[Indicators of oral fluid and their correction by means of hygiene in elderly people with general somatic diseases.]

The results of the study of oral fluid in older persons with somatic pathology, which was followed for 1 month, are presented. The acid-base state of the oral fluid was evaluated, and the viscosity of the oral fluid was determined. According to the results of the study of oral fluid and its correction by means of hygiene in older persons with somatic diseases, the dynamics of the indicators of the acid-base state of the oral fluid, its shift to the alkaline side and the positive dynamics of the effect of the viscosity of the oral fluid were noted. To ensure that the risk of adverse effects from changes in the state of the oral fluid is reduced, a joint approach involving all health professionals is needed, taking into account the determinants of health and ensuring the development of effective methods for the prevention of dental diseases in older persons.

[Study of the functional state of the periodontium in older persons and its correction by means of oral hygiene.]

The study involved 258 older persons with generalized chronic periodontitis, who were monitored for a month. For an in-depth study of the properties and effectiveness of toothpastes recommended for older and elderly people with preventive anti-inflammatory purpose, tests were conducted to determine the true characteristics and properties of the studied pastes. Periodontal indices PMA and PI were used to study the anti-inflammatory effect of toothpastes. The most pronounced anti-inflammatory effect was revealed in the samples, the active components of which were oat extract, thymol, anise and essential oils of tea tree, as well as eucalyptus. Proper selection of means of individual oral hygiene and the development of «Individual hygienic program of prevention of chronic generalized periodontitis in older and elderly people¼ can reduce the phenomenon of inflammation in the periodontium, the development of mediators of inflammation and improve dental health of older and elderly people.

[The detection of antibodies to HCV F protein with immune enzyme analysis using synthetic peptide.]

Alternative reading frame encoding a single protein known as protein F or core + 1 / ARFP is located in the core region of the hepatitis C virus (HCV) genome. The presence of antibodies to the F protein of HCV in the serum of patients with chronic hepatitis C indicates the expression of this protein in vivo. In this study, to determine antibodies to the F protein of HCV in serum samples the methodology of the enzyme immunoassay (ELISA) was developed using the synthetic peptide F10 corresponding to the antigenic determinant of the F protein of the HCV subtype 1b. The immunogenicity and immunochemical specificity of synthetic F10 peptide has been demonstrated in laboratory animals (mice).

Spatial distribution of disease-associated variants in three-dimensional structures of protein complexes.

Next-generation sequencing enables simultaneous analysis of hundreds of human genomes associated with a particular phenotype, for example, a disease. These genomes naturally contain a lot of sequence variation that ranges from single-nucleotide variants (SNVs) to large-scale structural rearrangements. In order to establish a functional connection between genotype and disease-associated phenotypes, one needs to distinguish disease drivers from neutral passenger variants. Functional annotation based on experimental assays is feasible only for a limited number of candidate mutations. Thus alternative computational tools are needed. A possible approach to annotating mutations functionally is to consider their spatial location relative to functionally relevant sites in three-dimensional (3D) structures of the harboring proteins. This is impeded by the lack of available protein 3D structures. Complementing experimentally resolved structures with reliable computational models is an attractive alternative. We developed a structure-based approach to characterizing comprehensive sets of non-synonymous single-nucleotide variants (nsSNVs): associated with cancer, non-cancer diseases and putatively functionally neutral. We searched experimentally resolved protein 3D structures for potential homology-modeling templates for proteins harboring corresponding mutations. We found such templates for all proteins with disease-associated nsSNVs, and 51 and 66% of proteins carrying common polymorphisms and annotated benign variants. Many mutations caused by nsSNVs can be found in protein-protein, protein-nucleic acid or protein-ligand complexes. Correction for the number of available templates per protein reveals that protein-protein interaction interfaces are not enriched in either cancer nsSNVs, or nsSNVs associated with non-cancer diseases. Whereas cancer-associated mutations are enriched in DNA-binding proteins, they are rarely located directly in DNA-interacting interfaces. In contrast, mutations associated with non-cancer diseases are in general rare in DNA-binding proteins, but enriched in DNA-interacting interfaces in these proteins. All disease-associated nsSNVs are overrepresented in ligand-binding pockets, and nsSNVs associated with non-cancer diseases are additionally enriched in protein core, where they probably affect overall protein stability.

