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Biomedical subjects

A Gnudi

Publications and source records attributed to A Gnudi.

At least 19 recordsLinked to original sources

The infusion of somatostatin reduces the arginine-vasopressin response to insulin-induced hypoglycemia in man.

The effect of an iv infusion of somatostatin (SRIH) (4.1 micrograms/min x 90 min) on the basal secretion of arginine-vasopressin (AVP) and on the AVP response to insulin (0.15 IU/Kg) - induced hypoglycemia was studied in 6 normal men. Basal AVP secretion was not modified by SRIH administration. The blood glucose decrements induced by insulin were similar in the control insulin-tolerance test (ITT) and in the ITT + SRIH test, whereas the AVP response to hypoglycemia was significantly lower in the presence of SRIH. The mean peak AVP increase was three times higher than the basal value in the control ITT, but only two times during SRIH administration. Infusion of higher doses of SRIH (7 micrograms/min x 90 min) produced similar results. These data suggest the involvement of a somatostatinergic mechanism in regulation of AVP response to hypoglycemia.

Adrenocorticotropic Hormone

Naloxone abolishes the inhibiting effect of somatostatin on the release of oxytocin evoked by insulin-induced hypoglycemia in humans.

The effect of somatostatin (SRIH) on the release of oxytocin (OT) in response to hypoglycemia during insulin tolerance test (ITT) was studied in seven normal men. Subjects were injected intravenously with 0.15 U/kg insulin alone (control test) or together with SRIH (4.1 micrograms/min x 90 min), naloxone (10 mg in an IV bolus), or the combination of the two substances. Plasma OT concentrations rose significantly during ITT; the OT response was significantly reduced by the treatment with SRIH and increased in the presence of naloxone. When both SRIH and naloxone were given, the OT response to hypoglycemia did not differ from that observed in the control test. These findings provide evidence that the effect of hypoglycemia on plasma OT levels is sensitive to the inhibition by SRIH and by naloxone-sensitive endogenous opioids. Because naloxone reversed the inhibiting effects of SRIH, an involvement of opioid peptides in SRIH action might be supposed. Alternatively, SRIH and naloxone-sensitive opioids might produce their inhibiting effects on OT rise in response to hypoglycemia through independent pathways.

Adult

Abnormal thyroid stimulating hormone, prolactin, and growth hormone responses to thyrotropin releasing hormone in abstinent alcoholic men with cerebral atrophy.

The thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) responses to thyrotropin releasing hormone (TRH), the Wechsler Adult Intelligence Scale (WAIS) for cognitive impairment, and computed tomographic scans were evaluated in 15 nondepressed alcoholic men after 4 weeks of abstinence and in 10 normal controls. Both cognitive impairment and cerebral atrophy were found in 13 of the alcoholics. Eight alcoholics (seven with cerebral atrophy) had blunted TSH and PRL responses to TRH and a TRH-induced paradoxical increase of GH. This study demonstrates that besides affecting the TSH response to TRH, alcoholism often induces alterations of the PRL and GH secretory patterns in response to TRH. The severe brain damage caused by long-term alcoholism might be involved in the pathogenesis of these neuroendocrine alterations.

Adult

Dopaminergic, but not cholinergic, involvement in regulation of hypoglycemia-induced oxytocin release in man.

The plasma oxytocin response to insulin-induced hypoglycemia was evaluated in 20 normal male subjects in the basal state (insulin tolerance test (ITT) alone) and after pretreatment with the muscarinic antagonist pirenzepine (40 mg IV 10 min before the ITT in six subjects), the nicotinic antagonist trimethaphan (0.3 mg/min IV for 30 min before the ITT in six subjects), and the dopaminergic receptor agonist bromocriptine (2.5 mg PO 1 hr before the ITT in eight subjects). The drugs did not modify arterial blood pressure nor produce side effects capable of altering oxytocin secretion. Neither pirenzepine nor trimethaphan administration changed the oxytocin response to hypoglycemia, whereas bromocriptine significantly reduced the oxytocin increase during the ITT. These data suggest the involvement of dopaminergic, but not of cholinergic, muscarinic or nicotinic, receptors in the oxytocin response to hypoglycemia.

Adult

Effects of the GABAergic agent sodium valproate on the arginine vasopressin responses to hypertonic stimulation and upright posture in man.

