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E Mocchegiani

Publications and source records attributed to E Mocchegiani.

At least 19 recordsLinked to original sources
PubMed1992

In vitro restoration by thymulin of NK activity of cells from old mice.

Old mice show a reduced natural killer (NK) cell activity. Among the causes proposed to explain this defect, both intrinsic failure of NK cells or age-related alteration of microenvironmental factors relevant for NK function, have been taken into consideration. The findings reported in the present paper, demonstrate that thymic peptides, and in particular the facteur timique serique (FTS), more recently called thymulin (ZnFTS) in its zinc-bound form, whose production and activity is generally reduced in old age, is able, when administered in vitro, to restore the crippled NK cytotoxicity of spleen cells from old mice. Neither the zinc-unbound form of the hormone (FTS) nor zinc ions alone are effective. The action is exerted on the basal NK activity and not on IFN-boosted NK cytotoxicity, at variance with the restoration obtained in similar experimental conditions with thyroid hormones, thus suggesting that different mechanisms or maturative steps of NK cells are involved.

Aging↗
PubMed1992

Arginine-containing compounds and thymic endocrine activity.

The frequent association of malnutrition, infectious disease and aging has stressed the role played by some nutrients on the immune efficiency and particularly on the age-dependent immunological decline. Since arginine has been proven to enhance immune efficiency as demonstrated by the observation that supplemental dietary arginine accelerates would healing and increases thymus weight, we have evaluated the influence of oral administration of arginine on the age-associated immune deficiencies and in particular on the reduced thymic endocrine activity, as measured by the circulating level of one of the best known thymic peptides, i.e. thymulin. Thirty days oral treatment with arginine at the dose of 0.03 g/Kg b.w./day in 20 month old mice induces a full recovery of thymic endocrine activity and a significant increase of PHA responsiveness by spleen cells, when compared with untreated age-matched controls. In humans, oral administration of a commercially available arginine-lysin combination (Lysargin, Baldacci, Pisa, Italia) at the dose of 4 gr. of arg. + 4 gr. of Lysine induces a significant increment of thymulin blood level both in elderly and in cancer patients and at peripheral level, an increase of CD4+ lymphocyte subpopulation. These findings confirm the immunomodulation role of arginine and suggest that on the target of arginine as the thymus and particularly its endocrine activity. Furthermore arginine and arginine-containing compounds may offer a new therapeutical approach to restore thymic immunodeficiencies associated with age or secondary to pathologies inducing thymic deterioration such as trauma, stress and cancer.

Animals↗
PubMed1991

Zinc and bromocriptine long-term administration in patients with prolactinomas: effects on prolactin and thymulin circulating levels.

Several studies have demonstrated zinc (Zn), prolactin (PRL) and thymulin (Zn-FTS) interplay: Zn inhibits, in a dose related manner, PRL release from lactotropes in vitro and stimulates thymulin synthesis in vivo both in humans and in animals. PRL receptors are present on thymic epithelial cells (TEC); PRL stimulates TEC trophism and activity. Little is known about the influence of PRL on Zn metabolism, though in prolactinomas we found reduced Zn and thymulin circulating levels. For this reason, we evaluated PRL, Zn, bioactive thymulin (Zn-FTS) and total thymulin (T-FTS: Zn-bound plus Zn-unbound form) serum levels in 58 patients with prolactinomas (PRL: 253 +/- 263 micrograms/L), Zn (82 +/- 23 micrograms/dl), Zn-FTS (2.2 +/- 0.20 log2(-1] and T-FTS (3.7 +/- 0.25 log2(-1] were significantly lower (p less than .01) than those found in age matched controls. Zn-unbound bioinactive thymulin form (FTS) levels were in the normal range. Bromocriptine administration (Brc) (2.5-5 mg p.o., b.i.d. for 9 months) to 20 patients with microprolactinomas lowered serum PRL levels (10.5 +/- 6.2 micrograms/L) and significantly increased (p less than .01) Zn (118.6 +/- 14.7 micrograms/dl), Zn-FTS (3.96 +/- 0.7 log2(-1)) and T-FTS (4.66 +/- 0.7 log2(1)) circulating levels. ZnSO4 administration (400 mg p.o. daily for 3 months) to 6 patients with microprolactinomas, significantly increased (p less than .01) Zn (136 +/- 18 micrograms/dl), Zn-FTS (4.5 +/- 0.5 log2(-1)) and T-FTS (5.6 +/- 0.9 log2(-1)) levels, while caused only a slight decrease in serum PRL concentrations (from 95 +/- 8 to 75 +/- 9 micrograms/L; p: NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Thymic endocrine activity in children with idiopathic growth-hormone deficiency.

