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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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 3708

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 3724

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 3572

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 3691

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 3739

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 4896

Kovriguine DA, Nikitenkova SP

In the last decade of April 2020, the second coronavirus epidemic wave in Iran has bloomed. The new wave has started in the vicinity of the critical point, marked by approximately 44,000 infections, where the rate of increase of the primary epidemic that appeared in Iran in mid-February 2020 was the highest. Today, this secondary wave almost has doubled the peak of the primary, and, passing the epidemic threshold of about 70,000 total cases in early June, generated the new third epidemic wave developing unpredictably and dynamically. The purpose of this work was to call into use a simple dynamical system represented by the discrete logistic equation with unknown parameters to predict secondary waves using the official statistical data. The mathematical modelling reveals the secondary epidemic waves in Sweden, the United States, Ukraine, Serbia, Romania, Czech Republic, Portugal, Luxembourg, Poland, and Ecuador. Also, the second waves appear in Russia and other countries. Despite many individual differences in the epidemic spread in different countries, we have traced regularity in the rise of secondary waves. The beginning of each new wave, if focusing on the number of total cases, practically coincides with the time of the maximum growth rate of the previous early epidemic. Thus, the passing through the threshold of the current wave should be the most responsible for strict observance of the rules of self-isolation and other sanitary standards.

Received: 2020-07-13

Published online: 2020-08-12

DOI: 10.24075/brsmu.2020.046

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VIEWS 4364

Kiryanov SA, Levina TA, Kirillov MYu

SARS-CoV-2 is a RNA coronavirus of the β-CoVs family responsible for the pandemic of the severe acute respiratory syndrome (COVID-19). It is hypothesized that the viral genome of the contemporary predominant founder clones is likely to be evolving in geographic-dependent manner. Thus, strains of different origin may be characterized by different mutation patterns. The study was aimed to perform the mutational and phylogenetic analysis of the Russian SARS-CoV-2 genomes at different time periods and in various regions, as well as to characterize the mutational profiles of isolates using the bioinformatics approaches. The mutation accumulation was compared in 86 SARS-CoV-2 whole-genome sequences from Russia and 220 from Europe and North America in order to reveal the characteristic gene variations, the possible positive selection patterns. Along with the known mutation variants in the structural proteins genes, typical for isolates of European origin, several additional mutations including the synonymous mutation in gene M (C26750Т) characteristic for Russian isolates were revealed. Double mutation R203K and G204R in the nucleocapside gene which previously emerged in Europe began spreading and rapidly (within a month) became the dominant form in Russia. The results obtained indicate that the viral genome of most Russian isolates evolves with accumulation of new mutations associated with increased viral transmission. Data on the SARS-CoV-2 genome specific mutation patterns might be used for the detection of the virus, as well as for tracking and controlling of its spread.

Received: 2020-06-26

Published online: 2020-07-27

DOI: 10.24075/brsmu.2020.045

Comments 0

VIEWS 5124