Search PubMed⌕ Search

Biomedical subjects

O Serri

Publications and source records attributed to O Serri.

At least 55 records · Page 3Linked to original sources

Plasma aldosterone response to metoclopramide is unmodified by hyperprolactinemia.

It has been previously demonstrated that patients with hyperprolactinemia have impaired PRL response to dopaminergic blockade and increased TSH response. Since inhibitory dopaminergic modulation of aldosterone is well established, we have examined whether prolactinoma patients have an altered aldosterone response to dopaminergic blockade. To investigate this possibility we compared the plasma PRL, TSH and aldosterone responses to the dopamine (DA) antagonist metoclopramide (MCP; 10 mg i.v.) in 10 women with prolactinomas and 7 healthy female controls. Basal PRL levels in prolactinoma patients were elevated and showed a blunted rise following MCP. Although basal TSH levels were similar in the 2 groups of subjects, they significantly increased (p = 0.017) in prolactinoma patients while in contrast they did not significantly change in control subjects. Basal supine plasma aldosterone was similar in patients with prolactinomas (0.23 +/- 0.03 nmol/l) and in healthy subjects (0.25 +/- 0.04 nmol/l) and the increased aldosterone concentrations from 15 to 120 min following MCP were not significantly different in prolactinoma patients and in control subjects. It is concluded that in patients with prolactinomas, the alteration in the dopaminergic regulation is specifically related to the lactotroph.

Adult↗

Somatotroph responsiveness to low dose dopamine infusion in normal subjects and acromegalic patients.

We have investigated the effects of intravenous administration of a low dose of dopamine (DA) on plasma growth hormone (GH) concentrations in acromegalic patients and normal subjects with the aim of defining the somatotroph responsiveness to peripheral (i.e., outside the blood-brain barrier) specific dopaminergic stimuli. DA (0.02 micrograms/kg/min) was infused for 180 min into 12 acromegalic patients and 10 normal subjects. DA infusion discriminated between two groups of acromegalics. In group I (n = 7), the elevated plasma GH levels (64.1 +/- 29.9 ng/ml, mean basal value +/- SEM) decreased significantly (mean overall GH inhibition, 26% reduction from basal levels; range, 10-49), whereas in group II (n = 5) plasma GH levels (29.8 +/- 12.5 ng/ml) remained elevated (mean GH variation, 8% above baseline; range, 0-15). Plasma GH concentrations showed a significant rebound above baseline values after stopping DA infusion only in group I. In contrast, the responsiveness to TRH was not significantly different between the groups (percentage increase 767 +/- 317% in group I vs. 382 +/- 210% in group II) and they were also comparable with regard to sex, age, glucose tolerance, plasma prolactin (PRL) concentrations and adenoma size. However, the mean duration of the disease was significantly (p less than 0.02) longer in group I (12.8 +/- 2.6 years) than in group II (4.5 +/- 1.5 years). Further, 3 patients with previous radiotherapy for invasive adenomas were nonresponders to DA. In normal subjects, DA infusion had no significant effect on plasma GH levels. It is concluded that: somatotroph responsiveness to DA is not a constant feature of acromegaly.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

Role of sulfate conjugation of catecholamines in blood pressure regulation.

Catecholamine sulfates were found to be inactive at vascular receptor sites. Only at one nonvascular receptor site important for blood pressure (BP) regulation was dopamine-3-O-sulfate found to be an inhibitory modulator of the adrenocortical secretion of aldosterone in vitro. However, sulfation of catecholamines (CA) does play an important role in BP regulation, as shown by the following observations: Sulfoconjugated CA with a long half-life are sometimes better markers of CA release than free CA, which have short half-lives. This is particularly true of dopamine (DA) sulfate because free DA, being rapidly sulfoconjugated, is usually undetectable. This led to the recognition of a previously unsuspected role of DA in paroxysmal hypertension and orthostatic hypotension. Measurements of CA sulfates reveal potentially important storage functions for sulfoconjugation that can rapidly inactivate excessive circulating free CA and so mitigate their cardiovascular impact while building up a pool of conjugated CA. The possibility that free CA can be generated from this pool through deconjugation whenever a need for them arises should be further investigated. Reproducible individual differences in the velocity of the sulfoconjugation of infused free CA can be detected, which suggests a genetic control of certain components of the sulfoconjugating process. These differences in sulfoconjugation probably modulate the cardiovascular action of CA and of some drugs with similar structure that also undergo sulfoconjugation.