Experimental and clinical evidences suggest that thymic endocrine function is modulated by the neuroendocrine network and in particular by growth hormone. The plasma of thymulin has been found reduced in congenital hypopituitarism and increased in acromegalic conditions when compared with the values observed in age-matched controls. In the present paper we have investigated in congenital GH-deficient children the effect of one year therapy with GH on the plasma level of thymulin, IGF-1 and plasma zinc; this last parameter has been checked because zinc is required for thymulin activity and modulates IGF-1 production. The basal thymulin and IGF-1 values are lower in GH deficient children than age-matched controls whereas zinc levels show a slight reduction. GH therapy induces a significant increment both of thymulin and IGF-1 levels and a slight increase of plasma zinc. A positive correlation has been found between zinc values and thymulin activity but not between GH and thymulin. Whether the recovery of thymulin production in GH deficient children by GH therapy is mediated by IGF-1 or by bioavailability of zinc ions remains to be established.

Adolescent↗
PubMed1990

Neuroendocrine-thymus interactions. I. In vitro modulation of thymic factor secretion by thyroid hormones.

Several in vivo experimental and clinical studies suggest that the production of thymic hormones, such as thymulin (Zn-FTS), is modulated by thyroid hormones. It was not determined in these studies, however whether such modulation is exerted directly on the thymic epithelial cells which synthesize and secrete thymic hormones. In order to discriminate between direct and indirect modulation, the effect of thyroid hormones on the in vitro production of thymulin by whole thymic organ culture, as detected by the rosette inhibition assay, has been investigated. Donors of thymuses were young 6N-propyl-2 thiouracil (PTU)-treated hypothyroid Balb/c mice and normal littermates. Thymuses from hypothyroid mice were shown to produce concentrations in vitro nearly undetectable of thymic hormone, when compared to thymuses from normal mice. The in vitro addition of triiodothyronine (T3) caused a complete recovery of the thymic hormone production by thymuses from hypothyroid mice and an increased synthesis even by normal thymuses over control values. The complete blockade of in vitro thymic hormone production with cycloheximide, which inhibits mRNA and protein synthesis but not thyroid hormone permissive actions, suggests that the T3 induced increment of thymic hormone level in the supernatant is due to de novo synthesis. Furthermore, the number of thymulin-producing cells, as detected by immunofluorescence using a specific antithymulin monoclonal antibody, which is quite low in thymuses from hypothyroid mice, is completely regained after in vitro incubation with T3. These findings support the idea that the modulation of thyroid hormones on thymic endocrine activity is directly exerted at thymic level.

Animals↗
PubMed1990

Prolactin, thymulin and zinc in chronic hemodialysis: effect of renal transplant.

