Succinate dehydrogenase as a new target for melatonin binding in the complex diabetes mellitus treatment

Elbekyan K.S., Markarova E.V., Unanyan L.S., Diskaeva E.I., Pervushin Y.V., Bidzhieva F.A.


Relevance. Alloxan, destroying the beta cells of the pancreas, provokes hyperglycemia, which causes a hypoenergetic state. Mitochondrial succinate dehydrogenase dysfunction plays an important role in the pathogenesis of diabetes. Pharmacotherapy of diabetes mellitus has been and remains the subject of numerous studies. Recently, the attention of researchers is increasingly attracted by the hormone of the pineal gland - melatonin, due to its biological and pharmacological properties. The aim of the study was to study the effect of melatonin on the activity of succinate dehydrogenase as a new target in experimental alloxan-induced diabetes mellitus. Materials and methods. The studies were carried out on male Wistar rats, with an average mass of 120-150 g, which were kept on a standard diet. The animals were divided into 4 groups. The control group was injected with saline solution, the second group was injected with melatonin at a dose of 1 mg/kg daily for 14 days, experimental diabetes in animals was simulated by intraperitoneal administration of alloxan at a dose of 150 mg/kg with diabetes. The fourth group of animals received melatonin on the background of alloxan. Succinate dehydrogenase activity was determined in liver and pancreatic tissues by photometric method. For the docking analysis, the AutoDock Vina and AutoDock Tools software packages were used. Results and Discussion. According to the results obtained, reciprocal relationships arise under the influence of alloxan in the activity of SDH in the liver and pancreas. Alloxan causes an increase in the activity of SDH in the liver by 1.9 times, and in the pancreatic tissue there is a significant decrease - by 5 times. The use of melatonin for animals with alloxan diabetes led to a decrease in the activity of succinate dehydrogenase in the liver by one and a half times in comparison with the indicators of rats with alloxan diabetes. In the pancreas, on the contrary, the activity of the enzyme increased by 3.3 times, which may indicate the restoration of the function of Langerhans beta cells. Conclusion. Melatonin blocking succinate dehydrogenase domain A reduces the hyperactivity of the enzyme in the liver, and in the pancreas through its specific receptors (MR1 and MR2) present on the surface of the membranes of β- and α-cells directly interferes with the function of the cellular elements of the islets of Langerhans, restoring them.

RUDN Journal of Medicine. 2022;26(3):221-231
pages 221-231 views

Supraoptic nucleus morphological features of the hypothalamus in the skin burn injury dynamics

Samotrueva M.A., Azhikova A.K.


Relevance. The relevance of the study of the large cell nucleus of the anterior hypothalamus in case of skin damage is due to the important role of accompanying reactive changes in the neuroendocrine regulatory complex in stress. Since the hypothalamus is part of neuroendocrine cooperation, it shows pronounced signs of structural disorganization of neurons. The purpose of the study is to study structural changes in the supraoptic nucleus of the hypothalamus of rats in the dynamics of thermal burn injury of the skin. Materials and Methods. The study was conducted in laboratory mature male rats. To assess the morphological features of the supraoptic nucleus of the hypothalamus in the dynamics of skin burn injury, histological examination methods were carried out. The morphological analysis evaluated the neurotopographic organization of the nucleus and its structural organization. Structural transformations were judged by the shape and location of neurons, by the shape of neuronal pericarions, by the presence of focal gliosis, swelling, spongiosis. Results and Discussion. The results of morphological analysis showed that in the conditions of burn damage to the skin in the supraoptic nucleus of the hypothalamus, pronounced destructive changes in the form of focal gliosis, swelling, spongiosis, reversible and irreversible damage to nerve cells occurred in the initial post-traumatic period (on days 2-4). Weak structural tissue transformations on days 7-10 after burn exposure reflected the dynamics of repair of damaged nerve cells, testifying to of partial disorganization of nerve cells of a restorative nature. Conclusion. Thus, the revealed structural disorders in the supraoptic nucleus of the hypothalamus can be regarded as insignificant, which indicates the complex internal organization of the supraoptic nucleus of the hypothalamus and its high resistance to damaging exogenous influences. The morphological features of the supraoptic nucleus of the hypothalamus confirm the involvement of the neurosecretory apparatus in the process of adaptation to stress against the background of burn exposure, the selective participation of their neurohormones in the regulation of normal and pathological conditions, exerting a wide range of physiological influences in the development of protective and adaptive mechanisms.

