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H Vierhapper

Publications and source records attributed to H Vierhapper.

At least 127 records · Page 7Linked to original sources
PubMed1991

The effects of suramin on human adrenocortical cells in vitro: suramin inhibits cortisol secretion and adrenocortical cell growth.

Suramin, a polycyclic and polyanionic drug, has been successfully used in the therapy of inoperable adrenocortical cancer. The present study was undertaken to investigate the effects of suramin on normal human adrenocortical cells in primary monolayer cultures. The proliferation and the basal, as well as the adrenocorticotropin (ACTH)-stimulated, cortisol secretion of these cells were studied. The data show that suramin decreases basal, as well as ACTH-stimulated, cortisol secretion in a dose-dependent manner (P less than .05 from 300 mumol/L upward). At a suramin concentration of 3 mmol/L, cortisol secretion was inhibited by 70% +/- 4% in ACTH-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was also inhibited by suramin at concentrations from 300 mumol/L upward, maximal suppression (71% +/- 6%, P less than .01) being observed at a concentration of 10 mmol/L. Both inhibition of cortisol secretion and inhibition of adrenocortical cell proliferation were not due to toxicity of the compound, as could be shown by restimulation of cortisol secretion in suramin-treated cells with ACTH. Our results indicate that suramin exerts an inhibitory influence on the cortisol secretion and on the proliferation of normal human adrenocortical cells. Suramin may not only be useful in the treatment of adrenocortical cancer, but may also have an ameliorative effect on other malignant conditions with augmented steroid hormone production, resistant to conventional forms of therapy.

Adrenal Cortex↗
PubMed1991

Diagnostic relevance of suppressed basal concentrations of TSH compared with the negative TRH test in detection and exclusion of hyperthyroidism.

To evaluate the sensitivity of basal TSH concentrations as determined by an "ultrasensitive" IRMA-assay (RIA-gnost h-TSH-monoclonal, Behring) versus a "negative" TRH test (defined as an increment of TSH less than or equal to 0.2 mU/l 20 min after administration of 400 micrograms TRH iv) in the diagnosis of hyperthyroidism we examined 193 consecutive patients from our thyroid outpatient clinic: 34 patients displayed hyperthyroidism (total T4: 184.4 +/- 26.0 mumol/l, effective thyroxine index: 1.25 +/- 0.08), whereas 12 had isolated T3-hyperthyroidism (total T3: 3.47 +/- 0.48 nmol/l). Employing the producer's definition of subnormal ("suppressed") bTSH concentrations (less than or equal to 0.1 mU/l), only 19 (41.3%) hyperthyroid patients would have been detected; on the other hand, one euthyroid patient would have been recognized false positively as hyperthyroid. Using the TRH test as criterion led to the correct diagnosis in 42 (sensitivity: 91.3%) hyperthyroid patients, whereas two had low bTSH concentrations (less than or equal to 0.5 mU/l), but a normal TSH response to TRH (greater than 2.0 mU/l). Raising the threshold concentration to 0.2 and, subsequently, to 0.4 mU TSH/l increased the number of correct results to 38 (sensitivity: 82.6%) and 43 (93.5%), respectively. This was associated with a concomitant decrease in specificity in the diagnosis of hyperthyroidism from 93.7 (0.1 mU/l) to 27.9% (0.4 mU/l). In conclusion, despite ultrasensitive methods for estimation of low TSH concentrations, the TRH test remains an irreplaceable tool for the correct diagnosis of hyperthyroidism.

Adult↗
PubMed1991

Impaired conversion of cortisol to cortisone in chronic renal insufficiency--a cause of hypertension or an epiphenomenon?

