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, Khovryakov AV

Today, increasing attention is being paid to the role of circadian rhythms in pathology. There are time-of-day-dependent immune markers that provide valuable information about disease progression. The aim of this study was to measure evening and morning concentrations of a few cytokines (interleukins, adhesion molecules, tumor necrosis/growth factors, etc.) in the peripheral blood of patients with stage II essential hypertension and to investigate how they correlate with a nocturnal blood pressure decline. Blood samples were collected from 90 patients with stage II EH at 7:00 a.m. and 8:00 p.m. Cytokine concentrations were measured using immunoassays. Based on 24-h blood pressure monitoring, the patients were distributed into 3 groups: dippers, non-dippers and night-peakers. The morning to evening ratios of cytokine concentrations in patients with EH differed from those in healthy controls due to an increase in the evening concentrations of somnogenic cytokines (IL1β, IL1α) and LIF, sLIFr, and M-CSF whose daily fluctuations patterns remain understudied. On the whole, the fluctuation patterns of the measured cytokines in patients with stage II EH who had had the condition for 10 to 14 years and were receiving no antihypertensive treatment at the time of our study differed from those displayed by healthy controls. A twenty percent rise in the evening concentrations of IL1α, LIF, sLIFr, M-CSF, and erythropoietin contributes significantly to pathological blood pressure rhythms (as demonstrated by the groups of non-dippers and night-peakers) in patients with stage II EH receiving no antihypertensive therapy. Understanding the pathophysiological role of cytokine levels and their fluctuations over a 24-h cycle could inspire new methods for EH prevention and reduce end-organ damage.

Received: 2018-07-16

Published online: 2019-03-13

DOI: 10.24075/brsmu.2019.011

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VIEWS 3410

Voroshilina ES, Zornikov DL, Panacheva EA

Among other things male sterility can be caused by inflammatory diseases of the urogenital tract, often associated with opportunistic microorganisms. Thus, it is necessary to implement modern methods for the detection and identification of opportunistic microorganisms in the urogenital tract. The aim of the work was to conduct comparative analysis of the ejaculate microbiota from men of the reproductive age and studied using quantitative polymerase chain reaction (PCR) and culture method. 86 samples of ejaculate collected from men aged 18–57 years after observing sexual abstinence for 3–5 days were examined. With culture study in 50% of samples we observed growth of gram positive facultative anaerobic bacteria in the amount less than 103 CFU/ml; in 16.3% of samples — the growth of bacteria was not observed. With real-time PCR in each sample 8–15 groups of microorganisms were detected (including the prevailing groups) in the amount of 102–106 GE/ml. In all 86 samples obligate anaerobes that cannot not be cultured in vitro were detected. The predominant groups of microorganisms, as determined by real-time PCR, were detected by the culture method only in 24.4% of cases.

Received: 2019-02-11

Published online: 2019-03-11

DOI: 10.24075/brsmu.2019.009

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VIEWS 3707

Manturova NE, Stenko AG, Petinati YaA, Chaikovskaya EA, Bolgarina AA

To a large extent, age-related facial skin changes, wrinkles and flabbiness, are attributed to the structural alterations in dermis, including of collagen fibers fragmentation and disorganization. There are various cosmetological correction methods that aim to activate neocollagenesis and dermal remodeling. From this perspective, intradermal injections of exogenous collagen preparations seem logical. This study aimed to investigate the efficacy and safety of Collost 7% collagen complex applied to correct the age-related facial skin changes, as well as clarify the possible mechanisms of skin rejuvenation resulting from a course of intradermal injections. 35 participants entered the study, 30 of them finished it. A set of indicators describing age-related skin changes was assessed with the help of clinical scales; the assessment revealed a pronounced improvement in the quality of the patients' skin, including smoothed relief in the area of localization of fine wrinkles. The therapy resulted in a statistically significant improvement of the skin's elasticity, which, combined with the changes discovered through US scanning (greater dermis thickness and echodensity), is an indirect indication of skin restructuring associated with accumulation of fibrous protein structures. These results allow parallels with the experimental data that shows activation of neocollagenesis in the skin of laboratory animals after a course of Collost 7% gel. The research revealed no serious adverse events. A course of collagen administered intradermally can be recommended as an aesthetic correction procedure, as well as means of prevention of atrophy that has a significant effect on skin's appearance and health status.

