Search PubMed⌕ Search

Biomedical subjects

F Cavagnini

Publications and source records attributed to F Cavagnini.

At least 109 records · Page 6Linked to original sources
PubMed1984

Metergoline in the management of normoprolactinemic secondary amenorrhea. A multicentric controlled trial.

In a multicentric study, the effect of the antiserotoninergic agent metergoline was evaluated in the management of patients with idiopathic normoprolactinemic secondary amenorrhea (NSA). The awareness that psychological factors might lead to a spontaneous reappearance of menses was also taken into account, and all the patients, after physical, gynecological and laboratory examinations, and the performance of the progesterone withdrawal bleeding test (100 mg i.m.) and the clomiphene citrate test (100 mg p.o./day for 5 days), were treated for 60 days with placebo; only patients showing no menses during placebo administration were later treated with metergoline. 108 patients entered the trial: of these, 48 experienced menses on admission or during placebo administration, and were withdrawn. Of the 60 patients not responding to placebo, 50 were treated for 90 days with metergoline (4 mg t.i.d.), and 23 had menses, ovulatory in 68.4% of cases. A new placebo treatment was accompanied, in the majority of cases, by recurrence of amenorrhea. These results indicate that many patients with NSA may experience a spontaneous disappearance of the disease: in cases more seriously affected metergoline might be a useful therapeutic agent.

Amenorrhea↗
PubMed1984

Dynamic testing of prolactin and growth hormone secretion in patients with neuroendocrine disorders.

Prolactin (Prl) and growth hormone (GH) responses to different pharmacologic probes acting at the central nervous system (CNS) or the anterior pituitary (AP) level were evaluated in patients with distinct neuro-endocrine disorders. Thirteen patients with Prl-secreting tumours (PST), 10 acromegalics (A) and 8 patients with hypothalamic lesions (HL), as assessed on clinical, radiological and surgical grounds, underwent on separate occasions acute testing with the opioid peptide FK 33-824 (0.5 mg iv), the indirect dopamine (DA) agonist nomifensine (NOM, 200 mg po), the DA receptor antagonist domperidone (DOM, 10 mg iv), TRH (200 microgram iv) and insulin (ITT, 0.10-0.15 IU/kg iv). All patients were evaluated pre-surgery and 4 of them also post-surgery. Prl and GH were evaluated by RIA at different time intervals following treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1983

Cholinergic and histaminergic involvement in the growth hormone releasing effect of an enkephalin analog FK 33-824 in man.

Studies were performed in healthy subjects to ascertain the neurotransmitter systems involved in the growth hormone (GH)-releasing effect of the potent enkephalin analog FK 33-824. Concomitant evaluation of prolactin (PRL) secretion was also performed in the same subjects. FK 33-824 at a dose of 0.5 mg IV elicited a clear-cut rise in plasma GH and PRL concentrations with peak levels at 45 min. Blockade of muscarinic cholinergic receptors by atropine (0.5 mg SC) or histaminergic H1 receptors by diphenhydramine (50 mg IV bolus plus 50 mg infusion) completely suppressed the GH release induced by FK 33-824, without significantly altering the PRL rise induced by the peptide. Pretreatment with the alpha-adrenergic antagonist phentolamine (0.5 mg IV/min for 120 min) or the dopamine receptor blocker metoclopramide (10 mg IV) did not alter the GH-releasing effect of FK 33-824. Phentolamine failed to alter the PRL rise induced by FK 33-824, while combined FK 33-824-metoclopramide administration induced a greater PRL increase than FK 33-824 alone. These results indicate that cholinergic and histaminergic H1 receptors play an important role in the GH-release induced by FK 33-824 in man, whereas this action seems to occur independently of catecholaminergic mediation. The same receptors are not involved in the PRL-releasing effect of the peptide.

Adult↗
PubMed1983

Different rebound rise in plasma prolactin during the postdopamine infusion phase in puerperal women and patients with pathological hyperprolactinemia.

