Vol 24, No 4 (2025)

Objective. To study the acute toxicity of antigens of Klebsiella pneumoniae, Escherichia coli, Proteus vulgaris , Staphylococcus aureus following intraperitoneal administration in mice, and to investigate the toxicity of their complex variants after a single subcutaneous injection and six repeated intranasal administrations in mice and rats. Methods. The toxicity of individual antigens was studied in SHK mice after intraperitoneal injection at doses ranging from 50 to 200 μg. The acute toxicity of an antigen complex, with and without the addition of a copolymer of 2-methyl-5-vinylpyridine and N-vinylpyrrolidone hydrochloride (used as an additional immunostimulant), was also investigated. Variants of the antigen complexes were administered to CBA mice and Wistar rats either subcutaneously once at doses of 150-300 mg/kg (mice) and 90-150 mg/kg (rats), or intranasally six times at doses of 120-180 mg/kg. Clinical observations and body weight monitoring were performed daily for 14 days. Results. The study of acute toxicity of S. aureus, E. coli, P. vulgaris , and K. pneumoniae antigens showed no toxic effects, except for reversible body weight loss. Intranasal administration of the complexes at the tested doses did not cause intoxication or mortality. Subcutaneous administration resulted in reversible dose-dependent changes (reduced activity, tremor, changes in coat condition), most pronounced at 300 mg/kg, but without lethal outcomes. No sex-related differences or differences between complex variants were observed. LD₅₀ could not be determined due to the absence of mortality; the maximum doses tested (300 mg/kg subcutaneously and 180 mg/kg intranasally) exceeded the estimated therapeutic dose for humans by more than 100,000 and 60,000 times, respectively. Conclusion. The results of acute toxicity studies of individual antigens and antigen complex variants at the highest feasible doses confirm their safety, supporting further preclinical evaluation of the antigen complexes, including studies of immunotropic activity, allergenicity, subchronic, and reproductive toxicity

Objective. To study the historical stages of the formation of scientific thought, the final result of which was the «Bazett formula». Methods. Analysis and synthesis of scientific and patent literature was carried out using the information-search system PubMed, ScholarGoogle, electronic library systems IPR SMART (IPR BOOKS), foreign electronic resources of publishing houses Springer Nature and Elsevier. Results. The article examines the history of the origin of the Bazett formula. The focus is on the concept of the corrected QT (QTc) interval from the moment of the emergence of the idea of a mathematical model for the relationship between the heart cycle and the seat to the publication of the now widely accepted calculation formula of QTc, named Henry K. Bazett. Based on the results of the study, it was found that the so-called «Bazett' formula» was proposed not by Henry K. Bazett, as it is considered in the general scientific circles, but by other authors. The idea of calculating the corrected interval QT and its designation as QTc belongs to Taran L.M. and Szilagyi N. In their publication of 1947, the authors justified the proposed method of investigation. Conclusion. The presented historical study of the origin of «the formula of Bazett» showed that when mentioning the formula it would be more correct to refer to the publication Taran L.M. & Szilagyi N., 1947, while the authors themselves, the proposers of the concept QTc and its calculation method pointed in their work to the publication Bazett H.C.

Objective. To highlight the epidemiology and main features of the choice of antimicrobial therapy for enterococcal infective endocarditis. Methods. Based on the available sources of information, data on the recommended principles of managing patients with enterococcal infective endocarditis are presented. Results. Along with the increasing role of Staphylococcus aureus in infective endocarditis, there is also a tendency to increase the isolation of Enterococcus spp. The probable reason for this is the high frequency of pathology of the abdominal cavity and the small pelvis, and as a result, the fact that Enterococcus spp. is currently one of the main causes of outpatient and nosocomial cases of bacteremia. Conclusions. The significance of the infective endocarditis problem is confirmed by the lack of a downward trend in the incidence and mortality rates of this pathology. Improving the management of patients with infective endocarditis is impossible without knowledge of the diagnostic and therapeutic features, a clear understanding of the etiological structure, and consideration of global and local data on antimicrobial therapy.