RUDN Journal of Medicine. 2022;26(3):232-242
pages 232-242 views

Local hardware hypothermia influence on the physiological processes

Guseynov N.A., Hammouri M.H., Muraev A.A., Ivanov S.Y., Lukianova E.A., Klimenko A.S., Noeerazlighi M.A.


Relevance. Cold vasodilation is a response to a decrease in local and general temperature. Dose-controlled hypothermia is a therapeutic method for treating various pathological processes. Materials and Methods. In our study, we analyzed various indicators of the general condition of the human body under the influence of local controlled hypothermia. The study involved 25 healthy volunteers from the age of 21 to 34, including 14 males and 11 females. The study was carried out at a constant temperature of 25 ºС, relative humidity of 30 ± 5%, and an atmospheric pressure of 765mm Hg in silence and moderate illumination. The instruments of these indicators were bio-impedancemetry, angioscanning, as well as general thermometry. We also performed local thermometry of the buccal mucosa to identify temperature correlations between local hypothermia and buccal mucosa temperature. Local сontrolled hypothermia of the face was carried out by applying an elastic mask to the subject’s face. The mask had a system of irrigation tubes connected to the «ViTherm» device, which cooled the liquid and maintained its circulation. Due to the circulation of the cooled liquid in the mask the face was cooled. The mask covered the parotid-chewing, buccal, zygomatic, and infraorbital regions on the right and left. LCG lasted 50 minutes, and the circulating fluid temperature was 18 ºС. Results and Discussion. The effect of local controlled hypothermia at 18-20 °C did not affect vital signs in healthy adults: active cell mass, electrical reactance, extracellular fluid, oxygen saturation, the duration of systole. pulse. general temperature. At the same time, a decrease in tissue hydration was recorded. The revealed physiological effect of local hypothermia justifies using this temperature regime to reduce postoperative edema. Conclusion. Due to the absence of negative effects of local controlled hypothermia on the vital signs of the human body, the development and application of this tool in clinical practice, including the dental surgeon. is relevant.

RUDN Journal of Medicine. 2022;26(3):243-258
pages 243-258 views

Rat adrenal medulla modular organization

Kemoklidze K.G., Tyumina N.A.


Relevance. The concept of the tissue morpho-functional units (modules) of the adrenal medulla is currently not fully developed for adrenaline-storing (A-) cells and completely undeveloped for noradrenaline-storing (NA-) cells. Aim. Separately for A- and NA-cells, establish modules in adrenal medulla based on criteria developed by fundamental histology. Materials and Methods. The study used serial, semithin, and ultrathin sections of the adrenal glands, 7-9 µm thick, from 6 adult male Wistar rats (weight 335 ± 25 g). The sections were stained according to the Honoré method with additional staining with toluidine blue, which allows one to reliably distinguish between A and HA cells in the medulla. A cells are stained blue and HA cells are stained green. Light and electron microscopy was used to visualize serial, semithin, and ultrathin sections of the adrenal glands of adult male rats with A- and HA-cell differentiation. Results and Discussion. A-cells formed round clusters, in which they were located in one layer on the basement membrane. Their lateral sides closely adjoined each other, while the inner sides (the central part of the complexes) formed intercellular expansions, microprotrusions, and primary cilia. Less firmly pressed NA-cells formed polyhedral beams. Both types of cell complexes were associated with auxiliary components (stromal, nervous, circulatory, etc.). The central expansions of A-cell round clusters apparently to serve to retain some of the already produced adrenaline, which increases the readiness of the medulla to rapidly release large amounts of adrenaline in case of hyperacute stress. Accordingly, the adherence of A-cell complexes to a rounded shape is determined by the need to create such central isolated storage expansions. NA-cells are located more freely and do not form isolated intercellular expansions. This allows NA-cells to wedge between stably round A-cell complexes and form polyhedral beams as a result. Conclusion. It was found that the rat adrenal medulla contains two logically and morpho-functionally distinct types of specific modules. A-module are A-cells rounded cluster and NA-module is polyhedral NA-cells beam, both associated with auxiliary components.

RUDN Journal of Medicine. 2022;26(3):259-273
pages 259-273 views

Redox intensity and psychoemotional status of rats in burn skin injury

Azhikova A.K., Samotrueva M.A.


