[Influence of the pineal gland's factors on the cell composition of the bone marrow in animals of different age in conditions of changed thymus functional state].

The role of the thymus in the influence of pineal gland on the number of stromal precursor cells to colonies of fibroblasts (CFU-F), progenitor cells to granulocyte-macrophage colonies (CFU-GM), CD3+, CD4+ and CD8+ cells in the bone marrow of adult and old mice CBA/Ca was investigated. False-operated and thymusectomized mice were injected Melatonin in the evening (spring season) or Epithalamin in the morning (summer and autumn). After the injection of Melatonin into adult mice the number of CFU-F and the value of the ratio CFU-F/CFU-GM decreased in false-operated animals, whereas the same indicators increased in thymusectomized animals. Under the influence of Melatonin, the ratio of CD4+/CD8+ cells increased in mice with an intact thymus and reduced in mice with a removed gland by increasing the number of CD8+ cells. The injection of Epithalamin led to the increasing in the number of CFU-F in summer, but did not lead to that in the autumn; the effect diminished in mice with a removed thymus. The orientation of changes of the indices under the influence of the pineal gland's factor in adult mice with an intact thymus corresponds to their seasonal fluctuations. After the injection of Melatonin into old mice CFU-F/CFU-GM ratio slightly reduced in false-operated animals and did not change in thymusectomized ones. Under the influence of melatonin the CD4+/CD8+ ratio of cells slightly increased in old mice with and without the thymus. Thus, the influence of the pineal gland' factors (Melatonin, Epithalamin) on the cellular structure of bone marrow, first of all on the cells of the microenvironment, in adult mice has an adaptive character and is realized with the participation of the thymus. In old mice, the thymus is also involved in the action of Melatonin on bone marrow, but the effect is less pronounced and is manifested mainly through changes in amount of CFU-GM.

[Thymus and adaptive changes of bone marrow cell composition in animals of different age].

The influence of thymus removal or administration of thymalin, thymic peptide factor, on number of cells-precursors for colonies of fibroblasts (CFC-F) and for granulocyte-macrophageal colonies (CFC-GM), CD(4+)-cells in bone marrow in CBA mice of different age in some seasons was investigated. It was shown that in adult mice the orientation of influence thymic activity modulation on amount of these types cells is dependent from seasons. It was shown the season possibility of direct effect of thymic stroma supernatant, in which was thymic serum factor (FTS), or the synthetic FTS on the amount of CFC-F and CFC-GM in bone marrow of adult mice; in old mice thymic supernatant increased in vitro the amount of CD(4+)-cells. FTS level in old mice increased after administration of thymalin, the rhythm of CD(4+)-cells number in bone marrow and of corticosterone serum content restored.

Effect of tripeptides on lymphoid and stem cells.

Tripeptides T-36 and, particularly, T-38 in concentrations of 0.1, 1, and 10 ng/ml inhibited proliferation of primary trypsinized embryonic mesenchymal stem cells, rat transplantable KF-1 fibroblasts, and human erythromyelosis K-562 cells. Inhibition of proliferation in embryonic and immortalized cells under the influence of tripeptides probably reflects antitumor activity of these substances. Tripeptides had no effect on lymphocyte survival and their adhesive, cytotoxic, and induced proliferative activities. T-36 did not modulate the proliferative properties of erythromyelosis K-562 cells. Tripeptides did not change engulfment activity and spontaneous and induced bactericidal activities of granulocytes. T-36 in a concentration of 0.1 ng/ml increased spontaneous proliferation of normal lymphocytes. These data suggest that tripeptides stimulate nontumor immune cells in adult people.

[THYMIC HORMONES, ANTIOXIDANT ENZYMES AND NEUROGENESIS OF BULBUS OLFACTORIUS IN RATS WITH PARKINSONISM: THE EFFECT OF MELATONIN].

