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Background. According to the hypothesis of the study, the therapeutic efficacy of measures to treat hypoxic (ischemic) emergencies can be significantly increased by using an artificial gas mixture with normal or increased oxygen content and a high content of argon, being bioactive despite its chemical inertness.Objective. To experimentally evaluate the antihypoxic effects of argon on the example of acute massive blood loss in experimental animals.Methods. The study was carried out on 72 albino male gray rats with a baseline body weight of 220–250 g. The experiments were performed at the premises of the Konstantinov St. Petersburg Nuclear Physics Institute of the Kurchatov Institute and the Smorodintsev Research Institute of Influenza (Russia). Prior to the experiment, the animals were quarantined for 2 weeks in the vivariums of the performing organizations. Acute massive blood loss in rats was formed by taking blood (12 ± 1% of body weight on average) using syringe method by transcutaneous cardiac puncture. Rats were randomized into 3 groups (24 individuals each) depending on the gaseous medium where the animal was placed after artificial blood loss. Composition of the applied gaseous medium in the comparison groups: medium No. 1 — oxygen 21% vol.; argon — 30% vol.; nitrogen — the rest; medium No. 2 — oxygen 21% vol.; argon — the rest; medium No. 3 (control) — air. The postoperative follow-up (post-conditioning) for 8 hours involved assessing and recording the following indicators: survival/lethality rates; recovery rates (anesthesia recovery, somatic mobilization); clinical symptoms of possible intoxication with the gas mixture during inhalation exposure. The surviving animals were then monitored for 4 days to evaluate their health and behavioral performance. Upon completing the observation period, the animals were euthanized.Results. After artificially-induced blood loss, all the non-survivors died within 1.5–8 hours after the operation. In group 1 (post-conditioning in medium No. 1), the lethality of laboratory animals amounted to 4 individuals out of 24 (16%); in group 2 (post-conditioning in medium No. 2) — 2 individuals out of 24 (8%). In the control group, the lethality rate was significantly higher — 10 animals out of 24 (42%). The surviving animals demonstrated no lethality or morbidity within 4 days after the exposure. Analysis of outcomes between experimental groups and controls revealed that the significance of differences in the lethality index between group 1 and control (by Fisher’s two-sided criterion) comprised p = 0.06; between group 2 and control — p = 0.017. When the statistical “power” of the experimental group was increased (by combining samples 1 and 2), the significance of differences in outcomes in this group compared to the control accounted for p < 0.001.Conclusion. The conducted studies confirmed the hypothesis about the pronounced antihypoxic effect of argon, which significantly increased the survival rate of experimental animals after massive artificially-induced blood loss.

Аim: to study the role of serum and ultrasonometric markers in the early diagnosis of malignant transformation of periductal fibrosis of the liver during the formation of cholangiocarcinoma against the background of chronic invasion of Opisthorchis felineus, in the population of endemic regions.Methods. A comprehensive one-stage comparative study was conducted in a case-control design, using the assessment of biochemical parameters (lactate, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, glucose, direct and indirect bilirubin, high-density lipoproteins and low-density lipoproteins, triglycerides, urea and total protein), immunological parameters (transforming growth factor beta) and tumor markers (CA 19-9, СYFRA 21-1) in blood serum samples obtained from patients with O. felineus infection, with and without periductal fibrosis, O. felineus-infected patients with cholangiocarcinoma and representatives of control groups. During the analytical stage, the relationship between the structural features of the liver ac- cording to the results of ultrasound examination (presence of opisthorchiasis-associated periductal fibrosis), clinical parameters, parasitological study data (infection intensity), and changes in biochemical, immunological parameters and tumor markers in patients against the background of O. felineus infection was assessed. Statistical analysis was performed using the R programming language (version 3.6.1).Results. Evaluation of the relationship between the presence of ultrasound signs of stage 1–2 opisthorchiasis-associated periductal fibrosis and changes in serum levels of the biochemical, immunologic parameters and oncomarkers in patients with O. felineus infection demonstrated that the levels of alkaline phosphatase, conjugated bilirubin, AST, glucose and CA 19-9 oncomarker were significantly higher in the serum of patients in the group with cholangio-carcinoma and opisthorchiasis (p < 0.01).Conclusion. The first pilot data on the relationship between ultrasonometric signs of periductal liver fibrosis and the increase of CA 19-9 oncomarker as well as biochemical parameters (alkaline phosphatase, direct bilirubin, aspartate aminotransferase, glucose), which can be used for early diagnosis of malignant transformation of periductal liver fibrosis with the formation of cholangiocarcinoma in O. felineus-infected population in endemic regions, were obtained.

