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Biomedical subjects

M Marchi

Publications and source records attributed to M Marchi.

At least 127 records · Page 7Linked to original sources

Age dependent changes in choline uptake of the chick iris.

The kinetics of the uptake of choline, the rate-limiting substrate in the in vivo synthesis of acetylcholine, were studied during the period 1--7 years in the iris of the chick. These changes were correlated to the endogenous levels of acetylcholine and choline in the same organ. Vmax values per iris decrease significantly at 5 years and continue to decrease at 7 years, to 64% and 37% of the one year value, respectively. If the variation in Vmax is calculaed per protein the decline is 34% between 1 and 5 years. Km does not change significantly during the period 1--7 years. Total acetylcholine and choline levels follow a similar trend, decreasing progressively from 1 to 7 years. Sensitivity to hemicholinium (5.5 X 10(-5) M) decreases significantly between 5 days of incubation (d.i.) and 5 years. Inhibition by ouabain (10(-4) M) shows an opposite trend, increasing significantly from 20% at 5 d.i. to 52% at 3 months. At 5 years sensitivity to ouabain is the same as at 3 months. Nardependence decreases significantly between 5 d.i. and 5 years but no significant changes are seen between 5 d.i. and 3 months. Uptake at 27 degrees C decreases from 59% of control at 5 d.i. to 45% at 3 months, and is not changed at 5 years. Our observations suggest that the effect of aging on peripheral cholinergic neurons is not generalized, but is specifically directed toward the neuronal periphery (terminals) as opposed to cell bodies.

Acetylcholine↗

Norepinephrine uptake in aging adrenergic nerve terminals.

Norepinephrine (NE) uptake has been studied in the adult (3-6 months) and aging (5 yr) chick iris, in which there is a discrete population of norepinephrine containing nerve terminals. although total accumulation of 3H-NE in the iris does not change with age, there is a decline in Na+-dependence, temperature-sensitivity, ouabain-and inhibitor -sensitivity of uptake. The results indicate either a loss of active, carrier-mediated NE uptake during aging, or a change in the biochemical and pharmacological characteristics of this uptake. changes in the composition of the organ and in the sites of accumulation of NE are considered.

Aging↗

Development and aging of cholinergic synapses. II. Continuous growth of acetylcholine and choline levels in autonomic ganglia and iris of the chick.

We have followed the pattern of variation in the endogenous levels of acetylcholine (ACh) and choline (Ch) in sympathetic (lumbar) and parasympathetic (ciliary) ganglia, and in the iris of the chick from 1 to 7 years of age. Levels of ACh and Ch seem to undergo a continuous process of growth which is initiated in the first week of embryonic development and continues into adulthood up to 2 years of age. The early increase in ACh and Ch levels are most marked in the ciliary ganglion. In the ciliary ganglion, morphological and biochemical observations show that this period corresponds to one of 'continuous synaptic growth'. In a second period starting around 2 years, which can be defined as one of 'synaptic regression', a phase of progressive and marked decrease in ACh and Ch levels is visible in all three organs examined. In all three organs Ch levels parallel rather well the ACh levels, but the Ch/ACh ratio progressively decreased from 1 to 7 years from 3.5 to 1.5 (ciliary ganglia and iris) and from 2.5 to 1 (sympathetic ganglia). The low levels of ACh reached at 7 years in the three organs have clear implications with regard to physiology of aging cholinergic synapses.

Acetylcholine↗

Development and aging of cholinergic synapses. III. Choline uptake in the developing iris of the chick.

Choline (Ch) uptake in the iris of the chick has been characterized from 4 1/2 days of incubation to 1 year of age, in conjunction with an electron microscopic ultrastructural study of the innervation of the iris. Uptake has been shown to constitute an early and reliable biochemical marker for the presence of innervation in target organs. The characteristics of Ch uptake, including Na+ and temperature dependence and inhibitor sensitivity, change during development, and the Vmax increases steadily while the Km does not vary significantly during the period of study. The relationships among uptake and other cholinergic functions also change with development of the iris. Acetylcholine (ACh) and Ch uptake but not Ch levels appear to develop together, while cholinergic enzyme activities follow a developmental course more closely related to neurotransmission. The significance of these findings in relation to proposed regulatory relationships in cholinergic biosynthetic mechanisms in discussed.

Aging↗

Development and aging of cholinergic synapses. IV. Acetylcholinesterase and choline acetyltransferase activities in autonomic ganglia and iris of the chick.

Age-related changes in the activities of choline acetyltransferase an acetylcholinesterase in avian sympathetic ganglia, ciliary ganglia and iris have been determined throughout the posthatching life span. Kinetic characteristics of these enzymes have been analyzed in the nerve terminals in the iris from early embryonic stages to the latest periods of life. Enzyme activities and kinetics have been related to each other and also to the endogenous levels of acetylcholine. The regulation of the biosynthetic mechanism for acetylcholine through choline uptake and choline acetyltransferase activity in the developing nerve terminal have been examined. The activities of both enzymes in all tissue are reduced at later ages, which is referred to declines in Vmax, as the Km values do not vary significantly at any age. Declines with age are most pronounced in the iris, both in choline acetyltransferase activity and Vmax and in acetylcholine levels, supporting our view of the peripheral autonomic nerve terminal as a major locus for the effects of aging on the peripheral nervous system.

