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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Hamad A, Chumakov SP

Recombinant herpesviruses can be used as oncolytic therapeutic agents and high packaging capacity vectors for delivering expression cassettes into the cell. Herpesvirus saimiri is a gamma-herpesvirus that normally infects squirrel monkeys but also has a unique ability to infect and immortalize human lymphocytes while allowing them to retain their mature phenotype and functional activity. Recombination of the Herpesvirus saimiri genome in permissive cells is impeded by its resistance to chemical transfection and electroporation. The aim of this study was to develop an effective method for incorporating expression cassettes into the genome of Herpesvirus saimiri without having to transfect a permissive cell culture. Transfected HEK-293T cells expressing glycoproteins of the measles virus vaccine strain were co-cultured with permissive OMK cells infected with Herpesvirus saimiri. Cell fusion and formation of syncytia stimulated recombination between the viral genome and the expression cassette; this allowed us to obtain a recombinant Herpesvirus saimiri variant without chemical transfection in permissive cells. The genetically modified virus expressed a selectable marker and retained its ability to persist in the cell in the latent state; it also caused immortalization of primary lymphoid cells. The proposed approach allows engineering recombinant Herpesvirus saimiri strains carrying a variety of expression cassettes in its genome.

Received: 2019-11-11

Published online: 2019-12-11

DOI: 10.24075/brsmu.2019.079

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VIEWS 5583

Bushkova YuV, Ivanova GE, Stakhovskaya LV, Frolov AA

Motor recovery of the upper limb is a priority in the neurorehabilitation of stroke patients. Advances in the brain-computer interface (BCI) technology have significantly improved the quality of rehabilitation. The aim of this study was to explore the factors affecting the recovery of the upper limb in stroke patients undergoing BCI-based rehabilitation with the robotic hand. The study recruited 24 patients (14 men and 10 women) aged 51 to 62 years with a solitary supratentorial stroke lesion. The lesion was left-hemispheric in 11 (45.6%) patients and right-hemispheric in 13 (54.4%) patients. Time elapsed from stroke was 4.0 months (3.0; 12.0). The median MoCa score was 25.0 (23.0; 27.0). The rehabilitation course consisted of 9.5 sessions (8.0; 10.0). We established a significant moderate correlation between motor imagery performance (the MIQ-RS score) and the efficacy of patient-BCI interaction. Patients with high MIQ-RS scores (47.5 (32.0; 54.0) achieved a better control of the BCI-driven hand exoskeleton (63.0 (54.0; 67.0), R = 0.67; p < 0.05). Recovery dynamics were more pronounced in patients with high MIQ-RS scores: the median score on the Fugl-Meyer Assessment scale was 14 (8.0; 16.0) points vs 10 (6.0; 13.0) points in patients with low MIQ-RS scores. However, the difference was not significant. Thus, we established a correlation between a patient’s ability for motor imagery (MIQ-RS) and the efficacy of patient-BCI interaction. A larger patient sample might be necessary to assess the effect of these factors on motor recovery dynamics.

Received: 2019-11-12

Published online: 2019-12-07

DOI: 10.24075/brsmu.2019.078

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VIEWS 5991

Revina DB, Balatskiy AV, Larina EB, Oleynikova NA, Mishurovsky GA, Malkov PG, Samokhodskaya LM, Panina OB, Tkachuk VA