[VIRAL HEPATITIS C: EVOLUTION OF THE EPIDEMIOLOGIC PROCESS, EVOLUTION OF THE VIRUS].

Periodization of the evolution of epidemic process of hepatitis C is given based on the results of phylodynamic, phylogeographic, historic and demographic studies: invasion of the virus into European and North-American population in 1700-1850; primary activation of the epidemic process in the years of the World War 1; expansive giowth of prevalence in 40--60s of the 20th century due to mass parenteral interventions; new rise due to heroine drug abuse in 60--80s of the 20th century; manifold reduction of incidence of acute hepatitis C in industrial countries for the last 10-15 years as a result of general medical measures of prevention of hemocontact infec-tions. A problem of possibility of hepatitis C management and necessity of evaluation of effectiveness of existing prophylaxis measures involving quantitative analytical methods of epidemiology is discussed. Data from phylogenetic studies on stages of hepatitis C virus evolution (HCV) are provided: division of its root genetic lineage with homologous hepaciviruses of animals 985--2013 years ago; division of HCV into genotypes 500--2000 years ago; division of genotypes into subtypes 70--300 years ago. Contribution of mutations and genetic recombinations into HCV evolution is discussed. Genotyping is stated as an inefficient approach for determination of pathogenicity determinants, immune evasion, non-responsiveness to therapy, as well as search for predictors of infection outcome. A necessity of genomic approach for these aims is justified, as well as for risk monitoring, ensuing from continuing evolution and biodiversity of HCV and other hepaciviruses.

[Genome organization and life cycle of the hepatitis c virus].

The review summarizes the current data about the hepatitis C viral genome and polyprotein organization. The functional role of the structural and non-structural viral proteins including their interaction with cellular regulatory proteins and cell structural elements is discussed. Specific peculiarities of the life cycle of the hepatitis C virus important for the understanding of the viral hepatitis C pathogenesis are summarized.

[Phylodynamic of HCV Populations].

Hepatitis C virus is an actual public health problem worldwide since its discovering in 1989. It is explained not only by the wide spreading and frequent adverse outcomes of disease, the lack of effective preventive vaccine, but also by the high genetic variability of the virus. The current review summarizes the results of phylodynamic and phylogeographic studies of different HCV populations that allowed to characterize epidemic processes, to analyze the divergence of HCV into genotypes and subtypes, and to determine the geographic origin of the current HCV epidemic variants.

[Possibilities for the improvement of the quality of knowledge and their evaluation in the course of studying clinical medicine].

The authors consider objective and subjective factors exerting negative influence on the quality of knowledge of physicians. The generally accepted methods for its evaluation (testing and rating-systems) have limitations. Testing reflects the level of knowledge with respect to the mode of thinking of its designer while rating mostly characterizes diligence of the trainee. It is proposed to improve the quality of knowledge by teaching the theory of diagnostics and to evaluate the amount of knowledge from the contents of the descriptive part of the medical history. The quality of knowledge can be assessed based on the contents of professional comments on the clinical picture described in the model case history.

[Age peculiarities of the sebaceous glands in the temporal area of the scalp skin in men].

The changes of the sebaceous gland number, size and sebocyte proliferative activity were studied in the temporal area of the scalp skin in the male individuals aged 10 to 70 years (n=77, autopsy material). The minimal number of the sebaceous glands was observed in children. This index rapidly increased thereafter, reaching a peak at 20 years, then gradually decreased. These parameters correlated with the sebaceous gland size, sebocyte proliferative activity and total blood testosterone level. In older men the size of the sebaceous glands was increased.

[The natural triterpenoid miliacin prevents methotrexate-induced oxidative stress and normalizes the expression of genes encoding the cytochrome P-450 2E1 isoform and glutathione reductase in the liver].

