EPIGENETIC MODIFICATION UNDER THE INFLUENCE OF PEPTIDE BIOREGULATORS ON THE "OLD" CHROMATIN.

In the present study, on the one hand, the epigenetic modification of condensed "old" chromatin was determined, and on the other hand, the influence of peptide bioregulators (Ala-Glu-Asp-Gly-Epitalon; Lys-Glu-Asp-Ala-Livagen; Ala-Glu-Asp-Pro - Cortagen and Lys-Glu - Vilon) on condensed chromatin in lymphocytes from old individuals. Were used molecular-cytogenetic methods: differential scanning calorimetry; activity of ribosomal genes of acrocentric chromosome satellite stalks-NORs; polymorphism of structural pericentromeric C-heterochromatin; variability of the facultative heterochromatin (sister chromatid exchanges - SCE) in the culture of lymphocytes from 75-88-year-old individuals. The analysis of results shows the chromosome progressive heterochromatinization (condensation of eu - and heterochromatin regions) occur in aging. Epigenetics process - heterochromatinization can deactivate many previously functioning active genes. It blocks certain stages of normal metabolic processes in the cell, which inhibits many specific enzymes and leads to aging pathologies. We show that peptide bioregulators induced unrolling deheterochromatinization (decondensation) of total heterochromatin, deheterochromatinization of satellite stalks of acrocentric chromosome, activating synthetic processes of ribosomal genes, does not cause deheterochromatinized of pericentromeric structural heterochromatin. This data also indicates that each of the studied peptide bioregulators (Ala-Glu-Asp-Gly; Lys-Glu-Asp-Ala; Ala-Glu-Asp-Pro and Lys-Glu) has a selective effect on definite regions of chromosomes. Thus, short peptide bioregulators induce selective heterochromatinization and deheterochromatinization of chromosome regions (remodeling of facultative heterochromatin) in individuals 75-88 years old that opens up new opportunities in the treatment of aging diseases.

[FREQUENCY OF POLYMORPHIC VARIANTS OF GSTT1 AND GSTM1 GENES IN PATIENTS WITH PULMONARY TUBERCULOSIS IN GEORGIAN POPULATION].

A study was made for determining the frequencies of polymorphic variants of GST genes - GSTM1 and GSTT1, both among healthy individuals of the Georgian population (the Tbilisi population, populations of Eastern and Western Georgia), and among patients with tuberculosis; was also conducted a study on the relationship of certain genotypes with hepatotoxicity in patients taking anti Pulmonary Tuberculosis (PT) treatment. As a result of the analysis, it turned out that the general population indicator for healthy individuals for GSTT1 and GSTM1 positive variants of GST genes was 82%; for GSTT1 (-) / GSTM1 (+) variant was 13%; The GSTT1 (+) / GSTM1 (-) genotype was observed in 2%; as for the double null genotype - GSTT1 (-) / GSTM1 (-), the total population indicator was 3%. As for individuals suffering pulmonary tuberculosis, it turned out that 79% of studied patients revealed positive genotypes by the studied genes - GSTT1 (+)/GSTM1 (+); 3% have the GSTT1(-)/GSTM1(+) genotype; the genotype GSTT1(+)/GSTM1(-) was observed in 6% of investigated individuals, and the double null genotype - GSTT1 (-) / GSTM1 (-) - in 12%, which significantly exceeds the general population indicator for healthy individuals. The results of the studies also showed that there is a relationship between the double null genotypes of GSTM1 and GSTT1 genes and drug induced liver injury in patients with pulmonary tuberculosis, in Georgian population. It has been suggested that it is possible to recommend a preliminary analysis of the polymorphism of GSTM1 and GSTT1 genes in patients with pulmonary tuberculosis, before starting antituberculotic treatment, for preventive measures in the case of detection of double null genotypes. It should be noted, that this study has been conducted in Georgia first time.