Biomedical subjects

F Mantero

Publications and source records attributed to F Mantero.

At least 163 records · Page 9Linked to original sources

PubMed1985

Effect of ketanserin in primary aldosteronism.

Serotonin is known to have aldosterone-stimulating properties in humans, which are counteracted by the serotonin-antagonist metergoline. Suppression of aldosterone levels by cyproheptadine in patients with idiopathic aldosteronism has also been shown. Since ketanserin, a more specific 5-HT2-serotoninergic (5-HT2) antagonist, has been shown to affect aldosterone secretion in essential hypertension, we have further investigated this mechanism by injecting ketanserin (10 mg i.v.) in 10 patients with primary aldosteronism (four adenoma, six idiopathic aldosteronism). A transient decrease (20% when compared with the basal levels) of plasma aldosterone was seen at 30 min. A concomitant decrease of plasma cortisol was also noticed, whereas plasma renin activity and potassium did not change. Blood pressure decreased in all cases. These observations suggest that ketanserin acts directly at the adrenal level by interfering with a possible modulatory activity of serotonin. However, an adrenocorticotropic hormone-mediated effect cannot be completely ruled out at the present time.

Aldosterone↗

PubMed1985

A new family with dexamethasone-suppressible hyperaldosteronism: aldosterone unresponsiveness to angiotensin II.

A family with nine siblings in which three siblings have been shown to have dexamethasone-suppressible hyperaldosteronism was studied. All three showed no significant changes of plasma aldosterone during angiotensin II infusion at incremental rates under baseline conditions. After dexamethasone administration (2 mg/d for 4 weeks) plasma renin activity (PRA) rose to normal-supranormal range, while plasma and urinary aldosterone were maintained at low-normal levels. No restoration of aldosterone response to angiotensin II was observed on dexamethasone. Two other siblings were found to be hypertensive with normal baseline data; however, both showed plasma aldosterone hyperresponsiveness to ACTH. In the four normotensive siblings aldosterone response to ACTH was normal. The family pedigree was consistent with autosomal dominant transmission of the disorder. HLA typing showed haplotype A3 Bw35 in all five hypertensive sibs and in one normotensive. In conclusion, low aldosterone compared to PRA, and plasma aldosterone unresponsiveness to angiotensin II infusion before and during dexamethasone, show functional impairment, at least temporary, of the zona glomerulosa. These findings support the hypothesis that aldosterone may be derived from the zona fasciculata in this disorder.

Adrenocorticotropic Hormone↗

PubMed1985

In-vivo metabolites of spironolactone and potassium canrenoate: determination of potential anti-androgenic activity by a mouse kidney cytosol receptor assay.

We have established a sensitive and specific radioreceptor assay for androgen receptor active materials in plasma, using tritiated methyltrienolone ([3H]R1881) as tracer, and spayed mouse kidney cytosol receptor as the binding species. On radioreceptor assay, plasma from mice chronically administered spironolactone contained approximately 10 times higher levels of androgen receptor active material than from mice administered potassium canrenoate. In parallel bioassays (antagonism of the effect of testosterone on seminal vesicle weight), spironolactone was greater than 4 times as potent an antiandrogen as potassium canrenoate. Administered potassium canrenoate circulates as canrenoic acid, in equilibrium with its lactonized congener canrenone. Since over 80% of administered spironolactone is irreversibly converted to canrenone/canrenoic acid, its much higher anti-androgen activity on radioreceptor assay and bioassay may point to the generation of unidentified, minor metabolites with very high affinity for androgen receptors and/or a very long plasma half-life.

Animals↗

PubMed1985

Adrenal scintigraphy in the morphological and functional evaluation of Cushing's syndrome.

