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Biomedical subjects

W Wörner

Publications and source records attributed to W Wörner.

34 records · Page 2Linked to original sources
PubMed1987

Concomitant induction of cytosolic but not microsomal epoxide hydrolase with peroxisomal beta-oxidation by various hypolipidemic compounds.

The effects of two cholesterol-lowering (probucol and 1-benzyl-imidazole), three triglyceride- and cholesterol-lowering (clofibrate, tiadenol and fenofibrate) and one triglyceride-lowering (acetylsalicylic acid) compounds on the specific activities of two lipid-metabolizing enzymes (cyanide-insensitive peroxisomal beta-oxidation and palmitoyl-CoA hydrolase) and two xenobiotic metabolizing enzymes (cytosolic (cEH) and microsomal epoxide hydrolase (mEHb] from the livers of male Fischer F-344 rats were investigated. With the exception of probucol and acetylsalicylic acid, all compounds tested caused a dose-dependent hepatomegaly. Taken on a weight basis fenofibrate was the most effective inducer, causing a 20-fold induction of peroxisomal beta-oxidation, a 13-fold induction of cEH activity and a 16-fold induction of palmitoyl-CoA hydrolase activity. The other compounds with triglyceride-lowering activity also induced cEH as well as peroxisomal beta-oxidation and palmitoyl-CoA hydrolase activity. The potency of each individual drug was similar for induction of cEH activity as compared with that of peroxisomal beta-oxidation and palmitoyl-CoA hydrolase activity, but very dissimilar for mEHb, which upon treatment with any of the triglyceride-lowering compounds was either not or only minimally (less than 1.5-fold) induced. 1-Benzylimidazole possessing exclusively cholesterol-lowering activity increased mEHb much more than either cEH or peroxisomal beta-oxidation. The absence of an enhancement of cEH activity in in vitro studies confirmed that the increase in enzyme activity by the test compounds is not caused by activation. cEH activity was also induced in the kidney but only about 2-fold by fenofibrate, tiadenol and acetylsalicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Distribution and inducibility of cytosolic epoxide hydrolase in male Sprague-Dawley rats.

Cytosolic epoxide hydrolase (cEH) activity has been determined in liver and various extrahepatic tissues of male Sprague-Dawley rats using trans-stilbene oxide (TSO) and trans-ethylstyrene oxide (TESO) as substrates. Large interindividual differences in the specific activity of cytosolic epoxide hydrolase in the liver from more than 80 individual rats were observed varying by a factor of 38. In a randomly selected group of five animals liver cEH varied by a factor of 3.9 and kidney cEH by a factor of 2.7, whereas liver microsomal epoxide hydrolase and lactate dehydrogenase showed only very low variations (1.4- and 1.1-fold, respectively). The individual relative activity of kidney cEH was related to that of the liver. Cytosolic epoxide hydrolase activity was present in all of six extrahepatic rat tissues investigated. Interestingly specific activities were very high in the heart and kidney (higher than in liver), followed by liver greater than brain greater than lung greater than testis greater than spleen. TSO and TESO hydrolases in subcellular fractions of rat liver were present at highest specific activities in the cytosolic and the heavy mitochondrial fraction. As indicated by the marker enzymes, catalase, urate oxidase and cytochrome oxidase, this organelle-bound epoxide hydrolase activity may be of peroxisomal and/or mitochondrial origin. In the microsomal fraction, TSO and TESO hydrolase activity is very low, whereas STO hydrolase activity is highest in this fraction and very low in cytosol. In kidney, subcellular distribution is similar to that observed in liver. None of the commonly used inducers of xenobiotic metabolizing enzymes caused significant changes in the specific activities of rat hepatic cEH (trans-stilbene oxide, alpha-pregnenolone carbonitrile, 3-methylcholanthrene, beta-naphthoflavone, isosafrole, butylated hydroxytoluene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, dibenzo[a,h]anthracene, phenobarbitone). However, clofibrate, a hypolipidemic agent, very strongly induced rat liver cEH (about 5-fold), whereas microsomal epoxide hydrolase activity was not affected. Specific activity of kidney cEH was increased about 2-fold.

