Dynamics of the content of reactive oxygen species and the state of the glutathione system in the oral cavity during subchronic intoxication wuth the fungicide thiram and its antioxidant correction.

Thiram is a dithiocarbamate derivative, which is used as a fungicide for seed dressing and spraying during the vegetation period of plants, and also as an active vulcanization accelerator in the production of rubber-based rubber products. In this study the content of reactive oxygen species (ROS) and the state of the glutathione system have been investigated in the oral fluid and gum tissues of adult male Wistar rats treated with thiram for 28 days during its administration with food at a dose of 1/50 LD50. Thiram induced formation of ROS in the oral cavity; this was accompanied by an imbalance in the ratio of reduced and oxidized forms of glutathione due to a decrease in glutathione and an increase in its oxidized form as compared to the control. Thiram administration caused an increase in the activity of glutathione-dependent enzymes (glutathione peroxidase, glutathione transferase, and glutathione reductase). However, the time-course of enzyme activation in the gum tissues and oral fluid varied in dependence on the time of exposure to thiram. In the oral fluid of thiram-treated rats changes in the antioxidant glutathione system appeared earlier. The standard diet did not allow the glutathione pool to be fully restored to physiological levels after cessation of thiram intake. The use of exogenous antioxidants resviratrol and an Echinacea purpurea extract led to the restoration of redox homeostasis in the oral cavity.

[MR-guided non-invasive typing of brain gliomas using machine learning]. / Pervye rezul'taty neinvazivnogo tipirovaniya gliom golovnogo mozga po dannym magnitno-rezonansnoi tomografii s pomoshch'yu mashinnogo obucheniya.

Gliomas are the most common neuroepithelial brain tumors. The modern classification of tumors of central nervous system and treatment approaches are based on tissue and molecular features of a particular neoplasm. Today, histological and molecular genetic typing of tumors can only be carried out through invasive procedures. In this regard, non-invasive preoperative diagnosis in neurooncology is appreclated. One of the perspective areas is artificial intelligence applied for neuroimaging to identify significant patterns associated with histological and molecular profiles of tumors and not obvlous for a specialist. OBJECTIVE: To evaluate diagnostic accuracy of deep learning methods for glioma typing according to the 2007 WHO classification based on preoperative magnetic resonance imaging (MRI) data. MATERIAL AND METHODS: The study included MR scans of patients with glial tumors undergoing neurosurgical treatment at the Burdenko National Medical Research Center for Neurosurgery. All patients underwent preoperative contrast-enhanced MRI. 2D and 3D MR scans were used for learning of artificial neural networks with two architectures (Resnest200e and DenseNet, respectively) in classifying tumors into 4 categories (WHO grades I-IV). Learning was provided on 80% of random examinations. Classification quality metrics were evaluated in other 20% of examinations (validation and test samples). RESULTS: Analysis included 707 contrast-enhanced T1 welghted images. 3D classification based on DenseNet model showed the best result in predicting WHO tumor grade (accuracy 83%, AUC 0.95). Other authors reported similar results for other methods. CONCLUSION: The first results of our study confirmed the fundamental possibility of grading axial contrast-enhanced T1 images according to the 2007 WHO classes using deep learning models.

Participation of the HIM1 gene of yeast Saccharomyces cerevisiae in the error-free branch of post-replicative repair and role Polη in him1-dependent mutagenesis.

In eukaryotes, DNA damage tolerance (DDT) is determined by two repair pathways, homologous repair recombination (HRR) and a pathway controlled by the RAD6-epistatic group of genes. Monoubiquitylation of PCNA mediates an error-prone pathway, whereas polyubiquitylation stimulates an error-free pathway. The error-free pathway involves components of recombination repair; however, the factors that act in this pathway remain largely unknown. Here, we report that the HIM1 gene participates in error-free DDT. Notably, inactivation RAD30 gene encoding Polη completely suppresses him1-dependent UV mutagenesis. Furthermore, data obtained show a significant role of Polη in him1-dependent mutagenesis, especially at non-bipyrimidine sites (NBP sites). We demonstrate that him1 mutation significantly reduces the efficiency of the induction expression of RNR genes after UV irradiation. Besides, this paper presents evidence that significant increase in the dNTP levels suppress him1-dependent mutagenesis. Our findings show that Polη responsible for him1-dependent mutagenesis.

