Vol 27, No 4 (2023): PHYSIOLOGY. EXPERIMENTAL PHYSIOLOGY

PHYSIOLOGY. EXPERIMENTAL PHYSIOLOGY

History of aviation physiology

Grebennikov E.K., Grebennikova I.N., Subotyalova A.M., Subotyalov M.A.

Abstract

Relevance. In studying the history of medical and biological disciplines, an important part is the identification of the stages of their formation and development. In this regard, it seems important to make a historical and scientific analytical review of the development of ideas about aviation physiology, covering different stages of the history of science and reflecting the contribution of researchers from different regions. It will be useful for teaching historical and scientific and special disciplines, as well as for researchers involved in the study of aviation physiology. The need to understand how the human body functions in flight arose along with the development of aeronautics. The study is devoted to the analysis of the main stages in the development of aviation physiology. The purpose of the study - to characterize the stages of formation and development of aviation physiology. Research methods. In preparing this publication, articles in publications included in the RSCI, PubMed, and Scopus were mainly used. Preference was given to materials published in the last 15 years. The main results present the stages of development of aviation physiology with a description of the contribution of the main researchers in this field. The achievements of domestic scientists, doctors, physiologists I.M. Sechenov, L.A. Orbeli, G.M. Zarakovsky are analyzed, their scientific priorities in the development of this scientific direction are presented. The process of formation and development of aviation physiology as a direction of biomedical knowledge is presented. Before the advent of aviation (19th century), hypoxia was studied in the study of balloon flights. With the advent of high-speed and maneuverable aircraft, aviation physiology began to study the body’s response to overloads caused by highly maneuverable flights. Conclusion . The development of aviation physiology can be divided into two stages. 1. Pre-aviation, within which the emergence of this area of medico-biological knowledge takes place. 2. Aviation, at this stage scientists have the opportunity to study different multidirectional overloads and their effect on the human body. Currently, aviation physiology is one of the important branches of physiology, aviation and space medicine.

RUDN Journal of Medicine. 2023;27(4):411-418
pages 411-418 views

Blood pressure status in patients with metabolic syndrome

Sorout J., Kacker S., Saboo N., Kumar M.

Abstract

Relevance. Metabolic syndrome (MetS) is existence of many abnormalities, such as abdominal obesity, hypertension, dyslipidemia, and glucose intolerance. The occurrence of MetS in hypertensive people is linked to poorly managed hypertension. One of the parameters for the diagnosis of the syndrome is the presence of increased blood pressure; nevertheless, research shows that MetS patients are likely to experience hypertension often. Materials and Methods. 300 metabolic subjects were selected from the medicine OPD as study participants based on the joint interim statement’s 2009 definition of the metabolic syndrome. They were divided into three groups (normotensive, pre-hypertensive, and hypertensive) based on blood pressure readings that met the American Heart Association’s (AHA) Asian blood pressure criteria. The following parameters were recorded for data collection: anthropometric (Weight, Height, Body Mass Index Waist Hip Ratio), Blood pressure, biochemical (Fasting blood glucose, Lipid profile parameters). Results and Discussion. According to the resting blood pressure readings, out of 300 metabolic syndrome participants, 37 were normotensive [male (40.54 %); female (59.45 %)], 115 were pre-hypertensive [male (58.26 %); female (41.74 %), and 148 were hypertensive [male (52.7 %); female (47.3 %)]. In several parameters, there was no such significant difference between male and female participants across all groups. However, the levels of blood total cholesterol, triglycerides, and low-density lipoprotein were considerably greater in hypertensive and pre-hypertensive metabolic participants than in normotensive subjects, while the levels of high-density lipoprotein were lower. Conclusion. Study findings suggest, hypertension and pre-hypertension were more prevalent in the group with metabolic syndrome. Additionally, hypertensives have a higher chance of manifesting dyslipidemia.

RUDN Journal of Medicine. 2023;27(4):419-427
pages 419-427 views

Monitoring of Neuromuscular block during emergency abdominal surgery

Dhunputh N., Petrova M.V., Moroz V.V., Butrov A.V., Magomedov M.A.