Adrenal Cortex↗

Decreased sensitivity to insulin in women with microprolactinomas.

To determine whether there exists an altered sensitivity to insulin in hyperprolactinemia, we studied, in 15 women with microprolactinomas, the insulin effects on glucose, PRL, GH, and cortisol before and after successful adenoma removal. Our results show that in women with microprolactinomas, the sensitivity to insulin is lower in hyperprolactinemia than in normoprolactinemia achieved by selective adenomectomy.

Adenoma↗

Effects of alloxan-induced diabetes on dopaminergic receptors in rat striatum and anterior pituitary.

The binding of [3H]-spiroperidol after 4 weeks of hyperglycemia was determined in the rat striatum and anterior pituitary. Alloxan-induced diabetes increased the number of dopaminergic binding sites in the striatum but not in the anterior pituitary. The interaction of metoclopramide with striatal dopaminergic receptors was slightly modified, while that of dopamine, bromocriptine and haloperidol was unaffected. These results suggest that chronic hyperglycemia exerts selective effects on nigrostriatal dopaminergic system in the rat.

Alloxan↗

Acromegaly: biochemical assessment of cure after long term follow-up of transsphenoidal selective adenomectomy.

This study reports the clinical and biological follow-up 5-11 yr after transsphenoidal selective adenomectomy in 25 patients with acromegaly. Eight patients had microadenomas, and 17 had macroadenomas. Initial normalization of plasma GH levels (basal values, less than 5 ng/ml; glucose-suppressed concentrations, less than 2.5 ng/ml) was achieved in all 8 patients with microadenomas and in 13 patients with macroadenomas. Of these, 3 patients with normal GH levels and dynamics had relapse of GH hypersecretion after intervals between 1-6 yr after microadenoma removal. Recurrence of pituitary adenoma was documented by surgery in 1 patient and by computed tomographic scanning in 2 others. Normal basal and glucose-suppressed plasma GH concentrations were maintained 7.4 +/- 0.5 (+/- SEM) yr after adenomectomy in 7 patients with microadenomas and in all 10 patients with macroadenomas. Thus, 88% of the patients with microadenomas and 59% of the patients with macroadenomas were cured, and the overall cure rate was 68%. We conclude that recurrence of acromegaly after successful surgery may occur late after adenoma removal and that it cannot be predicted by normal postoperative GH levels and dynamics. However, in view of the overall cure rate, transsphenoidal adenomectomy remains a most valuable treatment for acromegaly.

Acromegaly↗

Dopaminergic binding sites in human pituitary adenomas other than prolactinomas.

Binding studies of [3H]-spiroperidol, a potent dopamine antagonist, were performed on dispersed cells obtained from 2 mixed PRL- and GH-secreting adenomas, 3 GH-secreting adenomas and 4 'nonsecreting' pituitary tumors. Saturable, high affinity binding sites for [3H]-spiroperidol were identified in the two adenomas of mixed PRL and GH secretion, in 2 of 3 GH-secreting adenomas and in 2 of 4 'nonsecreting' adenomas. These data indicate that dopaminergic binding sites are present in some GH-secreting adenomas in the absence of PRL hypersecretion and in some 'nonsecreting' pituitary adenomas.

Adenoma↗

Interaction of sulpiride with human pituitary dopaminergic receptors is sodium dependent.

The effects of various drugs on [3H]-spiroperidol binding to human anterior pituitary and prolactinoma membranes are studied in the presence and in the absence of sodium chloride in the incubation medium. It is shown that in the absence of NaCl, 1-sulpiride is significantly less potent in displacing the radioactive ligand from its dopaminergic binding sites than in the presence of NaCl. On the contrary, the interaction of neuroleptics (d-butaclamol and haloperidol) and dopamine agonists (apomorphine and bromocriptine) was unaffected by the NaCl conditions.

Binding, Competitive↗

Recurrence of hyperprolactinemia after selective transsphenoidal adenomectomy in women with prolactinoma.