Influence of electro-osmosis on physicochemical parameters and microstructure of clay soils.

The change in properties and structure of clay soils due to electro-osmosis was studied. These alterations were exemplified by mantle loam and kaolin. It is shown that electro-osmotic treatment of the soils on the open scheme resulted in the transformations in their moisture content, total and dry density, salinity, pH, and the parameters of their particles. The most notable changes occurred within the diffuse double layers (DDLs) of soil particles such as their recharge in the anodic zone. The transformations of the loam particles DDLs resulted in their aggregation in the cathodic and anodic zones. Also, electro-osmotic flow caused the redistribution of pore sizes within the soils between the electrodes. In the case of the kaolin, electro-osmosis resulted in the formation of the anisotropic, flow-oriented structure. The change in the types of soil particles contacts formed was observed during electro-osmosis as well. The obtained data can be used to study the behavior of soil during electro-osmosis as a function of the soil type.

Regulation of clay particles charge for design of protective electrokinetic barriers.

Coupled electrokinetic protective reactive barriers (PRB) are considered as a perspective technology for the treatment of contaminated groundwater. Design of PRB is directly connected with a problem of barrier material choice. Clays can be considered as an appropriate material due to high adsorptive properties and relative cheapness. The barrier internals are formed by clay surface charge properties. We revealed that acidic and alkaline treatment of clay is an effective way to affect its protective properties so that clay can be used to treat various pollutants. Surface charge and electrokinetic properties of clays were characterized by point of zero charge (p.z.c.), point of zero net proton charge (p.z.n.p.c.) and ζ-potential at different pH. Suspensions of 3 main clay types were studied by microelectrophoresis and potentiometric titration methods. At pH > p.z.n.p.c. clayey barrier adsorbs predominantly cationic toxicants and at pH < p.z.c. - anionic ones. The barrier is seemed to be the least effective in pH range between p.z.c. and p.z.n.p.c. Given the physicochemical and electrokinetic parameters, the most efficient clays for barrier design are Cambrian illite and all montmorillonite clays.

[The role of remodeling complexes CHD1 and ISWI in spontaneous and UV-induced mutagenesis control in yeast Saccharomyces cerevisiae].

Chromatin remodulators are special multiprotein machines capable of transforming the structure, constitution, and positioning of nucleosomes on DNA. Biochemical activities of remodeling complexes CHD1 and ISWI from the SWI2/SNF2 family are well established. They ensure correct positioning of nucleosomes along the genome, which is probably critical for genome stability, in particular, after action of polymerases, repair enzymes, and transcription. In this paper, we show that single mutations in genes ISW1, ISW2, and CHD1 weakly affect repair and mutagenic processes in yeast cells. At the same time, there are differences in the effect of these mutations on spontaneous mutation levels, which indicates certain specificity of action of protein complexes ISW1, ISW2, and CHD1 on expression of different genes that control repair and mutation processes in yeast.

[Dot1 and Set2 Histone Methylases Control the Spontaneous and UV-Induced Mutagenesis Levels in the Saccharomyces cerevisiae Yeasts].

