Vestnik of the Smolensk State Medical Academy
ISSN (print): 2225-6016, ISSN (online): 3033-5906 Founder: Smolensk State Medical University Editor-in-Chief: Kozlov Roman S., Corresponding Member of the RAS, Doctor of Sc., Full Professor Frequency / Assess: 4 issues per year / Open Included in: Higher Attestation Commission list, RISC
HYPOXIC TRACE OF STRESS: HIF-1Α, ERYTHROPOIETIN, AND CORTISOL AS KEY MARKERS OF POST-TRAUMATIC STRESS DISORDER IN COMBATANTS
Objective. The study aimed to perform a comparative analysis of pathophysiological profiles based on levels of hypoxia-inducible factor-1α, erythropoietin, and cortisol in combatants with different consequences of combat trauma.Methods. A comparative cross-sectional study included three groups: combatants with verified post-traumatic stress disorder (PTSD) (n=15), combatants with traumatic amputations without PTSD (n=45), and those who survived critical conditions in the intensive care unit (ICU) (n=20). Biomarker levels were determined by enzyme-linked immunosorbent assay. Statistical analysis included non-parametric tests with Bonferroni correction and ROC analysis.Results. Specific biomarker patterns were identified. The PTSD group was characterized by a significant increase in hypoxia-inducible factor-1α (median 79.07 pg/mL) and decreased cortisol (198.24 nMol/L) compared to the amputation and ICU groups (p<0.001). The erythropoietin level was highest in the ICU group (76.20 pg/mL), reflecting systemic hypoxia. A combined model of hypoxia-inducible factor-1α and cortisol demonstrated high diagnostic accuracy for PTSD verification (AUC=0.88, specificity 84.4%).Conclusion. The combination of hypoxia-inducible factor-1α and cortisol forms a specific biomarker profile reflecting PTSD pathophysiology associated with the phenomenon of cellular hypoxia and dysregulation of the hypothalamic-pituitary-adrenal axis. The proposed diagnostic algorithm based on these markers is promising for the objective diagnosis and risk stratification of PTSD development.
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PRECLINICAL ACUTE TOXICITY STUDY OF ANTIGENS FROM OPPORTUNISTIC BACTERIA AND THEIR COMPLEXES
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
SOME ASPECTS OF THE PRESENCE OF PLASTIC PARTICLES IN DIFFERENT TISSUES OF THE HUMAN BODY
Objective. To show the features of the distribution and impact of plastic particles in different tissues of the human body from a morphological point of view. Methodology. Full-text versions of literary sources on the spread and impact of plastics on humans were used. These sources were obtained from international and domestic databases (PubMed, Web of Science, Scopus, eLibrary, RSCI) through a systematic online search. The electronic search for information was conducted on works published in peer-reviewed journals from April 1995 to April 2025. Different search queries were used, including combinations of keywords. To ensure methodological rigor, a structured selection process was employed, which included predefined exclusion and inclusion criteria. The articles identified during the search process were evaluated for inclusion in the review using a two-step selection process. These steps were: 1) selecting articles that met the inclusion criteria, and 2) conducting a conceptual, process, situational, logical, and systematic analysis, as well as summarizing the data obtained from the selected articles. The studies were carefully selected based on their relevance. Priority was given to original research. The information obtained was organized to create a review. Results. These data show that plastic is currently found in most human organs and tissues. The impact of plastic on cells and biological environments can lead to oxidative stress, changes in metabolism and biochemical parameters, slowing down cell proliferation, tissue degeneration, abnormal development and organ dysfunction, inflammation, impaired immune system functions and altered gene function. However, despite a large number of studies on deciphering the mechanisms of plastic exposure, they are mainly obtained through experiments on animals and cell cultures. Conclusions. Given the ubiquity of plastic particles in nature, humans will be exposed to it for a very long time, even if they completely abandon polymers. Although there is evidence of the adverse effects of plastic in the human body, the detailed mechanisms of biotransformation and exposure of different types of plastic in certain organs and tissues remain unclear, both in the short and long term. The connection of plastic with many existing diseases (for example, atherosclerosis), as well as its possible involvement in the emergence of new nosological forms of diseases, is also unclear. Given the progress in the study of plastic pathology, new nosological forms of diseases may be described in the near future. They are likely to be grouped into a group of diseases called, for example, "plastiosis." Perhaps what this group has in common is not only the detection of plastic particles, but also the presence of productive inflammation with the presence of predominantly monocytic cells with the outcome of sclerosis. However, this requires further extensive research.
