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 20, No 4 (2020)

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Review
Neutrophilic granulocytes: phagocytes and more
Aleshina G.M.
Abstract

Neutrophilic granulocytes are one of the key cellular factors of innate immunity. The review presents data on the morphology, migration and utilization of neutrophilic granulocytes, phagocytosis and degranulation processes, neutrophilic extracellular traps, plasticity of neutrophils, their role in systemic inflammatory reactions and regulation of adaptive immunity.

Medical academic journal. 2020;20(4):5-16
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Pathophysiological and age-specific mechanisms of morpho-functional changes in spermatozoa in infertility
Dotsenko A.A., Polevshchikov A.V.
Abstract

The aim of the review is to analyze the causes and pathophysiological mechanisms of sperm alteration accompanying the development of male infertility, the sequence of the development of their dysfunctions in individuals of different ages. Male infertility is a worldwide problem; up to 20% of married couples are childless. In the Russian Federation, the problem is even more acute, which complicates the unfavorable demographic situation. Based on the generalization of the results of various screening studies, from 30 to 50% of men in the Russian Federation have impaired fertility. The review examines the main classifications and pathophysiological mechanisms of the development of male infertility. An extended assessment of changes in the morphology and functional properties of spermatozoa, relevant for the practice of in vitro fertilization, was carried out. The mechanisms of damage to spermatozoa and the sequence of development of degenerative changes in the cell are considered in detail. The mechanisms of sperm dysfunction development in men of different ages are compared. The conclusion is made about the need for further studies of the molecular mechanisms of fertility, deciphering the entire set of interactions between molecules and cells involved in the implementation of the reproduction function.

Medical academic journal. 2020;20(4):17-26
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Basic studies
1-desamino-8-D-arginin-vasopressin, DDAVP, increases the content of brain-derived neurotrophic factor (BDNF) in blood plasma of rats in model of post-traumatic stress disorder
Belokoskova S.G., Krytskaya D.V., Beznin G.V., Karpenko M.N., Tsikunov S.G.
Abstract

Objective. We aimed to analyze the effect of an agonist of vasopressin type 2 receptors, 1-desamino-8-D-arginine-vasopressin, DDAVP, on the content of the brain neurotrophic factor, BDNF, in the hippocampus and blood plasma of rats exposed to vital stress.

Material and methods. The study carried out on female Wistar rats divided into 4 groups: first group included control animals, 2 — those who received DDAVP intranasally in small doses (once 2 ∙ 10–9 g, course 20 ∙ 10–9 g), 3 — those who exposed to the stress of a threat to life caused by the experience of the death of a partner from the actions of a tiger python, 4 — those who exposed to stress and received DDAVP. BDNF concentration in samples was measured by immunohistochemical method.

Results. An increase in the content of BDNF in blood plasma in rats exposed to acute psychogenic stress and received DDAVP therapy was revealed on the tenth day after stress. There was no effect of stress, DDAVP, or their combined effect on the BDNF content in the homogenate of hippocampal tissues.

Conclusion. The results of this pilot study indicate that DDAVP has a modulatory effect on BDNF metabolism in rats exposed to vital stress. It is assumed that an increase in the level of neurotrophin in the blood of rats reflects the activation of compensatory processes.

Medical academic journal. 2020;20(4):27-34
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The peculiarities of pulmonary macro- and microhemodynamics changes after treatment with agonists and blockers of cholinoceptors
Evlakhov V.I., Poyassov I.Z., Berezina T.P.
Abstract

Background. The pulmonary arterial and venous vessels are innervated by parasympathetic cholinergic nerves. However, the studies, performed on the isolated rings of pulmonary vessels, can not give answer to the question about the role of cholinergic mechanisms in the changes of pulmonary circulation in full measure.

Aim. The comparative analysis of the changes of the pulmonary macro- and microhemodynamics after acetylcholine, atropine, pentamine and nitroglycerine treatment.

Materials and methods. The study was carried out on the anesthetized rabbits in the condition of intact circulation with the measurement of the pulmonary artery pressure and flow, venae cavae flows, cardiac output, and also on isolated perfused lungs in situ with stabilized pulmonary flow with measurement of the perfused pulmonary artery pressure, capillary hydrostatic pressure, capillary filtration coefficient and calculation of the pulmonary vascular resistance, pre- and postcapillary resistances.

