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Biomedical subjects

H Ebel

Publications and source records attributed to H Ebel.

At least 109 records · Page 6Linked to original sources

[Treatment of essential hypertension with a combination of propranolol, spironolactone-thiabutazide and dihydralazine (author's transl)].

In 61 out-patients with essential hypertension, grade I or II, propranolol was administered alone in increasing doses (3 x 40 mg/d or 3 x 80 mg/d) or, if there was insufficient response, with a double or triple combination consisting additionally of spironolactone (50 mg/d)-thiabutazide (5 mg/d) and dihydralazine (3 x 25 mg/d). This treatment schedule achieved normal pressures in 51 patients, in 22 on 40 mg, in 7 on 80 mg propranolol, in 16 after the addition of the diuretic, and in 6 with the triple combination. Four patients had to be excluded from the study because they developed either marked bradycardia or anxiety states or paraesthesias after propranolol (3 x 40 mg/d). On chronic beta-adrenergic blockade the serum potassium level increased slightly, but remained within normal limits. The initial value of plasma-renin activity was highest in the group of those who responded to the propranolol treatment.

Anxiety↗

Endocrinological aspects of PTH metabolism in the kidney.

Various methods for the measurement of intact PTH, PTH fragments and PTH binding to receptors were applied to clarify the role of renal receptors for the bioexpression of PTH. Glomerular receptors may contribute approximately 20% of the renal PTH catabolism. PTH also binds to tubular receptors at the luminal side (brush border membranes) as well as at the antiluminal site (basal-lateral membrane). Scatchard plot analysis of PTH binding to these receptors allows the calculation of an equilibrium dissociation constant and binding capacity, if correction is made for inactivation of bioactive PTH (measured by LAMA). Binding to receptors is--in our systems--invariably associated with degradation of the intact hormone to N-terminal and C-terminal fragments of different molecular weight. Antibodies against basal lateral membranes and against brush border membranes are able to inhibit PTH binding to tubular membranes. Sera of uremic patients with inappropriately high PTH contain a globulin which interferes with PTH binding to the receptor, suggesting that uremia may be another example for a "hormone receptor antibody disease".

Animals↗

[Behaviour of plasma renin activity during long-term treatment with propranolol (author's transl)].

17 patients (40 +/- 9 years) with essential hypertension were included in the study. A monotherapy of 120, 160 or 240 mg propranolol per day was administered orally according to the antihypertensive effect. Four weeks after treatment, blood pressure and heart rate showed a statistically significant decrease and remained unchanged over a period of six months. Plasma renin activity decreased significantly from 5.7 +/- 6.3 ng/ml/h at the beginning of the study to 1.8 +/- 1.3 ng/ml/h after 4 weeks. 5 months later however plasma renin activity increased again to 5.0 +/- 0.9 ng/ml/h. The difference was statistically significant. From 17 patients 7 (41%) had lower levels of plasma renin activity after 6 months treatment when compared with pretreatment values. In only 3 patients (18%) was plasma renin activity lower after 6 months than after four weeks. We conclude that the increase in plasma renin activity is a reactive mechanism to the reduced blood pressure under long-term conditions. The decrease of plasma renin activity in short-term treatment of essential hypertension is not a mechanism responsible for the antihypertensive effect of propranolol during long-term treatment.

Adult↗

(Na+K+)-activated ATPase in human cornea. Distribution within the cornea and properties of the enzyme from epithelial cells.

