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Biomedical subjects

H Vierhapper

Publications and source records attributed to H Vierhapper.

At least 109 records · Page 6Linked to original sources
PubMed1993

Endothelin-1 in adult respiratory distress syndrome.

Endothelin-1 (ET-1), a potent vasoconstrictor peptide produced by endothelial cells and degraded predominantly in the pulmonary vasculature, has been implicated in the development of various organ dysfunctions. To determine the pathophysiologic role of ET-1 in adult respiratory distress syndrome (ARDS) and the impact of impaired lung function on transpulmonary peptide handling, we compared plasma levels and pulmonary ET-1 balance in 14 patients with ARDS and in seven healthy control subjects. To obtain comparable conditions in both groups, the ET-1 level was raised in the control group by exogenous infusion (0.4 pmol/kg/min) to 9.4 +/- 0.8 pmol/L. ARDS was accompanied by a hyperdynamic circulatory pattern with increased cardiac output and depressed total vascular resistance but, simultaneously, pulmonary hypertension. Venous ET-1 concentration was massively increased in ARDS (9.8 +/- 1.2 versus 2.1 +/- 0.2 pmol/L, p < 0.001). In control subjects, the lung cleared the major fraction of ET-1 (fractional extraction 43 +/- 8.8%, uptake 12.5 +/- 2.5 pmol/min). In contrast, in ARDS there was a pronounced pulmonary releases into the circulation (32.8 +/- 10.3 pmol/min). We conclude that ET-1 concentrations are elevated in ARDS as the result of both increased formation and decreased disposal. Lung failure affects not only gas exchange but also nonrespiratory, metabolic pulmonary functions.

Adolescent↗
PubMed1993

Dose relationship of stimulated insulin production following intravenous application of glimepiride in healthy man.

This study evaluates stimulated insulin production rate (incremental AUC x MCR (metabolic clearance rate) of C-peptide) and blood glucose (BG) response after i.v. administration of glimepiride (Hoe 490, GLI, CAS 93479-97-1) (0.25, 0.50, 0.75, 1.00, 1.25, 1.50 mg) in healthy man (27 +/- 4 yrs). It was shown that i.v. bolus administration of GLI (0.25, 0.50, 1.25 and 1.50 mg) caused a dose-related rise in insulin production from 18 +/- 17 to 25 +/- 13, 36 +/- 14 and 54 +/- 34 pmol/kg body weight, respectively. This effect did not yet plateau at 1.5 mg GLI and was paralleled by a fall in BG (decremental area below BG baseline) by 40 +/- 36, 69 +/- 20, 161 +/- 47 and 113 +/- 62 mmol.min/l. It is concluded that insulin release is increased by i.v. GLI in a dose related manner, while a parallel decline in BG was induced only up to 1.25 mg GLI. The less marked fall of BG after injection of 1.50 mg GLI may reflect interference by insulin-counterregulatory hormones secondary to induced hypoglycaemia.

Adult↗
PubMed1993

Anabolic steroids and blood cell production.

In the past anabolic steroids were the first-choice treatment for pancytopenic disorders that were often poorly classified. They are now superseded by other more recently developed methods of treatment--for example bone marrow transplantation and immunosuppression. This contrasts to the authors' experience, and to that of many other haematologists, who have noted anabolic steroid-induced responses in patients who were unsuitable for or unresponsive to the new treatments. Anabolic steroids did not, however, demonstrate an obvious effect in recent controlled trials involving patients with aplastic anaemia. Their use with immunosuppressive treatment is currently under investigation. Although anabolic steroids rarely reverse the course of anaemia in a myelodysplastic syndrome, even a slight haemopoietic improvement is desirable. Children with Fanconi's anaemia may benefit from a reduced transfusion requirement. Uraemic patients may experience significant side effects on standard erythropoietin (epo) treatment. There have been no controlled trials comparing epo versus anabolic steroids or epo versus epo in conjunction with anabolic steroids. Data from uncontrolled studies indicate a better response to anabolic steroids in children and females than in men. In spite of the fact that anabolic steroids have been used for almost 30 years, they should be carefully re-evaluated in scientifically controlled trials to test their efficacy and to compare them with the new treatments. Such trials, however, are impeded by the limited knowledge available with regard to pharmacological parameters and optimal treatment schedules.

