Medical academic journal

The journal “Meditsinskiy Akademicheskiy Zhurnal” published since 2001 is an official journal of the Northwest Branch of the Russian Academy Sciences. Its initiator and Editor-in-Chief in 2001-2009 was Academician of the Russian Academy of Medical Sciences Boris Ivanovich Tkachenko whose contribution to the development of the journal is invaluable. The first Deputy Editor-in-Chief of the journal was Academician of RAMS V.A. Nagornev, and its Executive Secretary was Corresponding Member of RAMS N.S. Sapronov.

In September 2009, the position of Editor-in-Chief was taken by Corresponding Member of RAMS I.P. Dudanov, of Deputy Editor-in Chief, by Corresponding Member of RAMS N.S. Sapronov, and of Executive Secretary, by Prof. P.D. Shabanov.

The high publication level and wide appreciation by specialists in the course of formation and development of the journal were ensured by outstanding contributors, including Academicians E.K. Ailamazyan, N.A. Belyakov, Yu.D. Ignatov, Yu.V. Lobzin, V.I. Mazurov, N.A. Maystrenko, and A.A. Totolyan, and Corresponding Members of RAS I.A. Yeriukhin, S.A. Ketlinskiy, M.M. Odinak, Ye.A. Selivanov, and S.A. Simbirtsev.

Since 2010 up to the present time, Editor-in-Chief of the journal is Academician G.A. Sofronov. Since 2012, its Deputy Editor-in-Chief is Academician N.A. Belyakov, and its Executive Secretary is A.B. Dmitriyev PhD. The Editorial and Advisory Boards of the journal include prominent scientists representing the Northwest of Russia and distinguished scientific schools of Saint Petersburg.

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Vol 22, No 1 (2022)

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Original research

Effect of 3-formylchromone derivatives on neuroinflammation reactions and JNK and NF-κB regulatory pathways
Pozdnyakov D.I.
Abstract

BACKGROUND: Neuroinflammation is a significant component of the pathogenesis of cerebral ischemia. The JNK and NF-κB signaling pathways play a leading role in the progression of brain tissue inflammation, which may represent a promising target for therapeutic effects.

AIM: To evaluate the effect of new derivatives of 3-formylchromone on the course of neuroinflammation reactions and the activity of JNK and NF-κB translational pathways in brain tissue in rats with cerebral ischemia.

MATERIALS AND METHODS: Cerebral ischemia was modeled in Wistar rats by irreversible right-sided occlusion of the middle cerebral artery. The studied compounds and the reference (ethylmethylhydroxypyridine succinate) were administered per os at doses of 30 and 100 mg/kg, respectively. After 72 hours of ischemia, changes in the concentration of proinflammatory cytokines were evaluated in the cerebrospinal fluid: IL-6, IL-1β, IL-8 and TNF-α. The content of JNK and NF-κB in brain tissue was determined by enzyme immunoassay.

RESULTS: The use of the test compounds 3FC1, 3FC2, 3FC4 and 3FC5, as well as the reference medicine, contributed to a decrease in the content of proinflammatory markers in the liquor. At the same time, the most significant decrease was noted when the compound 3FC5 was administered to animals, namely, the concentration of IL-1β, IL-6, IL-8 and TNF-α was lower relative to similar indicators of the group of animals without treatment by 30.0% (p < 0.05); 64.5% (p < 0.05); 48.5% (p < 0.05) and 56.6% (p < 0.05), respectively. The use of the fluorine-containing compound 3FC3 did not significantly affect the course of brain tissue inflammation reactions in rats. Evaluation of changes in the activity of JNK and NF-κB showed that the studied substances inhibit the NF-κB translational pathway and do not affect JNK, which is probably due to the activation of these signaling pathways and the antioxidant potential of the studied molecules.

CONCLUSIONS: The use of compounds that are derivatives of 3-formylchromone in conditions of experimental cerebral ischemia contributes to the reduction of neuroinflammation reactions by inhibiting the NF-κB pathway, without affecting the activity of the JNK-dependent signaling system. The substance with the highest pharmacological effects is the compound 3FC5, which contains a spatially hindered phenolic hydroxyl in its structure.

