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.
VIEWS 5221
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.
VIEWS 5008
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.
VIEWS 5358
In the context of strengthening the fight against doping and limiting the use of synthetic pharmaceuticals, the effective remedies to increase physical performance and accelerate the recovery of athletes are being sought. One of such remedies is exposure to low-level laser radiation (LLLR, LLLT). The study was aimed to investigate the physiological response of highly qualified female rowers’ functional systems to the LLLR irradiation course. To monitor the body of athletes, we used laser Doppler flowmetry (LDF), mathematical analysis of heart rate, neuroenergy mapping, as well as pedagogical testing using the Concept 2 simulator. After irradiation of the neck in the projection of the carotid arteries with pulsed infrared LLLR, the blood perfusion rate increased by 38% (р < 0.05) and cell oxygen utilization rate increased by 48% (р < 0.05). The decrease in the hemoglobin oxygen saturation by 16% (р < 0.05) was also observed. Due to LLLT, the activity of the autonomous regulation mechanism increased with an increase in the total power of the heart rate variability spectrum (TP) by 41% (р < 0.05), and in high-frequency power (HF) by 73% (р < 0.05). The influence of central mechanism decreased with a decrease in amplitude mode (AMo) by 71% (р < 0.05), and in stress-index (SI) by 175% (р < 0.05). Irradiation by LLLR promoted the efficiency of oxygen delivery to certain cerebral cortex areas with the increase of SPL. Аfter LLLT, the speed of 2000 meters distance "passing" by athletes also increased by 3.32% (p > 0.05). The discovered effects of LLLT allow one to expand the range of physiotherapeutic agents that enhance the special physical performance of athletes and accelerate recovery.
VIEWS 4943
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.
VIEWS 5185