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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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 4402

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 4250

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 4024

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 4433

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 3978

Frolov MA, Kazakova KA, Dushina GN, Frolov AM, Gonchar PA

A patient presented to our clinic with stage Ia open-angle glaucoma of the right eye and stage IIa surgically corrected open-angle glaucoma of the left eye. The condition of the ocular surface was interpreted as toxic/allergic conjunctivitis provoked by brimonidine 0.15 %. Brimonidine was substituted with non-selective 0.5%; additionally, topical steroids were prescribed. After steroids were discontinued, some of the symptoms came back, including moderate hyperemia and conjunctival edema, which was interpreted as intolerance to a preservative contained in the eye drops. A decision was made to switch from the β-blocker to its preservative-free formulation; regular IOP monitoring was continued. IOP measured during the next visit was above tolerated, so a preservative-free form of the ocular hypotensive combination drug (an analog of prostaglandin 0.005% with non-selective β-blocker 0.5%) was introduced to the regimen, with further IOP monitoring. Because the initial diagnosis was wrong, damage to the ocular surface had been aggravated by inadequate therapy. Preservative-free hypotensive eye drops are beneficial for the corneal surface and have a positive effect on a patient’s adherence to the regimen.

Received: 2019-12-26

Published online: 2020-01-27

DOI: 10.24075/brsmu.2020.005

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VIEWS 4032

Tsimbalist NS, Suftin BA, Kriuchkova AV, Chupyatova EA, Babichenko II

Buerger's disease is a rather rare pathology characterized by nonatherogenic vascular lesion associated with the inflammation in the intima of the vessel and the thrombus formation. Most often the pathological process affects small and medium caliber arteries. Vascular occlusion can lead to tissue ischemia and the trophic ulcers, and cause the extremity amputation. The disorder pathogenesis has not been fully explored. Literature data indicate that the disease development may be associated with autoimmune processes. The paper presents the results of immunohistochemical study of the material obtained after amputation of the lower extremity in a patient diagnosed with Buerger's disease. The patient had a 15-year tobacco smoking experience. In the inflammatory cell infiltrates around the affected vessels, lymphocytes with CD4, CD8 antigens and IgG immunoglobulin deposits were found, which could be considered as the evidence of the autoimmune mechanisms’ involvment. Immunohistochemical reactions with markers of NK cells CD56 and the central component of the C3d complement system were negative. The results of the study suggest that the key role is played by helper and suppressor T lymphocytes, as well as by humoral antibodies of the IgG class.

Received: 2019-12-09

Published online: 2020-01-24

DOI: 10.24075/brsmu.2020.004

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VIEWS 3914

Bochkova AG, Domozhirova AS, Aksenovа IA

In Russia, for more than 10 years, within the framework of national projects, the activities have been carried out aimed at restructuring of the primary and specialized (including high-tech) medical care, as well as strengthening of primary health care directed at early detection of malignant neoplasms. The study was aimed to evaluate the effectiveness of the patient examination rooms for women in improvement of the adjusted cumulative survival of patients with gynecologic malignancies detected actively in 2005–2015 in the Chelyabinsk Region. Using the Population Based Cancer Registry (PBCR) of the Chelyabinsk Region database, the adjusted cumulative survival calculation for patients with cervical cancer (389), uterine corpus cancer (373) and ovarian cancer (161) detected actively in the patient examination rooms of the Chelyabinsk Region (treatment group), as well as for cervical cancer (395), uterine corpus cancer (380) and ovarian cancer (163) detected in patients who sought medical assistance (control group), was performed for the first time. The staging of cervical cancer detected in the examination rooms in 2010–2017 was characterized by the high proportion of I/II stage tumors compared with the rest of patients’ population of the Chelyabinsk Region (an average of 50.8 and 46.1% respectively). For uterine corpus cancer the average proportion was 85.5 and 82.0% respectively, and for ovarian cancers it was 42.0 and 37.4% respectively. Analysis of the PBCR of the Chelyabinsk Region for a 10-year period revealed the 5-year adjusted cumulative survival improvement in the actively detected cervical cancer patients compared to the control group (62.3 and 55.8%) respectively (p = 0.11). In patients with uterine corpus cancer, it was 82.0% for the main group and 70.4% for the control group (p = 0.001). In ovarian cancer patients, no significant differences in the 5-year adjusted cumulative survival were observed (47.5% in the main group, 43.2% in the control group) (p = 0.49). Thus, the patient examination rooms are the effective model of the cancer secondary prevention available in the Chelyabinsk Region.

Received: 2019-12-23

Published online: 2020-01-23

DOI: 10.24075/brsmu.2020.003

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VIEWS 3619