BIOPHYSICAL PROPERTIES OF CELL SURFACE AND FUNCTIONAL ACTIVITY OF GRANULOCYTES OF PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA DURING MODELING OF ATP LOAD IN VITRO

The current study is devoted to the investigation of the biophysical properties of the cell surface and the functional activity of granulocytes in patients with acute lymphoblastic leukemia when simulating the ATP load in vitro. The experiment was performed on the peripheral blood of patients with acute lymphoblastic leukemia (ALL) who underwent a standard course of chemotherapy. In experimental tests, exogenous loading with ATP was simulated in vitro by adding 100.0 μM adenosine-5-triphosphate disodium salt trihydrate to the granulocyte suspension. Incubation with the drug was carried out for 15 min at 370 C. As a control, a suspension of granulocytes in RPMI 1640 medium from the same patient, but without the addition of the drug, was used, this was incubated for 15 min at a temperature of 370 C. After the incubation time, the biophysical properties (rigidity, charge of the cell surface, the strength of intercellular adhesion) of granulocytes in experimental and control samples were studied using atomic force microscopy, and the migration activity of cells was also assessed in a direct capillary test under agarose. A model with exogenous ATP in ALL patients showed a decrease in the rigidity and potential of the plasma membrane surface, an increase in the adhesive properties and migration activity of granulocytes. The revealed effects point to the key role of the ATP molecule in the mechanisms of intercellular signaling in the microvasculature.

ASSOCIATION OF OVARIAN VITAMIN D AND HORMONE RECEPTORS EXPRESSION IN WOMEN WITH POLYCYSTIC OVARY SYNDROME

Infertility is one of the most common diseases of the reproductive system, which carries a significant medical and social burden, affecting from 10 to 15% of married couples, and one of the causes of which is polycystic ovarian syndrome (PCOS), associated with menstrual and endocrine disorders. Changes in the concentration of key enzymes of the metabolic pathway of vitamin D in PCOS may affect the regulation of local tissue homeostasis. Mechanisms of inhibition of cell proliferation under the action of vitamin D have not been fully explored. The aim of the study is to investigate the expression of VDR and hormone receptors in the ovaries of women with PCOS. Material and methods. Patients were divided into main (I) and control groups (II), that included women (n=60) aged 18 to 44 years (mean age - 29.1±3.3 years), who at diagnostic laparoscopy due to infertility of unknown cause. Immunohistochemical (IHC) study of ovarian cysts was performed according to a standard protocol using antibodies to VDR, AR, ERß, PR. The expression of VRD, 1α-OH, 24-OH in samples of ovarian cysts was determined by polymerase chain reaction in real time (PCR-RT). Results. The following IHC expression of the studied markers was observed in the samples of the 1st group cysts of women with PCOS: VDR - 67.7±2.1%; AR - 51.7±1.3%; ERß - 23.1±1.2%; PR - 89.3±2.1%. According to PCR-RT data, the relative VDR expression in group I was 4,31±0,18 arb. u., vs 2,17±0,11 arb. u. in the control group. Conclusions. The key role in PCOS pathogenesis is played by complex metabolism disorder of vitamin D and androgen-estrogen balance as well as decrease of ERß and increase of PR expression level.

NON-SPECIFIC IMMUNOLOGICAL RESISTANCE IN DIFFERENT

Tuberculosis (TB) is a socially significant disease for the entire world community. An important challenge in successfully combating this infection is the avalanche increase in the number of drug-resistant tuberculosis. Currently, among the reasons for the development of pulmonary tuberculosis, a complex of etiological and pathogenic factors contributing to the disruption of the immune response to M. tuberculosis and the formation of secondary immunological failure (SIF) accompanying the disease are of particular importance. However, the issues of discoordination of cellular components of the local immune system of the lungs leading to T-cell deficiency, as well as the ineffectiveness of the B-cell link, reduction of lymphocyte proliferative activity and activation of apoptosis, cytokine imbalance and activation of immunosuppression mechanisms are not fully studied and have a scattered nature, which does not allow us to assess the overall picture of violations. The goal: determining the immunophenotype of lymphocyte population in lung tissue biopsy specimens of patients with various forms of secondary tuberculosis depending on resistance in case fibrosecavernous tuberculosis (FCT). The material in the study was pulmonary tissue fragments of 30 patients with the verified diagnosis of FCT, and distributed in 2 main groups: resistant forms of secondary tuberculosis (n = 15) and 15 patients not resistant forms of secondary tuberculosis. The standard histological method was used. Immunohistochemically panel of markers included CD68, CD4, CD8, CD20, CD138. The study was conducted at the Center for the collective use of scientific equipment «Molecular Biology» of the Medical Academy named after S.I. Georgievsky in the framework of the grant № ВГ 09/2019, supported by federal state autonomous educational institution of higher education «V.I. Vernadsky Crimean Federal University». The results of the study have shown that in the conditions of secondary tuberculosis, regardless of resistance, the formation of local immunodeficiency with an immune response along the Th-2 pathway is determined. The prevalence of cytotoxic lymphocytes in the area of specific granulation tissue and the draining bronchus indicated the prolongation of inflammation and its transfer to the latent phase. The increase in the number of T-helpers and activated plasma cells can serve a reliable prognostic and diagnostic marker for the reactivation of the tuberculosis process.

