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Biomedical subjects

W Rascher

Publications and source records attributed to W Rascher.

At least 163 records · Page 9Linked to original sources

A low affinity vasopressin V2-receptor in inherited nephrogenic diabetes insipidus.

Congenital nephrogenic diabetes insipidus (NDI) is an X-linked inherited disorder characterized by renal resistance to the antidiuretic hormonal action of vasopressin. This study describes the molecular basis of nephrogenic diabetes insipidus in a dog family. Kidney membranes prepared from NDI-affected male huskies were examined for vasopressin binding and response. Compared to membranes from unaffected canines, those from the kidney inner medulla of NDI-dogs possessed normal V2-receptor numbers, but with 10-fold lower affinity for [Arg8] vasopressin (AVP). Adenylate cyclase stimulation by AVP in contrast to that by forskolin or GTP-analogues was similarly reduced in a dose responsive manner. The NDI-affected dogs showed antidiuretic responses to very high doses of V2-specific agonists, consistent with their possessing V2-receptors of lower affinity. Prolonged treatment with V2-agonists, 1-deamino [D-Arg8] VP (dDAVP) and 1-deamino [Val4, Sar7] AVP (dVSAVP), rendered the NDI-affected dogs near normal in terms of water intake and urine osmolality.

Adenylyl Cyclases↗

Involvement of adrenergic and angiotensinergic receptors in the paraventricular nucleus in the angiotensin II-induced vasopressin release.

The role of hypothalamic paraventricular adrenoceptors and angiotensin II (ANG II)-AT 1 receptors in mediating the vasopressin (AVP) release into the plasma in response to i.c.v. and local paraventricular ANG II injections was investigated in conscious chronically instrumented rats. Noradrenaline (NA) administered bilaterally into the paraventricular nucleus (PVN) dose-dependently stimulated AVP release. Bilateral PVN microinjections of the alpha 1 adrenoceptor agonists methoxamine and phenylephrine, or of the alpha2 adrenoceptor agonist clonidine, did not affect plasma AVP when given alone, but increased plasma AVP when methoxamine and clonidine were given in combination. In contrast, PVN microinjections of both the beta 1 adrenoceptor agonist dobutamine and the beta 2 adrenoceptor agonist salbutamol significantly reduced basal plasma AVP. Bilateral PVN pretreatment with the alpha 1 and alpha 2 adrenergic antagonists prazosin, idazoxan and rauwolscine, but not of the beta 1 and beta 2 adrenoceptor antagonists atenolol and ICI 118 551, significantly attenuated the i.c.v. ANG II-induced AVP release. ANG II injected bilaterally into the PVN dose-dependently increased plasma AVP. Bilateral PVN pretreatment with the specific ANG II-AT 1 receptor antagonist losartan partially inhibited the i.c.v. ANG II-induced AVP release. We conclude: 1) Beta 1 and beta 2 adrenoceptors in the PVN exert an inhibitory action on basal AVP secretion. 2) ANG II can release AVP by directly stimulating its ANG II-AT 1 receptors in the PVN. 3) PVN mediated AVP release in response to periventricular ANG II-AT 1 receptor stimulation is at least partially effected through ANG II-AT 1 receptors in the PVN impinging on alpha adrenergic terminals.

Angiotensin II↗

Sudden death in cystinosis.

We report on an 8-year-old boy with infantile cystinosis. The patient died in hospital for unknown reason after cardiopulmonary arrest although resuscitation was started immediately. As opposed to other cases [1-3], neither laboratory investigations nor autopsy in out patient gave an explanation for the sudden death.

Child↗

[24-hour blood pressure measurement in normal children and adolescents].

Blood pressure was continuously monitored over 24 h in 33 healthy children and adolescents (18 girls, 15 boys, age 6-17 years) using a portable monitor. The results were compared with European blood pressure centiles for normal children and adolescents. On average, 67% (57-88%, median and quartiles) of the measurements were completed. The day's mean for systolic blood pressure for girls was 0.04 (-0.67-1.00) standard deviations above the mean of the reference group with corresponding body-height, and for diastolic blood pressure, 1.08 (0.50-1.63) standard deviations. The corresponding values for boys were 0.42 (0.09-0.45) for systolic and 1.11 (1.00-1.39) for diastolic blood pressure. Mean systolic blood pressure for girls decreased during the night by 10% (5-13%) compared to the day time measurements, and the diastolic blood pressure decreased overnight by 23% (12-28%). Systolic blood pressure for boys decreased overnight by 8% (6-11.5%), and diastolic blood pressure decreased by 15% (12-19%).