Objective. To study the socio-psychological aspects of the quality of life of families with children with ASD receiving early intervention services, to identify correlations between the duration of early intervention services provided to children and their families and the quality of life of families. Methods. This study is an analysis of the socio-psychological aspects of the quality of life of families with children with autism spectrum disorders receiving early intervention services. The study included a questionnaire to collect information on the socio-demographic characteristics of families, their financial situation, housing conditions and experience of receiving early intervention services. The quality of life of families was assessed using the FEIQoL and BCFQoL scales. The DASS-21 scale was used to identify affective disorders, and parent-child relationships were analyzed using the Schaeffer and Bell method. The dynamics of quality of life was monitored depending on the duration of early intervention services, and correlations between the duration of support and the quality of life of families were studied. Results. The impact of early intervention services on the quality of life of families with children with autism spectrum disorders, the psychological state of mothers, and parent-child relationships is demonstrated. Conclusion. Early detection of communication problems, the choice of a competent strategy for teaching a child with autism spectrum disorders, timely correction of existing disorders and effective interaction with the family within the framework of early intervention ensure successful adaptation and socialization of the child.

Objective. To study the peculiarities of rheumatologic changes in the musculoskeletal system in patients with both types of diabetes mellitus. Methods. The staff of the Department of Therapy of the Pediatric and Dental Faculties of Smolensk State Medical University presented a review of 18 Russian and 25 foreign reference sources over the past 20 years, concerned with various changes in the musculoskeletal system in patients with both types of diabetes mellitus. Results. The authors presented the pathogenetic stages of osteoarticular and muscular lesions, the clinical features of pathological conditions of the musculoskeletal system in patients with type 1 and type 2 diabetes mellitus, modern diagnostic methods and treatment principles for each nosological form of osteoarthropathy. Conclusions. Analyzing the available Russian and foreign sources, the authors emphasize the indisputable presence of so-called osteopenia, or a decrease in bone mineral density in patients with diabetes mellitus. Secondary osteoporosis caused by diabetes mellitus may lead to long-term bone pains and impaired physical activity in patients, increasing the risk of their disabilities. The influence of type 1 and type 2 diabetes mellitus on an increased risk of bone fractures is emphasized by all authors. However, the mechanisms of this influence are different. Type 1 diabetes mellitus is characterized by insulinopenia, which affects the anabolic tone of bones and leads to a decrease in their mineral density. Most patients with type 2 diabetes have normal or high bone mineral density, and their risk of fractures is due to microscopic changes in bone structure and the humoral environment that stimulates the activity of osteoclasts that destroy bone tissue. This review is important in doctors’ practice of various specialties and focuses their attention not only on glycemic control in patients with diabetes mellitus, but also on the condition of their musculoskeletal system.

Objective. To study and analyze current aspects of using a remote monitoring (RM) system for implanted antiarrhythmic devices (IAD) in patients with life-threatening cardiac rhythm and conduction disorders, as well as to identify factors that hinder the widespread implementation of this essential element of digitalization in healthcare. Methods. Collection, analysis, and systematization of available information on the possibilities and prospects for implementing continuous RM in patients with IAD. Results. The review article presents a systematic analysis of modern RM technologies and organizational aspects of implementing this process. Detailed information on the legal and ethical requirements for the implementation of RM is provided, and issues of cybersecurity of personal data, including information on the health status of patients, are outlined. Progress in the technology of creating universal implantable antiarrhythmic devices (IAD) has contributed to a steady increase in the number of patients - carriers of these devices around the world. Due to the steady increase in the number of patients with IAD, it is relevant to widely use the RM strategy, which allows for timely detection of disorders/complications of these devices and prompt response to clinical consequences. Conclusion. The implementation of the automatic contactless RM technology demonstrated high efficiency and safety of remote control of the IAD, and also improved patient compliance to comply with RM recommendations. Furthermore, economic incentives for reimbursement would likely allow the use of RM in all patients with IAD, as discussed in clinical guidelines.