The adult rats received both neurotoxin 6-hidroxidophamine and neurotoxin and melatonin. It was investigated a link between the disturbances of the brain antioxidant enzymes activity and thymic endocrine function, as possible pathogenic factors of parkinsonism, with changes in the number of neural stem cells (NSC) in the bulbus olfactorius. Rats with motor asymmetry in the apomorphine test and significant damage of the dopaminergic neurons in the-substantia nigra have decreased levels of superoxide dismutase, catalase and glutathione peroxidase activities in striatum (1.3-1.4 times) and blood thymulin content (8 times) compared to control group. On the contrary, examined indices were not changed in rats without motor asymmetry and correspondingly partly damaged neurons. The number of nestin(+)-cells in the bulbus olfactorius of rats without motor asymmetry increased from 91.2% to 99.3% and remained unchanged after melatonin administration course (10 mg/kg during 18 days). Melatonin administration resulted in the decrease in the number of nestin(+)-cells along with significant elevation of the decreased antioxidant enzymes activity and blood thymulin content in rats with circulatory movements. Possibilities of the enhancement of NSC differentiation in bulbus olfactorius into neuronal direction in such animals has been discussed. The conclusion about the potential use of melatonin as a neuroprotector in parkinsonism therapy has been made.

Effect of thymus grafts of various ages on the immune system formation in CBA mice.

An attempt has been made to govern the development of immunological capability in CBA mice by means of transplantation at an early postnatal period of thymus from donors of various ages. The results have shown that in thymectomized animals, apart from a well known gradual decline with the donor's age in restorative functions of the transplanted thymus, there was at the age of 22 months a phase of inhibitory influence on the recipient's immune system. In intact animals, transplantation of the thymus from a 5-day-old donor caused a decrease and that from a 22-month-old donor caused an increase in the development of the capacity for immune response. Taken together, our findings indicate an active role of the thymus both in the formation of the immune system and in its alteration with aging.

Increased glycation and pigmentation of collagen in aged and young parabiotic rats and mice.

Changes of non-enzymatic collagen glycosylation were followed in 2- and 24-month-old rats and mice and in parabiotic animals of the same age. With advancing age increased glycation of collagen was observed in both old male Wistar rats and white mice. Further it was demonstrated that both aortal and skin collagen of young animals is rapidly non-enzymatically glycosylated in the common milieu created by parabiotic animals and the proportion of non-enzymatically incorporated glucose approaches in the young counterparts the level found in old individuals. Similar trends as with non-enzymatic glycosylation were found with a fluorescent (370/440 nm) product present in both categories of collagen preparations. This fluorescence was higher in old animals and was considerably increased in the young counterpart of the parabiotic couple 6 weeks after operation. The nature of the fluorescent product appears different from pyridinoline and remains to be elucidated.

Functional rearrangement of lymphohemopoietic system in heterochronically parabiosed mice.

This study examines some characteristics of the lymphohaemopoietic system of heterochronically parabiosed CBA mice. It was found that a decline of the primary immune response in a young mouse sutured with an old one is accompanied with the diminution of: bone marrow and thymus cellularity; thymus weight; haemopoietic stem cells (CFC-S) and granulocyte-macrophage precursor cells (CFC-C) contents in the femur, and stromal precursor cell (CFC-F) contents both in the femur and thymus. All the indices tested, including the immune response level, in old parabionts vs. old single mice remained unchanged. In the spleen, the considerable variations of splenic weights in the mice of different control and experimental groups have been found. At the same time, no significant changes in the cellularity and CFC-F number in the spleen of all examined groups of animals have been observed. The findings strongly indicate the considerable rearrangement of lymphohaemopoietic and stromal tissues in the central organs of the immune system, namely, bone marrow and thymus of young mice due to the parabiosis with old ones.

Stromal hemopoietic microenvironment in aging.

The bone marrow content, proliferative potential and proliferative activity of precursor cells for stromal fibroblast colony forming cells (CFC-F) were investigated in young and old CBA mice. The relationship between CFC-F and the number of bone marrow nucleated cells and granulocytic-macrophagal precursors (GM-CFC) was studied as well. The results obtained showed increased CFC-F contents in old animals. The proliferative potential of old mice CFC-F did not appear to differ from that of young animals. The proliferative activity of bone marrow CFC-F and hemopoietic stem cells--spleen colony forming cells (CFC-S) was studied by determining the sensitivity to hydroxyurea administration. The responses were almost the same in young and old mice. A direct correlation between CFC-F and nucleated cells and GM-CFC precursors was found in young mice, but not in the old animals. The results of the present study have pointed to the reorganisation of the stromal tissue microenvironment in bone marrow in old age.

Age-related changes of cells involved in immune responses.