The interrelationships between PRL, thymulin and Zn, were studied in 25 patients with chronic renal failure (CRF) undergoing kidney transplantation and immunosuppressed with cyclosporine A (CsA). The possible role of serum PRL levels in predicting allograft rejection was also investigated. Before the kidney transplant serum PRL levels were significantly higher than in normals (mean +/- SE, 28.3 +/- 7.1 vs 7.5 +/- 0.6 micrograms/l, p less than 0.001) and their response to TRH (200 micrograms iv) was impaired (mean delta % at peak, 45.4 +/- 9.5 vs + 641 +/- 47.5, p less than 0.001). After kidney transplantation a dramatic decrease in serum PRL concentrations was observed in all patients, followed by a slight upward trend in the following two weeks, while TRH test administered on 3rd, 7th and 14th day, induced a progressive increase in serum PRL responses (delta % at peak, 201 +/- 43.3, 220 +/- 37.1 and 305 +/- 15.5, respectively). No difference in serum PRL patterns was observed between patients with (8 cases) and without (17 cases) clinical features and kidney fine needle biopsies suggestive of rejection. Basal serum Zn levels of patients with CRF (18.1 +/- 0.6 mumol/l) were similar to those observed in normals (17.7 +/- 0.2 mumol/l) and without any correlation with serum PRL levels. A decrement in serum Zn was recorded during CsA infusion and on the first day after the surgery, followed by a slight and slow upward trend. Basal serum thymulin titers were low [2.92 +/- 0.18 (1/log2)], were further reduced after CsA infusion [1.68 +/- 0.15 (1/log2)] and returned to the pretransplant levels in the two weeks after grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Zinc and thymic hormone-dependent immunity in normal ageing and in patients with senile dementia of the Alzheimer type.

Plasma zinc levels were measured in young controls, aged controls, patients with dementia of the Alzheimer type and patients with non-Alzheimer type dementia. Zinc levels decreased with age; however, no difference was found between patients with dementia and age-matched controls. Plasma levels of active or inactive thymulin, a nonapeptide produced and released by the thymus gland, were also determined in young controls, aged controls, patients with dementia of the Alzheimer type and patients with non-Alzheimer type dementia. Basal levels of active thymulin were decreased in aged controls and in patients with dementia. In vitro reactivation of thymulin after zinc addition to plasma samples was decreased in aged controls. A further impairment of thymulin reactivation was present in patients with dementia. A significant age-dependent decrease in lymphocyte proliferation after mitogen stimulation was found; however, no difference was present between aged controls and patients with dementia of the Alzheimer type. Interleukin-2-induced cell activation and its effect on mitogen-induced proliferation were also measured; once again only an age-associated decrease was found. The endocrine function of the thymus of patients with dementia appears to be more compromised than that from aged controls.

Adult↗
PubMed1990

Recovery of low thymic hormone levels in cancer patients by lysine-arginine combination.

Thymic hormones are required for maturation and maintenance of the immune efficiency. It has been previously demonstrated that with advancing age there occurs a progressive reduction of the plasma level of one of the best known thymic peptides, i.e. thymulin, and that the administration of an amino acid combination (lysine-arginine, as present in the commercial preparation Lysargin, Baldacci, Italy) to elderly individuals is able to increase the synthesis and/or release of thymulin to values comparable to those recorded in young subjects. In the present paper we report evidence that cancer patients show much lower thymulin values than those recorded in healthy age-matched individuals and that the oral administration of the amino acid preparation is able to significantly increase thymulin levels even over the values of age-matched controls and to increase the number of peripheral T-cell subsets. It is suggested that such an effect is mediated through the known secretagogue activity of the amino acids on the pituitary release of growth hormone, which has a modulating effect on the thymic endocrine activity.

Adult↗
PubMed1990

Influence of growth hormone on thymic endocrine activity in humans.

The thymus produces humoral factors that induce the proliferation and differentiation of T cells which are responsible for cell-mediated immunity. Experimental data have suggested that this thymic hormone production is modulated by the neuroendocrine network and, in particular, by growth hormone (GH) and thyroid hormones. To study the role played by GH in thymic endocrine activity in humans, the circulating level of one of the best known thymic peptides, i.e. thymulin (Zn-FTS), has been determined, after a washout period of 2 weeks without GH treatment, in GH-deficient children before and after a single injection of GH. The basal thymulin level is consistently lower in GH-deficient children than in healthy age-matched controls. A single injection of GH induces a significant increment of the thymulin level for at least 48 h. Since thymulin activity may also depend on zinc bioavailability, on thyroid hormone turnover and on the eventual presence of thymulin-inhibitory substances, all these aspects have been checked. No supporting evidence regarding the existence of these kinds of interferences in GH-deficient children has been substantiated. A positive correlation has been found between the serum level of insulin-like growth factor I, but not of GH, and thymulin activity. These data suggest that GH may directly or indirectly modulate the thymic endocrine function in humans. Whether and to what extent such a modulation is relevant to the functioning of the immune system remains to be ascertained.