Heart failure is one of the most important medical and social problems. Despite recent successes in the treatment of this disease, which have been achieved with guideline-recommended medical treatment, some patients become insensitive to the interventions. Refractoriness to treatment recommended by the guidelines means that patients cannot hope for symptom relief or prolongation of life. These individuals develop the phase of advanced heart failure and have the worst survival rates compared to other stages of chronic heart failure. In the absence of contraindications, heart transplantation is indicated for this group of patients. In the recent years, organ transplantation has been legalized and the work of cadaver donation institutions has been organized in Ukraine. These changes helped to significantly increase the annual number of heart transplantations in the country. The aim of the work is to systematize current knowledge about end-stage heart failure, to provide methods to timely diagnose advanced heart failure and indications for referral for heart transplantation. At least every tenth patient with heart failure may deteriorate to the advanced stage. The article details clinical trajectories of patients with heart failure, and a particular emphasis has been given to refractory patients in accordance with present guidelines and recommendations. The main pathophysiological links and corresponding clinical manifestations of advanced heart failure have been outlined. The problems of life expectancy prognosing and possible predictors of refractoriness to the treatment recommended by the guidelines have been discussed. Current diagnostic criteria for advanced heart failure have been specified, including physical, laboratory and imaging methods of examination. The principles of differential diagnosis, especially between symptomatic and advanced heart failure, have been considered. Triggers for referring patients to a heart transplant center have been detailed. Current guidelines for heart transplantation related to advanced heart failure have been given. Conclusions. Advanced heart failure is the progression of heart failure due to refractoriness to treatment. Diagnostic criteria for advanced heart failure have been developed relatively recently. This diagnosis requires an utmost understanding of pathophysiology and skills to examine cardiac patients using modern tools. Due to the extremely unfavorable prognosis, diagnosis of advanced heart failure is an absolute indication for referral to a heart transplant center.

INTRODUCTION. The risk of liver damage correlates with the severity of COVID-19. However, a growing number of studies have shown an association between liver function impairment and combinations of medicinal products used to treat COVID-19.AIM. The study aimed to analyse the annual consumption of medicinal products associated with a high risk of drug-induced liver injury (DILI) used as part of combination therapy in COVID-19 patients and to review a number of medication administration records in order to develop measures to prevent DILI.MATERIALS AND METHODS. The study used the ATC/DDD methodology to study consumption data for 2020, 2021, and 2022 and analysed a sample of 1250 inpatient medical records and medication administration records of COVID-19 patients treated in a Volgograd region hospital converted into a COVID-19 care centre. For genetically engineered biologicals and cyclophosphamide, which were lacking DDDs, the authors calculated the volume of consumption using the average dose per treatment course. The authors identified medicines capable of causing clinically apparent liver damage (according to the LiverTox database and Russian clinical practice guidelines) and/or elevated liver enzymes in ≥1% of patients (according to safety reports).RESULTS. The study found that 28% of the medicinal products used in combination for inpatient treatment of COVID-19 were associated with a high risk of DILI. In 2020, 2021, and 2022, the total consumption of medicinal products associated with a high risk of DILI was 342.3, 425.3, and 402.3 DDDs per 100 bed days, and the total consumption of genetically engineered biologicals (administered as a single dose) and cyclophosphamide was 3.5, 16.9, and 29.7 average course doses per 100 patients, respectively. According to the selective analysis of medical records, 19.8% (247/1250) reported concomitant use of 5 or more medicinal products associated with a high risk of DILI, which increased the risk of adverse drug interactions leading to DILI. In 2022, the most prescribed medicinal products with a high risk of DILI were omeprazole (188.7 DDDs per 100 bed days), non-steroidal anti-inflammatory drugs and paracetamol (54.4 DDDs per 100 bed days), atorvastatin (46.2 DDDs per 100 bed days), levofloxacin (26.4 DDDs per 100 bed days), ceftriaxone (20.5 DDDs per 100 bed days), favipiravir (17.3 DDDs per 100 bed days), and genetically engineered biologicals (24.0 DDDs per 100 bed days).CONCLUSIONS. To reduce the risk of DILI in COVID-19 patients admitted to infectious disease units, including the risk of DILI due to drug interactions, it is necessary to limit the use of hepatotoxic antibacterial agents, proton-pump inhibitors, and non-steroidal anti-inflammatory drugs, or consider alternative medicinal products with a lower risk of hepatotoxicity.

