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C Viticchi

Publications and source records attributed to C Viticchi.

34 records · Page 2Linked to original sources
PubMed1986

Impaired adaptive receptor regulation: an index of aging?

Many neuroendocrine functions are altered in old animals and their study may represent important steps in the understanding of the mechanisms of aging. A deeper insight, however, can be achieved by investigating the responsiveness to stimuli, which may reveal alterations not evident in the unstimulated conditions. At this level of study, many of such impairments have been found to be caused by receptor changes. In the present paper a third level of study is suggested in order to gain evidence of some remote failure of adaptive processes strictly linked to intimate mechanisms of aging. As at the second level of study different receptor characteristics can frequently be found at the basis of age-related alterations of biological responsiveness, at the proposed third level altered capacity of receptor regulation may be hypothesized as responsible for altered cell adaptation following hormone and drug stimuli. Experimental data are given which support this view. The possibility that receptor regulation may be used as an index of aging is suggested. This hypothesis leads to the problem of judging the validity of biological parameters deputed to represent good indices of aging. In order to solve this problem, the potential use of a mathematical model of mortality kinetics is discussed.

Adaptation, Physiological↗
PubMed1985

Thymic regulation of brain cortex beta-adrenoceptors during development and aging.

The influence of the thymus on beta-adrenoceptors has been studied in the brain cortex of mice during developing and aging. Affinity of beta-adrenoceptors shows no statistically significant changes in the various animal models investigated. Receptor density shows a fall in both athymic nude mice and in old normal mice. Receptor density, in particular, decreases progressively with advancing age. It has been demonstrated that thymus exerts a regulatory role in both development and aging, as a neonatal thymic graft is capable of reversing the receptor impairments found in young athymic nude mice and in old normal mice.

Aging↗
PubMed1984

Centrophenoxine-induced increase of beta-adrenoceptor density in brain cortex of old mice.

The influence of centrophenoxine treatment on beta-adrenoceptor density has been studied in the brain cortex of old mice. One group of 21-mth-old mice was injected intraperitoneally with 3.8 mg/day centrophenoxine daily for 5 days. A second group received the same daily treatment for 40 days. Two other groups of untreated mice of the same age served as controls. Receptor affinity showed no statistically significant changes in the four different groups investigated. As regards the receptor density, an increasing trend has been elicited between the 5-day treated mice and their controls; however, the increase was not statistically significant. The second group of old mice treated with centrophenoxine for 40 days exhibited a statistically significant increase in receptor density when compared with untreated animals. The modulation of beta-adrenoceptor density may be explained as the result of either a direct action on synaptic structure or an indirect effect mediated by thyroid hormones.

Aging↗
PubMed1982

Age-dependent decrease of beta-adrenoceptor density in the submandibular glands of mice and its modulation by the thymus.

Beta-adrenergic receptors were characterized in submandibular glands of ageing mice and old mice grafted with a neonatal thymus. No statistically significant changes of receptor affinity were found in the animal models investigated. On the contrary, receptor density showed a progressive decrease with advancing age. The age-related decrease has been found partially corrected in thymus-grafted old animals, which show a statistically significant recovery of receptor density when compared to their untreated littermates. Receptor modulation can be responsible for the age-related impairment and the thymus-dependent correction of beta-adrenergic responsiveness of submandibular glands previously observed in vivo. Hormonal balance and thyroid hormones, in particular, are suggested as being involved in the age- and thymus-dependent regulation of receptor density. In the accompanying Appendix, we describe the mathematical method used to calculate both specific and nonspecific binding from total binding data.

Aging↗
PubMed1980

[High and low affinity beta adrenergic receptor sites from submandibular glands of mice].

Beta-adrenergic receptors from submandibular glands of mice were studied by equilibrium binding experiments. Due to the fact that some discrepancies were previously observed among different author data, we compared two methods for non specific binding substruction, that represents the major source of errors in such experiments. Data were obtained strongly suggesting the presence of multiple population of binding sites and/or negative cooperativity.

Animals↗
PubMed1979

Age-dependent change of the protein-bound phosphorus in rat liver cell nuclei.