Anabolic Agents↗
PubMed1993

Equivalent discrimination among states of thyroid function by immunochemiluminimetric and immunoradiometric determination of thyrotropin.

New immunochemiluminometric assays (ICMA) of thyrotropin (TSH) have been reported to facilitate the diagnosis of hyperthyroidism. To compare the accuracy of ICMA-TSH with that of a conventional immunoradiometric assay (IRMA-TSH), we examined 115 consecutive patients of a thyroid outpatient clinic. On the basis of complete thyroid-function testing, including thyroliberin tests, the untreated patients (n = 89) were subclinically hyperthyroid (n = 21), subclinically hypothyroid (n = 13), or euthyroid (n = 55). The receiver-operating characteristic (ROC) curve, used for comparing the TSH values obtained by these two methods, was shifted to the left for the IRMA-TSH. The area under the curve was greater for IRMA-TSH than for ICMA-TSH (0.984 vs 0.869, respectively), which suggests equal or better clinical performance of IRMA-TSH vs ICMA-TSH in discriminating between hyperthyroidism and euthyroidism. Both assays displayed similar clinical sensitivity/specificity for evaluating thyroid function in hypothyroid and treated patients. We conclude that the ICMA-TSH tested is not more accurate than an IRMA in distinguishing between hyperthyroidism and euthyroidism.

Adult↗
PubMed1992

Polar secretion of endothelin-1 by cultured endothelial cells.

The aim of this study was to determine the permeability of endothelial monolayers for endothelin-1 and a possible directionality of the endothelin-1 secretion process. Human umbilical vein endothelial cells were cultured on acellular amniotic membranes, dividing the tissue culture wells into an apical (luminal) and a basolateral (abluminal) compartment. Whereas in the absence of endothelial monolayers 44.9 +/- 2.3 and 43.5 +/- 2.0% of the unilaterally added endothelin-1 permeated from the apical to the basolateral side and from the basolateral to the apical side, respectively, only 6.5 +/- 0.6 and 6.6 +/- 0.4% diffused in the presence of endothelial cells. Analyzing endothelin-1 secretion, approximately 80% of the total amount of synthesized endothelin-1 was found in the basolateral compartment; thrombin (10 units/ml) stimulated the production of endothelin-1 approximately 2-fold, but did not change the relative distribution of endothelin-1 between the apical and basolateral compartments. In the presence of dexamethasone (10(-7) M), a decrease in the level of endothelin-1 was found in the apical compartment, whereas the total amount of endothelin-1 produced was not affected. Dexamethasone did not influence the permeability of human umbilical vein endothelial cell monolayers for endothelin-1. These results strongly support the hypothesis that endothelin-1 is a local paracrine regulator of vasotone.

Amnion↗
PubMed1992

Endothelin-1 stimulates chloride and potassium secretion in rabbit descending colon.

The vasoactive peptide endothelin-1 (ET-1) which is present in high concentrations in the colon, causes concentration-dependent electrogenic Cl- secretion in rabbit descending colon. This effect is half-maximal at 0.11 mumol/l. Like other secretagogues, ET-1 also stimulates K+ secretion. The secretory effect of ET-1 is associated with increased release of prostaglandin E2 from the serosal surface of the mucosa. ET-1-induced Cl- secretion is completely inhibited by the loop diuretic bumetanide and by indomethacin and quinacrine, inhibitors of prostaglandin synthesis. Neuronal mechanisms do not seem to be involved, as tetrodotoxin did not affect the secretory response to ET-1 significantly. On the other hand, neither the catalytic activity nor the transport function of the Na+/K(+)-ATPase of rabbit colon epithelium is affected by endothelin-1 (ET-1) in concentrations up to 10 mumol/l. It is concluded that ET-1 causes Cl- and K+ secretion by stimulating phospholipase A2 and release of prostaglandins, whereas Na+ transport is not altered.

Animals↗
PubMed1992

Effects of islet amyloid polypeptide on hepatic insulin resistance and glucose production in the isolated perfused rat liver.

