Clonidine and growth-hormone secretion.
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Adolescent↗
Biomedical subjects
C Ferrari
Publications and source records attributed to C Ferrari.
[The relationship between alpha-lipoproteins and longevity].
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Aged↗
Improved oral glucose tolerance following antiserotonin treatment in patients with chemical diabetes.
The effects of short-term treatment with either placebo or two serotonin antagonists, cyproheptadine and metergoline, on oral glucose tolerance and insulin secretion have been evaluated in normal subjects and in patients with chemical diabetes. Placebo treatment was not associated with any significant change in the parameters examined. Glucose tolerance in chemical diabetics was significantly improved both after cyproheptadine and metergoline; fasting plasma glucose was also reduced by metergoline. Treatment with the latter drug was also associated with a significant decrease in incremental glucose area in healthy subjects, which was not affected by cyproheptadine. Basal and glucose-stimulated insulin secretion were not affected by either drug in any subjects. Cyproheptadine and metergoline improve glucose metabolism in chemical diabetes probably by reducing insulin resistance. This may depend either on decreased secretion of counter-regulatory hormones or on a direct pharmacological action of the drugs on glucose utilization, possibly mediated by their common antiserotoninergic properties.
Adult↗
Prolactin release by intravenous cimetidine in man: evidence for a suprapituitary locus on action.
In an attempt to identify the sites at which cimetidine stimulates prolactin release, the drug was administered intravenously (6 mg/kg body weight) to healthy subjects under basal conditions, during dopamine infusion (1 microgram/Kg-min for 120 min) and after pretreatment with L-dopa plus carbidopa (250 plus 25 mg every 6 for 1 day). The serum prolactin response to cimetidine was abolished by dopamine infusion and almost completely suppressed by L-dopa plus carbidopa administration. These findings suggest that the drug acts on the central nervous system to stimulate prolactin release. Although the mechanism of this action is unclear, it does not seem to depend on an antidopaminergic effect and may be related to blackade of brain H2 histamine receptors.
Adult↗
Cardiomegaly and heart failure in a patient with prolactin-secreting pituitary tumour.
Unexplained cardiomegaly with cardiac failure was observed in a 42-year-old woman in whom a pituitary tumour had been treated by radiotherapy five years previously. She had been amenorrhoeic for 10 years. Thyroid and adrenal function was normal. Despite treatment with digitalis and diuretic, her cardiac disease progressed until she died suddenly at the age of 45. Hyperprolactinaemia was evident some weeks before death, her serum concentration of 68 ng/ml being well above both the reported normal range (2--20 ng/ml) and the concentrations in eight female controls being treated for severe cardiac failure (5--25 ng/ml). Although the association of these two disorders might merely represent coincidence, heart disease with similar features is common in acromegaly and does not correlate with plasma growth hormone concentration. Since prolactin is known to exert metabolic growth hormone-like effects in animals and in man, the possibility should be considered that prolactin hypersecretion might induce or maintain cardiac disease in some patients with pituitary tumours. A preliminary survey of 35 subjects with hyperprolactinaemia has shown five with raised blood pressure and four, two of whom were normotensive, with cardiomegaly on chest radiography.
Adult↗
Restoration of the prolactin response to sulpiride by metergoline administration in hyperprolactinemic patients.
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Adenoma↗
Thyrotropin secretion in patients with central hypothyroidism: evidence for reduced biological activity of immunoreactive thyrotropin.
TSH concentration was measured in plasma before and after TRH administration (200 micrograms, iv) in 89 patients with documented hypothyroidism consequent to various hypothalamic-pituitary disorders. Basal plasma TSH was less than 1.0 microI/ml in 34.8%, between 1.0-3.6 microU/ml in 40.5% and slightly elevated (3.7-9.7 microU/ml) in 24.7% of the cases. The plasma TSH response to TRH was absent in 13.5%, impaired in 16.8%, normal in 47.2%, and exaggerated in 22.5% of the cases, with delayed and/or prolonged pattern of response in 65% of the cases. The dilution curves of several plasmas drawn before and after TRH were parallel to those obtained with TSH standard preparation. After gel filtration, the elution pattern of TRH-stimulated plasmas from 4 patients did not show any major difference from that of pooled plasmas from normal subjects given TRH or from that of patients with primary hypothyroidism. Plasma TSH values determined by cytochemical bioassay on both basal and TRH-stimulated samples of 5 patients were markedly lower than those obtained by RIA. The serum T3 response to TRH was absent or low in 40 out of 53 patients in whom it was evaluated. The administration of T3 (100 micrograms/day for 3 days) or dexamethasone (3 mg/day for 5 days) respectively suppressed or reduced both basal and TRH-induced plasma TSH levels. Two patients became hypothyroid shortly after pituitary surgery in spite of basal and TRH-induced plasma TSH levels similar to or higher than those before surgery. Though thyroid atrophy due to chronic understimulation could explain the low T3 response to TRH in secondary hypothyroidism, it is difficult to reconcile thyroid understimulation with normal or increased plasma TSH unless the immunoreactive material has low biological activity. Present data suggest that several patients with hypothyroidism consequent to hypothalamic-pituitary diseases secrete a material which is immunologically similar to pituitary standard TSH and responds to stimulatory and suppressive agents in a manner similar to normal TSH but has low or absent biological activity. Thus, hypothyroidism due to insufficient TSH stimulation can be termed central hypothyroidism and can be due 1) to pituitary insufficiency (secondary hypothyroidism), 2) to a hypothalamic defect (tertiary hypothyroidism), or 3) to the secretion of biologically inactive TSH.
