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Biomedical subjects

M Mannelli

Publications and source records attributed to M Mannelli.

At least 73 records · Page 4Linked to original sources
PubMed1988

Measurement of catecholamines, met-enkephalin, somatostatin and substance P-like immunoreactivities in 12 human pheochromocytomas.

The present study was designed to evaluate the simultaneous presence of epinephrine (E), norepinephrine (NE), met-enkephalin (ME)-, somatostatin (SRIF)- and substance P (SP)- like immunoreactivities (LI) in extracts of 12 pheochromocytomas obtained at the time of surgery from 10 patients. Moreover, catecholamines and ME-LI levels were measured in peripheral plasma of each patient. Each pheochromocytoma was characterized by a high variability of ME-LI, SRIF-LI, SP-LI, E and NE levels. The highest E concentrations were found in tumors from patients with Multiple Endocrine Adenomatosis (MEA) IIa syndrome, whereas in sporadic pheochromocytomas NE was the main catecholamine. Among the neuropeptides ME-LI showed the highest intratumoral concentration, and SP-LI the lowest. No correlations were found between intratumoral levels of catecholamines and any of the neuropeptides or between any of the different neuropeptides measured. Plasma catecholamine levels were not correlated with intratumoral catecholamine levels. Plasma ME-LI was higher than normal in only one patient. No correlation was observed between tumoral CA or peptide content and the clinical picture. Our study confirms that human pheochromocytoma cells can synthetize different neuropeptides. The variability of the clinical picture very likely depends on the biochemical and biological heterogeneity of this chromaffin tumor.

Adrenal Gland Neoplasms↗
PubMed1988

Endogenous dopamine (DA) and DA2 receptors: a mechanism limiting excessive sympathetic-adrenal discharge in humans.

We studied the effects of presynaptic dopamine (DA) 2 receptor blockade on the sympathetic-adrenal response to graded exercise in seven normal men. DA2 receptor blockade was achieved by means of domperidone (DMP) administration. The exercise consisted of progressive cycling activity, from 30-80% of the predetermined maximal oxygen consumption for each man. Systolic, diastolic, and mean arterial pressures; heart rate; and plasma norepinephrine (NE), epinephrine (E), PRL, glucose, lactate, FFA, sodium, potassium, cortisol, and PRA were measured at rest, during exercise, and during recovery after placebo or DMP administration. Graded exercise caused significant increases in systolic and mean arterial pressures and plasma NE, E, lactate, sodium, potassium, FFA, cortisol, and PRA. DMP administration before exercise caused a significant increase in plasma PRL (P = 0.0009), a greater increase in plasma NE at the end of the exercise (P = 0.002), and an overall increase in plasma E (P = 0.02) and FFA (P = 0.02) concentrations. These results strongly suggest that endogenous DA limits catecholamine release during sympathetic-adrenal stimulation by activating DA2 receptors.

Adrenal Glands↗
PubMed1987

Usefulness of basal catecholamine plasma levels and clonidine suppression test in the diagnosis of pheochromocytoma.

In the present paper we report our experience on the utility of basal plasma catecholamine (CA) measurement and of the clonidine-suppression test in the diagnosis of pheochromocytoma. Basal noradrenaline (NA) and adrenaline (A) were assayed in plasma samples of 27 subjects affected by pheochromocytoma. When compared to basal values obtained in hypertensive patients without pheochromocytoma, one or both the CA resulted pathologically elevated in all patients except one. The response to the clonidine-suppression test was evaluated in 41 hypertensive patients suspected of having a pheochromocytoma measuring plasma NA and A in basal conditions and 2 and 3 h after oral administration of 300 micrograms clonidine. Extensive laboratory and instrumental findings confirmed the presence of pheochromocytoma only in 12 patients. Among the other 29 patients basal plasma CA resulted higher than normal in 4 patients. In patients without pheochromocytoma clonidine induced a significant fall in both NA and A plasma levels. The decrease in NA was observed in each patient. The 12 patients with pheochromocytoma showed a pathological elevation of one or both the CA. In this group clonidine did not significantly suppress plasma CA. The individual responses were extremely variable. Our data confirm the validity of plasma CA measurement as a diagnostic tool for the diagnosis of pheochromocytoma. The results of the clonidine-suppression test were generally confirmatory of the basal CA plasma values but in the 4 hypertensive patients without pheochromocytoma who showed basal plasma CA higher than normal clonidine resulted a useful tool in excluding the presence of pheochromocytoma.

Adolescent↗
PubMed1987

Acute effect of furosemide on renal kallikrein and prostaglandin systems in mild to moderate essential hypertension.

