Vol 25, No 4 (2024): ОПУБЛИКОВАН 27.12.2024

The use of warfarin is the only possibility of thromboprophylaxis in patients with prosthetic heart valves. During pregnancy, the use of warfarin poses a danger to the fetus due to its teratogenic properties. Immersion in nanoparticles can make it possible to modify the distribution of many drugs in the body. 

Goal. Synthesis, study of the kinetics of release and bio-distribution of a new drug system containig warfarin loaded into a polymer nanocarrier (PLGA).  

Material and methods. Nanoparticles of PLGA loaded with warfarin were synthesized and described. The resulting product containing 10 mcg of warfarin was injected into the tail vein of 6 pregnant mice in an amount of 100 mcl on the 10th and 14th days of pregnancy. After 60 minutes, the light signal from the indocyanine green was analyzed on a fluorescent tomograph, tissues were selected for subsequent determination of warfarin concentrations by HPLC-MS. 

Results. The resulting nanoparticles had a size of 150 nm, and the warfarin capture efficiency was 63%. After 90 minutes, 10% of warfarin was released, 100% were released by 70 hours. 60 minutes after intravenous administration to pregnant mice, warfarin was distributed to all organs and tissues, creating minimum values in the brain, maximum values in the liver. In fetal tissues, warfarin was detected at a content of less than 0.5% of the plasma content.  

Conclusion. The proposed PLGA nanoparticles loaded with warfarin are characterized by sufficient stability. The data on biodistribution suggest a possible modification of the kinetics of warfarin with the creation of maximum concentrations in the liver and insignificant in the body of fruits.  

Prospects for transferring laboratory data to the clinic  

It is assumed that the resulting product, in case of further positive research results, can form the basis for the creation of a dosage form for human use in order to limit the teratogenic effect of warfarin on the fetus with preserved therapeutic activity in pregnant women with prosthetic heart valves.  

There has been increasing interest to gastrointestinal factors, their role in the development of metabolic disorders and new directions of incretinotropic therapy. Among them, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are particular interest. The purpose of the work was to study the mechanisms of incretins action on the human body and modern directions of incretinotropic therapy. The article discusses the history of discovery, composition and physiological effects of incretins, as well as the significance of these factors in the pathogenesis of obesity, non-alcoholic fatty liver disease (NAFLD) and diabetes mellitus type 2 (DM 2). According to many authors, interstitial factors are involved in stimulating insulin secretion, as well as activating the process of lipogenesis and inhibiting lipolysis that is, increasing the amount of fat in subcutaneous fat. The vast majority of patients with DM 2 have disturbances in the secretion of incretin hormones, which increase as carbohydrate metabolism disorders progress. Peptides, as potential therapeutic agents, continue to gain increasing importance in the search for active substances for the treatment of numerous human diseases. To date, many of the most important pleiotropic properties of gastrointestinal peptides have been established, and the role of incretins in the development of obesity, NAFLD, type 2 diabetes and other metabolic diseases has been proven. It is possible to use GLP-1 analogues and dipeptidyl peptidase type 4 inhibitors (incretinotropic therapy) both as monotherapy and in combination with other glucose-lowering drugs for type 2 diabetes. 

Introduction. Incidence and prevalence of any pathology are the main indicators in the epidemiology. The analysis of these indicators is conducted by almost all medical offices, as it is necessary for developing organizational decisions. Idiopathic nephrotic syndrome (INS) is the most common primary glomerular disease in children. INS is characterized by proteinuria > 40 mg/h/m2, or urine protein/urine creatinine ≥200 mg/mmol (≥2 mg/mg), hypoalbuminemia (<30 г/л) and edema. Considering the relapsing course of the disease in most patients, it is important to study the structure of INS and secondary prevention aimed at preventing relapses and maintaining remission. In this context, knowledge of the epidemiological situation regarding INS in children in various regions, countries, and continents is necessary. 

Objective. To analyze the epidemiological situation of INS in different countries based on a review of literature data from the past 50 years. 

Materials and Methods. We conducted a literature search in July 2024. Articles from PubMed, SpringerLink, Elibrary, and Pediatrics Eastern Europe were reviewed. Additionally, literature was searched using the Google and Yandex search engines. Search queries related to INS and the age group from year to 18 years were used. Articles in Russian, English, French, and German were examined. The analysis excluded data related to congenital, infantile nephrotic syndrome, and secondary nephrotic syndrome, including those associated with glomerulonephritis, systemic connective tissue diseases, and systemic vasculitis. 

Results. A total of 57 studies on INS were found for the period from 1968 to 2024. We selected 29 articles from 20 countries focused on the epidemiological situation of INS in children. It was found that the incidence of primary (idiopathic) nephrotic syndrome in North America and European countries did not differ significantly, averaging 2.9 and 2.03 per 100,000 children respectively, while these indicators varied in countries of the Asian part of the Eurasian continent and South America. Differences in the incidence of INS were identified among children of certain ethnic backgrounds, with higher incidence in patients of Asian ethnicity compared to those of European nationality. The steroid-sensitive NS predominates in the structure of INS in children. Among primary nephrotic syndrome in children minimal change disease is the most common morphological type followed by focal segmental glomerulosclerosis. Membranous nephropathy is a rare variant of INS in children. 