In the Saccharomyces cerevisiae yeasts, the DOT1 gene product provides methylation of lysine 79 (K79) of hi- stone H3 and the SET2 gene product provides the methylation of lysine 36 (K36) of the same histone. We determined that the dot1 and set2 mutants suppress the UV-induced mutagenesis to an equally high degree. The dot1 mutation demonstrated statistically higher sensitivity to the low doses of MMC than the wild type strain. The analysis of the interaction between the dot1 and rad52 mutations revealed a considerable level of spontaneous cell death in the double dot1 rad52 mutant. We observed strong suppression of the gamma-in- duced mutagenesis in the set2 mutant. We determined that the dot1 and set2 mutations decrease the sponta- neous mutagenesis rate in both single and d ouble mutants. The epistatic interaction between the dot1 and set2 mutations and almost similar sensitivity of the corresponding mutants to the different types of DNA damage allow one to conclude that both genes are involved in the control of the same DNA repair pathways, the ho- mologous-recombination-based and the postreplicative DNA repair.

[EFFECT OF POLYCOMPONENT PROBIOTICS ON THE COMPOSITION OF COLON MICROBIOCENOSIS DURING EXPERIMENTAL DYSBIOSIS].

AIM: Study the effect of RioFlora Immuno Neo and Bifiform probiotics on the colon microflora composition under the conditions of experimental dysbiosis in mice. MATERIALS AND METHODS: Medicinal dysbiosis was modelled in animals by gentamicin administration, probiotics were administered intragastrally by the end of dysbiosis formation. Quantitative and qualitative study of mucous microflora of mice colon was carried out by a bacteriological method. RESULTS: Correction of dysbiosis by probiotics has resulted in correction of the intestine microflora composition, and more pronounced when RioFlora Immuno Neo was used. CONCLUSION. The results of the study allow to recommend the use of these preparations for selective correction of colon dysbiosis.

[CHANGES IN COLON MICROBIOCENOSIS COMPOSITION AND ANTIOXIDANT PROPERTIES OF COLONOCYTES UNDER THE CONDITION OF EXPERIMENTAL DYSBIOSIS AND EMOXIPIN PROPHYLAXIS].

AIM: Study the composition of colon microbiocenosis and antioxidant properties of colonocytes under the conditions of experimental dysbiosis and prophylaxis application of emoxipin. MATERIALS AND METHODS: With the aim of prophylaxis, antioxidant emoxipin was administered to mice, in which medicinal dysbiosis was formed by intraperitoneal administration of gentamicin. Quantitative and qualitative study of mucous microflora of the mice colon was carried out by a bacteriological method. The state of lipid peroxidation system was judged by the content of acylhydroperoxides and malonic dialdehyde, system of antioxidant protection--by enzyme activity (catalase and superoxide dismutase). RESULTS: Experimental dysbiosis of the colon manifested by changes in the composition of mucous microflora of the animals and antioxidant properties of colonocytes. Dysbiosis prophylaxis by emoxipin resulted in normalization of the activity of antioxidant protection enzymes and products of lipid peroxidation in intestine tissue. CONCLUSION: The study results allow to consider, that use of emoxipin results in an increase of adaptive-compensatory capabilities of the macroorganism during experimental dysbiosis.

[CONTROL OF HYPERGLYCEMIA IN THE CLINICAL PRACTICE].

The diagnosis of hyperglycemia was based on the fasting plasma glucose, the 2-h value in the 75-g oral glucose tolerance test and the determination of glycated hemoglobin. The purpose of investigation is determination of glycated hemoglobin by patients with the risk of critical condition. For it the three patients groups were investigated: with cerebrovascular diseases, with hyperasotemia and with the renal insufficience. We discoved that hyperglycemia and HbA1c formates important factor in the change of the tone of cerebral arteries. Hyperasotemia makes ponderable percent of distribution in the general population of people. The level of glycated hemoglobin by patients with latent renal insufficience was increased. The determination of HbA1c can use for patients with critical conditions.

[Clinical and radiological study on tissue regeneration after alveolar bone augmentation with various osteoplastic materials and membranes].

