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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Polunina NV, Tyazhelnikov AA, Pogonin AV, Kostenko EV

The paper reports the results of survey carried out in order to assess patients’ opinion on the remote medical care provided by the telemedicine center of theDepartment of health of Moscow during the pandemic. Survey of 216 COVID-19 patients who received outpatient care made it possible to assess their healthcondition and determine the factors contributing to satisfaction with care provided. Patients’ health condition was evaluated based on the course of underlyingdisease and comorbidities, which were revealed in 24.3% of COVID-19 patients. The following three groups were formed: patients with favorable (37.5%),satisfactory (36.7%) and unfavorable (25.8%) health condition. The majority of patients (76.4%) were satisfied with telemedicine consultations; men (79.8%),individuals with favorable condition (83.1%) and patients under 50 (81.9%) demonstrated significantly higher level of satisfaction. The following arguments in favourof telemedicine consultations were specified by patients: appointment of the specialist’s consultation, promptness of treatment appointment, provision of medicalrecommendations, including recommendations on a healthy lifestyle, as well as promptness of house call and ambulance call. The main dissatisfaction reasons wereas follows: lack of appropriate equipment, difficulties when setting up the equipment, complexity of the instructions for connecting to telemedicine consultations,poor quality of video/audio conferencing; these indicated the patients’ inadequate technical resources. Telemedicine consultations may be considered an effectivemethod of outpatient care provision for COVID-19 patients, especially since 64.7% of patients plan to use telemedicine consultations in the future, and 72.3% ofpatients are ready to recommend them to others.

Received: 2020-11-27

Published online: 2020-12-27

DOI: 10.24075/brsmu.2020.084

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VIEWS 3782

Mdinaradze DS, Kozlov IB, Pavlova KS, Kofiadi IA, Kurbacheva OM

Standard asthma therapy includes prescription of β2-agonists. Changes in the functional activity of β2-adrenergic receptor are associated with ADRB2 gene polymorphism and related to the low therapeutic response to β2-agonists. Identification of carriers of the clinically significant gene variants will help to avoid ineffective treatment and prescribe an alternative therapy. This study aimed to assess clinical significance of the ADRB2 gene polymorphisms (Arg16Gly and Gln27Glu) associated with the therapeutic response to β2-agonists in the group of asthma patients. We subjected a small group of adult nonsmoking patients (n = 21) with moderate asthma (III–IV stage of GINA) to clinical and genetic examination. The group included patients with the new theratype, those that poorly respond to β2-adrenergic drugs but significantly to M-cholinergic agonists. The first group included patients responding well to both salbutamol and ipratropium bromide. The second group was comprised of the patients for whom salbutamol was not effective but who tested positive for response to ipratropium bromide. The analysis of distribution of polymorphic variants of Arg16Gly and Gln27Glu revealed no significant relationship between alleles and genotypes and the efficacy of β2-agonists (0.52 for the rs1042713 variant, p = 1.0; 1.0 for the rs1042714 variant, p = 0.74, respectively). The genotype of patients that did not respond to salbutamol was either Arg16Gly or Gly16Gly. Further studies are needed that would involve a larger number of patients and an expanded list of the tested polymorphic variants.