The impact of (pancreatic) islet amyloid polypeptide on glucose metabolism and insulin sensitivity was examined in isolated rat livers perfused in a non-recirculating system. Continuous infusion of 10(-7) mol/l islet amyloid polypeptide affected neither basal nor glucagon (10(-9) mol/l)-stimulated glucose output by livers from fed rats, but it did increase the hepatic cyclic AMP release within 44 min (7.91 +/- 12.07 vs control: 0.07 +/- 0.03 pmol x 100 g body weight-1). The effect of the peptide on the ability of insulin to inhibit glucagon-induced hepatic glycogenolysis was measured in three experimental groups (n = 6). As expected glucagon (7 x 10(-11) mol/l) increased integral hepatic glucose release within 84 min (763.4 +/- 161.7 vs -25.7 +/- 73.2 mumol x 100 g body weight-1 in the control group, p less than 0.001), while insulin (100 mU/l) decreased the glucagon-stimulated glucose production (395.2 +/- 180.0 mumol x 100 g body weight-1, p less than 0.01). Simultaneous infusion of 10(-7) mol/l islet amyloid polypeptide however, was not able to reverse insulin-dependent inhibition of glucagon-stimulated hepatic glucose output (370.0 +/- 102.5 mumol x 100 g body weight-1, NS) or to enhance lactate-induced gluconeogenesis of livers from 24 h fasted rats (n = 8). The glucose production stimulated by 10(-9) mol/l glucagon was slightly greater in islet amyloid polypeptide-pre-treated livers than in a control group without addition of islet amyloid polypeptide (5 min: 3.60 +/- 3.36 vs 1.67 +/- 1.28 mumol.min-1 x 100 g body weight-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1992

Endothelin-1-stimulated glucose production in vitro in the isolated perfused rat liver.

The effect of endothelin-1 (ET-1) on production rates of glucose, lactate and cyclic adenosine monophosphate (cAMP) was studied in isolated rat livers perfused in a non-recirculating system. Continuous infusion of ET-1 (0.5 to 10 nmol/L) resulted in a dose-dependent increase in hepatic glucose production, reaching a maximum of 7.56 +/- 1.04 mumols.min-1.100 g bodyweight (BW)-1 at 10(-9) mol/L ET-1 versus 1.32 +/- 0.13 mumols.min-1.100 g BW-1 (P less than .01) after 60 minutes in control experiments. The integral ET-1-induced glucose release (37 +/- 20 mumols.g liver-1) was accompanied by a 15% decrease in hepatic glycogen content (basal, 116 +/- 12, after ET-1, 99 +/- 8 mumols glucose.g liver-1, P less than .05), while 10(-9) mol/L ET-1 affected neither hepatic lactate nor cAMP release versus control experiments. ET-1-induced glucose output was abolished during nominally Ca(2+)-free perfusions (-41.3 +/- 65.2 mumols.100 g BW-1, P less than .01), but was unaffected by 10(-6) mol/L verapamil and only slightly attenuated by 10(-6) mol/L nicardipine (376.3 +/- 101.4, NS, and 244.4 +/- 70.0 mumols.100 g BW-1, P less than .05, respectively). Dantrolene (10(-5) mol/L), an inhibitor of Ca2+ release from the endoplasmic reticulum, reduced glucose release elicited by 10(-9) mol/L ET-1 to 241.1 +/- 57.3 mumols.100 g BW-1 (P less than .05). Pharmacological concentrations of insulin (1 U/L) were required to inhibit ET-1-dependent glucose release by 59% (P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Monitoring daily insulin needs--an important follow-up parameter in late pregnancy in diabetic mothers?].

