CLINICAL MEDICINE
Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Despite the progress achieved in predicting the risk of development and adverse cardiovascular outcomes, there remains a large number of patients who are not recognized using standard predictive models. Objective: to assess the possibility of using machine learning to build a multi-marker model for predicting the outcome of acute coronary syndrome in the form of acute myocardial infarction or unstable angina. Materials and methods. The development of predictive models was carried out in the Python programming language (Pandas, Seaborn and Scikit-learn libraries) using a database compiled from the results of clinical and laboratory studies of 60 patients aged 18 to 59 years with acute coronary syndrome. Results. From a total list of 181 indicators (10,860 values), 3 most informative biomarkers were selected to identify the established endpoints (patient diagnosis). The random forest classifier outperformed other models in terms of accuracy, sensitivity and specificity, which allowed us to determine the occurrence of an unfavorable outcome of ACS with 96% accuracy. Conclusion. Based on the obtained data, a computer program "Calculator for calculating the probabilistic outcome of acute coronary syndrome" was developed for practical use in healthcare institutions.
Objective - to present a review of literature data concerning the main stages of changing the paradigm of prognosis-modifying pharmacotherapy for patients with chronic heart failure. The article discusses the dynamics of the pharmacological treatment strategy for patients with chronic heart failure (CHF) with different left ventricular ejection fractions. Changes in pharmacotherapeutic approaches to the use of prognosis-modifying drugs are based on randomized clinical trials completed in recent years, which have shown the significant contribution of sodium-glucose cotransporter-2 inhibitor (SGLT2i) in reducing the risk of developing negative outcomes in patients with heart failure with reduced left ventricular ejection fraction (СHFrEF), mildly reduced (CHFmrEF) and preserved ejection fraction (CHFpEF). Currently, in patients with symptomatic CHFrEF, the priority is quadruple therapy, including one of the blockers of the renin-angiotensin-aldosterone system (angiotensin-converting enzyme inhibitors (ACE-I), angiotensin-receptor blocker (ARB), angiotensin receptors-neprilysin inhibitor (ARNI) - preferably ARNI or ACE-I); beta-blocker (BB); mineralocorticoid receptor antagonist (MRA); SGLT2i. In patients with CHFmrEF and CHFpEF, the highest class of recommendations is given to SGLT2i and diuretics (in the presence of congestion), while ARNI/ACE-I/ARB, MRA, BB were assigned a lower class - IIb - in patients with CHFmrEF. In patients with CHFpEF, SGLT2i and diuretics (if necessary) can be rationally combined with ARNI, MRA, ARB (if ARNI are intolerant).
This paper presents a technique developed by us for three-dimensional cultivation of fibroblasts isolated from the dermis of 20-day-old rat embryos of the Wistar line, filling with them a matrix obtained from fish collagen by freeze drying. The method is suitable for creating scaffolds in regenerative medicine, experimental models with approximate conditions for their subsequent study for confocal, electron microscopy, implantation of tissue engineering structures in experimental animals. Objective - to develop an improved method for colonizing collagen 3D matrices with a culture of dermal autofibroblasts. Materials and methods. 3D collagen matrix carrier; experimental animals (Wistar rats), the skin of 18-20 day old embryos was used as a source of fibroblasts, from which they were isolated by trypsinization in the cold, followed by cultivation under standard conditions: 5%, CO2, 37°С, absolute humidity, growth medium (DMEM, antibiotics (1%, streptomycin-penicillin), glutamine and fetal calf serum). The process of colonization of the matrix by cell cultures consisted of 4 consecutive stages. The filling efficiency was monitored using electron microscopy. Results. As a result of the proposed method, a sterile 3D collagen matrix was filled with pre-isolated dermal autofibroblast cells in the amount of 5×106 cells/ml. According to the results of scanning electron microscopy, it was shown that the inter-fiber spaces are filled with living fibroblast cells, some of which are at the stage of division. Conclusion. The method developed by us made it possible to achieve effective colonization and adhesion of fibroblasts to the matrix and avoid the formation of cell conglomerates, improves contact with the surface and subsequent survival of the introduced cell culture. It allows to increase the rate of obtaining a donor cell culture and reduce the time of sample preparation before implantation. It also allows you to create 3D systems based on other cell types, which opens up great opportunities in reconstructive surgery.
MEDICOBIOLOGICAL SCIENCES
Objective - study of the features of the elemental chemical composition and resistance of tooth enamel of permanent residents of Kursk of different ages. Materials and methods. The study was conducted on 68 samples of medically removed teeth of patients permanently residing in the city of Kursk and belonging to different age groups using X-ray spectral microprobe and mass spectrometric analyses. The obtained data were processed statistically. Results. The data on the macro- and microelement chemical composition of tooth enamel of Kursk residents of young, middle, elderly and senile age were obtained and analyzed. The values of the coefficients Ca/P, Ca+Mg/P, Ca+Na/P, Ca+K/P, Ca+Mg+Na/P, Ca+Mg+K/P, Ca+Na+K/P, Ca+Mg+Na+K/P are determined, allowing to judge the resistance of tooth enamel, first of all, caries resistance. Conclusion. The conducted research revealed the peculiarities of the chemical composition of the tooth enamel of Kursk residents of different ages and is the theoretical basis for the development of regionally oriented therapeutic and preventive measures for diseases of hard tooth tissues.
