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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Radaeva OA, Simbirtsev AS, Gromova EV, Iskandiarova MS, Belyaeva SV

Leukemia inhibitory factor (LIF) exerts multidirectional effects in the setting of essential hypertension (EH). There is a mounting body of evidence refuting the postulate about identical STAT3 signaling in cardiomyocytes and endothelial/smooth muscle cells, which is important in the situation of extended exposure to gp 130 ligands (LIF in particular). At the same time, there are no reports on the circadian dynamics of peripheral blood LIF concentrations and possible secondary changes to the pathophysiological effects of this cytokine. This study aimed to analyze the circadian dynamics of LIF concentrations in the peripheral blood serum measured at 5 different time points in patients with stage II EH in the presence/absence of antihypertensive therapy and their relationship with the frequency of complications developing within a 5-year follow-up. Blood serum LIF was measured in 60 patients with stage II EH using ELISA at 8:00, 14:00, 20:00, 2:00, and 8:00 o’clock before putting the patients on antihypertensive therapy and one year after its onset. The identified patterns of diurnal LIF concentrations (a rise by ≥15% at 20:00, p < 0.001; a further rise by ≥22% peaking at 2:00, p < 0.001 relative to the values at 8:00) can be regarded as pathologic; their persistence after one year of antihypertensive therapy is a sign of EH progression and puts the patients at 6-fold risk for cardiovascular complications, including myocardial infarction and acute cerebrovascular events.

Received: 2020-03-11

Published online: 2020-03-29

DOI: 10.24075/brsmu.2020.017

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VIEWS 2855

Borisova OYu, Chaplin AV, Gadua NT, Pimenova AS, Alexeeva IN, Rakitsky GF, Afanas'ev SS, Donskikh EE, Kafarskaya LI

In 2018, a few sequencing studies were published revealing the existence of two monophyletic clusters within the C. diphtheriae species, meaning that this species can be divided into two subspecies: C. diphtheriae subsp. diphtheriae and C. diphtheriae subsp. lausannense. The objective of our study was to describe the genotype and the phenotype of 2 nontoxigenic C. diphtheriae strains isolated in Russia in 2017–2018, which were classified by us as C. diphtheriae subsp. lausannense based on the aggregated data yielded by a variety of techniques, including microbiological and molecular genetic techniques, as well as a bioinformatic search for subspecies-specific genes in the publicly available genomes of C. diphtheriae. The isolated strains had morphological and biochemical characteristics of C. diphtheriae. The strains were assigned to the MLST type ST199 included in the clonal complex associated with subsp. lausannense. PCR revealed that both analyzed strains of C. diphtheriae subsp. lausannense carried the ptsI gene encoding phosphoenolpyruvate-protein phosphotransferase and did not carry the narG gene encoding the synthesis of nitrate reductase subunits, whereas the strains of C. diphtheriae subsp. diphtheriae had the narG gene and did not have ptsI. We experimentally proved the ability of lausannense strains to ferment N-acetylglucosamine. Our findings expand the knowledge of the biological diversity of C. diphtheriae and indicate the need for estimating the spread of these microorganisms in Russia, as well as their pathogenic potential.

Received: 2020-02-09

Published online: 2020-03-18

DOI: 10.24075/brsmu.2020.015

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VIEWS 3066

Spiridonova NV, Demura AA, Katyushina VO

Ovarian neoplasms can develop at any age, carry a high risk for malignant transformation, reduce the reproductive potential of a woman and are an indication for surgery. The search for optimal screening algorithms for ovarian tumors is still ongoing. The aim of this study was to evaluate the prognostic efficacy of ultrasonography (US) features in differentiating between benign, malignant and borderline tumors in reproductive-age women. We examined 168 reproductive-age women with ovarian masses who underwent surgery in 2012–2015 and compared the results of histopathological examinations with pulsed-Doppler US findings. We did not establish a correlation between the size/volume of the tumor and their morphological structure. We identified the echotexture characteristics associated with malignancy, including the presence of a solid component (р < 0.001); septations (р = 0.029) and projections on the internal surface of the tumor capsule (р < 0.001); moderate or significant buildup of free fluid in the small pelvis (р = 0.007), and the nodular surface of the tumor capsule (р = 0.008). Solid ovarian masses were at increased (31.69-fold) risk of transformation into malignant or borderline tumors, whereas for a mixed (cystic and solid) type the risk of such transformation increased 3.46-fold. We also identified Doppler parameters that can clearly discriminate between benign and malignant growths, including the blood flow rate in the tumor over 1.85 cm/s (р = 0.007) and RMI over 0.16 (р = 0.013). The sensitivity and specificity of our diagnostic model are 87% and 68%, respectively, with a probability threshold of 0.3.

