THE STUDY OF VDR FOKI RS2228570 SNP IN AUTOIMMUNE THYROIDITIS.

Autoimmune thyroid disease (AITD) is a common organ-specific autoimmune disease. A strong influence of genetic and epigenetic modifications has been demonstrated to take part in the development and progression of autoimmune thyroid diseases. The linkage between the Vitamin D receptor (VDR) polymorphism and several autoimmune disorders, including the AITD. In this article, we aim to investigate the Frequency of VDR Fokl (rs2228570) genotypes (CC, CT, TT) and alleles (C,T) in autoimmune thyroiditis. The investigation of VDR Fokl (rs2228570) was conducted on 150 samples (control (75 healthy women) and diseased women (75 diseased with autoimmune thyroiditis)) patients from the Adjara (Georgia) Population. It also examined some clinical and laboratory characteristics of the study population. Autoimmune thyroiditis's disease was diagnosed by measuring blood antibodies, determining the level of thyroperoxidase, and conducting an ultrasound examination. Anti-TPO and TSH were studied using the ELISA method. The genomic DNA was extracted from the peripheral blood. The polymerase chain reaction was evaluated to examine the VDR Fokl rs2228570 SNP polymorphism. According to VDR Fokl (rs2228570) genotypes (CC; CT, TT) frequency, in the control group, the Frequency of CC-genotype is 48%, CT-heterozygous genotype is 29.33%, and TT-genotype is 22.67%; in the diseased population, the Frequency of CC-genotype is 57.33%, CT-genotype is 34.67%, and TT-genotype is 8%. According to VDR Fokl (rs2228570) alleles (C, T), the Frequency of the C-allele is high, and the Frequency of the T-allele is low in both populations. The Frequency of the CC and CT genotypes of VDR Fokl (rs2228570) is high in the population with autoimmune thyroiditis compared to the control group; the TT genotype is relatively low in the population suffering from autoimmune thyroiditis; According to VDR Fokl (rs2228570) alleles (C, T), the Frequency of C-allele is high both population.

EPIDEMIOLOGY AND MOLECULAR TYPING OF BRUCELLA STRAINS CIRCULATING IN GEORGIA.

In 2009-2013, 851 cases of brucellosis were registered in Georgia. Most cases of brucellosis were found in eastern Georgia (91.3% of cases). Mainly men were infected with brucellosis (81.0%).The age group with the most frequent cases of brucellosis is 30-59 years (48.5%). Brucellosis is rarely found among children(0-4 years - 2.0%, 5-14 years - 8.0%). Brucellosis cases were linked to professional activity; mainly by farmers (33.0% of those infected) and shepherds (27.0%). Biotyping Brucella by microbiological methods alone has limitations, so molecular typing was implemented in this study to confirm species. Isolates from human blood and ruminant milk or blood were identified by a bacteriological algorithm and confirmed by real-time PCR (Brucella T1, Idaho Technology). Species identity was confirmed using the AMOS conventional PCR assay, which differentiates four human pathogenic species but cannot recognize certain biovars within them. This gap was addressed by using more universal species-specific Single Nucleotide Polymorphism (SNP) assays. Real-time PCR was used to confirm 86 Brucella strains (48 human, 38 animal isolates) obtained 2009-2011. AMOS PCR supported the biochemical test results for 53 B. melitensis and four B. abortus strains, but not for 29 suspected B. abortus human and animal isolates. SNP typing of all 86 isolates supported the AMOS PCR results but also confirmed the species of the 29 strains not amplified by AMOS PCR. In 2009-2013 years the prevalence of brucellosis was still high. Nowadays cases of brucellosis are higher in the western part of Georgia than in the 1991-2005 period by a factor of 2.62. Brucellosis continues to be mainly an infection in males, because men are mostly engaged in sheep and cattle care. Combined AMOS PCR and SNP typing in this study provided the first genetic confirmation that both B. abortus and B. melitensis are actively circulating in humans and animals in Georgia.

Geographical heterogeneity of multidrug-resistant tuberculosis in Georgia, January 2009 to June 2011.