Abstract

Relevance. Sixty percent of cases of residual neuromuscular block (rNMB) were recorded globally, yet this issue of rNMB in critically ill patients remains taboo. To predict any leftover NMB, a train-of-four stimulation (TOF) Watch SX was utilized to track the depth of muscle relaxant in emergency patients both during and after surgery, even when they were transported to the intensive care unit. This study aimed to investigate differences in the variability of neuromuscular block between two distinct surgical procedures: laparoscopic cholecystectomy (the control group) and emergency abdominal surgery (the investigation group). Materials and Methods. Using two different muscle relaxants and assessing their depth using accelerometry notably the TOF Watch SX. A total of 140 patients, aged 18-60 years with a BMI of 18-30 kg/m², participated in the study. Group I underwent planned cholecystectomy (control group), while Group II underwent emergency abdominal surgery (investigation group). The muscle relaxants Ridelat-C, generic of atracurium benzilate (Verofarm OOO, Harabovsk, Russia) and Kruaron, generic of rocuronium bromide (Verofarm OOO, Harabovsk, Russia) were administered, with various monitoring methods, including Drager Fabius, ECG, and lab results, Microsoft Office Professional Plus 2021 advanced with graphs and ANOVA. Results and Discussion. The results demonstrated profound skeletal muscle relaxation for planned cholecystectomy, with TOF 0 achieved at 165.9 ± 95 seconds for Kruaron and 183.3 ± 90 seconds for Ridelat-C. In emergency abdominal surgery, it took 207.1 ± 120 seconds with Kruaron and 255.5 ± 109.5 seconds with Ridelat-C at TOF0. Notably, Kruaron exhibited prolonged effects in Group II, leading to residual neuromuscular block in critically ills even 2.5 hours post-surgery. Conclusion . Neuromuscular blocking agents modestly exacerbated neuromuscular dysfunction, potentially contributing to acquired critical illness polyneuropathy/myopathy, severe sepsis/septic shock, and massive blood loss/haemorrhagic shock. In critically ills, a minimal calculated dose of Kruaron is recommended, while Ridelat-C, which metabolized within the blood plasma without involving the kidneys or liver, might be a better choice. Suggamadex was suggested for reversing Kruaron effects due to its rapid effect as compared to proserine.

RUDN Journal of Medicine. 2023;27(4):428-440
pages 428-440 views

Macrophage population state and proliferative activity of spleen cells under liver regeneration conditions

Mamedov A.T., Gantsova E.A., Kiseleva V.V., Lokhonina A.V., Makarov A.V., Turygina S.A., Bicherova I.A., Arutyunyan I.V., Vishnyakova P.A., Elchaninov A.V., Fatkhudinov T.K.

Abstract

Relevance. Currently, the participation of immune system cells in the regulation of reparative processes is attracting more and more attention of researchers. There is an anatomical connection between the liver and spleen by means of portal vein. Thus, cytokines and other biologically active substances can enter the liver from the spleen through the portal vein, as well as cells can migrate to the liver. However, the specific mechanisms of mutual influence of the mentioned organs, including in reparative processes, remain poorly studied. The aim of our work was to study the state of spleen monocyte-macrophage population after liver resection, as well as the proliferative activity of spleen cells during liver regeneration . Materials and Methods . The model of liver regeneration after 70 % resection in mouse was reproduced in this work. The animals were taken out of the experiment after 1, 3 and 7 days. The marker of cell proliferation Ki67 was immunohistochemically detected, the state of spleen monocyte-macrophage population was evaluated by markers CD68, CD115, CD206, F4/80 by methods of immunohistochemistry and flow cytometry. Results and Discussion . The liver regeneration had a pronounced effect on the cytoarchitectonics of the spleen. In 1 day after liver resection in the spleen there was observed a decrease in the share of Ki67+cells, according to the flow cytometry data there was a decrease in the number of CD115+cells, in 3 and 7 days there was a decrease in the number of F4/80+ macrophages. Conclusion . Liver resection causes changes in the state of cell populations of the spleen as well. First of all, to the decrease in the activity of proliferative processes in it, as well as to the changes in the state of the monocyte-macrophage system. A decrease in the content of CD115+ and F4/80+ cells in the spleen was found, which indirectly indicates the migration of monocytes/macrophages after liver resection, which can also influence the course of reparative processes in the liver.

RUDN Journal of Medicine. 2023;27(4):441-448
pages 441-448 views

Migration, proliferation and cell death of regenerating liver macrophages in an experimental model

Grinberg M.V., Lokhonina A.V., Vishnyakova P.A., Makarov A.V., Kananykhina E.Y., Eremina I.Z., Glinkina V.V., Elchaninov A.V., Fatkhudinov T.K.