The interaction between T- and B-lymphocytes in the immune response to sheep reythrocytes was revealed by estimating the direct plaque-forming cells in mice CMA of various age. Investigations with a transfer of cells to irradiated and intact recipients were performed. We found a 23-fold diminution of the immune response in mice aged 26-28 months, when compared with that in mice aged 8 months. The first signs of a disturbed activity of the immune system were found in animals whose age did not exceed the half of their average lifespan. The injection of B-lymphocytes from young animals does not give rise to the immune response of old nonirradiated recipients. The injection of young b-lymphocytes to old irradiated recipients, being primed by antigen using Playfair's technique before irradiation, results in the highest response than it is in other combinations. The effect of disturbances in the interaction between T- and B-cells on the mechanism of age-related changes of the immune response is discussed.

[Regulating effect of pineal gland peptides on development of T-lymphocytes in CBA aging mice: role of microenvironment of immune system organs and neuroendocrine factors]. / Reguliruiushchee vliianie peptidov épifiza na razvitie T-limfotsitov u myshei linii CBA pri starenii: rol' mikrookruzheniia organov immunnoi sistemy i neiroéndokrinnykh faktorov.

Studies were undertaken on the development of T-lymphocytes in adult and old CBA mice and its changes at aging after injections of pineal gland peptides. It was shown that in old mice the disturbances of T-cells differentiation are registered in bone marrow, thymus, spleen and characterized by the changes of lymphocyte markers expression, migration and proliferation of cells. In old mice FTS titer, melatonin and testosterone levels decreased, the balance of noradrenalin and serotonin in hypothalamus and the cell composition of microenvironment immune systems organs impaired. After chronic (18 mo) administration of the pineal gland preparation epithalamin the amount of stromal cells-precursors, CD4+ and Mac-1(+)-cells in old bone marrow increased, improved the migration of T-cell precursors from bone marrow to thymus and their proliferative potential. The proportion of CD3+, CD4+CD8-, CD4-CD8+, Mac-1(+)-cells in old thymus increased, while that of CD44(+)-cells decreased. The proportion of CD4-CD8(+)-cells in spleen increased. The most number of indices and their balance showed a pattern of adult mice. In old mice after epithalamin the balance of amines in hypothalamus improved, concentration of melatonin in pineal gland, testosterone and FTS titer in blood increased. Epithalon has also the possibility to increase of thymic endocrine function.

[The pineal gland's peptides factors and the rhythms of functions of the thymus and bone marrow in animals during aging]. / Peptidnye faktory épifiza i ritmy funktsii timusa i kostnogo mozga u zhivotnykh pri starenii.

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.

[Effect of the transplantation of heterochronic thymus on the development of immunological reactivity in CBA mice. 2. Transplantation to intact animals]. / Vliianie peresadki geterokhronnogo timusa na stanovlenie immunologicheskoi reaktivnosti u myshei CBA. 2. Transplantatsiia intaktnym zhivotnym.

The effect of transplantation of thymus from donors of different age on the immune system development was studied in the newborn CBA mice. The thymuses of 22 month and 5 day old donors were shown to exert different effects: accelerated (early attainment of the plateau) and decelerated (late attainment of the peak) maturation of the immune system in the recipients. This fact is discussed with respect to interaction of transplanted and host thymuses.

[Effect of antihypertensive therapy with captopril on gluco- and mineralocorticoid receptors of peripheral blood lymphocytes in hypertensive patients of various age]. / Vliianie gipotenzivnoi terapii kaptoprilom na retseptory gliuko- i mineralokortikoidov v limfotsitakh perifericheskoi krovi bol'nykh gipertonicheskoi bolezn'iu raznogo vozrasta.

Binding of 3H-dexamethasone and 3H-aldosterone by peripheral lymphocyte receptors was investigated in healthy persons and hypertensive patients before and after 2-week captopril treatment. The number of glucocorticoid and mineralocorticoid binding sites was increased in hypertensives vs normotensives. The treatment with the ACE inhibitor captopril led to activation of hormone-receptor interactions. There was a more marked rise of the number of receptors in middle-aged (44-55 years) hypertensives vs elderly (61-80 years) subjects after captopril treatment.