Received: 2020-11-25

Published online: 2020-12-27

DOI: 10.24075/brsmu.2020.083

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VIEWS 3393

Rusanov AL, Kozhin PM, Romashin DD, Karagyaur MN, Luzgina NG

HaCaT cell line is a widely used model for studying normal human keratinocytes. However, mutations of TP53 gene are typical for this cell line, which have a substantial impact on functions of the encoded protein. The features of this regulatory circuit should be considered when using HaСaT cells for assessment of human skin physiology and pathology in vitro. The study was aimed to assess the features of differentiation realization in HaCaT cells with modulated activity of p53 protein. The expression of р53 was reduced by knockdown of ТР53 gene by shRNA (by 2.2 times, p < 0.05), and the elevated concentration of the р53 active forms was achieved via exposure of cells to Nutlin-3a, the MDM2 inhibitor and the major negative regulator of р53. It has been found that regulation of at least three differentiation markers, СASP14, IVL (expression increase by 3.9 and 3.7 times respectively in the p53-knockdown cells, p < 0.05) and TGM1 (twofold expression decrease in the p53-knockdown cells, and 1.7-fold expression increase under exposure to Nutlin-3a, p < 0.05) in HaCaT cells is p53-mediated. The positive correlation has been revealed for expression of TGM1 and p53 that might be realized indirectly via ΔNp63 expression alteration. At the same time, modulation of p53 does not result in significant alterations in expression of cytokeratins.

Received: 2020-11-27

Published online: 2020-12-26

DOI: 10.24075/brsmu.2020.082

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VIEWS 3812

Anufriev PL, Tanashyan MM, Gulevskaya TS

The angio- and neurovisualization methods vigorously developing in recent decades determine the relevance of improvement of etiopathogenetic ischemic stroke classification used for the treatment tactics selection and for secondary prevention of the disorder. The study was aimed to clarify the capabilities of clinical diagnosis for pathogenetic variants of ischemic stroke. For that, in 125 postmortem cases, the macro and microscopic examination of brain and cardiovascular system was carried out in order to verify the stroke pathogenesis established as a result of the previous patients’ examination. The study demonstrates the great potential of the major pathogenetic stroke subtypes (large-artery atherosclerosis, cardioembolism, small-artery occlusion) diagnosis using the complex of contemporary clinical and instrumental methods and the main morphological criteria of these subtypes in accordance with the TOAST classification. Moreover, the clinical and pathomorphological assessment allowed us to differentiate stroke resulting from various alterations of single cerebral artery, the atherothrombotic occlusion (44% of cases for the subtype), arterio-arterial embolism (13%) and critical stenosis (10%), as well as stroke resulting from cerebrovascular insufficiency (33%), within the “large-artery atherosclerosis” subtype. Thus, the high informativity of the existing examination methods allows for a more differentiated understanding of the cause of ischemic stroke, which is fully in line with modern personalized medicine.

Received: 2020-11-24

Published online: 2020-12-25

DOI: 10.24075/brsmu.2020.081

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VIEWS 3628

Balanovska EV, Petrushenko VS, Koshel SM, Pocheshkhova EA, Chernevskiy DK, Mirzaev KB, Abdullaev ShP, Balanovsky OP

The lack of information about the frequency of pharmacogenetic markers in Russia impedes the adoption of personalized treatment algorithms originally developed for West European populations. The aim of this paper was to study the distribution of some clinically significant pharmacogenetic markers across Russia. A total of 45 pharmacogenetic markers were selected from a few population genetic datasets, including ADME, drug target and hemostasis-controlling genes. The total number of donors genotyped for these markers was 2,197. The frequencies of these markers were determined for 50 different populations, comprised of 137 ethnic and subethnic groups. A comprehensive pharmacogenetic atlas was created, i.e. a systematic collection of gene geographic maps of frequency variation for 45 pharmacogenetic DNA markers in Russia and its neighbor states. The maps revealed 3 patterns of geographic variation. Clinal variation (a gradient change in frequency along the East-West axis) is observed in the pharmacogenetic markers that follow the main pattern of variation for North Eurasia (13% of the maps). Uniform distribution singles out a group of markers that occur at average frequency in most Russian regions (27% of the maps). Focal variation is observed in the markers that are specific to a certain group of populations and are absent in other regions (60% of the maps). The atlas reveals that the average frequency of the marker and its frequency in individual populations do not indicate the type of its distribution in Russia: a gene geographic map is needed to uncover the pattern of its variation.