BAZETT'S FORMULA. BACKGROUND OF THE ISSUE
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.
PROBLEMS AND PROSPECTS OF XEROSTOMIA PHARMACOTHERAPY
Objective. Improving drug therapy for patients with xerostomia. Methods. Collection, systematization, and analysis of literature data on the effectiveness and safety of pharmacological treatment of xerostomia. Results. A comparative analysis of the therapeutic efficacy and safety of using various medications in the objective and subjective forms of xerostomia has been conducted. The results of clinical studies on the effectiveness of pharmacological correction of xerostomia, which is achieved by activating the secretory function of the salivary glands with parasympathomimetics and irritants with reflex and local effects, are discussed. The advantages and disadvantages of replacement therapy (artificial saliva preparations) are considered. The rationale for choosing medications for various forms of xerostomia, taking into account their pharmacodynamics, is proposed. The article analyzes the prospects for pharmacotherapy of xerostomia, depending on the etiopathogenesis and age-related changes in the structure of the salivary glands. Conclusion. A comprehensive approach is preferred in the treatment of xerostomia. The priority is to eliminate the cause (if possible). Patients with preserved salivary gland function may be prescribed stimulants for the production of their own saliva. Systemic secretion stimulants (parasympathomimetics) are the most effective, but their use is associated with the development of a number of adverse effects. In case of xerostomia caused by the death of acinar tissue of the salivary glands (Sjögren's syndrome, sarcoidosis, radiation therapy), optimal means of replacement therapy (saliva substitutes) are selected. If necessary, other (auxiliary) means can be prescribed to prevent and treat complications of xerostomia (anesthetics, antiseptics, anti-inflammatory, antifungal, antioxidants and antihypoxants).
FEATURES OF CHOICE OF THE ANTIMICROBIAL THERAPY OF INFECTIVE ENDOCARDITIS
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.
CONTENT OF CIRCULATING ANNEXIN V MONONUCLEAR CELLS AT DIFFERENT STAGES OF APOPTOSIS IN VACCINATED AGAINST INFLUENZA AND PNEUMOCOCCAL INFECTION DURING EXACERBATION OF CHRONIC MUCOPURULENT BRONCHITIS
Objective. To study the content of circulating annexin V mononuclear cells at different stages of apoptosis in individuals vaccinated against influenza and pneumococcal infection during exacerbation of chronic mucopurulent bronchitis and in somatically healthy individuals. Methods. Observation of 92 patients with exacerbation of chronic mucopurulent bronchitis and 30 somatically healthy individuals was carried out. Mononuclei in apoptosis were investigated using the reagent set «Annexin-V-FITC/7AAD» («Beckman Coulter», USA). The specific weight of intact cells, cells at early and late stages of apoptosis and necrotic cells was determined. Statistical analysis was performed using SPSS program, version 26.0 (USA). Results. On the basis of the conducted research we found out that at exacerbation of chronic mucopurulent bronchitis there is an intensification of apoptotic processes, which is manifested by an increase in the content of both the total number of apoptotic cells and cells at each stage of apoptosis. Conclusion. We found no intersex differences in any of the apoptosis indicators in both observation groups. We also found no statistically significant differences depending on influenza and pneumococcal vaccination both among patients with chronic mucopurulent bronchitis and in the control group.