In recent years, cholesterol adrenal scintigraphy has been employed in the morphofunctional study of adrenal hypercorticism. Particularly in Cushing's syndrome, this noninvasive procedure can give a determinant contribution to distinguish ACTH-dependent from ACTH-independent forms. In our Institute, adrenal scintigraphy was performed in 77 patients with Cushing's syndrome diagnosed on clinical grounds confirmed by laboratory investigations and functional tests (17 with cortisol-secreting adenoma, 54 with pituitary ACTH-dependent bilateral adrenal hyperplasia, 2 with ectopic ACTH-dependent bilateral hyperplasia and 4 with bilateral nodular hyperplasia). Three distinct scintigraphic patterns have been identified. The 56 patients with ACTH-dependent Cushing's syndrome showed bilateral symmetric or slightly asymmetric visualization of the adrenal glands; in the 17 patients with ACTH-independent Cushing's syndrome the adrenal scintigraphy only visualized the gland harboring the adenoma; finally, a marked asymmetric visualization of the glands was observed in the 4 patients with adrenal nodular hyperplasia. These data confirm that adrenal scintigraphy is able to distinguish between ACTH-dependent and ACTH-independent Cushing's syndrome and reliably lateralizes adenomas when they are present. Moreover, the morphofunctional information obtained by this procedure, together with the high resolution morphological data by computerized tomography, allows to recognize the presence of bilateral nodular hyperplasia, an uncommon cause of Cushing's syndrome.

ACTH Syndrome, Ectopic↗

PubMed1985

Prolonged treatment of Cushing's disease by ketoconazole.

Ketoconazole, used in clinical practice as an antifungal medication, recently was found to be a potent inhibitor of gonadal and adrenal steroidogenesis in vitro and in vivo. The effects of prolonged treatment with this agent in Cushing's disease were investigated in five patients who had recurrent severe hypercortisolism after selective transsphenoidal surgery. The patients received the drug for at least 2 months. Urinary cortisol markedly decreased in all patients immediately after the beginning of treatment with ketoconazole (800 mg/day) and remained within low normal levels when the daily dose was lowered to 600 mg/day. Plasma cortisol also decreased. After 4-6 weeks of treatment, the clinical features of the disease regressed in all patients without signs of toxicity. These findings indicate that ketoconazole may be a valuable drug for the management of patients with Cushing's disease because of its ability to correct hypercortisolism quickly.

Administration, Oral↗

PubMed1985

Usefulness of dynamic reno-scintigraphy in the follow-up of patients treated by surgery or percutaneous transluminal angioplasty for renovascular hypertension.

The aim of this study was to assess the role of dynamic reno-scintigraphy (DRS) in follow-up of 21 hypertensive patients who underwent surgery or percutaneous transluminal angioplasty (PTA) for renal artery stenosis. Dynamic reno-scintigraphy was recorded following injection of 0.12 mCi/kg 99Tcm-glucoheptonate i.v. before and after reconstructive vascular surgery or PTA. Serial images and renal time activity were analysed according to established criteria of interpretation. In terms of blood pressure response, 14 patients were cured or improved after surgery or PTA; DRS normalized or markedly improved in all these cases. Dynamic reno-scintigraphy did not change in seven patients who did not benefit from surgery or PTA. In three of them, repeated angiography showed, respectively, a by-pass occlusion, a renal artery re-occlusion after PTA, and a renoparenchymal disease. Dynamic reno-scintigraphy appears to reflect well the recovery of renal perfusion in patients treated by surgery or PTA for suspected renovascular hypertension.

Adult↗

PubMed1984

Primary tissue culture of human adrenocortical Conn's adenomata. Bromocriptine as a possible agonist-antagonist of angiotensin at the cellular level.

Angiotensin II-induced the hypertrophy of the cytoplasmic compartment and significantly increased (5-3H)uridine incorporation into RNA species by Conn's human adult adenomatous cells in primary tissue culture. On its own, bromocriptine, while enlarging only the nucleolar compartment, also intensely stimulated the incorporation of (5-3H)uridine into RNA species by the cultured adrenocortical adenomatous cells. However, an equimolar mixture of angiotensin II and bromocriptine was totally ineffective, eliciting no change in cellular morphometry or isotope incorporation with respect to the control specimens run in parallel. The present findings support the view that bromocriptine can influence the metabolism of Conn's cells directly at the cellular level by acting as an agonist-antagonist of angiotensin.