Pregnancy is a state of natural insulin resistance, which is due to placental production of human placental lactogen (HPL), an insulin antagonising hormone, leading to a remarkable increase of insulin requirement in pregnant diabetics in the 2nd and 3rd trimester. Aim of the prospective study was the quantification of daily insulin requirement during the last 28 days before delivery in pregnant women suffering from insulin-dependent diabetes mellitus (n = 20) with and without evidence of "placental insufficiency syndrome" employing peripheral rheography as indirect parameter for placental haemoperfusion. All diabetic women included controlled carbohydrate metabolism by means of a functional insulin therapy (FIT; HbA1c in normal range < 5.8%), a multiple injection regime with frequent blood glucose self-control at least from the 2nd trimester of pregnancy. According to the results of peripheral rheography in the 34th gestational week, an impedanceplethysmographic method for quantifying peripheral haemoperfusion, patients were subdivided in a group with (B: n = 8) and without (A: n = 12) indirect evidence of placental dysfunction. Groups did not differ in maternal age, duration of diabetes, maternal weight and week of delivery (A: 39.08 +/- 1.44; B: 39.12 +/- 1.46). Mean weight of neonates was lower in group B (3319 +/- 619 g) compared to group A (3613 +/- 437 g). During a comparable state of near-normoglycaemia in both groups, 7 out of 8 women in group B, but only 1 out of 12 women in group A displayed a significant decrease in daily insulin requirement from day -28 to day -3 before delivery (linear regression; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Regional hemodynamic effects and clearance of endothelin-1 in humans: renal and peripheral tissues may contribute to the overall disposal of the peptide.

We investigated the regional balance of endothelin-1 across the renal and leg vascular bed as well as the hemodynamic effects of exogenously administered endothelin-1 in six healthy men. Net regional endothelin-1 balance was calculated from the respective arteriovenous differences in plasma concentrations and the corresponding plasma flow, the latter being determined by para-aminohippurate or indocyanine-green dye using appropriate catheter techniques. During constant intravenous (i.v.) infusion of endothelin-1 (0.4 pmol/kg/min), a slight increase in diastolic blood pressure (p less than 0.05) and a decrease in heart rate (p less than 0.01) were observed. In contrast, no significant changes in leg hemodynamics were noted. Renal plasma flow decreased by approximately 30%, and renal vascular resistance increased by 50% as compared with the control (placebo) period (p less than 0.01). Renin plasma concentrations did not change substantially during endothelin-1 infusion. During the control (placebo) period, arterial endothelin-1 plasma concentrations averaged 2.1 +/- 1.0 pM. An equilibrated peptide balance across the leg and a slight renal uptake of endothelin-1 was observed. After endothelin-1 infusion, arterial plasma concentrations of the peptide increased to 4.9 +/- 1.3 pM (p less than 0.01), and a net overall renal and limb uptake of endothelin-1 accounted for approximately 9 and 6% of the infused endothelin-1 amount, respectively. Results showed that at systemic endothelin-1 plasma concentrations, comparable to those which occur in a variety of pathologic conditions such as hypertension or cardiogenic shock, besides pulmonary clearance, renal and limb uptake of the peptide may also contribute to the short half-life (t1/2) of endothelin-1 in humans.

Adult↗
PubMed1992

Regional effects and clearance of endothelin-1 across pulmonary and splanchnic circulation.

To determine the impact of i.v. endothelin-1 on systemic, pulmonary and splanchnic circulation, as well as the peptide's regional clearance, hepatic venous and right heart catheterization was performed in healthy volunteers. During the peptide's continuous i.v. administration (0.4 pmol x kg-1 x min-1, 60 min) its plasma concentration rose from 2.1 +/- 0.5 to 9.5 +/- 5.3 pmol/l (pulmonary artery), from 2.1 +/- 0.9 to 5.0 +/- 1.6 pmol/l (femoral artery), and from 1.5 +/- 0.6 to 2.9 +/- 1.2 pmol/l (hepatic vein). This was accompanied by an increase in mean systolic arterial pressure from 127 +/- 14 to 131 +/- 12 mmHg (P less than 0.05). Concomitantly, cardiac output and heart rate decreased from 7.0 +/- 1.1 to 5.8 +/- 1.0 l/min and from 63 +/- 6 to 56 +/- 5 beats/min, respectively, while total vascular resistance increased from 964 +/- 273 to 1204 +/- 338 dyn x cm x s-5 (P less than 0.01). No major changes in pulmonary circulation were observed, while splanchnic vascular resistance increased from 4472 +/- 1056 to 5361 +/- 1420 dyn x cm x s-5 (P less than 0.01) and estimated hepatic blood flow decreased from 1403 +/- 218 to 1218 +/- 219 ml min-1 (P less than 0.01). During endothelin-1 infusion the pulmonary vascular bed accounted for approximately 53% of the peptide's overall disposal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of endothelin-1 in man: pretreatment with nifedipine, with indomethacin and with cyclosporine A.

