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Biomedical subjects

H Vierhapper

Publications and source records attributed to H Vierhapper.

225 records · Page 13Linked to original sources
PubMed1978

Comparison of the corticotropic action of two synthetic, substituted analogues of ACTH: ACTH1--17 and ACTH1--18.

The effect of a recently synthesized analogue of ACTH, Ala1, lys17-ACTH(1-17-4-amino-n-butylamide; (ACTH1-17) upon serum cortisol levels in 9 healthy males was compared with that of ACTH1-18, D-ser1-lys17, 18-ACTH(1-18). Both compounds induced an identical rise in serum cortisol which lasted for at least 8 hours. It is concluded that the amino acid in position 18 is not essential for the corticotropic properties of the synthetic heptadecapeptide. The prolonged effect of these compounds indicates a potential therapeutic significance for ACTH analogues of low molecular weight.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Quantitative and qualitative differences in basal and glucose- and arginine-stimulated insulin secretion in healthy subjects and different stages of NIDDM.

To determine quantitative and qualitative differences in insulin secretion equimolar amounts of glucose and arginine were infused in 9 healthy subjects, in 8 individuals each with obesity without and with impaired glucose tolerance, and in non-obese and obese non-insulin-dependent diabetic patients (NIDDM). Insulin secretion was calculated after individual determination of metabolic clearance rate of C-peptide (MCRcp) both as the area under the C-peptide concentration curve times MCRcp, and by a mono-compartment mathematical model, both yielding identical results. MCRcp fell consistently with increasing C-peptide infusion rate (e.g.: healthy subjects: C-peptide, 10 nmol/h, 4.2 +/- 0.4; 20 nmol/h, 3.3 +/- 0.3; 30 nmol/h, 3.1 +/- 0.2 ml/kg.min; p less than 0.05 to p less than 0.01). Basal insulin secretion was 2.1-fold greater in the obese with impaired glucose tolerance than in healthy subjects, but was unchanged in non-obese NIDDM. Glucose and arginine triggered insulin release was greater than in healthy subjects at almost identical area under the respective substrate concentration curve (AUC/kg body weight) in obese subjects without (2-fold) and with impaired glucose tolerance (4-fold), and in NIDDMs following i.v. arginine (2-fold). The mean ratio of incremental insulin release to i.v. glucose and arginine was smaller in NIDDM (normal weight, 1.3 +/- 0.4; obese, 1.0 +/- 0.2) than in healthy (2.0 +/- 0.3), or obese subjects with impaired glucose tolerance (2.8 +/- 0.7). Stimulated C-peptide/insulin ratio was reduced in all patients vs that in healthy subjects (p less than 0.05). We conclude that (a) MCR of C-peptide is in part a saturable process; (b) insulin clearance may be impaired in obesity and NIDDM; and (c) insulin secretion differs in obese states and NIDDM both quantitatively and qualitatively, and thereby separates the two disorders as different entities. In addition, quantitation of insulin release in obese states may also help (d) to better define primary algorithms for insulin replacement in normal- and overweight insulin-dependent diabetic patients.

Adult↗
PubMedDate not supplied

Atrial natriuretic factor production and secretion during clinical total artificial heart-bridge-to-transplantation.

In 5 total artificial heart (TAH)-bridge-to-transplant (BTT) patients production and secretion of atrial natriuretic factor (ANF)1 was studied before, during, and after TAH implantation. Bridging periods lasted between 9 and 28 days. Atrial biopsies were taken during implantation, and after TAH explantation for histologic and histochemical investigations to evaluate differences in morphology and ANF-content of the specific atrial granules. Plasma concentrations of ANF (pANF), aldosterone (PAC) and renin (PRC) were measured daily, as were hemodynamic parameters. In the preoperative state, pANF was always markedly elevated, while during TAH bridging, pANF remained moderately elevated with fluctuations. A positive correlation between pANF levels and right atrial pressure (RAP) was seen in all patients (p less than 0.05). Slight correlation was also observed between pANF and left atrial pressure (LAP), but no correlation was seen between pANF and systemic blood pressure, and no consistent pattern was seen in the plasma concentrations of either renin or aldosterone. After heart transplantation (HTX), which was performed in 3 patients, pANF levels were significantly higher than during TAH, and continued to show a positive correlation with RAP. From our data, we conclude that ANF production sites and secretory mechanisms remain intact during TAH-bridging, although upon implantation of a TAH, the remaining atria are deprived of all coronary blood supply and most autonomic innervation.

Adult↗
PubMedDate not supplied

Release and vasoactive actions of catecholamines during inhibition of prostaglandin synthesis in normal man.

To assess the effect of prostaglandin inhibition upon the vasoactive actions of endogenous and exogenous catecholamines in healthy man, indomethacin (150 mg/day for 3 days) was administered to six healthy men in the sodium-repleted state. Pretreatment with indomethacin did not interfere with the response of blood pressure and pulse rate to orthostasis (10 minutes), a cold pressor test (2 minutes), and the intravenous (i.v.) administration of norepinephrine (NE) (50, 100, and 200 ng kg-1 min-1). Basal plasma concentrations of epinephrine (E) and NE as well as the concentrations of E during orthostasis and cold pressor test remained uninfluenced by pretreatment with indomethacin. While the release of NE during orthostasis appeared to be suppressed in the indomethacin-treated state, it was unchanged during the cold pressor test. These results indicate that inhibition of endogenous prostaglandin synthesis may suppress the release of NE, but does not have a major impact on the vasoactive actions of endogenous and exogenous catecholamines in normal men.

Adult↗
PubMedDate not supplied

Effect of exogenous insulin on blood pressure regulation in healthy and diabetic subjects.