SOCIAL AND PSYCHOLOGICAL ASPECTS OF THE QUALITY OF LIFE OF FAMILIES WITH CHILDREN WITH AUTISM SPECTRUM DISORDERS RECEIVING EARLY INTERVENTION SERVICES
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.
REGIONAL EXPERIENCE IN OUTPATIENT MEDICAL REHABILITATION OF OBESE CHILDREN
Objective. Analysis of the practical experience of medical rehabilitation of children with constitutionally exogenous obesity in outpatient settings using the example of the Department of medical rehabilitation of the Children's City Polyclinic No. 1 in Astrakhan. Methods. A retrospective analysis of extracts from medical records of 76 patients under the age of 18 who received course rehabilitation treatment in the Department of medical rehabilitation of the Children's City Polyclinic No. 1 in Astrakhan from 2022 to 2024 was carried out. A content analysis of medical documentation data (f026u, f003u) and patient interviews were conducted. Results. The analysis of the structure of treated patients with diseases of the endocrine system was carried out. The proportion of obese patients in the structure of pathology with which children underwent outpatient medical rehabilitation at stage III in the Department of medical Rehabilitation of the Children's City Polyclinic No. 1 in Astrakhan 1 from 2022 to 2024 has been established. Conclusion. Outpatient rehabilitation of obese children has shown its effectiveness with a comprehensive approach to treatment. The results of the study demonstrated positive dynamics in terms of body weight and body mass index. The limitations of the program have shown that it is impossible to radically change the physical fitness of children in a short period of time.
RHEUMATOLOGIC CHANGES OF THE MUSCULOSKELETAL SYSTEM IN PATIENTS WITH DIABETES MELLITUS
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.
DIET THERAPY AND APPROACHES TO ASSESSING THE NUTRITIONAL STATUS OF PATIENTS WITH INFLAMMATORY BOWEL DISEASES
Objective. To analyze the methods of assessing the nutritional status of patients with IBD and to study modern approaches to diet therapy in this category of patients. Methods. A review of domestic and foreign literature devoted to the methods of determining malnutrition and diet therapy in patients with IBD was carried out. Results. This article describes methods for determining malnutrition, such as body mass index (BMI), waist circumference and skinfold thickness, universal malnutrition screening tool, subjective global assessment of malnutrition, dual-energy X-ray absorptiometry, bioimpedance analysis, computed tomography with skeletal muscle index, lumbar muscle density using average Hounsfield units. It also discusses nutritional interventions used for nutritional support of patients with IBD, including rehydration, enteral, parenteral nutrition and dietary therapy, which differ in patients in the acute stage and in remission. The role of diets relevant in the complex therapy of IBD is discussed: low/high fiber, FODMAP, specific carbohydrate, CD-Treat, CDED, AIP (autoimmune), gluten-free, lactose-free and Mediterranean. Conclusions. These data reflecting the current state of the problem highlight the importance of timely diagnosis of patients with IBD and nutritional deficiency condition. When used correctly, nutritional therapy becomes a valuable component of treatment, helping to achieve therapeutic goals in the treatment of IBD, prevent complications, and improve key aspects such as growth, bone health, and overall well-being.
POSSIBILITIES AND BARRIERS TO USING A REMOTE MONITORING SYSTEM IN PATIENTS WITH IMPLANTED ANTIARRHYTHMIC DEVICES
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.