The rise in blood pressure following the intravenous administration of endothelin-1 remained unchanged in healthy male volunteers pretreated with either the calcium-channel antagonist nifedipine (10 mg orally), the cyclo-oxygenase inhibitor indomethacin (150 mg day-1 for three days) or the immunosuppressive agent cyclosporine (5 mg kg-1 body weight for five days). Following administration of nifedipine the rise in plasma concentrations of endothelin-1 during the infusion of the peptide was markedly higher (P less than 0.01) than during control experiments without nifedipine. It is concluded that, in healthy men, nifedipine, indomethacin and cyclosporine do not exert a major influence on the pressor action of endothelin-1. However, nifedipine apparently influences the elimination of endothelin-1 from the circulation in healthy men.

Adult↗
PubMed1992

Diminished release of atrial natriuretic factor in calves with a total artificial heart.

Venous hypertension after total artificial heart (TAH) replacement, a common problem in humans as well as experimental animals, is thought to be related to reduced release of atrial natriuretic factor (ANF) due to atrial damage. To verify this hypothesis, we stimulated the release of ANF in 6 calves before (-7 days) and after TAH replacement (+25, +50, +80, and +100 days) by the rapid (+ = 10 min) infusion of 2 L of Ringer's solution. In normal calves (-7 days) this procedure induced a rise in plasma concentration of ANF from 18.5 +/- 12 to 31.6 +/- 12 pmol/L (p < 0.05). After TAH the ANF release continuously decreased (analysis of variance, p < 0.02). Thus, ANF increased by 9.8 +/- 9.3, 6.8 +/- 17.5, 0.4 +/- 5.2, and 0.5 +/- 3.2 pmol/L at days 25, 50, 80, and 100, respectively. The central venous pressure increased by 3.4 +/- 1.5 mm Hg (before TAH) and by 6 +/- 2.9 mm Hg (after TAH) during this procedure. A decrease in plasma concentrations of aldosterone, most likely due to extracellular volume expansion and a decrease in total protein plasma concentrations and in hematocrit due to the dilution of blood, was seen in each experiment. Necropsy demonstrated massive atrial dilatation and myocardial dystrophy with atrial fibrosis. ANF granules were present to a small extent in every calf. We conclude that rapid intravenous infusion is an adequate stimulus to release ANF in normal calves. After TAH implantation the release of ANF by high venous pressure declines although ANF granules are still present in the damaged atrial stumps. Therefore, the loss of stimulated ANF could contribute to the observed increase in venous pressure in TAH calves although other pathophysiologic mechanisms cannot be excluded.

Aldosterone↗
PubMed1992

Suramin affects differentiated and undifferentiated human thyroid epithelial cells in vitro.

In the last decade, suramin has become known for its antiproliferative, differentiation-inducing effects on cells and has been successfully used in the therapy of cancer patients. The present study was undertaken to investigate the effects of suramin on normal human thyroid cells in primary monolayer culture and to analyse whether it also affected cells from thyroid carcinomas. The results show that suramin, at concentrations similar to serum levels obtainable during therapy, inhibited the proliferation of thyroid cells as well as the secretion of thyroglobulin. It suppressed the activation of adenylyl cyclase in thyroid membranes and decreased the immunogenicity of the cells by reducing their surface expression of HLA-DR and ICAM-1. Although the morphology of differentiated thyroid cells remained unaffected by suramin, morphological changes compatible with differentiation were observed in cells from undifferentiated thyroid carcinomas when suramin was added to the culture medium. In conclusion, the data demonstrate that suramin has pronounced in-vitro effects on normal and neoplastic thyroid cells. It may, therefore, also be effective in patients with thyroid cancer, for whom no other form of treatment is available.

Adenylyl Cyclases↗
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↗