Adolescent↗

[Congenital malformations of the urinary tract. Rational postpartum diagnosis].

More than one third of the anomalies diagnosed antenatally by ultrasound comprises the urinary tract. The criteria of the diagnostic and therapeutic approach, which resulted from our experience in children with symptomatic urinary tract anomalies cannot be necessarily applied to asymptomatic newborns. Not all urinary tract anomalies are obstructive and need surgical correction. Therefore, rational diagnostic approach after birth is necessary, which starts with ultrasonography. The first radiological diagnostic procedure is always a voiding cystourethrography in order to diagnose or exclude infravesical obstruction or a vesicoureteric reflux. The dynamic radionuclide nephrography (123I-Hippuran) under standardized conditions with adequate hydration and Furosemide-induced diuresis is able to detect a significant obstruction at the pelvi-ureteric or uretero-vesical junction. The intravenous urography is limited to specific questions and a computerized tomography is rarely indicated. In rare cases when dynamic investigations are equivocal, antegrade pressure flow studies according to Whitaker can be reliably exclude or prove obstruction.

Congenital Abnormalities↗

Effect of somatostatin on kidney function and vasoactive hormone systems in health subjects.

The acute effects of i.v. somatostatin (250 mcg bolus followed by 250 mcg/h continuous infusion for two hours) on renal hemodynamics, renal electrolyte and water handling, and urinary excretion of catecholamines and prostaglandins, as well as on plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, dopamine, glucagon, and plasma renin activity were studied in seven normal subjects. Somatostatin decreased effective renal plasma flow and glomerular filtration rate, osmotic and free water clearances, urine volume, and sodium and potassium excretion, while urinary osmolality, fractional excretion of sodium, and phosphate excretion increased significantly. Plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, and dopamine remained unchanged, while plasma renin activity (3.0 +/- 0.25 vs 2.4 +/- 0.2 ng AngI/ml/h; p less than 0.01) and glucagon levels (40 +/- 11 vs 20 +/- 16 pg/ml; p less than 0.01) decreased. Urinary excretion of norepinephrine, epinephrine, dopamine, PGE2, and PGF2 alpha was suppressed under somatostatin. A significant positive correlation was found between urinary dopamine and sodium excretion (r = 0.7; p less than 0.001) and urinary prostaglandin E2 and glomerular filtration (r = 0.52; p less than 0.01). Without accompanying changes in plasma osmolality and vasopressin concentration significant antidiuresis occurred, suggesting a direct tubular effect of somatostatin. However, the hormone-induced changes are due mainly to the decrease in renal plasma flow. The results demonstrate that somatostatin at supraphysiological doses exerts significant effects on the kidney.

Adult↗

G-protein coupling and signalling of Y1-like neuropeptide Y receptors in SK-N-MC cells.

We have studied [125I]neuropeptide Y-binding sites and neuropeptide Y-mediated second messenger responses in human SK-N-MC neuroblastoma cells with special reference to the role of G-proteins. Neuropeptide Y stimulated two second messenger responses in SK-N-MC cells, inhibition of cAMP accumulation and mobilization of Ca2+ from intracellular stores. Both effects were completely abolished by pretreatment with pertussis toxin. Binding of [125I]neuropeptide Y to intact cells or SK-N-MC cell membranes was rapid, reversible, characterized by high affinity and low capacity, and had pharmacological characteristics of a homogeneous population of Y1-like neuropeptide Y receptors. In permeabilized cells, [125I] neuropeptide Y binding was inhibited by GTP gamma S in a concentration-dependent manner. Saturation experiments in the absence and presence of GTP gamma S demonstrated a reduction in the number of high-affinity [125I]neuropeptide Y-binding sites without a decrease in affinity of the remaining sites. Pretreatment of intact cells with pertussis toxin completely abolished the inhibition of [125I]neuropeptide Y binding by GTP gamma S. Moreover, pertussis toxin treatment reduced the number of high-affinity [125I]neuropeptide Y binding sites. We conclude that the agonist ligand [125I]neuropeptide Y identifies functional neuropeptide Y receptors in SK-N-MC cells; however, the number of specific [125I]neuropeptide Y-binding sites may not necessarily reflect the number of neuropeptide Y receptors, because the former is affected by the functional state of cellular G-proteins.

Calcium↗

Atrial natriuretic peptide and blood volume during red cell transfusion in preterm infants.

