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 21, No 2 (2021)

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Mast cells and neuroinflammation in pathogenesis of neurologic and psychiatric diseases
Grigorev I.P., Korzhevskii D.E.

The review summarizes current data on the role of neuroinflammation and mast cells in the pathogenesis of nervous and mental diseases, such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, depression, autism, migraine, schizophrenia and some others. The contribution of neuroinflammation to the pathogenesis of many of these diseases has been demonstrated. The involvement of mast cells in the development of the neuroinflammatory process has with varying degrees of evidence been shown for multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s disease and migraine. There is still no convincing evidence that mast cells contribute to neuroinflammation in Parkinson’s disease, depression, schizophrenia and autism spectrum disorder, although it is possible that they play a role in the pathogenesis of these diseases. Data on the causal role of neuroinflammation and mast cells in the development of neuropsychiatric diseases may become the basis for the development of new approaches to their pharmacological treatment. The review provides data on the first clinical trials of anti-inflammatory and mast cell activity-modulating drugs for the treatment of migraine, Alzheimer’s disease, multiple sclerosis and amyotrophic lateral sclerosis.

Medical academic journal. 2021;21(2):7-24
pages 7-24 views
The physicochemical properties and distribution of aluminum in the environment, the effect on living organisms, the reduction of its toxic effect
Kutai V.E., Tsygankov V.Y.

The review examines the physicochemical properties, distribution in the environment, the effect on living organisms, including toxicity and ecotoxicity, ways of removing aluminum and its compounds from the human and animal organism. Analysis of scientific literature has shown that the widespread use of aluminum in nature, its use in the agricultural, food, cosmetic, aluminum, oil-producing industries, medicine, water treatment processes and other fields of activity leads to an increased intake of this element into the human body. The cumulative nature of the toxic effect of aluminum and its compounds leads to negative consequences for the respiratory, nervous, musculoskeletal systems, and mammary glands.

Medical academic journal. 2021;21(2):25-36
pages 25-36 views
Inhibition of the complement anaphylatoxin activities in the central nervous system disorders
Nekrasova K.A., Ischenko A.M., Trofimov A.V.

The review is devoted to inhibition of the complement anaphylatoxin activities in diseases of the central nervous system. Here we present epidemiological data on the prevalence of cerebrovascular diseases, in particular, ischemic stroke and craniocerebral trauma. The mechanisms of complement activation and complement-mediated pathology in the central nervous system are considered in detail. Clinical data confirming the role of the complement system in the pathogenesis of stroke and of traumatic brain injury secondary injury are presented. We also summarize the results of in vivo specific activity studies of the complement anaphylatoxin inhibitors using animal models of stroke and traumatic brain injury. Briefly described is the present state of the art in developing drugs that target the effector compounds of the complement cascade.

Medical academic journal. 2021;21(2):37-52
pages 37-52 views

Basic studies

The degree of severity and structure of cognitive disorders in patients with cerebrovascular disease, depending on the level of 25-hydroxycalciferol
Shvartsman G.I., Pervova E.M., Goldobin V.V., Tertyshnaya N.M.

BACKGROUND: In recent years, a significant increase in cerebrovascular pathology, which is often accompanied by cognitive deficits, has been noted all over the world.

AIM: The aim of this study is to determine the severity and structure of cognitive disorders depending on the level of 25(OH)D in patients with cerebrovascular disease.

MATERIALS AND METHODS: 146 patients with cerebrovascular disease aged from 30 to 80 years were examined. The comparison group consisted of 40 patients, comparable in age and gender, without the studied pathology. During the study, the level of 25(OH)D, interleukin-6, highly sensitive C-reactive protein in the peripheral blood was determined in patients and a neuropsychological examination was performed.