Relevance. Currently, the problem of regeneration of damaged skin, including of a burn nature, remains relevant. The work describes the results of the study of the redox intensity and of the psychoemotional status of rats in thermal skin injury. The aim of the study is an experimental study of the redox intensity and of the psychoemotional status of rats in burn skin injury. Materials and Methods. The study was conducted on nonlinear male rats of average weight 250 grams for 6-8 months. To assess psychoemotional status, studies were carried out using standard psychophysiological methods: «Open Field», «Elevated cruciform maze», «Suok Test» and «Porsolt.» The intensity of redox processes in the hypothalamic and prefrontal regions of the brain was assessed by determining the intensity of lipid peroxidation and catalase activity. The activity of lipid peroxidation was determined by the initial content of malonic dialdehyde, as well as by the rate of spontaneous and ascorbic peroxidation of lipids. Results and Discussion. During the study, it was found that burn damage to the skin was accompanied by an increase in the concentration of TBC-active products of lipid peroxidation in the hypothalamic and prefrontal regions of the brain of rats, which resulted in the development of oxidative stress. Burn injury initiated peroxidation processes in the studied areas of the brain, the most pronounced in the early period of the burn process (on days 2-4), with varying degrees decreasing in the following periods (on days 7, 10). The results of the assessment of the psychoemotional status of animals in burn skin injury in standard behavioral tests confirm the involvement of the nervous system in response to stress, the reflex activity of which under stressful conditions manifests itself in a change in behavioral reactions. In the conditions of burn damage to the skin, signs of an alarming-depressive state, in particular disorientation in space, suppression of the psychoemotional state, and a change in the nature of behavioral reactions were noted. Conclusion. Thus, the revealed changes in the intensity of redox processes and the peculiarities of the psychoemotional status of rats in burn skin damage are the result of biochemical and functional disorders of the brain, activated during protective and adaptation reactions in burn injury.

RUDN Journal of Medicine. 2022;26(3):274-288
pages 274-288 views

Prognostic value of autoantibodies to cardiomyocyte proteins in the diagnosis of chronic physical overexertion

Levochkina E.D., Belyaev N.G., Baturin V.A., Rzhepakovsky I.V., Abasova T.V., Smyshnov K.M., Piskov S.I.


Relevance. In conditions of ever-increasing volume of training loads, the frequency of cases of chronic physical overstrain (CPO) among athletes is increasing. It determines the importance of early diagnosis of the formed pathology of the cardiovascular system in order to prevent its further development. The aim of the study was to study the dynamics of autoantibodies to cardiomyocyte proteins using an experimental model of CPO and to determine the prospects of a laboratory method for the determination of autoantibodies for early diagnosis of pathomorphological changes in the heart. Materials and Methods. The study was conducted on male white rats. A treadmill was used to model CPO. In animals, the heart rate was measured, electrical phenomena in the heart were recorded. The content of hemoglobin and erythrocytes was determined in the blood. The level of cardiospecific autoantibodies (auto-AB) to troponin I, to alpha-actin 1, and to the heavy chain of beta-myosin 7B was measured. Heart mass was measured and histomorphological assessment of the state of cardiomyocytes was carried out. Results and Discussion. While modeling CPO, a decrease in body weight of the animals, the development of anemia, and cardiac hypertrophy were recorded. A decrease in body weight by more than 30 % was recorded from days 25 to 35 of the modeled CPO. A decrease in the number of erythrocytes in the blood was noted on day 25 with a peak fall on days 30-35. The mass of heart of animals in the dynamics of 0-15-35 days was 0.39±0.003; 0.41±0.001; 0.44±0.005 g/100 g, respectively. On day 25, sinus tachycardia was recorded in 2 % of the animals. On days 30 and 35, in 10 % of the studied rats, a violation of the processes of repolarization of the left ventricle by the type of subepicardial ischemia was recorded. On the 25th day, fibrosis of the perivascular region was visualized, passing into the interstitial field between the myofibrils. Reticulate structures of connective tissue fibers between cardiomyocytes were found. The period of 30-35 days was characterized by even greater severity of pathomorphological changes: myocardial hypertrophy, moderate myocardial dystrophy, interstitial and perivascular fibrosis. An increase in the number of detectable auto-ABs to cardiomyocyte proteins was noted on the 10th day of the experiment. A multiple increase in autoantibodies to cardiomyocyte proteins was recorded earlier than functional disorders in the heart and morphological changes in cardiomyocytes were detected. Conclusion. The laboratory method for determining auto-ABs to myocardial proteins can be the earliest of the complex methods for diagnosing disorders that are formed in the body in conditions of adaptation to intense and prolonged physical exertion.