MORPHOLOGYCAL CHANGES IN THE TESTES OF EXPERIMENTAL ANIMALS IN CHRONIC ALCOHOL POISONING

The experiment with the chronic effects of alcohol on experimental animals reflects the picture of long-term use of alcoholic beverages by a person with alcoholism. It is impossible to fully study the ultrastructural changes in internal organs, including the reproductive system, in humans, both in acute and chronic alcohol consumption, but the results obtained in the experiment can be extrapolated to humans. The results obtained showed that changes in the parenchymal-stromal elements of the testicles during chronic alcoholization are reduced to dystrophic transformation of the spermatogenic epithelium. The testicular stroma is characterized by pronounced circulatory disorders with plethora and stasis in the postcapillaries and small veins, edema, phenomena of perivascular and interstitial sclerosis, with foci of pronounced hyalinosis, most expressed by 2-3 months of alcoholism. By 6 months of the model experiment, there was no dynamics of the growth of morphological changes, partial adaptation to constant intoxication with ethyl alcohol.

EFFECT OF MYOKINES ON THE QUANTITY OF HORMONE SENSITIVE LIPASE IN MSCS AND THE PRODUCTS OF THEIR ADIPOGENIC DIFFERENTIATION

The basic metabolic process associated with white and beige/brown adipose tissues is lipolysis – the sequential enzymatic process of the hydrolysis of triglycerides in the adipose tissue. It has been repeatedly shown that physical activity activates lipolysis. It has recently been shown that skeletal muscles have an endocrine role; producing a host of myogenic hormones – myokines. Current literature has an incomplete understanding of the interdependent relationship between skeletal muscles and adipose tissue. We researched the influence of myocyte secreted cytokines (myokines) – meteorin-like protein (METRNL) and β-aminoisobutyric acid (BAIBA), and the adrenergic agonist isoproterenol on the levels of total and phosphorylated (Ser552) hormone sensitive lipase (HSL) in adipose tissue derived mesenchymal stromal cells (MSCs) and the cellular products of their adipogenic differentiation. The MSCs were obtained from 5 healthy donors. The adipogenic differentiation protocol was carried out for a span of 21 days. After procuring the adipocyte cultures, the following stimulators were added – 5 μM METRNL, 5 μM BAIBA, and 5 μM isoproterenol. With the help of western blot, the change in the amount of total and activated levels of HSL were monitored in cells of three different adipogenic differentiation protocols in MSCs. We observed that HSL and its activated form are produced in cell cultures induced with factors for white, beige, and brown adipogenic differentiation.

CORONAVIRUS (TAXONOMY, VIRUS STRUCTURE)

The review is devoted to the little-known and insufficiently studied until recently taxonomic group of viruses - coronaviruses. The publication provides definitions: «coronaviruses» and «coronavirus infection». The issues of modern taxonomy of coronaviruses and its development from the discovery of the first coronavirus to the emergence of the last pandemic species - SARS-CoV-2 are discussed. The modern results of studying the morphology, structure and structure of the viral cell in coronaviruses, the characteristics of various representatives that cause diseases in humans and are of medical importance are described. The differences in the structure and structure of viruses of different types are pointed out and it is proposed to conditionally divide into «especially dangerous» and «banal» groups of coronaviruses. To analyze virological problems, modern literary sources, the opinion of international organizations, articles in the world’s leading medical and biological journals were used. In subsequent publications, the topic of coronaviruses and coronavirus infection will be continued.

