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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Multiple drug resistance of nosocomial bacterial strains provoked by the unwise and uncontrolled use of antibiotics in medicine and agriculture seriously threatens modern healthcare: minor and trivial infections are about to kill again. A solution may lie in the development of new alternatives to antibiotics. This review highlights the most interesting approaches to the development of antibacterial drugs focusing on the most promising ones, such as phage therapy and phage lytic enzymes (lysins).

Received: 2018-01-23

Published online: 2018-03-05

DOI: 10.24075/brsmu.2018.002

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VIEWS 4074

Komech EA, Lebedev YuB, Koshenkova AV, Syrko DS, Musatkina EA, Lukyanov SA, Chudakov DM, Zvyagin IV

Recent studies of T-cell clonal repertoires of patients with ankylosing spondylitis (AS) have led to the discovery of AS-associated T-cell clones with a highly homologous T-cell receptor structure. The role of T-lymphocytes in the disease progression cannot be elucidated without analyzing the diversity and abundance of functionally different T-cell clones found in patients with AS. Using a state-of-the-art technique for T-cell repertoire profiling based on massively parallel sequencing, we, for the first time, studied the T-cell receptor repertoire of activated T-cells from the peripheral blood of a patient with AS. We have demonstrated that a subpopulation of CD38+HLA-DR+ T-lymphocytes is highly diverse both in terms of clonal diversity and abundance of the identified clonotypes, suggesting diverse antigen specificity of the activated peripheral blood T-cells. Most of the activated T-cell clonotypes had low abundance in total population of peripheral blood T-cells. In the repertoire of activated T-cells we have found the clonotype TRBV9_CASSVGVYSTDTQYF_TRBJ2-3, previously discovered in AS and reactive arthritis, and a few other clonotypes of cytotoxic and helper T-cells that may have a role in promoting inflammation in AS patients. Presence of the AS-associated clonotype in activated T-cell subset suggests that the T-cells might play an active role in ongoing inflammation during the disease progression. This provides rationale for further research of their antigen specificity and role in triggering or maintaining AS.

Received: 2017-12-15

Published online: 2018-02-16

DOI: 10.24075/brsmu.2018.001

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VIEWS 3846

Pozdniakova NV, Turobov VI, Garanina EE, Ryabaya OA, Biryukova YuK, Minkevich NI, Trubnikova EV, Shevelev AB, Kuznetsova TV, Belyakova AV, Udovichenko IP

In this work we explore the temporal dynamics of cytokines in Dark Agouti rats with experimentally induced autoimmune encephalomyelitis (EAE). The main group consisted of 11 animals who were injected with 100 μl (per leg) of spinal cord homogenate obtained from random-bred rats and combined with incomplete Freund’s adjuvant to the hind footpads. The control group included 7 animals who received 100 μl of normal saline mixed with incomplete Freund’s adjuvant. Blood samples (500 μl) were collected daily, starting from day 1 through day 7. We ran a Bio-Plex-based multiplex cytokine assay on the samples using the Bio-Plex Pro Rat Cytokine 24-plex Assay kit. EAE in rats was shown to simulate progression of multiple sclerosis in humans in terms of temporal dynamics of lymphoproliferative and hematopoietic factors IL-1b, IL-2, IL-4, IL-5, IL-6, and IL-7. The studied model satisfactory imitates the dynamics of factors stimulating migration of lymphocytes, monocytes and other immune cells, including IL-17, RANTES (CCL-5) and MCP-1 (CCL-2) but excluding GRO/KC (CXCL1), which shows a different dynamics. The model also resembles patterns of human multiple sclerosis in terms of factors affecting cytotoxic and apoptotic reactions, including IFNγ, IL-6 and IL-17, but excluding TNFα.

Received: 2017-12-15

Published online: 2018-01-25

DOI: 10.24075/brsmu.2017-06-12

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VIEWS 3883

Bilan DS, Kelmanson IV, Belousov VV

Studies of ischemic brain injury are an important area of modern biomedical research. So far, a lot of ischemic stroke models have been proposed, along with different imaging and staining modalities aimed to visualize the damaged tissue. In this work we use a rat model to investigate how the experimental setup affects the interpretation of experimental data obtained in the acute phase of ischemic stroke (5 hours after the occlusion of the middle cerebral artery). We show the association between the choice of the type of anesthesia and the severity of ischemic injury: in our experiments brain damage was the most pronounced in the animals anesthetized with a combination of chloral hydrate and Rometar; the least damage was observed for isoflurane. Staining was performed using the popular dye 2,3,5-triphenyltetrazolium chloride (TTC). We demonstrate that parameters of brain slices incubation in TTC also need to be accounted for when interpreting the results obtained during the acute phase of stroke, the optimum incubation time being 30 min and temperature 37 °С.