Results. In the conditions of intact circulation after acetylcholine, pentamine and nitroglycerine treatment the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance did not change as a result of decreasing of pulmonary artery flow and left atrial pressure due to diminution of venous return and venae cavaе flows. On perfused isolated lungs acetylcholine caused the increasing of pulmonary artery pressure, capillary hydrostatic pressure, pulmonary vascular resistance, pre- and postcapillary resistance and capillary filtration coefficient. After M-blocker atropine treatment the indicated above parameters of pulmonary microcirculation increased, on the contrary, after N-blocker pentamine treatment they decreased. Nitroglycerine infusion caused less decreasing of the parameters of pulmonary microcirculation in comparison with effects of pentamine, but capillary filtration coefficient decreased to a greater extent. These data indicate that nitroglycerine decreases endothelial permeability of pulmonary microvessels.

Conclusion. After activation or blockade of cholinergic mechanisms in the condition of intact circulation the calculated parameter of pulmonary vascular resistance is depended from the ratio of the pulmonary artery pressure and flow and left atrial pressure, which are determined by the venous return. The different character of the changes of pulmonary microcirculatory parameters after M-blocker atropine and N-blocker pentamine treatment is evidence of reciprocal relations of M- and N-cholinoceptors in the nervous regulation of the pulmonary microcirculatory bed.

Medical academic journal. 2020;20(4):35-44
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The role of hypoxia in the integrity of the genetic apparatus and the formation of memory in drosophila in the paradigm of conditioned reflex suppression of courtship
Medvedeva A.V., Tokmacheva E.V., Nikitina E.A., Vasilieva S.A., Zalomaeva E.S., Savvateeva-Popova E.V.
Abstract

M.E. Lobashev and V.В. Savvateev in 1959 obtained unique data on the expansion of the adaptive capabilities of the organism when training the properties of higher nervous activity by the formation of conditioned food reflexes to stimuli that exhaust the nervous system. Apparently, the formation of a conditioned connection help to overcoming stressful effects, adaptation to restrictive conditions, and changes in the functioning of the nervous system. To test this assumption, the influence of stressful influences hypoxia on learning and memory of Drosophila in the paradigm of conditioned reflex suppression of courtship was studied. The results were obtained on the enhancement of the ability to learn under hypoxic exposure. These experimental conditions did not affect memory formation. The effect of hypoxia on chromosomes through the formation of double-stranded breaks was revealed. The data are discussed in light of the relationship between neuroplasticity processes and mechanisms of adaptation to stressors.

Medical academic journal. 2020;20(4):45-54
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Evaluate the role of mercury chloride in the development of toxic pulmonary edema in laboratory animals during intoxication with substances of acylating action
Tolkach P.G., Basharin V.A., Chepur S.V., Sizova D.T., Vengerovich N.G.
Abstract

Relevance. Intoxication of acylate pulmonotoxicants causes disturbance of structure and function of air-blood barrier, the output of liquid in the interstitial and alveolar space and manifestation of lung edema. Aquaporins play an important role in the transportation of fluid through the alveolar-capillary membrane, including pathological conditions. Water permeability through aquaporins is blocked by mercury ions. Using mercury chloride may reduce severity of the acute lung edema after intoxication of the pulmonotoxicants.

Intention. The goal is to evaluate the role of mercury dichloride in the development of toxic pulmonary edema in laboratory animals during intoxication with pulmonotoxicants with an acylating effect.

Methodology. Laboratory animals (rats and rabbits) were exposed to inhalation intoxication of carbonic acid dichloride and perfluoroisobutylene at concentrations of 1,5LC50. In 30 minutes after exposure were administrated of 0,3LD50 mercury chloride to the animals subcutaneously. The oxygenation index, acid-base state, pulmonary coefficient, histological changes in lung was investigated in 6 hours after exposure.

Results. It was found that intoxication with carbonic acid dichloride and perfluoroisobutylene at concentrations of 1,5LC50 led to the development of toxic pulmonary edema in rats and rabbits 6 hours following exposure. The administration mercury chloride to 30 minutes following exposure to the pulmonotoxicants under study, led to a decrease (p < 0.05) in the pulmonary coefficient, an increase (p < 0.05) in the oxygenation index and normalization of the acid-base state according to compared with animals receiving 0.9 % NaCl following intoxication. When conducting a histological examination, in animals treated with mercury chloride less pronounced changes in the histoarchitectonics of the lung tissue were noted.

Conclusion. Considering the fact that the administration of mercury chloride to animals led to a decrease in the manifestations of pulmonary edema in animals, it was suggested that aquaporins play an important role in the pathogenesis of toxic pulmonary edema caused by intoxication with pulmonotoxicants with an acylating effect. The use of selective blockers of aquaporins (less toxic than mercury chloride) may be a new direction in the pathogenetic therapy of toxic pulmonary edema due to exposure to pulmonotoxicants.