Relevance. Hemorrhagic fever with renal syndrome (HFRS) is leading among natural focal human diseases in Russia, the causative agents of which - orthohantaviruses - belong to the order Bunyavirales, family Hantaviridae. More than 98% of HFRS cases in Russia are caused by the Puumala virus. It is a serious zoonosis for which there is still no specific treatment. The WHO has not approved a vaccine. The aim of this study was to investigate the effect of formaldehyde, β-propiolactone, hydrogen peroxide, ultraviolet rays, gamma irradiation and thermal inactivation on the immunogenic activity of inactivated vaccine preparations against HFRS Materials and methods. To achieve this aim, experimental vaccine preparations based on the PUU-TKD/VERO strain of Puumala virus were prepared and inactivated using the methods described above. The time intervals required for complete inactivation of the virus were determined, and the effects of the inactivators on viral RNA and immunogenic activity of the vaccine preparations were evaluated in BALB/c mouse and Syrian hamster models. Results. According to our results, vaccine preparations inactivated by different chemical and physical methods, which differ significantly in the mechanism of the mechanism of interaction with the virus, show no significant differences in immunogenic activity, except for thermal inactivation. Conclusion. A certain advantage of β-propiolactone is the short virus inactivation time, its complete degradation into non-toxic compounds within a few hours, and the reduction of total protein content after sterilization filtration, which is probably due to less aggregation of virus particles and cellular proteins

The year 2023 saw a challenging epizootiological and epidemiological situation regarding highly pathogenic avian influenza. The virus affected 150 bird species and dozens of mammal species. More than 650 outbreaks were reported in poultry across 29 countries, resulting in the death or destruction of approximately 19 million specimens. There was a high incidence of the influenza among wild birds (approximately 3,000 outbreaks in 65 countries) and mammals (more than 16,000 cases). The majority of outbreaks in wild birds, poultry and mammals were caused by influenza A(H5N1) clade 2.3.4.4b viruses. Many countries in Europe, Asia, Africa, North and South America experienced the outbreaks throughout the year. For the first time, a polar bear death from A(H5N1) virus was documented. Moreover, molecular markers of virus adaptation to mammals were found in PB2 proteins of 50 % of influenza A(H5N1) viruses that caused the death of animals. During the year 2023, human infections with highly pathogenic avian influenza A(H5N1) viruses were reported in Cambodia, Chile, China, and the UK. In addition, human infections with A(H3N8), A(H5N6), A(H9N2) and A(H10N5) viruses were reported in China. In Russia in 2023, outbreaks among wild birds and poultry were registered in 25 regions, as well as an outbreak among fur seals in the Sakhalin Region. The stated outbreaks were caused by highly virulent influenza A(H5N1) clade 2.3.4.4b. Hemagglutinin sequences of all Russian viruses analyzed in this study in 2023 were genetically close to the WHO candidate vaccine strains A/Astrakhan/3212/2020 (H5N8), A/chicken/ Ghana/AVL-763_21VIR7050-39/2021 (H5N1) and A/American Wigeon/South Carolina/22-000345-001/2021 (H5N1). All studied A(H5N1) viruses were antigenically similar to the A/Astrakhan/3212/2020 vaccine strain.

