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Biomedical subjects

M Muzzioli

Publications and source records attributed to M Muzzioli.

46 records · Page 3Linked to original sources

Recovery of age-related decline of thymic endocrine activity and PHA response by lysin-arginine combination.

The frequent association of malnutrition, infectious diseases and aging has stressed the role played by some nutrients on the immune efficiency and by nutrient supplementation on the age-dependent immunological decline. In the present paper there are reported evidences that oral administration of two amino acids--lysine and arginine--recovers, in old Balb/c mice, the mitogen responsiveness, the expression of T-cell markers and the production of thymic serum factor (thymuline). The effect of the amino acids or of their combination, as present in a commercially available form (Neoiodarsolo), seems to consist mainly of the reactivation of the endocrine activity of the thymus. Similar reactivation is achieved also in old humans. These data suggest that the age-dependent decline of thymic hormonal activity is not an intrinsic and irreversible event and that some nutritional intervention, such as amino acid treatment, likely through the stimulation of neuroendocrine network, may reactivate the endogenous production of thymic hormones.

Aging↗

Amiloride inhibits the PHA-evoked mouse splenic lymphocyte proliferation.

The present study was aimed to ascertain whether Na+ influx can be involved in regulation of blastogenesis and proliferation of PHA stimulated mouse splenic lymphocytes. The cells were cultivated in the presence of different concentrations of amiloride, an inhibitor of passive Na+ influx, and cellular activation was monitored by 3H-thymidine incorporation and blast index determination. The drug was not toxic and inhibited cell growth in concentrations ranging from 1 X 10(-3) to 1 X 10(-5) mmol/ml. The results are in agreement with the hypothesis that Na influx is necessary for PHA evoked mouse splenic lymphocyte activation.

Amiloride↗

In vitro block of murine L 1210 leukemia cell growth by amiloride, an inhibitor of passive Na+ influx.

The present study was aimed to decide whether Na+ influx can be involved in regulation of murine L 1210 leukemia cell growth. Cells were cultivated in the presence of different concentrations of amiloride and cellular growth was monitored by 3H-thymidine incorporation/10(5) cells. This drug inhibited cell growth in concentrations ranging from 1 X 10(-5) to 1 X 10(-3) mmol/ml. Even short time treatments with amiloride caused irreversible alterations: the cells, although survived, lost their ability to divide. The results support the hypothesis that Na+ influx is necessary for the duplication of tumor cells.

Amiloride↗

Decline of thymus-cell potential in diabetic and aged men.

Human peripheral blood thymus lymphocytes are capable of forming, when stimulated by phytohemagglutinin, single-cell-derived colonies in an in vitro soft-agar system. Blood samples were obtained from 33 healthy men ranging in age from 20 to 96 years of age and from 11 diabetic men ranging in age from 42 to 60 years and 11 age-matched controls. With increasing age a reduction in the number of single-cell-derived colonies and a decrease in their residual in vitro proliferation potential was observed. Such a defect appeared at an earlier age in diabetic men. The defect in proliferative potential of cells of either old or diabetic men did not depend on factors present in their blood plasma.

Adult↗

Age-dependent decline of T-cell cloning potential in mice.

Mice spleen cells capable of forming, under stimulation by phytohemagglutinin (PHA), single-cell derived colonies in an in vitro soft-agar system, show with advancing age a progressive reduction of their number, which occurs earlier than the decline of PHA response in fluid phase. In addition to their reduced number, old colony-forming T-cells show the same phenomena recorded in fibroblasts; for example, a decrease of their residual in vitro proliferation potential, as measured by the size of the colonies, reached during the culture period. The reduced number of responding units and the decreased colony size seem to be distinct phenomena, since in the immunodeficiency state of hypopituitary dwarf mice only the first defect is observable, whereas the size distribution is normal. Both the reduced number of T-cell colonies and their decreased proliferative potential in vitro observed in old age, can be restored by transplanting a neonatal FTS ("facteur thymique serique")-producing thymus, but not by injecting isolated thymocytes into old mice. A correlation seems to exist between the decline of T-cell colony potential with advancing age and the progressive deterioration of thymic endocrine activity.

Aging↗

Recovery of age-dependent immunological deterioration in Balb/c mice by short-term treatment with L-thyroxine.

The progressive decline of immune efficiency with advancing age has been investigated in Balb/c mice by measuring the spleen-cell responsiveness to both T- and B-mitogens and the capacity to form plaques after immunization with sheep erythrocytes. While the responsiveness to concanavalin A and lipopolysaccharide is not significantly decreased in old mice, the responsiveness to phytohaemagglutinin and the plaque-forming-cell capacity progressively diminish with advancing age. Such a functional decline has been correlated with the age-associated deterioration of the neurohormonal balance and particularly with the reduction of thyroxine blood levels. Reconstitution experiments carried out by treating animals of increasing ages with 15 daily injections of L-thyroxine have demonstrated that such a treatment is able to restore the age-related decline of immune efficiency, and that this recovery is associated with the reactivation of the thymic endocrine activity. These data are consistent with the idea that the neurohormonal balance may influence the immune efficiency and that its derangement with advancing age may represent one of the factors responsible for the aging of the immune system.

Animals↗

Thymus-endocrine interactions during ageing.

The hypotesis of the thymus acting as biological clock for ageing is revisited. On the basis of data on the endocrine action of the gland, the age-dependent involution of the thymus is postulated to play a fundamental role on the deterioration of the immunological as well as the endocrine functions. Data either on beta-adrenergic responsiveness to Isoproterenol or on hormonal balance, tested on animal model with different degree of thymus efficiency, support this hypothesis.

Aging↗

Thymus-dependent reversibility of physiological and isoproterenol evoked age-related parameters in athymic (nude) and old normal mice.

In order to assess the relationship between the thymus and aging processes, a linear age-dependent parameter in mice such as the response of the submandibular gland to an injection with isoproterenol has been evaluated in athymic (nude) and thymectomized Balb/c mice. The IPR-induced DNA synthesis is reduced in both experimental groups when compared to untreated normal littermates and is recovered by grafting a neonatal thymus. Moreover, the impairment of IPR response in old animals is recovered to young levels by grafting one neonatal thymus one month before test. Neonatal thymus grafts in old recipients are also able to correct their abnormal serum levels of triiodothyronine and insulin. The influence of neonatal thymus on such non-immunological and age-related parameters suggests that this gland can control aging processes, probably through its implication with the endocrine system.

Age Factors↗

Differential effect of pregnancy or gestagens on humoral and cell-mediated immunity.

The reactivity of spleen lymphocytes in a mixed lymphocyte culture and the in vivo PFC response to sheep erythrocytes have been evaluated in pregnant female mice and data compared with those observed in virgin sexually mature female mice daily treated either with progesterone or human chorionic gonadotropin (HCG) or human prolactin. The mixed lymphocyte reactivity is depressed at mid-pregnancy, whereas PFC response is increased. Comparable immunological modifications have been found in mice treated with HCG, but not in animals treated with progesterone or prolactin. The similarity between HCG treatment and pregnancy suggests that the rate of gonadotropin release may be one of the earliest events responsible for the immunological disturbances present during pregnancy, although its action on the lymphoid system seems to require the presence of the ovary. From these data and from the observation that HCG increases the PFC response also in thymusless nude female mice, it can be deduced that it acts on both T and B cells.

Animals↗