Adolescent↗
PubMed1990

Levels of zinc and thymulin in plasma from patients with Crohn's disease.

Levels of zinc in plasma from patients with Crohn's disease were significantly lower than those of sex and age matched controls. We also measured the level of plasmic thymulin, a hormone released by the thymus gland, which in its active form binds one zinc molecule. The zinc unbound form of thymulin is biologically inactive and its level in the blood is a very sensitive marker of even marginal zinc deficiency. Levels of active thymulin were significantly reduced in plasma from patients with Crohn's disease, whereas plasma concentrations of the inactive form was higher than in controls. The in vitro addition of zinc ions restored thymulin activity in plasma from patients with Crohn's disease, and induced the disappearance of the inactive form. These findings suggest the existence of a zinc dependent alteration regarding the biological function of thymic hormones in patients with Crohn's disease. Such a defect might explain some of the immunological abnormalities observed in these pathological conditions.

Adult↗
PubMed1989

Thyroid-thymus interactions during development and aging.

A good body of experimental and clinical evidences suggests that bidirectional interactions do exist between the neuroendocrine system and the thymus activity. In particular, thymic endocrine activity seems to be strongly influenced by neuroendocrine signals. In this context, studies performed in hyper- and hypothyroid subjects and in the low triiodothyronine (T3) syndrome, which affects premature infants, have clearly shown that thyroid hormones and in particular T3 physiologically modulate thymic peptide secretion. In vitro experiments, with thymic whole-organ cultures, have demonstrated that thyroid hormones exert their action on the epithelial cells of the thymus deputed to synthesize and secrete thymic peptides and that such an effect does not seem to depend on the known permissive action of thyroid hormones.

Adolescent↗
PubMed1989

Effect of oral zinc administration on prolactin and thymulin circulating levels in patients with chronic renal failure.

High serum PRL and low zinc (Zn) levels are common findings in patients with chronic renal failure (CRF); in such patients serum Zn concentrations have been reported to be inversely correlated to serum PRL levels. Moreover, Zn regulates both thymus growth and the biological activity of the thymic hormone thymulin, and PRL-thymic interrelationships have been described. To determine whether hypozincemia alters serum PRL and plasma thymulin concentrations in CRF, 9 men with CRF treated by chronic hemodialysis were given 400 mg/day Zn sulfate, orally (4.96 meq/day Zn), for 6 months. Before treatment, serum PRL levels were significantly higher (P less than 0.001) in these patients than in normal men [mean, 28.7 +/- 20.7 (+/-SD) vs. 7.5 +/- 3.7 micrograms/L], and their serum PRL response to TRH (200 micrograms, iv) was impaired (mean maximal percent increase, 38.2 +/- 10.9 vs. 641 +/- 335; P less than 0.001). The plasma Zn-bound bioactive thymulin titer (1.3 +/- 0.7 1/log2), total thymulin titer (Zn-bound plus Zn-unbound forms, 2.1 +/- 0.8 1/log2), and serum Zn (13.1 +/- 2.4 mumol/L) were lower (P less than 0.001) in men with CRF than in normal men. Zn therapy did not induce any significant change in basal and TRH-stimulated serum PRL levels, while serum Zn levels significantly increased, reaching the normal range after the first week of treatment (17.8 +/- 6.3 mumol/L). Plasma total thymulin increased rapidly, reaching normal levels after 1 week, but Zn-bound thymulin increased modestly during the first month of treatment and more after 3 and 6 months of treatment. There was no age-related difference in plasma thymulin levels during therapy. We conclude that oral Zn administration in patients with CRF significantly increases both total and Zn-bound thymulin, but does not modify basal and TRH-stimulated serum PRL levels. The observation that Zn supplementation markedly increased plasma thymulin levels in uremic patients suggests that Zn is a potent stimulus for thymic hormone synthesis, and it can reverse the age-related diminution of thymic activity in CRF patients.

Adult↗