Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Kazimirskii AN, Salmasi JM, Poryadin GV

Antiviral system of innate immunity includes two main components: the mitochondrial antiviral sensor — the mitochondrial outer membrane protein and peripheral blood neutrophils capable of forming neutrophilic extracellular traps. Depending on the activation pathway of the mitochondrial antiviral sensor (MAVS), two possible variants of cells death, apoptosis or cellular degeneration with necrotic changes, develop during cell infection with an RNA-containing virus. The development of virus-induced apoptosis of infected cells causes the formation of neutrophilic extracellular traps, the secretion of inflammatory cytokines, ROS generation, tissue damage, hemocoagulation and the development of an acute inflammatory process with the development of COVID-19 pneumonia. Violation of the prion-like reaction of MAVS in response to viral infection of the cell triggers an alternative pathway for activating autophagy. Cells under conditions of prolonged activation of autophagy experience necrotic changes and are eliminated from the organism by monocytes/macrophages that secrete anti-inflammatory cytokines. This type of reaction of the antiviral system of innate immunity corresponds to the asymptomatic course of the disease. From the most significant aspects of the pathogenesis of the coronavirus infection COVID-19 given, recommendations for the prophylactic treatment of this dangerous disease follow. The proposed treatment can significantly decrease the severity of COVID-19 disease and reduce mortality.

Received: 2020-08-31

Published online: 2020-09-21

DOI: 10.24075/brsmu.2020.054

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VIEWS 4174

Chernevskaya EA, Meglei AYu, Buyakova IV, Kovaleva NYu, Gorshkov KM, Zakharchenko VE, Beloborodova NV

The term “chronic critical illness” (CCI) refers to patients with prolonged dependence on intensive care. In most patients, CCI is triggered by severe brain injury. Ever more studies researching the microbiota in pathologic conditions are published every year, but a lot is yet to be elucidated about the composition of the gut microbiota in CCI. The aim of this study was to investigate possible correlations between changes in the taxonomic abundance of the gut microbiota, levels of proinflammatory and neurological serum biomarkers and the severity of central nervous system injury in patients with CCI. Our prospective observational pilot study included 29 patients with CCI. Using real-time PCR allowed us to detected changes in the taxonomic abundance of the gut microbiota. The correlation analysis of serum biomarkers and the taxonomic composition of the gut microbiota revealed statistically significant correlations between cortisol levels and the abundance of F. prausnitzii (r = ‒0.62; p < 0.05) and B. thetaiotaomicron (r = ‒0.57; p < 0.05) in vegetative state patients; between the CRP/albumin ratio and the abundance of S. aureus (r = 0.72; p < 0.05); between the abundance of B. fragilis group/F. prausnitzii and S100 levels (r = 0.45; p <0.05) in conscious patients; between Glasgow coma scale scores and the abundance of Enterococcus spp. (r = ‒0.77; p <0.05) in both groups. Thus, the association between the changes in the taxonomic composition of the gut microbiota and the severity of neurologic deficit can be evaluated using PCR-based diagnostic techniques and blood serum biomarkers. This approach will help to optimize antibacterial treatment regimens and/or develop alternative strategies to minimize the aggressive effect of antibiotics on the gut microbiota.

