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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Kulinich TM, Krastelev EG, Bykov YuA, Smirnov VP, Shishkin AM, Ivanov AV, Bozhenko VK

Research into the effects of radiation delivered at ultrahigh dose rates > 1 × 107 Gy/min to biological objects is a new promising area of radiobiology. The unique characteristics of the high-current nanosecond electron accelerator Mir-M enable its use in medical and biological research, specifically in the experiments aimed at investigating the effect of therapeutic doses at a dose rate up to 100 MGy/s. In this work we study the effects of ultrahigh dose rate photon radiation on human lung carcinoma (A549) and melanoma (MelMtp-x) cells lines and compare them with those of the therapeutic gamma unit Rokus-AM. We show that ultrahigh dose rates induce more significant damage in the studied cell lines at doses between 2 and 7 Gy, radioresistant melanoma being more sensitive to photon radiation delivered at ultrahigh dose rates.

Received: 2018-08-15

Published online: 2018-12-09

DOI: 10.24075/brsmu.2018.066

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VIEWS 3432

Denisov IN, Zaugolnikova TV, Popova TS, Morozova TE

Early detection of dorsopathies is an urgent task for primary care physicians, since such conditions can combine with other chronic noncommunicable diseases (NСD) and adversely affect the course all comorbidities, consequently disimproving the quality of life of patients and increasing the frequency of their requests for medical assistance. This study aimed to determine the value of routine checkups in the context of detection of dorsopathies, NCD, and identification of risk factors (RF). We have retrospectively analyzed the patient records database of a rural outpatient clinic in the Tver region (years 2015 to 2017). The prevalence of dorsopathies and NCD RF were the subjects investigated. Fisher's exact test and Spearman's rank correlation coefficient (SRCC) were applied for the purposes of statistical processing of the results. We discovered that dorsopathy most often was a comorbidity to arterial hypertension and gastrointestinal tract diseases; it was strongly related to the NCD (SRCC = 0.506), age (SRCC = 0.383), slightly less so — to hypodynamia (SRCC = 0.146), type of the patient's occupation (intellectual or physical labor) (SRCC = 0.07). Routine checkups improve the rate of detection of dorsopathy: the more patients undergo such examinations, the more cases of dorsopathy are diagnosed. Thus, it is necessary to increase the number of working people attending the checkups in order to detect dorsopathies early and prevent them effectively.

Received: 2018-09-06

Published online: 2018-12-07

DOI: 10.24075/brsmu.2018.065

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VIEWS 3578

Israelson MA, Stepanov AV, Staroverov DB, Shagina IA, Misorin AK, Evstratieva AV, Merzlyak EM, Bogdanova EA, Britanova OV, Lukyanov SA

In the last decade there has been a tendency to move away from the symptomatic treatment and embrace targeted therapies. This process is underpinned by the accumulated knowledge of the mechanisms underlying the pathogenesis of diseases and driven by the advances in biotechnologies. T-cell receptors with variable TRBV9 β-chain regions have been recently associated with spondyloarthritis including its subtype, ankylosing spondylitis. The aim of this work was to engineer a chimeric monoclonal antibody targeting the variable region of the T-cell receptor β-chain encoded by the TRBV9 gene segment and assess its specificity and cytotoxicity. Using flow cytometry and next generation sequencing, we demonstrate that the engineered chimeric antibody is highly specific and exhibits cytotoxic activity against its target. Approaches based on the use of therapeutic chimeric antibodies against pathogenic T-clones may hold great promise for the therapy of autoimmune disorders in general and AS in particular.

Received: 2018-09-13

Published online: 2018-12-05

DOI: 10.24075/brsmu.2018.064

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VIEWS 4899

Osipova ZM, Shcheglov AS, Yampolsky IV

Modern biomedical research technologies actively use bioimaging for studying cells, tissues and whole organisms. Multicolor bioimaging is applied when simultaneous observation of different events at the molecular and cellular level is needed. Bioluminescent imaging methods are the most sensitive, however, their use for multicolor labeling is complicated due to the insufficient number of available uciferin-luciferase pairs. Having a number of advantages compared to previously studied bioluminescent systems, the new bioluminescence systems of higher fungi and marine polychaete Odontosyllis could become a useful expansion of the bioimaging toolbox.

Received: 2018-11-02

Published online: 2018-12-04

DOI: 10.24075/brsmu.2018.063

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VIEWS 3647

Lipengolts AA, Vorobyeva ES, Cherepanov AA, Abakumov MA, Abakumova TO, Smirnova AV, Finogenova YuA, Grigorieva EYu, Sheino IN, Kulakov VN

Contrast-enhanced radiotherapy (CERT) is a binary treatment modality in which the absorbed radiation dose is not only determined by the parameters of the external radiation source but also affected by the concentration of a dose-enhancing agent (DEA) in the studied object. In this work we assessed the distribution of the absorbed dose in a murine B16F10 melanoma injected with a single dose of an aqueous Bi-DTPA solution. The mice were exposed to a single fraction of X-ray irradiation for 28.5 min. In vivo measurements of DEA concentrations were done on a micro-CT scanner using the radiopacity values of malignant tissues from the obtained CT images. We found that the presence of DEA enhanced the absorbed dose more than twofold in 6% of the tumor volume; in 29% of the tumor volume the absorbed dose increased more than onefold. The tumor growth delay time calculated for our model was 0.76 days (we only accounted for the damage caused directly by radiation), whereas in our previous research study tumor growth delay was 10 days. This discrepancy may indicate that in the tumors exposed to contrast-enhanced radiotherapy growth delay results from both the damage directly caused by radiation and other antitumor mechanisms.