ANTIBIOTIC-INDUCED NEUROLOGICAL SYNDROMES: PROBLEMS AND SOLUTIONS
Objective. Systematization of data on the clinical manifestations of neurotoxic effects caused by antibiotics, the study of their underlying mechanisms and the development of ways to solve this problem. Methods. A systematic review of scientific literature using PubMed, Scopus, and Cochrane Library databases. Results. Neurotoxic side effects can manifest in various neurological forms, including encephalopathy, seizures, myoclonus, and peripheral neuropathy. Patients with previous diseases of the central nervous system (CNS), renal insufficiency, and the elderly are at increased risk of developing these complications. Treatment usually includes withdrawal of the causative antibiotic and symptomatic therapy. Conclusion. The review systematizes data on the neurotoxicity of aminoglycosides, cephalosporins, penicillins, carbapenems, tetracyclines, trimethoprim/sulfamethoxazole, macrolides, quinolones, oxazolidinones, streptogramines, polymyxins, metronidazole, and other antibiotics that cause encephalopathy, seizures, myoclonus, peripheral neuropathy, and other neurological disorders. Patients with central nervous system and kidney diseases, the elderly, and the seriously ill are particularly at risk. Withdrawal of the antibiotic, symptomatic treatment and dose adjustment are recommended. An algorithm of actions is proposed: dose adjustment, drug withdrawal, anticonvulsant therapy and, if necessary, hemodialysis. The optimization of antibiotic therapy requires an integrated approach, including the participation of clinical pharmacologists, the rational administration of antibiotics based on microbiological data, and the implementation of protocols. A promising direction is the use of chatbots based on artificial intelligence.
SOME EPIDEMIOLOGICAL ASPECTS OF VERTEBROBASILAR INSUFFICIENCY
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.
A CLINICAL CASE OF NEUROENDOCRINE CELLULAR HYPERPLASIA OF INFANTS IN CHILDREN OF THE FIRST YEAR OF LIFE
Objective. To present a clinical case of neuroendocrine cellular hyperplasia of infants in children of the first year of life. Methods. Patients aged 7 months and 11 months with interstitial lung disease: neuroendocrine pulmonary hyperplasia of infants were under observation. physical, clinical, laboratory, instrumental examination and treatment were performed. the analysis of domestic and foreign literature sources on the nosology of neuroendocrine cellular hyperplasia in infants has been carried out. a comparative analysis of the clinical manifestations, diagnosis and treatment in other previously described cases of this problem has been carried out. Results. Neuroendocrine cellular hyperplasia of infants refers to rare lung diseases, which is manifested by respiratory failure syndrome. the etiology of necgm is currently not fully established. we present cases of observation of children in the first year of life with necgm, data from objective examination, diagnostic search and treatment. Conclusions. The clinical cases presented by us demonstrate the problem of late diagnosis in the detection of necgm pathology in children of the first year of life, due to the similarity of symptoms with other respiratory diseases, the rare occurrence and little studied disease. early detection of necgm in children, adequate treatment and prevention of complications are important.
APPLICATION OF ULTRAVIOLET ABSORPTION SPECTROSCOPY IN THE STUDY OF PROPRANOLOL AND TISOL GEL IN A TWO-COMPONENT MIXTURE
Objective. Development of a method for quantitative analysis of the components of a new propranolol ointment using the pharmacopoeial method of spectrophotometry in the ultraviolet region. Methods. Active pharmaceutical substance Propranololi hydrochloridum (CAS № 318-98-9, PM.2.1.0170), tisol gel (СPM-42-3157-06), citrate buffer solutions (CBS) (pH = 2-4) and ointment “Propranozol” on hydrophilic base with the concentration of propranolol 10.0 % were used in the experimental work. The study was carried out by multi-wavelength spectrophotometry in the near ultraviolet range using the device SF-2000. Statistical processing of the experimental results was carried out by methods of variation statistics, regression analysis in the application program package STATISTICA 10.0 and Microsoft Office Excel 2016. Results. Absorption spectra of propranolol hydrochloride and tisol gel were recorded in citrate buffer solutions (pH range from 2 to 4), analytical wavelengths were determined, and the stability of tisol gel for quantitative analysis was studied. It was found that citrate solutions of tisol gel with pH = 3 and pH = 4 were stable for 60 minutes under the tested conditions. Based on the spectral characteristics of both components, the optimum analytical conditions were selected using CBL of pH = 4 and analytical wavelengths of 245 nm and 292 nm for tisol gel and propranolol, respectively. The contents of propranolol and tisol gel in the same suspension were determined by the system of Firordt equations. Using the developed methodology, 0.9976-1.0427 g of propranolol and 8.7892-9.2489 g of tisol gel were found in the ointment samples. Conclusions. Based on the results of the study the optimal conditions for spectrophotometric analysis were selected, on the basis of which a method for quantitative determination of propranolol and tisol in their combined presence in 10 % propranolol ointment with a relative error of the mean result not exceeding ± 1.91 % was developed and proposed in accordance with pharmacopoeial requirements. The method demonstrates a sufficient level of accuracy, which makes it suitable for quality control of the drug product.