To study the possible impairment of 11 beta-hydroxysteroid-dehydrogenase in patients with chronic renal insufficiency, urinary excretion rates of the four main glucocorticoid-metabolites, tetrahydrocortisol, tetrahydrocortisone, allotetrahydrocortisol and allotetrahydrocortisone were determined by capillary gas chromatography in 22 patients with chronic renal insufficiency with (N = 15) and without (N = 7) hypertension, but without hemodialysis treatment. Whereas the sum of all 41 steroid metabolites determined by capillary gas chromatography was reduced (p less than 0.001) in patients with chronic renal insufficiency as compared with 22 healthy individuals, the relative contribution of the four glucocorticoid metabolites to total steroid excretion was similar in patients with renal insufficiency (22 +/- 12%) and in healthy subjects (20 +/- 5%). However, the excreted amount of tetrahydrocortisol exceeded that of tetrahydrocortisone in all but 3 (normotensive) patients with chronic renal insufficiency, but only in one healthy subject resulting, in patients with chronic renal insufficiency, in a ratio of tetrahydrocortisone vs tetrahydrocortisone of 0.7 +/- 0.4 (hypertensive patients 0.5 +/- 0.2; normotensive patients 1.1 +/- 0.4; controls 1.9 +/- 0.9, p less than 0.001 vs patients with chronic renal insufficiency). This ratio of tetrahydrocortisone/tetrahydrocortisol showed a correlation with serum concentrations of creatinine (p less than 0.001). These results provide indirect proof of an impaired conversion of cortisol to cortisone in moderate renal insufficiency and may suggest a relationship with the hypertension frequently seen in this group of patients.

Adult↗
PubMed1991

Metabolic effects of fish-oil supplementation in patients with impaired glucose tolerance.

To determine the impact of fish-oil supplementation on glucose and lipid metabolism in patients with impaired glucose tolerance (IGT), 30 ml fish oil containing 3.8 g eicosapentaenoic acid (EPA; 20:5 omega 3) and 2.5 g docosahexaenoic acid (DHA; 22:5 omega 3) were given to eight obese subjects with IGT (mean +/- SD age 50.3 +/- 8.0 yr) in addition to their regular diet for 2 wk. Studies were performed in randomized order versus an isocaloric control period with a washout phase of 3 wk. Hyperinsulinemic clamp examinations (1 and 10 mU.kg-1.min-1) were performed. Glucose disposal rate (M value) rose from basal 14.3 +/- 5.1 to 17.9 +/- 4.4 mumol.kg-1.min-1 after fish oil (P less than 0.001) during the 1-mU clamp, whereas no change was seen during the 10-mU clamp (without fish oil, 42.2 +/- 8.9 mumol.kg-1.min-1; with fish oil, 45.1 +/- 9.8 mumol.kg-1.min-1;NS). Basal hepatic glucose output remained unaffected by fish oil, whereas fractional glucose clearance after intravenous glucose loading (2.4 mmol/kg body wt, t = 30 min) tended to increase (K value: without fish oil, 2.15 +/- 1.02%/min; with fish oil, 2.74 +/- 1.26%/min; NS). Neither the fasting concentrations of glucose and insulin nor induced glycemia and insulin response during intravenous glucose loading calculated as incremental area under the curve changed after fish-oil supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1991

Suramin and the human adrenocortex: results of experimental and clinical studies.

Suramin, a sulfonated drug, has been used successfully in the treatment of inoperable adrenocortical cancer. This study was undertaken to investigate the effects of suramin on the basal and the adrenocorticotropin-stimulated cortisol and pregnenolone secretion and on the proliferation of primary monolayer cultures of normal human adrenocortical cells. Suramin decreases basal and adrenocorticotropin-stimulated cortisol secretion in a dose-dependent manner (p less than 0.05 from 0.3 mmol/L upward). At a suramin concentration of 3 mmol/L cortisol, secretion was inhibited by 70% +/- 4% in adrenocorticotropin-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was inhibited by suramin at concentrations from 0.3 mmol/L upward, maximal suppression (71% +/- 6%; p less than 0.05) being observed at a concentration of 10 mmol/L. Neither down-regulation of cortisol secretion nor inhibition of adrenocortical cell proliferation was caused by toxicity of the compound, as could be shown by adrenocorticotropin-restimulating cortisol secretion in suramin-treated cells. The results indicate that suramin exerts an inhibitory influence on the cortisol secretion and the proliferation of normal human adrenocortical cells and may be useful in treating adrenocortical cancer.