Received: 2020-08-20

Published online: 2020-09-16

DOI: 10.24075/brsmu.2020.053

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VIEWS 4287

Tanashyan MM, Shabalina AA, Roitman EV, Vavilova TV, Kuznetsova PI

Thrombogenicity and its causes in patients with ischemic stroke (IS) and pre-existing polycythemia vera (PV) is a significant clinical concern. The aim of this study was to identify the range of factors associated with increased thrombogenicity in patients with IS and pre-existing PV. We performed a physical examination and laboratory tests on 127 patients in the hyperacute stroke stage and 16-18 months after. Of them, 68 patients had PV (the main group) and 59 did not have this condition (the comparison group). Laboratory tests were conducted to evaluate blood rheology, hemostasis, endothelial function, angiogenesis, proinflammatory cytokine levels; we also tested patients for the presence of the V617F mutation in the JAK2 gene and analyzed the contribution of all studied parameters to the development of thrombotic and hemorrhagic complications. We found that the neurological picture did not differ between the groups: mean NIHSS scores were 12 and 13 points, respectively. Morphological and functional characteristics of red blood cells and platelets, hemostasis and cytokine profiles were compared between patients with IS and pre-existing PV and the comparison group. One of the key elements in potentiating thrombotic complications in patients with IS and PV was JAK2 V617F allele burden. The obtained data suggest the cumulative effect of the identified factors promoting thrombus formation in post-stroke patients with PV and overpowering the effect of antiplatelet therapy.

Received: 2020-08-11

Published online: 2020-08-31

DOI: 10.24075/brsmu.2020.052

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VIEWS 3960

Rybakova PA, Koroleva YuI, Ivanova GE, Zarubina TV

Currently, the new model of stroke care is actively implemented. There is a number of problems thereby related to digitalization. The study was aimed to work up the information model of the post-stroke rehabilitation at the first stage. The following basic objects of the rehabilitation system information model were identified and described using system analysis and business process modelling, based on studying laws, regulatory and legal acts, clinical guidelines, the “Development of the System of Medical Rehabilitation in Russia” pilot project protocol, and the problem area experts’ findings: patient, health information system (HIS) of a healthcare organization, document management. The objects’ properties and interaction are discussed, the information model is been constructed, main directions are described.

Received: 2020-07-25

Published online: 2020-08-31

DOI: 10.24075/brsmu.2020.051

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VIEWS 4020

Andreevskaya SN, Smirnova TG, Antonov EN, Chernousova LN, Bogorodsky SE, Larionova EE, Popov VK, Ergeshov A

Sustained-release drugs against tuberculosis are a promising approach to therapy since they positively affect patient compliance with long regimens, especially when it comes to the multidrug-resistant form of the disease. Conventional UV-visible spectroscopy does not work well with multicomponential culture media used for growing M. tuberculosis. The aim of this study was to develop a method for evaluating the kinetics of anti-tuberculosis drug released from bioresorbable polymeric carriers suitable for screening a wide range of encapsulated prolonged-release drugs and identifying the best performing candidate. While studying the growth dynamics of the laboratory susceptible strain M. tuberculosis H37Rv in the presence of different levofloxacin concentrations (from 0.03 to 0.4 μg/ml), we developed a model, which is essentially a set of 2 parallel experiments evaluating the kinetics of drug release into the culture medium. The results of these 2 experiments conducted on 3 encapsulated forms of levofloxacin loaded onto bioresorbable polymeric PLGA carriers (particles sized 50 μm and 100 μm and the matrix) revealed that release kinetics of the drug largely depended on the type of polymeric carrier. The best encapsulation of the antibiotic and its gradual release into the culture medium was observed for the matrix. All experiments were run in 3 replicates. The obtained data were analyzed using descriptive statistics.

Received: 2020-08-06

Published online: 2020-08-30

DOI: 10.24075/brsmu.2020.050

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VIEWS 3857

Maltseva DV, Shkurnikov MYu, Nersisyan SA, Nikulin SV, Kurnosov AA, Raigorodskaya MP, Osipyants AI, Tonevitsky EA

The integrity of the intestinal epithelial cell lining is crucial for the normal intestinal function. As a rule, intestinal inflammation is associated with additional tissue hypoxia, leading to the loss of epithelial monolayer integrity. However, in the absence of visible damage to the epithelium, there still might be a risk of infection driven by changes in the intracellular transport of bacteria-containing vesicles. The aim of this study was to investigate the effects of hypoxia on transcytosis using a human intestinal enterocyte model. We found that hypoxia enhances transcytosis of the model protein ricin 1.8-fold. The comparative transcriptome and proteome analyses revealed significant changes in the expression of genes involved in intracellular vesicle transport. Specifically, the expression of apoB (the regulator of lipid metabolism) was changed at both protein (6.5-fold) and mRNA (2.1-fold) levels. Further research is needed into the possible mechanism regulating gene expression in intestinal erythrocytes under hypoxic conditions.

