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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Kuptsov NS, Kornienko MA, Gorodnichev RB, Danilov DI, Malakhova MV, Parfenova TV, Makarenko GI, Shitikov EA, Ilina EN

The ever-rising prevalence of multidrug-resistant bacteria necessitates the search for a therapeutic alternative to antibiotics. Using therapeutic products based on virulent bacteriophages might provide such an alternative. The aim of our study was to evaluate the efficacy of commercial phage products and natural bacteriophage monoisolates recovered from environmental sources against clinical strains of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. We compiled a collection of 147 strains that were subsequently genotypes using the MLST method. The efficacy of bacteriophages was evaluated in spot tests. The highest efficacy was demonstrated by "Staphylococcal bacteriophage" (86%, effective against S. aureus), "Purified polyvalent pyobacteriophage" (87.8%, effective against K. pneumoniae), and a group of phage products against P. aeruginosa, including "Pseudomonas aeruginosa bacteriophage" (87.5%), "Complex pyobacteriophage" (79.5–90%) and "Purified polyvalent pyobacteriophage" (90–92.5%). The efficacy of "Intesti bacteriophage", which targets E. faecium, was 4.2%. The efficacy of commercial phage products against S. aureus and K. pneumoniae was higher than the efficacy of individual phage monoisolates (60% for the S. aureus phage vB_SauP-436-3w and 5.9% for the K. pneumoniae phage vB_Kp_M_ Seu621). Thus, all tested commercial phage products were highly effective against P. aeruginosa, K. pneumoniae and S. aureus. There are no commercial phage products on the market against other ESKAPE pathogens, including Acinetobacter baumannii and Enterobacter cloacae. Besides, there are no effective phage products against E. faecium. This dictates the need for new effective bacteriophages against these species.

Received: 2020-05-06

Published online: 2020-05-25

DOI: 10.24075/brsmu.2020.029

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VIEWS 6200

Abdullaeva AI, Prityko AG, Voronin PA, Mikhailova EG

Chronic apical periodontitis (CAP) is characterized by tissue inflammation around the tooth tip. Unstable outcomes of current treatments against CAP dictate the need for novel therapeutic techniques and medications. The aim of this study was to analyzed the effects of hirudotherapy on the treatment course in patients with CAP. Forty-one study participants aged 25 to 40 years were divided into the main group (20 patients) and the control group (21 patients). Pain level and the gingival index (GI) were measured in all study participants. During the first visit, pain scores did not differ significantly between the control (5.81 ± 0.65) and the main (5.75 ± 0.92) groups. During the second visit, pain was almost unnoticeable in the main group patients (1.05 ± 0.34), whereas pain scores were higher in the control group (4.10 ± 0.7). Our findings suggest a positive effect of hirudotherapy used in combination with standard treatment regimens.

Received: 2020-05-01

Published online: 2020-05-18

DOI: 10.24075/brsmu.2020.028

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VIEWS 4629

Osikov MV, Davydova EV, Boyko MS, Bakeeva AE, Kaygorodtseva NV, Galeeva IR, Fedosov AA, Ilyinyh MA, Vorgova LV

Research into the accumulation patterns of protein oxidative modification (POM) products and lipids in Crohn’s disease (CD) and ulcerative colitis (UC) could have important implications for understanding the pathogenesis and improving the diagnosis and therapy for these diseases. The aim of this study was to investigate the aspects of free radical oxidation (FRO) in the large bowel and their possible correlations with clinical symptoms of UC and CD. In the Wistar rat model used in the experiment, CD was induced with 2,4,6-trinitrobenzenesulfonic acid, and UC was induced with oxazolone. Clinical status was assessed using the Disease activity index (DAI). Lipid peroxidation (LPO) products were measured in the heptane and isopropanol phases of the intestinal mucosa extract. POM products were measured following spontaneous and stimulated oxidation. The DAI ( Me (Q25–Q75)) was increased in both CD and UC on days 3 and 7 of the experiment: for CD, it was equally increased on days 3 and 7 (7 (3-7)) and was 11 (11–11) and 11 (9–11) for UC on days 3 and 7, respectively. The amount of primary, secondary and end LPO products in the heptane and isopropanol phases, as well as the total amount of POM products, was increased in the homogenized mucosa of the large bowel. In the CD group, the relative content of secondary basic POM products was increased on day 7 of the experiment. The following patterns of FRO were revealed: accumulation of LPO products in the UC group and accumulation of POM products in the CD group; UC is characterized by the accumulation of mostly LPO products in the heptane phase and secondary LPO products in the isopropanol phase; CD is characterized by the accumulation of secondary basic POM products. DAI scores were correlated with the amount of LPO products in the isopropanol phase and the amount of POM products in the spontaneous oxidation mode. The highest number of strong correlations was observed in the UC group. Our findings suggest a very serious contribution of FRO changes to the pathogenesis of UC and CD, meaning that LPO and POM products could be regarded as diagnostic markers and indicators of treatment efficacy.

Received: 2020-04-18

Published online: 2020-05-08

DOI: 10.24075/brsmu.2020.027

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VIEWS 5239

Kuznetsova NA, Pochtovyy AA, Nikiforova MA, Gushchin VA

High population density in the cities with bustling transportation systems and a thriving tourism industry can promote the global spread of a viral infection in a matter of days. The novel SARS-CoV-2 coronavirus has already infected over 2,000,000 people worldwide and caused upwards of 156,000 deaths. One of the factors driving the rapid unfolding of the pandemic is the absence of diagnostic tests for SARS-CoV-2 detection. Molecular techniques allow SARS-CoV-2 RNA to be quickly detected in clinical samples, aiding the differential diagnosis in severely ill patients and facilitating identification of asymptomatic carriers or presymptomatic individuals. Real-time PCR with fluorescent hybridization is the most available, highly sensitive and specific technique for SARS-CoV-2 RNA detection in biological samples. More RT-PCR assay kits are needed for mass screening, which will help to identify infected individuals and contain the current outbreak of COVID-19 in Russia.

