HFE Gene Mutation Associated with the Severity of Gestational Diabetes Mellitus in Belarusian Women

To determine whether the H63D and C282Y mutations in HFE (hemochromatosis) gene are associated with the risk of gestational diabetes mellitus (GDM), we conducted the study of 65 incident cases. The class of gestational diabetes (A1, A2, B) in pregnant women was defined based on the results of glycemic profile and 75-g oral glucose tolerance test. Two single nucleotide polymorphisms (H63D and C282Y) in HFE gene were genotyped by PCR and RFLP (Restriction Fragment Length Polymorphism). The frequencies of mutations in patients cohort were: 0.14 for H63D and 0.02 for C282Y, which are similar to the data reported for Belarusian population (0.16 and 0.04 respectively). The detailed analysis of case subjects indicated association of H63D mutation with the severity of gestational diabetes mellitus. In the frequencies of H63D mutation and genotypes between the case subjects with A1 and B gestational diabetes were detected significant differences. Our data indicated that the presence of H63D mutation in pregnant women with GDM aggravates the disease—odds ratio 7.4 (95% CI 1.8 - 30.5). Women with gestational diabetes have severe increased risk for illness progressing to class B if they are H63D mutation carriers.

Do reactive oxygen species damage or protect the heart in ischemia and reperfusion?Analysis on experimental and clinical data

The role of reactive oxygen species(ROS)in ischemic and reperfusion(I/R)injury of the heart has been discussed for more than 40 years.It has been demonstrated that reperfusion triggers a multiple increase in free radical generation in the isolated heart.Antioxidants were found to have the ability to mitigate I/R injury of the heart.However,it is unclear whether their cardioprotective effect truly depends on the decrease of ROS levels in myocardial tissues.Since high doses and high concentrations of antioxidants were experimentally used,it is highly likely that the cardioprotective effect of antioxidants depends on their interaction not only with free radicals but also with other molecules.It has been demonstrated that the antioxidant N-2-mercaptopropionyl glycine or NDPH oxidase knockout abolished the cardioprotective effect of ischemic preconditioning.Consequently,there is evidence that ROS protect the heart against the I/R injury.

Influence of hyperbaric oxygenation treatment (HBOT) on clinical outcomes (recurrent myocardial infarction and survival rate) during five-year monitoring period after acute myocardial infarction

Surgical treatments of acute myocardial infarction (MI) possess a high clinical effectiveness, but there are fixed limitations, related to the patient’s state, which are limited by medical resources and organizational problems. The development of new medical technologies provides a better and effective non-surgical treatment of acute MI and increases long-term prognosis in this category of patients. The study aims to investigate the influence of hyperbaric oxygenation treatment on clinical outcomes (survival rate and recurrent myocardial infarction (rMI)) during the five-year period of monitoring. The study involved 697 patients who suffered from acute MI, having undergone the standard treatment. The patients were randomly divided into two groups: Group 1 (reference, n = 363);Group 2 (test, n = 334). Patients of Group 2 were given the traditional treatment, accompanied with HBOT (isopression for forty minutes at a working pressure of 0.03 MPa). HBOT was applied first through the fifth day following MI. The treatment course included six cycles, once per day. The clinical assessment was focused on clinical outcome: rMI and mortality related to cardiovascular events. HBOT application that accompanied the acute MI with traditional pharmacotherapy has been proved to reduce rMI within five years following inpatient discharge (rMI rate was 14% in the reference group and 5.4% in the test group, χ2 = 13.3, р < 0.05). The combination of HBOT with traditional methods in treating acute MI makes it possible to raise the five-year survival rate from 84.4% up to 95.9%.

Prognostic Significance of Comparison of Clinical Indicators with Manifestations of Genetic Polymorphism of Glutathione-S-Transferases in Non-Small Cell Lung Cancer