Some aspects of the metabolism of the protein-bound phosphorus were examined on isolated rat liver cell nuclei in function of age. The protein complement of the nuclei was separated into 5 non-histone and one histone fractions by means of salt and acid extraction. The phosphorus content of the fractions was determined and the rate of phosphorylation and dephosphorylation was measured after 32P labelling. The supernatant of the in vitro phosphorylation system contained a lower amount phosphorus but showed high phosphorylation rate. For several parameters such as the relative amounts of the non-histone proteins, the net phosphorus contents, the newly incorporated phosphorus/unit protein and the phosphatase activity in the nuclei a common pattern was found in function of age; intermediate, maximum and low or intermediate values for the age-groups of 4--6 months, 16--18 months and 24--28 months respectively. The possible implication of the nuclear non-histone proteins in the process of ageing is discussed.

Aging↗
PubMedDate not supplied

Beta-adrenoceptor changes in submandibular glands of old mice.

The hypothesis that modifications in beta-adrenergic receptors may be responsible for age-dependent change previously observed in vivo, has been investigated. Beta-adrenoceptor characteristics of submandibular glands of mice were studied by using the beta-adrenergic antagonist (-)-[3H]dihydroalprenolol. Data from such studies indicated the presence of two functional populations of binding sites in membrane preparations from young animals, displaying high and low affinity, respectively. Experiments performed on old mice membrane preparations revealed a 50% decrease in the high-affinity population receptor number when compared to the preparations from young animals. However, the affinity did not change significantly with advancing age. With regard to the low-affinity population, no statistically significant changes were observed. From these data it can be reasonably assumed that beta-adrenoceptor alteration during ageing may play a major role in the age-dependent impairment of beta-adrenergic responses in vivo.

Aging↗
PubMedDate not supplied

Functional interrelationships in aging processes: alterations and reversibility.

The problem of assessing the relevance of the reversibility of age-related functional alterations for aging studies has been presented. Transduction mechanisms of adrenergic stimulation have been chosen as the target of age-related changes and thymus as the effector of some corrective interventions performed at advanced age. Both alterations of adrenoceptor characteristics and their reversibility have been reviewed. beta-adrenoceptors have been studied in organs bearing only one subtype of receptors or both, revealing an age-related decrease in density only in the beta1-subtype. It has been shown that a similar age-related decrease is present in alpha1-adrenoceptor density. Such alterations are corrected by grafting a neonatal thymus into old mice. On the contrary, thymus fails to correct the alteration of T4-induced upregulation of beta-adrenoceptors indicating some limits to its corrective effect when the net of functional interrelationships becomes relatively complex. Both failures and successes of thymic grafts and thymic extracts in reversing age-related changes are discussed taking into account the effects induced on the life span of the animals. Different unsolved problems stemming from the previous considerations are also presented. Among them the controversial question about linearity and non-linearity of biological parameters presumed to be good indices of aging is discussed, with the aid of a simple model as a schematic example.

Journal Article↗
PubMedDate not supplied

Parallel decrease of adenylyl cyclase activity and beta1-adrenoceptor density in brain cortex of aging mice.

Beta-adrenergic receptors (betaARs) and adenylyl cyclase (AC) activity have been found to undergo progressive alterations in the brain cortex of aging mice. In particular, betaAR changes are in charge of the beta1 subpopulation (beta1AR), beta2-adrenoceptors (beta2ARs) showing no age-related impairments. On these bases, the question arises whether AC alterations can be accounted for by beta1AR changes or, alternatively, whether there are also receptor independent AC modifications. Experiments have thus been performed on the brain cortex from young and old mice assaying beta1AR and beta2AR characteristics and isoproterenol (IPR) and forskolin stimulated AC activity in the same membrane preparations. Other membranes were previously treated with the reducing agent dithiothreitol (DTT) which is known to specifically destroy the binding capacity of beta1ARs. No statistically significant differences in basal AC activity have been found among the groups studied. Data on IPR-stimulated AC activity in old animals confirm previous findings demonstrating impaired responsiveness when compared with that of young mice. DTT treated membrane preparations from both young and old mice show decreased AC activities. The entity of the decrease is lower in aged animals due to the lower initial level of beta1ARs. Forskolin stimulation, which is assumed to directly activate AC, has been found impaired in aged mice when compared with young animals, suggesting that also post-receptor alterations occur with advancing age.

