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Biomedical subjects

W Klinger

Publications and source records attributed to W Klinger.

At least 145 records · Page 8Linked to original sources
PubMed1977

The influence of NADH on the ethylmorphine-N-demethylation in liver microsomes from control and phenobarbital-treated rats or different ages.

The ethylmorphine-N-demethylation by liver microsomes from control and phenobarbital-treated rats of different ages was investigated by means of adding NADPH in combination with NADH to the incubation medium. The rate of ethylmorphine-N-demethylation in the presence of NADPH without NADH is greater in adult than in young rats and greater in induced that in control rats. The higher the activity of ethylmorphine metabolism with NADPH alone the more it is abolsutely enhanced by NADH. The relative increase in ethylmorphine metabolism caused by NADH is equal in all groups of animals. It is concluded that there are no differences in the introduction of the second electron from NADH to the oxygenated cytochrome P-450 but there are differences in the concentration of cytochrome-substrate complex and, consequently, in the oxygenated cytochrome-substrate complex. The enhancing effect of NADH is higher at lower NADPH concentrations. In the presence of NADH, the NADPH concentrations necessary to obtain a msximum metabolic rate are lower than without NADH.

Animals↗
PubMed1976

Developmental aspects of xenobiotic transformation.

In most laboratory animals monooxygenases are apparently absent or barely detectable in fetal organs until just before birth. In this contribution hepatic cytochrome P-450-dependent reactions in the rat are considered only. The results are interpreted on basis of the reaction scheme of Estabrook. To avoid methodological pitfalls the basic kinetics for all reactions investigated have been investigated with liver preparations from newborn and adult rats. The low monooxygenase activity of rat liver during the perinatal period can be observed even under optimal conditions for the in vitro enzyme assay. There are different developmental patterns for various reactions O-demethylation of codeine, phenazone-hydroxylation, first and second steps on N-demethylation of amidopyrine, N-demethylation of ethylmorphine. There are marked differences not only in Vmax but also in the postnatal development of Km and the inductibility by phenobarbital. Thus the existence of a different cytochrome P-450 is evident also by this approach. The low monooxygenase activity of rat liver during the perinatal period is not due to a lack of NADPH or NADH, to an age-dependent NADPH cytochrome P-450 reductase activity or to an age-dependent NADH-cytochrome P-450 reduction. Moreover this low activity is not due to an insufficient mitochondria-endoplasmic reticulum interaction. It is accompanied by low delta Amax after addition of a typical type I substrate (hexobarbital) and by a small amount of metyrapone-binding centers: it can be explained by a smaller percentage of active cytochrome P-450 in comparison to adult rat liver.

Aminopyrine↗
PubMed1976

Drug stimulated biotransformation of hormonal steroid contraceptives: clinical implications.

On the basis of well documented biochemical and pharmacological data about the influence of drug mediated enzyme induction on the biotransformation of natural and synthetic sex steroids, practical consequences for hormonal steroid contraception are described and discussed. Clinical reports dealing with this problem are still sparse. The clinical symptoms of drug stimulated biotransformation of hormonal steroid contraceptives are characteristic. Spotting or breakthrough bleeding are observed and in the extreme case conception may occur despite the regular intake of the contraceptive. The appearance of these symptoms differs from one individual to another. With a strong enzyme inducer, bleeding disorders can be provoked artifically in 50 to 60% of the women receiving hormonal contraceptive treatment. The range of drugs which stimulate biotransformation of hormonal contraceptives with consequent loss of their biological effectiveness is not completely known. For practical purposes, it is recommended that bleeding disturbances under hormonal steroid contraception in a previously regular cycle be regarded as loss of reliability; they should be remedied and taken as a sign to search for uncontrolled drug taking.

Ampicillin↗
PubMed1976

The binding of hexobarbital and aniline to cytochrome P-450 of liver microsomes from control and phenobarbital-treated rats of different ages.

The spectral changes due to the binding of hexobarbital and aniline to cytochrome P-450 of rat liver microsomes were investigated in 10-day- to 15-month-old rats. The Ks values for both substances and consequently the affinity for cytochrome P-450 do not change during ageing. Phenobarbital treatment does not alter the affinity of hexobarbital, but enhances the Ks value for aniline. The maximal spectral changes (delta A max) due to aniline are nearly equal in all age groups whereas delta A max due to hexobarbital is very small in young rats and increases considerably during ageing. The age-dependence of the hexobarbital-induced delta A max is similar to the development of drug-metabolizing reactions. delta A max due to hexobarbital and aniline is enhanced by phenobarbital treatment of the rats. The addition of aniline to microsomes enhances the Ks value and diminishes delta A max for hexobarbital.

Aniline Compounds↗
PubMed1976

[Sleeping time and awaking blood concentration of hexobarbital influenced by glucose and adrenaline in rats of both sexes].

Sleeping times in male and femal rats are prolonged after the simultaneous i.p. administration of adrenaline and hexobarbital sodium. The blood concentration of hexobarbital at awakening is unchanged in male rats, while in females this concentration is decreased. When adrenaline is given s.c., no change in sleeping times is observed in female and male rats, while the blood concentration of hexobarbital for the two sexes is decreased. Glucose, given p.o. or i.p., has no influence on sleeping times or on hexobarbital concentrations. The hexobarbital concentrations at awakening is higher in female than in male rats.

Animals↗
PubMed1975

The NADPH-dependent cytochrome P-450 reduction in liver microsomes of rats of different ages with and without phenobarbital pretreatment.

The activity of NADPH-cytochrome P-450 reductase in liver microsomes of 10- to 60-day-old rats was determined. Neither the half life time of cytochrome P-450 reduction nor the absolute amount of cytochrome P-450 reduced per time unit depend on age. Phenobarbital pretreatment enhances the reduction rate in all age groups. The addition of hexobarbital or ethylmorphine to microsomal suspension accelerates the reduction of cytochrome P-450 in some age groups only. Age differences corresponding to developmental changes in drug-metabolizing activities are not detectable. The NADPH-cytochrome P-450 reductase seems to be not responsible for the age dependence of drug metabolism.

Animals↗
PubMed1975

On the selectivity of aryl hydrocarbon hydroxylase induction after 3-methylcholanthrene pretreatment.

The development of aryl hydrocarbon (benzo(a)pyren)hydroxylase (AHH), succinate dehydrogenase and glucose-b-phosphatase activities in the liver and the kidney and of liver weight and glycogen were investigated in 7-day-old rats treated i.p. with 1, 10, and 100 mg 3-methylcholanthrene (MC)/kg body weight. 3-MC highly specifically influenced the AHH activity, which was increased dose dependent. The higher the dose, the higher and the longer was the induction effect. The other biochemical parameters investigated were not influenced. At the maximum of the induction effect after pretreatment with the highest dose of 3MC no morphological alterations in the liver could be observed by light and electron microscopy. Therefore the 3-MC mediated AHH induction seems to be a suitable model for the examination of dose dependent inducer-inhibitor interactions in the intact animal.

Animals↗
PubMed1975

[The effect of symphathicotropic substances on liver microsomes in vivo and in vitro].

Ephedrine and propranolol shorten hexobarbital sleeping time and increase amidopyrine-N-demethylation activity. Pholedrine only scarcely acts on these parameters, dihydroergotamine is effective. In vitro, ephedrine, pholedrine, propranolol and above all dihydroergotamine proved to be inhibitors of amidopyrine-N-demethylation. Noradrenaline, cAMP and dibutyryli cAMP were ineffective. An influence of the sympathetic nervous system on biotransformation activity cannot be recognized.

Aminopyrine↗