Received: 2018-09-27

Published online: 2019-03-10

DOI: 10.24075/brsmu.2019.010

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VIEWS 3388

Kostyuk AI, Kotova DA, Demidovich AD, Panova AS, Kelmanson IV, Belousov VV, Bilan DS

With each year, millions of people remain targeted by brain stroke, it still is by all means a global concern of the mankind. Despite all efforts to understand this disease better, there is still a lack of information on pathophysiology of ischemic stroke. Scrutinized data on biochemical changes at early stages of ischemia may help understand the mechanisms of the disorder and possibly reveal ways to finding the cure. The key role in the pathogenesis of stroke belongs to lipids as well as to the molecules associated with their biosynthesis and functionality. On the one hand, stroke evokes a deep oxidative stress leading to damage to biomolecules including lipids while on the other hand, due to the lack of reducing equivalents, the cellular biosynthesis processes are interrupted. The focus of this work was to study the changes taking place in the tissues of rat brain as a result of ischemia including estimation of levels of total cholesterol, FFA, MDA, GSH, and NADP(H). It was shown that in 24 hours from the onset of ischemia, there was a significant decrease in levels of FFA, total cholesterol and GSH, and an increase in the level of MDA, a marker of lipid peroxidation. NADP(H) pool level decreases twice in 6 hours from MCAO.

Received: 2018-12-12

Published online: 2019-03-10

DOI: 10.24075/brsmu.2019.008

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VIEWS 3444

Filipenko ML, Oscorbin IP, Khrapov EA, Shamovskaya DA, Cherednichenko AG, Shvartz YaSh

To identify genetic mutations a rather time-consuming and expensive method of polymerase chain reaction (PCR) is widely used. The aim of the present work was to evaluate the possibility of using the two schemes of the method of allele-specific isothermal loop amplification (LAMP) to detect the TCG/TTG (S450L) mutation in the rpoB gene of Mycobacterium tuberculosis. 48 clinical isolates of M. tuberculosis and 11 samples of sputum were used, randomized and obtained in the microbiological laboratory of the city of Novosibirsk from incident patients. It is shown that the use of an analysis scheme using the allele-specific primer FIP compared to F3 has the best resolution: the difference between the amplification time of the mutation and the wild type allele was 22 ± 2,4 versus 13 ± 4,1 minutes (p = 0,0011). When using 100 DNA genomic equivalents a true positive signal (amplification of the rpoB gene with a mutation using the corresponding allele-specific primer) was detected after 29,4 ± 3,4 minutes. A positive signal was visualized after adding SYBR Green I to the reaction, both when illuminated with daylight and when using a UV transilluminator. Using the developed method the DNA sample of 20 RIFR isolates from M. tuberculosis was analyzed containing the Ser450Leu mutation in the rpoB gene, 10 RIFR isolates containing other mutations in the rpoB gene and 18 RIFs isolates without any mutations; the presence of mutations in the samples was determined using classical Sanger sequencing. The sensitivity and specificity of LAMP for detecting a Ser450Leu mutation in the rpoB gene was 100%. This approach allows the use of crude lysates of mycobacteria as DNA, which reduces the total analysis time to 1,5 hour.

Received: 2018-12-07

Published online: 2019-03-09

DOI: 10.24075/brsmu.2019.007

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VIEWS 3715

Radaeva OA, Simbirtsev AS

Essential hypertension (EH) is one of the most common modifiable risk factors for cardiovascular diseases and death. The aim of this study was to investigate a correlation between the levels of some cytokines (interleukins, adhesion molecules, tumor necrosis and growth factors, etc.) in the peripheral blood of patients with stage II EH and the rate of complications (myocardial infarction, acute cerebrovascular events, and transient ischemic attacks) occurring in a 5-year follow-up period. Twenty-eight cytokines were measured using ELISA, including IL1β, IL1α, IL1ra, IL18, IL18BP, IL37, IL6, sIL6r, LIF, sLIFr, IGF-1, IGFBP-1, TNFα, sTNF-RI, sVCAM-1, IL17, IL2, IL4, IL10, TGF-β1, IL8, CX3CL1, CXCL10, INFγ, M-CSF, IL34, VEGF-A, and erythropoietin, and a few vasoactive peptides, including NО, iNOS, eNOS, ADMA, SDMA, Nt-proСNP, and Nt-proBNP, in the peripheral blood samples of 200 patients with stage II EH who had been suffering from this condition for 10 to 14 years and were receiving comparable therapies to bring their blood pressure down. The patients were followed up for 5 years to keep track of complications. The retrospective analysis revealed that the group of patients who developed complications during the 5-year follow-up period exhibited a decline in the levels of IL1ra (р < 0.001) and IL10 (р < 0.001) and a rise in IL1β (р < 0.001), TNFα (р < 0.001) and M-CSF (р < 0.001) in comparison with the group of those who did not develop any complications. The multivariate Cox regression analysis was applied to the following parameters: IL1β > 18.8 pg/ml; IL1ra < 511 pg/ml; IL6 > 23.8 pg/ml; IL10 < 26.3 pg/ml; 389 pg/ml < M-CSF < 453 pg/ml; ADMA > 0.86 μmol/L; total cholesterol > 4.9 mmol/L; LDL> 3.0 mmol/L; HDL in men < 1.0 mmol/L; HDL in women < 1.2 mmol/L. The analysis revealed that M-CSF in the range from 389 to 453 pg/ml (р < 0.001) and LDL above 3.0 mmol/L (р < 0.01) correlated with an increase in the risk for end-organ damage in stage II EH. Changes in the cytokine levels can be regarded as a predictor of myocardial and cerebral damage in patients with stage II EH. Measurement of peripheral blood M-CSF can be included into the classic risk assessment schemes for the cardiovascular complications in the studied cohort of patients.

