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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Kazakova AV, Uvarova EV, Limareva LV, Trupakova AA, Mishina AI

At present, there is a paucity of research studies that comprehensively investigate the factors causing vulvovaginitis in young females. The aim of this work was to propose an algorithm for predicting the risk of vulvovaginitis in young girls and adolescents. The study recruited 252 healthy girls, who were stratified into a few groups depending on their sexual development on the Tanner scale. The composition of vaginal microbiota was determined in all the participants using real-time polymerase chain reaction (PCR); distribution of allele and genotype frequencies was assessed for the polymorphic variants of genes coding for pro- and anti-inflammatory cytokines. Based on the obtained data, we created a functional model for predicting the risk of vulvovaginitis in girls at different stages of sexual development. Favorable risk factors for Tanner I girls included predominance of obligate anaerobes in vaginal microbiota and the polymorphic IL10 variant (С-819Т) homozygous for TT. The sensitivity of the model was 80%, its specificity was 78%. Favorable risk factors for prepubertal and pubertal girls included predominance of aerobes in the composition of vaginal microbiota and the presence of the TT allele in the polymorphic IL10 gene variant (С-3953Т). The sensitivity of the model was 58.3%, whereas specificity, 94.1%. This study provides the rationale conforming with the principles of evidence-based medicine for using prevention measures in the groups at risk for vulvovaginitis at young age. The proposed measures allowed us to reduce the relapse rate of bacterial vulvovaginitis threefold.

Received: 2019-09-27

Published online: 2019-10-29

DOI: 10.24075/brsmu.2019.070

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VIEWS 4833

Balanovsky OP, Petrushenko VS, Gorin IO, Kagazezheva ZhA, Markina NV, Kostryukova ES, Leybova AN, Maurer AM, Balanovska EV

Prediction of eye and hair color from DNA is being increasingly employed in forensics and the studies of ancient populations. HIrisPlex-S is a prediction tool trained on the Dutch dataset and verified using a few other European populations. The accuracy of its predictions for other regions of the world has not been studied yet. Russian populations pose a special interest because, unlike the majority of world populations, their representatives can have not only dark but also light color eyes and hair. The aim of this work was to evaluate the accuracy of eye and hair color prediction in Russian populations. We recruited 144 representatives of indigenous peoples of Russia (Avar, Aleut, Buryat, Itelmen, Karelian, Koryak, Mari, Nanai, Russian, Rutulian, Chuvash, Chukchi, Evenk, and Even populations). All study participants were photographed. Eye and hair colors were identified from the anthropological images by anthropologists. The SNP markers included in the HIrisPlex system were genotyped. Phenotypes were predicted from the obtained genotypes and subsequently compared to the actual phenotypes. Quality metrics were calculated for HIrisPlex prediction accuracy in the populations of European Russia and Siberia. On the whole, HIrisPlex prediction accuracy was satisfactory, although a bit lower than in Western European datasets. Further research could focus on identifying additional markers to improve the accuracy of predictions in Russian populations.

Received: 2019-10-22

Published online: 2019-10-27

DOI: 10.24075/brsmu.2019.069

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VIEWS 5333

Shradqa AS, Kumar V, Frolov MA, Dushina GN, Bezzabotnov AI, Abu Zaalan KA

Glaucoma is one of the main causes of irreversible blindness in the Russian Federation and it is the leading cause of visual impairments among working age population. The primary goal of glaucoma therapy is to preserve the visual function, which is mainly achieved through persistent normalization of IOP by instillation of hypotensive drugs, laser therapy and/or surgery/ In this clinical study safety and efficacy of a glaucoma surgical technique implying valve cyclodialysis ab externo with implantation of a non-absorbable collagen implant (NACI) (Xenoplast, Dubna-Biofarm, Russia) in the supraciliary space were evaluated. All patients exhibited moderate and severe primary open-angle glaucoma (POAG). The efficacy assessment criterias were intraocular pressure (IOP) dynamics, use of hypotensive medications, need for repeat surgical intervention and complications. A total of 26 patients (26 eyes) were operated upon and under observation. Twelve months after surgery, 34% IOP decrease from the baseline level was observed: from 29.5 ± 6.8 to 18.8 ± 4.3 mmHg. The amount of hypotensive medications used reduced from 2.8 ± 0.9 to 0.6 ± 0.9. Applying the criteria recommended by the World Glaucoma Association, complete success was registered in 73.1% of patients and partial success — in 26.9% patients. No surgery ended in a failure through the follow-up period. Post-operatively, one patient developed hyphema, 2 patients had some blood elements in aqueous humor and 1 patient had shallow anterior chamber (AC). The suggested surgical technique proved to be an efficient and safe way to decrease IOP and reduce the number of hypotensive medications and had a minimal number of complications associated with the surgery, therefore it can be recommended as a method of choice in patients with advanced stage POAG.