The activity of basal 24-hour urinary kallikrein activity (UKA), prostaglandin E2 (U. PGE2) and thromboxane B2 (U. TxB2) and their relationship to natriuresis (U. Sodium), urinary aldosterone (U. Aldosterone) and plasma renin activity (in supine position: PRA1; in standing position: PRA2) were evaluated in 20 patients with early-moderate hemodynamically defined (first pass and gate blood pool radionuclide angiocardiography) essential hypertension (H) and in 13 age-matched normotensive patients (N). In basal conditions, UKA and PRA2 were significantly reduced (p less than 0.005 and p less than 0.05, respectively) in H compared with N. However, no differences between N and H were found for U. TxB2, U. PGE2, U. Aldosterone, U. Sodium, and PRA1. All parameters were also evaluated both in H and N before and after the administration of furosemide (40 mg i.v.). In H, but not in N, furosemide induced an increase of UKA (p less than 0.05), U. TxB2 (p less than 0.05) and U. Sodium (p less than 0.001). In both H and N furosemide caused a significant rise of PRA1 (p less than 0.001 in H and p less than 0.01 in N) and PRA2 (p less than 0.001 in H and p less than 0.05 in N). In H a significant correlation was found between percent increases of U. Sodium and U. Kallikrein (r = 0.54, p less than 0.01) and between percent differences of PGE2 and TxB2 (r = 0.59, p less than 0.01). It is proposed that reduction of basal UKA may be an early evidence of the first stages of hypertension, i.e., in absence of renal and cardiovascular alteration. The finding is not accompanied by significant changes in urinary excretion of arachidonic acid metabolites and aldosterone. Finally, any relation between UKA values and systemic hemodynamics is lacking.

Aldosterone↗
PubMed1986

Altered renal and platelet arachidonic acid metabolism in cirrhosis.

Urinary excretion rates of prostaglandin (PG) E2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane (TX) B2 were evaluated in three groups of cirrhotic patients [without ascites (group 1, 13 cases), with ascites and normal renal function (group 2, 15 cases), and with ascites and renal failure (group 3, 5 cases)] and in 14 healthy controls. All urinary arachidonate metabolites were significantly increased in group 2 patients. Patients with renal failure showed lower PGE2, PGF2 alpha, and TXB2 values than those from group 2; PGF2 alpha values were also lower than controls. Platelet TXA2 production during whole blood clotting was significantly reduced in all groups of patients. Administration of low-dose aspirin and sulindac, two cyclooxygenase inhibitors selectively sparing renal cyclooxygenase activity, effectively inhibited platelet TXA2 production without affecting urinary TXB2 excretion, thus ruling out platelets as a possible source of urinary TXB2. We conclude that patients with ascites and normal renal function show an overall activation of the renal PG system. Renal production of vasodilating PGE2 and PGI2 may be involved in supporting renal function in these patients. A reduced platelet synthesis of proaggregatory TXA2 also occurs in cirrhotic patients. This may play a role in the bleeding tendency of cirrhosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

An analogue of met-enkephalin attenuates the pituitary-adrenal response to ovine corticotrophin releasing factor.

The met-enkephalin analogue, DAMME, suppresses the pituitary-adrenal axis in normal subjects; it is not clear whether this occurs at the level of the pituitary or above. We therefore administered synthetic ovine corticotrophin releasing factor (CRF-41) 100 micrograms i.v. to a group of normal male subjects, with or without pretreatment with DAMME 250 micrograms i.v., and monitored the response of plasma ACTH and serum cortisol. CRF-41 caused a marked stimulation of ACTH and cortisol release, but this was significantly attenuated by pretreatment with DAMME. It is therefore concluded that DAMME either directly inhibits the corticotroph at the level of the pituitary, or that it suppresses release of an additional factor which normally potentiates the action of CRF-41 on the pituitary.

Adolescent↗
PubMed1986

Opioid modulation of normal and pathological human chromaffin tissue.

To evaluate whether opioid receptor blockade might modulate sympathetic-adrenal activity, we studied the effects of placebo or naloxone administration on plasma catecholamine (CA) levels in a group of 13 normal subjects and 15 hypertensive patients suspected to have a pheochromocytoma. Diagnostic evaluation confirmed the presence of pheochromocytoma in 9 patients. Among these, 4 had a unilateral epinephrine (E)-secreting tumor, 3 had bilateral E-secreting tumors due to multiple endocrine adenomatosis type IIa, and 2 had a unilateral norepinephrine (NE)-secreting tumor. In each subject studied, CA secretion was evaluated by calculating the area (0-30 min) under the plasma hormone curves after placebo or naloxone administration. In normal subjects naloxone caused a significant increase (P less than 0.005) of E secretion, whereas NE did not change. Similarly, in the group of hypertensive patients, E secretion increased after naloxone (P less than 0.01). In pheochromocytoma patients naloxone caused a significant increase in E (P less than 0.05) and NE (P less than 0.01) secretion from E-producing tumors but no increase in the patients with NE-secreting pheochromocytomas. The study suggests that CA secretion from normal and pathological chromaffin tissue is modulated by endogenous opioids; this modulation seems particularly evident in patients with E-secreting pheochromocytoma.