Dopamine infused at a rate of 4 micrograms/kg . min for 120 min induced at the end of the infusion period a clear-cut and similar suppression of circulating PRL levels in normal and puerperal women as well as in patients with hyperprolactinemia either due to a tumor or of unknown etiology. At the discontinuation of the infusion there was a marked PRL rebound above baseline levels in normal subjects and a rapid return to basal levels in subjects with pathological hyperprolactinemia. In contrast, there was no increase in plasma PRL in puerperal women, in whom PRL levels remained suppressed during the whole postinfusion period. The reason(s) for this pattern in puerperal women is presently unknown, although previous estrogen loading of the lactotropes during pregnancy may be involved.

Adolescent↗
PubMed1982

gamma-Aminobutyric acid- and benzodiazepine-binding sites in human anterior pituitary tissue.

The existence of a gamma-aminobutyric acid (GABA) system in human anterior pituitary tissue was examined. Crude membrane fractions prepared from human anterior pituitary tissue bound tritiated GABA. The binding was saturable, and Scatchard analysis indicated a single binding site of high affinity (Kd = 40 nM) and a maximum binding of 1.2 pmol/mg protein. Binding was displaced in a dose-related manner by the GABA agonists muscimol (KI = 1 X 10(-8) M), isoguvacine (KI = 6 X 10(-7) M), THIP (4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol); KI = 5 X 10(-6) M), and the antagonist (+)bicuculline (KI = 5 X 10(-5) M) but not its inactive stereoisomer (-)bicuculline (KI greater than 10(-3) M). In anterior pituitary tissue, a significant concentration of GABA was found (mean, 2.5 +/- 0.5 nmol/mg protein) but no glutamic acid decarboxylase activity, the enzyme synthesizing GABA, was detected using a highly sensitive assay. In addition, benzodiazepine binding was present. An affinity of approximately 15 nM and a Bmax of approximately 0.75 pmol/mg protein were observed when using [3H]diazepam as the ligand. No saturable clonazepam binding occurred, and only slight GABA stimulation of diazepam binding was observed (mean, 18%; range, 6-38%). The ability of GABA and benzodiazepine to alter PRL secretion in rats suggests that the human pituitary GABA-binding sites described here might also mediate effects on PRL release.

Adult↗
PubMed1982

Effects of gamma aminobutyric acid (GABA) and muscimol on endocrine pancreatic function in man.

The high concentrations of gamma aminobutyric acid (GABA) in the pancreatic islets and the neurotransmitter role played by this amino acid in the central nervous system, make it plausible that GABA also intervenes in the control of endocrine pancreatic function. In 12 normal subjects, a single oral dose of 5 or 10 g GABA, as compared to placebo, caused a significant (p less than 0.01) and dose-dependent (p less than 0.01) increase of plasma levels of immunoreactive insulin, C peptide and glucagon, without affecting plasma glucose concentration. By contrast, in 15 additional subjects, a single oral dose of 5 mg muscimol, a specific GABA receptor agonist, did not consistently influence the above parameters. Although the lack of effects of muscimol might indicate that the action of GABA is not mediated through specific receptors, the results with GABA suggest that this amino acid plays a specific role in the regulation of endocrine pancreatic function.

Adolescent↗
PubMed1980

Effect of gamma-aminobutyric acid on growth hormone and prolactin secretion in man: influence of pimozide and domperidone.

To investigate the possibility that GH release induced by gamma-aminobutyric acid (GABA) in man is mediated by a dopaminergic mechanism(s), we evaluated the effect of two antidopaminergic compounds, pimozide and domperidone, on the plasma GH response to acute GABA administration (5 g, orally). Only the former compound can freely cross the blood-brain barrier. In 9 normal volunteers, GABA caused a significant increase of plasma GH levels (P < 0.0001 vs. GH levels in a group of 14 controls). In these subjects, pimozide (6 mg/day, orally, for 4 days) significantly blunted the GH elevation induced by GABA (P < 0.01). Unlike pimozide, in 8 additional subjects, domperidone (4 mg injected iv immediately before GABA administration) did not influence the GABA-induced GH response. GABA did not alter either baseline or pimozide-stimulated plasma PRL levels. Likewise, it did not significantly modify the brisk PRL rise after domperidone injection. These findings are consistent with the hypothesis that GABA-stimulated GH secretion is mediated via dopamine release at a suprapituitary level. With regard to PRL secretion, no GABA-dopamine interactions are readily apparent.