Abstract

Relevance . Macrophages are the leading regulatory cell-lineage taking part in reparative processes in mammals, and the liver is no exception. The ratio of monocyte migration, proliferation and death of macrophages during liver regeneration requires further studies. The aim was to quantify the intensity of monocyte migration, cell proliferation and apoptosis of resident liver macrophages after its 70 % resection in a mouse model. Materials and Methods. We performed 70 % liver resection in sexually mature male BalbC mice. Cells of liver monocyte-macrophage system were obtained by magnetic sorting by marker F4/80. The immunophenotype of the isolated cells was further studied by cytofluorimetry, the level of proliferation and cell death, the content of cyclins and P53 was determined by western blot. Results and Discussion . It was found that after partial hepatectomy there is a marked migration of monocytes/macrophages positive for Ly6C and CD11b markers to the liver, the migration process starts already in the first day after the operation. On the same terms there is a rise in proliferative activity of macrophages, established by Ki67 marker, the peak of proliferation - 3 days after partial hepatectomy. A significant increase in the number of dying macrophages was found early after liver resection. Conclusion . The obtained data indicate that liver regeneration in mammals on the model in mice is accompanied by proliferation migration and cell death of macrophages. Taking into account the immunophenotype of macrophages, we can conclude that Ly6C+ blood monocytes migrate to the liver, and resident macrophages participate in proliferation. The obtained data confirm the universality of the course of reparative processes in mammals.

RUDN Journal of Medicine. 2023;27(4):449-458
pages 449-458 views

Experimental models of tumor growth in soft tissue sarcomas

Tretyakova M.S., Bokova U.A., Korobeynikova A.A., Denisov E.V.

Abstract

Soft tissue sarcomas are rare tumors (about 1 % of all malignant neoplasms) and include more than 70 histological subtypes, the pathogenetic features of which remain unclear. This is largely due to both quantity and volume of clinical material and high heterogeneity of the disease. Given the rarity and heterogeneity of each individual subtype of soft tissue sarcoma, there is an urgent need to develop universal model systems to understand the molecular changes that determine tumor biology. Such systems include CDX models (cell line-derived xenograft), created from cell lines, PDX (patient-derived xenograft), obtained from primary tumor/metastasis cells, both a whole fragment of surgical material and from a cell suspension; humanized animals containing various human immune cells, and GEM (genetically engineered mouse) models, which are created through transfection of genetic changes characteristic of different subtypes of soft tissue sarcomas. To create these systems, not only widely available mouse models are used, but also other animals, such as fish (Danio rerio) , rats, pigs, and dogs. Another important goal of using animal models is to screen the effectiveness of modern drugs. To date, treatment of various subtypes of soft tissue sarcomas is based on standard protocols of chemotherapy (doxorubicin, epirubicin, dacarbazine, ifosfamide) and surgical resection. In the case of inoperable forms or late stages of soft tissue sarcomas, animal models are a potential tool in predicting the effectiveness of therapy and personalized selection of treatment regimens. In this regard, studies of the mechanisms of targeted action on specific molecules and the use of humanized animals for the development of new approaches to immunotherapy are of particular relevance. The current review discusses animal model systems of the three most common types of soft tissue sarcomas: liposarcomas, undifferentiated pleomorphic and synovial sarcomas, as well as the use of these models to find new therapeutic solutions. Conclusion. Currently, PDX and GEM models are widely used to identify molecules and signaling pathways involved in the development of sarcomas, identify tumor-initiating cells, and assess the chemoresistance of known drugs and new drugs at the level of the entire tumor ecosystem. However, the key problems of animal models of soft tissue sarcomas remain changes in their composition and phenotype compared to the original tumor, poor survival of surgical material, and lack of cellular immunity in immunocompetent models, high cost, and the length of time it takes to create and maintain the model. A solution to one of the problems may be the use of humanized animals with PDX, which implies the presence in the model of immune, stromal and tumor components that are as close as possible to the human body.

RUDN Journal of Medicine. 2023;27(4):459-469
pages 459-469 views

IMMUNOLOGY

Mechanisms of Regulation Allergic and Autoimmune Reactions by Bacterial Origin Bioregulators

Guryanova S.V., Sigmatulin I.A., Gigani O.O., Lipkina S.A.