Placental insufficiency (PI) and its complications are multifactorial conditions that cause perinatal morbidity and mortality. Since the urokinase system is involved in placentation, it should have a role in PI pathogenesis. The aim of this work was to study the associations between single nucleotide polymorphisms (SNPs) of genes coding for protein components of the urokinase system and PI, as well as investigate their effect on the expression of these proteins in the placenta and placental structure. We examined 114 women with uncomplicated pregnancy and delivery, 48 female patients with pre-eclampsia and/or intrauterine growth restriction (IUGR), and 95 newborns, (pre-eclampsia and/or IUGR: n = 60; uncomplicated pregnancy and delivery: n = 35). Maternal and fetal DNAs were genotyped using real-time PCR. Placenta fragments were subjected to morphometry and immunohistochemistry. We discovered the associations between PI and the maternal C allele of rs4065 (PI group: СС-СТ 64.1%, TT 35.9%; controls: СС-СТ 25.6%, TT 74.49%; OR (95%CI): 6.83 (2.63–17.79)), the maternal A allele of rs2302524 (GG-GA 20.5%, AA 79.5% vs. GG-GA 48.1%, AA 51.9%, OR (95%CI): 0.27 (0.1–0.71)), the fetal C allele of rs4065 (СС-СТ 76.4 %, TT 23.6% vs. СС-СТ 69.6%, TT 30.4%, OR (95%CI): 1.37 (0.45–4.17)), and the fetal C allele of rs344781 (TT-TC 69.1%, СС 30.9% vs. TT-TC 95.7%, СС 4.3%, OR (95% CI): 5.02 (1.07–23.6)). The multivariate analysis confirmed the significance of the fetal rs4065 genotype. In patients with PI, uPA expression was lower (ME (95%CI): 116.45 (100.5; 128.74) vs. 126.09 (113.76; 139.19); р < 0.05). No associations were established between SNPs and protein expression. The degree of vascularization depended on the maternal rs4065 genotype (the stroma-to-vessel ratio for the CC genotype was 0.17 (0.15; 0.19); for the CT genotype, 0.18 (0.15; 0.21) and for the TT genotype, 0.23 (0.2; 0.27); p < 0.05). We conclude that high placental uPA and the presence of the fetal TT rs4065 genotype are protective against the risk of PI.

Received: 2019-10-31

Published online: 2019-12-07

DOI: 10.24075/brsmu.2019.076

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VIEWS 5628

Gaydina TA, Dvornikov AS, Skripkina PA

Tumors of the skin/skin adnexa are astonishingly diverse. The diagnostic algorithms for skin neoplasms includes history taking, the assessment of clinical data, dermoscopy and a histopathological examination. Literature descriptions of a histologically confirmed pilomatricoma are scarce. If the lesion is localized to an esthetically sensitive body area, it is important to minimize the postoperative cosmetic defect. In the case described below, we were able to achieve a positive esthetic outcome in a patient with a facial pilomatricoma sized < 2 cm2 using a СО2 laser.

Received: 2019-11-14

Published online: 2019-12-01

DOI: 10.24075/brsmu.2019.077

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VIEWS 5529

Dergachova DI, Klein OI, Marinichev AA, Gessler NN, Bogdanova ES, Smirnova MS, Isakova EP, Deryabina YI

Non-alcoholic fatty liver disease is associated with a number of disorders (diabetes, obesity, cardiovascular diseases), and can also be induced by drugs or toxic compounds. Recently the important branch of medicine is the search for effective means of prevention and treatment of fatty hepatosis. Our work was aimed to study the effect of some biologically active natural polyphenols (resveratrol and pinosylvin stilbenes as well as dihydromyricetin dihydroflavonol) on the function and histologic features of the liver. In the experimental model of thioacetamide-induced toxic hepaptitis, the male rats of the Wistar line daily received the effective doses of polyphenols intragastically by gavage together with 0.05% thioacetamide added to drinking water. All studied polyphenols contributed to stabilization of rat weight and a two-fold significant (p < 0.05) decrease in the level of direct bilirubin in the blood serum of animals treated with thioacetamide. Histological analysis of the liver confirmed a decrease in inflammation and hemorrhage in animals treated with polyphenols amid continued administration of thioacetamide for 30 days. Based on the data obtained, it can be concluded that the natural polyphenols which belong to the classes of dihydroflavonols (dihydromyricetin) and stilbenes (resveratrol and pinosylvin) have a positive effect on liver function in the experimental model of toxic hepatosis. The studied polyphenols can be considered as potential hepatoprotective drugs used as a part of the liver diseases complex therapy.