Objective. Studying the epidemiology of vertebrobasilar insufficiency and strokes in the vertebrobasilar basin is important for understanding the problem and developing effective measures for prevention and treatment. Methods. Of particular interest is the epidemiological situation with vertebrobasilar insufficiency and strokes in the vertebrobasilar basin in the countries of Central Asia (Kazakhstan, Kyrgyzstan, Uzbekistan, Tajikistan, Turkmenistan). Data for this region remain fragmentary, but the available information indicates the high relevance of the problem. Results. According to the data provided in the world literature, about 20-25% of all ischemic strokes and transient ischemic attacks occur in the vertebrobasilar basin. Pathology of the posterior circulation of the brain ranks second in frequency of occurrence after lesions of the carotid basin. Overall, Central Asia has historically high rates of stroke incidence and mortality, with stroke being the second leading cause of cardiovascular mortality (167 per 100,000 population), behind only ischemic heart disease (416 per 100,000 population). Central Asia is predicted to have a high incidence of diabetes mellitus and prediabetes, as well as arterial hypertension. Conclusion. Epidemiological data indicate a significant prevalence of vertebrobasilar insufficiency and strokes in the vertebrobasilar basin worldwide. At the same time, in Central Asian countries, an increase in the burden of these conditions is predicted, which is associated with a high prevalence of risk factors, primarily diabetes mellitus and arterial hypertension.

Objective. Technological justification for the creation and standardization of a syrup based on the herb of Melissa officinalis L. Methods. The object of the study was the herb of Melissa officinalis . The collection was carried out in July 2024 (Alekseevka village, Samara region). At the first stage of the technological process, a water-alcohol extraction was obtained from the herb of Melissa officinalis L. Further, by the method of modified maceration using 40% ethyl alcohol as an extractant, alcohol extraction is obtained, in the ratio of «raw material-extractant» - 1:5. Sucrose and sorbitol were used as the basis for the preparation of syrup samples. The analyzed preparations were prepared according to standard technology for sugar syrup - 64% by weight, for sorbitol syrup - 50% by weight. Sucrose and sorbitol are moistened with a small amount of water, the remaining water is added and dissolved when heated. To substantiate the optimal content of phenylpropanoids in the studied preparations (in terms of rosmarinic acid), 2%, 3%, and 5% tinctures in 40% ethyl alcohol were added to previously prepared syrups. The syrup samples were analyzed by spectrophotometry (UV spectroscopy). Results. As a result of the conducted studies, it was determined that the content of the amount of phenylpropanoids (in terms of rosmarinic acid) in sugar syrup and sorbitol syrup with the addition of 5% tincture in 40% ethyl alcohol based on the herb of Melissa officinalis is 0,05±0,002% and 0,045±0,002%, respectively. The error of a single determination with a 95% confidence probability is ±5,11%. Conclusion. The results obtained in the course of the study substantiating the technology and standardization of syrup based on Melissa officinalis herb can serve as the basis for the creation and introduction of drugs based on Melissa officinalis herb into medical and pharmaceutical practice. In our opinion, from the point of view of the content of active substances in the syrup, it is advisable in terms of concentration to ad 5% tincture in 40% ethyl alcohol based on the herb of Melissa officinalis .

Objective. The purpose of the study is to study the characteristics of the accumulation of flavonoid compounds in the medicinal plant raw materials of the synanthropic flora of the Voronezh region. Methods. Methodology. Raw materials from characteristic representatives of the synanthropic flora of the Voronezh region - highlander bird grass ( Polygonum aviculare L.), motherwort five-lobed grass ( Leonurus quinquelobatus Gilib.), Containing flavonoids as one of the main groups of active substances, were used as study objects. Raw materials were harvested in natural thickets of the studied plants in protected (control) territories, in agrocenoses and urbocenoses with different nature and internality of economic activity. Determination of the amount of flavonoids in the raw material was carried out according to compendial methods. Results. The accumulation of flavonoid compounds in plant samples was characterized by significant variability depending on the place of harvesting. In a number of grass samples collected under conditions of a number of urbocenoses, an induction of flavonoid accumulation was noted compared to samples of control territories, which can be explained by the activation under anthropogenic load of a key enzyme of flavonoid biosynthesis. Samples prepared under conditions of significant anthropogenic impact (mainly near highways and industrial enterprises) are characterized by a relatively reduced content of flavonoid compounds, which is probably due to excessive environmental pollution, which goes beyond the endurance of species and causes inhibition of enzyme systems in them. Conclusion. Based on the correlation analysis, both the inducing effect on the accumulation of polyphenolic compounds of heavy metals, which is characteristic mainly for their relatively low concentrations, and the inhibitory effect of high concentrations of elements were confirmed.

