[Prospective thoughts concerning DEA and doctoral studies in medicine].
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Biomedical subjects
Publications and source records attributed to J F Cier.
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In 112 patients with essential hypertension (HTA), free of any therapeutic and receiving the standard ward, a significant inverse relationship was found between age and plasma renin activity (PRA) and plasma aldosterone (PA), measured in the supine and upright position. Urinary epinephrine and norepinephrine were not related with age. When dividing the patients in 4 different age groups, it appeared that those younger than 30 years exhibited a significantly higher PRA and PA values and a higher frequency of borderline hypertension (45 p. 100) than the older ones (12 p. 100). So as to determine the characteristics associated with borderline HTA, it was necessary to eliminate the influence of age. This was achieved by comparing two groups of carefully age-matched patients, one with borderline HTA and the other with stable HTA. The only significant difference found was a significantly more marked increase in PRA in response to orthostatism, in patients with borderline HTA. Since renin responses to an orthostatic stress are largely mediated by renal nerves, this result suggest that borderline HTA could be associated with an increased reactivity of the sympathetic nervous system.
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In 149 children between 6 days and 15 years of age, plasma renin activity (PRA) and aldosterone (PA) were measured by radioimmunoassay and plasma dopamine beta hydroxylase activity (DBH) by the method of Nagatsu. PRA and PA decreased with age from 496 +/- 119 ng/1/min for PRA and 643 +/- 158 pg/ml for PA in 6 to 30 day-old newborns to 37.8 +/- 4.7 ng/1/min for PRA and 43. 1+/- 8.3 ph/ml for PA in 9 to 15 year-old children. DBH increased with age from less than detection limit values (< 2 IU) in 6 day to 3 month-old newborns to 17.2 +/- 5.1 IU in 9 to 15 year-old children. In addition a significant relationship was found between PRA and PA (log PA = 0.99 log PRA -0.058, r = 0.732, n = 104, p < 0.001) and PRA and DBH (log DBH = -0.41 log PRA +1.62, r = 0.404, n = 80, p < 0.001). These results demonstrate the opposite evolution of the Renin-Angiotensin-Aldosterone System and of the sympathoadrenal system during development.
The experimental facts presented here allow us to establish a relationship between DA motor effects on isolated rat duodenum, studied in a previous work, (excito-motor between 10(-9) M and 10(-5) M and inhibitor beyond 10(-5) M) and the functional aptitude of this duodenum to answer to 5-HT : 5-HT excito-motor effects are amplified by DA at concentrations less than or equal to 2.6 X 10(-6) M and on the contrary antagonized by DA at concentrations above 5 X 10(-6) M. On the other hand, DA excito-motor effects do not appear on 5-HT-desensitized duodenums. The study of 5-HT dose-response curves in the presence of different concentrations of DA suggests that the amplification of serotonergic effects observed with small DA concentrations can be possibly related to the additional effects of 5-HT on its own receptors and of DA on another receptor. The receptor involved in DA excito-motor action seems to be closely related to the 5-HT receptor since its effects are blocked by the same molecules (methylsergide, cyproheptadine) and since DA excito-motor action is no more evident on 5-HT-desensitized duodenums, but several arguments support the specificity of this receptor for DA (though it is not blocked by haloperidol). Some of its effects are in line with those of DA receptors made conspicuous in other territories and not blocked by haloperidol : central and human colon receptors. On the contrary, DA used at high concentrations (greater than or equal to 5 X 10(-6) M) seems to be able to occupy serotonergic sites, preventing 5-HT access to its receptors until its concentration is high enough to displace DA. From a functional point of view, this antagonistic effect of DA at high concentrations against 5-HT excito-motor effects could facilitate alpha- and beta-mediated inhibitory effects.
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In this report we have tried to determine whether or not catecholamines are involved in the progressive muscular dystrophy. Catecholamines and their metabolites were studied in urines of children with Duchenne disease or other forms of myopathy (limb-girdle and facio-scapulo humeral myopathies). Catecholamine deaminated metabolites were normal in either form of myopathy; in contrast, Duchenne patients, contrarily to other children, eliminated excessive amounts of most amines (catecholamines and methoxylated amines) in relation to age and degree of disease evolution. Our results indicate that catecholamines are not the primary factors involved in the pathogenesis of Duchenne myopathy, but are rather secondary to some disease effects. It is suggested that the high excretion of catecholamines and their methoxylated amine metabolites observed in severely affected Duchenne boys might be related to thermoregulatory process or/and to alterations in some enzymatic systems.
Studying the effects, on the isolated rat duodenum motricity, of ten compounds precursors or metabolites of catecholamines, the following results were obtained: The direct metabolites of epinephrine and norepinephrine (metanephrine, normetanephrine), are either ineffective at concentrations below 5 X 10(-6) M, or weakly inhibitory at higher concentrations. Such inhibitory effects are prevented by alpha- and beta-blockers. 3-methoxy, 4-hydroxyphenylglycol and vanylmandelic acid have no significant effect. The catecholamine precursor, dopamine, the related compounds DOPA, 3 methoxytyramine, and to a lesser extent, 3-O methyl DOPA and homovanillic acid, have excito-motor effects at concentrations ranging mainly from 10(-7) M to 10(-5) M. At higher concentrations, the same compounds frequently exhibit inhibitory effects. The excito-motor effects might be due to a serotoninergic mechanism, since they are suppressed by the serotoninergic blocking agents methysergide and cyproheptadine. Furthermore, in the case of DOPA, we were able to establish a relationship between the excito-motor effects and duodenal serotonin stores. As for the inhibitory effects, they may be prevented by using alpha and beta blocking agents. Dihydroxyphenylacetic acid has no effect on the isolated rat duodenum motricity. The fact that dopamine and related compounds may have excitomotor effects at some concentrations, correlated with some physiopathological observations in man and animal allows some considerations about the eventual role of dopamine on intestinal motricity.
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