Background. The study of drug availability for patients with chronic obstructive pulmonary disease (COPD) represents one of the priority tasks in the organization of effective counteraction to COPD in the Russian Federation.Objective: to assess drug prices, affordability, and availability for COPD patients.Material and methods. The analysis of drug availability for COPD patients was carried out according to the methodology of the World Health Organization and Health Action International (WHO/HAI). Bronchodilator and anti-inflammatory therapy of originator brands and lowestpriced generics was evaluated. The consumption volume of the studied drugs was also analyzed using the ATC/DDD (Anatomical Therapeutic Chemical classification / defined daily dose) pharmacoepidemiologic methodology over a three-year period (from 2020 to 2022), taking into account their share of total DDD (drug utilization analysis, DU90%).Results. According to the results of DU90% analysis, the most purchased drugs for bronchodilator and anti-inflammatory therapy for all the years under study were drugs from the groups of short-acting bronchodilators (salbutamol, fenoterol, ipratropium bromide + fenoterol) and inhaled glucocorticoids (budesonide, beclomethasone). The obtained data were confirmed by the results of the physical availability study. Thus, the highest percentage of physical availability was for short-acting inhaled beta-2-agonists (SABA) (salbutamol). Analysis of drug affordability also revealed a tendential superiority of SABA and short-acting anticholinergics over baseline bronchodilators and antiinflammatory drugs.Conclusion. Low affordability of the main drugs of baseline therapy contributes to the burden of COPD and necessitates improvement of drug supply mechanisms for individuals, especially those with low material income, which in the long term will significantly reduce the costs of the healthcare system for the treatment of these patients by decreasing the severity and frequency of exacerbations.

The aim of the work was to compare the effects of ademethionine, acetylcysteine and taurine on the zoosocial behavior of rats in a post-intoxicated state after an acute ethanol poisoning.Materials and methods. The study was conducted on male rats of the Wistar line. The post-intoxication state was modeled by a single injection of ethanol (3 g/kg, intraperitoneally). 30 min after awakening, the animals were injected with a physiological solution, acetylcysteine (1 g/kg), ademetionine (100 mg/kg) or taurine (40 mg/kg). A zoosocial interaction test was performed 30 min after the administration.Results. Among the behavioral indicators investigated, the following were validated: the number of acts of freezing, their duration, the number of acts of sniffing in front, the number of acts of avoidance and the number of vertical stances without support (p 0.05). Alcoholization reduced the number of vertical stances by 65% (p

Background. The pattern and duration of the grape plant growing season depends both on biological characteristics of plants and the environmental conditions of their habitat. Studying meteorological conditions and their effect on the growing phases of grape cultivars of different origin is important to optimize the deployment of these cultivars.Materials and methods. Eight introduced and domestic grape cultivars served as the research material. Phenological observations were carried out according to M. A. Lazarevsky, ANOVA was performed according to B. A. Dospekhov, the dependence of the duration of growing phases on weather conditions was assessed using pairwise correlations, and Student’s t-test was applied to determine statistical significance. Meteorological data were taken from the agrometeorological bulletins for Krasnodar Territory. The studies were conducted in the period from 2018 to 2021 under the agroecological conditions of the Black Sea viticulture zone.Results. Specific features of the temperature regime for grape growing phases in the environments of the Black Sea viticulture zone were ascertained. Indicators of heat supply and duration of the growing season according to Lazarevsky were used to identify the studied cultivars as early (‘Podarok Dmitriya’, ‘Reliance’, ‘Brigantina’ and ‘Anapskiy Ranniy’), medium (‘Concord’ and ‘Venus’), mid-late (‘Prikubanskiy’), and late (‘Kyoho’) genotypes. The sum of active temperatures required for the growing season of early cultivars was 2522–2603°C, for medium ones 2755–2760°C, for mid-late ones 2835°C, and for late ones 2970°C. According to the international classification, ‘Podarok Dmitriya’, ‘Reliance’, ‘Brigantina’ and ‘Anapskiy Ranniy’ are early, ‘Concord’, ‘Venus’ and ‘Prikubanskiy’ are mid-early, and ‘Kyoho’ is medium-ripening. All cultivars had a close direct relationship between the duration of their growing phases and the sum of air temperatures above +10°C.