Distribution and principal characteristics of (Na+K+)-activated ATPase in human cornea were investigated. (Na+K+)-ATPase was present in both epithelium and endothelium, whereas the corneal stroma did not exhibit significant enzyme activity. In homogenates specific activity of the (Na+K+)-ATPase was 2.3-fold higher in endothelium than in epithelium. Calculation of total enzyme activity revealed a 6.1-fold higher content of (Na+K+)-ATPase in the epithelium. In the epithelium a 7-fold enrichment of (Na+K+)-ATPase compared to the homogenate was obtained in the 150-1500 X gav fraction. Maximum enrichment in the endothelium was 3.5-fold and was achieved in the 1500-2500 X gav fraction. Both fractions showed, however, the same specific activity. The pH-optimum of (Na+K+)-ATPase in the 150-1500 X gav fraction ranged from 8.0-8.2 in both epithelium and endothelium. In the epithelial 150-1500 X gav fraction the apparent Km-values were 4.0 mM for Na+, 2.8 mM for K+ and 0.12 mM for Mg2+ - ATP in equimolar concentrations. The inhibition constant of epithelial (Na+K+)-ATPase for ouabain was determined as Ki = 3.3 X 10(-7) M. The present data support the view that control of corneal hydration in man is a function of both endothelium and epithelium.

Adenosine Triphosphatases↗

Isolation of the basal and lateral plasma membranes of rat kidney tubule cells.

A method was developed to isolate renal basolateral membranes from cortical kidney tubule cells of single rats. The isolated membrane fraction was characterized by the measurement of marker enzyme activities and by electron microscopy. 1. After centrifugation of crude plasma membranes on a discontinuous sucrose density gradient the basolateral membranes accumulated at a sucrose density of p= 1.14-1.15 g/ml. The yield was 147 mug membrane protein/g kidney wet weight. Protein recovery was 0.1%. 2. (Na+ + K+)-ATPase was enriched 22-fold from the homogenate. The recovery was 2.6%. The (Na+ + K+)/Mg2+-ATPase ratio was 4.1. 3. The contamination by brush borders was small. Alkaline phosphatase was 1.6-fold enriched and 0.2% was recovered. Aminopeptidase was 1-fold enriched with a recovery of 0.1%. The contamination by mitochondria, lysosomes and endoplasmic reticulum was negligible. 4. In electron micrographs the basolateral membranes showed a typical triple layered profile and were characterized by the presence of junctional complexes, gap junctions or tight junctions.

Adenosine Triphosphatases↗

The effect of Ca ion antagonist verapamil on ouabain inhibition of renal sodium reabsorption. Studies in the isolated perfused rat kidney.

Evaluation of a possible role of NaK-ATPase in transtubular sodium reabsorption is difficult, since ouabain doses that inhibit this enzyme system in vitro completely [1, 11], cannot be applied in vivo. Thus studies in the isolated perfused rat kidney were carried out [3, 11, 13, 15]. However, in this model, supramaximal doses of ouabain as used to block NaK-ATPase completely induced a potent vasoconstriction, which lowers the filtered load of sodium. Thus, a meaningful quantitative comparison of sodium transport in control and in experimental phases of ouabain inhibition has not been possible. At submaximal doses, in which filtered Na-loads are still comparable, transport activity was only reduced to approximately 50% [15]. In the following experiments we reinvestigated the relationship between inhibition of renal NaK-ATPase and the reduction of Na-reabsorption by ouabain under more appropriate conditions. Previously we have observed that verapamil (syn.: iproveratril, Isoptin), a Ca ion antagonist [2, 4, 6], effectively prevents autoregulation, and a fact which is pertinent for the present experiments, blocks this vasoconstrictive action of ouabain. Thus, using the Ca antagonist verapamil, it was possible to evaluate the inhibiting effect of this glycoside on renal sodium transport quantitatively without the hazards introduced by ouabain vasoconstriction which by the same token lowers filtered load.

Adenine Nucleotides↗

Magnesium concentrations in plasma and bone following enteral administration of Br-, Cl- and Mg++ in the form of different compounds and combinations.

In accordance with the results achieved in previous experiments the intestinal absorption of magnesium and its uptake into bone of rats were significantly improved when MgCl2 or mono-magnesium-mono-aspartate-hydrochloride (Mg asp. HCl) were used instead of mono-magnesium-di-l-aspartate (Mg asp.). Treatment with mono-magnesium-mono-aspartate-hydrobromide (Mg asp. HBr) resulted in remarkably elevated magnesium concentrations in plasma and bone. Since the animals were strongly sedated at the same time, we had to differentiate the influence of anesthesia from unspecific distress and specific actions of bromide and chloride, e.g. on intestinal uptake and/or renal excretion of Mg. Experiments in which the narcotic effect of bromide was reduced to moderate sedation by additional treatment with chloride would appear to suggest that both specific and unspecific mechanisms were involved. In additional experiments it was shown that the effects of Mg asp. plus KBr or Mg asp. plus KCl or CaCl2 were similar to those of the corresponding magnesium aspartate hydrohalogenides.