Received: 2020-02-12

Published online: 2020-03-14

DOI: 10.24075/brsmu.2020.016

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VIEWS 2726

Boeva VV, Zavyalov AN

Prevention of type 2 diabetes mellitus (T2DM) in prediabetic patients is a pressing concern due to its increasing prevalence. The aim of this study was to evaluate the efficacy of preventive pharmacotherapy in delaying progression of incident impaired glucose tolerance (IGT) and impaired fasting glycemia (IFG) to T2DM. The participants of the study (1,136 subjects) found healthy by a regular annual checkup underwent repeat screening for T2DM. Blood samples were processed following the guidelines for good preanalytical sample preparation. Patents with incident IGT/IFG were prescribed medication therapy with metformin or/and acarbose. The rate of IGT/IFG conversion to T2DM was evaluated in years 3 and 10 of observation. Carbohydrate metabolism disorders were detected in 18.5% (n = 210) of the re-screened patients: 5.0% had T2DM, 5.5% had IGT, 8.0% had IFG. Patients with incident T2DM were prescribed blood sugar lowering therapy and they were excluded from further analysis. Patients with IGT/IFG (n = 151) were given recommendations on lifestyle modification and prescribed metformin (77%) or a combination of metformin and acarbose (23%). Three years after the start of observation, the rate of conversion to T2DM was 6.8% in patients undergoing monotherapy with metformin and 11.4% in patients undergoing combination therapy with metformin and acarbose. After the active follow-up phase was over, the majority of the patients (n = 85) decided to discontinue preventive therapy without consulting their physicians. Ten years after the active follow-up phase, the rate of NGT/IFG conversion to T2DM was 38.8% in patients who had discontinued their treatment and 0% in patients still taking metformin (р < 0.01). Long-term therapy with metformin prevented progression to T2DM in the long run in 83.3% (р < 0.05).

Received: 2020-01-09

Published online: 2020-03-06

DOI: 10.24075/brsmu.2020.014

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VIEWS 2983

Bakulin IS, Zabirova AH, Kopnin PN, Sinitsyn DO, Poydasheva AG, Fedorov MV, Gnedovskaya EV, Suponeva NA, Piradov MA

Despite intensive study, the data regarding functional role of specific brain regions in the working memory processes still remain controversial. The study was aimed to determine the activation of cerebral cortex regions at different stages of the working memory task (information encoding, maintenance and retrieval). Functional magnetic resonance imaging (fMRI) with the modified Sternberg task was applied to 19 healthy volunteers. The objective of the task was to memorize and retain in memory the sequence of 7 letters with the subsequent comparison of one letter with the sequence. Activation was analyzed during three periods of the task compared to the rest period, as well as temporal dynamics of changes in BOLD signal intensity in three regions: left dorsolateral prefrontal, left posterior parietal and left occipital cortex. According to the results, significant activation of the regions in prefrontal and posterior parietal cortex was observed during all periods of the task (р < 0.05), but there were changes in its localization and lateralization. The activation pattern during the maintenance period corresponded to the fronto-parietal control network components. According to the analysis of temporal dynamics of changes in BOLD signal intensity, the most prominent activation of the dorsolateral prefrontal cortex and parietal cortex was observed in the end of the encoding period, during the maintenance period and in the beginning of the retrieval period, which confirmed the role of those areas in the working memory processes. The maximum of occipital cortex activation was observed during encoding period. The study confirmed the functional role of the dorsolateral prefrontal cortex and posterior parietal cortex in the working memory mechanisms during all stages of the Sternberg task.