Received: 2018-09-28

Published online: 2018-12-01

DOI: 10.24075/brsmu.2018.062

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VIEWS 3894

Averkova AO, Brazhnik VA, Speshilov GI, Rogozhina AA, Koroleva OS, Zubova EA, Galyavich AS, Tereshenko SN, Boyeva OI, Zateyshchikov DA

The actual prevalence of genetic variants causing familial hypercholesterolemia (FH) in every population remains unknown. The aim of this work was to determine the spectrum of pathogenic variants in patients with acute coronary syndrome (ACS) and clinically diagnosed FH using targeted sequencing. We selected 38 patients with ACS from the sample of 2,081 participants of two multicenter observational studies (2004–2007; 2014–2016) who had a clinical diagnosis of FH based on the Dutch Lipid Clinic Network score and Simon Broome criteria. The men and women included in the study were ≤ 55 and ≤ 60 years of age, respectively. Molecular genetic screening was done by targeted next-generation sequencing. We started by sequencing 3 genes associated with FH, including LDLR, APOB, and PCSK9. If no relevant variants were detected, the panel was expanded. Of 38 patients, 24 (63.2%) were shown to have mutations that could cause clinical manifestations of FH and premature coronary artery disease. All patients were heterozygous carriers. Mutations were detected in three “classic” genes LDLR, APOB, and PCSK9 associated with FH, as well as in other genes involved in lipid metabolism, such as APOE, ABCA1, ABCG5, ABCG8, LPL, ANGPTL3, and MTTP. Five variants detected in our study sample had not been described previously: the pathogenic p.Val273_Cys313del variant of the LDLR gene, the likely pathogenic p.Arg160His variant in the APOE gene, two variants of uncertain significance p.Glu612Lys and c.*415G>A in the PCSK9 gene, and the mutant variant p.Ala776Ser in the LDLR gene. We conclude that the use of clinical diagnostic criteria in patients with ACS and FH enables identification of carriers of both “classic” mutations associated with FH and rare genetic variants that can be phenotypically expressed as FH.

Received: 2018-09-30

Published online: 2018-11-23

DOI: 10.24075/brsmu.2018.061

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VIEWS 3545

Eliseeva YuV, Voytovich AA, Milushkina OYu, Istomin AV, Eliseev YuYu

In a number of occupations, there is a shortage of labor force that can be filled with economically active part of the population, including people with disabilities (handicapped, HC). Unfortunately, observance of hygienic requirements in the context of HP adolescents vocational training has not been studied sufficiently: most scholars have researched only the conditions of teaching healthy adolescents. This study aimed to examine the HC adolescents vocational training conditions and develop measures to improve their working conditions with pathologies factored in. We examined adaptation potential, anxiety level, mental efficiency, sick rate and personal well-being assessment in HC adolescents (n = 120) aged 16–18, not impaired intellectually, studying sewing equipment operation, shoe repairs in the boarding scool. In the context of the study, we applied Smirnov hygiene criteria, Giessen Symptom Questionnaire, Spielberger's Test Anxiety Questionnaire, Sivkov scale, correction tables, Baevsky adaptation index. For the purposes of statistical analysis, we used parametric (Student t-test) and non- parametric (Mann–Whitney) criteria. The Spearman's correlation coefficient helped determine interrelationship of the studied parameters. We identified the following key adverse hygienic factors that have a significant impact on the students' health: intense character of labor performed, insufficient artificial lighting, noise level above the norm, high content of organic solvents and dust in the workshop's air. The timetable of the boarding school was also found to be inefficient. The results of this study allowed developing and introducing a software program to automatically compile the school's timetable with the aim to improve psychosomatic health of the students and halve the number of health-related complaints.

Received: 2018-06-17

Published online: 2018-11-23

DOI: 10.24075/brsmu.2018.060

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VIEWS 3353

Polunina NV, Soltamakova LS

In their daily life teachers go through a lot of stress ensuing from abrasive relationships with the administrative staff, colleagues or students, and family conflicts. Long-term exposure to stressors leads to the syndrome of emotional burnout, which can be avoided is preventive care is taken. The aim of this study was to identify burnout symptoms in the humanities teachers working for higher educational institutions and to propose adequate preventive measure. We recruited 1,489 teachers who were offered to anonymously fill out a questionnaire and also collected information about their health from sickness leaves. Statistical analysis included calculation of means, their errors, intensive and extensive variables, and confidence intervals. Two in three teachers reported fatigue, regular back/chest pain, and headache. The use of a scoring scale allowed us to conclude that a lot of respondents (43.2%) had severe burnout symptoms. Every second teacher demonstrated poor health awareness. To prevent staff burnout, measures should be taken aimed at stimulating a positive attitude to medical care, improving health literacy and motivating teachers to lead a healthy lifestyle.

Received: 2018-08-05

Published online: 2018-11-21

DOI: 10.24075/brsmu.2018.059

Comments 0

VIEWS 3622