Adult↗
PubMed1980

Effect of acute and repeated administration of gamma aminobutyric acid (GABA) on growth hormone and prolactin secretion in man.

A single oral dose of 5 g gamma aminobutyric acid (GABA) was given to 19 subjects and serial venous blood samples were obtained before and 3 h after drug administration. A placebo was administered to 18 subjects who served as controls. GABA caused a significant elevation of plasma growth hormone levels (P less than 0.001), but did not consistently alter plasma prolactin concentration since only 5 out of 15 subjects showed an increase of the hormone. Eight additional subjects were submitted to an insulin tolerance test before and after per os administration of 18 g GABA daily for 4 days. Protracted GABA treatment significantly blunted the response of growth hormone and enhanced that of prolactin to insulin hypoglycaemia (P less than 0.01). These results indicate that pharmacological doses of GABA affect growth hormone and prolactin secretion in man. The precise nature of GABA's effects as well as its mechanism of action remains to be clarified.

Administration, Oral↗
PubMed1979

Effect of two prostaglandin synthesis inhibitors, indomethacin and acetylsalicylic acid, on plasma ACTH and cortisol levels in man.

The aim of this study was to investigate the possible role of prostaglandins (PG) in the control of the hypohtalamic-pituitary-adrenocortical axis in normal volunteers. Acute oral administration of 100 mg indomethacin (ID) or 1.5 g acetylsalicylic acid (ASA) did not alter ACTH and cortisol plasma levels. Administration of 300 mg daily ID for 4 days delayed the onset, but increased the magnitude, of the response of ACTH to insulin hypoglycaemia, while it blunted the cortisol response. Administration of 3.2 g ASA daily depressed ACTH response to hypoglycaemia leaving the cortisol response unchanged, except for a 15 min delay in onset. These results are interpreted assuming that ID and ASA chiefly acted at the pituitary and hypothalamic level, respectively, and that ID, but not ASA, interfered with adrenocortical cortisol production. Our findings support the concept, based on animal studies, that PG enhance hypothalamic CRF release and adrenocortical steroidogenesis and may restrain ACTH secretion in the pituitary.

Administration, Oral↗
PubMed1977

Effects of acetylsalicylic acid and indomethacin on growth hormone secretion in man.

To investigate the possibility that prostaglandins (PG) take part in the control of growth hormone (GH) secretion in humans, we have studied the effects of protracted and acute administration of acetylsalicylic acid (ASA) and indomethacin (ID), two PG synthesis inhibitors, on basal and insulin-stimulated GH secretion in normal volunteers. In eight subjects, oral administration of 3-2 g daily of ASA for 4 days clearly reached GH response to insulin hypoglycemia (p less than 0.01, ANOVA). In six additional subjects, GH response to hypoglycemia was not modified by a 4-day oral treatment with 300 mg daily of ID. The pattern of plasma free fatty acids (FFA) and blood glucose during the insulin tolerance test was not significantly affected by ASA treatment. After ID the O time value of the above parameters was somewhat higher than under basal conditions, while the drop of blood glucose, but not to FFA, was slightly more pronounced. Acute oral administration of 1.5 g ASA in 12 subjects did not appreciably modify baseline plasma GH, FFA, and blood glucose levels. By contrast, a single oral dose of 100 mg ID in 12 subjects caused a moderate but significant rise (p less than 0.05) of plasma GH levels together with a clear elevation (p less than 0.01) of plasma FFA and blood glucose levels with respect to a group of controls treated with a placebo. Collectively these results are compatible with the possibility that PG play a physiologic stimulating role in the control of GH secretion, although an effect of ASA and ID unrelated to PG inhibition cannot be ruled out, In any event, in view of the number of endocrine and metabolic alterations induced by ASA and ID, these drugs seem to merit further study.

Adult↗
PubMed1976

Effect of an antiserotoninergic drug, metergoline, on the ACTH and cortisol response to insulin hypoglycemia and lysine-vasopressin in man.

