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Age-related modifications of monoamine oxidase-A and -B (MAO-A and MAO-B) and amine metabolite concentrations were studied in human frontal cortex taken postmortem from 22 subjects of various ages (21-75 years). Qualitative and quantitative analysis for MAO-B was provided by kinetic studies with a specific radioligand, [3H]lazabemide. The data demonstrated a significant (P < 0.05) positive correlation between the density of [3H]lazabemide binding sites (Bmax) and age of the subject, without showing an apparent modification in the dissociation constant (KD) of the radioligand. In parallel experiments, MAO-B but not MAO-A activity was shown to correlate with age (P < 0.05). The concentrations of the amine metabolites 4-hydroxy-3-methoxyphenylacetic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG) were all devoid of a correlation with age. Neither did the concentrations of these metabolites relate to the respective subject's MAO-B enzymatic activity nor to [3H]lazabemide Bmax. A correlation, though rather weak, was obtained between MAO-A activity and MHPG concentration (P = 0.045). The MAO-A and -B enzyme characteristics in subjects who had committed suicide (n = 9) did not differ from those of subjects deceased for other causes (n = 13). Among the measured monoamine metabolites the concentrations of DOPAC and HVA were higher in the suicide versus control group (P < 0.05). The present data confirm in a direct manner that the increase in MAO-B activity in aging brain is due to an enhancement of the number of active sites of the enzyme and not through modifications of its kinetic characteristics. Furthermore, that neither the characteristics nor the activity of the enzyme are changed in the frontal cortex of suicide victims compared to control subjects.

Summary. Plasma concentrations of adrenaline and noradrenaline were measured radio-enzymatically in nine patients with diabetic autonomic neuropathy, seven diabetic patients without autonomic neuropathy and nine normal subjects, in the recumbent position and after standing. Furthermore, in six patients with autonomic neuropathy and in the normal subjects, plasma noradrenaline and adrenaline concentrations were determined during and after cyclo-ergometer exercise. No differences in plasma adrenaline concentrations were found at any time in the study. Basal plasma noradrenaline levels were significantly lower in diabetic patients with autonomic neuropathy than in the non-neuropathic diabetics or healthy control subjects. After standing, plasma noradrenaline rose to significantly higher levels in both control and diabetic subjects without neuropathy than in the patients with autonomic neuropathy. During exercise (up to 100 W load), plasma noradrenaline rose to similar levels in healthy controls and in patients with diabetic neuropathy. These data indicate that in diabetic autonomic neuropathy there is reduced peripheral neurosympathetic tone at rest but a normal response to moderate exercise. Blunted neurosympathetic responses to standing seem to be a consistent feature of diabetic autonomic neuropathy, particularly in those patients with severe postural hypotension.Key words: Plasma catecholamines, adrenaline, noradrenaline, sympathetic nervous activity, diabetes mellitus, autonomic neuropathy, postural stimulation, orthostatic hypotension, muscular exercise.Autonomic neuropathy in diabetes mellitus produces a variety of different symptoms and signs due to variable involvement of the sympathetic and parasympathetic branches of the autonomic nervous system [6,14,16].Plasma catecholamine levels have been investigated in only a few studies in recent years, as a possible humoral index of sympathetic function in complicated or uncomplicated diabetes. While the results obtained from these studies indicate that plasma catecholamine levels in uncomplicated diabetes are normal, the frequency of sympathetic deficiency, as reflected by subnormal plasma noradrenaline concentrations, in diabetic autonomic neuropathy and its possible importance in relation to symptoms, such as postural hypotension, is less clear [1,9,10,12,19]. This uncertainty could be due, at least in part, to difficulties in the accurate measurement of catecholamine responses and also in the characterization of diabetic autonomic neuropathic syndromes.The present investigation was aimed at evaluating peripheral sympathetic function and reactivity to appropriate stimuli, such as standing and muscular exercise, in diabetic patients with autonomic neuropathy, compared with diabetics without neuropathy and normal subjects. For this purpose, the presence of diabetic autonomic neuropathy was ascertained from a series of clinical and instrumental evaluations. Plasma adrenaline and noradrenaline concentrations, measured by a sensitive and specific radio-enzymatic me...

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