Abstract

Relevance. The increase in allergic and autoimmune diseases observed in recent decades highlights the need for therapy and prevention, which requires detailed research into the mechanisms of their occurrence. The onset and progression of allergic and autoimmune diseases are influenced by genetic predisposition, lifestyle, environmental factors, and disruptions in the coordinated operation of the immune system, and as a consequence of immune homeostasis. Treatment of these diseases is primarily symptomatic and often accompanied by undesirable side effects. Immune system disorders in various pathologies have their own characteristics for each type of disease, and at the same time have common mechanisms. Considering the presence of a large number of various microorganisms in the human body, taking their influence into account is of paramount importance. Microorganisms are a source of biologically active molecules, the action of which can either prevent and reduce the severity of the disease or exacerbate it. The aim of this study was to analyze the cytokine profile of the effects of fragments of cell walls of Gram-negative and Gram-positive bacteria - lipopolysaccharide (LPS) and muramyl peptide (MP), as well as nisin - an antimicrobial peptide of bacterial origin on human mononuclear cells. Materials and Methods. Mononuclear cells were obtained from peripheral blood of healthy volunteers using Cell separation media Lympholyte CL 5015, and were cultured in the presence of LPS, GMDP and bacteriocin nisin. The cytokine activity of LPS, GMDP and bacteriocin nisin was examined using the multiplex cytokine analysis; the analysis of surface markers was determined flow cytometry. Results and Discussion. It was shown that bacterial cell wall fragments to a much greater extent than nisin induce the production of cytokines, chemokines, and growth factors. It was established that LPS and MP increase the expression of CD11c on dendritic cells, while bacteriocin nisin does not affect the increase of CD11c+ DCs. LPS and MP in the conducted ex vivo studies did not affect the emergence of CCR7. Conclusion. Bacterial origin bioregulators trigger a negative feedback mechanism by inducing the synthesis of anti-inflammatory factors, that can prevent the inflammatory process. Understanding the molecular mechanisms of the influence of bacterial origin bioregulators on the human body opens new approaches in the prevention and development of personalized therapy strategies.

RUDN Journal of Medicine. 2023;27(4):470-482
pages 470-482 views

SOCIAL HEALTH AND HEALTH PROTECTION

Cerebrovascular diseases epidemiology in the Stavropol region rural residents in the implementation context of the regional program «Fighting mediavascular diseases in the Stavropol region»

Abramov A.Y., Muravyeva A.A., Mikhaylova J.V., Sterlikov S.A.

Abstract

Relevance. During the implementation of the program for the prevention and treatment of cardiovascular diseases in the Stavropol Territory, measures were taken to prevent hemorrhagic and ischemic strokes, train medical personnel in methods of timely detection of cerebrovascular diseases (CVD), recognition (including through training of the general population) and routing patients with acute cerebrovascular accidents; during a pandemic, opening specialized departments. This organizational experiment required an assessment of its impact on the most medically complex group of the population - rural residents. The aim was to study in dynamics the epidemic situation of CVD among the rural population in the Stavropol Territory in comparison with the Russian Federation. Materials and Methods. Information from official statistical observation forms on the incidence of CVD and mortality from them was studied. Results and Discussion. In the period from 2010 to 2022, there was an increase in the incidence of CVD in the rural population from 464.6 to 1045.1 per 100,000 rural population, which is partly due to the aging of the population, and partly due to improved diagnosis of CVD. The overall incidence of CVD increased from 1275.5 to 3416.1, which suggests an improvement in patient survival. The incidence of strokes of all types tended to decrease, which indicates the effectiveness of the impact on the risk factors for their development. The incidence of unspecified strokes decreased significantly, which led to an increase in the primary incidence of cerebral infarctions (which, however, grew more slowly in the Stavropol Territory than in the Russian Federation as a whole; the coefficients of the regression equations were 2.5 and 4.3, respectively). Between 2015 and 2022. the mortality rates (from 208.4 to 161.1) and mortality (from 5.8 to 2.8) from CVD decreased rapidly (relative to mortality from CVD in the Russian Federation). Conclusion. The proposed set of measures for the prevention and treatment of CVD, including preventive measures, a system of social mobilization, FAST-test, patient routing systems with the delivery of eligible persons to vascular centers within an hour, timely response to new risk factors for the development of CVD, was effective and can be recommended for implementation in similar areas with a high proportion of rural population.

