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Biomedical subjects

V Kh Khavinson

Publications and source records attributed to V Kh Khavinson.

At least 19 recordsLinked to original sources

Interleukin-2 concentration in hypothalamic structures of rats receiving peptides during mild stress.

The number of hypothalamic IL-2-containing cells changed in rats receiving Vilon and Epithalon during mild stress (handling). The number of IL-2-positive cells in hypothalamic structures decreased 24 h after intramuscular injection of Epithalon and 2 h after intranasal administration of the test peptides. Adaptation of animals to experimental conditions prevented the decrease in the number of IL-2-positive cells in the supraoptic nucleus after intranasal administration of Epithalon.

Animals↗

Molecular mechanism of interaction between oligopeptides and double-stranded DNA.

Formation of Ala-Glu-Asp-Gly peptide complex with duplex DNA [poly(dA-dT):poly(dA-dT)] at neutral pH and ambient temperature was studied experimentally. Peptide binding to duplex DNA was associated with hyperchromic effect indicating local separation of the double helix. Energies of paired interactions between amino acid residues and nucleotide bases were compared with the energy of bond between two bases in the nucleotide pair (dA-dT). A new concept of interaction between two types of information-carrying molecules is put forward. This interaction underlies triggering of protein synthesis mechanism and can explain the emergence of life on the Earth.

Chromatin↗

[Effect of epitalon and melatonin on life span and spontaneous carcinogenesis in senescence accelerated mice (SAM)].

Female senescence accelerated mice SAMP-1. (prone) and SAMR-1 (resistant) were exposed 5 times a week monthly to melatonin (with drinking water 20mg/ml during the night hours) or to s.c. injections of epitalon (Ala-Glu-Asp-Gly) at a single dose 1mkg/mouse. Control mice were intact or exposed to injection of 0.1 ml normal saline. The body weight and temperature, food consumption, estrous function were monitored regularly. The life span and tumor incidence were evaluated as well. As age advanced, the weight increased whereas food consumption and body temperature did not change. There was no significant substrain difference in these parameters. Exposure to melatonin or epitalon also failed to influence those indices. As age advanced, the incidence of irregular estrous cycles increased both in SAMP-1 and SAMR-1, whereas the treatment with both melatonin and epitalon prevented such disturbances. SAMP-1 revealed some features of accelerated aging as compared to SAMR-1. The mean life span of the 10% of the last survivors among treated SAMP-1 was shorter than that of SAMR-1, aging rate increased and mortality doubling time decreased. There was a direct correlation between body mass of the two substrains at the age of 3 and 12 months matched by body mass increase and longer life span. Melatonin or epitalon treatment was followed by longer mean and maximum survival in the 10% of the last survivors among SAMP-1. Melatonin involved decreased aging rate and increased mortality doubling time. Malignant lymphomas predominated in SAM without any significant difference in frequency between the substrains. While melatonin failed to influence tumor incidence or term of detection in SAMP-1, neither did epitalon affect frequency. However, it was followed by longer survival in tumor-free animals. No link between melatonin or epitalon treatment, on the one hand, and carcinogenesis, on the other, was reported in SAMR-1.

Aging↗

[Peptide bioregulator efficacy in the correction of reduced thyroid gland function in the residents of Magadan Region].

Thyroid gland pathology is one of the most widespread diseases. Age is the main risk factor in the development of hypothyroid states, alongside with biogeochemical and climatic adverse factors of the environment. Disturbed hormonal status of the organism affects the quality of life in patients with subclinical and manifested hypothyroidism forms, especially in old age, and requires adequate correction methods. In this connection Thyramin bioregulator is noteworthy, exerting tissue specific effect on thyroid gland cells and enabling the restoration of the disturbed thyroid tissue function.

Adult↗

[Vilon effect on consequences of repeated radioactive and mercuric impact in small doses].

The purpose of the study was to determine the efficacy of vilon administration in rats after reiterated exposure to ecotoxicants (mercury in concentration near to maximum allowable one and gamma-radiation in small dose). In 24 hours after repeated radioactive and mercuric impact (RMI) and for 30 consecutive days the animals reported lymphopenia. At the same time the indices of DNA leucocytes content and structure did not differ from the parameters of intact animals, this could evidence the development of adaptation reactions. Vilon administration led to the normalization of the lymphocytes number by the 30th day after repeated irradiation (contrary to the radioactive- chemical control), while the number of granulocytes in the test group was higher than that in the intact control group. Study of the survival rate in rats revealed that Vilon reduced morbidity of rats in the course of 15 months after RMI.