Animals↗
PubMed1986

Rat cytosolic epoxide hydrolase.

Rat liver microsomal and cytosolic epoxide hydrolase may be distinguished through differences in substrate specificity: styrene 7,8-oxide is preferentially hydrolyzed by the microsomal form, while trans-stilbene oxide is the preferred substrate for cytosolic epoxide hydrolase. Large interindividual differences in the specific activity of Sprague-Dawley (outbred strain) liver cytosolic epoxide hydrolase were observed, varying from 2 to 77 pmol/min X mg protein. Interindividual variations were much lower for microsomal epoxide hydrolase. The specific activity of Fischer F-344 (inbred strain) liver cytosolic epoxide hydrolase varied only by a factor of 2. The specific activity of cytosolic epoxide hydrolase using trans-stilbene oxide as the substrate was highest in kidney and heart, followed by liver, brain, lung, testis, and spleen. For microsomal epoxide hydrolase, the specific activity was much lower in extrahepatic tissues than in liver. None of the commonly used inducers of xenobiotic metabolizing enzymes caused significant changes in rat liver cytosolic epoxide hydrolase. However, peroxisome proliferating drugs were found to drastically increase cytosolic epoxide hydrolase activity. Treatment for one week with a diet containing clofibrate (0.25%), tiadenol (0.5%) or acetylsalicylic acid (1%) caused a 8, 13 and 5 fold increase in cytosolic epoxide hydrolase activity respectively in the liver which parallelled the induction of peroxisomal beta-oxidation activity (13, 19 and 5 fold, respectively).

Animals↗
PubMed1986

[Possibilities for the use of formula diets for tumor patients].

Malnutrition is a frequent problem in cancer patients. Nearly 50% of all tumor patients lose more than 10% of their pre-illness weight during the various stages of their disease. Ingestion-dependent abdominal pain in patients with gastrointestinal tumor complications is a major problem among the causes which are under discussion. Elemental diet has a safe analgetic effect in these patients because of its quick and complete resorption in proximal parts oft the jejunum. Tube feeding with elemental diets can be provided fully ambulatory and leads to a significant increase in the quality of life of cancer patients. This was demonstrated in a group of 38 malnourished cancer patients. The effect of tube feeding combined with chemotherapy was investigated in a small group of 10 patients with low Karnofsky index. The outcome was compared to the results of 9 international chemotherapy studies using the same chemotherapeutic regime without artificial feeding.

Adult↗
PubMed1985

Vitamin K epoxide reductase activity in the metabolism of epoxides.

The importance of vitamin K epoxide reductase for the metabolism of a range of structurally diverse epoxides has been investigated. Vitamin K1 epoxide is reduced by rat liver microsomes at a rate of 0.47 nmoles/g liver/min. The rate of menadione oxide reduction is not significantly higher than the non-enzymatic reduction rate. No measurable reduction of benzo[a]pyrene 4,5-oxide, benzo[a]pyrene 7,8-oxide, phenanthrene 9,10-oxide, styrene 7,8-oxide, and dieldrin has been detected, nor could trichothecene T-2 toxin inhibit reduction of vitamin K1 epoxide. Thus, vitamin K epoxide reductase is very specific for vitamin K1 epoxide. Taking into account the range of structurally diverse epoxides investigated and the high specific activities of microsomal epoxide hydrolase and cytosolic glutathione transferase for these epoxides it may be concluded that vitamin K epoxide reductase, in all likelihood, generally does not significantly contribute to the control of epoxides metabolically formed from xenobiotics.

Animals↗
PubMed1984

Identity of dihydrodiol dehydrogenase and 3 alpha-hydroxysteroid dehydrogenase in rat but not in rabbit liver cytosol.

