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Vol 23, No 1 (2023)

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Analytical reviews

Role of the intestinal microbiota in the pathogenesis of multiple sclerosis. Part 2. Gut microbiota as a predisposition factor for the multiple sclerosis development

Abdurasulova I.N.

Abstract

This part of the review focuses on the proposed involvement of the gut microbiota in the realization of the genetic risk of multiple sclerosis, the formation of the intestinal microbiome in early life, and provides data supporting the hypothesis that aberrant formation of the intestinal microbiota in early life may be a predisposing factor to multiple sclerosis.

Medical academic journal. 2023;23(1):5-40
pages 5-40 views

The concept of endothelial transcytosis as a theoretical prerequisite for the development of prevention and treatment of atherosclerosis

Parfenova N.S., Tanyanskiy D.A.

Abstract

Understanding how focal atherosclerotic lesions are formed in the vascular wall currently remains clearly incomplete, and primarily because the discussion of this issue is usually considered at the stage when low-density lipoproteins are already in the intima; the situation is largely clarified if attention is paid primarily to the mechanisms of intima infiltration by lipoproteins. From the modern point of view, we are talking about the molecular mechanisms of transcytosis, previously detected by the electron microscopy on endothelial cells of rat capillaries, which were injected with gold or ferritin nanoparticles to trace their path in the cytoplasm. Transcytosis as an active process, in which a number of receptors are involved, is contrasted with passive lipoproteins infiltration of the vascular wall. In addition to these concepts, the review discusses possible conditions for the implementation of low-density lipoproteins transcytosis, as well as the issues of regulation of transcytosis.

Medical academic journal. 2023;23(1):41-51
pages 41-51 views

Original research

Impact of beta-D-glucan on survival and hematopoietic parameters of mice after exposure to X-rays

Murzina E.V., Sofronov G.A., Simbirtsev A.S., Aksenova N.V., Zagorodnikov G.G., Veselova O.M., Zhirnova N.A., Dmitrieva E.V., Klimov N.A., Vorobeychikov E.V.

Abstract

BACKGROUND: There is a high need for drugs to reduce the side effects of radiation exposure on people in extreme, military, marine, space medicine, at nuclear facilities, in hematology and oncology.

AIM: To evaluate the antiradiation efficacy of beta-D-glucan derived from Oyster mushroom (Pleurotus ostreatus) after total body irradiation of mice in terms of survival and hematopoiesis.

MATERIALS AND METHODS: The study was conducted on a mouse model of the acute radiation hematopoietic syndrome caused by exposure to X-rays. Radioprotective effect of intragastrically administered beta-D-glucan derived from Pleurotus ostreatus at a dose of 500 mg/kg was studied. The parameters of the 30-day survival of irradiated mice were analyzed using the Kaplan–Meyer method. Dose reduction factor of X-ray radiation was calculated to evaluate the radiomodifying effect. The hematopoiesis was assessed by the endogenous colony formation test and hematological parameters in irradiated mice. Statistical analysis was performed using the Statistica 8.0 software.

RESULTS: The antiradiation efficacy of orally administered beta-D-glucan has been shown. DRF was 1.16 when the drug was administered 0.5 hours before irradiation and 1.06 during therapeutic use (after 1 or 2 hours). There was a decrease in weight loss in lethally irradiated mice and its faster recovery. Single oral administration of beta-D-glucan at a dose of 500 mg/kg stimulated the growth of splenic endogenous colony-forming units in mice on day 9 after total body irradiation at doses of 7 and 7.8 Gy, contributed to a decrease in the severity of leukopenia and thrombocytopenia. The antiradiation effect of beta-D-glucan was associated with an increase in the viability of bone marrow stem cells and a faster restoration of hematopoiesis.

CONCLUSIONS: The results obtained indicate the possibility of using beta-D-glucan from P. ostreatus both before irradiation to increase the radioresistance and for early therapy of the hematopoietic syndrome of acute radiation sickness.

