA-specific antibodies (IgG, IgG1, IgG2а) and cytokines (IFNγ, IL-2, IL-10, IL-12) were detected in BALB/c mice immunized with OVA. Results. The tested fucoidans activate the effector functions of innate and adaptive immunity cells loaded with OVA in vitro and act as adjuvants, stimulating both Th1 (IgG2а, INFγ, IL-2) and Th2 (IgG1, IL-10) immune response to OVA in vivo. Conclusions. The immunoadjuvant effect of the enzymatically modified fucoidan (F1) on effector functions of innate and adaptive immunity cells are comparable to those of the native fucoidan (F2). The findings determine the possibility of F1 use as an adjuvant for a wide range of prophylactic and therapeutic vaccines.

The study is devoted to the study of acute toxicity of a new quinazoline compound — 3-[2-Oxo-2-(4-phenylpiperazine-1-yl)ethyl]quinazoline-4(3H)-one (VMA-10-21), promising as an antimicrobial agent active against opportunistic microorganisms. Purpose. Assessment of acute toxicity of the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl] quinazoline-4(3h)-oh, exhibiting antimicrobial activity. Material and methods. All experiments were carried out on non-linear mature female rats with a body weight of 180–190 g. Female individuals were in the diestrus stage. The rats were divided into groups (n=6) by a random sample, there were 4 individuals in each group and were kept in cages for a week before the experiment, getting used to laboratory conditions: animals receiving intragastric equiobjection of distilled water (control); experimental animals treated with the compound VMA-10-21 at doses of 1000, 2000; 5000 mg/kg (the doses were selected based on the fact that the study of the toxicity of pyrimidine derivatives with a similar chemical structure showed their relative safety and the absence of lethality from a dose of 500 mg/kg). Results. Assessment of acute toxicity of the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl]quinazoline-4(3h)-oh with intragastric administration showed that this compound belongs to class 5 toxicity and is low-toxic according to. Under these conditions, and for LD₅₀, the maximum dose is 5000 mg/kg. However, despite the results obtained, when this compound was administered at a dose of 5000 mg/kg, changes in hemoglobin, the number of leukocytes and platelets, as well as total protein were observed, which may indicate the possible development of pathological changes in the hematopoietic and hepatobiliary systems. Conclusion. Thus, the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl]quinazoline-4(3h)-oh with intragastric administration is low-toxic and belongs to the 5^th class of toxicity, and therefore the maximum dose is 5000 mg/kg for LD₅₀. However, given the fact that there are changes in hematological and biochemical parameters, this compound needs to be studied in detail under the conditions of course effects on the body of animals.

An experimental study of the antiseptic properties of the Anolyte solution was carried out. The developed anolyte solution has an antiseptic effect, especially active against Escherichia coli, which indicates the possibility of its use in the complex therapy of purulent wounds.

Background. Estrogen receptors beta (ERβ) are an important biological regulator and target of antiestrogens, however, unlike estrogen receptors alpha (ERɑ), their significance in the prognosis and treatment of breast cancer remains unclear. Purpose. Evaluation of the ERβ prognostic value in the comparative assessment of frequency and level of the marker expression in groups with good and poor prognosis by Ki-67 proliferative index score in breast cancer. Methods. ERβ expression level (% of cells expressing the marker) in 68 breast tissue samples was quantified by immunofluorescence and flow cytometry. Primary antibodies to ERβ (clone 14C8, ab288) and secondary antibodies conjugated with DyLight650 (ab98729) were used. In the same samples, the Ki-67 expression level was assessed by the immunohistochemical method. Results. The ERβ and Ki-67 were detected in 100% breast tissue samples with high heterogeneity of the markers’ expression in different patients. Statistical analysis of good and poor prognosis in accordance with the Ki-67 proliferative index score (Ki-67≤20% and Ki-67>20%) showed the prognostic value of the ERβ expression level of 50%. There was no association between the Ki-67 and ERβ expression levels in the same tumor sample (Spearman's rank correlation coefficient R=–0,16; P>0,05). At the same time, high expression of ERβ≥50% was 2,3 times more frequently detected in the good vs poor prognostic group by Ki-67 — 41% vs 18%, P=0,02. Conclusion. The ERβ expression level ≥50% in the tumor can be considered as a factor of good prognosis of breast cancer.