Adenoma↗

PubMed1984

The contact phase of blood coagulation and renin activation in essential hypertension before and after captopril.

The contact phase of blood coagulation in a group of patients suffering from essential hypertension was studied before and after captopril administration. The baseline levels of factor XII, factor XI and plasminogen were significantly higher than in normals and correlated with baseline diastolic blood pressure levels. On the contrary, plasma prekallikrein was not significantly different from normal. These results suggest the presence of a hypercoagulable state in essential hypertension. After captopril administration, factor XII, factor XI and prekallikrein rapidly decreased, perhaps as a consequence of the drug's effect on the vascular endothelial surface. There was no correlation between the changes of active and inactive renin and the changes of prekallikrein and plasminogen levels. Our data do not support the view that factor XII-plasma kallikrein or plasmin dependent pathways are involved in the activation of inactive renin in vivo. Captopril, by provoking rapid pressure changes, appears to be able to affect the clotting system.

Adult↗

PubMed1984

Effect of atenolol and metoprolol on the anticoagulant activity of acenocoumarin.

In patients receiving long-term acenocoumarin treatment, the effect on anticoagulant activity of atenolol (100 mg once-daily) and metoprolol (100 mg twice daily) was compared in a randomised within-patient open trial. No significant differences were demonstrated between mean prothrombin time and Thrombotest during treatment with atenolol, metoprolol or placebo. These data do not suggest the existence of an interaction between acenocoumarin and the moderately lipophilic beta-adrenoceptor blocker metoprolol, or the hydrophilic beta-adrenoceptor blocker atenolol. The results are discussed in the light of published data for the highly lipophilic beta-adrenoceptor blocker propranolol.

Acenocoumarol↗

PubMed1983

Complement-fixing adrenal autoantibodies as a marker for predicting onset of idiopathic Addison's disease.

In a prospective investigation of the role of adrenal autoantibodies (AA) in predicting the onset of idiopathic Addison's disease, 9 initially non-addisonian AA-positive autoimmune subjects were followed for 42 months. In 4 of these subjects Addison's disease developed within 1-31 months. A fifth had reduced adrenocortical reserve at the start and at the end of the investigation. An AA capable of fixing the membrane attack complex of complement [(C5-C9) F-AA] was detected before onset of the disease in the sera of the 4 patients in whom Addison's disease developed. (C5-C9) F-AA may be involved in the pathogenesis of idiopathic Addison's disease and may be regarded as a marker for individuals in whom idiopathic adrenal insufficiency is likely to develop.

Addison Disease↗

PubMed1983

The Prader-Willi syndrome: neuroendocrine study of identical twins.

Identical twins with the Prader-Willi syndrome are reported. Apart from hypogonadism, hypomentia, hypotonia and obesity, they presented shorter than normal stature and the peculiar facies of this syndrome. Both twins also suffered from arterial hypertension with secondary hyperaldosteronism, an abnormality never previously recorded. The endocrinological study showed the presence of hypogonadotrophic hypogonadism in both twins. The GnRH and clomiphene tests suggested a hypothalamic disorder. Although the vast majority of cases with the Prader-Willi syndrome are isolated, the expression of this disorder in two identical twins enhances the possibility of a genetic determination.

Adolescent↗

PubMed1983

Effect of metergoline on the aldosterone-stimulating properties of metoclopramide.