SUBSTANTIATION OF THE TECHNOLOGY OF CREATION AND STANDARDIZATION OF A SYRUP BASED ON THE HERB MELISSA OFFICINALIS (MELISSA OFFICINALIS L.)
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 .
JUSTIFICATION OF THE DOSAGE FOR CHILDREN OF THE MEDICINAL PRODUCT «MEROPENEM, POWDER FOR PREPARATION OF SOLUTION FOR INTRAVENOUS INJECTION»
Objective. To substantiate the optimal dosage of the pediatric dosage form of the drug “Meropenem, powder for the preparation of a solution for intravenous administration.” Methods. The objects were instructions for the medical use of the drug “Meropenem, powder for the preparation of a solution for intravenous administration” (n=19), posted on the website of the State Register of Medicines and data from the State Register of Maximum Selling Prices. The study used the methods of content analysis, copying, and situation modeling, economic calculations. Results. Assessment of the completeness of use of meropenem dosage form packaging in a pediatric hospital allowed us to substantiate the optimal dosage of the pediatric dosage form. Analysis of a simulated situation showed that material losses would amount to 80 and 90% of the weight of the drug in the vial, respectively. Financial losses for a course of treatment with meropenem at a dosage of 500 mg amounted to 4,956 rubles, when using a dosage of 1000 mg - 11,151 rubles. In a similar situation, when a child was prescribed a single dose of meropenem 200 mg three times a day for 7 days, material losses were about 60 or 80% of the drug per bottle. Financial losses for the course of treatment with meropenem amounted to 3,717 and 9,912 rubles. respectively. Children's dosage forms “Meropenem, powder for the preparation of solution for intravenous administration” in dosages of 100 and 200 mg are proposed for industrial production. The use of pediatric dosages of meropenem in a pediatric hospital would reduce material losses of drugs. Conclusion. Based on the calculation of material and financial losses, the feasibility of producing the drug “Meropenem, powder for the preparation of solution for intravenous administration” in pediatric dosages of 100 and 200 mg was justified.
PECULIARITIES OF FLAVONOID COMPOUNDS ACCUMULATION IN MEDICINAL PLANT RAW MATERIALS OF SYNANTHROPIC FLORA OF CENTRAL CHERNOZEM
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.