Received: 2020-04-21

Published online: 2020-04-30

DOI: 10.24075/brsmu.2020.026

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VIEWS 5048

Chebotar IV, Shagin DA

This article analyzes the possibility of employing immunotherapy and preventive immunization to fight COVID-19. The authors think that treatment and prevention of the infection with anti-SARS-CoV-2 antibodies can have unpredictable outcomes. Although these antibodies can neutralize virus antigens (S-proteins), they also have the ability to enhance virus entry into the host cell. The article emphasizes the importance of solid evidence of efficacy and safety for candidate anti-COVID-19 therapies and protective measures.

Received: 2020-04-21

Published online: 2020-04-30

DOI: 10.24075/brsmu.2020.025

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VIEWS 4624

Nersisyan SA, Shkurnikov MYu, Osipyants AI, Vechorko VI

Coronavirus SARS-CoV-2, the cause of the COVID-19 pandemic, enters the cell by binding the cell surface proteins: angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). The expression of these proteins varies significantly in individual organs and tissues of the human body. One of the proteins’ expression regulation mechanisms is based on the activity of the microRNA (miRNA) molecules, small non-coding RNAs, the most important function of which is the post-transcriptional negative regulation of gene expression. The study was aimed to investigate the mechanisms of the interactions between miRNA isoforms and ACE2/TMPRSS2 genes in the colon tissues known for the high level of expression of the described enzymes. The search for interactions was performed using the correlation analysis applied to the publicly available paired mRNA/miRNA sequencing data of colon tissues. Among the others, such miRNAs as miR-30c and miR-200c were identified known for their involvement in the coronavirus infection and acute respiratory distress syndrome pathogenesis. Thus, new potential mechanisms for the ACE2 and TMPRSS2 enzymes regulation were ascertained, as well as their possible functional activity in a cell infected with coronavirus.

Received: 2020-04-17

Published online: 2020-04-29

DOI: 10.24075/brsmu.2020.024

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VIEWS 5648

Gerasimova AA, Shamarakova MV, Klimenko PA

Borderline ovarian tumors (BOTs) are common in women in their reproductive years. In more than one-third of patients tumors are detected at the age of 15–29, the average age at initial diagnosis is 40. The study was aimed to improve methods for BOTs diagnosis in pregnancy and to determine the possibilities of organ preservation treatment. A group of 300 pregnant women with various tumor-like formations and ovarian tumors was examined. Of them, 25 patients had borderline epithelial tumors (22 patients had serous and 3 patients had mucinous tumors). Ultrasound examination together with blood serum СА-125, sFas, VEGF and IL6 level assessment were performed prior to surgery. The results obtained were compared with the results of morphological studies. Organ preservation and radical surgical treatment were carried out, and chemotherapy, if necessary. Perinatal outcomes were studied when performing the cross-comparison. It was discovered, that ultrasonography and logistic regression analysis made it possible to distinguish between benign ovarian tumors, BOTs and malignant ovarian tumors. The levels of VEGF above the 500 pg/ml, IL6 above the 8.1 pg/ml and СА-125 above the 300 U/ml indicated the high probability of malignant ovarian tumors in pregnant women. Only the morphological study of ovarian tissue, obtained regardless of surgical methods, ensured understanding of the ovarian tumor’s true nature during pregnancy. At the same time, in three pregnant women with ovarian tumors, the morphological examination revealed some tissue areas common both for BOTs and malignant ovarian tumors. Thus, the predominance of the tumor early stages, relatively mild course and, favorable prognosis in patients with BOTs make it possible to use gentle surgical treatment making it possible to preserve menstrual function and fertility.

Received: 2020-04-07

Published online: 2020-04-26

DOI: 10.24075/brsmu.2020.023

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VIEWS 4449

Tynio YaYa, Morozova GV, Biryukova YuK, Sivokhin DA, Pozdniakova NV, Zylkova MV, Bogdanova ES, Smirnova MS, Shevelev AB

At present, there is a need for a simple, noninvasive, highly specific and sensitive diagnostic test for hepatobiliary system disorders. Compounds labeled with carbon isotopes are widely used in various diagnostic breath tests; they are safe and can reliably detect a metabolic disorder or enzyme deficiency. The aim of this study was to synthesize 13С- and 14С-labeled linoleic acids suitable for use in hepatobiliary breath tests in terms of purity. In the synthesis of 13С-labeled linoleic acid, the chemical yield for 1-bromo-8,11-heptadecadien was 86.4% and the chemical yield for barium carbonate-13С, 96.0%. In the synthesis of 14С-labeled linoleic acid, the chemical yield for 1-bromo-8,11-heptadecadien was 87.39%; for barium carbonate-14С it was 97.1%. The specific radioactivity of 14С-labeled linoleic acids was 45.36 ± 0.02 mCi/g. The radiochemical yield of the reaction was 96.0%. The proposed method is suitable for batch production.

Received: 2020-03-31

Published online: 2020-04-25

DOI: 10.24075/brsmu.2020.022

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VIEWS 4725