The effect of metergoline, a specific antiserotoninergic drug, on ACTH secretion was investigated in 29 normal volunteers and in 4 patients with increased ACTH production (3 with Addison's disease, 1 with Cushing's disease). In 15 normal subjects, a 4-day treatment with 10 mg daily of metergoline significantly blunted the ACTH response to insulin hypoglycemia. Mean peak ACTH values before and after treatment were, respectively, 333 +/- 39.2 (SE) and 235 +/- 38.8 pg/ml (P less than 0.05). The corresponding values of plasma cortisol were 29.6 +/- 2.96 and 20.5 +/- 2.67 mug/100 ml (P less than 0.05). In contrast, metergoline failed to affect the ACTH response to lysine-vasopressin (LVP) administered iv (8 subjects studied) and im (6 subjects studied). In 3 patients suffering from Addison's disease, an appreciable although not statistically significant lowering of the plasma ACTH levels was noted during metergoline administration. The mean pre- and post-treatment values of plasma ACTH in these patients were, respectively, 1116 +/- 192.2 and 666 +/- 100.8 pg/ml, 4240 +/- 50.0 and 3398 +/- 368.0 pg/ml, and 431 +/- 44.0 and 352 +/- 23.9 pg/ml. In one patient with Cushing's disease caused by a pituitary adenoma, metergoline did not appreciably modify plasma ACTH levels. Taken together, these results lend support to the concept of a physiological stimulating effect of serotonin on ACTH secretion. Moreover, they are compatible with the view that serotonin exerts its action chiefly at the hypothalamic level while LVP promotes ACTH release by a primary action on the pituitary.

Addison Disease↗
PubMed1975

Inhibition of ACTH response to oral and intravenous metyrapone by antiserotoninergic treatment in man.

Plasma ACTH levels after oral and iv metyrapone administration were studied in 7 and 5 healthy women respectively both under basal conditions and after a 4-day treatment with metergoline, a specific antiserotoninergic agent. In 3 additional women, the effects of methysergide, another antiserotoninergic drug, on the plasma ACTH rise induced by oral metyrapone, were evaluated. A significant lowering of the plasma ACTH levels attained after either oral or iv metyrapone was observed following metergoline administration: 149+/-64.3 vs 239+/-49.1 pg/ml (mean peak values), P less than 0.05 in the oral test and 331+/-19.7 vs 221+/-19.5 pg/ml, P less than 0.02 in the iv test. The fall of plasma cortisol caused by metyrapone was comparable before and after the antiserotoninergic treatment. An interference of metergoline in the ACTH radioimmunoassay was also excluded. After metergoline administration, a slight reduction in the baseline plasma ACTH values was noted: 79+/-7.7 vs 67+/-7.7 pg/ml (NS). A decrease, however not statistically significant, of the metyrapone-induced plasma ACTH elevation occured after methysergide administration: 421+/-150.7 vs 344+/-135.1 pg/ml. These results can be interpreted as indicating that antiserotoninergic treatment caused an inhibition of hypophysial ACTH release in response to metyrapone. Caution is recommended, however, before concluding, on the basis of these findings, that serotonin as such plays a physiological stimulating role on ACTH secretion.

Administration, Oral↗
PubMed1975

[Changes in the secretion of somatotropin and insulin in hyperthyroidism].

Twenty hyperthyroid patients were investigated for growth hormone (GH) and immunoreactive insulin (IRI) secretion in response to insulin hypoglycaemia, arginine infusion and glucose-induced hyperglycaemia. GH response to either insulin hypoglycaemia or arginine infusion was significantly reduced in these patients compared with 20 normal subjects. Thyrotoxic patients also displayed an abnormal GH pattern after a 100 g oral glucose load: in fact, serum GH underwent a paradoxical increase in spite of abnormally high levels attained by blood glucose. IRI secretion was also clearly reduced in response to arginine infusion and moderately blunted after oral glucose. In a group of patients re-evaluated under euthyroid conditions, a fair increase of GH response to the provocative stimuli jointly with the restoration of a normal suppressibility of serum GH by glucose were noted; by contrast, no significant change of IRI response to arginine or glucose took place. Likewise, the impairment of glucose tolerance was not improved. These findings indicate that an impairment of GH and IRI secretion is present in hyperthyroidism. The possibility that a potentiation of the catecholamine effects caused by the thyroid hormones is involved in this alteration deserves consideration.

Adult↗