PubMed Health⌕ Search

Biomedical subjects

W Klinger

Publications and source records attributed to W Klinger.

At least 127 records · Page 7Linked to original sources
PubMed1980

Comparison of the effects of cholestyramine and aluminium hydroxide on the biliary bile acid excretion in rats. An experimental model for the depletion of bile acids in bile.

Bile flow and biliary excretion of dihydroxy- and trihydroxy-bile acids have been determined in control, cholestyramine (250--2000 mg/kg p.os)- and aluminium hydroxide (250--2000 mg/kg p.os)-pretreated rats. Cholestyramine proved to be a more potent bile acid depleting agent than aluminium hydroxide. The depressing effect of cholestyramine on bile flow was also more significant than that of aluminium hydroxide. Cholestyramine-pretreatment seemed to be a suitable experimental model for the depletion of bile acids in rat bile.

Aluminum Hydroxide↗
PubMed1979

Influence of cycloheximide on normal and induced delta-aminolevulinic acid synthetase (aminoketone synthesis) of rat liver in vivo and in vitro.

2 and 5 mg/kg cycloheximide given i.p. 30 minutes prior to the inducer allylisopropylacetamide (AIA) diminished or prevented the enhancement of delta-aminolevulinic acid synthetase (ALAS) activity in newborn rats. In adult rats the small AIA effect 24 hours after pretreatment was enhanced by 2 mg/kg cycloheximide i.p., when the inhibitor was injected 2 hours prior to the inducer. The basic aminoketone synthesis was inhibited by cycloheximide alone. 150-600 microgram/ml cycloheximide had no effect on the aminoketone synthesis of rat liver slices in vitro during 4 hours of incubation. The in vitro induction by 0.6 mg/ml AIA was enhanced by cycloheximide, if the inducer was added 1 hour after preincubation with cycloheximide. It is supposed, that the cytoplasmically localized precursor-ALAS is activated at the beginning of the induction process prior to the initiation of de novo enzyme synthesis, at least in vitro.

5-Aminolevulinate Synthetase↗
PubMed1979

Enzyme-inductive effect of a hypolipidemic compound N-bis-(p-chlorophenoxy)-acetyl-urea in man and rat.

Besides its antilipidaemic effect, the new clofibric acid derivative (N-bis-(p-chlorohenoxy)-acetyl-urea) has an enzyme-inductive effect. The drug was administered (100 mg/kg orally) to male, Wistar rats for three days. The treatment raised the weight of the liver, the content of liver microsomal protein and cytochrome p-450 and shortened the hexobarbital sleeping time. The increase of cytochrome p-450 dependent biotransformation was found by in vitro methods in 9000-g supernatant of liver homogenate. There was a growth in biotransformation of substrates of type I (ethylmorphine, aminopyrine) and an extreme increase in reduction of nitrobenzene. We did not find any change in biotransformation of the type-II substrate aniline. In 16 patients suffering from Gilbert's syndrome, there was a decrease in the level of serum bilirubin, and increase of D-glucuric-acid output in urine and bromsulphophthalein transport maximum following the treatment of this drug given in 150 mg/day orally for three weeks. After this treatment, the level of gamma-glutamyl-transpeptides did not change. The authors highly recommend the serious consideration of metabolic interaction during the clinical application.

Adolescent↗
PubMed1979

[Effect of metyrapone on bile flow and bile acid excretion in Wistar rats].

The influence of metyrapone on bile flow and excretion of mono-(MBA), di-(DBA) and trihydroxy-(TBA)-bile acids was investigated in adult male Wistar rats after single and repeated pretreatment. MBA were not found in the rat bile. Metyrapone administration (200 mg/kg b.w. i.p.) 1 h before onset of a 3-hour bile collection period diminished bile flow and excretion of DBA and TBA. The relation TBA/DBA was changed towards DBA. Similar results were found after repeated administration 12 h after the last metyrapone injection (4 x 50 mg/kg b.w. i.p. per day for 4 consecutive days). But 60 h after the last metyrapone administration bile flow and the excretion of TBA were enhanced and the TBA/DBA ratio was changed towards TBA. The possible influence of metyrapone on bile acid hydroxylation is discussed and compared with metyrapone action on hydroxylation of foreign compounds.