To assess the long-term prognosis for women with prolactinoma after selective transsphenoidal adenomectomy, we followed 44 patients for 6.2 +/- 1.5 years. Group 1 (28 patients) had microprolactinomas, and Group 2 (16 patients) had macroprolactinomas. After surgery, normal plasma prolactin levels, resumption of menses, and cessation of galactorrhea were observed in 24 Group 1 patients (85 per cent) and 5 Group 2 patients (31 per cent). Hyperprolactinemia recurred in 12 of the 24 Group 1 patients and in 4 of the 5 Group 2 patients after 4 +/- 1.3 and 2.5 +/- 1.6 years of remission, respectively. There was no radiologic evidence of tumor recurrence in any patient, and no relation was found between the occurrence of pregnancy after surgery and the recurrence of hyperprolactinemia. Clinical and biologic features before surgery could not predict the long-term outcome. However, the immediate postoperative level of plasma prolactin was significantly lower in patients in whom normal prolactinemia (6.4 +/- 1.1 ng per milliliter) was maintained than in those who relapsed (11.7 +/- 1.5 ng per milliliter) (P less than 0.02). We conclude that recurrence of hyperprolactinemia after successful surgery is frequent but delayed. The immediate postoperative level of plasma prolactin may be a predictive risk factor.

Adenoma↗

Differential effects of a low dose dopamine infusion on prolactin secretion in normal and hyperprolactinemic subjects.

The PRL inhibitory effect of dopamine (DA) in human in vivo studies has been previously demonstrated with DA infusions at rates generally exceeding 2 micrograms/kg . min. We report here the effects of a DA infusion administered at a rate of 0.02 microgram/kg . min for 180 min to 10 normal subjects and 25 hyperprolactinemic patients with pituitary tumors (13 microprolactinomas, 8 macroprolactinomas, and 4 expanding nonsecreting pituitary adenomas). Serum free DA concentrations during the 3-h DA infusion reached an average of 0.8 +/- 0.1 ng/ml (about an 8- to 10-fold rise from basal levels). DA produced a significant (P less than ) 0.001) decline in plasma PRL levels in both normal subjects and hyperprolactinemic patients. There was a negative linear correlation between the serum DA concentrations and the percent PRL variation from basal levels (r = -0.58; P less than 0.001). The comparison of RPL responses between the different groups revealed that the mean percent overall PRL inhibition was significantly lower in patients with microprolactinomas than in normal subjects (P less than 0.02). On the other hand, PRL inhibition was greater in patients with nonsecreting adenomas than in either patients with microprolactinomas or those with macroprolactinomas (P less than 0.001). From 90-180 min, PRL suppression was also greater in patients with nonsecreting adenomas than in normal controls (P less than 0.05). The present study shows that 1) slight elevations of plasma DA are sufficient to inhibit PRL secretion, suggesting that DA acts as major physiological PRL-inhibiting factor, 2) there is a relative PRL resistance to DA inhibition in microprolactinoma patients; and 3) PRL is hyperresponsive to DA in expanding nonsecreting pituitary tumors.

Adenoma↗

Effects of naloxone on insulin-induced release of pituitary hormones.

To evaluate the role of endogenous opiates on the regulation of the pituitary hormonal stress response, we have studied in six normal subjects the insulin-induced secretion of PRL, GH, and ACTH with and without naloxone, a specific opiate antagonist. During hypoglycemia, naloxone infusion reduced plasma PRL levels at 90 min, lowered the overall GH response, and enhanced that of ACTH. These observations suggest that endogenous opiates have a modulatory role in the stress-induced secretion of pituitary hormones.

Adrenocorticotropic Hormone↗

[In vitro studies of prolactinomas].

A few prolactinomas have been cultured into semipermanent cell lines. This transformation-like behavior is demonstrated. The tumor cells, obtained after transphenoidal surgery have been grown on extracellular matrix, using a mixture of Sephadex beads or a feeder layer of irradiated C.H.O. cells. The cells did survive to several sub-cultures and formed clones rapidly growing in soft agar. The PRL secretion evaluated through R.I.A. method declined with sub-culturing. A study of dopaminergic receptors on the same kind of material has shown the presence of those receptors and their persistence, even through sub-culturing.

Adenoma↗

Prolactin-secreting pituitary adenomas in males: transsphenoidal microsurgical treatment.

Fifteen male patients with prolactin-secreting pituitary adenomas were studied before and after transsphenoidal microsurgical treatment. Loss of libido and sexual impotence were the most frequent symptoms, being present in 12. Visual defects were present in seven patients, gynecomastia was observed in four and galactorrhea was noted in three. Most of the tumours were large; only one was a microadenoma. Four patients were cured by the operation. In all the other patients the plasma levels of prolactin were significantly lowered and the visual defects corrected or lessened, but sexual impotence was not modified. No important deficiency of the pituitary gland was induced by the operation. The results indicate that in males loss of libido and sexual impotence are frequent and early manifestations of prolactinomas, and that transsphenoidal resection is a safe therapeutic approach.