The mechanism by which metoclopramide stimulates aldosterone secretion is still unclear, since it cannot be explained by known regulatory systems. On the other hand we have recently shown that serotonin is also a potent aldosterone-stimulatory substance in man and its action can be blunted by the antiserotoninergic drug, metergoline. To test if metoclopramide could act through a serotoninergic pathway we have studied the effect of metergoline on the aldosterone response to metoclopramide in 8 normal subjects. The effect of metoclopramide (10 mg i.v.) on plasma aldosterone, PRA, cortisol, prolactin and K was studied before and after acute metergoline administration. Metergoline pretreatment significantly reduced the aldosterone response to metoclopramide, together with a slight reduction of prolactin, whereas no changes were seen on PRA, cortisol and K. In vitro, metoclopramide induced a significant aldosterone output from human adrenal adenoma cells, which was partially reduced by metergoline and not by bromocriptine. Despite a lack of specificity of metergoline these data may suggest the hypothesis of a serotoninergic component in the aldosterone-stimulating properties of metoclopramide.

Adenoma↗

PubMed1983

Effect of bromocriptine in pituitary-dependent Cushing's syndrome.

To assess the therapeutic value of a dopaminergic drug on abnormal ACTH secretion, we studied the effect of bromocriptine during short and long-term treatment in nine patients with active pituitary-dependent Cushing's syndrome. The single oral dose effect of bromocriptine (2.5 mg at 0800 h) on ACTH samples obtained every half hour for 3 h, was studied in six patients with Cushing's disease; in no case was suppression of ACTH observed. In five patients, the effect of bromocriptine was also investigated after its administration for two consecutive days (5 mg/d) with plasma samples taken every half hour for 12 h; in three cases no suppression of plasma ACTH was observed, while the other two showed a significant decrease. Three of our patients (a nonresponder to the single dose, a responder to the two-day treatment, and an untested patient) were subjected to prolonged bromocriptine administration (2-45 months). In the first two patients only, biochemical data and clinical symptoms showed improvement, while the other patient showed only initial benefit. These data show that bromocriptine may occasionally reduce ACTH secretion in pituitary-dependent Cushing's syndrome, and that a single oral dose bromocriptine test fails to identify the patients who will benefit from this treatment.

Adrenocorticotropic Hormone↗

PubMed1983

Insulin resistance in Cushing's syndrome.

It is well established that cortisol excess causes insulin resistance in man, but the mechanisms responsible for this insulin resistance are poorly understood. We studied five women with Cushing's syndrome with impaired oral glucose tolerance tests and seven normal subjects, plotting the shape of the insulin-induced disposal dose-response curve obtained by means of the euglycemic clamp procedure during four different plasma insulin plateaus at four infusion rates of 21, 73, 760, and 1200 mU/M2 . min. Glucose disposal (M = mg/M2 . min) was calculated as glucose amount infused to maintain euglycemia. In Cushing's syndrome the dose-response curve was shifted to the right in comparison with normal subjects, with a significantly lower M (337 +/- 35 vs. 657 +/- 76 P less than 0.01) during the highest insulin infusion rate [maximal glucose disposal (MGD)] without any significant difference in the levels of insulin half-maximally effective in the stimulation of glucose utilization. Neither erythrocyte nor monocyte maximum insulin receptor binding were different between the two populations. Four Cushing's syndrome patients were studied again after surgical treatment. A marked improvement of MGD was observed without any significant change in insulin-binding capacity. These results, particularly the marked decrease in MGD, a typical feature of postreceptor defects, indicate that cortisol-induced insulin resistance in man is due to an impairment of peripheral insulin action located beyond the hormone-receptor binding step.

Adult↗

PubMed1983

Effect of captopril on blood pressure and on the renin-angiotensin-aldosterone system in coarctation of the aorta.

