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Biomedical subjects

F Mantero

Publications and source records attributed to F Mantero.

At least 145 records · Page 8Linked to original sources
PubMed1987

ACTH response to corticotropin releasing hormone in Cushing's disease before and after ketoconazole: in vivo and in vitro studies.

Ketoconazole has been used as a palliative treatment of Cushing's syndrome, due to its ability to lower cortisol production. We evaluated the effects of ovine Corticotropin Releasing Hormone (oCRH) 100 micrograms i.v. on ACTH and cortisol levels in 6 patients with Cushing's disease before and after treatment with ketoconazole 600 mg/day. Both hormones increased after oCRH. During ketoconazole, cortisol was lowered to normal levels and its response to oCRH was impaired. After treatment, basal ACTH showed variable changes while the response to oCRH was markedly enhanced compared to that before ketoconazole. In vitro: In a continuous perfusion system of isolated anterior pituitary cells from rats or human anterior pituitary adenoma, producing ACTH, ketoconazole 10(-5)-10(-6) M showed no inhibitory effects on both basal or lisine-vasopressin and oCRH stimulated ACTH secretion. Our findings confirm the inhibitory action of ketoconazole on basal and stimulated cortisol secretion. No inhibition of ACTH levels was observed both in vivo and in vitro.

Adenoma↗
PubMed1987

The human adrenal cortex: ultrastructure and base-line morphometric data.

The morphology of the human adult female adrenal cortex was studied by electron microscopy and morphometry. Zona glomerulosa contains outer undifferentiated small cells and inner well-differentiated larger elements, which display mitochondria with tubulo-laminar cristae, abundant smooth endoplasmic reticulum (SER) and sparse lipid droplets. Zona fasciculata cells possess typical mitochondria with vesicular cristae, a well-developed SER, lipid droplets and some lipofuscin-pigment granules, which increase in number in the cells of the inner portion of the zone. Sometimes lipid-laden cells can be observed in the zona fasciculata. Zona reticularis cells have the same morphological features as the zona fasciculata elements, but display a striking rise in the number of lipofuscin-pigment granules.

Adrenal Cortex↗
PubMed1986

Erythrocyte Na+-Li+ countertransport and blood viscosity in arterial hypertension.

The aim of this study was to evaluate together the main hemorheologic parameters and one of the transmembrane ion transport systems in erythrocytes of subjects with normal and elevated blood pressure. Three sex-, age-, and weight-matched groups consisting of 15 normotensive subjects (NT) with no parental hypertension, 15 patients with essential hypertension (EH) at stage 1-II WHO, and eight patients with secondary hypertension (Sec.H), respectively, were studied. Red blood cell Na+-Li+ countertransport (CTT), blood viscosity (eta B) at shear rates of 230 X S-1, 115 X S-1, and 46 S-1 and plasma viscosity (eta P) at shear rate of 46 X S-1 were measured. Plasma proteins and fibrinogen were also evaluated. CTT was higher in EH than in NT (P less than 0.01), while no significant difference was found between NT and Sec. H patients. eta B at 115 X S-1 and 46 X S-1 was higher in EH, but not in Sec. H, than in NT patients (P less than 0.05). No difference in eta P, plasma proteins and fibrinogen levels was observed between EH and NT. Elevated eta B and/or CTT may indicate a structural alteration in the erythrocyte membrane of some essential hypertensive patients. This is consistent with the hypothesis that a widespread membrane disorder is involved in the pathogenesis of primary hypertension.

Adolescent↗
PubMed1986

HLA and hormonal studies in 5 patients with late-onset 21-hydroxylase deficiency syndrome (21OHDS).

Late-onset 21-hydroxylase deficiency (21OHD) presents biochemical evidence of 21OHD and virilization in peri-or postpubertal age; it has been demonstrated that late-onset 21OHD is linked to HLA system. We present the HLA typing, the baseline and the ACTH-stimulated hormonal levels in 5 patients with late-onset 21OHD and in their family members. We identified 3 HLA identical male sibs within their respective families, 2 sibs sharing one haplotype with the affected member and 2 homozygous normal sibs. We observed elevated baseline (greater than 4 ng/ml) and ACTH-stimulated 17-hydroxyprogesterone levels, increased baseline Androstenedione levels, slightly elevated or normal DHEA-S and Testosterone values and subnormal response of Cortisol levels to ACTH in patients and in the HLA-identical sibs, reduced SHBG levels in patients but not in their identical sibs. The heterozygous family members presented hyperresponsiveness of 17-hydroxyprogesterone but not of androgens after ACTH. We confirm that late-onset of 21OHD is an autosomal recessive disease linked to HLA-B; there is in fact biochemical evidence of mild 21OHD in patients and in their HLA identical sibs and 17-hydroxyprogesterone levels in the range of heterozygotes for classical 21OHD in parents and sibs predicted by HLA to be carriers. Thus HLA typing and hormonal data, particularly 17-hydroxyprogesterone, are useful, also in this form of congenital hyperplasia, in detecting heterozygotes.

17-alpha-Hydroxyprogesterone↗
PubMed1986

Serum levels of calcitonin in Cushing's syndrome.