Administration, Oral↗

[Pharmacology and pharmacokinetics of magnesium (author's transl)].

A dose-dependent fall in diastolic blood pressure, pulse rate, systolic pressure, inhibition of neuromuscular transmission and blockade of sympathetic ganglia could be demonstrated during infusion of magnesium in animal experiments. In sighting trials in two clinically healthy subjects, suggestions of a phasic course for plasma Mg were found, with a minimum in the morning. After administration of magnesium asparate hydrochloride in enteric coated capsules, the plasma Mg rose, depending on the dose, with a maximum at 3.7 hours. Raising the plasma Mg over 24 hours is possible with a total dose of 9 mg/kg Mg, divided into two or three doses daily. For reasons of absorption and better tolerance, division into three doses seems more advantageous.

Adult↗

Renal adenylate cyclase-effects of diuretics.

The in vitro effect of various diuretics on rat kidney adenylate cyclase was investigated in crude homogenates of the cortex, the outer and inner medulla. 10-3 M furosemide inhibited adenylate cyclase by 40% in the cortex, by 16% in the outer medulla and by 43% in the inner medulla. 10-3 M ethacrynic acid inhibited adenylate cyclase activity by 65% in the cortex, 59% in the outer medulla and by 57% in the inner medulla. Amiloride produced no significant inhibition of the adenylate cyclase reaction. In the cortex, furosemide partially inhibited adenylate cyclase under basal, fluoride-stimulated and parathyroid hormone-stimulated conditions. Ethacrynic acid produced a strong inhibition of adenylate cyclase activation by F- and parathyroid hormone. In the inner medulla 10-2 M F- and 1 mU antidiuretic hormone reversed the furosemide effect on adenylate cyclase. Ethacrynic acid produced a strong inhibition of adenylate cyclase in the presence of F- and antidiuretic hormone. It is suggested that inhibition of renal adenylate cyclase might be a possible mode of action of certain diuretics.

Adenylyl Cyclases↗

[Metabolism and toxicity of therapeutic chelating agents. 14. Effect of DTPA on hematopoiesis].

By use of 3-H-thymidine it is shown that toxic doses of Ca-DTPA lead to a reversible inhibition of DNA-synthesis in the lymphocytes, erythro- and myelopoietic cells of the rat. The incorporation of 59-Fe into the erythrocytes is markedly imparied. The hematological reaction, i. e. granulocytosis, lympho- and eosinopenia, is ascribed to the general adaptation syndrom. Zn-DTPA proved to be ineffective in all respects.

Animals↗

[Chromaffine tumours: diagnosis and catamnestic features based on the data collected at the Institute of Experimental Therapy between 1949 and 1974 (author's transl)].

From 1949 to 1974, urine samples of 1669 patients with unclarified arterial hypertension were tested for non-conjugated catecholamines. Chromaffine tumours--among them one pheochromoblastoma and two families with inherited forms--were found in 1.1% of all cases. With the procedure applied, adrenergic alpha- and/or beta-mimetic actions on the circulation of cats can be identified when the excretion of total catecholamines is increased by the factor 1.5 to 2.0. Hence, chromaffine tumours with smaller excretion rates (about 200 mug/24 h) are also detectable, so in one case where the excretion of vanillyl-mandelic acid was normal. Thus all prerequisites concerning sensitivity and specificity of a screening method are fulfilled. The large variety of symptoms of chromaffine tumours becomes obvious from the catamnestic data of 19 patients indicating problems which may arise in differential diagnosis.

Adolescent↗