An insufficient perfusion of the brain tissue can cause a decrease in cognitive functions, and long-term ischemia also leads to emotional and motor disorders. At the same time, check-up of the state of the cerebral blood flow is an important aspect of monitoring the progression of many pathological conditions. The amino acid glycine has been widely used in neurological practice for over 30 years, which helps improve hemodynamic characteristics and metabolic processes in the brain tissue.

The aim of the work was to analyze the effect of a sublingual administration of glycine on the cerebral blood flow velocity in practically healthy subjects using transcranial Doppler (TCD) sonography.

Material and methods. The pilot randomized controlled study included 20 healthy subjects aged 25 to 65 years, equally divided into 2 groups, one of which took glycine sublingually at a dose of 300 mg/day for 30 days, and the second group was a control group and did not receive the drug. In the first group, a load testing was carried out with 1000 mg of glycine, and in the control group – with 1000 mg of placebo. All the subjects underwent an assessment of the blood flow in the extracranial and intracranial vessels using standard protocols of TCD.

Results. In Group I, after a month of glycine intake, the peak systolic (by 11.9 cm/s) and average maximum (by 6.3 cm/s) velocities in the left middle cerebral artery (MCA) increased significantly (p <0.01), while in the right MCA there was an increase in the peak systolic (by 9.3 cm/s), and diastolic (by 2.8 cm/s) and average maximum (by 5.8 cm/s) velocities. In turn, in the control group, there was no significant increase in velocity. During the load testing with glycine / placebo, the relative increase in the peak systolic velocity in the MCA in the main group was 7.6% [1.2; 10.9], in control group was 1.5% [-3.6; 5.5] (p=0.03).

Conclusion. Glycine intake for 30 days contributes to a reliable improvement in cerebral hemodynamics in healthy individuals, such as an increase in the linear blood flow velocity in the MCA. At the same time, a single dose of 1000 mg of glycine leads to an increase in the peak systolic and average maximum intracranial blood flow velocities up to 10%.

The aim of the work was to identify the presence and strength of association between the use of anti-inflammatory genetically engineered biological drugs and the development of secondary bacterial infections in COVID-19 patients.

Materials and methods. We used 1 296 medical records of patients hospitalized in the infectious diseases hospital of the Volgograd region with a diagnosis of COVID-19 in September 2020, March and September 2021, March, September and November 2022, have been analyzed. A matched case-control study was performed with 275 pairs identical in gender, age (±2 years), the severity of the lung damage according to computed tomography / chest X-ray, a COVID-19 outcome, concomitant carbohydrate metabolism disorders. Patients with the signs of the secondary bacterial infection (leukocytes ≥12×109/l, procalcitonin ≥0.5 ng/ml and/or viral-bacterial pneumonia according to the autopsy data) were presented as a case. The “control” group included patients without signs of any bacterial infection (leukocytes <11×109/l, procalcitonin <0.5 ng/ml, no description of clinical signs of the bacterial infection in the medical record during the hospitalization). The prescription of 6 anti-inflammatory genetically engineered biological drugs (tocilizumab, sarilumab, olokizumab, levilimab, netakimab, secukinumab) has been studied for these groups.

Results. The use of any anti-inflammatory genetically engineered biological drug was associated with the development of the secondary bacterial infection signs (OR=2.41; 95% CI: from 1.54 to 3.77; p <0.001): for levilimab, the OR was 3.44 (95% CI: from 1.64 to 7.23; p <0.001), for tocilizumab – OR=1.75 (95% CI: from 0.73 to 4.17; p=0.201), for olokizumab – OR=1.28 (95% CI: from 0.81 to 2.03; p=0.292).

Conclusion. Among the three drugs (tocilizumab, olokizumab, levilimab), the Russian biosimilar olokizumab, a monoclonal antibody to circulating interleukin-6, has shown itself as the safest drug in terms of preventing the secondary bacterial infection signs. Further studies of developing bacterial complications risk in COVID-19 patients receiving anti-inflammatory genetically engineered biological drugs are required.

Mitochondrial-targeted antioxidant SkQ1 demonstrates a high efficiency in animal models and potentially can be used for minimizing postoperative complications in an on-pump open-heart surgery.

The aim of study was to the assessment of preservation degree and changes in the isolated rat heart characterized by prolonged cardioplegic ischemia, under the condition of donation of different SkQ1concentrations.

Material and methods. Isolated Langendorff-perfused rat hearts of Wistar line (n=15) were included in the presented study; the effectiveness of 12 ng/mL and 120 ng/mL of SkQ1 was analyzed. A biochemical analysis (superoxide dismutase 2 [SOD2], malondialdehyde [MDA], Troponin-I, heart-type fatty acid-binding protein [H-FABP]), a histological analysis of tissues (hematoxylin and eosin staining), scanning electron microscopy using backscattered electrons and immunofluorescence staining for cytochrome C and cytochrome P450 reductase were performed. The quantitative data were processed using GraphPad Prism 7 (Graph Pad Software, USA).

Results. The optimal myocardial preservation was discovered while using 12 ng/mL of SkQ1: the lowest concentrations of MDA (49.5 [41.1; 58.9] mmol/g), Troponin-I (22.3 [20.3; 23.9] pg/mL) and H-FABP (0.8 [0.6; 16.0] ng/mL) were associated with extensive areas of tissues with preserved transverse dark and light bands and a moderate interstitial edema. Moreover, non-deformed mitochondria were located mainly between the contractile fibers. Cytochrome C immunofluorescence was distributed locally, the luminescence intensity was 40% higher compared to the control group (p <0.0001). Increasing SkQ1 concentration to 120 ng/mL contributed to the aggravation of oxidative stress: MDA (63.8 [62.5; 83.0] mmol/g) and H-FABP (12.8 [4.1; 15.3] ng/mL) concentrations were closer to the control group values. Myocardial tissue in this group was characterized by a pronounced edema and a fragmentation of muscle fibers. There were signs of cardiomyocyte decay, myocytolysis and an intracellular edema. Cytochrome C was distributed evenly.