Aim - to present up-to-date data on the extra- and intraorgan vasculature (arterial and venous) of the spleen in different sex, age and body type groups. Materials and Methods. The search was carried out using the Russian Science Citation Index. The selection of materials for inclusion in the review was performed by two independent researchers. The exclusion of unsuitable works occurred in two stages: on the first, papers with inappropriate titles and annotations were excluded, on the second, articles with unsuitable full texts. The analysis was performed using the statistical software R (version 4.1) and the metafor R extension package. Random effects models were used for all analyses. I2 and t2 statistics were used to measure the heterogeneity between studies. Results. The analysis included 32 papers, the publication period of which is from 2001 to 2023. The results of a meta-analysis of the diameter of the splenic artery show that the average diameter of this artery is estimated at about 5.42 mm, with a standard error of 0.27 mm. The results of the meta-analysis of the diameter of the splenic vein also show significant heterogeneity between the studies, which is confirmed by the high statistical values of I2 (99.9%) and H2 (1007.9). This indicates differences in results between studies, which may be caused by differences in methodology, the study group, and other factors. Conclusions. Knowledge of the variant anatomy of the spleen vessels is important for planning and performing operations on the spleen and abdominal organs in general.
Objective - to study the effects of thymogen and its structural analogs on the functional activity of blood neutrophils in toxic liver damage with tetrachloromethane and hydrazine hydrochloride. Materials and methods. Carbon tetrachloride hepatopathy accompanied by an increase in immune reactivity was modeled by a 5-fold intragastric administration of carbon tetrachloride. Liver damage with hydrazine associated with immunosuppression was induced by a single intraperitoneal administration of a hepatotropic poison. Rats were administered thymogen (1 μg/kg) and its structural analogues (1.2 μg/kg) intraperitoneally for 5 days. In carbon tetrachloride hepatopathy, peptides were administered simultaneously with the hepatotropic poison, in hydrazine - 24 hours after intoxication. Phagocytic and oxygen-dependent activities of neutrophils were assessed. Results. It was found that in liver damage by carbon tetrachloride, thymogen does not exert a corrective effect on the functional activity of neutrophils. Structural analogues reduced the activity of neutrophils under conditions of hyperactivation of the immune system. In hydrazine hepatopathy, all peptides exhibited immunostimulating activity, with its greater expression in structural analogs of thymogen. Conclusion. Thymogen analogues modified with D-alanine exert an immunomodulatory effect in toxic hepatopathies with different levels of immune reactivity.
Objective - to evaluate changes in the processes of mitochondrial biogenesis and mitophagy in the cerebral cortex and hippocampus in Wistar rats of both genders in experimental Alzheimer's disease. Materials and methods. Alzheimer's disease was modeled in male and female Wistar rats by injection of β-amyloid aggregates 1-42 into the CA1 hippocampal part. After 30 days of exposure, the rats were decapitated, the brain was extracted, the hippocampus and cerebral cortex were isolated with further reception of the mitochondrial fraction, in which changes in the activity of succinate dehydrogenase, cytochrome c oxidase (biomarkers of mitochondrial biogenesis) and citrate synthase (biomarker of mitophagy) were evaluated by spectrophotometric method. Results. It was found that in Wistar rats of both genders under conditions of experimental Alzheimer's disease, compared to sham operated animals, there is a decrease in the activity of succinate dehydrogenase, cytochrome c oxidase and citrate synthase, both in the cerebral cortex and in the hippocampus were observed. At the same time, there were no gender differences in the activity of the studied enzymes in the hippocampus, whereas in the cerebral cortex, the activity of succinate dehydrogenase and cytochrome c oxidase in female rats was lower than in males by 23.4% (p<0.05) and 25.3% (p<0.05), respectively. Conclusion. The study showed that in Wistar rats there are gender differences in the reactions of mitochondrial biogenesis in the cerebral cortex, while in the hippocampus there are no significant differences in the reactions of mitophagy and mitochondrial biogenesis in female and male Wistar rats.