RUDN Journal of Medicine. 2022;26(3):289-303
pages 289-303 views


Drug dependence analysis in young adults living in Moscow and across Russia for the years 2010-2020

Abramov A.Y., Koshkina E.A., Kicha D.I., Alekseyenko A.O.


Relevance. A statistical study of drug addiction among young people for 2010-2020 is needed in order to develop recommendations for the treatment of drug addiction. The aim of the research was to analyze trends of substances dependence disorder among adolescents. Materials and Methods. The present research is based on the national statistics data collected and presented in Federal Statistical Monitoring Form № 11 ‘Data on substances dependence disorder cases’; Federal Statistical Monitoring Form № 37 ‘Data on drug and toxic substances (inhalant) addicted adults’, which include estimates about adolescents aged 15-17 who seek addiction treatment initiation at public medical health facilities across Russia and in Moscow. The monitoring period is from 2010 to 2020. All substances dependence disorder morbidity rates were analyzed according to ICD-10 and presented as a breakdown of: drug addiction (dependence) syndrome and health detrimental abuse, first admissions; diagnostic groups, and medical conditions - mental disorders and deviant behaviors caused by drug and non-narcotic psychoactive substances abuse. The data were collected, compiled and Microsoft Office Excel 2016-processed to underlie a database. Results and Discussion. Alcohol and psychoactive substances abuse disorders showed the downward trend, both across Russia and Moscow. Drug abuse disorders showed the decline across Russia, while Moscow saw the same rates growing. Conclusion. The set of the government-backed programs adopted across Russia and in Moscow to fight the spread of adolescent substances dependence disorders delivered a positive result.

RUDN Journal of Medicine. 2022;26(3):304-315
pages 304-315 views

Development and application experience of the clinical and organizational management algorithm for tuberculosis medical care at the regional level

Kostin A.A., Abramov A.Y., Tsvetkov A.I., Kicha D.I., Rukodaynyy O.V., Goloshchapov-Aksenov R.S.


Relevance. The high incidence, prevalence and mortality in tuberculosis determines the relevance of improving clinical and organizational processes in terms of algorithmization. The aim of the study was to develop and evaluate the effectiveness of the clinical and organizational management algorithm for tuberculosis medical care at the regional level. Materials and Methods. The object of the study (2007-2021) were the tuberculosis medical care system of the Sverdlovsk region, Russian Federation. The scientific and methodological bases were Department of Health Organization, Drug Supply, Medical Technologies and Hygiene of the Peoples’ Friendship University of Russia topic SRW № 214791-3-000. The development of the algorithm was carried out on the basis of a scientifically proven universal clinical management system. The epidemiological tuberculosis author data and of Rosstat in the Sverdlovsk region for 2007-2020 were used - general and structural morbidity, prevalence, mortality, as well as the number of 3, 4 and 6 groups of dispensary registration of patients. The efficiency of the algorithm was evaluated by the dynamics of the complex of epidemiological indicators of tuberculosis. Research methods were applied: content analysis, analytical, statistical, comparative, expert. Significance was assessed using the t-White test. Differences in the compared parameters were considered significant at p<0.05. Results and Discussion. The effectiveness of the developed algorithm for managing regional tuberculosis medical care, including the components of needs analysis, systematization, automation and telecommunications, interdisciplinary integration, resource provision and performance evaluation, was confirmed by a significant decrease in the Sverdlovsk region for the period 2007-2020 general incidence by 2.05 times (from 119.9 to 51.7 per 100 thousand of the population), the incidence of children 0-14 years old by 1.48 times (from 18.7 to 12.6 per 100 thousand children of the corresponding age), prevalence in the population by 1.8 times (from 258.6 to 143 per 100 thousand of the population) and mortality from tuberculosis by 2.675 times (from 21.4 to 8.02 per 100 thousand of the population) (p<0.001). The COVID-19 pandemic (2020-2021) did not worsen the epidemiological situation for tuberculosis in the region. In 2020, an active form of tuberculosis was detected in 2201 people, which is 16 % less than in 2019 (p<0.05). The prevalence of epidemiologically dangerous bacillary forms of the disease for the period 2019-2020 decreased by 15.4 %, from 73.2 to 61.9 per 100 thousand population (p<0.05). Conclusion. Clinical and organizational management of tuberculosis medical care based on the algorithmization of scientifically evidence processes increases the effectiveness of therapeutic and preventive measures and the social and epidemiological well-being of the population.