Acetylcholinesterase↗

Development and aging of cholinergic synapses. I. Endogenous levels of acetylcholine and choline in developing autonomic ganglia and iris of the chick.

Acetylcholine (ACh) and choline (Ch) levels were measured by means of a sensitive micromethod in developing irises, ciliary and sympathetic ganglia of the chick, starting at 5--7 days of incubation (DI) up to 1 year of age. The neurotransmitter is present in all three organs at relatively low levels (1--10 pmol) from 5 DI (iris) or 7 DI (ciliary and sympathetic ganglion). This is followed by a rapid and sustained 9-fold increase in all three tissues up to 14 DI. Thus, it appears that low levels of ACh may be sufficient for neurotransmission to occur in the primitive ciliary ganglion and iris. After hatching, total ACh levels continue to increase up to 1 year of age in the iris and ciliary ganglion and up to 3 months in the sympathetic ganglion. The increase may depend on either an increased functional demand for the neurotransmitter or an increased number of preganglionic terminals. In general Ch levels parallel closely the levels of ACh in each organ throughout development. It is concluded that ACh and Ch are present since the earliest detectable stages of development in the ganglia and iris, and their first increase seems to be correlated to the phase of innervation of the organs. The subsequent increase probably correlates to synaptogenesis. The close relationship between Ch and ACh levels indicates a regulatory role of Ch for ACh synthesis during neuronal development.

Acetylcholine↗

Metabolism and biological activity of a thiamine new salt. I. Urinary excretion and tissue content of vitamin B1 in rats treated with thiamine chloride ester monophosphate of Bis-glucosamine.

Research has been carried out on the metabolism of thiamine chloride ester monophosphate of bis-D-glucosamine (TCMPG) evaluating the urinary excretion, the blood and the hepatic content of thiamine in the rat after intraperitoneal injection of this compound. The results obtained have shown a greater retention of vitamin B1 when it is administered as glucosamine salt. In fact, the amount of thiamine excreted by the rats which have received the TCMPG is lower while the blood and liver levels of vitamin are higher, compared with the control rats treated with thiamine monophosphate only, or with thiamine and glucosamine. These results permit the conclusion that glucosamine increases the utilization of the vitamin and its penetration into the cells.

Animals↗

Studies on metabolism of thiamine chloride ester monophosphate of bis-D-glucosamine. II. Effect of TCMPG in vitamin B1-deficient rats.

In order to investigate the metabolism of thiamine chloride ester monophosphate of bis-D-glucosamine (TCMPG) urinary excretion, blood levels and tissue content of thiamine in vitamin B1-deficient rats were measured after intraperitoneal injection of this compound or of thiamine monophosphate or of a mixture of thiamine monophosphate and glucosamine. The greater retention and the higher levels of vitamin observed in the blood and in the tissues of animals treated with TCMPG compared with the control rats confirm the hypothesis that a more efficient utilization of vitamin B1 is obtained by the organism when it is administered salified with glucosamine.

Animals↗

Non-parametric maximum likelihood estimators for disease mapping.

A Non-Parametric Maximum Likelihood approach to the estimation of relative risks in the context of disease mapping is discussed and a NPML approximation to conditional autoregressive models is proposed. NPML estimates have been compared to other proposed solutions (Maximum Likelihood via Monte Carlo Scoring, Hierarchical Bayesian models) using real examples. Overall, the NPML autoregressive estimates (with weighted term) were closer to the Bayesian estimates. The exchangeable NPML model ranked immediately after, even if it implied a greater shrinkage, while the truncated auto-Poisson showed inadequate for disease mapping. The coefficients of the autoregressive term for the different mixtures have clear interpretations: in the breast cancer example, the larger cities in the region showed high rates and very low correlation with the neighbouring areas, while the less populated rural areas with low rates were strongly positively correlated each other. This pattern is expected since breast cancer is strongly correlated with parity and age at first birth, and the female population of the rural areas experienced a decline in fertility much later than those living in the larger cities. The leukemia example highlighted the failure of the Poisson-Gamma model and other general overdispersion tests to detect high risk areas under specific conditions. The NPML approach in Aitkin is very general, simple and flexible. However the user should be warned against the possibility of local maxima and the difficulty in detecting the optimal number of components. Special software (such as CAMAN or DismapWin) had been developed and should be recommended mainly to not experienced users.

Algorithms↗

On surveillance methods for congenital malformations.

This paper presents an 'optimal' procedure for the use of the 'sets' method, a system proposed for surveillance of congenital malformations. Comparisons over a number of examples shows that the given procedure represents a clear improvement over the one originally proposed, and, in some conditions, is more efficient than the cusum scheme.

Biometry↗

Exploratory tools for disease mapping in geographical epidemiology.

In the present paper a new shrinkage estimator of relative risk, useful in disease mapping, is compared with the empirical and full Bayes estimators, using death certificate data for lung cancer (males and females) and breast cancer (females) 1982-1988 in the Emilia-Romagna region (Italy). The estimates are obtained averaging the relative risks obtained from recursive partitioning of the set of observed values. The number of partitions is fixed in advance and behaves as a smoothing parameter, the lower the number the higher the degree of shrinkage toward the overall mean of the observed values.

Algorithms↗