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Biomedical subjects

R Caldara

Publications and source records attributed to R Caldara.

At least 73 records · Page 4Linked to original sources

Oral glucose tolerance and insulin response after one week's clonidine treatment in hypertensive patients.

Acute clonidine administration is known to induce a significant rise in plasma glucose in man. In order to evaluate the possible effect of prolonged drug treatment on glucose metabolism, paired OGTTs were performed in 12 hypertensive patients (6 with normal and 6 with abnormal glucose tolerance) in basal conditions and following 1-week's administration of clonidine (0.15 mg every 8 h) Basal plasma glucose and serum insulin concentration as well as glucose tolerance and insulin response to oral glucose did not change in either group after treatment. Although the mechanism(s) mediating the transient hyperglycemic action of clonidine are not fully understood, the present findings indicate that this drug does not exert diabetogenic effects during chronic treatment, and suggest that homeostatic mechanisms may counteract the acute effect of clonidine on glucose metabolism.

Adult↗

Inhibition of the renin-angiotensin-aldosterone system by L-dopa with and without inhibition of extracerebral dopa decarboxylase in man.

1. The present study was undertaken to investigate the possibility that central nervous system mono-aminergic pathways may play a role in the control of the renin-angiotensin-aldosterone system in man. 2. Eight normal subjects received in a randomized order placebo, L-dopa (500 mg, orally) and L-dopa (100 mg, orally) plus carbidopa (35 mg, orally) after pretreatment with carbidopa (50 mg every 6 h for four doses). 3. L-Dopa administration elicited a significant fall in plasma renin activity (PRA) (P less than 0.01 at 120, 150 and 180 min) and in plasma aldosterone levels (P less than 0.05 at 90, 120, 150 and 180 min); L-dopa plus carbidopa induced a decrease in PRA (P less than 0.05 at 120 and 150 min, P less than 0.01 at 180 min) and in plasma aldosterone concentration (P less than 0.05 at 30 and 60 min, P less than 0.01 at 90 and 120 min), in comparison with placebo administration; between-drugs analysis revealed no difference in the decreases in PRA and plasma aldosterone levels induced by the two regimens. 4. Since L-dopa, as well as L-dopa plus carbidopa, has been shown to augment catecholamine levels in the brain of various animal species, the present data suggest that in man PRA and plasma aldosterone concentration might be inhibited by increased central nervous system catecholamine levels.

Adult↗

Serum Gastrin concentration in patients with rheumatoid arthritis: effect of long-term immunosuppressive or antidopaminergic treatment.

In an attempt to further evaluate the conflicting incidence of hypergastrinemia in patients with rheumatoid arthritis (RA), serum gastrin concentration has been determined in 58 RA patients and in 58 healthy subjects. Mean levels were significantly higher in RA patients than in controls, although clearly high values were only found in 3 subjects with severe hypochloridria. During one year of immunosuppressive treatment in 12 RA patients with cyclophosphamide plus colchicine serum gastrin levels did not change, while a significant decrease was observed in another 12 patients after 2 months' treatment with haloperidol, a dopamine receptor blocker; this decrease was sustained throughout the one year treatment. Indomethacin administration up to 6 months did not change serum levels in a control group of 12 RA patients. Serum gastrin concentration in patients treated with haloperidol was significantly lower than in those treated with indomethacin at 2 and 6 months, while no significant differences were observed between cyclophosphamide- and indomethacin-treated groups. These results confirm and extend previous studies showing inhibition of gastrin secretion by antidopaminergic drugs. No correlations were observed between serum gastrin levels and inflammatory indices, both in basal conditions and during any drug treatment.

Adult↗

Effect of loperamide and naloxone on gastric acid secretion in healthy man.

The effect of acute oral administration of three different doses (4, 8, and 16 mg) of loperamide, a peripheral opiate agonist, on basal and submaximal pentagastrin-stimulated gastric acid secretion was evaluated in healthy volunteers. Both basal and stimulated gastric secretion were significantly lowered by 8 and 16 mg of the drug in comparison with a control study, while 4 mg was ineffective. Naloxone, a specific opiate antagonist, decreased slightly but not significantly both basal and pentagastrin-stimulated gastric acid secretion, when infused intravenously at the rate of 30 micrograms/kg/h, but completely abolished the inhibitory effect of loperamide on gastric acidity. These data also suggest that opiates may be involved in the regulation of gastric acid secretion in man by acting at a peripheral site, as loperamide does not cross the blood-brain barrier.

Adult↗

Central nervous system and pituitary mechanisms in dopaminergic stimulation of growth hormone release in women.

