[Prostaglandins and gastrointestinal functions (author's transl)].
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Animals↗
Biomedical subjects
E Beubler
Publications and source records attributed to E Beubler.
[Plasmapheresis in the elimination of toxic substances with marked plasma protein-binding properties (author's transl)].
Plasmapheresis is a method used to eliminate toxic substances with high plasma protein-binding properties. Poisoning by strongly plasma protein-binding substances cannot be treated by haemodialysis or peritoneal dialysis. Hence, an attempt was made to hasten the elimination of phenylbutazone, a suitable model substance (plasma protein binding affinity 98%), by plasmapheresis. Some of the experiments were performed with oxygen under high pressure (OHP). A singly plasmapheresis of the total blood volume or triple plasmapheresis of half of the blood volume, performed at 20 min intervals accelerated the elimination of phenylbutazone significantly and all animals survived. A single plasmapheresis of the threefold blood volume had the greatest effect in lowering the concentration of phenylbutazone in the blood, but only one of three animals survived. OHP had no influence on the half-life of phenylbutazone and did not increase the survival rate.
Animals↗
[Interactions between oxygen under high pressure and drugs (author's transl)].
A. The clinical applications of oxygen under high pressure (OHP) are limited by oxygen toxicity. Hence, an investigation was carried out in mice on the influence of drugs on the lethal effect of OHP. 1. The lethal effect of OHP is diminished by phenobarbitone, propranolol, clonidine, succinate and tris buffer. 2. The lethal effect of OHP is enhanced by methamphetamine, acetazolamide and guanethidine. 3. The lethal effect of OHP is enhanced by reserpine two hours after administration, but diminished 12 hours after administration. B. The clinical usage of OHP is often necessarily connected with drug therapy. Hence, alteration in drug effects under OHP were investigated in mice and rats. 1. The convulsion threshold of pentetrazol is reduced under OHP by 26%. 2. The duration of the hypnotic effect of hexobarbitone is reduced under OHP by 27%. 3. The analgesic effect of morphine is unchanged by OHP. Practical aspects with regard to the use of drugs during clinical use of OHP are discussed.
Acetazolamide↗
The function of prostaglandins in transmucosal water movement and blood flow in the rat jejunum.
1. Jejunal loops of anaesthetized rats were perfused with isotonic buffer containing PGE1, PGF2alpha or indomethacin. Intestinal blood flow, absorption and secretion of tritiated water were measured. 2. PGE1 at the low concentration of 0.1 microgram ml-1 did not influence intestinal blood flow but increased secretion and decreased absorption of tritiated water. In higher concentrations (0.5 and 6.5 microgram ml-1), blood flow, secretion and absorption were enhanced. 3. PGF2alpha, even in the high concentration of 50 microgram ml-1, did not influence intestinal blood flow but enhanced secretion and decreased absorption of tritiated water. 4. Indomethacin (1 microgram ml-1) decreased intestinal blood flow and secretion but enhanced absorption of tritiated water. 5. The effects of indomethacin on blood flow can be prevented and those on secretion can be even reversed by an additional infusion of PGE1 (0.5 microgram ml-1). 6. PGs appear to play a physiological role in the regulation of intestinal blood flow and transmucosal water movement, since inhibition of endogenous PG synthesis by indomethacin results in effects opposite to those of intraluminally applied PGE1. The results obtained with the low concentration of PGE1 (0.1 microgram ml-1) and with PGF2alpha (50 microgram ml-1) strongly indicate that intestinal water movement can be changed independently of intestinal blood flow.
Animals↗
Convulsions induced by hyperbaric oxygen: inhibition by phenobarbital, diazepam and baclofen.
1. The anticonvulsive potencies of diazepam, phenobarbital and baclofen against convulsions induced by oxygen under high pressure (OHP), by isoniazid and by strychnine were investigated in mice and rats. 2. The anticonvulsive potency of diazepam was much higher than that of phenobarbital and baclofen against all three types of convulsions. 3. The selective activity of diazepam against isoniazid induced convulsions in rats (dose ratio ED50 phenobarbital/ED50 diazepam: 400) could not be confirmed in mice (dose ratio ED50 phenobarbital/ED50 diazepam: 20-40), where diazepam was equipotent against all three types of convulsions. 4. Baclofen which does not inhibit strychnine induced convulsions was equipotent in inhibiting convulsions evoked by isoniazid and OHP in mice. 5. The results are in agreement with the postulated GABA-inhibitory mechanism of OHP induced convulsions, whereas they make a glycine inhibitory mechanism very unlikely. Although the results do not allow further conclusions about the mode of action of diazepam, a clinical trial of diazepam in OHP-induced convulsions should be considered.
Aminobutyrates↗
Methylxanthines and intestinal drug absorption.
1. Jejunal loops of anaesthetized rats were filled with buffered isotonic solutions of tritiated water (HTO), urea, antipyrine and salicylic acid at pH 6-8. The venous outflow and the appearence rate of the substances in the intestinal venous blood were determined. Blood pressure was kept constant by adjustable supply of blood from donor rats throughout the experiment. 2. The absorption of urea, antipyrine and salicylic acid was, in concentrations from 0.001 to 1.0 mg/ml found to be directly proportional to the intraluminal concentration. 3. Theophylline and caffeine (2 mg/ml), when injected into the lumen, increased the blood flow to 188% and 166% of controls. 4. The theophylline induced increase in blood flow caused an enhancement in the absorption of antipyrine to 153%, HTO and urea to 135% and salicylic acid 123% of controls. 5. Caffeine influenced the absorption of HTO and salicylic acid similar to theophylline.
Animals↗
Effects of PGE2 and colchicine on the intestinal fluid volume.
a) Colchicine, prostaglandin E2 (PGE2) and carbachol increase the intestinal fluid volume in the rat. b) The effect of carbachol and prostaglandin E2 is augmented whereas that of colchicine is diminished in the pithed rat. c) The effect of colchicine is diminished in anaesthesia whereas that of PGE2 remains unchanged. d) The effect of PGE2 and of colchicine are both inhibited by atropine. e) The effects of PGE2 and of colchicine are both enhanced by phentolamine. f) Pretreatment with indomethacin decreased the effect of colchicine whereas that of PGE2 remained unchanged. g) The PGE2-induced increase in intestinal fluid volume may partly be mediated by a peripheral mechanism involving acetylcholine receptors. h) The increase in intestinal fluid volume by colchicine can mainly be explained by a central action of the drug which is mediated by cholinergic neurones.
Animals↗
[Pharmacokinetics and biotransformation of N-propylajmaline hydrogen tartrate in man].
10 and 20 mg of N-Propyl-ajmalin-hydrogentartrate (N-PAB, Neo-Gilurytmal) were administered i.v. and orally respectively to healthy volunteers. In the study 14C-labelled N-PAB was used. The pharmacokinetics and the metabolic behaviour was examined. A fast and complete absorption of the compound could be observed. The bioavailability was 78%. The terminal plasma elimination half-life (beta-phase) was in the range of 4 to 6 hours. A total of 33% of the administered radioactivity was excreted via the kidney. 35 to 48% of the radioactivity found in urine was unchanged N-PAB. The excretion-kinetics of the three main metabolites as well as of the parent compound were determined. The possible presence of non-metabolizers is suggested.
Adult↗
Proabsorptive properties of nitric oxide.
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Animals↗