To define the role of insulin in blood pressure regulation, the hormone's action on renal sodium handling, potassium balance, pressor reactivity, and the release of catecholamines and aldosterone are summarized. Insulin-stimulated renal sodium reabsorption induces expansion of the extracellular volume, increase in cardiac output, and ultimately, hypertension. On the other hand, the insulin-induced shift of potassium into the cell interior is transient and appears to be of little consequence for long-term blood pressure control. Although the release of norepinephrine is stimulated by insulin, a norepinephrine-mediated pressor effect is prevented in healthy men by a simultaneous norepinephrine-antagonistic action of insulin. The latter causes the fall in blood pressure seen after intravenous insulin in patients with autonomic dysfunction who lack the rise in norepinephrine release. Both in healthy and in diabetic men, exogenous insulin does not modify the pressor effect of angiotensin II, although it impairs the secretion of aldosterone during stimulation by supraphysiological doses of angiotensin II.

Adult↗
PubMedDate not supplied

Salt wasting in simple virilizing congenital adrenal hyperplasia.

OBJECTIVE: To evaluate possible derangement in sodium balance in patients with the simple virilizing (SV) form of congenital adrenal hyperplasia (CAH) which might have implications for therapeutic procedures. DESIGN: Patients were sodium loaded throughout the protocol and studied after interruption of cortisone therapy for 4 days, after treatment with dexamethasone 1 mg/m2/d for 3 days and after additional therapy with 9alpha-fluorocortisone (9alphaF) 0.1 mg/m2 for 3 days and 9alphaF 0.2 mg/m2 for 3 days. After each phase, basal and stimulated (2 h in an upright position), aldosterone and plasma renin concentrations (PRC) were evaluated. METHODS: Nine children aged 5.0 to 12.8 years with the clinical classification of SV CAH were studied. Diagnosis was established at the age of 2.9 +/- 1.9 years (mean +/- SD) and the patients were treated with oral hydrocortisone at a mean dose of 22.5 mg/m2/d, given in two or three daily doses. Seven patients were heterozygous for the Ile172Asn point mutation in exon 4, and two for the Pro30Leu mutation in exon 1 of the CYP21 gene. All of them had a more severe mutation or deletion in the second allele. PRC was determined by RIA and expressed as Goldblatt units (GU). Aldosterone was determined by RIA. Genotyping for disease-causing deletions and mutations was performed by Southern blot analysis, PCR and direct sequencing of CYP21. RESULTS: PRC was significantly higher in patients off hydrocortisone replacement therapy than in age matched control subjects (basal 3.3 +/- 0.5 vs 1.2 +/- 0.2 GU 10(-4)/ml [mean +/- SEM], p<0.001; stimulated 8.6 +/- 0.5 vs 2.4 +/- 0.4 GU 10(-4)/ml; p<0.05). Upon treatment with dexamethasone, patients with CAH demonstrated a decrease in basal (2.1 +/- 0.5 GU 10(-4)/ml) but not in stimulated PRC (8.8 +/- 2.6 GU 10(-4)/ml). When dexamethasone treatment was supplemented by 9alphaF, both supine (0.9 +/- 0.1 GU 10(-4)/ml) and stimulated (1.6 +/- 0.3 GU 10(-4)/ml) PRC were suppressed into the normal range. Aldosterone concentrations were elevated after interrupting hydrocortisone treatment only under basal conditions. Dexamethasone caused a decrease below the reference level and 9alphaF resulted in further suppression of aldosterone concentration. CONCLUSIONS: All patients were hemizygous for a CYP21 mutation that is usually considered not to be associated with clinically relevant salt loss. However, we demonstrated an aldosterone secretion disturbance in patients with SV CAH which cannot be corrected by glucocorticoid treatment alone. Additional mineralocorticoid therapy should be considered in order to suppress PRC and reduce the glucocorticoid dose required for adequate control.

17-alpha-Hydroxyprogesterone↗
PubMedDate not supplied

Endothelin-induced venoconstriction is unaffected by type 2-diabetes: in vivo effect of histamine on the endothelin action on veins.

In vitro studies indicate that the intact endothelium prevents the access of circulating endothelin to vascular smooth muscle cells. Disease states like diabetes, that are associated with endothelium dysfunction, might facilitate the access of endothelin to vascular smooth muscle, causing increased vasoconstriction. To investigate whether differences between diabetic and nondiabetic subjects could be detected on superficial veins, venous diameter changes in response to local infusions of endothelin (1.53, 3.11 and 6.22 pmol/min) were compared in type 2-diabetics with albuminuria (greater than 300 mg/day) and borderline hypertension (diastolic blood pressure 90-95 mmHg), and in healthy volunteers. In addition, we studied the effect of histamine on the endothelin-induced venoconstriction. The dorsal hand vein compliance technique was employed. Endothelin caused a dose-dependent, slow-onset constriction of the hand vein in all subjects, without any difference in endothelin responsiveness between diabetic and control subjects. The maximal venoconstriction at 6.22 pmol endothelin/min was 29 +/- 26% (% of venous diameter at base line) in diabetics and 23 +/- 22% in controls (p greater than 0.02). Co-infusion of endothelin and a dose of histamine with minimal venodilatory effect ("ED5-ED20") had no influence on the endothelin responsiveness of the hand veins, in that the maximal venoconstriction after 6.22 pmol endothelin/min was 25 +/- 23% without, and 23 +/- 16% with added histamine. Submaximally venodilating histamine doses ("ED60-ED90") markedly attenuated the endothelin-induced venoconstriction (maximal venoconstriction: 63 +/- 43%). These data, obtained in veins, argue against a generalized defect in vascular responsiveness to endothelin associated with diabetes.

Adult↗