Biological Assay↗
Parietal cell mass after short and long term cimetidine treatment of duodenal ulcer.
The parietal cell mass (PCM) was evaluated on endoscopically obtained biopsy specimens of fundus mucosa from 20 duodenal ulcer patients before and after cimetidine treatment. Patients were given cimetidine, 1 g/day, for 28 days. Six out of the 18 cases which healed after short-term therapy went on taking 400 mg/day of cimetidine for 9 months. The PCM was expressed by means of an index (PI) obtained by multiplying the mean cell number per mm of section surface by the mean parenchymal thickness. The analysis of the obtained data failed to demonstrate any significant difference between the PI observed before and after 28 days treatment with cimetidine, while after long term treatment for 9 months, a significant increase of the PI was achieved.
Adult↗
Antagonistic properties of N-methyl-N'-[2-(5-ethyl-4-imidazolyl-methylthio)ethyl]thiourea.
In the present paper the Authors describe the synthesis and the biological effects of N-methyl-N'-[2-(5-ethyl-4-imidazolylmethylthio)ethyl]thiourea (etiamide). This compound appeared to inhibit, to a certain extent, the effect of histamine on H2-receptors. This inhibition, however, was less pronounced than that elicited by metiamide and in some of the preparations examined appeared to be of the non-competitive type.
Animals↗
Metergoline treatment of hyperprolactinemic states.
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Adult↗
Restoration of cyclic ovarian function by metergoline treatment in a patient with a prolactin-secreting pituitary microadenoma.
A patient with amenorrhea due to a prolactin-secreting pituitary microadenoma was treated with the antiserotoninergic drug metergoline for 8 months. The first menstruation occurred after 1 month of therapy, and it was followed by regular menses by the 3rd month. Presumptive evidence of ovulation was obtained in at least some instances by serum progesterone and gonadotropin determination. Serum prolactin was only slightly lowered by treatment. The patient had menses and possibly ovulation in the 2 months following drug withdrawal. Metergoline might restore ovarian function in hyperprolactinemic amenorrhea either by prolactin suppression or perhaps by direct stimulation of gonadotropin release.
Adenoma↗
Inhibition of prolactin release by serotonin antagonists in hyperprolactinemic subjects.
Metergoline (4 mg) and methysergide (3 mg), two serotonin antagonists known to inhibit prolactin secretion in normal subjects, and the dopaminergic agonist, bromocriptine (2.5 mg) were orally administered in hyperprolactinemic patients. Mean serum prolactin concentration was significantly decreased between 120 and 240 min following the ingestion of all three drugs in comparison with a placebo; a consistent reduction to below 50% of basal values occurred in 10 of 14 patients after metergoline, in 5 of 10 after methysergide, and in 11 of 14 after bromocriptine administration. These data indicate that serotonin antagonists may acutely lower serum prolactin levels in hyperprolactinemic patients similarly to bromocriptine, though their mechanism of action is most likely different.
Adult↗
Increased glucose disappearance rate after short-term clofibrate administration in normal subjects and in patients with chemical diabetes.
Following seven days clofibrate administration, the glucose disappearance rate during an intravenous glucose tolerance test was significantly increased in 6 normal subjects and in 11 patients with chemical diabetes. Both the acute and the total insulin secretory response were unchanged. Though fasting serum levels of free fatty acids, triglycerides, and cholesterol were significantly lowered by treatment, no correlation was found between the decrease in serum lipids and the increase in glucose disappearance rate. It is suggested and clofibrate improves glucose utilization by reducing insulin resistance irrespective of its effects on serum lipids concentration.
Blood Glucose↗
Evaluation of the results of trans-sphenoidal surgery in acromegaly by assessment of the growth hormone response to thyrotrophin-releasing hormone.