Dihydrodiol dehydrogenase and 3 alpha-hydroxysteroid dehydrogenase activity in rat and rabbit liver cytosol have been analyzed by isoelectric focussing and subsequent activity staining. Identity of the two enzymes in rat liver cytosol is demonstrated. At least 4 main enzyme forms possessing dihydrodiol dehydrogenase activity can be detected in rabbit liver cytosol. However, in this species, only one of these forms has measurable activity towards 3 alpha-hydroxysteroids.

3-Hydroxysteroid Dehydrogenases↗
PubMed1982

Kirromycin-resistant elongation factor Tu from wild-type of Lactobacillus brevis.

Properties of the elongation factor Tu from Lactobacillus brevis which is naturally insensitive to kirromycin are described. The protein is characterized by an unusual nucleotide-binding site with increased affinity for GTP and extreme heat stability. EF-Tu is sensitive to pulvomycin in the assay of polyphenylalanine synthesis. However, the failure of the protein to display pulvomycin-dependent GDP-binding and GTPase activity indicates that pulvomycin action in L. brevis differs from that in E. coli.

Aminoglycosides↗
PubMed1981

Metabolic products of microorganisms. 200 Isolation and characterization of niphithricins A, B, and elaiophylin, antibiotics produced by Streptomyces violaceoniger.

Fermentations of Streptomyces violaceoniger TU 905 produce the antifungal antibiotics niphithricins A, B, elaiophylin and nigericin. The niphithricins have been characterized as new macrolide antibiotics, and the previously unknown structure of elaiophylin was determined to be a macrodiolide. The niphithricins were biologically active against Gram-positive bacteria and fungi. The mode of action is attributed to an alteration of the membrane permeability.

Anti-Bacterial Agents↗
PubMed1979

[Gastric bypass in the surgical treatment of extreme adiposity].

The gastric bypass is an effective surgical procedure for the treatment of extreme obesity. A small gastric reservoir and a narrow anastomosis are combined (to limit the possibility of food intake). In patients with a mean weight of 94% above the Broca value the normal weight is reached 18 months after the operation. Failure to lose weight can be caused by technical errors during the procedure or by a continuous food intake by the patients. Surgical complications are rare. The operative lethality is less than 1%, and anastomotic ulcers occur in 2% of cases. There is no reason to expect metabolic derangements as after jejunoileal bypass.

Acute Disease↗
PubMedDate not supplied

Kinetics of drug binding to human serum albumin: allosteric and competitive inhibition at the benzodiazepine binding site by free fatty acids of various chain lengths.

The inhibition of dansylsarcosine (DS) binding at the benzodiazepine binding site of human serum albumin has been studied in the presence of saturated and unsaturated free fatty acids (FFA) of various chain lengths (C6-C20, C18:1, C18:2). In order to determine the mechanism of displacement, velocity constants for association (k2) and dissociation (k-2) and binding constants (KA and KA') have been measured using the stopped-flow method. The inhibitory effect of FFA on DS binding kinetics at site II is dependent of their structure. With increasing amounts of FFA the association velocity constant of DS binding decreases from 520 s-1 (fatty acid free albumin) by a factor of 3-10 and affinity decreases according to FFA chain length. Inhibition is strongest in the presence of caprylic, capric and lauric acid (C8-C12) i.e. with more than one mole FFA per mole albumin, DS association could no longer be measured. Short chain caproic and the long chain FFA C14-C20 showed only a less inhibitory effect since in the presence of a twofold excess k2 ranged between 100 and 200 s-1. Dissociation velocity of DS from the benzodiazepine binding site could be measured in relationship to FFA chain length using ibuprofene, another drug binding at site II. Dissociation velocity constants k-2 remained constant up to 2 moles FFA per mole albumin (k-2 = 16-18 s-1). A rise in k-2 to 70 s(-1) was seen, however, when 2-4 moles capric, lauric, myristic and palmitic (C10-C16) acid were bound, whereas no change was observed when increasing concentrations of caproic, caprylic, stearic and arachic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding, Competitive↗