Medical academic journal. 2022;22(1):7-15
pages 7-15 views
The impact of nebivolol, carvedilol and propranolol on pulmonary microhemodynamics in case of experimental pulmonary thromboembolism in rabbits
Evlakhov V.I., Poyassov I.Z., Berezina T.P.
Abstract

BACKGROUND: Beta-adrenoblockers nebivolol, carvedilol and propranolol are used in clinical cardiology for the treatment of patients with ischemic heart disease. Pulmonary thromboembolism can develop in such patients. However, its unknown, what will be the pulmonary microcirculatory changes in case of pulmonary thromboembolism after pretreatment with beta-blockers.

AIM: The comparative analysis of the pulmonary microhemodynamics changes following experimental pulmonary thromboembolism in rabbits after pretreatment with nebovolol, carvedilol and propranolol.

MATERIAL AND METHODS: In 35 isolated perfused rabbit lungs we investigated the changes of pulmonary microcirculation in case of experimental pulmonary thromboembolism after pretreatment with β1-blocker — nebivolol, combined blocker of α1- and β1, 2-adrenoceptors — carvedilol, and blocker of β1, 2-adrenoceptors propranolol.

RESULTS: After administration of β1, 2-adrenoceptors blocker — propranolol and β1-blocker — nebivolol the most of the pulmonary microcirculatory parameters increased. Combined α1-, β1, 2-blocker carvedilol caused mainly vasodilatory effects of the pulmonary arterial vessels, however, the pulmonary venous resistance increased. Pulmonary thromboembolism after pretreatment with beta-blockers caused pronounced increase of pulmonary artery pressure, precapillary and pulmonary vascular resistance. In that case after pretreatment with carvedilol capillary filtration coefficient was increased two times more than after propranolol administration; after pretreatment with nebivolol capillary filtration coefficient increased less, than after propranolol administration.

CONCLUSIONS: Acute pulmonary embolism caused less pronounced increasing of capillary filtration coefficient in case of nebivolol administration, than after pretreatment with carvedilol and propranolol.

Medical academic journal. 2022;22(1):17-27
pages 17-27 views
Metabolic and structural changes in the myocardium of rats with hypercholesterolemia after prolonged administration of simvastatin
Belousova E.S., Mikashinowich Z.I., Vinogradova E.V.
Abstract

BACKGROUND: The use of statins in cardiovascular pathologies in some cases is associated with the risk of developing statin-induced myopathy, the mechanisms of which are not fully understood. Only a few studies of molecular changes in the myocardium in statin myopathy are presented in the literature. However, the myocardium, as a type of muscle tissue, can also be involved in the pathological process. In this regard, in our opinion, it is advisable to analyze the biochemical changes in the rat myocardium against the background of the use of simvastatin.

AIM: To analysis of the dynamics of changes in the end products of glycolysis and the isoform composition of the giant protein titin in the heart muscle in animals with experimental hypercholesterolemia on the background of long-term administration of simvastatin.

MATERIALS AND METHODS: The study was carried out on outbred male rats divided into 3 groups: control group (35 individuals) — intact animals; comparison group (35 animals) — intact animals treated with simvastatin for two months; experimental group — divided into: subgroup 1 (35 individuals) — animals with induced alimentary hypercholesterolemia, subgroup 2 (35 individuals) — animals with induced alimentary hypercholesterolemia, which were administered simvastatin for two months. During the experiment, the content of the giant sarcomere protein titin, as well as changes in the concentration of pyruvate and lactic acid in the myocardium of the animals of the studied groups were studied.

RESULTS: In animals with a physiological course of metabolic processes, the administration of simvastatin caused the accumulation of lactic acid in the myocardium. Under conditions of alimentary hypercholesterolemia under the influence of simvastatin, a decrease in the elevated level of pyruvate and lactic acid was revealed, which is obviously due to a decrease in pathobiochemical shifts in energy metabolism. The determination of the isoform composition of titin made it possible to establish that the administration of simvastatin under conditions of alimentary hypercholesterolemia contributed to the appearance of early dystrophic changes in the myocardium, which is consistent with the results of earlier studies of impaired myocardial contractile activity under the influence of statins.

CONCLUSIONS: The results obtained indicate the need for a more thorough study of statins in terms of their safe use in patients with cardiovascular pathology.

Medical academic journal. 2022;22(1):29-36
pages 29-36 views
Serum matrix metalloproteinase type 9 in patients with coronary heart disease
Pigarevsky P.V., Maltseva S.V., Tanyansky D.A., Firova E.M., Tatarinov A.E., Chivikova N.V.
Abstract

BACKGROUND: The study sends to quantify type 9 matrix metalloproteinase in serum in patients with coronary heart disease, since this enzyme is able to provoke an immunoinflammatory process leading to destabilization of atherosclerotic plaque, the development of unstable angina and acute coronary syndrome.