Received: 2019-08-16

Published online: 2019-10-23

DOI: 10.24075/brsmu.2019.068

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VIEWS 4653

Zhorina YuV, Abramovskikh OS, Ignatova GL, Ploshchanskay OG

Bronchial asthma is a multifactorial disease underpinned by chronic inflammation. The atopic phenotype of BA implies the presence of similar molecular mechanisms of pathogenesis between the patients. The aim of this study was to analyze the associations between the development of atopic BA/its remission and the following polymorphisms of interleukin genes: IL4 (rs2243250; C-589T), IL10 (rs1800896; G-1082A; rs1800872; C-592A), and IL13 (rs20541; Arg130Gln). Using allele-specific polymerase chain reaction (PCR), we studied the listed SNPs in the mixed urban sample of patients with BA (n = 53) and the controls (n = 30) residing in South Ural. The analysis revealed that genotype АА of IL10 (rs1800872) occurred more frequently in the control group (23.3%) than in the patients with atopic BA (5.7%) (OR = 0.197; 95% CI [0.047–0.832]; р = 0.031). No differences in genotype frequencies were observed between the patients with atopic BA and the controls for other studied polymorphisms. Our study failed to demonstrate the association of the listed polymorphisms and BA remission.

Received: 2019-09-25

Published online: 2019-10-21

DOI: 10.24075/brsmu.2019.067

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VIEWS 4512

Kiseleva YaYu, Shishkin AM, Ivanov AV, Kulinich TM, Bozhenko VK

Adoptive immunotherapy that makes use of genetically modified autologous T cells carrying a chimeric antigen receptor (CAR) with desired specificity is a promising approach to the treatment of advanced or relapsed solid tumors. However, there are a number of challenges facing the CAR T-cell therapy, including the ability of the tumor to silence the expression of target antigens in response to the selective pressure exerted by therapy and the dampening of the functional activity of CAR T cells by the immunosuppressive tumor microenvironment. This review discusses the existing gene-engineering approaches to the modification of CAR T-cell design for 1) creating universal “switchable” synthetic receptors capable of attacking a variety of target antigens; 2) enhancing the functional activity of CAR T cells in the immunosuppressive microenvironment of the tumor by silencing the expression of inhibiting receptors or by stimulating production of cytokines.