The research studied the clinical and laboratory characteristics of COVID-19 patients against the background of cardiovascular diseases. A high prevalence of cardiovascular diseases (CVD) was revealed among COVID-19 patients: arterial hypertension (93.4%), chronic heart failure (60.9%), cardiac arrhythmias (40.1%), coronary heart disease (21.9%). A reliable correlation was established between the timing of hospitalization from the onset of the disease and the severity of the infection, mortality was higher in persons hospitalized on the 5–7 day of the disease (59.8%). Patients with CVD are significantly more likely to develop complications, as well as higher deaths (11.53% vs. 4.30%). Pulmonary embolism (44%), acute respiratory distress syndrome (22%), acute kidney injury (20.6%) prevailed in the structure of causes of death. Gender differences in the course and outcomes of COVID-19 were found: the severity of the course and mortality rates were higher among males. According to clinical and laboratory indicators, patients with diseases of the cardiovascular system had a more severe course and a high degree of immuno-inflammatory reactions compared with the group of patients without a premorbid background. Upon admission to the hospital, patients with COVID-19 and CVD were significantly more likely to have a lesion of the pulmonary parenchyma of CT 3 and CT 4 (P<0.05), whereas in the group without concomitant cardiac pathology, lung lesion corresponded to CT 1 (P<0.05); CT of the lungs in dynamics showed differences in the study groups: in patients with COVID-19 and CVD, CT 3 was recorded significantly more often, and in the comparison group — CT 1 (45% vs. 10%, (P<0.05)).

Aim. Evaluation of the effectiveness of anti-interleukin drugs used in the pathogenetic therapy of COVID-19 in relation to the relative risks of 28-day mortality and the odds ratio of 14-day improvement of symptoms of the disease. Materials and methods. A systematic review of publications concerning the evaluation of the effectiveness of these drugs recommended for use as COVID-19 pathogenetic therapy, with meta-analysis and indirect comparison of the data obtained, was carried out. Results. The meta-analysis included 15 randomized and 8 non-randomized studies. In direct comparison of anti-interleukin drugs with controls, it was demonstrated that only tocilizumab and anakinra surpass standard therapy in terms of the relative risk of 28-day mortality (RR 0.85 [95% CI 0.74; 0.97] and 0.5 [95% CI 0.32; 0.80], respectively). Statistically reliable data were also obtained in favor of the effectiveness of levilimab in comparison with standard therapy according to the criterion of «improvement by the 14^th day of the disease», which was 2.29 [1.31; 4.01]. With an indirect comparison of tocilizumab and anakinra, the latter showed greater effectiveness in reducing the 28-day mortality rate: the RR was 1.2 [95% CI 1.16; 1.25], P=0.0001. Conclusion. The meta-analysis of the results of the systematic review demonstrated the effectiveness of tocilizumab and anakinra in relation to the 28-day mortality rate, and levilimab in relation to the indicator «Improvement by the 14^th day of the disease».

Antimicrobial resistance is considered by WHO as one of the most important threats to public health in the twenty-first century. According to forecasts, by 2025, many first-line antimicrobials will lose their effectiveness and the «post-antibiotic era» will begin. Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and representatives of the genus Mycobacterium are classified by the American Society of Infectious Diseases as microorganisms that play a predominant role in the development of infections associated with medical care and leading to fatal consequences. The review highlights the mechanisms of antibiotic resistance and many variants of microbial resistance to antibiotics. Knowledge of the molecular mechanisms of the formation of resistance of microorganisms allows us to develop strategic directions for overcoming it. The search for new ways to prevent and overcome the formation of resistance of pathogens to antibiotics is an extremely important task of modern medical science. The effectiveness of hybrid antibiotics associated with chemical compounds with various specific effects is presented. The use of the main active factor of the bacterial virus, endolysin, both in its pure form and as part of homodimers, for example, lysoprotein, which is a complex of endolysin with human immunoglobulins, is considered promising. Phage therapy of the future is a personalized phage therapy that requires the creation of a library or bank of phages.

The review presents a theoretical rationale for the effectiveness of including topically NPWT therapy and meglumine sodium succinate intravenously in the complex therapy of wounds of various etiologies. The biochemical pathways accompanying the formation of normoxia and hypoxia of varying severity, the significance of succinate in their formation, including depending on the form of its intake into the body (exogenous and endogenous pathways), are given. Thus, when endogenous production of succinic acid is decompensated, the tricarboxylic acid cycle is inhibited and anaerobic glycolysis is activated. At this moment and before the onset of irreversible biochemical damage, the restoration of energy exchange processes begins to depend on succinate, including its exogenous intake. Additional, but no less important, antihypoxic effects of exogenous succinate include stimulation of succinate oxidase oxidation of succinic acid with the restoration of its consumption in the mitochondrial respiratory chain and an increase in the activity of the antioxidant function of glutathione, as well as stimulation of protein metabolism. Reamberin (meglumine sodium succinate) significantly accelerates tissue recovery during hypoxia due to its antihypoxic, cytoprotective and other effects due to the activation of HIF-1ɑ biologically active factors.

In modern conditions, the problem of bacterial arthritis (BA) is very relevant. The leading etiological agent of BA is Staphylococcus aureus. The frequency of deaths in BA has not changed significantly over the past 25 years and is 5-15%. The article highlights current data on the etiology, pathogenesis, clinical picture, diagnosis of BA. Indications for open surgical drainage of an infected joint are presented. The main schemes of empirical and etiotropic antibacterial therapy of BA are presented.