Objective. Development of a technique for the quantitative determination of the amount of phenylpropanoids in verbena herb by spectrophotometry. Methods. The crushed and dried herb of verbena officinalis was used as the object of the study. Direct spectrophotometric method was used to quantify phenylpropanoids in extracts from verbena raw materials. Results. The analytical absorption maxima of the studied compounds, 330 nm, which corresponds to the maximum absorption of chlorogenic acid, were determined by direct spectrophotometry in alcohol extracts from verbena grass. Optimal conditions for the extraction of phenylpropanoids from the raw materials of this plant are substantiated (extractant - ethyl alcohol 70%; the ratio of "raw material - extractant" is 1:100; extraction time is 60 minutes; the degree of grinding of raw materials is 1.0 mm). Conclusion. A method for the total content of phenylpropanoids in verbena officinalis herb, in terms of chlorogenic acid, has been developed and validated. The standard for the total content of phenylpropanoids in terms of chlorogenic acid is at least 3.4%.

Objective. Development of a technique for the quantitative determination of the amount of flavonoids in the herb of Astragalus onobrychis L. Methods. The objects of the study were samples of the herb Astragalus esparcet ( Astragalus onobrychis L.) produced by LLC Herbs of the Mountain Crimea, Russia, Crimea, 2024; LLC Russian Roots, Russia, Rostov region, 2024. The electronic spectra were measured using a UNICO 2800 UV spectrophotometer, a Vilitek VBS ultrasonic bath, a LAB-TB-6/Sh water bath, and an IR-1 LT rotary evaporator. Results. The article reflects the proposed method for quantifying the amount of flavonoids in the raw materials of Astragalus esparcet ( Astragalus onobrychis L.), based on the extraction of biologically active substances by vacuum boiling, at a temperature of 60°C, for 10 minutes. This approach makes it possible to achieve the maximum yield of flavonoids - up to 2,95% in terms of hyperoside. The technique is characterized by simplicity of execution and minimal time costs, which makes it effective for the analysis of plant raw materials. Conclusions. During the development of a method for the quantitative determination of the active components of the herb astragalus esparcet, optimal extraction conditions for raw materials were determined, which contributes to a significant increase in the yield of flavonoids with minimal time spent on research.

Objective. Theoretical substantiation of the use of biologically active substances of the roots of Polygonatum officinale All. as substances of plant origin in the pharmaceutical industry. Methods. Scientific and theoretical analysis of domestic and foreign literature on the chemical composition and pharmacological activity of biologically active substances of the roots of Polygonatum officinale All. Results. The composition of the roots of Polygonatum officinale All. includes biologically active substances belonging to the groups of flavonoids, polysaccharides and saponins, which can be further used as substances of plant origin. The value of compounds of the roots of Polygonatum officinale All. is determined by their pharmacological action, which consists in the manifestation of antioxidant, immunomodulatory, antibacterial, antidiabetic, probiotic and antiviral properties. Given the wide range of chemical composition of the roots of of Polygonatum officinale All., it seems advisable to develop a technology for isolating these substances from the proposed plant raw materials as phytosubstantiations for the production of medicines. Conclusion. The result of a preliminary scientific and theoretical analysis of the specialized literature is the justification of the relevance of the use of the identified chemical compounds of the roots of Polygonatum officinale for their further experimental study: the development of technology for isolation from plant raw materials, the study of the technological properties of the obtained substance in order to select the dosage form and draft regulatory documentation.