Adrenal Cortex↗
PubMed1991

Contribution of leg vascular tissues to the overall metabolic clearance of human atrial natriuretic factor (hANF) in man.

From experimental studies it has been suggested that considerable peripheral clearance of human atrial natriuretic factor (hANF) might occur. In healthy men (n = 7) the peripheral fractional extraction of hANF was about 35% under basal conditions resulting in hANF-uptake across the leg vascular bed of 2.1 +/- 2.4 pMol/min and regional leg clearance rate of 102.6 +/- 88.2 ml/min, which is approximately 2.5% of the total metabolic clearance rate. During a primed constant i.v. infusion of hANF (bolus 100 micrograms; infusion 100 micrograms/h, t = 1h) arterial and venous plasma concentrations of hANF increased about 10-fold (p less than 0.05), however, estimated leg blood flow as well as leg fractional extraction, leg uptake and clearance rates of hANF did not significantly change as compared to baseline. Total metabolic clearance rates and apparent production rates of hANF were 4.05 +/- 1.93 l/min and 84.1 +/- 29.9 pMol/min, respectively. We conclude that in healthy man the leg vascular bed does not play a major regulatory role in the metabolism of exogenously infused hANF. However, our results suggest that the peripheral vasculature is, to a certain extent, involved in the metabolic clearance of endogenous hANF and thus, contributes to the peptide's overall disposal.

Adult↗
PubMed1990

Renal disposal of human atrial natriuretic peptide in man.

In healthy men (n = 7) the renal fractional extraction of human atrial natriuretic factor (hANP) as determined by the renal venous catheter technique was approximately 50% both under basal conditions and during the administration of exogenous hANP. When arterial and venous plasma concentrations of hANP were maintained about tenfold above basal concentrations by a bolus- (100 micrograms) primed intravenous (IV) infusion (100 micrograms/h for 1 hour) of hANP, renal uptake of hANP increased from, basal, 11.2 +/- 6.7 pmol/min to 126.5 +/- 64.8 pmol/min (P less than .05), while estimated renal plasma flow (ERPF) decreased by about 25% (P less than .05). Total metabolic clearance rates (MCRs) of hANP, renal clearance rates, and production rates of hANP were 3.89 +/- 1.21 L/min, 0.42 +/- 0.18 L/min, and 76.1 +/- 52.7 pmol/min, respectively. In healthy men, one kidney accounts for about 10% of total hANP clearance.

Adult↗
PubMed1990

Formation of androstanediol from 13C-labeled testosterone in humans.

The determination of urinary 5 alpha-androstane-3 alpha,17 beta-diol (3a-Diol) by gas chromatography/mass spectometry during and after the infusion of stable-labeled testosterone (T) represents an alternative to the use of radioactive label for turnover studies in vivo. Using this methodology to assess the urinary excretion rates of T and 3a-Diol in healthy men (n = 6) and women (n = 5) during and after the intravenous infusion (t = 4 hours) of 20 mg (men) or 5 mg (women) [13C]testosterone, the cumulative renal excretion of 13C-labeled T was found to be 15.6 +/- 9.6 micrograms/24 hours (men) and 1.1 +/- 1.6 micrograms/24 hours (women), equivalent to 0.08% +/- 0.05% and 0.02% +/- 0.03% of the infused amount of 13C-T, respectively. The cumulative excretion of 13C-3a-Diol was 67.7 +/- 19.9 micrograms/24 hours (men) and 10.0 +/- 6.0 micrograms/24 hours (women), equivalent to 0.3 +/- 0.1% and 0.2 +/- 0.1% of the infused dose of 13C-labeled testosterone, respectively.