Eighteen acromegalic patients GH-responsive to TRH were reinvestigated following trans-sphenoidal surgery and radiotherapy. Basal serum GH decreased below 10 microgram/1 in thirteen cases; nine of them became GH-unresponsive to TRH 1 month after operation, and another one following conventional pituitary irradiation. Four of these ten patients also showed a normal GH response to L-Dopa after treatment, and five responded normally to insulin-induced hypoglycaemia; two patients had a normal GH secretory pattern after both these stimuli. No recurrences were observed over a follow-up period of 15-80 months among the ten patients who became GH-unresponsive to TRH following operation, while one of the three subjects still responsive to TRH in spite of normalized basal serum GH concentration relapsed 10 months after surgery. Three patients with normalized TRH test following operation were repeatedly reinvestigated over a 3-6 years period and always found unresponsive. The present study shows that the 'paradoxical' GH responses to TRH and L-Dopa frequently disappear after surgery, that complete normalization of GH secretory pattern may rarely be attained, and that the disappearance of GH response to TRH probably indicates satisfactory treatment of acromegaly. These data suggest that the 'paradoxical' GH responses frequently found in acromegaly are dependent on the adenoma per se and not on hypothalamic dysfunction.
Acromegaly↗
Effect of dopamine infusion on gastric and pancreatic secretion and on gastrin release in man.
The effect of dopamine infusion on basal and pentagastrin-stimulated gastric secretion, on basal and secretin-CCK-PZ-stimulated pancreatic secretion, and on basal and meal-induced gastrin release has been evaluated in healthy volunteers. Both basal and stimulated gastric acid secretion were significantly inhibited during dopamine infusion with a significant rebound to pre-infusion values after discontinuing dopamine. These effects were prevented by pretreatment with the antidopaminergic drug, metoclopramide. A slight but now significant decrease in amylase and bicarbonate outputs was also observed during dopamine infusion, while gastrin release did not change. These data suggest the existence of dopaminergic mechanisms in the regulation of gastric acid secretion in man.
Adult↗
Prolactin suppression by serotonin antagonists in man: further evidence for serotoninergic control of prolactin secretion.
To further investigate the role of serotonin in human prolactin (Prl) secretion, serotonin antagonists have been administered to healthy volunteers in basal conditions and after pretreatment with the selective blocker of dopamine receptors, pimozide (Pim). Highly significant falls (p less than 0.001) in serum Prl were observed at 120, 180, and 240 min following the oral administration of metergoline (Met) (4 mg; N = 34) and methysergide (Meth) (3 mg; N = 20) in comparison with placebo. No significant difference was found in the degree of Prl suppression induced by these two serotonin antagonists and by hte dopaminergic drug bromocriptine (Br) (2.5 mg; N = 20). After Pim pretreatment (1 mg every 6 h for 7 days) the elevated serum Prl levels were reduced to 27.1% +/- 8.1 (SEM) of basal after Met and to 54.5% +/- 8.9 after Meth administration (N = 5 for each study). It is concluded that Met and Meth inhibit Prl secretion by mechanisms which are not or only partially related to dopaminergic receptors. These data are consistent with a stimulatory role for serotonin in human Prl release.
Adolescent↗
Effect of short-term clofibrate on glucose metabolism and insulin secretion in patients with mild maturity-onset diabetes mellitus.
The effect of 1 week clofibrate administration on glucose and insulin responses to oral glucose and to intravenous tolbutamide was evaluated in 21 patients with mild maturity-onset diabetes (fasting plasma glucose 108-152 mg/100 ml). After treatment, oral glucose tolerance and hypoglycaemic effect of tolbutamide were significantly improved; plasma insulin response was reduced after glucose and unmodified after tolbutamide; fasting plasma glucose was also significantly reduced. These findings did not correlate with the observed fall in serum lipids. Short-term clofibrate improves glucose metabolism in mild diabetes irrespective of its effects on lipid metabolism. It is suggested that the drug's action may be mediated by reduced insulin resistance.
Blood Glucose↗
Inhibition of gastrin secretion by sulpiride treatment in duodenal ulcer patients.
The serum gastrin response to whole beef extract was measured in 14 duodenal ulcer patients before and after sulpiride administration. A significant inhibition of response was found both after acute intramuscular injection of the drug and after oral administration for 1 week. Fasting serum gastrin was also significantly reduced after chronic treatment; gastric acid secretion did not change. Although the mechanism of the gastrin-lowering action of sulpiride is unknown, it could be mediated by some known effects(s) of the drug, such as modifications in brain monoamine metabolism or perhaps reduced growth hormone secretion.
Administration, Oral↗