Medical academic journal. 2023;23(1):53-66
pages 53-66 views

The effect of prolonged emotional and pain stress on the expression of the bdnf gene in the brain of rats with contrast excitability of the nervous system

Shalaginova I.G., Zachepilo T.G., Dyuzhikova N.A.

Abstract

BACKGROUND: The neurotrophic factor BDNF performs important functions in synaptic plasticity and functional activity of neurons, involve in the stress response and the pathogenesis of post-stress disorders. The specificity of post-stress changes in the bdnf mRNA level due to genetically determined features of excitability of the nervous system has not been studied.

AIM: To study the level of bdnf mRNA in the prefrontal cortex, hippocampus and amygdala of rats of two strains with contrasting excitability of the nervous system in normal condition and at different times after prolonged emotional and painful stress exposure (after 24 hours, 7, 24, 60 days).

MATERIALS AND METHODS: The study was carried out on adult male rats of two strains with a different level of excitability of the nervous system (HT — high threshold and LT — low threshold of excitability). As a model of chronic stress, a long-term emotional and painful exposure according to Hecht was used. The bdnf mRNA level was determined using quantitative real-time PCR. Changes in the level of bdnf mRNA in the prefrontal cortex, hippocampus and amygdala of control and experimental groups of rats of two strains were studied at different time points (24 hours, 7, 24 days, 2 months) after prolonged emotional and painful stress exposure.

RESULTS: It was found that in highly excitable LT rats, a decrease in the expression of the bdnf gene in the prefrontal cortex occurs 24 hours and persists up to 7 days after exposure, in the hippocampus — 2 months after exposure. In rats of the low-excitable HT strain, the decrease in bdnf mRNA was not detected.

CONCLUSIONS: In highly excitable LT rats, prolonged emotional and painful stress causes a decrease in the expression of the bdnf gene in the prefrontal cortex and hippocampus. In low-excitable rats of the HT strain, no significant decrease in the mRNA level of this neurotrophin was found in any of the studied brain regions. The possible association of this specificity of changes in the level of bdnf mRNA with a greater severity of post-stress anxiety-like behavior disorders in highly excitable rats compared with low-excitable ones is discussed.

Medical academic journal. 2023;23(1):67-74
pages 67-74 views

Reducing of the respiratory effects of dizocilpine by recombinant interleukin-1β in experiment

Tumanova T.S., Merkurjev V.A., Danilova G.A., Aleksandrov V.G.

Abstract

BACKGROUND: For a deeper understanding of the pathogenesis of COVID-19, it is necessary to study the mechanisms that implement the influence of pro-inflammatory cytokines on the processes of regulation of the external respiratory system. In experiments on anesthetized rats, the effect of the pro-inflammatory cytokine interleukin-1β on the respiratory effects of dizocilpine (MK-801), which has an inhibitory effect on neurotransmitter systems involved in the control of the respiratory system, was studied. It was considered that, first of all, dizocilpine is a highly effective non-competitive NMDA-type glutamate receptor blocker.

AIM: The objectives of the study were to identify the effect of the influence of dizocilpine on the parameters of the breathing pattern and to assess the degree of change in this effect when dizocilpine was administered against the background of an elevated systemic level of interleukin-1β.

MATERIALS AND METHODS: The study was performed on 24 anesthetized tracheostomy spontaneously breathing rats. To register the volume-time parameters of external respiration, a pneumotachographic technique was used. In the process of processing the obtained results, the value of the recorded parameter was determined immediately before the introduction of MK-801 and 1 min after its introduction

RESULTS: At a dosage of 0.1 mg/kg, dizocilpine was found to cause a reversible short-term decrease in respiratory rate, tidal volume, and minute respiratory volume. It has been shown that this effect of dizocilpine does not appear after intravenous administration of interleukin-1β (at a dosage of 2 μg/kg). The results obtained confirm the assumption about the effect of an elevated systemic level of interleukin-1β on the state of neurotransmitter systems involved in the control of respiration.

CONCLUSIONS: Based on the correlation of the obtained results with the literature data, an assumption was made about a change in the state of NMDA-type glutamate receptors under the influence of pro-inflammatory cytokines, which may be one of the mechanisms of cardiorespiratory dysfunctions observed in a systemic inflammatory reaction accompanied by hypercytokinemia.