Received: 2020-08-08

Published online: 2020-08-28

DOI: 10.24075/brsmu.2020.049

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VIEWS 3954

Chagovets VV, Starodubtseva NL, Frankevich VE

Investigation of the triazole-derived drugs action mechanisms and understanding of their affinity and specificity molecular basis may contribute to the new drugs development. The study was aimed to investigate the triazoles class representative (fluconazole) complexes with amino acids using mass spectrometry, molecular dynamics and ab initio quantum chemistry calculations. During the experimental study, the fluconazole, alanine, lysine and threonine solutions were analyzed by electrospray ionization mass spectrometry and tandem mass spectrometry. The molecular dynamics modeling of the fluconazole–amino acid complexes was performed using the CHARMM force field. The quantum chemistry calculations of the complexes structure and energy parameters were carried out using the density-functional theory by B3LYP calculations (3-21G and 6-311++G** basis sets). Mass spectra indicated that fluconazole formed stable complexes with amino acids in the 1 : 1 stoichiometric ratio. In accordance with the tandem mass spectrometry with varying fluconazole–amino acid associates ion fragmentation energy, the following sequence was obtained: [Fluc + Ala + H]+ < [Fluc + Lys + H]+ < [Fluc + Thr + H]+. The fluconazole–amino acid interaction energy values resulting from the quantum chemistry calculations formed the sequence similar to that obtained by experiment. Thus, as seen in the case of fluconazole–amino acid complexes, it is possible to combine the experimental mass spectrometry studies with quantum chemical modeling for the complexes properties assessment.

Received: 2020-07-22

Published online: 2020-08-22

DOI: 10.24075/brsmu.2020.048

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VIEWS 3991

Bobrov PD, Biryukova EV, Polyaev BA, Lajsheva OA, Usachjova EL, Sokolova AV, Mikhailova DI, Dement'eva KN, Fedotova IR

Cerebral palsy (CP) is one of the most severe central nervous system diseases in childhood associated with motor impairment. The study was aimed to assess the efficiency of the complex comprising brain-computer interface (BCI) and hand exoskeleton as an instrument for the motor function recovery in patients with CP complementing the essential therapy. The Fugl-Meyer Assessment scale, ARAT test and Jebsen–Taylor function test were used in 14 children and adolescents for the motor function improvement assessment after the therapy complemented by 7–10 BCI-exoskeleton based procedures. The EEG mu-rhythm sources properties during the motor imagery BCI control were studied. After the procedures completion, the significant improvement of the Fugl-Meyer Assessment scale score (7 (2; 11) for hand active movements; 4.5 (1; 6) for proximal arm and 2.5 (0; 5) for hand), ARAT test score (7.5 (1; 31) for total score, 1.5 (0; 12) for grasp movement and 1.5 (0; 8) for grip movement), as well as significantly different from the zero execution time reduction in three out of seven Jabsen–Taylor function test items (–1 (–4.13; 0.25) for simulated feeding; –1 (–2; 0) for moving light and heavy cans) were identified. The average BCI detection level was 0.51 (0.45; 0.54) (max = 0.70). In most EEG recordings the mu-rhythm sources were detected, both for intact and affected hemispheres. The mu-rhythm desynchronization associated with motor imagery was observed, significantly affecting the BCI accuracy. The results obtained indicate that the use of BCI-exoskeleton complex effectively complements the standard rehabilitation methods for children with CP, and suggest that its clinical effectiveness in individuals with CP may be proven by enrollment of more patients.

Received: 2020-07-31

Published online: 2020-08-20

DOI: 10.24075/brsmu.2020.047

Comments 0

VIEWS 5304