In 2011, Georgia, in the Caucasus, reported that 11% of new and 32% of previously treated tuberculosis (TB) cases nationally had multidrug-resistant TB (MDR-TB). To help understand the mechanisms driving these high risks of drug-resistance and plan for targeted interventions, we identified geographical variability in the MDR-TB burden in Georgia and patient-level MDR-TB risk factors. We used routinely collected surveillance data on notified TB cases to estimate the MDR-TB incidence/100,000 people and the percentage of TB cases with MDR-TB for each of 65 districts and regression modelling to identify patient-level MDR-TB risk factors. 1,795 MDR-TB cases were reported (January 2009­June 2011); the nationwide notified MDR-TB incidence was 16.2/100,000 but far higher (837/100,000) in the penitentiary system. We found substantial geographical heterogeneity between districts in the average annual MDR-TB incidence/100,000 (range: 0.0­5.0 among new and 0.0­18.9 among previously treated TB cases) and the percentage of TB cases with MDR-TB (range: 0.0%­33.3% among new and 0.0%­75.0% among previously treated TB cases). Among treatment-naïve individuals, those in cities had greater MDR-TB risk than those in rural areas (increased odds: 43%; 95% confidence interval: 20%­72%). These results suggest that interventions for interrupting MDR-TB transmission are urgently needed in prisons and urban areas.

Outcomes of children treated for tuberculosis with second-line medications in Georgia, 2009-2011.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a major public threat in countries of the former Soviet Union, including Georgia. There are few studies of pediatric DR-TB cases, especially at a national level. OBJECTIVE: To report the characteristics and treatment outcomes of pediatric multidrug-resistant TB (MDR-TB) cases in Georgia. METHODS: We extracted data on all pediatric (age <16 years) MDR-TB cases notified in Georgia from 2009 to 2011. We assessed the baseline and treatment characteristics and treatment outcomes of this cohort. RESULTS: Between 2009 and 2011, there were 45 notified pediatric DR-TB cases in Georgia. Just over half had previously received anti-tuberculosis treatment and the median age was 7.7 years. Time from diagnosis to treatment was short (median 16 days), and the median length of treatment was 20.2 months. Of those not still on treatment, 77.1% (95%CI 61.0-87.9) had a successful outcome. CONCLUSIONS: One of the first reports of pediatric DR-TB treatment outcomes at a national level, this study demonstrates that successful outcomes can be achieved.

Synaptic and non-synaptic mitochondria in hippocampus of adult rats differ in their sensitivity to hypothyroidism.

Hypothyroidism in humans provokes various neuropsychiatric disorders, movement, and cognitive abnormalities that may greatly depend on the mitochondrial energy metabolism. Brain cells contain at least two major populations of mitochondria that include the non-synaptic mitochondria, which originate from neuronal and glial cell bodies (CM), and the synaptic (SM) mitochondria, which primarily originate from the nerve terminals. Several parameters of oxidative stress and other parameters in SM and CM fractions of hippocampus of adult rats were compared among euthyroid (control), hypothyroid (methimazol-treated), and thyroxine (T4)-treated hypothyroid states. nNOS translocation to CM was observed with concomitant increase of mtNOS's activity in hypothyroid rats. In parallel, oxidation of cytochrome c oxidase and production of peroxides with substrates of complex I (glutamate + malate) were enhanced in CM, whereas the activity of aconitase and mitochondrial membrane potential (ΔΨm) were decreased. Furthermore, the elevation of mitochondrial hexokinase activity in CM was also found. No differences in these parameters between control and hypothyroid animals were observed in SM. However, in contrast to CM, hypothyroidism increases the level of pro-apoptotic K-Ras and Bad in SM. Our results suggest that hypothyroidism induces moderate and reversible oxidative/nitrosative stress in hippocampal CM, leading to the compensatory elevation of hexokinase activity and aerobic glycolysis. Such adaptive activation in glycolytic metabolism does not occur in SM, suggesting that synaptic mitochondria differ in their sensitivity to the energetic disturbance in hypothyroid conditions.

Outcomes among tuberculosis patients with isoniazid resistance in Georgia, 2007-2009.

BACKGROUND: The optimal management strategy for patients with isoniazid (INH) monoresistant forms of tuberculosis (TB) has been widely debated. The current daily 9-month regimen of rifampin, pyrazinamide and ethambutol was established based largely on trials in settings with low TB rates and low rates of drug resistance. OBJECTIVE: To explore the outcomes of patients with INH-monoresistant TB in the country of Georgia, a setting with both high TB rates and drug-resistant forms of the disease. METHODS: Retrospective record review of all patients diagnosed with smear-positive pulmonary TB resistant to either INH or INH+SM (streptomycin) in Georgia between 2007 and 2009. RESULTS: Of 8752 patients with pulmonary TB registered in Georgia, 909 were found to have INH or INH+SM resistance. Treatment outcomes were relatively poor in this group, with only 71% treatment success. Outcomes were significantly worse among patients with older age and a history of previous treatment. CONCLUSIONS: INH or INH+SM resistance in pulmonary TB patients in Georgia is common. The low rates of treatment success suggest the need for an improved treatment regimen for patients with resistance to these first-line drugs; this need is particularly pronounced among the subset of patients with a history of previous treatment.