Animals↗

[Effect of peptide Livagen on activity of digestive enzymes in gastrointestinal tract and non-digestive organs in rats of different ages].

It is stated that Livagen (Lys-Glu-Asp-Ala) is a weakly hydrolyzed peptide. Peptide hydrolases of small intestine do not hydrolyze Livagen even to a small extent. Under in vitro conditions Livagen reduces glycil-L-leucinedipeptidase activity in small intestine by 50%. After two weeks of Livagen administration per os in rats the digestive enzymes activity in young animals reduces, while in old animals it increases. It should be mentioned that the activity of enzymes in old rats after Livagen administration in the majority of cases approaches to the level of the activity in young animals of control group.

Age Factors↗

[Application of peptide bioregulator in complex treatment of elderly cancer patients].

Improvement of elderly cancer patients' treatment is an acute issue in oncology. The results of stage III rectal and colon cancer complex treatment are far from being satisfactory in this category of patients. In this connection the search for new adjuvant drugs supplementing radio and chemotherapy is urgent. The article describes pioneer experience in complex radical treatment of elderly cancer patients with immunomodulator Vilon included into the scheme of treatment. The obtained preliminary results of investigation suggest recommendation of Vilon application to increase 2-year survival of patients, prevention of post-operative complications, remote complications, recurrences and tumor dissemination, as well as the improvement of the quality of life after employment of aggressive methods of treatment.

Adult↗

[The effect of vilon (Lys-Glu) on 1.2-dimethylhydrazine-induced neoplasia].

The influence of vilon (Lys-Glu) on 1.2-dimethylhydrazine-induced neoplasia in mice has been studied. After treatment with 10 microg/kg, tumors developed in 14.3% which survived until first tumor detection (46 weeks) while, in control group, tumors occurred in 60%. Vilon-related inhibition of preneoplastic alterations in the kidneys was reported.

1,2-Dimethylhydrazine↗

Effect of melatonin and tetrapeptide on gene expression in mouse brain.

A microchip technique was used to study expression of 16,897 clones from a cDNA library in the brain of mice receiving melatonin or tetrapeptide Epithalon (Ala-Glu-Asp-Gly). Expression of 53 transcripts in mouse brain underwent significant changes after treatment with the preparations. Melatonin and Epithalon modified expression of 38 and 22 transcripts, respectively. These preparations produced similar changes in the expression of 6 transcripts. Expression of 1 transcript (Rp119) was inhibited by melatonin, but induced by Epithalon. The target genes are physiologically related to the cell cycle, apoptosis, biosynthesis, processing, and transport of nucleic acids. Comparative study of gene expression in the brain and heart of CBA mice receiving melatonin and Epithalon suggest that these preparations have a tissue-specific biological effect.

Animals↗

Effects of short peptides on lymphocyte chromatin in senile subjects.

Effects of synthetic short peptides (Vilon, Epithalon, Livagen, Prostamax, and Cortagen) on activity of ribosome genes, parameters of common heterochromatin melting, polymorphism of structural heterochromatin (C segments) of chromosomes 1, 9, and 16, and variability of facultative heterochromatin were studied in leukocytes of subjects aged 75-88 years. All the studied peptides induced activation of ribosome genes, decondensation of densely packed chromatin fibrils, and release of genes repressed as a result of age-specific condensation of the cellular euchromatin regions (deheterochromatinization of facultative chromatin). Treatment with Epithalon, Livagen, and Prostamax led to decondensation of chromosome 1 pericentromeric structural chromatin, while Epithalon and Livagen treatment led to changes in chromosome 9 as well. Hence, short peptides activate heterochromatin and heterochromatinized regions of cell chromosomes in senile subjects.

Aged↗

Effect of peptide preparation epithalamin on circadian rhythm of epiphyseal melatonin-producing function in elderly people.

Circadian rhythm of plasma melatonin concentrations in healthy elderly subjects was studied before and after a course treatment with Epithalamin (peptide preparation from the pineal gland). Epithalamin modulated the melatonin-producing function of the pineal gland. During the dark period plasma melatonin concentration increased in subjects with initially lowered activity of the pineal gland, while in subjects with normal epiphyseal function plasma melatonin concentration tended to decrease.

Aged↗

Peptide promotes overcoming of the division limit in human somatic cell.