Objectivе - to carry out a systematic analysis of the data available in the modern literature on the pathophysiological role of copper and zinc metabolism in carcinogenesis and tumor progression. Materials and methods. In preparing the review, the publications of the biomedical literature information databases Scopus (307), PubMed (378), Web of Science (104) were analyzed, eLibrary.ru (219). To obtain full-text documents, the electronic resources PubMed Central (PMC), Science Direct, Research Gate, eLibrary.ru. Results. Copper and zinc play a significant pathophysiological role in carcinogenesis, often being functional antagonists of each other, but sometimes synergists in neoplastic processes. Future prospects for the study of drugs capable of selectively influencing the intrathumoral concentration of these elements create attractive additions to drug therapy. At the moment, all potential drugs are in the early stages of research, but the results for individual nosologies are already promising. Conclusion. It is necessary to continue comprehensive research on the use of copper and zinc ions as therapeutic targets, which may in the future become an alternative to highly toxic classical chemotherapy. The specificity and sensitivity of markers based on the analysis of the concentration of copper and zinc in blood serum and their ratio remains at a fairly low level. This can be a useful tool for assessing the dynamics of copper and zinc levels in the process of antitumor drug therapy of various tumors. In addition, our understanding of the pathophysiological role of these elements allows us to create a complete picture of molecular alterations in each case.
Objective - investigation of changes in the microstructure and mineral density of the proximal parts of the femur (head, neck) and tibia in experimental postmenopausal osteoporosis and its therapy with resveratrol and analysis of their possible mechanisms. Materials and methods. The study was performed on 15 female Wistar rats. A model of postmenopausal osteoporosis was created by bilateral ovariectomy with a follow-up period of 56 days. Resveratrol therapy in the experimental group was performed by its daily intraperitoneal administration at a dose of 2 mg / kg during the same observation period. Histological examination with image analysis and morphometry, absorption X-ray densitometry of the proximal epiphysis of the femur and proximal half of the tibia were performed. Results. Bilateral ovariectomy in experimental animals - Wistar rats, leads after 8 weeks to a complex of structural changes in the proximal parts of the femur and tibia and a decrease in bone mineral density in them, which can be extrapolated to osteoporotic skeletal damage in humans. Resveratrol at a dose of 2 mg/kg has osteoprotective and regenerative effects in experimental postmenopausal osteoporosis. Conclusion. Resveratrol at a dose of 2 mg/kg has a cytoprotective effect for osteocytes and osteogenic progenitor cells, exhibits a proliferative and osteoblastic committal effect on bone marrow stromal precursors, inhibiting the adipocytic differentiation pathway and thereby providing an anti-osteoporotic effect in hypoestrogenism. Based on comparisons with literature data, the key factor realizing the effects of resveratrol is most likely the sirt1 protein.
PHARMACEUTICAL SCIENCES
Objective - to study the fatty acid composition of Elaeagnus argentea fruit oil growing in the Astrakhan region. Materials and methods. The fruits of Elaeagnus argentea were harvested in August 2023 in the Astrakhan region. Analysis of the total amount of fatty oils according to the OFS.1.5.3.0014 "Determination of the content of fatty oils in medicinal plant raw materials and medicinal products of plant origin". The component qualitative and quantitative analysis of the fatty acid composition of the oil of the fruits of the Elaeagnus argentea was carried out by gas chromatography on Chromatek - Crystal 5000.2 using a flame ionizing detector on a quartz capillary column Select for FAME (100m × 0.25mm × 0.25microns), according to GOST 31663 - 2012. Results. During the gas chromatographic analysis of the fruits of Elaeagnus argentea , the total amount of fatty oils was determined, which averaged 28.37%. Conclusion. The results obtained confirm the possibility of using Elaeagnus argentea fruits as a source of polyunsaturated fatty acids.
Objective - to study the effect of preliminary heat pre-treatment, defatting and their combinations on aqueous extraction of hydroxycinnamic acids (HCA) from dandelion roots during the preparation of infusions, decoctions and teas. Materials and methods. The object of the study was dandelion roots. The HCA content was determined spectrophotometrically by the reaction with Arnov's reagent. To obtain infusions and decoctions, the effect of the infusion mode and the preparation method on the release of HCA into water was studied. When obtaining teas - the ratio of medicinal plant raw materials and water, the material of the brewing container, the duration of brewing in a closed container and in a thermos, the presence and parameters of filter bags and the frequency of brewing. Preliminary processing of medicinal plant raw materials by heat pre-treatment, degfatting and their combination was used. Results. When obtaining infusions and decoctions, the maximum content of YCF was noted when obtaining a decoction according to the instructions for medical use with a combination of heat pre-treatment and subsequent degreasing. When obtaining teas, the following technological parameters were revealed: the ratio of medicinal plant raw materials and water (g to ml) - 1 to 50; brewing container - glass or enamel; duration of brewing in a closed container - 30 min, in a thermos - from 3 to 6 hours; brewing frequency - single; without a filter bag. The highest content of HCA in teas was achieved with a combination of defatting and subsequent heat re-treatment. An increase in polyphenol oxidase activity during the production of aqueous extracts was usually accompanied by a decrease in the content of HCA. The content of HCA during the production of decoction and tea in a container is comparable, in a thermos it is almost twice as high, and during daily infusion it is 2.5 or more times lower. Conclusion. When producing a decoction, it is recommended to use raw material processing by a combination of heat pre-treatment followed by defatting; when producing tea, by a combination of defatting followed by heat pre-treatment.
ISSN 1998-5754 (Online)