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H Kewitz

Publications and source records attributed to H Kewitz.

14 recordsLinked to original sources
PubMed1992

The effect of the new immunosuppressive drug FK506 on the formation of secondary metabolites of cyclosporin A.

Interactions of FK506 with the cyclosporin A (CsA) metabolism are described. These interactions were not differentiated between the primary and secondary part of metabolism. The combination-therapy with cyclosporin A and diltiazem has shown, that not only the blood levels of CsA were increased, but also the blood levels of the primary CsA-metabolite M17. In the presented in in-vitro-investigations 1.7 microM tritium-labelled CsA was incubated for 90 min with human liver microsomes. The inhibitory effect of FK506 (6 microM) was observed with coincubation under the same conditions. The metabolites were quantified by detection of radioactivity of the elution-fractions after HPLC. The results showed strong inhibition on the formation of both, the primary and secondary CsA-metabolites by FK506. With the same concentration diltiazem and erythromycin exhibited only an inhibition of the formation of secondary CsA-metabolites. In clinical investigations with FK506 in combination with CsA it is necessary to control blood levels of CsA and also its primary metabolites.

Biotransformation↗
PubMed1977

Reserpine and breast cancer in women in germany.

Exposure to reserpine was compared in 181 women interviewed prior to biopsy and found to have breast cancer and 307 women found to have a benign disorder of the breast. The age-adjusted relative risk of breast cancer in those who had taken reserpine was 0.6 (95% confidence limits: 0.4 and 1.1). When the 181 breast cancer patients were compared with a second control group of 101 women with a benign condition requiring surgery, the relative risk was 0.9 (95% confidence limits: 0.4 and 1.7). Neither long-term exposure nor its timing, gave any evidence of an association with breast cancer. The findings in this study do not support the hypothesis that rauwolfia derivatives initiate or promote breast cancer.

Adult↗
PubMed1977

Inhibition of choline incorporation into brain lipids in rats by urethane, a proposed mechanism of depression of the central nervous system.

Concentrations and specific radioactivities of choline, acetylcholine, phosphorylcholine, lipid choline, and sn-glycero-3-phosphorylcholine after i.v. injection of methyl-14C-choline were measured in the brain of untreated controls and of rats anesthesized with urethane. The specific activity was found to be decreased during deep anesthesia by 40% in acetylcholine, 20-30% in phosphorylcholine, 50-75% in lipid choline, and 30-40% in sn-glycero-3-phosphoryl-choline. No significant change was detected in the specific activity of choline. The brain concentration of acetylcholine was increased by 40%, the concentration of sn-glycero-3-phosphorylcholine, however, was diminished by 10% during anesthesia. No change was found in the concentration of the other choline containing compounds investigated. Measuring choline incorporation into 4 subcellular fractions of brain tissue specific activities were found to be decreased by the same percentage, although 2 fractions (nuclei and microsomes) were higher labelled than the 2 other fractions (crude mitochondria with synaptosomes and lysosomes). A correlation between the biochemical and the functional alterations is supported by the dose-effect relationships on both parameters. It is suggested that urethane reduces turnover of lipids and by that mechanism inhibits the exocytotic release of the transmitter from presynaptic nerve endings.

Animals↗
PubMed1977

Mechanism of the enrichment of phosphatidylcholine in liver accompanying enzyme induction by phenobarbital.

The mechanism of the increase of phosphatidylcholine in liver, accompanying enzyme induction by phenobarbital, has been studied in rats. Using radioactively labeled precursors, the two main pathways of phosphatidylcholine biosynthesis--the CDP-choline pathway and the methylation of phosphatidylethanolamine--were analyzed after pretreatment with 4 doses of phenobarbital (80 mg/kg) on 3 consecutive days. After i.v. injection of choline [Me-3H], choline [Me-14C] or NaH2[32P]O4 the specific radioactivity (sp. act.) of phosphatidylcholine (dpm/nmol) was decreased by 60%, and after methionine [Me-3H] or ethanolamine [1.2-14C] by 40% compared to control rats. These changes are partly due to the increased concentration of phosphatidylcholine and phosphatidylethanolamine, causing the incorporated precursors to dilute, and partly to a secondary effect which leads to a reduction of the sp. act. of free choline in pretreated animals. The concentration of glycerylphosphorylcholine, one of the metabolites of phosphatidylcholine catabolism, was also diminished by almost 50%. From these results it may be concluded that the increase of phosphatidylcholine is due to a retardation of its breakdown rather than to an increase of its synthesis.