Received: 2019-10-26

Published online: 2019-11-27

DOI: 10.24075/brsmu.2019.075

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VIEWS 5465

Tsitsiashvili MSh, Shipovskiy VN, Monakhov DV, Chelyapin AS, Huseynov AB

Transjugular intrahepatic portosystemic shunt is one of the few available options for treating complications of portal hypertension in patients with chronic diffuse liver diseases. Over time, shunt patency can become compromised, causing a recurrence of such complications. The clinical case presented below demonstrates the potential of TIPS and illustrates the use of an endovascular reintervention for re-establishing shunt patency, which improves the life expectancy of patients, as well as their quality of life.

Received: 2019-10-24

Published online: 2019-11-16

DOI: 10.24075/brsmu.2019.074

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VIEWS 5185

Broutian AG, Belyakova-Bodina AI, Dolgova SM, Pushkar TN, Abramova AA

Sleep is an important activator of epileptiform activity, with epileptiform discharge (ED) probability varying among sleep stages. The aim of our study was to analyze the association between epileptiform activity and sleep stages or wakefulness in adults with temporal discharges. We analyzed 32 long-term overnight EEG recordings. All focal discharges were marked, and the entire sleep was staged. Absolute general epileptiform discharge index (EDI), defined as a ratio of total ED number to the full recording time in hours, as well as absolute EDIs for REM, N1, N2 and N3 stages were calculated. The majority of patients (28) had the highest EDI in N3. EDI increased significantly while sleep progressed to deeper stages, reaching its peak in N3. In REM sleep, EDI sharply declined (p < 0.01) reaching the levels of wakefulness. Increasing synchronization of cortical neurons is thought to be the major mechanism of EDI rise in NREM sleep. Hence, N3 seems to be the most sensitive stage to capture EDs, which highlights the importance of deep sleep recording in patients with temporal epilepsy.

Received: 2019-08-23

Published online: 2019-11-07

DOI: 10.24075/brsmu.2019.073

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VIEWS 5618

Mikelov AI, Staroverov DB, Komech EA, Lebedev YuB, Chudakov DM, Zvyagin IV

Mechanisms of maintenance of immunological memory in the chronic course of seasonal allergic rhinitis remain poorly understood. The detailed understanding of these mechanisms is required for design of new approaches for allergy treatment. It is known that the level of allergen-specific IgE antibodies (sIgE), which play a key role in the development of the disease, is increased in patients with seasonal allergic rhinitis during pollination season. This study aimed to investigate the dynamics of serum IgE levels and characteristics of the clonal repertoire of IgE-secreting lymphocytes depending on the intensity of the patient's contact with the allergen. For three patients, allergic to birch pollen (22, 22, and 28 y.o.), we measured total IgE and birch pollen specific IgE levels at 6 time points with 2 week interval during the birch pollination season. Immunoglobulin heavy chain gene (IGH) clonal repertoire data for several B-cell subpopulations at different time points were obtained for one patient. We observe growth of the sIgE level (91%, 37%, and 64% compared to the baseline) at the peak of pollination season in all three donors. Initial increase in sIgE and IgE levels coincides with the birch pollination initiation; sIgE and total IgE levels correlate with the birch pollen air level (sIgE: R2 = 0.98 at p < 0.05; total IgE: R2 = 0.95 at p < 0.05). We detected IgE clonotypes only in samples obtained during the birch pollination, which indicates an increase of IGE-expressing cells concentration during this period. The frequency of IgE clonotypes was extremely low compared to that of the clonotypes of other isotypes (IgE — 0.01%, IgM — 48.4%, IgD — 14%, IgG — 17.4%, IgA — 19.8%). Hypermutation and phylogenetic analysis of the sequences from the 13 detected IgE-containing clonal groups showed that these IgE clonotypes could originate from IgG as a result of sequential isotype-switching.

Received: 2019-10-09

Published online: 2019-10-31

DOI: 10.24075/brsmu.2019.072

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VIEWS 5752