STUDING THE TECHNOLOGICAL CHARACTERISTICS AND NUMERICAL INDICATORS OF THE RAW MATERIALS OF PERSEA AMERICANA MILL
Objective. Determination of technological characteristics and selected numerical indicators of avocado seeds for the development of a draft pharmacopoeial monograph. Methods. Avocado seeds (Perseae americanae semina) were used as an object, which were previously freed from the endocarp, crushed and dried. The numerical parameters (raw material grinding and content of foreign impurities, total ash in plant material and insoluble in 10% hydrochloric acid solution, humidity, content of extractive substances in raw material) and technological characteristics (fractional composition, degree of flowability, bulk density, volumetric characteristics of specific, volume and bulk masses, porosity, voidage and free volume of the raw material layer, as well as the absorption coefficient of the extractant) were determined with three samples of each batch of avocado raw materials. It was determined by the methods described in the 15th edition of the State Pharmacopoeia of the Russian Federation and the scientific literature. Results. The humidity of the dry crushed avocado seeds is less than 7%. That doesn’t exceed the permissible limit for the raw material of that morphological group-not more than 15%. The total ash content is no more than 3%, and the ash content insoluble in hydrochloric acid is no more than 1%. This indicates low levels of plant-specific minerals and extraneous mineral impurities in the raw material, which were found during harvesting and drying. It was established that the extractive substances content when extracted with 40% ethyl alcohol is 26.85%. Purified water has the highest absorption coefficients. The water absorption coefficient of avocado seeds does not exceed 2.5 ml/g. This is less than the standard for this morphological group of raw materials (3.0 ml/g). The technological characteristics of the raw materials will be used in the development of an effective method for obtaining the target product, to determine the key stages in the technology. The main groups of biologically active substances have been identified: fatty and essential oils, the amount of flavonoids. Conclusions. During the conducted research the selected numerical indicators, that determine the quality of the non-pharmacopeia raw material of avocado seeds, were analysed and the technological characteristics were established. The received data may be used in the development of the project of the regulatory documentation for the raw materials of « Persea americana seeds» and when choosing the conditions for conducting technological processes in the manufacturing the herbal preparations and the cosmetics.
SPECTROPHOTOMETRIC TECHNIQUE FOR QUANTITATIVE DETERMINATION OF THE AMOUNT OF PHENYLPROPANOIDS IN THE RAW MATERIALS OF VERBENA OFFICINALIS
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%.
SORPTION ACTIVITY OF WATER-SOLUBLE POLYSACCHARIDES AND PECTIN SUBSTANCES FROM LEAVES VISCUM ALBUM L
Objective. To study the sorption activity of water-soluble polysaccharides (WSPS) and pectin substances (PS) of V. album leaves in order to expand the range of plant-based products with detoxifying activity. Methods. The adsorption activity of the analyzed WSPS and PS using methylene blue (MB), methyl orange (MO) and gelatin was determined according to the method described in the work of V.I. Reshetnikov. Results. We have experimentally proven that the adsorption activity index for MS (cation marker) for PS is significantly higher than for MO (anionic marker). The adsorption index of PS is 1,2 times higher than that of activated carbon and 2 times higher than that of Polysorb in relation to MS binding. The adsorption activity of PS is 1,1 times higher than that of activated carbon and 1,5 times higher than that of Polysorb in relation to MO. It is important to note that the adsorption index of PV is 4,3 times greater than that of Polysorb in relation to gelatin. Conclusion. The sorption activity of the studied PV to methylene blue and gelatin reliably exceeds the activity of the comparison preparations activated carbon and Polysorb. PV of V. album leaves exhibit high activity in binding toxins with an average molecular weight and they can be used as agents with detoxifying activity.
DEVELOPMENT OF A METHOD FOR THE QUANTITATIVE DETERMINATION OF THE HERB OF ASTRAGALUS ESPARCET ASTRAGALUS ONOBRYCHIS L
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.
DEVELOPMENT OF CONDITIONS FOR SPECTROPHOTOMETRIC DETERMINATION OF FLAVONOIDS OF CANADIAN GOLDENROD HERB
Objective. To develop spectrophotometric conditions for quantitative determination of Canadian goldenrod herb flavonoids. Methods. The object of the study is Canadian goldenrod herb, dried by air-shadow method. We tested 16 methods for quantitative spectrophotometric determination of flavonoids from the State Pharmacopoeia of the Republic of Belarus on Canadian goldenrod herb. The choice of the basic method for the development of parameters for quantitative determination was carried out by comparing the results obtained by spectrophotometric methods with high-performance liquid chromatography. Statistical processing of the data was carried out using the Student criterion. Results. The basic method for the quantitative determination of flavonoids was selected. The absorption spectra of goldenrod extract and isoquercitrin standard sample are similar. The optimal parameters for spectrophotometric determination of Canadian goldenrod herb flavonoids are: concentration of aluminum chloride solution - 50 g/l; added volume of aluminum chloride solution - 3.0 ml; volume of diluted acetic acid - 50 μl; concentration of hexamethylenetetramine solution - 70 g/l; added volume of hexamethylenetetramine solution - 0.4 ml; reaction duration - 20 min. Conclusion. The parameters for spectrophotometric determination of total flavonoid content in Canadian goldenrod herb with recalculation to isoquercitrin have been developed. The choice of the method for quantitative determination of Canadian goldenrod flavonoids has been substantiated.