Animals↗
PubMed1976

Synthesis of choline from ethanolamine in rat brain.

Specific radioactivities of choline, acetylcholine, phosphocholine, lecithin, lysolecithin, and glycerophosphorylcholine have been measured in brain, blood, liver, and muscle after the intravenous injection of three labeled precursors: choline, methyl-labeled methionine, and ethanolamine. In relation to the specific activity of free choline in blood there was significantly more radioactivity in the free choline of brain after administration of methyl-labeled methionine and labeled ethanolamine than after labeled choline. Since the choline moiety of lipids, which returns back to the choline pool, contained less radioactivity after methyl-labeled methionine and labeled ethanolamine than after labeled choline, it is the most likely interpretation of the finding that choline, in brain can be formed by methylation of free ethanolamine. Data from liver confirm that lecithin is formed in the liver by methylation of phosphatidylethanolamine. No indication was found for the synthesis of choline in muscle. Rates of transfer and transport of choline in brain have been calculated as nmol x g-1 x min-1 as follows: turnover rate of choline, 36.5; rate of synthesis of choline by methylation and net loss of choline into the bloodstream, 6.3; inflow from the blood 6.2; outflow into the blood, 12.5; transfer into lipids and vice versa, 20; transfer to acetylcholine and vice versa, 4.

Acetylcholine↗
PubMed1976

[One hundred years pilocarpine in ophthalmology (author's transl)].

In 1876 A. Weber introduced chemically from P. jaborandi isolated Pilocarpium muriaticum into the ophthalmological therapy. One year later it was used as a local drug to lower the intraocular pressure in glaucoma and replaced in the following years the extract of Calabar bean (Eserine). Clinical and pharmacological data are discussed.

Germany↗
PubMed1975

Evaluation of in vivo parameters of drug metabolizing enzyme activity in man after administration of clemastine, phenobarbital or placebo.

The 24 h urinary excretion of 6beta-hydroxycortisol and D-glucaric acid, the plasma half lives and total clearances of aminopyrine, and serum gamma-glutamyl-transpeptidase activity have been measured in nineteen healthy male volunteers. The study was done double blind and was conducted as a test of induction of microsomal drug metabolizing enzymes during and after daily doses of 6 mg clemastine, 300 mg phenobarbital or a placebo. The urinary excretion of 6beta-hydroxycortisol and D-glucaric acid was significantly increased in the phenobarbital group, the standard for induction. No changes were observed after treatment with clemastine or placebo. Phenobarbital also reduced the half life of aminopyrine, but it was not affected by clemastine or placebo. Gamma-glutamyl-transpeptidase activity increased only in the phenobarbital group. The elimination constant k2 of aminopyrine and the excretion of glucaric acid in the pre-medication period were correlated (p less than 0.05) The results indicate that the tests were of diagnostic value in determination of microsomal enzyme induction by phenobarbital. Failure to observe similar changes after treatment with clemastine imply failure of induction of this activity under the experimental conditions.

17-Hydroxycorticosteroids↗
PubMed1975

[Detection of side effects by systematic and programmed research].

The need for data on efficacy and rate of adverse reactions after the admission of drugs for common use has become obvious in recent years, in order to evaluate benefit and risk in the long run. Due to the lack of knowledge severe hazards were realized rather late in the past. To improve this unsatisfactory situation it will be useful to explore different ways to get a systematic registration of harmful reactions. None of the procedures known so far for this purpose have been proven to provide sufficient information when used single. In the future voluntary reporting, hospital monitoring and a drug surveillance program may be included in a cooperative system to discover the seldom and unforseen diasters by drugs as early as possible. Much effort will be necessary to reach this aim. One among other useful techniques is the procedure developed by the "Boston Collaborative Drug Surveillance Program", which is discussed in some detail. It is thought to improve chances for the detection of certain associations between drug usage and health dangers in short-term as well as long-term treatments. These would allow for preventive measures. It has to be stressed, however, that protection cannot be expected for every event but is limited at least to the drugs monitored and to the hazards recognised.

Drug-Related Side Effects and Adverse Reactions↗