Received: 2020-11-06

Published online: 2020-12-19

DOI: 10.24075/brsmu.2020.080

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VIEWS 4836

Volkov AA, Budnik NV, Zuban ON, Abdulaev MA, Plotkin DV, Reshetnikov MN

At the current stage of development of urology, selection of the surgical method for cases of severe obstructive diseases of the upper urinary system remains a challenge. This study aimed to explore the results of application of a buccal graft (BG) to remedy extended recurrent strictures and obliterations of the distal ureter. Seven patients with the mentioned diseases had undergone surgery: for six of them, the method of choice was complete BG ureteroplasty, one had onlay ureteroplasty. One intervention was laparoscopic, the remaining surgeries were open. The length of the replaced ureteral defect was 5–8 cm. In five cases, the flap was additionally vascularized with the iliac muscle, in one we used omentum tissue, in another — both the iliac muscle and the omentum. There were no fatalities registered, nor severe complications as per the Clavien–Dindo classification. The patients were followed-up for 4–18 months; as of today, no recurrence cases were identified. Control examinations showed complete patency of the neoureter and good vascularization of the BG. Thus, this method can be an option in cases disallowing distal ureter restoration with tissues of the patient's own urinary tract or segments of the gastrointestinal tract.

Received: 2020-10-25

Published online: 2020-12-17

DOI: 10.24075/brsmu.2020.079

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VIEWS 3859

Maltseva DV, Poloznikov AA, Artyushenko VG

Intestinal epithelial cells are constantly exposed to physiologically hypoxic environment. The further reduction of tissue oxygen delivery may result in the intestinal epithelial cells function impairment, being a sign of active inflammation. The cultivation conditions are important when performing in vitro studies, since those may affect the cells’ properties. The study was aimed to assess the integrin receptor expression in the human colon adenocarcinoma Caco-2 cell line when simulating both hypoxic condition using the cobalt chloride and microcirculation. Transcriptome analysis revealed the significantly increased expression of the integrin receptors ITGA2 and ITGA5 α2- and α5-subunit genes under hypoxic conditions, as well as the reduction of ITGA5 during incubation in the microfluidic chip. The expression of β-subunits did not change. Analysis of microRNA transcriptomes revealed the decreased expression of hsa-miR-766-3p and hsa-miR-23b-5p microRNA. One of the validated targets for both microRNAs is mRNA of gene ITGA5. It has been shown that microcirculation makes it possible to bring the intestinal epithelial cells cultivation conditions closer to physiological conditions. The possible biological significance of the detected integrin expression profile alterations and the role of microcirculation have been discussed.

Received: 2020-11-09

Published online: 2020-12-17

DOI: 10.24075/brsmu.2020.078

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VIEWS 3579

Nikulin SV, Poloznikov AA, Sakharov DA

To increase the efficiency of drug development process, it is important to improve performance of preclinical experiments. A major drawback of the currently used in vitro intestinal barrier models is that it takes a significant time to obtain functional enterocyte monolayers with formed tight junctions. In this work, we have optimized various parameters such as cell density and different coatings, for a more rapid and efficient producing Caco-2 cell monolayers suitable for further experiments. In vivo microscopy and impedance spectroscopy were used to monitor cells state under various conditions. To determine possible biological mechanisms affected by exposure to various protein substrates, the transcriptomic analysis was applied. It was shown that collagen IV coating of the cell growth substrate significantly increased the rate of proliferation and migration of Caco-2 cells. This effect allows forming a functional monolayer of epithelial cells with tight junctions within 24 hours. Optimally, the initial cell density should be 90,000 to 200,000 cells/cm2. It was observed that collagen IV was poorly expressed by Caco-2 cells while the collagen IV receptor was expressed at a relatively high level in these cells. Laminin-332, another basement membrane component, was found to have no significant effect on times of formation of functional epithelial monolayers. Thus, using the optimal parameters determined in this study allows to significantly improve efficiency of using the in vitro intestinal barrier models.

Received: 2020-11-09

Published online: 2020-12-15

DOI: 10.24075/brsmu.2020.077

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VIEWS 3382