AIM: Is to conduct a comparative analysis of the quantitative content of MMR-9 in serum in patients with coronary heart disease (CHD) with a different course of angina and atherosclerosis and in relatively healthy individuals.

MATERIALS AND METHODS: Blood serum samples of 66 CHD patients were examined. All patients based on clinical examination were divided into 3 groups, depending on the severity of the disease. Quantitative MMR-9 analysis was performed using the Thermo Fisher ELISA kits (BMS2016-2). Determination of the amount of MMR-9 in serum was recorded in the ELX 800 ELISA reader plate. Data processing was carried out using Statistica 6.0 statistical analysis (StatSof, USA). The results were presented as means and mean errors.

RESULTS: The obtained results indicate a significant decrease in the concentration of MMR-9 in the serum of patients with an unstable course of the disease compared to the control group (relatively healthy people). This is probably due to the effect on the content and activity of its MMR-9 inhibitor TIMP-1. Further studies will investigate whether MMR-9 can be considered as a marker of destabilization of atherosclerotic plaque and act as an independent predictor of acute clinical complications in patients with cardiovascular pathology.

CONCLUSIONS: The study made it possible to establish a significant decrease in the concentration of MMR-9 in the serum of patients with an unstable course of atherosclerosis compared to the control group (relatively healthy people). In addition, in patients with an unstable course of atherosclerosis, a tendency to reduce the concentration of this enzyme compared to persons with stable atherosclerosis was revealed.

Medical academic journal. 2022;22(1):37-42
pages 37-42 views
The effect of vital stress on the bioelectric activity of the brain and the behavior of female rats
Avaliani T.V., Apraksina N.K., Tsikunov S.G.
Abstract

BACKGROUND: Identification of possible biomarkers that assess the severity of post-traumatic stress symptoms is an urgent task for the early diagnosis of post-traumatic stress disorders. The manifestation of emotional states, both human and animal, is reflected in altered behavior and in the violation of the ratio of basic rhythms and cross-correlation connections in the brain electroencephalogram, which indicates the development of pathological processes.

AIM: The aim of the study was to analyze the behavior and electrocorticogram indicators of rats in the delayed period (on day 7) after life-threatening stress, as a way to predict the formation of post-traumatic stress disorder.

MATERIALS AND METHODS: The study was performed on mature female Wistar rats weighing 180–200 g (n = 40). Mental trauma was modeled by the circumstances of experiencing the situation of the death of a partner from the action of a predator and the threat to their own life when placing rats in a terrarium with a tiger python. In rats, the behavior in the “Open Field” test and the bioelectric activity of the brain in the frontal and occipital regions on the left and right were analyzed before and on the 7th day after stress exposure.

RESULTS: It is shown that in the delayed period after vital stress in female rats, there is a decrease in motor and research activity and altered emotional behavior in the “Open Field” test. Reduction of interhemispheric asymmetry in the index of theta and delta activity and changes in cross-correlation connections in the right hemisphere, as well as changes in the ratio of the main rhythms and cross-correlation connections of the electroencephalography. The revealed changes in the delayed period indicate a pronounced aversive nature of the psychotraumatic effect.

CONCLUSIONS: Life-threatening stress is caused by changes in electrophysiological and behavioral parameters in experimental animals not only at the time of exposure, but also in the long-term period.

Medical academic journal. 2022;22(1):43-50
pages 43-50 views
Diurnal dynamics of rat blood electrolytes at constant lighting and chronic alcohol intoxication
Kirillov Y.A., Makartseva L.A., Kozlova M.A., Muratova M.V., Chernov I.A., Areshidze D.A.
Abstract

BACKGROUND: Violation of the lighting regime, as well as alcohol abuse, is significant factors in the disorganization of biorhythms in the modern world. Violation of rhythm leads to a mismatch of body functions, as a result to disadaptation, the occurrence of desynchronosis and the development of a number of socially significant diseases.

AIM: Study of influence of constant lighting, chronic alcohol intoxication and joint action of these factors on diurnal dynamics of several electrolytes in blood of rats.