We studied the role of the natural triterpenoid miliacin (3-3-methoxy-Al8-oleanene) in the regulation of oxidative stress in the liver of (CBAxC57B1(6))F1 mice exposed to methotrexate. Miliacin attenuated methotrexate-induced lipid peroxidation as determined by an attenuation of thiobarbituric acid-reacting products in the liver. Furthermore, miliacin normalized the expression of genes encoding the 2e1 isoform of cytochrome P-450 and glutathione reductase that were dramatically dysregulated by methotrexate. These results established the role of miliacin in modulation of redox genes, thereby providing evidence for a new mechanism of organ protection by this triterpenoid.

[Low-manifest infections in children and adolescents with consequences of perinatal damage of nervous system].

AIM: Study the specter of low-manifest infections (LMI) and their role in children and adolescents with diseases of central nervous system (CNS) against the background of consequences of perinatal damage of nervous system (PDNS). MATERIALS AND METHODS: Infectologic and neurologic examinations were carried out in 42 patients with consequences of PDNS (17 girls and 25 boys, 3 - 15 years). Detection of LMI resulted in etiotropic therapy with evaluation of clinical and laboratory data in dynamics. RESULTS: In 93% (39/42) of patients causative agents of LMI were diagnosed in various combinations and in various biological materials. Among those: Chlamydia spp.--in 71% of patients, Mycoplasma spp.--in 31%, Ureaplasma urealyticum--in 14% (in total the listed microorganisms were diagnosed in 83% of patients); Herpesviridae family viruses--in 75% (HHV-6--in 67%, VEB--in 36%, CMV--in 11%, HSV-1,2--in 11%). Combination of Chlamydia spp. with HHV-6 (R tetr = +0.61) and with VEB (R tet = +0.74) (P < 0.05) was detected. None of the patients had typical signs of encephalitis clinically or based on MRT. MRT signs of gliosis-atrophic changes in the CNS were detected in all the patients. Reduction of a number of psycho-neurologic and neurologic syndromes was noted in all the patients during LMI therapy. CONCLUSION: Most of the patients with consequences of PDNS had low-intensity inflammatory-degenerative process in the CNS determined by LMI, first of all by Chlamydia spp. as well as Mycoplasma spp.

[The development of secondary immunodeficiency in body when exposed to the effect of xenobiotics with immunosuppressive activity].

The State Education Institution of Higher professional education "The Orenburg State Medical Academy of Federal Agency in Public Health and Social Development". In the experiment on mice (CBA x C57Bl6) F1 and Wistar rats is shown the protective effect of triterpenoid plant--miliatsina (3-beta-methoxy-delta18-oleanena) in relation to the humoral immune response and clearance macrophage function hepatic xenobiotic conditions of use--methotrexate. The results define the term as used miliatsina immunoprotector with adverse effects on the body of environmental and industrial chemical factors that form the secondary immunodeficiency.

[Low-manifest infections with CNS damage in patients in prolonged unconscious state of non-inflammatory etiology].

AIM: Study of specter of low-manifest infections (LMI) with central nervous system (CNS) damage and their role in patients in prolonged unconscious state (PUS) of noninflammatory etiology. MATERIALS AND METHODS: 32 patients (23 male, 9 female; age 14-58) in PUS of various etiology were examined. The main group (18 patients) received therapy against all infectious diseases including LMI; control group (14 patients)--only against common and nosocomial microflora. Patients were immunologically, infectologically and neurologically examined in dynamic. The data obtained were treated by using STATISTICA for Windows (version 5.5). RESULTS: Significant differences in immune and infectologic status depending on the nature of primary CNS damage were not detected. Immunodeficiency was detected in all patients; 94% of patients had increased non-specific IgM and IgE. Among LMI agents Chlamydia spp. were predominant. Cultural and/or PCR methods detected this microorganism during the primary examination in cerebrospinal fluid samples in 56% patients and in blood samples in 56%; during the second diagnostics or autopsy--only in 13 and 25%, respectively. Detection of Bacteroides fragilis, Human Herpes Virus (HHV-6), Virus Epstein Barr (VEB), Cytomegalovirus (CMV) in cerebrospinal fluid, blood and on mucous membranes of nasopharynx and conjunctiva was grouped more frequently with the presence of Chlamydia spp. in the CNS (p < 0.05) than with other LMI agents. Sanation of CNS from LMI was significantly accompanied by regeneration of communicative activity in comparison with the control group. CONCLUSION: In patients with PUS high frequency of CNS infection by various LMI agents and primarily Chlamydia spp. should be considered. Sanation from LMI can become a "window" for effective neuro-regenerative treatment.