Adolescent↗
PubMed1985

Does endogenous dopamine modulate human sympathetic activity through DA2 receptors?

The effects of placebo and DA2 antidopaminergic agents on basal and stimulated catecholamine (CA) plasma levels in humans have been evaluated by administration either of domperidone or metoclopramide to separate groups of subjects. The latter group was subjected domperidone to sympathetic stimulation by handgrip coldpressor tests, and standing. Pharmacological DA2 receptor blockade, either peripheral by or central and peripheral by metoclopramide, did not modify plasma CA whilst resting or during acute sympathetic stimulation. It is concluded that endogenous dopamine does not seem to play a significant role in modulating NE release in man, at least not under the physiological conditions examined.

Adult↗
PubMed1985

Naloxone administration does not affect gonadotrophin secretion in male patients with isolated hypogonadotrophic hypogonadism.

We evaluated the gonadotrophin response to acute naloxone administration (10 mg iv) in 4 male patients with isolated hypogonadotrophic hypogonadism (age range 18.5-26 years) before and after pituitary priming with daily infusions of GnRH (25 micrograms/h for 4 h) for 4 days. A blunted gonadotrophin response to acute GnRH administration (100 micrograms iv) and a lack of response to naloxone was observed before pituitary priming. After repeated infusions of GnRH, pituitary gonadotrophin responsiveness to GnRH was restored, whilst naloxone still did not affect gonadotrophin levels. Our data suggest that in male isolated hypogonadotrophic hypogonadism 1) the lack of pituitary response to naloxone is not due to pituitary hyporesponsiveness to GnRH; 2) endogenous opioids do not exert any inhibitory influence on GnRH secreting neurons and thus are not involved in the pathogenesis of this disease.

Adult↗
PubMed1984

Vasoactive factors in decompensated cirrhosis. Effect of acute plasma expansion.

Plasma volume expansion was performed in 16 cirrhotic patients with ascites, 8 with avid sodium retention (sodium retainers) and 8 with normal sodium balance (sodium excretors). No natriuretic response was observed in sodium retainers (daily UNa = 7.1 +/- 1.5 mEq before expansion and 20.8 +/- 7.8 after expansion; p = not significant). After expansion plasma renin activity and plasma aldosterone showed a fall in both groups, whereas urinary kallikrein excretion decreased significantly in sodium retainers (27.1 +/- 9.7 before expansion and 7.8 +/- 6.4 after expansion; p less than 0.05). Baseline PGE were higher than normal in sodium retainers (997.0 +/- 134.3; p less than 0.02 vs. controls) and increased after expansion. Plasma octopamine was always within normal range. These results suggest that: a) reduction of effective plasma volume is not the main factor involved in sodium retention; b) the renin-angiotensin-aldosterone system has only a permissive role; c) prostaglandin system is activated and could have a protective role in maintaining renal function in cirrhotic patients.

Adult↗
PubMed1984

Vasoactive factors in the mechanism of renal sodium handling in cirrhotics: the effect of acute plasma expansion.

Twenty cirrhotic patients with ascites, divided into two groups of 10 each, according to their daily urinary sodium excretion (sodium retainers and sodium excretors) and given a diet of 75 mEq of sodium daily, underwent acute plasma volume expansion with 1,000 ml of 10% dextran in saline, infused through a catheter located in the right atrium. Even if a significant increase in sodium excretion was observed in both groups (p less than 0.001 in sodium excretors and p less than 0.05 in sodium retainers), plasma expansion did not reverse sodium retention in sodium retainers. A significant increase in creatinine clearance was found only in sodium retainers (p less than 0.02). Basal plasma renin activity and plasma aldosterone were elevated only in a few patients of both groups. The renin-angiotensin-aldosterone system was highly responsive to plasma expansion. Sodium retainers, who showed an ineffective natriuretic response after expansion, were able to suppress both plasma renin activity and plasma aldosterone in an analogous manner to the sodium-excreting group. This result lends strong support to the concept that the elevated aldosterone level in cirrhosis is not the major determinant of sodium retention. The kallikrein-kinin system was responsive to volume stimulus, since a decrease in kallikrein excretion was noted. It was significant in sodium retainers (p less than 0.05). Plasma PGE1,2 levels were significantly higher in sodium retainers than in controls. This may suggest that there is an activation of the intrarenal prostaglandin system, which could play a protective role against renal ischaemia. After volume expansion, PGE1,2 increased, but not significantly. Octopamine appeared unrelated to sodium excretion and unresponsive to volume stimulus. Endotoxins did not seem to be involved in renal sodium handling. Plasma volume expansion seemed effective in inducing a reduction of vasoconstrictor and sodium-retaining factors, such as the renin-angiotensin-aldosterone system. It is possible to suggest that volume expansion could increase PGE1,2. Plasma volume expansion produced different rates of sodium excretion in the two groups of patients and this suggests that impaired sodium handling in cirrhosis could, to some extent, be independent of effective plasma volume.