Received: 2018-07-16

Published online: 2019-03-07

DOI: 10.24075/brsmu.2019.006

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VIEWS 3504

Dolzhikova IV, Tukhvatulin AI, Gromova AS, Grousova DM, Tukhvatulina NM, Tokarskaya EA, Logunov DYu, Naroditskiy BS, Gintsburg AL

Ebola virus disease (EVD) is one of the deadliest viral infections affecting humans and nonhuman primates. Of 6 known representatives of the Ebolavirus genus responsible for the disease, 3 can infect humans, causing acute highly contagious fever characterized by up to 90% fatality. These include Bundibugyo ebolavirus (BDBV), Zaire ebolavirus (ZEBOV) and Sudan ebolavirus (SUDV). The majority of the reported EVD cases are caused by ZEBOV. Vaccine development against the virus started in 1976, immediately after the causative agent of the infection was identified. So far, 4 vaccines have been approved. All of them are based on the protective epitope of the ZEBOV glycoprotein GP. Because SUDV and BDBV can also cause outbreaks and epidemics, it is vital to design a vaccine capable of conferring protection against all known ebolaviruses posing a threat to the human population. This article presents systematized data on the structure, immunogenicity and protective properties of ebolavirus glycoprotein GP, looks closely at the immunodominant epitopes of ZEBOV, SUDV and BDBV glycoprotein GP required to elicit a protective immune response, and offers a rational perspective on the development of a universal vaccine against EVD that relies on the use of vectors expressing two variants of GP represented by ZEBOV and SUDV.

Received: 2018-12-06

Published online: 2019-03-03

DOI: 10.24075/brsmu.2019.005

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VIEWS 3745

Svirshchevskaya EV, Simonova MA, Matushevskaya EV, Fattakhova GV, Khlgatian SV, Ryazantsev DYu, Chudakov DB, Zavriev SK

Type I hypersensitivity is mediated by the production of IgE antibodies in response to normally harmless substances. Debate still continues about the mechanisms underlying allergic reactions. Reduced barrier tissue function can be one of the risk factors for allergies. The aim of the present work was to compare the humoral immune response to Epstein-Barr virus in patients allergic to the A. alternata fungus or D. farinae house dust mites and healthy donors. It is known that up to 90% of the world population are infected with EBV. This infection occurs at early age when a child develops allergy. The antibodies were analyzed using immuno-PCR and the recombinant EBV protein rEBNA. We were able to demonstrate that infection occurs at early age in both allergic patients and healthy donors. The proportion of EBP-seropositive individuals was comparable between the groups (75% and 74%). The proportion of patients with high IgG1 titers among patients with allergies was lower (7%) than in healthy donors (18%), suggesting a lower viral load. In patients with allergies (but not in healthy donors) IgG1 titers declined as children grew older (р = 0.037). Besides, IgA1 titers were increased in patients with allergies in comparison with healthy donors, but differed between patients allergic to A. alternata and house dust mites. In allergic individuals, production of IgM against EBV was triggered earlier than in healthy donors. We conclude that IgM production and the IgA1-mediated humoral response occur earlier in patients with allergies, causing a decline in IgG1 titers over time.

Received: 2018-09-12

Published online: 2019-03-01

DOI: 10.24075/brsmu.2019.004

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VIEWS 3747