MATERIALS AND METHODS: The study was conducted on 160 male of Wistar outbred stock at age of 6 months, with body weight of 300 ± 20 g, which were divided into 4 groups. Control group — animals, which were kept under conditions of fixed light regime (light:darkness = 10:14 hours), I group — animals, which were kept under conditions of fixed light regime, but received a 15% water solution of ethanol as a drink, II group — animals, which were kept under conditions of constant light regime, III group — animals, which were kept under conditions of constant light regime and received a 15% water solution of ethanol as a drink. In blood samples, taken at 9:00, 15:00, 21:00 and 3:00 o’clock, the concentration of total calcium, potassium, sodium, chlorine and phosphorus was measured. The reliability of circadian rhythmicity was determined through cosinor analysis.

RESULTS: The increase in the concentration of phosphorus in the blood plasma of animals of II and III experimental groups was found with the decrease in the concentration of total calcium in animals of I and III experimental groups. Constant lighting and chronic alcohol intoxication affect the amplitude-phase characteristics of the circadian rhythms of all studied ions, and the combined action of these factors causes the destruction of the circadian rhythms of the studied electrolytes.

CONCLUSIONS: It is established that the three-weeks-long influence of the studied chronodestructors leads to disruptions in metabolism of calcium and phosphorus, which are the most pronounced at joint action of darkness deprivation and chronic alcohol intoxication, and also to the significant disruptions in the structure of CRs of all of studied substances.

Medical academic journal. 2022;22(1):51-59
pages 51-59 views

Analytical reviews

Modern understanding of the consequences of lack of sleep
Gavrilov Y.V.
Abstract

Sleep deficit disrupts the normal function of systems and organs in humans and becomes ”epidemic” in nature. Knowledge of the physiology of sleep and the impact of sleep deprivation on the body has expanded in recent years and allows a new assessment of the scale and depth of the problem. In the review summarizes current ideas about the effect of lack of sleep on chronic diseases and pathological processes, taking into account various body systems. Different reviews and studies over the past years have been analyzed, related to lack of sleep which contributes to the development of various diseases, have been analyzed. The use of new information about the impact of sleep on human health and the consequences of its lack opens up additional perspectives in understanding experimental and clinical work. This information can be actively used in diagnostics and therapy within the framework of integrative medicine.

Medical academic journal. 2022;22(1):61-72
pages 61-72 views
Multiple functions of tumor supressor p53
Gudkova A.Y., Antimonova O.I., Shavlovsky M.M.
Abstract

One of the most investigated and inscrutable eukaryotic proteins is a factor positioned as tumor suppressor which structural changes are observed in 50% of malignant cells. In the literature this protein is referred to as p53. The generalized function of p53 resolves to maintaining of cell genetic stability and preventing cell automatization. Therefore, p53 was called the “keeper”, or “guardian”, of the genome. Suppressive activity of p53 in regard to appearance of malignant cells seems to be side function of this protein. The present review prоvides data on the role of p53 in various vital processes in eukaryotic cells. p53 is a complex protein in its domain structure, and the semi-autonomous role of individual domains is clearly discernible. Normally, p53 is not a crucial factor in ontogenesis. At the same time p53 modulates the activity of about 500 different genes and also maintains homeostasis in cells and organism directly via protein-protein interactions. In response to exogenous and endogenous impacts p53 provides a balance of cellular metabolism and either promotes elimination of abnormalities, or triggers an apoptotic cascade. The review summarizes current considerations of p53 multiple functions as well as discusses already established and not yet disclosed mechanisms concerning involvement of said factor in cellular metabolism.

Medical academic journal. 2022;22(1):73-88
pages 73-88 views
Molecular mechanisms of drug resistance of glial tumor of brain. Part 2: Proliferation, angiogenesis, metastasis and recurrency
Chernov A.N., Galimova E.S., Shamova O.V.
Abstract

The main reason for the low efficiency of glioblastoma therapy is its resistance to therapeutic procedures. The development of multidrug resistance occurs as a result of the selection of tumor clones during therapy. The resistant cell clones to radiotherapy and chemotherapy can proliferate, leading to tumor growth, in which its own vascular network is formed (angiogenesis), which promotes cell migration, invasion and the appearance of metastases and recurrent glioblastoma. The review examines the relationship at the molecular level of multidrug resistance with proliferation, angiogenesis, migration, metastasis, and the formation of glioblastoma relapses, with an emphasis on identifying new targets among proteins, microRNAs, signal transduction kinases, transcription factors, tumor-supressor genes and oncogenes.

Medical academic journal. 2022;22(1):89-117
pages 89-117 views

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