In order to evaluate the possible influence of GABAergic neurotransmission on the arginine vasopressin (AVP) response to osmotic and pressure volumetric stimuli, the GABAergic drug sodium valproate was administered by mouth (200 or 400 mg 16 h, 8 h and just before tests) to eight normal men before osmotic (i.v. infusion of 0.51 , NaCl for 2 h) and orthostatic (standing upright and maintaining an orthostatic position for 20 min) tests. In both experimental conditions, the AVP rise was significantly lower in the presence than in absence of sodium valproate. The maximum AVP responses in the control orthostatic and osmotic tests were respectively 2.3 and 2.5 times higher than basal levels. When 600 mg sodium valproate was given, the maximum AVP rise in response to hypovolaemic and osmotic stimuli were respectively 1.75 and 2.1 times higher than basal value. Similar results were obtained giving 1.2 g sodium valproate. These results suggest that in man a GABAergic pathway is involved in the AVP responses to hypovolaemic and hyperosmotic stimuli.

Adult

Glucose metabolism and larger molecule removal in long-term high efficiency hemofiltration.

High efficiency hemofiltration (HF) was carried out for 9 months in 6 patients on hemodialysis (HD). Comparative studies on carbohydrate metabolism and 500- to 1,500-dalton serum solute concentrations were performed during HD and HF. After 5 months of HF, intravenous glucose tolerance tests showed an improved peripheral glucose utilization, with unchanged insulin secretion. Larger solute concentrations, measured by gel chromatography, simultaneously dropped in serum suggesting that HF removes some toxic substances that inhibit peripheral insulin action. After 9 months of HF, an unexpected increase in the larger solute concentration coincided with an impaired glucose tolerance, stressing the probable toxic rule of such solutes. Changes in other glucoregulatory hormone secretions were not unequivocal. On account of the later increase in 500- to 1,500-dalton solute concentrations, HF failed to prevent larger toxic molecules accumulating in uremic sera.

Anuria

Lack of effect of nicardipine and diltiazem on glucose- and arginine-induced insulin release in obese subjects.

The metabolic effects of calcium channels blockers have already been studied both in normal and diabetic humans and results were quite controversial, depending on the drug used, the dose administered, and the type of patient. Little information exists on the use of Ca2+ antagonists in obese people, even if these persons are a population risk group for developing diseases in which these drugs may be requested for treatment. Thus, we evaluated, in obese humans, the metabolic effects of two Ca2+ antagonist drugs recently made commercially available to treat diseases such as hypertension and ischemic heart disease: nicardipine and diltiazem. Sixteen obese subjects were submitted to an intravenous glucose tolerance test (0.33 g/kg) (IVGTT) and an arginine test tolerance (30 g in 30 minutes) (ATT) before and after a week of oral treatment with nicardipine (60 mg/day) or diltiazem (360 mg/day). Plasma values of glucose, insulin, and C-peptide during IVGTT, and of glucose, insulin and glucagon during ATT did not show any modification during treatment with either drug. Thus the Ca2+ antagonists, nicardipine and diltiazem, at therapeutic doses in obese subjects do not significantly affect glucose tolerance or insulin and glucagon release.

Arginine

Metergoline, naloxone, and sodium valproate did not modify arginine vasopressin response to insulin-induced hypoglycemia in man.

The present study was carried out in order to determine whether insulin-induced hypoglycemia exerts its stimulatory effect on plasma concentrations of arginine vasopressin (AVP) by interacting with a serotonergic, a GABA-ergic or an opioid pathway. For this purpose, the effect of the serotonergic antagonist metergoline (10 mg/day for 4 days po), the GABA-ergic agonist sodium valproate (600 mg in three divided doses po) and the opioid-receptor blocker naloxone (10 mg in a iv bolus) on the AVP response during an insulin (0.15 IU/kg bw) tolerance test (ITT) was evaluated in three groups of 6 normal men each. In all men, control ITTs were performed without drug treatments. Basal and ITT-stimulated AVP secretion was not modified by drug administration, suggesting that serotonergic, GABAergic and naloxone-sensitive opioid receptors are not involved in the regulation of AVP secretion in response to insulin-induced hypoglycemia.

Adrenocorticotropic Hormone

Dopaminergic control of TSH secretion in endogenous depression.

To evaluate whether the inhibitory control exerted by endogenous dopamine on thyroid-stimulating hormone (TSH) secretion is altered in patients with major depressive disorder, 11 depressed patients and 9 normal controls were tested with the dopaminergic receptor antagonist domperidone (10 or 20 mg i.v.). The administration of domperidone induced a significant increase in circulating TSH levels in the normal controls, but not in the depressed patients. These data excluded the possibility that the dopaminergic inhibition of TSH secretion is enhanced in depression. To establish whether domperidone failure was due to a reduced dopaminergic tone, domperidone was administered before stimulation of TSH secretion with thyrotropin-releasing hormone (TRH) (200 micrograms i.v.). The TSH response to TRH was significantly lower in the depressed than in the control subjects, regardless of domperidone priming. However, in both groups domperidone enhanced the TRH-induced TSH release by 50%. These data suggest that the dopaminergic control of TSH secretion is not altered in patients with endogenous depression and that a reduced capacity of the pituitary to secrete TSH might be responsible for the reduced TSH responsiveness to TRH and domperidone.