The article presented the results of comparison of polymorphic variants of the genes GSTM1, GSTT1, GSTP1 and clinical manifestations of non-small cell lung carcinoma. The association of the genotype GSTT1 (del) with the risk of developing squamous cell lung cancer has been revealed (OR = 2.54 CI: 1.13 - 5.72, p = 0.035). Analysis of patient survival rate (n = 173) in groups of various histological types of lung cancer showed that in the group of squamous cell lung cancer (n = 91) in patients with genotype GSTT1 (del), the survival rate median was significantly higher—84 months (95% CI 12.4 - 155.7) than in patients with the genotype GSTT1 (+)—36 months (95% CI 25.2 - 46.8, p = 0.045). In contrast, in the adenocarcinoma group (n = 82), the survival rate median in patients with the genotype GSTT1 (del) was 19 months. (95% CI 6.2 - 33.5), and in patients with genotype GSTT1 (+)—67 months (95% CI 50.1 - 84.0), which is the basis for continuing this comparison in an additional group of testees, as the sampling did not achieve the reliability of p = 0.12. Hypothetically, these differences may be due to differences in the gender composition of squamous cell lung cancer and adenocarcinoma and the involvement of GST enzymes in the metabolism of estrogens in adenocarcinoma in women and other hormonal background and reactivity of the male body with squamous cell carcinoma. Further research and subsequent analysis of the results will be aimed at confirming this hypothesis.

Etiopathogenesis of reproductive tract infections and the emerging role of bitter taste receptors:A scoping review

Reproductive tract infections pose an immense public health concern worldwide as over 600 million new cases are recorded annually along with several complications,including infertility,ectopic pregnancy,preterm delivery,and neonatal death.Despite improved understanding of the mechanisms of pathogenic invasion,the etiopathogenesis of reproductive tract infections is yet to be completely understood.Recent data has suggested a critical role of bitter taste receptors of the reproductive tract in etiopathogenesis of reproductive tract infections.Here,we review the literature on current etiopathogenesis of reproductive tract infections and the role of bitter taste receptors of the reproductive tract in etiopathogenesis of reproductive tract infections.Emerging evidence suggests a critical role of microbiota disorder of the reproductive tract in reproductive tract infections.Several bacterial,protozoan parasitic,helminthic parasitic and viral pathogens have been identified as causative agents of reproductive tract infections.These pathogens subvert host defenses and activate specific architectural units of the uroepithelium such as Toll-like receptors,which recognize conserved motifs on the pathogens.The activated Toll-like receptors mediate downstream signaling,stimulating nuclear factor-κB,which in turn activates the production of proinflammatory cytokines.This pathway is also associated with recruitment of immunocytes to the site of aggression and release of proteinases,which drive tissue damage in the reproductive tract.Defects in detection of pathogenic components by the bitter taste receptors of the reproductive tract may play a critical role in the etiopathogenesis of reproductive tract infections.This review provides important information for identification of novel frontiers for the treatment of reproductive tract infections.

Theory of pleiotropic action of biologically active compounds and medicines—Basic principles and practical application

This article represents the main positions of the theory of pleiotropic action of biologically active compounds (BACs) and medicines, which has been designed by the author based on her own experimental researches. The term “pleiotropy” means the ability of the BACs and medicines to implement more than one mechanism of action resulting in the specific biological (pharmacological) effect. The interaction of these mechanisms forms a distinct pattern of biological response (pleiotropic pattern), which reflects the change in his character with the increased dose (concentration)-dependent efficacy of BACs and medicines. The article consists of description of different pleiotropic patterns established in experiments on the model of reactive oxygen species (ROS) generation by macrophages dependent on activity of specialized enzyme called Nox2-NAD(P)H oxidase (Nox2, EC 1.6.3.1). Moreover, it consists of explanation of pharmacodynamic nature of pleiotropic patterns by means of application Chou-Talalay median effect equalization and combination index (CI) theory. The novel theory explains unsolved until now universal aspects of activity BACs and medicines, such as slope angles of “dose-effect” dependences in the conditions relevant in vivo, and it is of fundamental interest. However, it has applications in experimental pharmacology, as it allows defining the choice of the individual compounds and combinations, modulating the trust effect selectively and efficiently. This knowledge opens up new approaches to medicines discovery and evaluation, their rational dosing and combining.

Association of Polymorphic Variants of <i>VEGF</i>and <i>KDR</i>Genes with Development and Metastasing of Non-Small Cell Lung Cancer

Vascular endothelial growth factor (VEGF) is one of the most important and specific factors affecting angiogenesis in tumor development. VEGFR2 is a receptor encoded by the KDR gene. VEGF and VEGFR2 transmit a signal to intracellular tyrosine kinase cascades. Polymorphic variants of the VEGF and KDR genes significantly influence the expression levels of the endothelial growth factor and its receptor, which leads to a change in the activation of angiogenesis in oncopathological processes. In this study, the relationship between the polymorphic variants rs2010963, rs699947 and rs3025039 of the VEGF gene and rs1870377 and rs2071559 of the KDR gene was analyzed with the development of a specific histological type of non-small cell lung cancer and its clinical and morphological characteristics. It was established that the development of squamous cell carcinoma is associated with -634CC genotype of the VEGF gene and the genotypes containing -2578A allele of the VEGF gene reduce the likelihood of this cancer type development. The development of adenocarcinoma is associated with +936CC VEGF/1719TT KDR and +936CT VEGF/1719TT KDR combinations. In women with non-small cell lung cancer, -634GC genotype of the VEGF gene is associated with a greater degree of the primary lesion spread. Genotype -2578СС of the VEGF gene is associated with a higher degree of the primary tumor spread in the general group of patients and with regional metastases in women. Haplotypes -634G/-2578C/+936C are risky for the occurrence of metastases in regional lymph nodes in women.