Serum levels of calcitonin (CT) were studied in 21 patients with Cushing's syndrome (CS), 18 females and 3 males aging from 16 to 59 years, and in 70 age and sex matched normal subjects. Patients with CS showed CT values significantly lower than those found in controls (9.9 +/- 5.0 pg/ml vs. 15.9 +/- 6.3 pg/ml, mean +/- SD; p less than 0.01), while no difference was observed in total serum calcium and phosphate and calcium corrected for albumin. No correlation between CT and serum calcium and phosphate, serum cortisol and urinary free cortisol was found. It is possible that low CT levels are involved in the pathogenesis of bone loss observed in CS.

Adolescent↗
PubMed1986

Effect of verapamil on the aldosterone-stimulating properties of metoclopramide: in vitro and in vivo studies.

The role of calcium in the regulation of aldosterone secretion has been recently clarified. Angiotensin II and potassium stimulate aldosterone secretion through a calcium-entry dependent mechanism, while ACTH action is both calcium and cyclic AMP dependent. To establish whether also the so-called aldosterone dopaminergic regulatory system is calcium-dependent we have studied, in vitro and in vivo, the effect of verapamil, a calcium entry blocker agent, on the aldosterone-stimulating properties of the antidopaminergic drug, metoclopramide. In the rat adrenal cells perfusion system, verapamil blocked both angiotensin II and metoclopramide-stimulated aldosterone. This effect on metoclopramide action seems to be present also in vivo in normal subjects: in fact aldosterone response was slightly but significantly reduced after pretreatment with verapamil. In conclusion the results suggest that also the dopaminergic system could regulate aldosterone secretion through calcium-mediated mechanisms.

Adrenal Glands↗
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↗
PubMed1986

Renin-angiotensin-aldosterone system: a long-term follow-up study in 17 alpha-hydroxylase deficiency syndrome (17OHDS).

We studied the mineralocorticoid pattern in 4 patients with 17OHD during long-term glucocorticoid treatment. We observed reduction of BP, normalization of K levels, a gradual increase in PRA and in urinary Aldosterone (ALDO); a normal response of plasma ALDO to ACTH and to angiotensin II was present only in one case. We observed a prompt decrease of mineralocorticoid hormones, normalized by long-term therapy only in one case. Discontinuation of treatment induced an increase of ALDO that became suppressed in late off-treatment. Thus, glucocorticoid treatment decreases abnormal steroid levels and activates zona glomerulosa (ZG) function, even if it may take years for ALDO to normalize. Brief discontinuation of therapy induces a surge in ALDO levels, revealing no biosynthetic defect in ZG, while in late off-treatment mineralocorticoids seem to come exclusively from zona fasciculata.

Adolescent↗
PubMed1986

Measurement of urinary free 20 alpha-dihydrocortisol in biochemical diagnosis of chronic hypercorticoidism.

Using liquid chromatography, we estimated the urinary excretion of 20 alpha-dihydrocortisol (20-DH) and urinary free cortisol (UFC) in normal subjects and in 40 patients with Cushing's syndrome of different etiologies. The median normal excretion rate (nmol/24 h) was 174 for 20-DH and 68 for UFC, the 20-DH/UFC ratio thus being 2.55. For patients with Cushing's syndrome, the excretion rate was 1798 for 20-DH and 298 for UFC, the ratio 6.03. We evaluated the effect of acute stimulation of adrenal secretion on 20-DH and UFC by administering corticotropin to six normal subjects. After such stimulation, the excretion rate was 566 for 20-DH and 1238 for UFC (ratio 0.45). Whereas 20-DH excretion rate exceeded the normal range in all patients, six patients had normal or even below-normal values for UFC excretion. Evidently, measurement of urinary 20-DH is a better test for chronic hypercorticoidism than is measurement of urinary UFC, and chronic hypercorticoidism can be differentiated from the acute state by the 20-DH/UFC ratio.

Adrenocorticotropic Hormone↗
PubMed1986

Effect of ketanserin on the in vitro regulation of aldosterone.

Serotonin (5-HT) is known to be a potent stimulator of aldosterone release in vitro and, to a lesser degree, in vivo. Since ketanserin, a specific 5-HT2-receptor antagonist, decreases aldosterone levels in some hypertensive patients, we have performed in vitro experiments to elucidate the mechanism by which ketanserin interferes with aldosterone regulation. After collagenase dispersion, rat zona glomerulosa cells were either perfused and resuspended in Biogel or incubated in Earle's medium and bovine serum albumin. The cells were stimulated with serotonin, angiotensin II, potassium (K+) and adrenocorticotrophic hormone (ACTH) in the presence or absence of ketanserin. Ketanserin did not decrease baseline aldosterone secretion although it reduced the stimulatory capacity of serotonin and K+, and had a minimal effect on ACTH. Furthermore, we demonstrated that ketanserin is able to have a significant effect on the adrenal response to angiotensin II. These data indicate that antiserotoninergic agents may act directly at the level of the adrenal glomerulosa by interfering with specific serotoninergic receptors and modifying the adrenal sensitivity to angiotensin II and K+. The importance of these findings in the clinical use of these antihypertensive drugs remains to be established.