RUDN Journal of Medicine. 2022;26(3):316-324
pages 316-324 views


Microenvironment influence on the development of epithelial-mesenchymal transformation in lung cancer

Kondratyuk R.B., Grekov I.S., Seleznev E.A.


Relevance. Epithelial-mesenchymal transformation (EMT) largely determines the biological behavior and prognosis of cancers of various localizations. It is known that the determining role in the control and implementation of the transition of the epithelial phenotype to the mesenchymal belongs to the microenvironment. At the same time, the histochemical and microscopic characteristics of stromal elements remain unclear; therefore, the aim of our study was to establish the morphological features of the stroma that affect the development of EMT in lung cancer. Materials and Methods. We studied 32 cases of lung cancer with hematoxylin and eosin staining of sections, Alcian blue at pH 1.0 and 2.5, PAS reaction, as well as immunohistochemical studies with monoclonal antibodies to HMW, AE 1 / AE 3, cytokeratin 18, c-erb B 2, vimentin E-cadherin, alpha-smooth muscle actin, GFAP and chromogranin A, Ki-67. In 16 cases, there was widespread epithelial-mesenchymal transformation (EMT), in 14 cases - focal and in 2 cases EMT was absent. In half of the cases of widespread EMT, it was complete; among the cases of focal EMT, it was not complete. The transition from the epithelial to the mesenchymal phenotype was facilitated by the activation of the stroma, namely, the presence of myofibroblasts and alcianophilia of the extracellular matrix, inflammatory cell infiltration, expression of the epidermal growth factor receptor (c-erb B 2) in stromal cells, proliferation and neurogenic differentiation of stromal cells of stromal cells. Results and Discussion. The activated stroma correlates with the frequency of EMT. Thus, large areas of activated stroma with the presence of myofibroblasts and alcianophilia of the extracellular matrix are more common in cases of widespread EMT (14 out of 16-87.5 %) than in cases of focal EMT (4 out of 14-28.6 %). The differences are statistically significant, p < 0.01. Inflammatory cell infiltration, which is the source of a signal for transformation, expression of the epidermal growth factor receptor (c-erb B 2) in stromal cells, proliferation, and neurogenic differentiation of stromal cells also correlated with the frequency of EMT. In all cases, the differences are statistically significant, p<0.01. Conclusions. The data obtained indicate the undoubted influence of signals from the activated stroma on the development of epithelial-mesenchymal transformation of tumor cells.

RUDN Journal of Medicine. 2022;26(3):325-337
pages 325-337 views

Suprascapular notch morphometric study

Chawla M., Sinsinwar P., Mishra A., Sorout J., Rao A.


Relevance. The suprascapular notch is one of the most crucial areas of the scapula from a clinical standpoint. Aside from its anatomical relevance, the suprascapular notch type may also have some clinical implications for suprascapular nerve entrapment. Aim of the study was the determination of the different dimensions of the suprascapular notch based on the maximum depth (MD) and superior transverse diameter (STD), as well as the clinical relation between those dimensions and suprascapular nerve entrapment. Materials and Methods. The study’s materials were 100 unknown dry human scapulae from the from the anatomy department of the Mahatma Gandhi Medical College, Sitapura, Jaipur, Rajasthan. Each scapula was studied for suprascapular notch. From each of the scapulae, maximum depth and superior transverse diameter were determined. Fifty were from right side and Fifty were from left side. Different types of suprascapular notches were observed based on maximum depth and superior transverse diameter. Results and Discussion. In this study, the overall percentage distribution frequency of the suprascapular notch in 100 scapulae is MD > STD (25 %), MD = STD (0 %), STD > MD (60 %) and SSN Absent (15 %) respectively. The most common SSN type is STD > MD (60 %) type and least common SSN type is MD = STD (0 %) type. Conclusion. Morphological examination of the scapular notch reveals a common site of nerve compression and also demonstrates the surgical importance of the scapular nerve during shoulder surgery.

RUDN Journal of Medicine. 2022;26(3):338-343
pages 338-343 views

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