MARIE FRANÇOIS XAVIER BICHAT (1771-1802)

The article tells about the great French surgeon, anatomist and physiologist Marie-François Xavier Bichat, the founder of science about tissues – histology, discoverer in an anatomy and creator of such medical disciplines, as a thanatology (science about death) and pathoanatomy. The most essential moments and facts from biography of scientist are described, his basic scientific insights are briefly expounded. Main scientific works and publications, and also described by Bichat anatomic structures and formations are enumerated. His name is carried on by several eponyms in anatomy fossa (pterygopalatine fossa), Bichat’s protuberance (buccal fat pad), Bichat’s foramen (cistern of the vena magna of Galen), Bichat’s ligament (lower fasciculus of the posterior sacroiliac ligament), Bichat’s fissure (transverse fissure of the brain) and Bichat’s tunic (tunica intima vasorum). The substantive provisions of the scientific conceptions offered to them in morphology and pathoanatomy are expounded. The critical importance of scientific works and discoveries of Marie-François Xavier Bichat for modern science and practical medicine is emphasized

BASIC APPROACHES AND USED METHODS IN THE TREATMENT OF COMBINED (LONGITUDINAL-TRANSVERSE) PLATFOOT

The article reflects the consideration of the problem of treatment of combined (longitudinal-transverse) flat feet and the use of various methods of correction of this pathology. The main approaches to the treatment of combined (longitudinal-transverse) flat feet are considered and a brief review of experimental studies and patent developments in relation to the treatment of combined (longitudinal-transverse) flat feet. The analysis of the experience of using various treatment methods for combined (longitudinal-transverse) flat feet in foreign and domestic practice is presented, problematic aspects of the fight against the pathology under consideration are highlighted. It is noted that the separate use of various treatment methods for combined (longitudinal-transverse) flatfoot has insufficient effectiveness and is associated with the risk of re-development of pathology, while the greatest effect in the early stages of the development of combined flatfoot gives the use of complex treatment, using both medication and various orthopedic methods, exercise therapy, and massage. The need for further scientific research in relation to the most effective combination of different treatment methods for combined flat feet was determined, which would give a positive dynamics of changes both in relation to the feet and lower extremities in general, and in relation to the entire musculoskeletal system. The necessity of considering the musculoskeletal system and the feet as a single mechanism, a kinematic chain with degrees of freedom (mobility and deformability in the joint), in which the transfer of reactive or reflected forces in the linking chain of the chain

VASOMOTOR REACTIONS ON LOCAL COOLING IN YOUNG INDIVIDUALS WITH NICOTINE ADDICTION

Tobacco smoking, as a harmful individual habit, aggravates the negative environmental effects on health in people living in the northern regions of Russia, by increasing the incidence of diseases of the cardiovascular and respiratory systems, and oncological diseases. This study was aimed at elucidating the vasomotor reactions on local cooling in young people with nicotine addiction. Materials and methods. Twenty four practically healthy people (13 m, 11 f) aged 18-27 years were enrolled to the study. Of these, 16 subjects with initial stage of nicotine addiction formed the study group, and 8 non-smoking subjects served as a reference group. The degree of nicotine addiction was assessed with the Fagerstrom test and the smoking index. The local cold test (LCT) was used to study vasomotor reactions. The autonomous regulation was estimated by analyzing the time- and frequency-domain characteristics of heart rate variability (HRV). Results. In the group with nicotine addiction, increased cold-induced vasoconstriction was revealed from the dynamics of the hand skin temperature during LCT. Also, this group mwas characterized by decreased vagotonia seen as lower values of time- (SDNN, RMSSD, pNN50 and CV) and frequency- domain (TP, HF and LF) parameters of HRV. The functional test with deep controlled breathing revealed in this group lower reactivity of neurogenic mechanisms of heart rate control. Among subjects with higher number of cigarette consumption, HRV changes which corresponded with adaptation disorders were more notable. Conclusion. Individuals with initial degree of nicotine addiction were characterized by the impaired reactivity of the central and peripheral parts of the circulatory system what means lower health capacity of the organism. Increased vascular reactivity during LCT, as well as the impaired adaptation seen with HRV analysis, could serve as early indicators of the systemic effects of tobacco smoking.

FEATURES OF EXPRESSION OF OCT4, NANOG AND ENDOGLIN IN RENAL CELL CARCINOMAS

Possibilities of the potential stem markers as cancer stem cells in renal cell carcnomas (RCC) and their prognostic significance are currently being studied. In this regard, the study of the expression pattern of transcription factors – NANOG and OCT4, as well as endoglin in the RCC is of great interest. The aim of the study was to conduct a comparative assessment of the expression of stem markers NANOG, OCT4, and CD105 in histological variants of renal cell carcinoma and determine their prognostic significance. Material and methods. The study was performed on surgical material from 225 patients with renal cell carcinoma. Antibodies used: NANOG, OCT4 and CD105. The nonparametric Pearson agreement test (χ2) was used to identify the differences between the compared groups. Results. NANOG expression was detected in 150 (66.7%) cases. Nuclear expression of OCT4 was detected in 72 (32%) samples in only single tumor cells. A positive response to CD105 was determined in 60 cases (26.7%). Conclusion. Reliable associations between the expression of CD105 and clinical parameters were revealed depending on the histological variant of renal cell carcinoma.