We previously showed that treatment of normal human diploid cells with Epithalon (Ala-Glu-Asp-Gly) induced expression of telomerase catalytic subunit, its enzymatic activity, and elongation of telomeres. Here we studied the effect of this peptide on proliferative potential of human fetal fibroblasts. Primary pulmonary fibroblasts derived from a 24-week fetus lost the proliferative potential at the 34th passage. The mean size of telomeres in these cells was appreciably lower than during early passages (passage 10). Addition of Epithalon to aging cells in culture induced elongation of telomeres to the size comparable to their length during early passages. Peptide-treated cells with elongated telomeres made 10 extra divisions (44 passages) in comparison with the control and continued dividing. Hence, Epithalon prolonged the vital cycle of normal human cells due to overcoming the Heyflick limit.

Cell Division↗

Effect of epithalamin on circadian relationship between the endocrine function of the thymus and melatonin-producing function of the pineal gland in elderly people.

The effect of epithalamin on circadian rhythms of thymic serum factor titers and melatonin concentrations in the blood of elderly people was studied. Course treatment with epithalamin modulated the rhythm of the thymic endocrine function. The increase in the titer of thymic serum factor at night coincided with the increase in blood melatonin concentration and shift of its acrophase to 3.00, which was characteristic of young people. In elderly people with preserved nocturnal peak of the thymic serum factor titer before therapy the nocturnal (3.00) concentration of melatonin was high and did not change after drug therapy. The correlation between melatonin concentration and titer of thymic serum factor increased after epithalamin treatment.

Aged↗

Effects of bioactive factors of the pineal gland on thymus function and cell composition of the bone marrow and spleen in mice of different age.

The effects of factors from the pineal gland on the titer of thymic serum factor in the supernatant of 3-h thymus stroma cultures, number of stromal precursor fibroblasts and CD4+ cells in the bone marrow, and CD8+ cells in the spleens of adult and old CBA mice were studied in vitro. Epithalamin, Epithalon, and melatonin appreciably increased the titer of thymic serum factor in the supernatant of thymus stroma cultures from mice of different age and increased the percentage of CD4+ cells in the bone marrow suspension from old animals in vitro. The percentage of CD8+ lymphocytes decreased after incubation of splenic cells from old mice with melatonin. The percentage of bone marrow fibroblast precursor cells from adult and old mice did not appreciably change after incubation with the preparations.

Animals↗

Expression of argyrophilic proteins in the nucleolar organizer regions of human thymocytes and thymic epitheliocytes under conditions of coculturing with vilon and epithalon peptides.

Vilon stimulated and Epithalon suppressed the expression of argyrophilic proteins in nucleolar organizer regions of thymocytes and epithelial cells, stimulating or reducing, respectively, the formation, assembly, and transport of ribosomes into the cytoplasm and thus determining the intensity of protein synthesis in these cells. A direct mitogenic effect of Vilon was also revealed: this peptide promoted thymocyte transformation into proliferating blast cells.

Cells, Cultured↗

[The pineal gland's peptides factors and the rhythms of functions of the thymus and bone marrow in animals during aging].

It was investigated the influence of pineal peptides on the aging changes both circadian rhythm of thymic serum factor (FTS) titer in male rats Wistar and circannual rhythms of FTS, the amount of stromal cells-precurcors (CFC-F), granulocyte-macrophage cells-precurcors (CFC-GM), CD4+, Mac-1+ and CD19+-cells in bone marrow of male mice CBA. Epithalamin was injected chronically beginning from 6 month in rats and 4 month in mice. In old animals the rhythmical disturbancers of the indices characterized by loss of fluctuations, displacement of seasonal acrophase, increased or diminished amplitude, inversion of rhythm and desynchronization. After epithalamin injections in rats of 11, 17, 27 months the FTS titer at night increased and in old mice of 23-24 months appeared the peak of hormone level in summer-autumn, restored the difference between the amount of CD4+, Mac-1+-cells in bone marrow in spring and autumn, increased CFC-GM amount in spring, diminished CFC-F in autumn and increased this indice in winter. Epithalon also diminished of CFC-GM and CFC-F amount in old mice in autumn. The retarding age-related disturbances of suprachiasmaticus nucleus of hypothalamus structure, the diminishing corticosterone and testosterone levels at night, the increasing hormones level in summer and the falling in winter plays role in the improvement of thymus and bone marrow rhythmical function in old animals, reseaved epithalamin. The rhythms of most indices rhythms in old animals showed a pattern of adult.

Aging↗