[Changes in the mechanisms of the phagocytic activity of peritoneal macrophages during aging]. / Izuchenie mekhanizmov izmeneniia fagotsitarnoi aktivnosti peritoneal'nykh makrofagov pri stareniia.

A study of the phagocytic activity in young and old rats showed that the amount of functionally active cells among macrophages of the peritoneal exudate falls with ageing. The ability of macrophages to fix, absorb and digest heterologous cells (chicken erythrocytes) decreases. This decrease of phagocytic activity is to a considerable extent due to serum factors. Probably, the age changes in the macrophages functional activity play a definite role in decreasing the efficiency of defence mechanisms during senescence.

[Effect of splenectomy on the development of neonatal lymphoid organs transplanted to animals of varying age]. / Vliianie splenéktomii na razvitie limfoidnykh organov novorozhdennykh, peresazhennykh zhivotnym raznogo vozrasta.

The effect of splenectomy on the development of newborn thymus and spleen grafted under the kidney capsule of young and old mice has been investigated. Preliminary splenectomy is shown to increase cell counts in grafted spleen that is more conspicuous in young recipients as compared with old ones. This result suggests a decrease with age in the inhibitory effect of the host spleen on the maturation of spleen grafted from newborn donor. Combined transplantation of newborn thymus and spleen has revealed a decrease of cell counts in the donor spleen grafted to the young splenectomized recipients and, on the contrary, increase of this parameter in old ones. Immune response in donor spleen with combined transplantation of the thymus to the old splenectomized recipients is much higher as compared with the same parameter in recipient without splenectomy. It is concluded that partial destruction of the old immune system is essential for its correction.

[Influence of the recipient's age on the effect of transplanting lymphoid organs from newborn donors]. / Vliianie vozrasta retsipienta na éffekt transplantatsii limfoidnykh organov novorozhdennykh donorov.

The development of immunological capacity of newborn thymus and spleen grafted under the kidney capsule of different-age recipients was investigated. The grafts functions appear to depend strongly upon the macroenvironment of the organism where their development occurs. Therefore+ the favourable influence of young environmental factors, gradually decreasing with the recipient age to become immunosuppressive in old animals is obtained. These data indicate a predominant significance of the macroenvironmental factors both in maturation of the immune system and its alteration during aging.

[Age-related changes in glucocorticoid and mineralocorticoid receptors in lymphocytes of healthy persons and patients with hypertension]. / Vikovi zminy retseptoriv gliuko- i mineralokortykoïdiv v limfotsytakh zdorovykh i khvorykh na gipertonichnu khvorobu liudei.

It has been found that the number of glucocorticoid receptors in lymphocytes of the peripheral blood of healthy elderly subjects increases, while the number of mineralocorticoid receptors decreases. The mechanisms of hormone-receptor interactions in hypertension are activated: the number of glucocorticoid and mineralocorticoid binding sites grows in hypertensive patients. Still a more essential rise in the number of receptors is observed in mid-age hypertensive patients than in elderly ones.

[Comparative immunological and electron microscopic study of the structure of E-RFC and OKT-3+ lymphocytes from human blood]. / Sravnitel'noe immunoélektronno-mikroskopicheskoe issledovanie stroeniia E-ROK i OKT-3+ limfotsitov krovi cheloveka.

Methods of immune electrone microscopy have revealed that OKT-3+ cells and E-RFC of human blood have a similar ultrastructure. Definite morphologic spectrum is observed within each of these fractions, that testifies to the heterogeneity of surface markers of circulating T-lymphocytes and their ultrastructure.

[Role of immune complexes in the pathogenesis of atherosclerosis: age-related aspect]. / Rol' immunnykh kompleksov v patogeneze ateroskleroza: vozrastnoi aspekt.

The experiments on 40 young and old rabbits which were given exogenous immune complexes (IC) for a month were made to study the changes in the blood levels of circulating IC (CIC), cholesterol and lipoproteins and their relation to the degree of atherosclerotic lesions to the vessels. The old animals that had low levels of minor CIC and insignificant transient increases in blood lipids were demonstrated to develop the same vascular atherosclerotic lesions as did the young animals that had higher levels of CIC and lipids. Some old animals retained a high immunological responsiveness (high CIC levels), which was accompanied by high incidence rates and extent of aortic lipid lesions. The findings make us conclude that the role of IC in atherosclerotic responsiveness increases with age.