[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. It was also shown that patients with atherosclerosis exhibit high level of genomic instability in all studied parameters, regardless of age, which may suggest that there is marked increase in chromatin condensation in atherosclerosis. It was also shown that Livagen (characterized by modifying influence on chromatin) separately and in combination with cobalt ions, promotes normalization of altered genomic indicators of atherosclerosis in both age groups. The results show that Livagen separately and in combination with cobalt ions has impact on chromatin of patients with atherosclerosis. The identified protective action of Livagen proves its efficacy in prevention of atherosclerosis.

[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. The studies were conducted using short-term mitoge -stimulated cell cultures of TB patients, before and after treatment. As an indicator of genome stability has been studied the frequency of structural and numerical chromosome aberrations and fragile sites. It is shown, that in intact cultures from patients with pulmonary tuberculosis, before treatment was significantly higher level of frequency of cells with structural chromosome aberrations, that still retained after the treatment. As for epithalon, it appears that was shown a pronounced protective effect after treatment, on the test of chromosome aberrations, by reducing both overall mean frequency aberrant cells and indicators for all individuals. In the study of fragility of chromosomes in patients with primary tuberculosis was found, that in intact cultures, the proportion of cells with chromosomal fragile sites was higher than in control group of healthy individuals, befor and after treatment. High frequency of chromosome fragility persisted by treatment with peptide bioregulator in both cases - before and after treatment. It is suggested that the identified patterns can be correlated with a high incidence of re- TB.

[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. As indicated according to the results of the analysis, the cells of the individuals with HCM and their first relatives were characterized by higher frequency of spontaneous quantitative - structural disorders in comparison with the cells of healthy individuals. The findings suggest a different effect of bioregulators. The most effective protective action in relation normalization of functional parameters of the genome shows Epithalon for lowering the level of chromosomal instability in patients with hypertrophic cardiomyopathy and relatives of patients with HCM. On the basis of identified protective action Epithalon concludes prospects of its application in the development of preventive measures for individuals at increased risk of morbidity HCM.

[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 2.5 per cell (in intact cells - 0.95) 3) reduced in the frequency of large segments of the options from the pericentromeric heterochromatin for the 1st and 9th chromosomes. Comparison of the results indicates the ability of Prostamax to decondensation, deheterchromatinization the chromatin during aging, and thus release by heterochromatinization repressed genes. On the other hand, the data obtained in this work suggest that the basis for the protective action of Prostamax its modifying effect on chromatin.

[Variability of C-structural heterochromatin in cells derived from the patients with cardiomiopathy and from their relatives].

Variability of C-structural heterochromatin segments in chromosome 1,9 and 16 has been studied in lymphocyte cultures of peripheral blood taken from the patients with the hypertrophy (HC) and dilatate (DC) forms of cardiomiopathy and their 1st degree relatives (32 individuals, in total). 10 healthy individuals composed the control group. C-segments were sorted according to Patil and Lubs: a<0.5 x 16p; b>0.5-1 x 16p; c>1.5 x 16p; d>1.5-2 x 16p; e>2 x 16p. The total amount of C-heterochromatin in all the studied chromosomes was tended to increase for DC patients and the relatives of the patients with the two forms of cardiomiopathy. Individual specificity within the group was found when the c-variants were assessed in chromosomes. In particular, the results obtained in cells of HC patients and their relatives did not differ from the control values, while the distribution pattern of C-segments within the group of DC patients and their relatives underwent changing. The elevated induces of pericentromeric inversion were found in all the patients with both forms of the disease and their relatives indicating C-structural heterochromatin polymorphism in the tested individuals.

[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. The analysis showed that the chromosomes of people from young and old age groups differ from each other by the expression pattern of fragile sites - the chromosomes of young individuals were found to be more active by spontaneous formation of fragile sites. They were also sensitive to their induction by heavy metals. Both tested bioregulators lessen heavy metals effect that was statistically reliable only for the young people group. As for the patients with breast cancer general elevated fragility of chromosomes and specific distribution of the fragile sites along the chromosomes were revealed.

[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. The correcting activity of the peptide bioregulator Livagen was tested. The investigation showed that cells from aged individuals maintained radiation adaptive feature. Preliminary exposure to radiation caused stimulation of adaptive response in copper-treated cells. Corrective activity of Livagen was observed.

[Chromosome instability in patients with different forms of cardiomyopathy and their relatives].

Comparative studies on spontaneous and induced by two agents (mytomycin C and Nickel chloride) chromosome instability have been conducted in cultured lymphocytes derived from patients with hypertrophic and dilated forms of cardiomyopathy (HCMP and DCMP) and their relatives compiling a high-risk group to develop mentioned pathologies. In patients with HCMP and DCMP, as well as in their relatives higher levels of spontaneous chromosome instability were found in comparison with the control group (comprising healthy individuals without cardiomyopathic anamnesis). Almost all the affected patients and their relatives revealed tendency to increased aneuploidy and significant elevation of polyploidy when compared with control values. It was demonstrated that nickel chloride-induced chromosome disorders registered more frequently in lymphocytes of the patients and their relatives than in cells of control subjects, but mytomycin C did not have such an affect. We assume to explain the similarity of studied parameters in patients with cardiomyopathy and their relatives as a consequence of identical rearrangements in genome functioning. The revealed analogy should be interpreted as a pre-illness condition for the individuals included in the risk-group.

Effects of Livagen peptide on chromatin activation in lymphocytes from old people.

We studied the effects of the synthetic peptide Livagen on activity of ribosomal genes, denaturation parameters of heterochromatin, polymorphism of structural C-heterochromatin, and variability of facultative heterochromatin in lymphocytes from old people. Livagen induced activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin, and release of genes repressed due to age-related condensation of euchromatic regions in chromosomes. Our results indicate that Livagen causes de-heterochromatinization (activation) of chromatin, which is realized via modification of heterochromatin and heterochromatinized regions in chromosomes from old people.

[Structural mutations of chromosome mutations induced by heavy metal salts during aging in vivo and in vitro]. / Izuchenie strukturnykh mutatsii khromosom indutsirovannykh soliami tiazhelykh metallov pri starenii in vivo i in vitro.

The cytogenetic effect of inorganic copper (CuSO4) and cadmium (CdCl2) salts was studied in cells of long-term (144-hour) human cultures (in vitro model of aging) and in elderly individuals (80-93 years old). Copper sulfate increased the incidence of aberrant cells both in elderly individuals (14.25 +/- 1.74%) and during in vitro aging (12.20 +/- 1.62%) (3.94 +/- 1.96% and 5.25 +/- 1.10% in the controls, respectively), whereas treatment with cadmium chloride did not induce any changes in the background index. Differences in the effect of the studied salts may be due to their different effects on chromatin modification.

[Effect of copper ions on chromosome structural mutations caused by Cs1 37 gamma rays in moist seed cells of Crepis capillaris L]. / Deistvie ionov medi na strukturnye mutatsii khromosom, vyzvannye gamma-luchami Csi 37 v kletkakh zamochennykh semian Crepis capillaris L

When seeds of Crepis capillaris were germinated in solutions of Cu(NO3)2 (at 0.55-10(-5) M and 1.1-10(-5) M concentrations) the frequency of structural chromosome mutations induced by gamma-rays (137Cs) at 200 and 400 r doses was higher as compared to that induced in the absence of copper ions.