In an attempt to evaluate the relative importance of brain and peripheral (i.e., outside the blood-brain barrier) dopamine (DA) receptor stimulation in the regulation of GH release, DA (5 microgram/kg/min infused i.v. for 120 min), L-dopa (500 mg p.o.), L-dopa (100 mg p.o.) plus carbidopa (35 mg p.o.) after pretreatment with carbidopa (50 mg p.o. every 6 h for 1 day), and nomifensine (200 mg p.o.) have been administered to healthy women. Significant elevations in serum GH were induced by all regimens in comparison with a control placebo study, although the effect of DA was only transient in spite of continuing infusion. The between drugs analysis revealed that L-dopa alone was significantly more effective in releasing GH than carbidopa plus L-dopa as well as DA infusion and nomifensine administration. These results suggest that both central nervous system and peripheral mechanisms are involved in dopaminergic stimulation of GH release in man. Since DA does not affect somatotropes directly, increased serum GH levels by DA infusion probably reflect stimulation of median eminence dopaminergic neurons.

Adolescent↗

Inhibition of luteinizing hormone release by dopamine infusion in healthy women and in various pathophysiological conditions.

To investigate the effect of dopaminergic stimulation on gonadotrophin release, serum LH and FSH concentrations were measured during dopamine infusion (5 microgram/kg/min for 120 min) in 8 healthy women in the early follicular phase, in 12 patients with hyperprolactinaemic amenorrhoea, in 5 subjects with premature ovarian failure and in 8 with polycystic ovarian disease and raised serum LH levels. Dopamine infusion produced a significant LH decrease compared with a control study using saline in all groups; there were no significant changes in FSH concentration. Between groups analysis showed a significantly greater LH fall in patients with polycystic ovarian disease than in the other groups. Dopamine inhibits LH release in healthy women and patients with anovulatory states of varying aetiology, and enhanced sensitivity to this inhibitory mechanism exists in polycystic ovarian disease. This finding suggests reduced dopamine activity at the median eminence level in this condition.

Adolescent↗

Spontaneous and induced pregnancies in hyperprolactinemic women.

Sixty-nine pregnancies were observed in 57 hyperprolactinemic women (5 with pituitary macroadenoma, 20 with microadenoma, and 32 with normal tomography of the sella turcica). Ten of these pregnancies took place spontaneously in women with mild to moderate hyperprolactinemia (up to 70 ng/ml); 2 were induced by exogenous gonadotropins, 2 by clomiphene, 42 by bromocriptine, and 9 by metergoline; and 4 occurred after pituitary selective adenomectomy. The observed complications included spontaneous abortion (10 cases); headache (7 cases); sellar enlargement (5 cases); and bitemporal hemianopsia (1 subject with macroadenoma). Among 24 women in whom prolactin levels were reevaluated at least 1 month after parturition and/or lactation, 8 showed a decrease in prolactin concentration (less than 50% of pregestational levels), with actual prolactin normalization in 3 and resumption of cyclic menses in 2 previously amenorrheic women. In contrast, no changes in prolactin levels occurred after pregnancies that ended in abortion. These data suggest the following: 1) conception is not uncommon in women with moderate hyperprolactinemia; and 2) pregnancy may be safely induced without prior surgery and/or radiotherapy in hyperprolactinemic women, except those with large pituitary adenomas, and a considerable number of these patients even show a clinical and biochemical improvement after pregnancy.

Adenoma↗

Effect of two antiserotoninergic drugs, methysergide and metergoline, on gastric acid secretion and gastrin release in healthy man.

The effects of acute oral administration of the antiserotoninergic drugs methysergide (3 mg) and metergoline (4 mg) on basal, submaximal (0.6 micrograms/kg i. m.) and maximal (6 micrograms/kg) pentagastrin-stimulated gastric acid secretion, as well as on basal and food-induced gastrin release, have been evaluated in healthy volunteers. Methysergide significantly increased basal and submaximal pentagastrin-stimulated gastric acid secretion, and metergoline significantly inhibited gastric acidity in all experiments. Basal and stimulated serum gastrin concentrations were not modified by either drug. The effect of methysergide on gastric acid secretion was opposed to that of serotonin and was probably dependent on its antiserotoninergic action, but the decrease in gastric acidity caused by metergoline is not easily explained. Although the effect is similar to that of a dopamine infusion, it does not depend on dopamine infusion, it does not depend on dopamine receptor stimulation, since it was not influenced by pretreatment with metoclopramide. It is suggested that it might be due to the weak anticholinergic and/or antihistaminic properties of metergoline.

Adult↗

Metabolic effects of prazosin.

The effects of oral administration of 2 mg prazosin on several metabolic and endocrine variables were evaluated in 12 patients with hypertension (6 with normal and 6 with abnormal glucose tolerance). Prazosin was followed by a rise in plasma glucose and serum free fatty acids (FFA) in both normal and diabetic subjects; there was a trend upward in serum albumin (IRI), but growth hormone (GH), prolactin (PRL), and gastrin did not change. Although these results are in general agreement with metabolic effects of other alpha adrenergic blockers already reported, the rise in plasma glucose is at variance with studies performed with phentolamine.