Female↗
PubMed1984

Effects of different dopaminergic antagonists on bromocriptine-induced inhibition of norepinephrine release.

In this study we evaluated the effects of placebo or acute bromocriptine (BC) administration (2.5 mg orally) on plasma catecholamines, systolic and diastolic blood pressure (BP), heart rate, and plasma PRL in six normal subjects [group I, mean age 33.2 +/- 5.4 (SD) yr] in the supine as well as upright position. BC induced a significant decrease in plasma norepinephrine in the supine [167.7 +/- 16.8 (SEM) vs. 101.9 +/- 33.7 pg/ml, P less than 0.005] and upright positions [397.3 +/- 27.7 vs. 211.3 +/- 26.7 pg/ml, P less than 0.005], a decrease in systolic and diastolic BP and a decrease in plasma PRL (P less than 0.01). After standing, epinephrine levels increased significantly (53.6 +/- 11.8 vs. 226.4 +/- 71.0 pg/ml, P less than 0.05). The study was repeated in a second group of seven normal subjects (mean age, 32.3 +/- 12.9 yr) after placebo or metoclopramide (20 mg orally) plus BC. In this group metoclopramide, a central and peripheral antidopaminergic agent, counteracted the BC-induced effects found in group I, both in the basal and stimulated conditions. Plasma PRL increased significantly (P less than 0.025). Finally, to assess the effect of peripheral dopaminergic blockade on BC-induced changes in sympathetic outflow, we repeated the study in seven normal subjects (group III, mean age, 30.1 +/- 5.0 yr) after placebo or domperidone (20 mg orally) plus BC. Domperidone blocked the effects of BC on norepinephrine and BP in the supine position. On standing there was a significant decrease in systolic (P less than 0.05) and diastolic (P less than 0.05) BP and an increase in epinephrine levels (58.9 +/- 12.2 vs. 109.8 +/- 24.6 pg/ml, P less than 0.05) was still observed. Plasma PRL increased significantly (P less than 0.025). The results of this study suggest that the inhibition of sympathetic outflow induced by BC is peripherally mediated. As peripheral dopamine receptor blockade did not counteract all the effects after BC during standing, dopaminergic modulation of central reflex sympathetic activation is suggested.

Adult↗
PubMed1984

Effects of naloxone on catecholamine plasma levels in adult men. A dose-response study.

To evaluate a possible role for endogenous opiates in modulating sympathetic-adrenal function in humans, we measured plasma epinephrine and norepinephrine (radioenzymatic method), blood pressure and heart rate in 8 normal men (aged 24-33 years) before and after placebo or different doses (0.4, 4.8, 10 mg) of naloxone. In 6 subjects plasma insulin and glucagon levels were also measured by radioimmunoassay after placebo and 10 mg naloxone. Naloxone had no significant effect upon blood pressure, heart rate, plasma insulin, glucagon or norepinephrine. Placebo, 0.4 and 4.8 mg naloxone caused no significant change in peripheral levels of epinephrine while 10 mg produced an increase in epinephrine concentrations 15 min after iv injection (186 +/- 23 vs 99 +/- 9 pmol/l, P less than 0.01). Since naloxone did not modify plasma levels of insulin and glucagon, an indirect effect of naloxone on adrenal medullary secretion seems to be excluded. These results are in agreement with in vitro experimental data obtained in animals and suggest that endogenous opiates also have a role in modulating adrenal medullary secretion in man.

Adrenal Medulla↗
PubMed1983

Plasma catecholamine response to orthostasis in longstanding hypothyroidism.

In seven normotensive women affected by long-standing hypothyroidism norepinephrine peripheral levels were found significantly higher than after replacement therapy and than normal controls. After standing norepinephrine peripheral concentrations increased further; such an increase, although percentually lower than after therapy was sufficient to assure an adequate clinical response to orthostasis.

Adult↗