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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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 4692

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 4678

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 4415

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

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VIEWS 5026

Shaskolskiy BL, Kandinov ID, Chestkov AV, Solomka VS, Kubanov AA, Deryabin DG, Gryadunov DA, Dementieva EI

Surveillance of multidrug-resistant infections is a priority task for contemporary epidemiology. The aim of this study was to genotype modern clinical isolates of N. gonorrhoeae using the NG-MAST technique (Neisseria gonorrhoeae multi-antigen sequence typing) and to compare the phylogeny of the gonococcal pathogens coming from Russia, European Union and Japan. We studied a total of 822 isolates collected in Russia from 2013 through 2018. We also used NG-MAST data from the following databases: PathogenWatch (European Union, 1,071 isolates) and PubMLST (Japan, 206 isolates). Russian isolates represented 301 different NG-MAST types. The most common were types 807, 228, 1993, 5714, and 9476 (8.3%, 3.3%, 3.2%, 3.2%, and 2.7%, respectively). There were only 3 isolates (0.4%) from Russia that represented the epidemiologically significant sequence type 1407 prevailing in many countries and characterized by multiple determinants of antimicrobial resistance. A phylogenetic tree for the NG-MAST types found in Russia and European countries was constructed. The cluster analysis of the proportion of isolates belonging to unique sequence types and the country population size allowed us to identify 2 clusters (significance level — 0.01): the first cluster included Russia and Japan, the second, European countries. A distribution pattern was identified for unique sequence types: the greater is the population size, the higher is their proportion. The phylogenetic analysis demonstrated a genetic distance between the most common Russian, European and Japanese sequence types, suggesting that the Russian population of N. gonorrhoeae has been evolving relatively locally.

Received: 2020-01-09

Published online: 2020-02-22

DOI: 10.24075/brsmu.2020.009

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VIEWS 4835

Samgina TA, Nazarenko PM, Polonikov AV, Lazarenko VA

Genetically determined features of the xenobiotic biotransformation system play an important role in the development of acute pancreatitis (AP) and its complications. The aim of this study was to assess the contribution of 3 SNPs (CYP1A1 -462 T>C rs1048943, CYP2E1 -1293 G>C rs3813867 and ABCB1 -3435 G>A rs1045642) to the development of AP and its complications. DNA samples were collected from 547 unrelated patients with AP (154 women and 393 men; mean age 48.9 ± 13.1 years) undergoing therapy at surgery departments of Kursk and 573 unrelated individuals without gastrointestinal diseases (161 women and 412 men; mean age 47.8 ± 12.1 years). The polymorphisms were genotyped by PCR using TaqMan probes for allele discrimination. Infected pancreatic necrosis (IPN) was observed in 97 patients; 101 patients developed a pseudocyst (PC); 111 patients had a peripancreatic necrosis (PN). AP was the most common in the carriers of the А allele in ABCB1 G>A (rs1045642) (p = 0.0008). The carriers of the G/G genotype rarely developed both AP (p = 5·10–4) and its complications: IPN (p = 0.03R), PN (p = 0.036R), PC (p = 0.04R). The carriers of the G/C–C/C CYP2E1 G>C (rs3813867) genotypes who had no long-term history of alcohol abuse rarely developed AP (p = 0.03). The carriers of the G/C CYP2E1 (rs3813867) genotype tended to develop pseudocysts (p = 0.05OD). AP was more frequently complicated by IPN (p = 0.009R), PN (p = 0.003R) and PC (p = 0.003D) in the carriers of the C/C CYP1A1 T>C (rs1048943) genotype. A milder course of AP was typical for the carriers of the G/G ABCB1 G>A (rs1045642) genotype; a more severe course was characteristic of the carriers of the C/C CYP1A1 T>C (rs1048943) genotype.

Received: 2020-01-05

Published online: 2020-02-16

DOI: 10.24075/brsmu.2020.008

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VIEWS 4576

Malygin AS, Demidova MA, Skachilova SYa, Shilova EV

Valproates are commonly used to treat various forms of epilepsy. Problems accompanying their clinical application include drug resistance, adverse effects, acute and chronic toxicity. Safer anticonvulsants with improved efficacy can be obtained through the chemical modification of valproic acid structure. Thiadiazole-linked amide derivatives of valproates hold great promise because 1,3,4-thiadiazole can improve the drug’s bioavailability and reduce its toxicity. The aim of this work was to synthesize a novel amide derivative of valproic acid and 1,3,4-thiadiazole exerting antiepileptic activity. The chemical structure of the synthesized valproate was studied by IR, proton NMR and 13С-NMR-spectroscopy, mass spectroscopy and elemental analysis. The purity and individuality of the compound was confirmed by thin-layer and high-performance liquid chromatography. Its antiepileptic activity was assessed in the test with intraperitoneally injected 250 mg/kg isoniazid and subsequent Probit analysis. The synthesized N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propyl pentane amide (valprazolamide) had the following characteristics. ESI+MS: m/z 256.1 [M + H]+; MRM transitions: m/z 256.1 — m/z 81.0 and m/z 130.1. The valproate exerted antiepileptic activity against isoniazid-induced seizures in mice. In the test with isoniazid, ED50 of intraperitoneally injected VPZ was 126.8 mg/kg (95% CI: 65.5–245.4). Its therapeutic index was 7.3.

Received: 2020-01-17

Published online: 2020-02-10

DOI: 10.24075/brsmu.2020.007

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VIEWS 5036

Nurmukhametova ET, Shlyapnikov ME

Recently specialists take an interest in organ-preserving methods of uterine fibroids treatment, one of which is uterine artery embolization (UAE). One of the method’s negative aspects is the severe postembolization syndrome (PES) development, requiring timely initiation of adequate treatment in order to avoid severe complications that could lead to the organ removal. The study was aimed to search for the prognostic criteria of the severe PES development during the preoperative period. The study included 81 UAE-treated women aged 19–50 with 7–17 week uterine myoma. The patients’ anthropometric measurements were used, as well as the skin microcirculation data obtained by laser Doppler flowmetry together with the occlusion test. Based on prognostic criteria, models with AUC (area under ROC curve) > 0.8 were presented. According to the models, the anthropometric predictors of the severe PES were the following: age under 38.5 (р < 0.05); BMI lower than 25 kg/m2 (р < 0.05), and microcirculation value (M) prior to UAE below 9.55 PU (р = 0.001). Microvascular blood flow during the occlusion test indicate that the higher the oxygen consumption index (I), intravascular resistance (Rc), capillary blood flow reserve capacity in the models, the higher the risk of the severe PES development (р < 0.05). Low alpha angle value obtained by the occlusion test (р = 0.003) as well as the UVLF value (р = 0.004) in the models also indicate the increased risk of severe PES. Multidimensional prognostic modelling admits to expect the severe PES development prior to UAE, which allows the doctor to prepare the woman for specific management and treatment.

Received: 2019-12-31

Published online: 2020-01-30

DOI: 10.24075/brsmu.2020.006

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VIEWS 4589