[Vaginosis in patients with antenatal foetus death].

Polymerase chain reaction (PCR) analysis of bacterial vaginosis as well as of vaginal anaerobe flora (Mycoplasma Hominis, Ureaplasma urealyticum, Gardnerella vaginalis, Bacteroides spp. and Mobiluncus curtisii) was performed in women with antenatal foetus death. Specimens from forty women with this pathology were studied. Control group consisted of 100 pregnant women of the adequate age groups and gestation periods, but with live foetus. Vaginal smears treated by the use of polymerase chain reaction method showed that in the cases of antenatal foetus death in 70% of women Lactobacillus spp. was completely absent. This bacterium was observed only in 30% of these women. In 75% of women with live foetus Lactobacillus spp. was observed, while in 25% it was not present. Increase of quantity of anaerobic vaginal flora was observed in women, where the antenatal death of foetus was diagnosed. Percentage significance of these indices in women with live foetus was comparatively lower.

[Investigation of physical activity among adults].

Lack of physical activity as well as smoking, overweight, high blood cholesterol level and hypertension are independent risk factors for development of various chronic diseases. Lack of physical activity is a main cause of non-communicable diseases morbidity and mortality in about 23% of cases (WHO, 2002). Goal of the survey was the identification and characteristics of physical activity among adults. We conducted epidemiologic survey among the school-children and students in Tbilisi. Survey was carried out in 40 schools from all regions of Tbilisi and 9 state and private institutes. Schools were selected by randomized trail in each region of Tbilisi and in each school were questioned all teen-agers from 14-17 year old. For selecting group of survey was used method of "proportional probability of value". There were questioned 2 500 school children and 1000 students, 38% boys and 62% girls. The results of survey ascertained that 23,5%-39,5% of respondents are training or engaged in sport everyday, or several times per week; 17,2% - once in a month; 9,3% once in a year; or 10,5% - never. Adults are less informed about useful effect of physical activity. Respondents had different point of on the role of physical activity: some of them thought it controls weight; others - prevents development of different diseases; the rest thinks that it copes with psycho-emotional stress, and none of them precise about effectiveness of physical activity in all cases mentioned above. Propaganda of healthy life stile must be associated with the effectiveness of physical activity on health.

[Youth health behavior survey].

High-risk behaviours -- smoking, drug use, alcohol use and etc. are the main risk factors of non-communicable diseases and main reasons of morbidity and mortality in many countries of the world. We conducted the "Youth Health Behaviour Survey" among the students in Tbilisi, Mtskheta and Dusheti. The survey included questioning of students (14-17 years old) by modified questionnaire. There were questioned 300 students, 100 in each region. Mtskheta is very close to Tbilisi, it's a peri-urban area; Dusheti is quite far rural area. The survey results show that teenagers both in central and peripheral areas are becoming familiar with alcohol in early ages and using alcohol is several times higher in Tbilisi. In Tbilisi as in Mtskheta and Dusheti students use wine and spirits with same frequency. Smoking is a bit high in Tbilisi and Mtskheta; regular smoking starts at age 13-14, boys are smoking more than girls. Drug use wasn't identified. Sexual intercourse had almost half of boys from Tbilisi and about one third of boys in Mtskheta and Dusheti. Safe sex methods more frequently are used in Tbilisi. Propaganda of healthy life style is essential in supporting healthy youth development. It's very important to set different interventions in different regions of Georgia, to adapt materials to real situation.

[Dipole cooperative model of ion channels of excitable biomembranes. Conductance of ion channels]. / Dipol'naia kooperativnaia model' ionnykh kanalov vozbudimykh biomembran. Provodimost' ionnykh kanalov.

An analysis of ionic channel conductance is presented in terms of dipole cooperative model. The dependence of conductance on displaced charge is found to be an S-shaped function. Basing on this function and kinetics of gating currents, the kinetic curves for the conductance are calculated. These curves are compared with Hodgkin--Huxley results on sodium channel. A good agreement may be observed for the case of positive jumps of the potential. Less accurate coincidence takes place for negative jumps of the potential.

[Dipole cooperative model of ion channels in excitable biomembranes. I. Gating currents]. / Dipol'naia kooperativnaia model' ionnykh kanalov vozbusimykh biomembran. I. Vorotnye toki.

The experimental data on gating currents are analyzed in terms of dipole cooperative model of ionic channel. The dependence of displaced charge on potential is calculated. A comparison between the theory and experiment allows to establish the cooperative part of the charged gating subunits energy. It is shown that kinetics of gating particles displacement is nearly exponential. The theoretical dependence of characteristic times on the potential during testing pulse of voltage agrees qualitatively with the experimental curves.