Medical academic journal. 2023;23(1):75-83
pages 75-83 views

Visualisation of kupffer cells in the rat liver with poly- and monoclonal antibodies against microglial-specific protein Iba-1

Nikitina I.A., Razenkova V.A., Kirik O.V., Korzhevskii D.E.

Abstract

BACKGROUND: A necessary attribute of any study, which is related to the cell biology of various structural components of the digestive tract, is the usage of modern immunohistochemical methods. One of the most difficult objects are resident liver macrophages, or Kupffer cells. This determines the high significance to develop a reliable approach for Kupffer cells visualization.

AIM: The aim of the study was to develop a protocol for the immunohistochemical research of Kupffer cells in rat liver using two types of primary antibodies against Iba-1, and to analyze the advantages and disadvantages of this approach, taking into account the use of zinc-ethanol-formaldehyde as a fixative.

MATERIALS AND METHODS: The study was carried out on liver samples of adult Wistar rats (n = 5). Goat polyclonal and rabbit monoclonal antibodies against calcium-binding protein Iba-1 were used for the ligh microscopy immunohistochemistry assay of resident liver macrophages.

RESULTS: Using two types of antibodies it was shown by quantitative analysis that rabbit monoclonal antibodies most completely reveal Iba-1-immunopositive structures compared to goat polyclonal antibodies. Fixation with zinc-ethanol-formaldehyde made it possible to reveal Iba-1-immunopositive cells in all studied rat liver samples.

CONCLUSIONS: Iba-1 immunohistochemistry using rabbit monoclonal antibodies was considered as the most optimal immunohistochemical approach. Fixation with zinc-ethanol-formaldehyde preserves the antigenic epitopes and allows the effective use of different antibodies.

Medical academic journal. 2023;23(1):85-94
pages 85-94 views

Clinical research

Anemia in patients with necrotizing soft tissue infections, pathogenetic and prognostic value

Serebryanaya N.B., Avdoshin I.V., Chernyshev O.B., Shatil M.A., Bubnova N.A.

Abstract

BACKGROUND: Necrotizing soft tissue infection is one of the most severe life-threatening surgical infections with a very high mortality rate. A characteristic feature of necrotizing soft tissue infection is the rapid development of anemia, the causes and prognostic value of which are not well understood.

AIM: The purpose of this study was to investigate the timing, development, and dynamics of anemia in generalized forms of necrotizing infection to identify clinical and bacteriological factors associated with its development.

MATERIALS AND METHODS: 129 patients with necrotizing soft tissue infection who were treated from 09.2015 to 12.2019 in the department of purulent-septic surgery at Hospital of the Holy Great Martyr George were examined. All patients received surgical treatment, laboratory hematological, biochemical examination, bacteriological examination of blood, and wound discharge. Overall, 22 patients suffered from systemic inflammatory response syndrome, 63 patients with sepsis, and 41 patients with septic shock.

RESULTS: The Counts of hemoglobin and red blood cells in necrotizing soft tissue infection patients with sepsis revealed the anemia already during the first day and then from the 15th day of the disease, the red blood cell values began to rise in the patients who survived. However, continued to decrease in the deceased patients. In the group of deceased sepsis patients from day 3 of hospitalization, correlations between red blood cells count and potassium ion concentration (r = –0.318; p < 0.01), and red blood cells count and total plasma protein (r = 0.30; p < 0.01) became significant. Among patients with hemoglobin <110 g/L on the day of hospitalization, 36 of 67 (53.7%) patients died, and among those with hemoglobin levels >110 g/L, 20 of 62 (32.2%) patients died (p = 0.004). The highest lethality was registered patients who suffered from wound discharge Klebsiella pneumoniae (12 of 18, 66.7%) or anaerobic infection, but marked anemia was noted only in patients with anaerobic infection (Proteus spp., Clostridium spp., Bacteroide spp.) (8 out of 12, 66.7%).

