We modeled acute disruption of the brain blood circulation (ADBC) by bilateral ligature of the common carotids in white outbred rats. This resulted in the formation of endothelial dysfunction of capillary network in the IV–V layers of the cortex and the vessels of the pia mater, choroids plexuses, and the branches of the middle cerebral and ophthalmic arteries, which was seen as a considerable decrease in the density of nuclei of endotheliocytes, a decrease in the RNA concentration in them, expression of vascular endothelial growth factor (VEGF), and a substantial decrease in the index of the proliferative activity of endotheliocytes. Intraperitoneal treatment of rats with ADBC with lysinium for 21 days at a dose of 50 mg/kg led on the 4th day to an increase in the density of endotheliocytes in the capillary network of the brain cortex and the walls of cerebral vessels and an increase in the RNA content in endothelial nuclei. At the end of the lysinium treatment, we observed an increase in the density of endotheliocytes in the capillary network of the brain cortex and the walls of cerebral vessels, an increase in the RNA content in nuclei of endotheliocytes, and an increase in the density of proliferating endotheliocytes in these vessels, which was associated with increased VEGF concentration. Administration of the control drug piracetam had no endothelium-protective effect.

COVID-19 leads to disruption of the blood coagulation system, to thrombosis, hypercoagulability, as a result, to an increased risk of strokes and heart attacks. During COVID-19, endothelial dysfunction develops associated with NO deficiency with decrease in the level of SH compounds. Tiazotic acid (Thiotriazoline) has immunomodulatory, anti-inflammatory, antioxidant, anti-ischemic, cardio- and endothelioprotective, antiplatelet, hepatoprotective activity. Our studies conducted at the National Research Medical Center “University Clinic of ZSMU” with the participation of 57 patients (from 30 to 65 years old) with post-COVID syndrome, who received thiotriazol with basic therapy in either tablets (200 mg each) or suppositories Dalmaxin (0.2 g each) twice a day for 30 days. Inclusion criteria for the study were a positive PCR test for COVID-19; if the PCR test was negative, then the presence of IgM COVID-19 or IgG COVID-19 (with radiologically confirmed pneumonia). The following biochemical parameters were studied: C-reactive protein - by immunoturbodimetric method; D-dimer - by enzyme immunoassay; ferritin - by immunochemiluminescent method; endothelial NO-synthase (eNOS) - by ELISA method; alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total bilirubin; international normalized ratio (INR) and determination of platelet aggregation. During treatment with thiotriazoline, significant increase in the eNOS content was recorded, which indicated the presence of endothelioprotective activity of the drug. Thiotriazoline significantly reduced the level of D-dimer in the blood of patients, and also led to the normalization of INR. The established effects testified to the presence of antiplatelet and fibrinolytic action of thiotriazoline and its ability to reduce the risks of heart attacks and strokes in post-COVID syndrome. Thiotriazoline led to an objective improvement in general clinical parameters in patients with post-COVID syndrome, complaints of palpitations disappeared, blood pressure stabilized.

Aim. A comprehensive study on the antimicrobial properties of new 1,2,4-triazole derivatives using the tools of in silico and in vitro studies. Materials and methods. Computer search techniques were used to find a compound with a strong antibacterial activity; in silico molecular docking (receptors for class A (PDB id: 1n9b) and class A SHV-1 (PDB id: 2zd8) beta-lactamase) and in vitro studies on 16 types of microorganisms. Then, the in silico analyzed compounds were tested in vitro for antimicrobial activity. After preparing solutions of different concentrations, the culture growth was measured on a zonal scale for detecting sizes of microbial growth inhibition zones after 24 hours (Antibiotic Zone Scale-C, model RW297, India) and a TpsDig2 software (2016, F. James Rohlf). Statistical analysis of the study results was carried out using the Statistica 13 software (StatSoft Inc., USA). Results. From the results of molecular docking, a strong binding affinity to class A enzymes has been found in compounds 2, 7, so they could be effective in the treatment of infection caused by K. pneumoniae. The ascending order of the predicted binding affinity through the calculated score for TEM and SHV enzymes was as follows: compound 4 < compound 3 < compound 1 < compound 7 < compound 2. According to our results, the studied chemical compounds 1–4, 7 inhibited the growth of many microbial species of the Enterobacteriaceae, Morganellaceae, Pseudomonadaceae, Enterococcaceae, Staphylococcaceae and Bacillaceae families. Conclusions. For the first time, studies on the complex inhibitory effect of chemical compounds 1–4, 7 were conducted using 16 bacterial strains. Evident antibacterial effects of the studied compounds have been established: compound 1 against 13, compound 2 – 9, compound 3 – 10, compound 4 – 7, compound 7 – 10 out of 16 tested polyresistant bacterial strains.

In the complex treatment of chronic heart failure (CHF) β-adrenoblockers (carvedilol, nebivolol, bisoprolol, metoprolol) are used, which due to their pharmacological properties increase the survival rate of patients, improve cardio- and haemodynamic parameters, metabolism. However, modern realities in medicine require creation of new more effective and safe β-adrenoblockers. In this regard, the potential drug Hypertirl is of interest. The aim was to evaluate the cardioprotective effect of 1-(b-phenylethyl)-4-amino-1,2,4-triazolium bromide (Hypertril) on cardiac electrical activity and autonomic regulation of heart rhythm in a model of CHF in comparison with β-adrenoblockers of different generations (Nebivolol, Carvedilol, Bisoprolol, Metoprolol). Materials and methods: Chronic heart failure was induced by 14-day administration of doxorubicin in a cumulative dose of 15 mg/kg to white mongrel rats weighing 190–220g (total 85). The investigated drugs were administered after doxorubicin course for 30 days: Hypertril at an experimentally substantiated dose of 3.5 mg/kg, Metoprolol succinate 15 mg/kg, Nebivolol 10 mg/kg, Carvedilol 50 mg/kg, Bisoprolol 10 mg/kg. At the end of drug administration under thiopental anaesthesia (40 mg/kg), electrocardiogram (ECG) and autonomic regulation of heart rhythm (ARHR) were analysed using a computer analyser CardioCom-2000plus (KAI-Medica, Ukraine). The results of the study were calculated using a standard statistical package “STATISTICA for Windows 6.0” (StatSoftInc., №AXXR712D833214FAN5), “SPSS 16.0” and “Microsoft Office Excell 2003”. Results and discussion: Hypertril administration resulted in a negative chronotropic effect, normalisation of atrial (P) and ventricular (R) spike amplitude, ST segment inversion below isoline, increased amplitude of ventricular myocardial repolarisation T. Myocardial repolarisation spike were observed, as well as normalised the duration of atrial (P) and ventricular depolarisation phase (QRS complex) to the intact value and restored the duration of electrical diastole (TR interval). Hypertril reduced systolic and diastolic myocardial dysfunction in animals with CHF. Hypertril restored autonomic mechanisms of heart rhythm regulation and balanced activity of sympathetic and parasympathetic parts of autonomic nervous system in the control of cardiac function. Conclusion: The obtained results demonstrated the undoubted advantage of the new original molecule (Hypertril) over basic β-adrenoblockers (Metoprolol, Nebivolol, Carvedilol and Bisoprolol) and experimentally justify further in-depth study to create on its basis a drug for the treatment of CHF.