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.

COMPARATIVE ANALYSIS OF WHOLE CARTILAGE TISSUE THERMOSTABILITY IN DISEASED PATIENTS VERSUS INJURED PATIENTS.

We conducted comparative thermodynamic analysis of femoral cartilages tissue of injured (healthy) patients and patients with congenital hip dislocation. It is shown, that temperature which corresponds to maximum of heat absorption peak of femoral cartilages tissue of diseased patient is on 6.4oC lower than heat absorption peak of femoral cartilages tissue of healthy patient.

[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.

[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.

Extracellular matrix thermostability of breast gland carcinoma.

Thermostability of epithelial cell matrix in composition of normal and breast ductal carcinoma tissues at various stages of the disease has been studied in the temperature range 40-90°C with help of differential scanning calorimeter (DSC). It has been shown that the denaturation process has three stages of transition in both cases. The temperatures corresponding to maxima of these structural transitions (Td) in case of normal and ductal carcinoma tissues equals to 55 , 66,78 C and 48, 55, 60, 85°C, respectively.

Influence of tetrapeptide on chromatin thermostability.

It is known that short peptides are capable to interact with DNA, as a result of changes in particular gene expression. In the given work, influence of Ala-Asp-Glu-Leu peptide on thermostability of white rat liver chromatin, in which H1 histone and non-histone proteins are depleted, have been studied. It was shown that in 10 nm chromatin filaments, in which nucleosomas do not interact, the tetrapeptide unfolds the nucleosomal nucleus (core) and this causes release of about 15% of core DNA that melts in the melting temperature range of internucleosomal linker DNA.

Effect of the peptide bronchogen (Ala-Asp-Glu-Leu) on DNA thermostability.

Thermodynamic parameters of DNA melting in the presence of a peptide bronchogen in various concentrations were estimated on a differential scanning microcalorimeter. Bronchogen was shown to serve as a DNA-stabilizing agent. Bronchogen increased the melting temperature of DNA from calf thymus and mouse liver by 3.

Remodeling of heterochromatin induced by heavy metals in extreme old age.

The levels of chromosome instability and heat absorption of chromatin have been studied in cultured lymphocytes derived from blood of 80-93- and 18-30-year-old individuals, under the effect of heavy metal Cu(II) and Cd(II) salts. The analysis of the results obtained indicates that 50 μM Cu(II) induced a significantly higher level of cells with chromosome aberrations in old donors (13.8 ± 1.

Impact of unfounded vaccine safety concerns on the nationwide measles-rubella immunization campaign, Georgia, 2008.

Vaccine safety fears following media reports of adverse events led to low (50.3%) coverage in a supplementary measles-rubella immunization campaign in Georgia in 2008. Review of adverse events associated with the campaign identified 432 reports (<0.

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.

Microcalorimetric study of human blood lymphocytes culture at presence of copper, cadmium and prostamax.

Research goal was study of separate and joint influence of bioregulator prostamax and Cu(II) and Cd(II) ions on the chromatin structure in situ. The thermal characteristics of the denaturation process of blood lymphocytes culture of aging people in the presence of some microg quantities of Cu(II) and Cd(II) ions have been determined. It has been shown that Cu(II) and Cd(II) ions at these low concentrations don't influence on the temperature stability of membrane, nuclear and cytoplasm proteins.

Mathematical model for satellite associations of human acrocentric chromosomes.

Short arms, satellite stalks and satellites of human acrocentric chromosomes (13, 14, 15, 21 and 22) represent heterochromatic regions. Enforced by mutual attraction of heterochromatic regions, the short arms of acrocentric chromosomes come close to each other and compose associations. The associations of human acrocentric chromosomes cause nucleolus formation, undergo age-related changes, account for elevated incidence of chromosome rearrangements and, consequently, can cause chromosome diseases.

Thermodynamic properties of blood plasma of patient suffering from atherosclerosis.

The goal of the work is to find out the changes in the heat parameters of blood plasma denaturation of a son and a granddaughter, in comparison with the same parameters of a 91 years old grandfather with atherosclerosis. The significant changes in heat (Q(d)) and denaturation temperature (T(d)) of albumin, globulins and fibrinogen of 91-year-old patient suffering from atherosclerosis relative to the norm (88-year-old man) are found out. In particular, Q(d) increase by 60% of albumin fat fraction and fibrinogen of F domain and the increase of their T(d) by 2.

The microcalorimetric investigation of cellular suspensions of blood lymphocytes from healthily and suffering from atherosclerosis individuals.

The denaturation thermodynamic parameters--enthalpy (DeltaH) and temperature of hetero-and active chromatin of lymphocytes and metabolic heat of these cells were determined for healthy and suffering from atherosclerosis individuals. It is supposed that atherosclerosis disease leads to chromatin rebuilding in the interphase state and decrease of cell survival. The chromatin rebuilding may be imagined as partially unfolding of 30 nm chromatin fiber into 10 nm one due to loss of some part of H1 histone.

[The effect of heavy metal ions and peptide bioregulators on the expression of chromosome fragile sites in the individuals of different age groups and breast cancer patients].

Expression rates of chromosome fragile sites in peripheral blood lymphocytes have been studied in clinically healthy individuals of different age groups (20-38 yrs and 75-86 yrs) and breast cancer patients (8 cases). In individuals with a normal check-up of different age groups the heavy metal (nickel, zinc and cobalt) ions were also examined on their influence on the expression of the fragile sites and the peptide bioregulators (Livagen and Epithalon) were tested on their ability to correct the pattern of expression. Short-term lymphocyte cultures were used as tested material.