[Computational method for prediction of protein functional sites using specificity determinants].

The current available data on protein sequences largely exceeds the experimental capabilities to annotate their function. So annotation in silico, i.e. using computational methods becomes increasingly important. This annotation is inevitably a prediction, but it can be an important starting point for further experimental studies. Here we present a method for prediction of protein functional sites, SDPsite, based on the identification of protein specificity determinants. Taking as an input a protein sequence alignment and a phylogenetic tree, the algorithm predicts conserved positions and specificity determinants, maps them onto the protein's 3D structure, and searches for clusters of the predicted positions. Comparison of the obtained predictions with experimental data and data on performance of several other methods for prediction of functional sites reveals that SDPsite agrees well with the experiment and outperforms most of the previously available methods. SDPsite is publicly available under http://bioinf.fbb.msu.ru/SDPsite.

[Effects of different methods of physical therapy on the course of autonomic dysfunction syndrome].

A comparative randomized controlled trial was made of efficacy of vegetative disorders correction with drugs and physiotherapeutic factors. A total of 120 patients with vegetative vascular dystonia entered this trial. Its results demonstrated that addition of physiotherapy to the rehabilitation complex allows differential functional changes in the autonomic nervous system. This can be used for optimization of rehabilitation programs.

Comparative genomics of regulation of heavy metal resistance in Eubacteria.

BACKGROUND: Heavy metal resistance (HMR) in Eubacteria is regulated by a variety of systems including transcription factors from the MerR family (COG0789). The HMR systems are characterized by the complex signal structure (strong palindrome within a 19 or 20 bp promoter spacer), and usually consist of transporter and regulator genes. Some HMR regulons also include detoxification systems. The number of sequenced bacterial genomes is constantly increasing and even though HMR resistance regulons of the COG0789 type usually consist of few genes per genome, the computational analysis may contribute to the understanding of the cellular systems of metal detoxification. RESULTS: We studied the mercury (MerR), copper (CueR and HmrR), cadmium (CadR), lead (PbrR), and zinc (ZntR) resistance systems and demonstrated that combining protein sequence analysis and analysis of DNA regulatory signals it was possible to distinguish metal-dependent members of COG0789, assign specificity towards particular metals to uncharacterized loci, and find new genes involved in the metal resistance, in particular, multicopper oxidase and copper chaperones, candidate cytochromes from the copper regulon, new cadmium transporters and, possibly, glutathione-S-transferases. CONCLUSION: Our data indicate that the specificity of the COG0789 systems can be determined combining phylogenetic analysis and identification of DNA regulatory sites. Taking into account signal structure, we can adequately identify genes that are activated using the DNA bending-unbending mechanism. In the case of regulon members that do not reside in single loci, analysis of potential regulatory sites could be crucial for the correct annotation and prediction of the specificity.

[Infrared laser therapy in distal diabetic polyneuropathy]. / Infrakrasnaia lazeroterapiia pri distal'noi diabeticheskoi polinevropatii.

A course of laser therapy was applied to 50 patients with diabetic polyneuropathy by laser irradiation of low intensiveness in the nearest infrared spectrum. 20 patients from the group were treated by monotherapy only by laser exposure. Control group consisted of 24 patients treated by conventional therapy without laser exposure. According to the changes of vibratory and algesic sensitivity and electromyographic data the efficiency of therapy was estimated. It was found that laser exposure resulted in more pronounced restoration of functional state of nervous fibers than conventional therapy. Application of laser irradiation of low intensiveness was effective while in combined therapy of distal diabetic polyneuropathy as well as monotherapy.