RESULTS: In patients with cerebrovascular disease, the level of 25(OH)D it was lower in comparison with patients without this pathology. Patients with higher rates of inflammatory factors had significantly lower concentrations of 25(OH)D in the peripheral blood. The study revealed a correlation between the level of 25(OH)D in peripheral blood and the results of neuropsychological testing: direct — MMSE, MoCA, FAB and reverse — Schulte tables (performance). When assessing cognitive disorders in patients with cerebrovascular disease, according to the results of neuropsychological testing, it was possible to identify significantly significant differences between the main and the comparison group according to the following scales: MMSE (p = 0.04), MoCA (p = 0.001), FAB (p = 0.007), Schulte Tables (performance) (p = 0.06), respectively. When interpreting the MMSE scale, significantly significant differences between the groups were found in the attention assessment (p = 0.03), and in the analysis of the MoCA scale — in the sections delayed reproduction (p = 0.03) and conceptualization (p = 0.04), respectively. In patients with cerebrovascular disease, memory is most affected by the type of delayed reproduction failure, which was observed in 53-76% of cases in our study.

CONCLUSIONS: The study found that the higher the concentration of 25(OH)D and the lower the level of interleukin-6 and highly sensitive CRP in the peripheral blood, the less likely it is to develop cognitive disorders. In patients with cerebrovascular disease, memory is most affected by the type of delayed reproduction failure.

Medical academic journal. 2021;21(2):53-61
pages 53-61 views
Visualisation of GABAergic neurons and synapses in the rat brain using immunohistochemistry for two forms of glutamate decarboxylase
Razenkova V.A., Korzhevskii D.E.

BACKGROUND: Taking into account the importance of GABAergic brain system research and also the opportunity to achieve specific and accurate results in laboratory studies using immunohistochemical approaches, it seems important to have a reliable method of visualization GABA-synthesizing cells, their projections and synapses, for the morphofunctional analysis of GABAergic system both in normal conditions and in the experimental pathology.

AIM: The aim of the study was to visualize analyze GABAergic neurons and synapses within rat’s brain using three different antibody types against glutamate decarboxylase and to identify the optimal conditions for reaction performing.

MATERIALS AND METHODS: The study was performed on paraffin brain tissue sections of 5 adult Wistar rats. Immunohistochemical reactions using three antibody types against glutamate decarboxylase isoform 67 (GAD67) and glutamate decarboxylase isoform 65 (GAD65) were performed. Additional controls on C57/Bl6 mice and Chinchilla rabbits brain samples were also carried out.

RESULTS: Antibodies used in the research made it possible to achieve high quality of GABAergic structures visualizing without increasing background staining. At the same time different antibody types are distinct in their efficacy to perform immunohistochemistry reaction on laboratory animal brain tissue samples. By performing additional controls, we discovered that there is necessary to adsorb secondary reagent’s immunoglobulins in order to eliminate nonspecific staining. It was found that GAD67 and GAD65 distribution in rat forebrain structures is different. It was stated that GAD67 immunohistochemistry most completely reveals GABAergic brain structures compared to GAD65 immunhistochemistry. The possibility of determining morphological features of GABAergic neurons and synaptic terminals, as well as performing quantitative analysis, was demonstrated.

CONCLUSIONS: The approach proposed makes it possible to specifically visualize GABAergic structures of the central nervous system of different laboratory animals. This could be useful both in fundamental studies and in pathology research.

Medical academic journal. 2021;21(2):63-73
pages 63-73 views
Myeloperoxidase/high-density lipoprotein cholesterol ratio in patients with arterial hypertension and chronic coronary heart disease
Churashova I.A., Sokolov A.V., Kostevich V.A., Gorbunov N.P., Runova O.L., Firova E.M., Vasilyev V.B.

BACKGROUND: Myeloperoxidase (MPO), the enzyme of leukocytes, catalyzes the production of reactive halogen species, which can modify the structure of lipoproteins. Chlorination and nitration of tyrosine residues in apolipoprotein A-1 lead to the formation of dysfunctional high-density lipoproteins (HDL-p), thus blocking the reverse cholesterol transport. Low level of high-density lipoprotein cholesterol (HDL-C) is associated with exacerbation of coronary heart disease, but the prognostic value of this index is not fully assessed.