Received: 2017-11-29

Published online: 2018-01-25

DOI: 10.24075/brsmu.2017-06-11

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VIEWS 3549

Grabovsky EV, Oleynik GM, Krastelev EG, Smirnov VP, Khmelevsky EV, Bozhenko VK, Shishkin AM, Ivanov AV, Kulinich TM

Relative biological effectiveness of ionizing radiation is determined by a number of factors, including a dose rate. Radiotherapy equipment employs low dose rates of up to a few Gy per minute. But very little is known about the biological effect of high and ultrahigh (≥ 10<sup>8</sup> Gy/min) dose rate radiation. Our study aimed to investigate the apoptotic effect of ultrahigh gamma dose rates on human peripheral blood lymphocytes. Blood samples were collected from seemingly healthy donors. Lymphocytes were isolated by density gradient separation. Lymphocyte suspensions were irradiated with low-rate doses on the Rokus- AM gamma-ray machine for clinical use (Russia) and with 10<sup>8</sup> Gy/s doses on the experimental pulse generators Angara-5-1 and Mir-M (Russia). Apoptosis was measured by flow cytometry using annexin V and propidium iodide double staining. We established that in comparison with low dose rates, ultrahigh gamma dose rates (with doses ranging from 1 to 6 Gy) induced significantly more pronounced apoptosis in peripheral blood lymphocytes (p < 0.05) with fewer necrotic cells. Total radiation-induced cell death did not differ significantly between the therapeutic gamma machine and the experimental pulse generators. Further research is needed to assess biological and medical significance of our findings.

Received: 2017-11-22

Published online: 2018-01-25

DOI: 10.24075/brsmu.2017-06-10

Comments 0

VIEWS 3768

Tsukanov KYu, Krasnenko AYu, Korostin DO, Churov AV, Stetsenko IF, Plotnikov NA, Zarubina SA, Belova VA, Kovyrshina AV, Vorotnikov IK, Mescheryakov AA, Ilinsky VV

Breast cancer (BC) is one of the most common malignancies. There is a need for novel approaches to screening for genetic mutations in patients with BC that will help to reduce high mortality rates caused by this disease and improve treatment outcomes. In this study we employed next generation sequencing to screen a few key genes associated with the risk of breast cancer for mutations. We also evaluated their pathogenicity using the previously proposed bioinformatics-based algorithm and analyzed the associations between some of the detected mutations and the clinical manifestations of the disease. Our study recruited 16 female patients with BC (mean age was 50.7 ± 11.3 years). A total of 58 mutations were detected in the oncogenes BRCA1, BRCA2, ATM, CDH1, CHEK2 and TP53. Bioinformatic analysis of the sequencing data revealed 14 mutations that affect the sequence of the encoded proteins. Most deleterious mutations were harbored by the genes BRCA1/2, ATM and TP53.

Received: 2017-12-12

Published online: 2018-01-24

DOI: 10.24075/brsmu.2017-06-09

Comments 0

VIEWS 3511

Manturova NE, Kochubey VV, Kochubey AV

In spite of accreditation programs, levels of professional skills vary among plastic surgeons: there are no requirements for the diversity and number of performed surgical interventions that a surgeon can specify in his/her portfolio. Rationale for elaborating such requirements can be explored by studying service reports of private medical practices certified to provide plastic surgery services to their in- and outpatients. In the course of out study we analyzed such reports using different statistical tools, including the variation coefficient, the Kolmogorov–Smironov, Mann–Whitney U and Kruskal–Wallis tests, and Spearman’s correlation coefficient. Differences were considered statistically significant at p < 0.05. Surgical interventions were divided into 9 categories: skin/soft tissue plasty, rhinoplasty, breast plasty, blepharoplasty, otoplasty, lip and palate repair, craniofacial plasty, repair of urogenital defects, and hand surgery. On average, each surgeon performed a total of 112.3 ± 326.4 surgeries (Мо = 1). About 30.4 % of surgeons performed 1 to 10 interventions a year. None of the surgeons performed all types of interventions and hand surgery. We found that the diversity and number of interventions performed by a surgeon does not depend on the qualification or academic title (r<sub>S</sub> = –0.8, р = 0.2 and r<sub>S</sub> = –0.2, р = 0.8, respectively). Skin/soft tissue repair accounted for 51.1 % of all services provided by private medical practices. The number of post-operative treatment services was 0.017 per surgery.

Received: 2017-11-28

Published online: 2018-01-23

DOI: 10.24075/brsmu.2017-06-08

Comments 0

VIEWS 3207

Sakhibgareeva MV, Zaozersky AYu

Diagnostic accuracy remains one of the central problems of medical care. In this work we attempt to apply artificial intelligence to solve this challenge. We propose an approach to medical prediction based on the intelligent analysis of patients’ data from 200 different laboratory tests. The initial sample included 7, 918 cases falling into 4 nosological categories: D50 (iron deficiency anemia), E11 (non-insulin-dependent diabetes mellitus), E74 (other disorders of carbohydrate metabolism), and E78 (disorders of lipoprotein metabolism and other lipidemias), and was further divided into the training and testing datasets. Using gradient boosting, we constructed a machine learning model. The model demonstrated a recognition rate of 89 % (AUC-ROC) and a mean certainty in the diagnosis of 92 %. Our study proves feasibility of using machine learning in the analysis of this type of medical data. We are currently implementing a web-service for medical prediction as part of our Healthcare platform aiming at automation of clinical practice.

Received: 2017-11-23

Published online: 2018-01-23

DOI: 10.24075/brsmu.2017-06-07

Comments 0

VIEWS 3377