Adenoma↗

Effect of gliclazide on monocyte-endothelium interactions in diabetes.

Enhanced monocyte-endothelial cell interactions have been documented in diabetes. Because adherence of monocytes to the endothelium is one of the earliest events in the development of atherosclerosis, its alteration may represent one of the mechanisms leading to accelerated atherosclerosis in diabetic patients. Previous studies have suggested that lipoprotein oxidation and protein glycation may contribute to the increased monocyte binding to the diabetic vasculature. Based on the recent finding that gliclazide has free-radical scavenging activity, we examined the ex vivo and in vitro effects of this drug on human monocyte binding to endothelial cells. Our results demonstrate that short-term administration of gliclazide to patients with type 2 diabetes lowers the enhanced adhesion of diabetic monocytes observed before gliclazide treatment (163+/-24% over control values, p<0.005) to levels similar to those observed in controls. They also show that gliclazide (10 microg/ml) reduces in vitro by approximately 35% both oxidized low-density lipoprotein (LDL)- and glycated albumin-induced monocyte adhesion to endothelial cells. Based on these results, we next investigated the molecular mechanisms responsible for the inhibitory effect of gliclazide on glycated albumin-induced monocyte adhesion to endothelium. In glycated albumin-treated endothelial cells, we observed induction of cell-associated expression of E-selectin (ELAM-1; 170+/-10% over control values, p<0.005), intercellular cell adhesion molecule-1 (ICAM-1; 131+/-8% over control values, p<0.005) and vascular cell adhesion molecule-1 (VCAM-1; 134+/-8% over control values, p<0.005), augmentation in the levels of the transcripts of these molecules, and an increase in the DNA binding of NF-kappaB in the promoters of these antigens. Gliclazide markedly inhibited the induction of all these parameters. Because the oxidative stress-sensitive transcription factor NF-kappaB is implicated in endothelial cell activation, the observed inhibitory effect of gliclazide on NF-kappaB activation and glycated albumin-induced expression of DNA binding activity for the NF-kappaB site in the ELAM-1, ICAM-1 and VCAM-1 promoters seems to be due to its antioxidant properties. These results suggest that gliclazide, by its ability to reduce endothelial activation, may exert potential beneficial effects in the prevention of atherosclerosis associated with type 2 diabetes.

Aged↗

Sulfoconjugation of catecholamines, nutrition, and hypertension.

Sulfoconjugation is an important metabolic pathway determining the fate and potential cardiovascular action of ingested phenolic substances. Among the three catecholamines, dopamine (DA) is to the highest degree sulfoconjugated and has the highest affinity toward the phenolsulfotransferase (PST). The concentration of some sulfated catecholamines, particularly of DA sulfate, increases following ingestion of catecholamines or their precursors. This can be confounded with blood-derived increases in DA sulfate associated with BP peaks in some hypertensive patients. We mimicked, therefore, the latter condition by infusion of free DA into normotensive subjects. At low DA infusion rates, plasma DA sulfate exceeded free DA concentrations, and there were no changes in blood pressure and pulse rate. At higher DA infusion rates, blood pressure and pulse rate increased only while plasma free DA concentrations exceeded those of DA sulfate, indicating that free DA remains biologically active only prior to being conjugated. A similar increase in DA sulfate from alimentary sources (e.g., eating a banana) remains without cardiovascular response and is not associated with an overflow of free DA, since all the ingested DA is conjugated in the gut. We describe a patient with pheochromocytoma who experienced repeated hypertensive crises after ingestion of food containing some biogenic amines, (once also documented by NE increase), possibly due to a phenol sulfoconjugation defect (e.g., substrate inhibition of the PST or its genetic deficiency). Platelet PST-determinations may serve as a screening tool to detect subjects with sulfoconjugation defects since they probably reflect the PSt activity in the gut where ingested phenols are sulfoconjugated.

Adrenal Gland Neoplasms↗

[Cushing's syndrome and pregnancy: apropos of a case and review of the literature].

The occurrence of Cushing's syndrome during pregnancy is rare. Sixty-eight cases have been reported in the literature of which 42.7% were secondary to an adrenal adenoma, 10.2% to an adrenal carcinoma, 26.5% to a bilateral adrenal hyperplasia and 11.8% to Cushing's disease. We report the case of a patient in whom the diagnostic of Cushing's syndrome with an adrenal adenoma was established during the postpartum period.

Adenoma↗