The aim of the study was to compare the efficiency of alveolar bone augmentation using a variety of osteoplastic materials and collagen membrane and healing under a clot. The study included patients undergoing the extraction of symmetric teeth. After extraction one of the sockets were filled with osteoplastic materials while symmetrically located socket with no bone grafting served as a control. In group 1 augmentation was performed using Bio-Oss Collagen Bio-Gide membrane, in group 2 - Osteodent-M and Collost membranes, in group 3 - BIOPLAST-dent and BIOPLAST-dent-MK membranes. Clinical and radiological evaluation revealed positive impact of bioplastic materials on the bone tissue healing and recovery rates. The best results showed Bio-Oss Collagen with barrier bioresorbable membrane Bio-Gide allowing the creation of the most favorable conditions for delayed implantation.

[The influence of melatonin on the content of lipid peroxidation metabolites and antioxidant enzyme activity in the liver of rats after immobilization].

The modeling of acute immobilization stress caused the increase of the content of lipid peroxidation metabolites and the decrease of the activity of superoxiddismutase and catalase in liver tissue within 4 days after stress. Melatonin in dose 0.2 mg/kg had a weak antioxidant effect and increased superoxiddismutase activity. The injection of melatonin in dose 1.0 mg/kg caused the significant decrease of lipoperoxidation metabolites content in liver tissue 39 hours after stress. On fourth and seventh days of the experiment there were no differences in malonic dyaldehyde content between these animals and naive ones. The concentration of acylhydroperoxides was significantly less than in control and naive groups at these days. The activity of superoxiddismutase and catalase was significantly more than in control rats at the fourth day after stress.

[Control levels of Sin3 histone deacetylase for spontaneous and UV-induced mutagenesis in yeasts Saccharomyces cerevisiae].

SIN3 gene product operates as a repressor for a huge amount of genes in Saccharomyces cerevisiae. Sin3 protein with a mass of about 175 kDa is a member of the RPD3 protein complex with an assessed mass of greater than 2 million Da. It was previously shownthat RPD3 gene mutations influence recombination and repair processes in S. cerevisiae yeasts. We studied the impacts of the sin3 mutation on UV-light sensitivity and UV-induced mutagenesis in budding yeast cells. The deletion ofthe SIN3 gene causes weak UV-sensitivity of mutant budding cells as compared to the wild-type strain. These results show that the sin3 mutation decreases both spontaneous and UV-induced levels of levels. This fact is hypothetically related to themalfunction of ribonucleotide reductase activity regulation, which leads to a decrease in the dNTP pool and the inaccurate error-prone damage bypass postreplication repair pathway, which in turn provokes a reduction in the incidence of mutations.

[Spontaneous mutation rate changes in saccharomyces cerevisiae at combinations of hsm3 and hsm6 mutations with rad52 mutation].

Long-term storage at +4 degrees C and cultivation at +30 degrees C changes the spontaneous mutation rate of the yeast Saccharomyces cerevisiae double mutants rad52hsm3delta and rad52hsm6-1. Combinations of hsm3 and hsm6 mutations with the rad52 mutation lead to a decrease of the spontaneous mutation rate mediated by DNA repair synthesis in multiply replanted strains in comparison with the same strains investigated right after RAD52 gene decay. Combinations of hsm3 and hsm6 mutations with mutations in other genes of the RAD52 epistatic group did not provide a spontaneous mutation rate decrease.

[The first experience in using elastography in combination with endobronchial ultrasonography for mediastinal pathology: Preliminary assessment of feasibility and comparison of characteristics via different approaches].