Because raised plasma concentrations of atrial natriuretic peptide indicate volume expansion, we studied the effect of red cell transfusion on plasma atrial natriuretic peptide concentration, packed cell volume, and intravascular volume in eight preterm infants. Red cell transfusion increased red cell mass, packed cell volume and erythrocyte count, but decreased plasma volume. Total blood volume, plasma atrial natriuretic peptide concentration, urine flow rate, and urinary sodium excretion did not change. We conclude that a slow transfusion of less than 10 ml red cells/kg body weight does not cause volume expansion with subsequent atrial natriuretic peptide release thereby affecting the cardiovascular system.

Anemia, Refractory↗

Enhanced exercise-induced rise of aldosterone and vasopressin preceding mountain sickness.

A possible contribution of exercise to the fluid retention associated with acute mountain sickness (AMS) was investigated in 17 mountaineers who underwent an exercise test for 30 min on a bicycle ergometer with a constant work load of 148 +/- 9 (SE) W at low altitude (LA) and with 103 +/- 6 W 4-7 h after arrival at 4,559 m or high altitude (HA). Mean heart rates during exercise at both altitudes and during active ascent to HA were similar. Exercise-induced changes at LA did not differ significantly between the eight subjects who stayed well and the nine subjects who developed AMS during a 3-day sojourn at 4,559 m. At HA, O2 saturation before (71 +/- 2 vs. 83 +/- 2%, P less than 0.01) and during exercise (67 +/- 2 vs. 72 +/- 1%, P less than 0.025) was lower and exercise-induced increase of plasma aldosterone (617 +/- 116 vs. 233 +/- 42 pmol/l, P less than 0.025) and plasma antidiuretic hormone (23.8 +/- 14.4 vs. 3.4 +/- 1.8 pmol/l, P less than 0.05) was greater in the AMS group, whereas exercise-induced rise of plasma atrial natriuretic factor and changes of hematocrit, potassium, and osmolality in plasma were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

[Therapy of hyperammonemia in carbamyl phosphate synthase deficiency with peritoneal dialysis and venovenous hemofiltration].

Inborn errors of metabolism with hyperammonaemia cause emergency situations with unconsciousness, convulsion, hyperpnoea and hyperpyrexia. Therefore hyperammonaemia has to be treated immediately after diagnosis to avoid irreversible damage. Two newborns with carbamylphosphates synthetase deficiency are described. Both, continuous peritoneal dialysis and venovenous haemofiltration have proved to be effective methods to reduce serum ammonia concentration to values of less than 300 mu/l. Because of the severity of the enzyme defect in both cases, (carbamylphosphate synthetase was not detectable in liver tissue), treatment finally had to be stopped, and both patients died.

Amino Acid Metabolism, Inborn Errors↗

Circadian rhythms of urine osmolality and renal excretion rates of solutes influencing water metabolism in 21 healthy children.

Circadian rhythms of urine excretion, urine osmolality and renal excretion rates of sodium, chloride, potassium, creatinine and urea were studied for 3 days at home in 21 healthy children aged 6-11 years. Urine production as well as renal excretion rates of all solutes studied increased significantly during daytime and had minimum values at night. The peak of potassium and chloride excretion rates occurred earlier in the day than that of sodium. Considering all children together, no circadian rhythm was seen for urine osmolality. However, 9 children had evident but individually different rhythms of urine osmolality, changes which did not seem to correspond to the daily distribution of water intake. Circadian rhythmicity of urine osmolality and renal excretion rates of the main solutes should be considered in diagnostic and therapeutic procedures concerning fluid and electrolyte metabolism.

Body Water↗

[Regulation of thirst in end-stage kidney insufficiency].

About 30% of hemodialyzed patients are suffering from chronic fluid overload despite advice to restrict the oral fluid intake. To investigate the cause of the abnormal drinking behaviour a clinical study was performed in 51 non-diabetic patients with endstage renal disease exhibiting lower interdialysis weight gain (less than 3 kg, n = 17) and increased interdialysis weight gain (greater than 3 kg, n = 34). Blood pressure, body weight self-estimated thirst intensity before and after hemodialysis were analyzed. Biochemical and behavioral variables were measured including hormonal factors of water and sodium metabolism. Significant differences of dry weight, creatinine, urea nitrogen and thirst intensity were found between the two groups. Catecholamines, renin, angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide exhibited a similar pattern in both groups. Atrial natriuretic peptide decreased during hemodialysis in both groups, angiotensin II, however, and norepinephrine showed an exaggerated response to ultrafiltration rate in polydipsic patients. These results suggest that changes in serum osmolality during hemodialysis did not contribute to thirst and drinking behaviour. It seems that postdialytic hypovolaemia together with higher plasma-angiotensin II-levels is responsible for increased oral intake of fluid and excessive weight gain.

Angiotensin II↗