AIM: The aim of this study was to examine a possible contribution of MPO to the atherosclerotic plaque development (the stable growth or the erosion and rupture) via the modification of HDL-p. That is to say we investigated the diagnostic values of measuring the total MPO (MPO-T), the active MPO (MPO-A) and the MPO/HDL-С relation in patients with hypertension and various forms of chronic coronary heart disease.

MATERIALS AND METHODS: The cohort under study included 44 patients with arterial hypertension and chronic coronary heart disease. All patients were divided into three groups according to the diagnosis: arterial hypertension without coronary heart disease (Group I, n = 20); arterial hypertension and the initially stable chronic coronary heart disease without acute complications in the anamnesis (Group II, n = 14); arterial hypertension and myocardial infarction (acute coronary syndrome) in the anamnesis (Group III, n = 10). The enzyme-linked immunosorbent assay (ELISA) for MPO-T and specific immuno-extraction followed by enzymatic detection (SIEFED) by fluorogenic substrate for MPO-A were applied. After that the ratio MPO-T/HDL-C or MPO-A/HDL-C was calculated.

RESULTS: The MPO-A and MPO-A/HDL-C ratio were significantly increased in the group III of patients with old myocardial infarction as compared with the patients of group II who had the initially stable coronary heart disease (p = 0.009 and p = 0.003, respectively). Besides, the level of HDL-C in the group III was significantly reduced (p = 0.013). Our measurements revealed the negative correlation between MPO-A and HDL-C concentrations (r = –0.31; p < 0.05), which is in line with the presumption of the study accomplished. Surprisingly, the correlation between MPO-T/HDL-C ratio and that MPO-A/HDL-C was stronger (r = 0.72; p < 0.05), than between MPO-T and MPO-A (r = 0.36; p < 0.05).

CONCLUSIONS: Our study demonstrates the importance of assessing MPO-T and MPO-A plasma concentrations and of calculating the ratio MPO/HDL-C as promising biomarkers in the complicated cases of chronic coronary heart disease. MPO-A and MPO-A/HDL-C values were elevated in the patients with old myocardial infarction, while the concentration of HDL-C remained decreased upon the transition from the acute to chronic phase of the disease.

Medical academic journal. 2021;21(2):75-86
pages 75-86 views
Study of immunogenicity and safety of a candidate rotavirus vaccine based on a recombinant hybrid protein
Varyushina E.A., Alexandrov G.V., Zakharov M.S., Kiryanova A.S., Huttunen O.E., Rumyantseva A.B., Mitrofanov I.D., Bendt I.V., Krylova A.E., Chistyakova A.B., Artemova N.A., Shatillo I.M., Bogomolova E.G., Dobrovolskaya O.A., Ischuk S.A., Dukhovlinov I.V., Simbirtsev A.S.

BACKGROUND: Rotaviruses are the main cause of acute gastroenteritis in children in both developed and developing countries. Vaccination is the only way to prevent severe and fatal course of this disease. Live attenuated viruses-based vaccines currently available can have a number of side effects. A candidate rotavirus vaccine reported is based on a hybrid recombinant protein FliCVP6VP8, which includes a VP6 protein fragment, a rotavirus A VP8 protein fragment, and S. typhimurium FliC flagellin components.

AIM: The aim was to evaluate the immunogenicity and safety of а preparation “Rotavirus vaccine, recombinant” in preclinical studies.

MATERIALS AND METHODS: The immunogenicity of vaccine (blood antibody titers, antigen-specific proliferative response of spleen cells) was evaluated in BALB/c mice. The acute and subchronic toxicity, the possible irritating effect, pyrogenicity and the anaphylactic effect and delayed type hypersensitivity were evaluated in laboratory mice, rats, Guinea pigs, and rabbits.

RESULTS: Double immunization of mice with the candidate vaccine demonstrated a significant increase in antibody titers in mouse sera compared to that in control mice. Evaluation of antigen-specific proliferative response after double immunization with a candidate vaccine demonstrated a significant increase in the values of stimulated proliferation. Evaluation of safety through acute and chronic toxicity studies demonstrated no toxicity. The immunostimulatory effect of vaccine was demonstrated when evaluating the number of antibody-producing cells with sheep red blood cells as antigens. The number of white blood cells was demonstrated to increase after the prolonged vaccine administration.