UNLABELLED: To investigate the role of the renin-angiotensin-aldosterone system in hypertension due to coarctation of the aorta (COA), upright mean arterial pressure (MAP), plasma renin activity (PRA) and plasma aldosterone (Aldo) were determined before and 90 minutes after a single oral dose of captopril (25 mg) in eight patients with COA and in fourteen with essential hypertension (EH). There was no significant difference in MAP, PRA or Aldo values between the two groups in baseline conditions. After captopril administration, MAP and Aldo decreased significantly in both groups (p less than 0.01), whereas PRA showed a marked increase in patients with COA (p less than 0.001) and no significant changes in EH patients (from 1.5 +/- 2.2 to 49.7 +/- 9.8 and from 5.6 +/- 0.9 to 8 +/- 1.5 ng/ml/3h respectively). CONCLUSIONS: 1) MAP reduction and marked renin increase after captopril in COA patients support the view that systemic hypertension in COA is, at least in part, renin mediated and 2) the evaluation of PRA after captopril could be helpful in the decision to proceed with more invasive procedures in patients with suspicious clinical features of COA or with residual post-coarctectomy hypertension.

Adolescent↗

PubMed1982

Peripheral and renal vein plasma renin activity in hypertensive urological patients.

Upright plasma renin activity (PRA) was measured in 112 patients suffering from urological diseases associated with hypertension, and was found to be predominantly low. In 40 cases with normal or elevated peripheral PRA, renal venous PRA was measured and their ratios calculated. There was a significant decrease of blood pressure in 14 patients who had undergone surgery and both ratios were significant. The patients whose blood pressure remained unchanged had no significant renal vein PRA ratios. However, one case with nonlateralising renal venous PRA ratios responded well to surgery. It is concluded that although peripheral vein PRA is of limited value in hypertension associated with urological diseases, the measurement of PRA in renal vein plasma offers, in a number of cases, useful prognostic information.

Adult↗

PubMed1982

Circadian secretion of ACTH, cortisol, and mineralocorticoids in Cushing's syndrome.

The behaviour of plasma levels of ACTH was studied in five untreated patients with pituitary-dependent Cushing's syndrome, with blood samples taken every half an hour for a total period of 24 hours; plasma cortisol, corticosterone, deoxycorticosterone (DOC) and aldosterone were also measured simultaneously. In all cases, above normal secretory impulses of ACTH and cortisol, at approximately the same height, were present throughout the day, while between these peaks the levels were in the normal range. Few peaks of ACTH and cortisol were simultaneous and rare secretory impulses of corticosterone, and deoxycorticosterone were in synchrony with those of ACTH or cortisol. DOC levels were found to have some peaks above normal levels while corticosterone levels presented rare elevated peaks during the day. Plasma aldosterone values on the other hand, were extremely low in all except in one case, where the variations may be interpreted as pure fluctuations. These findings confirm that: 1) In a number of cases, multiple samples of ACTH and cortisol (during the 24 hrs.) appear to be essential in order to distinguish pituitary-dependent Cushing's syndrome from normal; 2) In conditions of ACTH excess, DOC and corticosterone secretion seems to become progressively less ACTH-dependent as we proceed down the biosynthetic chain towards aldosterone, which is suppressed in most cases.

Adolescent↗

PubMed1982

Effect of captopril on inactive renin and contact phase of coagulation system.

It has been suggested that a Factor XII-plasma Prekallikrein dependent pathway might play an important role in the activation of inactive renin. Since Captopril has the potential to affect the kinin-kallikrein system, we have studied in a group of 16 patients with essential hypertension its acute effect both on the levels of active, inactive and total renin, and on the contact phase of the coagulation system. Our results show that a single dose of Captopril (25 mg) induces a rapid and persistent increase of active and total renin, while inactive renin tends to decrease. Together with blood pressure, plasma Prekallikrein(PK), Factor XII(FXII) and Factor XI(FXI) concomitantly decrease, although not significantly, and their values seem to return to basal levels soonafter. However, no correlation was found at any time between the levels of any of these coagulation factors, including PK, and those of inactive, active or the ratio inactive/total renin. In spite of that, it is still possible that an activation of PK, which is likely to occur under Captopril administration, may affect at least the conversion of vessel-bound prorenin rather than the circulating form.

Adolescent↗