Medical academic journal. 2020;20(4):55-61
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SMI-32 — a novel axonal injury marker for investigation of ischemic brain pathology
Tsyba D.L., Kirik O.V., Korzhevskii D.E.
Abstract

The relevance of this work is determined by the high prevalence and social significance of cerebrovascular diseases and the need to develop effective methods for verifying neuronal damage due to cerebral ischemia in experimental models.

The aim of this study was to assess the possibility of immunohistochemical revealing of neurofilaments to detect axonal injury in cerebral ischemia models.

Materials and methods. A model of transient focal cerebral ischemia by the left middle cerebral artery occlusion was reproduced in male Wistar, SHR and WKY rats. Axonal injury was assessed by immunohistochemical reactions for neurofilament proteins using SMI-32 and 2F11 antibodies.

Results. In cerebral ischemia, damage to nerve fibers occurs, manifested by thickening of axons, their varicose expansion and segmental accumulation of neurofilament proteins. These changes are more noticeable with an immunohistochemical reaction to the SMI-32 marker of neurofilament heavy chain.

Conclusions. The use of antibodies to the non-phosphorylated neurofilament heavy chain makes it easy to identify degenerating nerve fibers and can be recommended as an alternative method for detecting axonal injury.

Medical academic journal. 2020;20(4):63-68
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Lecture
SAS ENTERPRISE GUIDE 6.1: LINEAR REGRESSION.
Bunenkov N.S., Komok V.V., Bobylkov V.A., Grudinin N.V., Bunenkova G.F., Grinenko O.A., Nemkov A.S.
Abstract

Objective: to develop algorithm of prediction of troponin I elevation 3d day postoperatively depending on troponin I level on 1st after on-pump coronary artery bypass grafting using SAS Enterprise Guide 6.1 software.

Materials and methods

Data collection was performed according to prospective non-randomized clinical trial AMIRI — CABG in Pavlov First St. Petersburg State Medical University, Saint Petersburg, Russia between 2016-2019 years with 336 patients with indications to coronary artery bypass grafting.

Algorithm was developed for on-pump group (n=128). There is database which include following information: troponin I level 1st and 3в days postoperatively. There was determined distribution of variables and linear regression was used for predicting model construction and its precision was estimated as well.

Results. There was developed algorithm of prediction of myocardial damage after on-pump coronary artery bypass grafting with linear regression model using SAS Enterprise Guide 6.1 software.

Conclusion. Presented algorithm of linear regression allows to compare independent groups for nominal data.

Medical academic journal. 2020;20(4):69-79
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Clinical research
Evaluation of plasma levels of meropenem in septic patients during extracorporeal blood purification
Marukhov A.V., Murzina E.V., Zakharov M.V., Sofronov G.A., Buryakova L.V., Ivanov M.B., Zhurkovich I.K., Ostrovidova E.V.
Abstract

The relevance. Meropenem is a broad-spectrum carbapenem antibiotic widely used to treat patients with sepsis / septic shock. Critically ill patients are usually supported with one of the forms extracorporeal blood purification. However, data on the effect of various extracorporeal support techniques on the pharmacokinetics and pharmacodynamics of meropenem are insufficient or contradictory.

Aim: To evaluate the effectiveness of meropenem dosage regimens in the treatment of septic patients during extracorporeal blood purification.

Materials and methods. Plasma concentrations of meropenem were monitored in three critically ill patients with sepsis or septic shock. Patients were treated using various extracorporeal support techniques. Meropenem was used as empirical antibacterial mono- or complex therapy (1 g every 8 or 12 hours). Meropenem concentrations in plasma were determined by validated assay methods on Acquity ultraefficient liquid chromatography (UPLC) H-Class system.

Results. It is shown that the meropenem plasma concentration in critically ill patients changes significantly. It was found that the standard meropenem dosing regimens in patients with sepsis / septic shock during continuous hemodiafiltration do not ensure the achievement of the PK/PD target of 100% T>MIC for sensitive strains (MIC≤2 mg/L) and for intermediate resistance pathogens (2≤MIC<8 mg/L). Continuous hemofiltration and selective adsorption of lipopolysaccharide have a less pronounced effect on the clearance of meropenem.

Conclusion. To increase the effectiveness of antibacterial therapy, it is necessary to conduct research aimed at developing protocols for dosing antibacterial drugs for the treatment of sepsis during extracorporeal blood purification.

Medical academic journal. 2020;20(4):81-94
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