Animals↗
PubMed1979

Effect of 3-methylcholanthrene on the biliary excretion of bromsulphthalein and eosine in newborn rats.

The biliary excretion rates of bromsulphthalein (BSP), bromsulphthalein-glutathione conjugate (BSP-GSH) and eosine have been studied in 3-methylcholanthrene (3-MC)-pretreated (100 mg/kg i.p.) and control rats aged 10 days. Liver weight was invariably increased after 3-MC treatment, associated with enhanced biliary excretion of total BSP. The increase in the biliary excretion of total BSP was due solely to the increased excretion of BSP-GSH. Following 3-MC pretreatment, BSP-GSH and eosine appeared in the bile in the same amount as in the control rats after i.v. administration of BSP-GSH and eosine. Pretreatment with 3-MC increased the ratio of BSP-GSH to BSP in the liver and bile. Our results suggest that the increased biliary excretion of total BSP following 3-MC treatment was due to an enhanced conjugation of BSP with GSH.

Animals↗
PubMed1978

Influence of drugs on bile acid excretion.

The hydroxylation of bile acids in rat liver microsomes in cyt P-450 dependent (Björkhem et al., 1975). To find out possible interactions between drugs and bile acid hydroxylation and/or active transport mechanisms we investigated the influence of the microsomal inhibitor metyrapon, the microsomal inducer phenobarbital and the intrahepatic cholestasis producing agents chlorpromazine, phenylbutazone and progesteron on bile flow and bile acid excretion. The excretion in monohydroxy (MBA), dihydroxy (DBA) and trihydroxy (TBA) bile acids were estimated in bile-fistula rats in three one hour periods. MBA, DBA and TBA were separated with thinlayer-chromatography and estimated fluorimetrically. Bile flow, bile acid excretion and relation TBA/DBA were influenced by acute and subchronic administration of the above mentioned drugs in different ways.

Animals↗
PubMed1978

N,N-diethyl-4-aminoazobenzene (DEAB): acute actions with respect to possible carcinogenicity as well as the role of solvents. Morphological and pharmacological investigations.

The acute action of the azo dye DEAB was investigated in Sprague-Dawley (SD) and Wistar (Wi) rats. The substance was dissolved both in DMSO and sunflower oil and was administered once by stomach tube. Cytochrome P-450-DEPENDENT N-demethylation of ethylmorphine and dimethylnitrosamine are differentially altered depending on the solvent used. The excretion of DEAB as well as of N,N-dimethyl-4-amino-azobenzene (DAB) is delayed and diminished if the substances are dissolved in DMSO. Beside these effects the mitotic number in the adrenal cortex is significantly elevated in both strains of rats. But, in SD rats only DMSO-solution of DEAB is effective. In Wi rats both are effective, the oily solution more than that in DMSO. In this respect DEAB resembles DAB and various other carcinogens which are efficient in stimulating adrenocortical cell division. Considering the positive short-term assay after three other substances which revealed carcinogenic properties in long-term experiments we conclude that also DEAB may be carcinogenic in adequate long-term examination.

5-Aminolevulinate Synthetase↗
PubMed1978

[Effect of phenobarbital and chlorpromazine on bile flow and bile acid excretion in male Wistar rats].

