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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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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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 4281

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 4793

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 4792

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 4505

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 5106

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 4934

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

Comments 0

VIEWS 4668