THE RELEVANCE OF USE OF POLYGONATUM OFFICINALE ALL ROOTS IN THE PHARMACEUTICAL INDUSTRY
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.
DETERMINATION OF THE TOTAL CONTENT OF PHENYLPROPANOIDS IN THE GRASS FAGOPYRUM RUBRICAULIS, GROWING IN THE PENZA REGION
Objective. Identification and quantification of the total content of phenylpropanoids in the raw materials of red-stem buckwheat ( Fagopyrum rubricaulis ). Methods. The raw material for obtaining extracts was red-stemmed buckwheat grass harvested on the territory of the production fields of Parafarm LLC in the Kameshkirsky district of the Penza region during the mass flowering period (07.26.24-08.01.24). Ethanol of various concentrations (40%, 70% and 95%) was used as an extractant. Identification was carried out using thin-layer chromatography. The total content of phenylpropanoids in buckwheat raw materials was determined by differential spectrophotometry. Results. According to the results of qualitative identification using thin-layer chromatography, water-alcohol buckwheat extracts contained phenylpropanoids. Absorption peaks of the extracts were observed at a wavelength of 330 nm, which corresponded to the maximum absorption of the solution of the standard sample of chlorogenic acid. Based on the data obtained, the quantitative determination of the total content of phenylpropanoids was carried out in terms of chlorogenic acid. Optimal extraction parameters were determined: 40% ethyl alcohol was used as a solvent, the ratio of "raw material - extractant" was 1:50; extraction time was 30 minutes, the extraction rate was one time. Conclusion. The presence of phenylpropanoids in red-stem buckwheat grass has been proven using TLC. The biologically active food additive "Red-stem buckwheat" was analyzed using the technique. Kulyasovo & Mamadysh" produced by Parafarm LLC (Series: 0424). The amount of phenylpropanoids in terms of chlorogenic acid ranged from 2.67±0.07-2.98±0.12%. The results obtained indicate that this technique can be used to standardize medicinal raw materials of red-stem buckwheat.
CONTENT ANALYSIS OF FOREIGN CLINICAL GUIDELINES ON THE EXAMPLE OF DEEP VEIN THROMBOSIS OF THE LOWER EXTREMITIES AS A BASIS FOR CLINICAL AND ECONOMIC RESEARCH
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.
SYSTEMATIC REVIEW: ASSESSMENT OF QUALITY OF LIFE AND SEVERITY OF SYMPTOMS IN PATIENTS WITH DEEP VEIN THROMBOSIS OF THE LOWER EXTREMITIES AND POSTTHROMBOTIC SYNDROME
Objective. To conduct an analysis of the tools used in studies to assess the quality of life and severity of symptoms in patients with deep vein thrombosis of the lower extremities and/or post-thrombotic syndrome. Methods. Content analysis of studies focused on evaluating the quality of life and symptom severity in patients with deep vein thrombosis of the lower extremities and/or post-thrombotic syndrome, conducted using both specific and non-specific tools. Results. A total of 14 studies were analyzed concerning the assessment of quality of life and symptom severity in patients with deep vein thrombosis and post-thrombotic syndrome. Various tools were used in all studies to assess quality of life: VEINES-QoL/Sym, SF-36, EQ-5D-5L, CIVIQ. Additionally, 5 studies used scales to assess the presence and severity of PTS symptoms: the Villalta scale and the VCSS scale. Conclusion. Diseases of the veins of the lower extremities, including deep vein thrombosis, are widespread in modern society. Specific tools have been developed to assess the quality of life and severity of symptoms in patients with deep vein thrombosis of the lower extremities and/or post-thrombotic syndrome; in addition, non-specific tools are also used. This article presents a content analysis of this type of research.