Bile flow and excretion of monohydroxy-, dihydroxy- and trihydroxy-bile acids (MBA, DBA and TBA) were estimated after acute and subacute phenobarbital and chlorpromazine pretreatment in 60-day-old male Wistar rats. Bile was collected in bile-fistula rats in three 1-hour periods. MBA were not detected. Neither single nor repeated ip. administration of different amounts of saline before bile sampling nor oral water supply within the bile collection period influenced the bile flow and excretion of DBA and TBA. Phenobarbital administration (60 mg/kg b.w. ip.) 2 hrs before bile sampling did not influence bile flow and bile acid (BA) excretion. After 3 days pretreatment with phenobarbital (3 X 60 mg/kg b.w. ip.) the bile flow was somewhat increased, BA-excretion was unchanged and the relation TBA/DBA diminished. Chlorpromazine administration (40 mg/kg b.w. ip.) 1,5 hrs before bile sampling decreased bile flow and BA excretion within the first collection period, whereas bile flow and BA excretion increased in the thrid collection period. No signs of cholestasis were observed after chlorpromazine pretreatment once a day for 3 days. Bile flow and BA excretion were increased and the relation TBA/DBA was unchanged.

Animals↗
PubMed1978

[Effect of progesterone and phenylbutazone on bile flow and bile acid excretion in male Wistar rats].

Bile flow and excretion of monohydroxy-, dihydroxy- and trihydroxy bile acids (MBA, DBA and TBA) were estimated after acute and subacute progesterone and phenylbutazone pretreatment in adult male Wistar rats in three one-hour periods. Different pretreatment with sunflower oil did not influence bile flow and excretion of DBA and TBA. MBA were not detected. Different administration of progesterone and phenylbutazone did not significantly change the TBA/DBA ratio. Progesterone administration (50 mg/kg b. w. i. p.) 2 hours before bile sampling increased bile flow and bile acid excretion in the third one-hour period. After 3 days of pretreatment with progesterone (3 X 50 mg/kg b. w. i. p.) bile flow and TBA-excretion were diminished. Phenylbutazone (100 mg/kg b. w. i. p.) increased bile flow and TBA-excretion both after acute and subacute administration.

Animals↗
PubMed1977

Age-dependence of succinate dehydrogenase (SDH) in rat liver and its inducibility after barbital and phenylbutazone pretreatment.

SDH activity in liver homogenates increases threetimes from one day before to one day after birth. The plateau till the 13th day of life is followed by a minimum on the 15th day of life, thereafter the increase leads to a maximum on the 120th day. The influence of phenylbutazone and barbital on body and liver weight as well as on hepatic SDH activity was investigated in different age groups. Both drugs were administered in three single daily doses, phenylbutazone additionally 31 days long. Hepatic SDH activity based on liver wet weight or liver protein did not change in any of the experimental groups. But as a consequence of increased liver body weight ratio (mostly non-significant), hepatic activity per gram body weight exhibited a tendency to higher values.

Age Factors↗
PubMed1977

Ethylmorphine-N-demethylation by liver homogenate of newborn and adult rats; Enzyme kinetics and age course of Vmax and Km1.

Optimum incubation conditions for determination of ethylmorphine-N-demethylation with newborn and adult rat liver homogenate have been determined: 1 ml 1:20 liver homogenate in 1.15% KCl, 1 ml 0.1 M phosphate buffer with ethylmorphine, NADP, and glucose-6-P, final concentrations 10, 0.33 and 5 mM, respectively, no nicotinamide, no MgCl2, 1 ml 0.5 M phosphate buffer; 3 ml final volume, 20 min incubation time. With both age groups NADH increases the activity to the same extent. With NADPH, saturation could be achieved only with newborn liver, but not with adult liver homogenate. Postnatally, the activity increases about fivefold, with a break at the 10th day of life. The Lineweaver-Burk plot was linear with newborn liver homogenate, whereas for all other age groups the graphs showed an angle. Statistical analysis pointed out that a two-enzyme model fits the experimental data only insignificantly better than a one-enzyme model. From other experimental evidence and manifold reproduction without any exception of these results, however, it may be concluded that there are different monooxygenases which show different affinities towards one substrate (ethylmorphine) and which show different developmental patterns.

Age Factors↗