The intensive implementation of variable-frequency drive machines and installations in underground mining processes necessitates addressing several issues, with a primary focus on ensuring the quality of electric power. Elevating the energy resource of mining machines and enhancing the energy efficiency of mining operations requires maintaining the rated indicators of electric power quality in mine power distribution systems. Achieving this involves assessing the level and composition of higher harmonic components in voltage and current within power circuits equipped with variable-frequency drives (VFD). Key objectives encompass the development of a simulation model based on the equivalent diagram of the power distribution system substitution with a scraper conveyor VFD to scrutinize the spectral composition of higher harmonic components in the power circuits of the mine power distribution system (MPDS). Additionally, the study involves analyzing the impact of harmonic filters (HFs), reactors, and sine filters on the quality of electric power in the VFD system of a scraper conveyor. Further analysis extends to the spectral composition of higher harmonic components in circuits related to insulation leakage and metering circuits of the residual-current device. Practical recommendations for improving electric power quality in the VFD system of a scraper conveyor are then developed based on the research findings. The established model of a variable-frequency drive system for scraper conveyors facilitates the assessment of the effectiveness of electric power quality improvement measures. The harmonic composition of voltage and current in the mine power distribution system is determined under maximum distortion conditions and in the presence of HFs, reactors, and sine filters. Research methods are chosen to unveil the spectral composition of voltage and current in symmetrical and single-phase modes of insulation leakage, as well as in metering circuits of residual-current devices (RCDs). It is noted that the harmonic composition of leakage voltage and current is primarily influenced by the parameters of the output voltage modulated by the autonomous frequency converter inverter. Considering the high level of harmonic components in voltage and current, adjustments to RCD settings, capacitive current compensator, and the protective shunting unit are recommended for electrical safety. The study emphasizes the importance of scientifically substantiating the rated indicators of higher harmonic components for leakage circuits and further exploring the physiological effects of higher current harmonics on the human body. The feasibility of installing a harmonic filter (HF) directly on the low-voltage supply section of a scraper conveyor should be technically justified. Interestingly, the presence of HFs, reactors, and sine filters does not significantly impact the harmonic composition or the magnitudes of coefficients of the harmonic components in the phase voltage of the system concerning ground and leakage currents through insulation. However, higher harmonic components induced in leakage current circuits may pose a potential hazard, leading to a violation of magnetic compatibility and posing risks in case of contact with live parts of electrical equipment.

The European SocIn March 2024, the manual “Clinical and pharmacological characteristics of biotechnological drugs: from classifications to adverse events” was published under general ed. Kolbin A. S. This textbook discusses biotechnological drugs from the perspective of clinical pharmacology. Basic definitions and classifications are given. Pharmacodynamics, phar­macokinetics and adverse events are reviewed. Examples of interactions between biotechnological drugs and small molecules are presented. A separate chapter examines the interchangeability of biological products — from basic terms and definitions of the concept of biosimilarity to regulatory aspects. The Appendix provides examples of clinical applications of therapeutic proteins. The manual is intended for students, residents, graduate students, clinical pharmacologists and physicians of other specialties.

The aim of the work was to conduct an analysis of the current state and current trends in the approval of drugs, as well as some aspects of the methodology for their development based on biological molecules and registration.Materials and methods. The material for the analysis was taken from the abstract databases of PubMed, Google Scholar and e-library.ru. The search was carried out using publications for the period from 2008 to 2023, the keywords were as follows: “biologicals”, “new drug approval”, “drug authorization”, “drug development”, “biosimilar”, taking into account various spellings.Results. Over the past 15 years, scientists have been observing revolutionary trends and processes in the field of the drug development, especially biopharmaceuticals. Significant advances have been made in gene, immune and cell therapies, resulting in the approval of such drugs more than doubling over the past ten years. The development of biological drugs includes the identification and testing of molecular targets and requires a deep understanding of the structure and functioning of the polypeptides involved in the development of the effect. The features of these active pharmaceutical substances are a high molecular weight, a complex three-dimensional structure and a high immunogenic potential. Preclinical and clinical studies of biologics have unique challenges. Selecting appropriate animal species, understanding the immunogenicity, and assessing pharmacodynamics and toxicological properties require a multilevel, detailed approach. The article discusses the regulatory framework under which these drugs are registered, summarizing the guidelines provided by international organizations such as the International Council for Harmonization and various national agencies.Conclusion. The analysis highlights the current advances and prospects in the development of biologics, highlighting their key role in future transformations in the treatment of rare diseases and oncology, approaching the era of personalized medicine. Monitoring the development directions and technological approaches, as well as the commitment to global methodological and regulatory aspects can become a catalyst in the development of the Russian pharmacology.