Journal Article↗
PubMedDate not supplied

Modulation of mouse brain cortex adrenoceptor in old mice by supplementation of zinc and thymomodulin.

BACKGROUND: Previous experiments have shown that the age-related decrease of mouse brain cortex adrenoceptor density can be recovered by grafting a neonatal thymus into old recipients. The question arises whether similar results can also be obtained in the presence of a single thymic factor such as thymomodulin (TMD). It is worth noting that the activity of some thymic factors is strictly zinc (Zn) dependent and that their age-related decreased production is recovered in old mice supplemented with Zn. OBJECTIVE: The above-mentioned evidences prompted us to verify whether Zn and TMD, either alone or combined, are able to induce some corrective effects on age-dependent alterations of adrenoceptor characteristics of the mouse brain cortex. METHODS: Thus, we performed experiments on four groups of Balb/c mice treated with saline, Zn, TMD, or both Zn and TMD. Treatments started when animals were 18 months old and ran for 6 months. The alpha(1)- and beta-Adrenoceptor characteristics were assayed by steady state binding analysis using labelled prazosine and iodocyanopindolol, respectively. Data were analyzed using one-way analysis of variance, followed, when appropriate, by multiple-comparison analysis. RESULTS: Results show an increase of beta-adrenoceptor density and a decrease of alpha(1)-adrenoceptor density in both Zn- and Zn+TMD-treated animals when compared to saline-treated controls, while receptor affinities did not change significantly. CONCLUSIONS: The lack of action of TMD suggests that this type of treatment cannot mimic the effects of grafting the whole gland; it cannot be excluded that different time-dose schedule could be more effective. Zn treatment, on the other hand, does modulate adrenoceptors; however, it shows a corrective action on the age-related decreased density of beta-adrenoceptors, but further decreases that of alpha(1)-adrenoceptors. This differential action could be due to their differential physiological role.

Aging↗
PubMedDate not supplied

Assay of estrogen and progesterone receptors in small samples of breast cancer: I. Mathematical analysis of total binding data.

The quantitative determination of Estrogen and Progesterone receptors in breast cancer is performed using about 500 mg of tissue. Such an amount of tissue sample is available with ever increasing difficulty. In the present paper a mathematical method of analysis of the total (specific+nonspecific) binding data is given. In this way about 50% of tissue can be saved as only one set of test tubes is required; in fact, the method does not need the second set of tubes used to determine nonspecific binding in the conventional assay. Additional advantages from the statistical point of view are also presented.

Animals↗
PubMedDate not supplied

Assay of estrogen and progesterone receptors in small samples of breast cancer: II. The conventional procedure compared to the mathematical one.

Parallel assays of ER and PR receptors have been performed in the same tissue samples using both the conventional method employing two sets of test tubes and a mathematical method which does not need the second set of tubes containing excess cold ligand concentrations. Determinations have been performed in calf uterus and human breast cancer samples. Findings show that the two methods give quite similar results. In particular, they are very close in human BC tissues where receptor density values show a very wide range. The mathematical method seems quite useful when the samples are poor of receptors, a case where the precision of the method may influence both prognosis and therapy.

Animals↗
PubMedDate not supplied

Assay of total protein kinase activity in mouse brain cortex.

In previous studies we demonstrated that the adrenergic system is impaired in old animals and that the main alterations were observed at the level of receptor density and adenylate-cyclase activity. The decreased ability to produce cAMP could influence the activity of the cAMP dependent protein kinase (PKA), one of the enzymes responsible for the phosphorylation of protein substrates. Since protein phosphorylation is one of the most common and important mechanisms through which a cell regulates its activity, the characteristics of the phosphorus incorporation reaction were studied. Kinase activity was measured in homogenate of young mouse brain cortex prepared avoiding gross manipulations in order to maintain conditions as close to those present in the living animal as possible. Results show that phosphate incorporation is proportional to protein content and strictly dependent on ATP availability. Increasing the ATP concentration from 10 to 500 mumol/l, the length of incorporation phase increases, suggesting that the limiting point of the reaction is better represented by energy availability than by enzyme or protein substrate concentrations.

Adenosine Triphosphate↗