CONCLUSIONS: We attribute the development of anemia in sepsis patients to the destruction of red blood cells. The type of infectious agent influences both the mortality rate and the degree of anemia, which is probably related to the ability of bacteria to destroy red blood cells.

Medical academic journal. 2023;23(1):95-105
pages 95-105 views

The study of platelet microparticles and P-selectin expression in patients with the peripheral arterial diseases

Ermakov A.I., Gaikovaya L.B., Sirotkina O.V., Vavilova T.V.

Abstract

BACKGROUND: High platelet reactivity leads to the progression of atherosclerosis and its complications. Activated platelets adhere to the site of endothelium damage on the vessel wall and initiate the formation of an arterial thrombus, followed by acute ischemia of the organ. Biochemical and cellular marker such as platelet microvesicles and P-selectin can be analyzed using flow cytometry, which is based on a specific antigen-antibody interaction. Patients with peripheral arterial disease are at significantly greater risk of cardiovascular and cerebrovascular complications than individuals of the same age and sex. The use of antiplatelet agents is an important part of pathogenetic therapy and prevention of cardiovascular diseases and their complications.

AIM: This study was to evaluate the level of platelet microparticles and P-selectin expression in patients with peripheral arterial disease receiving antiplatelet therapy.

MATERIALS AND METHODS: The study included 49 people, which included three study groups: patients with obliterating disease of the arteries of the lower extremities (n = 14) on the background of long-term use (more than 14 days) of double (75 mg clopidogrel and 100 mg Acetylsalicylic acid) antiplatelet therapy, patients with COVID-19 (n = 15), who made up the positive control group in the determination of microparticles of platelet origin, and healthy volunteers (n = 20) without signs of acute respiratory disease, without a history of cardiovascular and thromboembolic episodes, not taking antiplatelet drugs. The functional activity of platelets was assessed by two methods: using light aggregometry and analysis of P-selectin expression on platelet surface by flow cytometry. The number of platelet’s microparticles in blood plasma was also determined using flow cytometry.

RESULTS: A significant decrease in platelet aggregation was found in patients with peripheral arterial disease taking antiplatelet agents, compared with controls by used light aggregometry. Similar changes were obtained when analyzing the expression of P-selectin on platelets. A higher percentage of platelet’s microparticles with the CD9+CD41+ phenotype was found in patients with severe inflammation compared with peripheral arterial disease patients treated with antiplatelet agents and compared with the healthy controls.

CONCLUSIONS: Thus, our study reflects the consistency of the results of three different laboratory tests in assessing the platelets reactivity in patients with the peripheral arterial diseases taking antiplatelet drugs.

Medical academic journal. 2023;23(1):107-114
pages 107-114 views

History of medicine

The activity of the outstanding histologist academician A.A. Zavarzin as the commissioner of the tomsk group of laboratories of the Institute of Experimental Medicine in the period of the Great Patriotic War

Korzhevskii D.E., Kirik O.V.

Abstract

Academician A.A. Zavarzin (1886–1945) — the founder of evolutionary histology and the creator of tissue parallelism theory, is known as an outstanding neurohistologist and organizer of the Department of General Morphology of the All-Union Institute of Experimental Medicine (AIEM). During the Great Patriotic War (World War II) A.A. Zavarzin was evacuated to Tomsk as part of the laboratories of the central part of AIEM (Moscow) and the Leningrad branch of AIEM (Leningrad). Some information about his scientific work in Tomsk is presented in the historical literature, however, up to the present, his organizational activities as a commissioner have not been known. Based on information from the archive of the Institute of Experimental Medicine (St. Petersburg), including previously unpublished materials from orders on personnel for 1941 and 1945 and those for the Tomsk Group of AIEM, this article presents new facts about the life and scientific and organizational activities of Academician A.A. Zavarzin during the Great Patriotic War. In the period from 1943 to 1944, he headed the Tomsk group of laboratories of the A.M. Gorky All-Union Institute of Experimental Medicine — the main scientific medical institution in the country, on the basis of which the USSR Academy of Medical Sciences was organized in 1945.

Medical academic journal. 2023;23(1):115-122
pages 115-122 views


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