ANALYSIS OF CONSUMER PROPERTIES OF VITAMIN MEDICINES
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.
STATISTICAL ASSESSMENT OF THE INCIDENCE OF VARICOSE VEINS AND MODERN METHODS OF PHARMACOTHERAPY
Objective. To study and analyze current data on morbidity statistics, on methods of treatment of chronic venous diseases at different stages of development, and to provide statistics on the pharmaceutical market of phlebotropic drugs. Methods. Collection, analysis and systematization of data obtained during the study of literature and market analysis. Results. The main causes of the development of chronic venous diseases are considered, the principles of therapy and prevention of the pathology under study are given. The analysis of the range of drugs used for the treatment of varicose veins and chronic venous insufficiency has been carried out, thereby identifying the leading groups of drugs based on their continuity to the manufacturing country, international nonproprietary name, and release form. Conclusion. To date, the issue of developing new drugs with a combined venotonizing effect remains relevant and requires further study.
WORTHY EXAMPLES OF SERVICE TO THE PROFESSION AND SOCIETY. ON THE 140TH ANNIVERSARY OF THE BIRTH OF PROFESSOR A.A.OGLOBLIN AND THE 120TH ANNIVERSARY OF THE BIRTH OF PROFESSOR A.N. KARTAVENKO
This article outlines the contributions to surgery and society of two prominent scientists, surgeons, and educators, Professors A.A. Ogloblin and A.N. Kartavenko, heads of the Department of Hospital Surgery from 1933 to 1976. The article is dedicated to the 140th anniversary of Professor A.A.Ogloblin's birth and the 120th anniversary of Professor A.N. Kartavenko's birth.
MECHANISMS OF DEVELOPMENT OF TOXIC EFFECTS OF CADMIUM IONS
Intraduction. Cadmium (Cd) is a toxic heavy metal that pollutes the environment primarily as a result of human activity. Chronic exposure to cadmium affects various organs, especially the kidneys. The aim of the study is to analyze modern literature sources on the mechanisms of development of toxic effects of cadmium ions. Materials and methods. More than 100 literature sources were reviewed, of which 38 articles were included in the review. Data collection was carried out on electronic databases: Pubmed, Elibrary, RSCI, Cyberleninka over the past 5 years. Results. Analyzing a sufficient amount of literature data, we present the opinion of domestic and foreign scientists on the toxic effect of cadmium with impaired heme synthesis, inhibition of key enzymes in iron metabolism, with the development of hemic hypoxia and oxidative stress. Cadmium damages biomolecules, disrupting endothelial function and reducing the bioavailability of nitric oxide (NO), which contributes to vasoconstriction and hypertension. Cadmium also affects ion transport across cell membranes and stimulates the production of angiotensin II and aldosterone, which regulate blood pressure. Exposure to cadmium leads to a violation of the concentrating function of the kidneys, the development of tubulointerstitial nephritis, electrolyte and lipid imbalances, contributing to an increase in blood pressure and the level of atherogenic LDL in the blood. Conclusion. These changes contribute to the development of the atherosclerotic process. Oxidative stress, endothelial dysfunction, and dysregulation of the RAAS are pathogenetic links in the development of kidney dysfunction, which accordingly contributes to the formation of hypertensive syndrome and pathology of the cardiovascular system. Conclusions. Disruption of the mechanisms of metabolic processes underlying the pathology of visceral systems includes damage to the kidneys, liver, and impaired myocardial activity.