Adult↗
PubMed1990

Permissive action of glucocorticoid substitution therapy on the effects of atrial natriuretic peptide (hANP) in patients with adrenocortical insufficiency.

To study the potential impact of glucocorticoids on the effects of human atrial natriuretic peptide (hANP) in man, the diuretic and natriuretic response to intravenous bolus doses of hANP (50 and 100 micrograms) was studied in seven male patients with deficient endogenous glucocorticoid synthesis, both during withdrawal of glucocorticoid therapy and during subsequent substitution with dexamethasone. Plasma concentrations of ACTH, though markedly suppressed by dexamethasone as compared to the unsubstituted state were not influenced by exogenous hANP either during deprival or substitution of glucocorticoids. Basal plasma concentrations of hANP were 10.3 +/- 8.4 pmol/l and 19.3 +/- 11.1 pmol/l during glucocorticoid withdrawal and following substitution with dexamethasone, respectively. When substituted with glucocorticoids, patients responded to hANP (100 micrograms) with an increase (p less than 0.025) in diuresis and sodium excretion, whereas no changes in diuresis and sodium excretion were seen following intravenous hANP during glucocorticoid withdrawal. These results suggest that glucocorticoids may have a permissive effect on hANP-mediated natriuresis and diuresis.

Adrenal Glands↗
PubMed1990

Action of endogenous atrial natriuretic peptide in calves with experimental acute central venous congestion and low cardiac output.

STUDY OBJECTIVE: The aim of the study was to investigate plasma concentrations of atrial natriuretic peptide, aldosterone, and renin during experimentally induced acute central venous congestion. DESIGN: Two experimental calf models were used: (1) right heart failure due to pulmonary artery obstruction; (2) inferior vena cava syndrome produced by inferior vena caval obstruction. Hormonal responses and haemodynamic variables were measured over 6 h. SUBJECTS: Experiments were performed on three female "Schwarzbund" calves, age 3 months, weight 92 +/- 8 kg. MEASUREMENTS AND MAIN RESULTS: In the pulmonary artery obstructed group there was an increase of plasma aldosterone from 6.5(SEM 1.6) to 22.1(3.2) ng.dl-1 (p less than 0.05), of renin from 0.7(0.1) to 2.5(0.3) Goldblatt units x 10(-4).ml-1 (p less than 0.05), and of atrial natriuretic peptide from 22.1(4.5) to 141.4(27.8) pmol.litre-1 (p less than 0.05). During inferior vena caval obstruction, aldosterone increased from 2.4(0.4) to 20.9(2.0) ng.dl-1 (p less than 0.05), and renin increased from 0.4(0.05) to 2.0(0.20) Goldblatt units x 10(-4).ml-1 (p less than 0.05). In this experiment, atrial natriuretic peptide remained unchanged. Cardiac output decreased in both groups. There was significant fluid and electrolyte retention during both experiments, with urine volume decreasing from 87.7(11.6) to 35.0(1.2) ml-h-1 in experiment (1), and from 185(14) to 95.7(8.6) ml.h-1 in experiment (2). CONCLUSIONS: The study suggests (1) that in an experimental acute state of reduced cardiac output due to pulmonary artery stenosis with constantly increased right heart pressures, raised endogenous atrial natriuretic peptide failed to induce diuresis and natriuresis; (2) that in acute right heart failure, renin and aldosterone secretion could not be suppressed by raised atrial natriuretic peptide concentrations; and (3) atrial natriuretic peptide secretion seemed to be exhausted after 6 h continuous atrial distension.

Acute Disease↗
PubMed1990

Plasma concentrations of endothelin in man: arterio-venous differences and release during venous stasis.