Adrenergic alpha-Antagonists↗

Growth hormone secretion in hypertensive patients: evidence for a derangement in central adrenergic function.

1. In an attempt to test the hypothesis of a derangement in central catecholaminergic function in hypertensive patients, the serum growth hormone and prolactin responses to the alpha-adrenergic agonist clonidine (0.15 mg infused intravenously) and to L-dopa administration (500 mg orally) were evaluated in 15 hypertensive and 15 normotensive subjects matched for sex, age and body weight. 2. Whereas L-dopa elicited a growth hormone response of similar magnitude in both groups, clonidine infusion induced a significant increase in serum growth hormone in normotensive, but not in hypertensive, subjects. 3. Prolactin levels were equally suppressed by L-dopa and did not change after clonidine in either group. 4. The present study adds neuroendocrine evidence to the concept of a derangement in central alpha-adrenergic function in human hypertension.

Adult↗

Metabolic effects of chronic prazosin treatment.

The effects of chronic (3 mg/day for 1 week) administration of the vasodilator drug prazosin on several metabolic and endocrine variables were evaluated in 12 hypertensive patients, 6 with normal and 6 with abnormal oral glucose tolerance test (OGTT). After 1 week prazosin treatment there were no significant modifications in fasting plasma glucose, serum free fatty acids (FFA), cholesterol, triglycerides, insulin (IRI), growth hormone (GH), prolactin (PRL) and gastrin levels; oral glucose tolerance and IRI response to glucose were unchanged in normal subjects, while in chemical diabetics there was a significant improvement in glucose tolerance and a slight increse in IRI secretion. Therefore, the untoward metabolic effects of acute prazosin administration, i.e. increased plasma glucose and serum FFA, are not sustained during chronic treatment, which may even improve glucose metabolism in diabetic patients.

Adrenergic alpha-Antagonists↗

Hyperprolactinemic primary amenorrhea: case report with successful prolactin-lowering treatment and review of the literature.

A 19-year-old girl with primary amenorrhea, galactorrhea, and hyperprolactinemia is described. Her high serum prolactin levels (95 ng/ml) did not increase after thyrotropin-releasing hormone and sulpiride, but markedly decreased after acute bromocriptine and metergoline administration. The results of other pituitary function tests were normal. Tomography of the sella turcica and CT scan of the skull were also normal. The patient was treated with metergoline, a prolactin-lowering drug which is believed to act as a serotonin antagonist, for 30 months. Serum prolactin rapidly decreased after institution of treatment, with actual normalization (less than 20 ng/ml) by the 3rd month. At this time the low serum luteinizing hormone levels began to rise and fluctuate in the normal follicular range. Galactorrhea disappeared, and menarche occurred during the 15th month of treatment. 15 further menstrual bleedings ensued over the following 15 months, albeit at irregular time intervals; ovulation was suggested by finding elevated serum progesterone levels in the presumed luteal phase by about 1 year following the menarche. The available data on 38 patients with primary amenorrhea and hyperprolactinemia reported in the literature are reviewed. 15 of them were treated with bromocriptine, and either pregnancy or cyclic menses occurred in 11. Hyperprolactinemic primary amenorrhea may be more common than previously recognized, and it may probably be successfully treated by prolactin-lowering drugs or by surgical ablation of a pituitary adenoma in a high percentage of cases.

Adult↗

Failure of nomifensine administration to discriminate between tumorous and nontumorous hyperprolactinemia.

It has recently been claimed that the PRL-lowering response to nomifensine administration (200 mg, orally) reliably discriminates patients with PRL-secreting tumors from those with so-called functional hyperprolactinemia. In the present study, this test was performed in 15 healthy controls, 7 hyperprolactinemic subjects without evidence of pituitary tumor, and 16 patients with prolactinoma. A decrease of serum PRL to below 65% of basal levels, which seemed to be the cut-off point in the previous study, was obtained in 11 subjects of the first group, in 4 subjects of the second group, and in 4 subjects of the third group. The decrease of mean serum PRL concentration after nomifensine was only significant in the first and second groups. Analysis of variance showed a significant difference in the PRL inhibition by nomifensine between the tumor group and the two groups without evidence of pituitary adenoma. Nevertheless, this study shows that the nomifensine test is unable to discriminate in the individual patient the tumorous or nontumorous origin of excessive PRL secretion.

Adenoma↗

Effect of four dopamine receptor antagonists on gastrin secretion in healthy subjects.

The effect of 1 week of oral treatment with four antidopaminergic drugs--metoclopramide, sulpiride, haloperidol, and pimozide--on fasting and meal-stimulated serum gastrin levels has been evaluated in healthy subjects. All of the four drugs significantly reduced the gastrin response to a meal, whereas basal concentration was unaffected. It is suggested that this action is mediated by central nervous system dopamine receptor blockade, which might act either via nervous or humoral mechanisms to inhibit gastrin release.

Adult↗