RUDN Journal of Medicine. 2023;27(4):483-495
pages 483-495 views

Parameters and indicators selection of clinical centers in predicting the patients enrollment for clinical trials

Milovanov S.S.

Abstract

Relevance. Recruitment of patients and its compliance with the clinical trial protocol is one of the main goals of conducting a feasibility study before starting any clinical trial. Study feasibility is a must before starting any international multicentre clinical trial, and one of the main goals of feasibility is to find clinical centers with a suitable pool of patients for their subsequent selection and prediction of patient recruitment according to protocol requirements. Well-conducted fitness is clinical centers that recruit eligible patients in compliance with the protocol framework and the recruitment numbers proposed by the centers. After conducting fability, the patient recruitment prediction coincides with the protocol patient recruitment prediction. However, more than half of international multicenter clinical trials fail due to unsuccessful patient recruitment. A widely used method in the study of feasibility is a questionnaire and the reasons for subsequent failures in a clinical trial can be both an underestimation of the information provided in the questionnaires, and the lack of appropriate parameters and indicators, and, as a result, the selection of inappropriate clinical centers. Exposure to the subjectivity of opinion in the selection of sites also leads to poor selection of sites and, therefore, relevance in an objective and independent assessment remains. The aim of the study was to analyze the set of patients in selected clinical trials, identify set-related parameters and measures, and find a statistically significant relationship with a successful set of analyzed parameters and measures. Materials and Methods: A retrospective analysis of 4 international multicenter clinical trials of II-III phases was carried out for the recruitment of patients. The selection criterion is a successful recruitment of patients. Statistical analysis: descriptive statistics, multivariate analysis, correlation analysis. Results and Discussion. Parameters and indicators were found that showed a strong statistical correlation with successful recruitment of patients in clinical centers. As a result of the study, conclusions were drawn about the need to expand the use of parameters and the ratio of parameters: instead of indicators of one parameter - the expected set of patients before inclusion in the mandatory assessment of sites is a calculated parameter, it is also necessary to additionally take into account the following parameters: type of site and initial response time in days. Conclusions. Using the proposed parameters and metrics will reduce the likelihood of failure in patient recruitment. These parameters will make it possible to evaluate clinical centers with a prediction of the number of patients and to select more qualitative clinical centers.

RUDN Journal of Medicine. 2023;27(4):496-514
pages 496-514 views

MEDICAL GENETICS

Abnormal methylation of PRDM16 and PTPRN2 genes in chorionic villi in miscarriage

Vasilyev S.A., Vasilyeva O.Y., Oppong-Peprah B., Demeneva V.V., Zuev A.S., Sazhenova E.A., Nikitina T.V., Tolmacheva E.N.

Abstract

Relevance. Abnormal epigenetic regulation of genes responsible for the development of the embryo and placenta is associated with many pregnancy pathologies. Aim. The aim of this work was to analyze the prevalence of abnormal methylation of the PRDM16 and PTPRN2 genes in chorionic villi of spontaneous abortions with normal karyotype and with the most frequent aneuploidies (trisomy 16 and monosomy X). Materials and Methods. The methylation profile was evaluated using targeted bisulfite massive parallel sequencing in chorionic villi of induced abortions (n = 10), spontaneous abortions with normal karyotype (n = 39), trisomy 16 (n = 17) and monosomy X (n = 20) and peripheral blood lymphocytes of healthy volunteers (n = 6). Results and Discussion. In analyzed genes, differential methylation of individual CpG sites was found in chorionic villi of spontaneous abortions. Despite the absence of significant differences between the groups in the average level of methylation in analyzed gene regions, abnormal methylation of the PRDM16 and PTPRN2 genes were detected for 33 % and 5 % of spontaneous abortions, respectively, indicating a high incidence of epigenetic abnormalities in these genes in the chorionic villi of spontaneous abortions. The level of methylation of the PRDM16 gene significantly correlated with the level of methylation of the retrotransposon LINE-1, which indicates the generalized nature of methylation disorders in spontaneous abortions. Finally, the level of methylation of the PTPRN2 gene depended on the age of mothers of spontaneous abortions with monosomy X, which raises the question of the influence of maternal factors on the methylation profile in this group of spontaneous abortions. Conclusion. The results indicate that epigenetic disorders of the PRDM16 gene may be associated with spontaneous termination of pregnancy in the first trimester.

RUDN Journal of Medicine. 2023;27(4):515-531
pages 515-531 views

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