Conclusion. 12 ng/mL of SkQ1 demonstrates pronounced antioxidant effects in the ischemic myocardium leading to a higher degree preservation of the heart muscle compared to 120 ng/mL of SkQ1 that was associated with an aggravated oxidative stress and structural changes of the tissue.

One of the new classes of drugs for weight loss in overweight and obesity, the safety and efficacy of which have been proven in large-scale studies, are glucagon-like peptide-1 receptor agonists (GLP-1 agonists). Separately, it is worth highlighting the main representative from the GLP-1 agonists class, semaglutide. At a dose of 2.4 mg, this drug demonstrated clinically significant results in terms of the body weight reduction and improvement of cardiometabolic health.

The aim of the work was to evaluate pharmacokinetic parameters, bioequivalence, safety, tolerability and immunogenicity of the Velgia® (WRYC12301) at doses of 0.25 mg (0.68 mg/ml) and 2.4 mg (3.2 mg/mL) in comparison with the reference drug Wegovy® (Novo Nordisk A/S, Denmark) at the doses of 0.25 mg (0.68 mg/mL) and 2.4 mg (3.2 mg/mL).

Materials and methods. The study was conducted between March and June 2024. The volunteers (n=60) were randomised into 4 groups (n=15 in each) in a 1:1 ratio to study the semaglutide dosages of 0.25 mg/dose (0.68 mg/mL) in Groups 1, 2 and 2.4 mg/dose (3.2 mg/mL) in Groups 3, 4. The study drug and the reference drug were injected subcutaneously into the anterior abdominal wall. Pharmacokinetic parameters, bioequivalence, safety, tolerability and immunogenicity of semaglutide (solution for subcutaneous administration, JSC Biochemik, Russia) were studied. Some parameters regulating the quality of the active pharmaceutical substance semaglutide, were determined.

Results. The obtained 90% confidence intervals (CIs) for the ratio of C_max and AUC_(0-t) values of the study and reference drugs (Groups 1, 2) at a dose of 0.25 mg (0, 68 mg/mL) were 85.19–114.36% for C_max and 81.35–112.60% for AUC_(0-t), respectively, while for Groups 3, 4, at a dose of 2.4 mg (3.2 mg/mL), C_max was 83.18–111.3% and AUC_(0-t) was 91.70–120.89%, respectively. The obtained 90% CI lies within the established limits, which confirms the bioequivalence of the study and reference drugs. All adverse events registered during the study were of mild severity. According to the results of the immunogenicity parameters analysis, no antibodies to semaglutide were detected in the serum of volunteers.

Conclusion. In the course of the study, the bioequivalence of the study and reference drugs was confirmed. A high safety profile and absence of immunogenicity were demonstrated for the Russian drug Velgia® (WRYC12301, semaglutide, solution for a subcutaneous administration, JSC Biochemik, Russia) in comparison with the reference drug (semaglutide, solution for a subcutaneous administration, Novo Nordisk A/S, Denmark) in doses of 0.25 mg/dose (0.68 mg/mL) and 2.4 mg/dose (3.2 mg/mL).

The aim of the work was to study the relationship of the minimum steady-state concentration of angiotensin II receptor blockers with polymorphic markers of CYP2C9 (Arg144Cys), CYP2C9 (Ile359Leu), AGTR1 (A1166C), AGT (Met235Thr, C4072T), ACE (I/D), CYP11B2 (C-344T) genes and the office blood pressure (BP) indices.

Materials and methods. The study included 179 patients of the Moscow region with newly diagnosed hypertension of stages 1–2, among whom there were 141 (78.8%) women and 38 (21.2%) men aged from 32 to 69 years (mean age — 58.2±6.4, median age — 60 (57–63 years), who had been randomized into treatment groups with valsartan and irbesartan in the form of mono- or combination therapy with hydrochlorothiazide. After 3 weeks of pharmacotherapy, polymorphic markers CYP2C9 (Arg144Cys), CYP2C9 (Ile359Leu), AGTR1 (A1166C), AGT (Met235Thr, C4072T), ACE (I/D), CYP11B2 (C-344T) were genotyped and the minimum steady-state concentrations of irbesartan and valsartan were determined. The office BP measurements were performed on each visit.

Results. The carriers of alleles *2 and *3 of the CYP2C9 gene, the genotype T/T of the AGT gene, the genotype I/I of the ACE I/D polymorphism achieved higher values of the minimum steady-state concentration of irbesartan after 3 weeks of pharmacotherapy. Homozygotes A/A for the genetic polymorphism of the AGTR1 gene (A1166C), homozygotes D/D for the ACE I/D polymorphism reached significantly higher values of the minimum-steady concentration of valsartan after 3 weeks of pharmacotherapy. In the patients taking irbesartan, a more pronounced decrease in the office systolic (SBP) and diastolic (DBP) BP was detected with an increase in the concentration for every 100 ng/mL after 3 weeks of therapy. Any association of the indicators with the valsartan concentration was found out.

Conclusion. The effects of irbesartan and valsartan indicate a maximum modulation of pharmacodynamic effects during 3 weeks of pharmacotherapy, followed by a consolidation in the therapeutic range and a stop in the increasing the effectiveness with a further increase in the steady-state concentration, which can be used to predict therapy, personalize it, a better control and a high safety profile.