Adrenocorticotropic Hormone↗
PubMed1986

Urinary excretion rates of 15 free steroids: potential utility in differential diagnosis of Cushing's syndrome.

To evaluate their potential usefulness in the differential diagnosis of Cushing's syndrome, we estimated the urinary excretion rates of the following non-metabolized, unbound steroid hormones: pregnenolone, progesterone, 17-OH-pregnenolone, 17-OH-progesterone, dehydroepiandrosterone (DHEA), androstenedione, testosterone, dihydrotestosterone, 11-deoxycorticosterone, 11-deoxycortisol, corticosterone, cortisol, 18-OH-11-deoxycorticosterone, 18-OH-corticosterone, and aldosterone. These were measured in normal subjects and in patients with Cushing's disease, adrenal adenoma, or ectopic corticotropin syndrome. We used "high-performance" liquid chromatography and subsequent radioimmunoassay. Our results indicate that simultaneous estimation of urinary free cortisol and DHEA may be useful in differential diagnosis of hypercorticoid states due to adrenal adenoma and Cushing's disease.

ACTH Syndrome, Ectopic↗
PubMed1985

Captopril-induced changes on active and inactive renin in a patient with factor XII congenital deficiency.

A linkage between prorenin, renin, and intrinsic coagulation systems has been suggested recently. We studied the behavior of renin, prorenin, and kallikrein in a patient affected by congenital factor XII deficiency. Captopril test, upright posture, and furosemide administration provoked in our patients changes of renin and prorenin similar to those found in normal and hypertensive subjects. Unchanged kallikrein levels confirmed that no interaction between prorenin activation and factor XII-kallikrein system appears to be present.

Adult↗
PubMed1985

Evidence for ectopic ACTH production years after bilateral adrenalectomy for Cushing's syndrome: in vivo and in vitro studies.

Three patients presented with hyperpigmentation and high plasma levels of ACTH 4-5 years after bilateral adrenalectomy for Cushing's "disease". X-rays and ct-scan of the lungs showed a small pulmonary mass in all. ACTH levels (1100-2000 pg/ml) were not suppressible by high doses hydrocortisone. A carcinoid tumor was removed in two cases and a chemodectoma in the third. Evidence for ACTH secretion by these tumors was provided by both decrease of ACTH levels after surgery and/or in vitro studies. Both carcinoid cultures showed a basal ACTH production, which was clearly increased by LVP (10(-7) M) and CRF (10(-7) M). Our findings in vitro studies suggest the presence of specific receptor sites for physiological stimuli (LVP and CRF) in tumor cell membranes.

Adrenalectomy↗
PubMed1985

Alpha-1 adrenergic blockade: a possible mechanism of action of dopaminergic drugs on ACTH secretion.

In some cases of Cushing's syndrome both bromocriptine and lisuride inhibit the secretion of ACTH but it is still unknown if they act at pituitary or at higher levels. In order to evaluate this aspect, we set up an in vitro perfusion system with anterior pituitary cells from rats and from human ACTH-secreting tumors. In both preparations lysine-vasopressin (LVP) and epinephrine (EPI) stimulated ACTH secretion; prazosin (alpha-1 blocker) inhibited the EPI but not the LVP-mediated stimulation. Similarly, the infusion of lisuride blocked ACTH response to EPI but not to LVP. These data may suggest that "dopaminergic" drugs could act by an adrenergic blockade and not necessarily by a dopaminergic inhibition.

Adenoma↗
PubMed1985

Effect of short and long-term administration of lisuride in Cushing's disease.

To define the role of dopaminergic drugs on pituitary ACTH secretion, we studied the effect of a dopamine-agonist, lisuride, on a group of 9 patients with pituitary dependent Cushing's syndrome. Lisuride (0.4-0.6 mg/day) was administered for two days: in only two out of eight cases the ACTH levels, sampled every 30 min for 6 h (08:00-14:00 h), showed some reduction when compared with the control day. Two of the nonresponders (R.P.; B.F.) and one untested patient (L.E.) were then treated chronically with a similar amount of lisuride per day for 20 days (L.E.) and for 4 months (B.F.; R.P.). One patient (L.E.) showed a clear decrease in urinary free cortisol without clinical improvement; while in the other two cases, followed for a longer period of time, a clinical improvement was observed together with a decrease of the hormonal parameters. In conclusion, lisuride may occasionally reduce ACTH secretion in patients with pituitary dependent Cushing's syndrome, but the acute test fails to identify the patients who would benefit from this treatment.

Adrenocorticotropic Hormone↗
PubMed1985

Resistance to captopril in hypertension of coarctation of the aorta.

Two patients with hypertension due to coarctation of the aorta were treated for 12 weeks with captopril at increasing doses. After an immediate response, resistance developed to captopril, which was associated with restoration of initially elevated renin and plasma aldosterone levels. Lack of hypertension control may be related to long-term reappearance of mechanisms which lead to excessive renin stimulation.

Adult↗