The First Case of Human Herpesvirus 7-Related Epilepsy in the Republic of Belarus

Background:Human herpesvirus(HHV)-7 is usually associated with febrile seizures.Later onset and higher frequency of seizures are characteristic of pediatric HHV-7,compared with HHV-6 infection.The HHV-7-related severe neurological disorders are predominantly observed in immunocompromised individuals.Reports of healthy individuals with HHV-7 infection and diverse neurological disorders are limited.Patient Description:We present a case of HHV-7-related epilepsy in an immunocompetent 11-year old boy and extensive infectious and autoimmune testing positive only for HHV-7 in the cerebrospinal fluid.The patient made a good recovery after treatment with intravenous immunoglobulin and methylprednisolone.Discussion:This is the first reported case of epilepsy associated with HHV-7 in a previously healthy individual.It also demonstrates that intravenous immunoglobulin and steroids may be used in the course of this disorder and may be beneficial for recovery.

Mesenchymal Bone Marrow-derived Stem Cells Transplantation in Patients with HCV Related Liver Cirrhosis

Background and Aims: To evaluate the effect of intrapar-enchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). Methods: Mononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+. Cells from each passage were evaluated for sterility, and they were transplanted intraparenchymally into liver tissue. Clinical and laboratory data were evaluated and morphological studies of liver biopsy were performed prior to and 6 months after transplantation. Results: On clinical evaluation, the general state of these patients was improved at 1 month following transplantation of BMSCs. At 1 and 6 months post-transplantation, jaundice was absent in four (67%) patients. After 6 months, functional hepatic indices were improved, i.e. decrease of ALT and AST activity and bilirubin level. However, these decreases were not statistically different (P>0.05). Expression of CD34 and α-SMA in liver biopsy samples were decreased at 6 months after transplanta-tion, consistent with structural improvements in mitochondria and nuclear compartments. Conclusions: Intraparenchymal transplantation of autologous BMSCs improved the functional condition of the liver, stimulated reparative processes in hepatocytes, and decreased extracellular matrix protein (EMP) count in hepatic tissues of patients with LC. It was well tolerated and was not associated with any complications both during and after BMSC transplantation.

Treatment of isolated and recurrent tracheoesophageal fistula in children: a case series and literature review

Background Despite improvements in the treatment of esophageal atresia with tracheoesophageal fistula(TEF)in recent decades,complications still exist.The rate of fistula recanalization after surgical repair is~5%in large cohorts.However,there is controversy regarding the gold standard of treatment.This research aimed to evaluate the efficacy of treatment of pediatric patients with isolated(H-type)and recurrent TEF in our clinic.Methods We retrospectively analyzed 12 patients(7 boys,5 girls)aged 35 days-14.6 years.The median age of our patients was 632 days[95%CI(confident interval)120.1 to 2118.7];the mean birth weight was 2713 g(95%CI 2258 to 3169;median:2763 g);and the mean gestational age was 37.1 weeks(95%CI 35.4 to 38.8;median:37 weeks).All patients were managed for isolated or recurrent TEF between January 1,2015 and December 31,2020 using endoscopy(laser de-epithelialization).Results Laser de-epithelialization alone was effective in 8 of 12 patients(66.67%),with a mean number of de-epithelializations of 2.25(range:1-4).After one attempt at de-epithelialization,success was achieved in only two patients(n=16.67%).The mortality rate was 0%.The median follow-up for patients who received endoscopic treatment exclusively(n=8)was 3.7 years(95%CI 1.38 to 4.87)after the last stage of de-epithelialization.Conclusion Flexible endoscopy is an alternative treatment to open surgical repair of isolated and recurrent TEF in children.The effectiveness of endoscopic laser de-epithelialization alone with subsequent fistula obliteration was 66.7%,with a median follow-up of 3.7 years.