OBJECTIVE: To preliminarily assess the feasibility of elastography in endobronchial ultrasonography and to compare characteristics via different accesses. MATERIAL AND METHODS: The investigation enrolled 3 patients (malignant, benign mediastinal adenopathy, paratracheal tumor). Elastography was carried out using a Pentax EB-1970UK echobronchoscope with a Hitachi Noblus ultrasound scanner. All the patients underwent fine-needle aspiration biopsy of mediastinal and pulmonary lymph nodes/masses with 22G needles (Cook, Medi-Globe). Sequential study of the same group of lymph nodes through different approaches through the esophagus and trachea was conducted, and its characteristics were compared in one patient. RESULTS: A total of 8 lymph nodes and one paratracheal mass (Group 4L-7-4R-2R) were assessed in three patients. Reproducible images acceptable for visual assessment were obtained in all cases. The wall of the trachea and bronchi had no significant negative impact on the quality of an obtained image. Both malignant lesion of lymph nodes and paratracheal mass was accompanied by decreased tissue elasticity in the area of interest. Assessment of the same benign lymph node through different approaches revealed a clear discordance between elastographic findings with a drastic decrease in elasticity values via an endobronchial approach. CONCLUSION: Endobronchial ultrasonography elastography is technically feasible. The wall of the trachea and bronchi has no significant impact on the quality of an obtained image; elastographic data are reproducible during re-measurements. Comparison of elastographic characteristics through different approaches suggests that there is a tendency to overestimate data on lymph node density during endobronchial examination versus a transesophageal approach. Thus, the direct transfer of the accumulated data and patterns of elastographic diagnosis to an endobronchial approach is impossible and likely to require a revision of criteria to estimate malignancy-associated changes during its application.

[Complications and pitfalls by bone augmentation of maxillary sinus floor].

The article includes description of mistakes and complications occurring during sinus floor elevation procedure, in early post-operate period or late post-operate period. Recommendations have been made to eliminate and prevent their occurrence. The review summarizes data of Russian and foreign literature and our own clinical experience. Conclusions and practical recommendations for doctors have been formed based on the analysis of that data.

[Morphological and functional changes of organs of female and male reproductive systems at change of sex].

The aim of the study was to identify the effects of virilizing and feminizing hormone replacement therapy on the morphology and function of the male and female reproductive systems in the application of technology for change of sex. The results of the pathomorphorogic examination of the uterus with appendages, testes, the corpora cavernosa, and biopsies of the prostate and mammary glands at different times of treatment in transsexual patients aged from 22 to 43 years are presented. It was found that prolonged exposure to high concentrations of exogenous hormones in the women and men significantly increases the risk of tumors and tumor-like processes, such as endocervicosis, cervical intraepithelial neoplasia, metaplasia of the endometrium, endocervical and endometrial polyps, endometrial hyperplasia, proliferative processes in tubular epithelium, ovarian polycystic disease, mammary tumors, hyperplasia and metaplasia of the ductal epithelium of the prostate gland.

[HSM6 gene is identical to PSY4 gene in Saccharomyces cerevisiae yeasts].

Previously, we isolated mutant yeasts Saccharomyces cerevisiae with an increased rate of spontaneous mutagenesis. Here, we studied the properties of HSM6 gene, the hsm6-1 mutation of which increased the frequency of UV-induced mutagenesis and decreased the level of UV-induced mitotic crossover at the centromere gene region, ADE2. HSM6 gene was mapped on the left arm of chromosome 11 in the region where the PSY4 gene is located. The epistatic analysis has shown that the hsm6-1 mutation represents an allele of PSY4 gene. Sequencing of hsm6-1 mutant allele has revealed a frameshift mutation, which caused the substitution of Lys218Glu and the generation of a stop codon in the next position. The interactions of hsm6-1 and rad52 mutations were epistatic. Our data show that the PSY4 gene plays a key role in the regulation of cell withdrawal from checkpoint induced by DNA disturbances.

[Advantages of multidisciplinary approach to diagnosis and treatment of mandible fractures in alcohol abusing patients].

The diagnosis of traumatic injuries in patients with chronic and severe alcoholic abuse is very complicated especially in cases with associated brain injuries. It is particularly difficult to provide anesthesia and resuscitation, complications arise when taking certain groups of drugs. The associated immune system disorders are risk factors for complications. The most reasonable approach to diagnosis and treatment of mandible fractures in such patients is a multidisciplinary approach involving expert team with maxillofacial surgeon playing a leading role.