CONCLUSIONS: The preclinical studies have demonstrated safety of the candidate rotavirus vaccine and its capability to produce the immune response.

Medical academic journal. 2021;21(2):87-98
pages 87-98 views
Morphological differences in the commissural connections of the forebrain in white outbred mice and BALB/C mice
Karpova I.V., Popkovsky N.A., Proshin S.N., Bychkov E.R., Tissen I.Y., Droblenkov A.V.

BACKGROUND: The study of the mechanisms of interaction of paired structures of the mammalian brain is a fundamental problem of modern neuroscience, which is of great applied importance. Even mild underdevelopment of the corpus callosum in humans can lead to autism. It is known that the intensity of intraspecific interactions in BALB/c mice is lower than in white outbred ones, while some BALB/c substrains are characterized by underdevelopment of the corpus callosum.

AIM: To compare the morphological parameters of the large brain commissures in white outbred mice and BALB/c mice grown in the Rappolovo nursery (Leningrad region).

MATERIALS AND METHODS: The morphology of the corpus callosum was studied in 13 male white outbred mice and 7 male BALB/c mice at the age of 8 months.

RESULTS: In mice of both subpopulations, the area of the anterior commissure of the left hemisphere was smaller than that of the right hemisphere (p < 0.05). There were no differences between subpopulations in this parameter. The area of the left section of the corpus callosum trunkus in outbred mice was larger than the right one (p < 0.001), while in BALB/c mice the areas of the left and right slices did not differ. Despite the absence of significant differences in the area of the anterior part (rostrum et genu) of the corpus callosum the density of the location of oligodendrocytes in this brain structure in the mice of the two subpopulations was different. The number of oligodendrocytes in 0.01 mm2 on the left section of the anterior part of the corpus callosum in BALB/c mice was greater than in white outbred mice (p < 0.05). A similar trend was revealed when comparing slices of the right hemisphere (p = 0.065).

CONCLUSIONS: The large area of the right parasagittal slice of the anterior commissure suggests that some of its constituent fibers do not cross the midline, but end within the same hemisphere, which may be the morphological basis for the functional dominance of the temporal cortex of the left hemisphere in mice of both subpopulations. The corpus callosum in BALB/c mice is developed symmetrically, and in white outbred ones – asymmetrically. This feature may be the morphological basis for the functional dominance of the parietal cortex of the right hemisphere in outbred animals.

Medical academic journal. 2021;21(2):99-105
pages 99-105 views

Clinical research

Multiple sclerosis progression and galanin receptor GALR2: is there evidence for a link?
Lioudyno V.I., Ilves A.G., Bisaga G.N., Abdurasulova I.N.

BACKGROUND: Given the recently proposed role of the rare galanin receptor-2 (GALR2) gene’s missense mutation (SNP rs61745847) in the etiology of MS, we genotyped rs61745847 in a group of MS patients that was enriched with an unfavorable disease course cases.

MATERIALS AND METHODS: Our study cohort consisted of 100 MS patients selected based on their progressive course, high disease progression rate and pediatric onset. To determine the nucleotide sequence of GALR2 gene fragment, surrounding the rs61745847 area, Sanger sequencing of PCR amplicons was performed.

RESULTS: No homozygous rs61745847 carrier was found in our cohort, and the region of exon 2 surrounding rs61745847 completely coincided with the reference sequence (Gene Bank NC_000017.11). In agreement with previously published data on Canadian and Brazilian populations of patients, our study of a Russian cohort confirmed the rarity of the rs61745847 variant, including among patients with rapidly progressive MS.

CONCLUSIONS: Thus, although structural changes in the GALR2 gene associated with rs61745847 may play a significant role in individual patients carrying this rare mutation, it is unlikely that such changes determine an unfavorable disease course of MS in general.

Medical academic journal. 2021;21(2):107-111
pages 107-111 views

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