Modern approaches to the treatment of type 2 diabetes mellitus (T2DM) are aimed not only at glycemic control, but also at reducing cardiovascular risks. The increasing prevalence of the disease and the need for effective treatment options highlight the importance of glucagon-like peptide-1 (GLP-1) receptor agonists in the pharmacotherapy structure.The aim of the work was to review the literature regarding the physiology of GLP-1 and the therapeutic potential and development trends of its agonists.Materials and methods. The search for the review materials was carried out using the abstract databases of PubMed, Google Scholar and e-Library. The search was carried out for publications from 2000 to 2023, using the following keywords: “GLP-1”; “GLP-1R agonists”; “GIP”; “exenatide”; “liraglutide”; “dulaglutide”; “semaglutide”; “lixisenatide”; “albiglutide”; “taspoglutide” taking into account various spellings.Results. The interaction of almost all food components with enteroendocrine cells of the intestine leads to the secretion of incretins (primarily GLP-1) into the blood, triggering a complex of physiological reactions aimed primarily at the rapid utilization of incoming glucose (regulation of insulin and glucagon secretion), as well as the central regulation of dietary behavior (slowing gastric emptying and the formation of a feeling of satiety). A wide distribution of the GLP-1 receptor in various tissues and organs, its connection with intracellular signaling cascades aimed at launching energy-consuming remodeling (recovery) processes in endothelial cells, heart, neurons, beta cells, etc., is the basis for a wide range of pleiotropic effects of GLP-1 unrelated to its hypoglycemic effect. The discovery of synthetic GLP-1 receptor agonists with a long period of action has made it possible not only to therapeutically influence various parts of carbohydrate metabolism disorders, but also to increase the functional reserves of the target diabetes organs, reducing the risk of developing complications of the disease. Incretin-like drugs are well tolerated, with nausea being the most common side effect. The factors limiting a wider use of the drugs include their high cost and the preferred form of a subcutaneous solution. The current research is focused on the development of long-acting, oral, dual and triple agonists, fixed-dose combinations, and small molecule drugs.Conclusion. GLP-1 receptor agonists are a class of effective and safe drugs for the treatment of diabetes and obesity, which is rapidly developing in the most advanced areas of pharmacy. A further development of this group and the solution of the identified problems will open up new opportunities for the treatment of diabetes and its complications.

Therapeutic drug monitoring (TDM) is used to increase the individualization of pharmacotherapy, especially in patient groups with a high interindividual variability in pharmacokinetic (PK) parameters. One of these groups of patients is newborn children, for whom drug therapy, especially drugs with a narrow therapeutic range, causes a few difficulties or cannot be used in principle.The aim of the work was to develop and validate quantitative HPLC-MS/MS methods for the determination of vancomycin in “dried blood spot” samples using new protocols and comparison of the results obtained with the results in plasma samples using standard sample preparation methods.Materials and methods. To prepare stock and standard solutions of vancomycin and norvancomycin as an internal standard, dry portions of the corresponding certified standards of vancomycin (Servier, France) and norvancomycin (Augsburg, Germany, purity grade >95.0%) were used. A chromatographic separation of the components was carried out on a Poroshell 120 C18 column (4.6×50 mm, 2.7 µm). When developing conditions for a mass spectrometric detection of the desired substances using the multiple reaction monitoring (MRM) method, precursor ions and their corresponding product ions were determined.Results. A quantitative HPLC-MS/MS method for the determination of vancomycin in «dried blood spot» samples was developed and validated. A comparison was made between vancomycin concentrations in «dried blood spot» samples and plasma samples. Moreover, more than 95% of the calculated average concentrations are within the limits of d-2s and d+2s, which correspond to the values of –10.2 and 12.2. That confirms the suitability of the developed method for the analysis of patient samples.Conclusion. The results obtained make it possible for us to recommend the “dried blood spot” method for therapeutic monitoring of vancomycin, additional studies of PK in this group of patients with subsequent use of this drug in newborns and pediatric patients.