Adult

Serotonin regulation of aldosterone secretion.

The circulating levels of aldosterone (A), cortisol (F), prolactin, ACTH and potassium and the PRA were studied in 8 (6 males and 2 females) healthy normotensive subjects after 5-hydroxy-tryptophan (5OHT), or pizotifen (Piz) or placebo oral administration. In the same subjects 5OHT was administered twice: after placebo and after dexamethasone pretreatment. The results showed a significant increase of A, ACTH and F after 5OHT plus placebo administration without any change of PRA, potassium or prolactin levels; dexamethasone pretreatment suppressed ACTH and F but was uneffective on the response of A to 5OHT. Only A levels showed a significant decrease after Piz administration, the other studied parameters were unaffected by the blockade of the 5HT2 receptors by Piz. The administration of placebo induced a slight but not significant decrease of the studied parameters. Our results suggest the existence of a physiologic serotonergic control of A secretion, a pituitary factor could be one of the putative links between the central serotonergic activation and the adrenal secretory response.

5-Hydroxytryptophan

Comparison of methimazole, methimazole and sodium ipodate, and methimazole and saturated solution of potassium iodide in the early treatment of hyperthyroid Graves' disease.

We have evaluated three regimens for the rapid control (10 days' therapy) of thyrotoxicosis in hyperthyroid Graves' disease: methimazole (MMI, 40 mg/day), MMI and sodium ipodate (MMI + Na Ipodate, 1 g/day and MMI and saturated solution of potassium iodide (MMI + SSKI, 6 drops twice daily). When serum T4 and T3 concentrations were analysed as the percent change from pre-treatment values, the following results were observed. Serum T4 concentration decreased in the three treatment groups and the decrease was similar in the MMI and MMI + SSKI groups but significantly lower than in the MMI + Na ipodate group. The serum T3 concentration decreased to the normal range in all seven MMI + Na Ipodate treated patients by the fourth day of treatment and the per cent decrease in serum T3 from pre-treatment values was significantly greater than in the MMI and MMI + SSKI treated patients. The decrease in serum T3 was similar in the latter two groups. Heart rate decreased in all three groups, but the decrease was significantly more in the MMI + Na Ipodate-treated patients. The present findings suggest that the rapid control of hyperthyroid Graves' disease is similar in patients treated with MMI and MMI + SSKI and that the combination of MMI + Na Ipodate is more efficacious since the decrease in serum T3 concentrations and heart rate was significantly greater in the MMI + Na ipodate-treated patients.

Adult

Perioperative management of diabetic subjects. Subcutaneous versus intravenous insulin administration during glucose-potassium infusion.

The purpose of this study was to validate methods for the perioperative management of diabetic patients that meet the prerequisites of simplicity, applicability in the absence of a diabetologist, and flexibility, to rapidly meet changing metabolic requirements. The patients were divided into two groups that were comparable for age, sex distribution, type of diabetes, and type of surgical procedures. The results show that intravenous insulin administration achieved better glycemic control during the intraoperative period, whereas it did not offer advantages over the subcutaneous route during the pre- and postoperative periods. The satisfactory degree of steady glycemic control achieved and the absence of hypoglycemic episodes indicate that the separate administration of insulin and glucose plus electrolytes is an effective and safe management modality for diabetic patients undergoing major surgery.

Adult

Effect of flunarizine on pituitary secretion by healthy men and in woman with migraine.

Flunarizine is widely used in the prophylaxis of migraine. It is both a calcium blocker and a histamine antagonist at H1-receptors and either of these effects could alter hormonal secretion. The effect of administration of flunarizine to 8 women with common migraine on pituitary secretion has been studied. The dopamine antagonist domperidone (10 mg) and gonadotropin releasing hormone (100 micrograms) were injected iv before and after one month of flunarizine therapy (10 mg orally at bedtime). The basal prolactin level was significantly increased by the drug, and the peak induced by domperidone stimulation was reduced. Basal TSH concentrations were not affected, but the increase after domperidone was blunted. After 90 days of therapy there were no significant differences from the baseline concentration. Neither basal nor gonadotropin releasing hormone-stimulated secretion of FSH and LH were affected by flunarizine. Twelve healthy men were given placebo and flunarizine (10 mg at bedtime) for 5 days in single-blind fashion. Flunarizine caused a significant increase in prolactin and TSH with no effect on basal gonadotropin and thyroid hormone levels. These results can be accounted for by the calcium blocking effect of the drug, although weak interference with dopaminergic transmission is a further possibility explanation.