Endothelin-1 is a recently described endothelium-derived vasoconstricting peptide. Plasma concentrations of immunoreactive (IR-) endothelin were investigated in six healthy young men applying a radioimmunoassay after extraction of endothelin from plasma. In venous plasma a mean concentration of 1.3 +/- 0.4 pmol l-1 was found, whereas the mean concentration in arterial plasma was 0.9 +/- 0.4 pmol l-1 (P less than 0.005). During venous stasis for 10 min the mean plasma concentration of IR-endothelin increased about twofold, from basal 1.1 +/- 0.3 pmol l-1 to 2.1 +/- 0.3 pmol l-1 (P less than 0.01). This manoeuvre may prove helpful to investigate the control of endothelin in vivo under a variety of pathological conditions.

Adult↗
PubMed1990

Effect of endothelin-1 in man.

The effect of an intravenous infusion of human endothelin-1 on blood pressure and plasma concentrations of endothelin-1, potassium, sodium, renin, aldosterone, and atrial natriuretic factor was investigated in six healthy, sodium-loaded men. During the peptide's exogenous application (1.0, 2.5, and 5.0 ng/kg.min), its plasma concentrations rose from a basal value of 1.2 +/- 0.3 to 3.2 +/- 1.9, 9.9 +/- 7.6, and 56.5 +/- 50.3 pmol/l (p less than 0.01), respectively, and mean blood pressure rose from a basal value of 87.1 +/- 7.3 to 92.6 +/- 8.2 mm Hg (p less than 0.01). A rise in serum concentrations of potassium (from 4.0 +/- 0.3 to 4.6 +/- 0.2 mmol/l; p less than 0.005) and a concomitant fall in serum concentrations of sodium (from 142.7 +/- 1.0 to 139.5 +/- 2.3 mmol/l; p less than 0.05) was seen in each subject. Plasma concentrations of renin, aldosterone, and atrial natriuretic factor did not change during the infusion of endothelin-1. Thus, in the doses used, endothelin-1 induces a rise in blood pressure and serum potassium concentrations.

Adult↗
PubMed1990

Metabolism of cortisol in anorexia nervosa.

In patients with anorexia nervosa 24-h mean plasma concentration of cortisol were 0.44 +/- 0.09 mumol/l (normal less than 0.28 mumol/l). Following stimulation by ACTH (1-24) urinary excretion rates of cortisol were stimulated from 0.22 +/- 0.08 to 4.85 +/- 2.78 mumol/24 h. Similarly, plasma concentrations of the glucocorticoid metabolite, tetrahydrocortisone, increased from 23.3 +/- 9.0 to 47.3 +/- 30.2 nmol/l; urinary excretion rates of tetrahydrocortisone increased from 3.61 +/- 0.90 to 8.40 +/- 1.72 mumol/24 h. The relative share of the sulphate, glucuronide and free fractions of tetrahydrocortisone in the patients' urine did not indicate any defect in metabolization of this steroid metabolite. Excretion rates of the four glucocorticoid tetrahydro-metabolites, tetrahydrocortisone, allotetrahydrocortisone, tetrahydrocortisol, and allo-tetrahydrocortisol, expressed as percent of total steroid excretion, were similar in patients with anorexia and in healthy women under basal conditions (24 +/- 6 vs 23 +/- 6%) and during stimulation by ACTH (1-24) (36 +/- 10 vs 45 +/- 6%). The share of the two androgen metabolites, androsterone and etiocholanolone, was 24 +/- 5% of total steroid excretion (basal; healthy women: 27 +/- 8%) and 13 +/- 2% (ACTH stimulation; healthy women: 12 +/- 4%) in patients with anorexia nervosa. Thus, analysis of urinary steroid excretion rates did not indicate a shift in adrenocortical function. The results confirmed enhanced secretion of cortisol in patients with anorexia nervosa under basal conditions and during/following stimulation by ACTH. The ACTH-induced increase in the concentrations of the tetrahydro-glucocorticoid metabolites in urine was less pronounced than that of cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