Received: 2020-01-22

Published online: 2020-03-01

DOI: 10.24075/brsmu.2020.013

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VIEWS 3300

Voroshilina ES, Zornikov DL, Koposova OV, Islamidi DK, Ignatova KYu, Abakumova EI, Kurbatova NV, Plotko EE

Chronic endometritis (CE) in women of the reproductive age is associated with infertility and recurrent pregnancy loss. The aim of this study was to evaluate the endometrial microbiota by means of real-time PCR in reproductive-age women depending on the morphological pattern of the endometrium. Using the Androflor real-time PCR kit, we analyzed endometrial aspirate collected from 23 patients with chronic endometritis, 30 patients with endometrial hyperplasia, and 19 healthy women. DNA of up to 9 groups of microorganisms was detected in all the analyzed samples in the amounts exceeding negative control. The total bacterial load (TBL) of the detected microorganisms was 103–106,4 (median 103,8) GE/ml. Lactobacillus spp. were detected the most often (86.1% of all samples). Opportunistic microorganisms (OM) were identified in 36.1% of all samples, including 22.2% of samples with lactobacilli and 13.9% — without lactobacilli. The variant of microbiota composition with Lactobacillus-dominance (more than 90%. in the TBL) was detected significantly less often in women with chronic endometritis compared to healthy women. Real-time PCR could be used for assessment of endometrial microbiota and allows us to determine its characteristics depending on the morphological pattern.

Received: 2020-02-03

Published online: 2020-02-29

DOI: 10.24075/brsmu.2020.012

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VIEWS 3349

Svirepova KA, Kuznetsova MV, Sogoyan NS, Zelensky DV, Lolomadze EA, Mikhailovskaya GV, Mishina ND, Donnikov AE, Trofimov DYu

Uterine leiomyomas are a worrying reproductive health issue that has serious social implications. The aim of this study was to conduct a search for marker single nucleotide polymorphisms (SNPs) associated with uterine leiomyoma. To test the hypothesis about the contribution of genetic predisposition to the pathogenesis of myomas, the initial group of 100 patients with a verified diagnosis of uterine leiomyoma was divided into 2 subgroups: subgroup Ia (women with a family history of the disease) and subgroup 1b (women with no family history of the disease). The control group consisted of 30 postmenopausal patients who did not have a medical history of uterine fibroids and denied uterine fibroids in their close female relatives. DNA sequences were read using Sanger sequencing. Statistically significant differences (p < 0.05) were discovered between the analyzed groups in terms of genotype frequencies for rs12637801 and rs12457644. Also, previously unknown protective SNPs were identified whose rare alleles could predict the reduced risk of uterine leiomyomas.

Received: 2020-02-05

Published online: 2020-02-29

DOI: 10.24075/brsmu.2020.011

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VIEWS 3150

Borozdenko DA, Lyakhmun DN, Golubev YaV, Tarasenko DV, Kiseleva NM, Negrebetsky VV

The development of methods of drug therapy and rehabilitation in different periods of ischemic cerebral lesion is currently an urgent problem. Our study was aimed to investigate the pharmacokinetics and anti-ischemic effect of the new 4-phenylpyrrolidone-2 derivative in rats. To study the drug pharmacokinetics, the Wistar rats were once administered with the substance at a dose of 250 mg/kg, then, the substance distribution in blood and cerebral cortex was evaluated. Elimination half-life value was determined, which was 83.2 min. The substance remained in the brain tissue for 24 hours. To assess the anti-ischemic effect, the stroke was modeled by endovascular middle brain artery transition occlusion, and the drug was administered intravenously for 5 days at two doses, 250 and 125 mg/kg. After that the lesion focus volume was evaluated by MRI, as well as the neurological deficit severity, locomotor and explorative behavior. The studied drug significantly decreased the neurological deficit in model animals compared to control group (1.72 vs 4.4, p < 0.05). According to the MRI data, the effect on the ischemic focus was negligible, while the explorative behavior significantly increased under the influence of the 4-phenylpyrrolidone-2 derivative (hole board test, horizontal activity 12.1 ± 6.8, 22.5 ±10.5, p < 0.05). The data obtained allow us to conclude that the studied substance penetrates the blood-brain barrier (BBB), and accumulates in the brain tissue promoting the neurological deficit correction and increasing the explorative behavior in the ischemic stroke model animals.

Received: 2020-01-28

Published online: 2020-02-23

DOI: 10.24075/brsmu.2020.010

Comments 0

VIEWS 3530