Adult

Cord blood iodothyronine and thyrotropin concentrations in newborns of mothers exposed to povidone iodine in the last trimester.

In the present study, we have evaluated thyroid function in neonates at delivery and in their mothers who used vaginal povidone-iodine (PVP-I) during the last trimester of pregnancy. Newborns and their mothers without a history of iodine exposure, admitted to the same department and residing in the same geographical area served as controls. Maternal serum thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and thyrotropin (TSH) concentrations at delivery were not significantly different between the two groups of pregnant women. Cord blood thyroid hormone concentrations in the newborns of iodine exposed mothers were not significantly different from those in control newborns. In contrast, cord blood TSH concentrations in the neonates of mothers exposed to PVP-I during the last trimester of pregnancy were significantly higher than values in control neonates (p less than 0.05). These data confirm that the fetal thyroid gland, even in the last trimester of pregnancy, does not adapt completely to the inhibitory action of iodine on thyroid hormone synthesis and/or release.

Adult

Naloxone decreases the inhibiting effect of ethanol on the release of arginine-vasopressin induced by cigarette smoking in man.

In order to establish whether ethanol exerts its inhibiting effect on the nicotine-induced release of arginine-vasopressin (AVP) by interacting with an opioid pathway, six normal volunteers were treated with naloxone (2 or 4 mg as IV bolus, plus 5 or 10 mg infused over 105 minutes) during (2 nonfilter) cigarette smoking and ethanol (50 mL to 110 mL of whiskey) drinking. In addition, control experiments with naloxone, ethanol, or cigarette smoking alone were performed. When given alone, naloxone and ethanol did not modify AVP secretion, whereas nicotine increased plasma AVP levels by about 2.5-fold. This effect was completely blocked by ethanol. In the presence of naloxone, AVP rose only by about 1.7-fold in response to nicotine. Since naloxone only partially reversed the inhibiting effects of ethanol, only a partial involvement of opioid peptides in ethanol action might be supposed. Alternatively, ethanol and naloxone-sensitive opioids might produce their inhibiting effects on AVP rise in response to nicotine through independent pathways.

Adult

Pirenzepine inhibits growth hormone, but not thyrotropin response to thyrotropin-releasing hormone in patients with endogenous depression.

In order to evaluate whether in endogenous depression the anomalous growth hormone (GH) response to thyrotropin-releasing hormone (TRH) is mediated by muscarinic cholinergic receptors, 12 patients were tested with TRH (200 micrograms iv) with and without previous treatment with the muscarinic cholinergic receptor blocker pirenzepine (40 mg iv 10 min before TRH). Control tests with normal saline also were performed. Administration of normal saline did not alter serum GH levels. In contrast, TRH injections significantly increased serum GH concentrations by about three-fold. This response was inhibited by pretreatment with pirenzepine. Another neuroendocrine marker of endogenous depression, the low TSH increase in response to TRH (delta less than or equal to 7 microU/ml), was observed in our patients. Pretreatment with pirenzepine did not modify this response. These data indicate that in patients with endogenous depression a muscarinic cholinergic mechanism is involved in the GH response but not in the TSH response to TRH.

Adult

Involvement of a dopaminergic mechanism in the response of growth hormone to thyrotropin releasing hormone in patients with major depression.

In an attempt to establish whether, in patients with major depression, dopaminergic receptors are involved in the release of growth hormone (GH) induced by thyrotropin releasing hormone (TRH), eleven subjects were tested with TRH (200 micrograms in an i.v. bolus) with or without concomitant treatment with domperidone (10 mg in an i.v. bolus 10 min before TRH), an antidopaminergic agent which does not readily cross the blood-brain barrier. In 7 out of the 11 patients, TRH strikingly increased GH levels (responders) (the mean peak level was 9 times higher than basal value), whereas it was without effect in the remaining 4 patients (non-responders). When the responders were treated with domperidone before TRH injection, TRH-induced GH increase was still present, but it was significantly lower (the mean peak level was 5.3 times higher than basal value) than in the TRH test (p less than 0.02). These data suggest that the paradoxical response of GH or TRH in patients with major depression involves a dopaminergic mechanism active at sites situated outside the blood-brain barrier.

Adult