Conclusion. The number of studies dedicated to the epidemiological research and structure of INS in children is limited. The incidence of idiopathic nephrotic syndrome is ambiguous and depends on the region of residence and the ethnic background of the children. INS is more frequently observed in boys, and the most common morphological variant is minimal change disease. An increase in the incidence of INS in children is noted in certain European and North American countries. We also identified differences in methodological approaches, particularly regarding age groups of children and clinic-morphological characteristics. To achieve a more comprehensive assessment of the epidemiological situation of INS in children in specific regions, it is necessary to create registries of children with this pathology. 

The physical development of children is a dynamic process of growth and biological maturation over a certain period. The dynamic growth process is understood as an increase in body weight and length, the development of organs and body systems. Purpose of the study: testing a standardized method for assessing the physical development of infants and young children using the Z-score criterion. Materials and methods. 137 girls of children aged 0 to 3 years were examined by a continuous study method as part of preventive examinations of minors on the basis of Order of the Ministry of Health of the Russian Federation N514n at the bases of city polyclinics in St. Petersburg. Of the examined patients, 89% were naturally fed. The examination included: talking with parents and collecting a history of life, working with medical documentation (child's developmental history f.112/y), direct examination of children, measuring body weight, body length (or height), circles of the head, chest and middle third of the child's shoulder, assessing the actual nutrition of children. Criteria for non-inclusion in the study were prematurity, burdened obstetric and gynecological history, congenital malformations, chronic diseases. Study results. In the range from 0 to 12 months, the majority were children 10-13 months (12%, 13%, 14%, and 15%, respectively), and at the age of 13-36 months - children 27-36 months (50%). According to the data obtained, 31% of girls had changes in height: 17.5% - values  below average (attention group) and 13.5% - pathological (high). 50% of the examined patients had high body weight indicators, of which 8% had pathological ones. This was confirmed by the BMI assessment (1.4% had malnutrition, 7.3% had obesity). 8% of the examined children had pathological values  of the head circumference: 3% had low values  (microcrania), 5% had high values  (macrocrania). Above-average changes in shoulder circumference scores were observed in 40.2% of girls. Conclusions. The study confirmed that the use of the Z-score criterion for assessing physical development is a convenient, reliable and highly sensitive method. When comparing the normal indicators developed by WHO, a large percentage of cases with deviation from the norm was revealed. This creates the prerequisites for the development of standards for growth (body length), body weight, head circumference and middle third of the shoulder for children living in the territory of the Russian Federation in modern conditions. 

The purpose of the study was to evaluate the protease activity of mast cells (MC) of cardiac tissue in the new coronavirus infection (NCI) COVID-19, as well as to analyze their correlations with clinical and laboratory parameters. 

Materials and methods. The formed sample consisted of 40 patients (21 men (52.5%), 19 women (47.5%), mean age 66.65 ± 7.40 years) with a severe or extremely severe COVID-19. The examination of patients included a clinical assessment of their condition, chest computed tomography, complete blood count, coagulation testing, as well as determination of the level of procalcitonin and potassium in the blood. Clinical and laboratory parameters were assessed on the first day of hospitalization and on the eve of death. During immunohistochemical analysis, quantitative assessment of tryptase-, chymase-, and carboxypeptidase A3 (CPA3) positive MCs was performed to determine their secretory activity. 

Results and conclusion. The largest number of MCs in the heart tissues were tryptase-positive, most of which had signs of degranulation. Correlation analysis revealed a number of relationships between the number of MCs of individual phenotypes and some markers of inflammation, hypoxia, and electrolyte disturbances. The presented data indicate a variety of mechanisms of cardiac MC involvement in the systemic pathological process in NCI. In addition, the study results contain evidence of the effectiveness of therapy with dexamethasone, unfractionated heparin, and IL-6 inhibitors in this cohort of patients, due to stabilization of MCs and suppression of their degranulation activity.  

Due to the fact that in modern clinical practice, doctors are increasingly faced with kidney disease of different origins, due to a set of concomitant pathologies such as arterial hypertension, diabetes mellitus, metabolic syndrome. In this regard, the influence of hypertension on the development of chronic kidney disease is of particular relevance. To date, it has been proven that: genetic factors, the presence and degree of albuminuria, high cholesterol, abdominal obesity, diabetes, the use of non-steroidal anti-inflammatory drugs, socio-economic factors, racial and ethnic differences, lifestyle are factors affecting the control and severity of hypertension. At the moment, this pathology is a global problem that affects the quality of life of people and mortality from the corresponding complications. When analyzing the statistical data of the Health Ministry of the Russian Federation, as well as other developed countries, we see an increase in morbidity and mortality from chronic kidney disease, especially in people over 60. According to forecasts, by 2025, the number of patients with arterial hypertension will increase to 1.5 billion people. In this regard, it is of interest to study the clinical case in order to extrapolate the idea of  the interconnected pathogenetic effect of pathological phenomena on the patient's health. 

Chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA) are accompanied by respiratory symptoms - shortness of breath, cough, wheezing, which are well objectified and can reflect the mechanisms of obstructive disorders of external respiration. 

The aim of the study is to analyze the “language”, amplitude-frequency characteristics (AFC) of wheezing in patients with bronchial asthma and COPD, their relationship with the degree of bronchial obstruction and the severity of dyspnea. 

Material and methods. The randomized clinical trial included 143 patients with confirmed diagnoses of bronchial asthma and COPD. The study included 72 patients with partially controlled bronchial asthma: with mild (n=15), moderate (n=25) and severe disease (n=32). The study included 71 patients with a diagnosis of COPD with moderate (n=34) and severe (n=37) disease severity with pronounced symptoms outside of exacerbation. 

All patients described wheezing using the comparison method, the degree of wheezing intensity and dyspnea was assessed using the Borg scale. Spirometry, recording and analysis of the frequency response of wheezing before and after the use of salbutamol were performed. 

Results. According to qualitative descriptors of wheezing, two groups of patients with bronchial asthma were distinguished. Group 1 with the sensation of wheezing of high-frequency AFC and medium intensity according to the Borg scale. Group 2 with the sensation of wheezing of medium and low frequency AFC and low intensity according to the Borg scale. Among patients with COPD, 2 groups were distinguished: Group 1 - patients with severe severity, the sensation of wheezing of medium frequency AFC and medium intensity according to the Borg scale. Group 2 - COPD patients with moderate severity, the sensation of wheezing of medium and low frequency AFC, low wheezing intensity, moderate dyspnea according to the Borg scale. 

Conclusion: Patients with audiogenic perception of high-frequency wheezing can be expected to have more pronounced bronchial obstruction, while those with perception of low-frequency wheezing will have less obstruction. 

Patients with asthma showed a marked improvement in subjective indicators of wheezing AFC perception in response to inhalation therapy with beta 2 -agonists. The relationship between wheezing perception and dyspnea severity in both patients with asthma and patients with COPD is not as pronounced, which may suggest other pathophysiological mechanisms for dyspnea formation (psychological, social, adaptive mechanisms). 

Introduction. The outbreak of the new coronavirus infection (COVID-19) has spread rapidly around the world, causing enormous economic and social difficulties. To date, it is unknown during what period there is a complete resolution of changes in the lung tissue according to computed tomography, restoration of the diffuse ability of the lungs in patients who have suffered severe COVID-19, and methods for their correction have not been developed. It is known that an excessive response of the immune system with a life-threatening cytokine release syndrome ("cytokine storm") plays a key role in the pathogenesis of a new coronavirus infection. Thus, a decrease in the systemic inflammatory response is one of the urgent problems in the treatment of this nosological unit. In order to stop the "cytokine storm" in severe COVID-19, systemic glucocorticosteroids and IL-6 blockers – tocilizumab, sarilumab, levilimab are recommended. However, to date, all the long-term consequences of taking this series of medications are not known, which can lead to "secondary" progressive immunosuppression. 

The purpose of the study was to substantiate the dynamic formation of the volume of HIV testing in the context of medical organizations and to assess the resource provision of HIV testing in the Voronezh region. Materials and methods. The information was obtained from the medical and laboratory information systems of the Regional Clinical Center AIDS Prevention and Control and official statistical reports (form No. 4 "Information on the results of blood tests for HIV antibodies"). Results. The following indicators were selected as reference indicators for the development of a survey plan: population size, hospitalization rates, and the incidence rate, taking into account the growth rate in each municipal territory. Based on a combination of indicators, the percentage of coverage is calculated, with an annual increase of 1% compared to the level of the previous year, taking into account the volume of financing for the purchase of diagnostic tools for ELISA. During the period of validity of this roadmap, the number of territorial defense ministries that do not meet the criteria has decreased to 5 in 2024. Due to the increase in volumes, the network of HIV ELISA diagnostic laboratories in medical organizations in the region has been expanded. Conclusion. In general, the criteria recommended by the State Strategy have been achieved in the region. Targeted provision of diagnostic tools has been established at the expense of budgetary and software resources. It is necessary to carry out dynamic monitoring for each municipal territory of HIV detection in different contingents in order to direct efforts to the identified key groups. 

This article is dedicated to Vorontsov Vasily Nikolaevich, whose social and scientific activities are closely connected with the Medical Faculty of Voronezh State University. A participant in the Great Patriotic War, a graduate student, an assistant, an associate professor, and then the head of the Department of Pharmacology. Contemporaries honor his memory and keep documents and scientific works left by him during his lifetime. Thanks to all this, we have the opportunity to learn details from the history of Russian and military medicine, as well as people who have made their invaluable contribution to the development of pharmacology. We should be proud of the scientists who have devoted half a century to the service of science and adopt their experience.