Received: 2019-10-03

Published online: 2019-10-18

DOI: 10.24075/brsmu.2019.066

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VIEWS 4907

Maksimova MYu, Dubovitskaya YuI, Krotenkova MV, Shabalina AA

Cerebral venous sinus thrombosis (CVT) becomes the cause of stroke in less than 1% of patients. In 20-30% of patients, the cause of thrombosis remains unclear, and thrombosis is considered idiopathic. Inherited hypercoagulable conditions significantly increase the risk of CVT. The aim of the study was to evaluate the frequency of prothrombogenic polymorphic variants of hemostatic and methionine-homocysteine metabolism genes alleles and genotypes in patients with aseptic CVT. Fifty one patients aged 18–75 with aseptic CVT were examined. The control group included 36 healthy volunteers. Neuroimaging methods included brain MRI in standard modes (T1, T2, T2 d-f (FLAIR), DWI) and MR venosinusography. All patients were surveyed to identify carriers of prothrombogenic polymorphic variants of hemostatic and folate metabolism genes alleles and genotypes. Prothrombogenic polymorphic variants of hemostatic genes were detected in 94% of patients, and the variants of the methionine-homocysteine metabolism genes were observed in 86% of patients. The differences between distributions of alleles and genotypes 5G6754G of the PAI-1 gene, G103T of the FXIIIA1 gene, A66G of the MTRR gene, A2756G of the MTR gene in the group of patients with CVT and in the control group were significant. Allele 4G, genotypes 4G/4G and 5G/4G of 5G6754G polymorphism of the PAI-1 gene; allele T of G103Т polymorphism of the FXIIIA1 gene; allele G and genotype A/G of A66G polymorphism of the MTRR gene; allele G and genotype A/G of A2756G polymorphism of the MTR gene correlated with aseptic CVT. It was concluded that the gene polymorphisms 5G6754G (PAI-1), G103T (FXIIIA1), A66G (MTRR) and A2756G (MTR) carriage increased the risk of aseptic CVT and did not affect the thrombosis clinical manifestations.

Received: 2019-08-19

Published online: 2019-10-16

DOI: 10.24075/brsmu.2019.065

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VIEWS 4542

Kalashnikova LA, Gulevskaya TS, Sakharova AV, Chaykovskaya RP, Gubanova MV, Danilova MS, Shabalina AA, Dobrynina LA

The causes of internal carotid artery (ICA) and vertebral artery (VA) dissection, as well as its provoking factors, remain understudied. The aim of this paper was to explore morphological changes in the ICA/VA walls, factors provoking dissection, clinical signs and biomarkers of connective tissue (CT) damage. A total of 271 patients were examined, of whom 54% were women. The mean age of the participants was 37.0 ± 10 years. Clinical signs and biomarkers of CT damage (matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1, hydroxyproline, sulphated glycosaminoglycans) were analyzed in 82 patients and 40 healthy volunteers. Histologic examination of dissected and seemingly intact arteries conducted in 5 cases revealed signs of arterial wall dysplasia similar to those characteristics of fibromuscular dysplasia: thinning and splitting of the internal elastic membrane, areas of fibrosis, irregular orientation of myocytes, and their necrosis in the tunica media. Clinical signs and biomarkers of CT dysplasia (CTD) were more pronounced in patients with arterial dissection than in the controls. The major provoking factors were head turns and physical activity (42%), minor head injury (10%), and acute respiratory infection in the month preceding arterial dissection (14%). We conclude that arterial wall dysplasia is a predisposing factor for ICA/VA dissection, both spontaneous and provoked. The analysis of CTD biomarkers and clinical signs suggests connective tissue pathology in patients with ICA/VA dissection.

Received: 2019-09-03

Published online: 2019-10-03

DOI: 10.24075/brsmu.2019.064

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VIEWS 4985

Priputnevich TV, Isaeva EL, Muravieva VV, Gordeev AB, Zubkov VV, Timofeeva LA, Mesyan MK, Shubina J, Makarov VV, Yudin SM

Currently, there are no criteria allowing to adequately assess composition and volume of the newborns' gut microbiota, which prevents early detection of the pathological processes and appropriate intervention. This study aimed to apply the methods of culturomics, proteomics and molecular genetic technologies to investigate the development of gut microbiota in healthy newborns delivered in the city of Moscow both vaginally and through a cesarean section. We examined 66 children, 33 of them delivered vaginally and 33 by cesarean section. The luminal bacterial flora samples were collected on the 1st, 7th and 30th days of life. There were 136 species of microorganisms belonging to 40 genera identified. We established that cesarean section slows down normal development of the gut microflora: through the follow-up period (1 month of life), gut microbiocenosis in such children did not yield the results on par with those registered in children born vaginally. Bifidobacteria were significantly more common in the vaginal delivery group: 84% of 109–1012 CFU/g versus 33% of 105–1012 CFU/g in the cesarean section group. At the same time, the former group had significantly less clostridia (33.3% and 65.4%, respectively) and lactose-negative Escherichia coli strains (2.4 and 19.4%, respectively) than the latter group.

Received: 2019-08-28

Published online: 2019-09-28

DOI: 10.24075/brsmu.2019.063

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VIEWS 5148