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.

[GENOMIC VARIABILITY DURING PREGNANCY TRIMESTERS].

The article presents data on the genome status of pregnant women in different trimesters of pregnancy, during the normal course of pregnancy. The variability of ribosomal cystone activation as well as the variability of genome stability (frequencies of chromosomal aberrations and fragile sites) in different trimesters of pregnancy have been studied to detect genome-specific functional variability for each trimester.It was found that the level of genome stability determined by the frequency of chromosomal structural disorders and fragile sites in all three trimesters of pregnancy did not differ significantly from similar rates for non-pregnant healthy women.

EPIGENETIC MODIFICATION UNDER THE INFLUENCE OF PEPTIDE BIOREGULATORS ON "AGED" HETEROCHROMATIN.

Following the completion of the Human Genome Project, the strategic direction of modern genetics has moved toward functional genomics, to explore the functions of non-coding regions of DNA. These non-coding regions are localized in heterochromatin. The functions of heterochromatin largely remain unclear.

[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.

[EVALUATION OF GENOMIC PARAMETERS IN DUCTAL BREAST CANCER PATIENTS AND THE ABILITY OF IT'S CORRECTION].

The level of DNA single strand breaks, chromosomal abnormalities and sister chromatid exchanges and the possibility of its normalization with oligopeptide bioregulator Livagen and cobalt ions in the lymphocyte culture from patients with breast cancer have been studied. The results show that the genome of ductal breast cancer patients is characterized by the high density of DNA single strand breaks, high frequency of chromosomal abnormalities and increased levels of chromatin condensation. The usage of Livagen and cobalt in the form of modifying agents has a protective effect by all studied parameters.

[GENOMIC VARIABILITY IN PATIENTS WITH DUCTAL FORM OF BREAST CANCER AND THE POSSIBILITY OF CORRECTION THE PEPTIDE BIOREGULATOR AND METAL IONS].

Level of genome stability (structural aberrations, aneuploidy and fragile sites) was studied in cells of the lymphocyte culture of ductal breast cancer patients (DBC). Was studied the correctional influence of separate and combinative action of peptide bioregulator (Ala-Glu-Asp-Gly) and heavy metal - nickel. It is shown that DBC patients are characterized by high level of genome instability, which is the result of the chromatin changing state.

[FREQUENCY OF POLYMORPHISM OF VKORC1 AND CYP2C9 GENES IN TWO REGIONS OF GEORGIA].

The aim of the research was to study the frequency of VKROC1 and CYP2C9 genes different alleles for healthy donors and for patients with thrombosis, in two regions of Georgia - in Samegrelo and in Tbilisi and to reveal the interdependence of the studied genes products in the treatment of thrombosis with warfarin. Warfarin is an anticoagulant, causing the inactivation of the VKORC1 gene product, which is one of the clotting factors. The protein product of CYP2C9 gene is involved in the metabolism of warfarin.

[Genomic instability in atherosclerosis].

A comparative study of the level of genomic instability, parameters of quantitative and structural mutations of chromosomes (aberration, aneuploidy, polyploidy) in lymphocyte cultures from patients with atherosclerosis of age 80 years and older (control group - 30-35 years old) was conducted. The possibility of correction of disturbed genomic indicators by peptide bioregulators - Livagen (Lys-Glu-Asp-Ala) and cobalt ions with separate application or in combination was also studied. Control was lymphocyte culture of two healthy respective age groups.

[Functional regulation of genome with peptide bioregulators by hypertrophic cardiomyopathy (by patients and relatives)].

In this paper, a comparative study of the functional genome indicators using lymphocyte cultures of patients with hypertrophic cardiomyopathy (HCM) and their first relatives. Studies conducted both in intact cultures and cultures exposed to the influence of peptide - bioregulators Epithalon, Vilon and Livagen. Last (Livagen) tested at separate and joint application with cobalt chloride salt.

[Genome instability in pulmonary tuberculosis before and after treatment].

Pulmonary tuberculosis is classified as a disease with a genetic predisposition, and therefore, as with other pathologies related to this group of diseases, by pulmonary tuberculosis, special importance is given to finding those markers that enable early identification of risk groups, such as skrinnig in general population and relatives of patients with tuberculosis, which in turn can provide the basis for preventive measures. One of this markers is the level of genome stability. The aim of this study was a comparative evaluation of the functional parameters of the genome variability in patients with sensitive form of pulmonary tuberculosis before and after treatment, and the possibility of its correction with anti-stress peptide bioregulator - epitalon.

[Deheterochromatinization of the chromatin in old age induced by oligopeptide bioregulator (Lys-Glu-Asp-Pro)].

In this work is presented the data on the variability of the functional characteristics of the chromosomes in the cells exposed by oligopeptide bioregulator - Prostamax from old individuals (75-86 years). Evaluated: the frequency of sister chromatid exchanges (SCE); Ag-positive NORs (in associations and nonassociations), as well as the variability of the structural C-pericentromeric heterochromatin. Prostamax changed the chromosomal parameters: 1) increased the frequency of SCE to 12,0±0,28 exchange in per cell (in intact cells - 5,9±0,2); 2) increased the frequency of Ag-positive NORs to 2.

Gerontology research in Georgia.

Gerontology research carried out in different scientific centers of Georgia follows the basic directions of most work in this field: epidemiology, investigation of the mechanisms of aging, and finding ways to prevent senile pathologies and to prolong life. The genealogy and epidemiology of long-living peaple have been studied in areas with high occurrence of these people by considering the sex ratio and social status of the long-living, the influence of environmental factors, and the development of senile pathologies. According to the centrosome (centriole) model of aging, the centrosomes and the cytoskeleton, important structures in cellular differentiation and morphogenesis, may be involved in the initiation of the replication senescence mechanism.

Natural and artefactual aneuploidy in human lymphocytes in extreme old age.

At present it is generally believed that aging is accompanied by an increase in the numbers of cells with altered chromosome sets. However, the problem of aneuploidy in extreme old age (80 years and over) has hardly been subjected to systematic investigation. The purpose of this study was to examine quantitative chromosome changes and relationship between "artefactual" and "natural" aneuploidy in subjects from 80 to 114 years of age using karyotype analyses.

[Variability of radiation-induced adaptive response in old age individuals and their correction by Peptide bioregulator -Livagen].

Effect of aging on adaptive response of cellular systems to low (stimulated) dozes of gamma-rays (0, 2 and 0, 5 Gy) and to disturbing dozes of radiation (1 and 2 Gy) has been investigated. PHA-stimulated cells were from 72-86 year-old individuals; control - 30-40 year-old individuals. The potentialities of induction of adaptive response in cells exposed to previously irradiated by stimulating dozes of gamma-rays with subsequent damaging effect of copper chloride (10(-3)M) has been investigated.

Anti-aging peptide bioregulators induce reactivation of chromatin.

The effect of synthetic peptide bioregulators (Epitalon, Livagen and Vilon) on structural and facultative heterochromatin of cultivated lymphocytes have been studied among old (75-88yr.) people. The data obtained indicate that epitalon, livagen and vilon: 1) activate synthetic processes, caused by reactivation of ribosomal genes as a result of deheterochromatinization (decondensation) of nucleolus organizer regions; 2) induce unrolling (deheterochromatinization) of total heterochromatin; 3) release genes repressed by heterochromatinization (condensation) of euchromatic regions forming facultative heterochromatin; 4) epitalon and livagen induce deheterochromatinization (decondensation) of pericentromeric structural heterochromatin of the chromosomes1 and 9.