Objective. To conduct a comparative assessment of foreign clinical guidelines (the United Kingdom of Great Britain and Northern Ireland, the Federal Republic of Germany (FRG), the People's Republic of China (PRC), the Republic of Korea, the United States of America (USA), the European Society of Vascular Surgeons) from the position of determining the place of DVT of the lower extremities in the nosological structure of venous thromboembolic diseases, as well as existing approaches to the diagnosis and treatment of DVT of the lower extremities. Methods. Content analysis of current foreign clinical guidelines containing tactics for the diagnosis and treatment of DVT of the lower extremities. Results. According to clinical guidelines of different countries, there is variability in the nosological structure of venous thromboembolic diseases and the place of DVT of the lower extremities in it. In the guidelines of the United Kingdom of Great Britain and Northern Ireland, the Federal Republic of Germany (FRG), the People's Republic of China, the USA and the European Society of Vascular Surgeons, DVT is considered within the framework of general guidelines for venous thromboembolic diseases. In the structure of the guidelines of the European Society of Vascular Surgeons, Germany and the PRC, LV DVT is considered as an independent nosology. There are clinical guidelines of the Republic of Korea for the diagnosis and treatment of LV DVT from 2016, the updated guidelines released in 2021 combined all venous thromboembolic diseases (VTED), however, information on the diagnosis of LV DVT is not presented in full and there is no information on the cancellation of the 2016 recommendations. All the recommendations reviewed demonstrate unity in the diagnosis of DVT, including LV DVT. The diagnostic algorithm includes an assessment of clinical probability using the Wells scale and laboratory confirmation by determining the D-dimer level. Instrumental diagnostics is based on ultrasound examination (US) of the lower extremities, if necessary, computed tomography (CT) or magnetic resonance imaging (MRI) - diagnostics. Conclusion. Among all the clinical recommendations studied in this work, LV DVT is considered as an independent nosology only in the clinical recommendations of the European Society of Vascular Surgeons, the Federal Republic of Germany, the People's Republic of China and the Republic of Korea (2016). At the same time, separate clinical recommendations devoted to LV DVT are only the recommendations of the Republic of Korea from 2016. According to clinical recommendations, the treatment of DVT, including LV DVT, in all countries is complex and includes the simultaneous use of pharmacotherapy, compression therapy, and, if necessary, surgical methods. Anticoagulant therapy is unanimously recognized as the main method of treatment. However, depending on the clinical features and national recommendations, additional methods are used. Such treatment is aimed at saving the patient's life, improving his quality of life and the prognosis of treatment.

Objective. Conducting an analysis of consumer properties of vitamin drugs presented on the Russian pharmaceutical market. Methods. The object of the study was vitamin drugs registered in the state register of medicines of Russia. The study used sociological, pharmacoeconomic research methods. Results. To determine the priority characteristics of vitamin drugs among consumers, a survey was conducted among the population, in which 162 respondents took part. It was revealed that the majority of the population (72.8%) buys vitamins in pharmacies in the form of drugs (36.4). It was found that 215 vitamin drugs are registered on the Russian pharmaceutical market, which correspond to 23 international non-proprietary names, mainly produced in Russia. The breadth coefficient (1) indicates the presence of almost all pharmacotherapeutic groups on the market of the Oryol region, and the depth coefficient (0.57) indicates an incomplete assortment, taking into account the various dosage forms and manufacturers. The population prefers vitamins in the form of capsules (29.7%), tablets (20.4%), film-coated tablets (19.1%) in the price category from 100 to 500 rubles. The majority of respondents consider the composition (61.1%), pharmacological action (49.4%), price (44.4%), and method of administration (42.5%) to be the most important consumer properties of vitamins, but many attach considerable importance to the color of the dosage form, taste, packaging, and labeling. Conclusion. The identified consumer preferences contribute to improving the quality characteristics of vitamin drugs and increasing their competitiveness in the pharmaceutical market.