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  • Articles: DFG German National Licenses  (5)
  • 1990-1994  (5)
  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 62 (1994), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The brain, with the exception of the choroid plexuses and Circumventricular organs, is partially protected from the invasion of blood-borne chemicals by the specific morphological properties of the cerebral micro-vessels, namely, the tight junctions of the blood-brain barrier. Recently, several enzymes that are primarily involved in hepatic drug metabolism have been shown to exist in the brain, albeit at relatively low specific activities. In the present study, the hypothesis that these enzymes are located primarily at blood-brain interfaces, where they form an “enzymatic barrier,” is tested. By using microdissection techniques or a gradient-centrifugation isolation procedure, the activities of seven drug-metabolizing enzymes in isolated microvessels, choroid plexuses, meningeal membranes, and tissue from three Circumventricular organs (the neural lobe of the hypophysis, pineal gland, and median eminence) were assayed. With two exceptions, the activities of these enzymes were higher in the three Circumventricular organs and cerebral microvessel than in the cortex. Very high membrane-bound epoxide hydrolase and UDP-glucuronosyltransferase activities (approaching those in liver) and somewhat high 7-benzoxyre-sorufin-O-dealkylase and NADPH-cytochrome P-450 reductase activities were determined in the choroid plexuses. The pia-arachnoid membranes, but not the dura matter, displayed drug-metabolizing enzyme activities, notably that of epoxide hydrolase: The drug-metabolizing enzymes located at these nonparenchymal sites may function to protect brain tissue from harmful compounds.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We report the allele frequencies of the apolipoprotein B (Apo B) signal peptide polymorphism in patients with myocardial infarction and compare them with controls. The first sample consists of 197 myocardial infarction patients and 168 controls from Belfast (UK). The second sample consists of 167 myocardial infarction patients and 205 controls from Strasbourg (France), and the third consists of 71 patients and 146 controls from Haute-Garonne (Toulouse, France). No significant differences were observed in the frequency distribution of genotypes among cases and controls or between populations. However, there were more rare homozygotes in the Belfast cases. Significant associations were observed between the Apo B signal peptide polymorphism and mean levels of total cholesterol, low density lipoprotein cholesterol, Apo B and lipoprotein particles containing Apo (a) [Lp(a)] in the Strasbourg control population. Individuals homozygous for the rare allele had higher levels of these lipid parameters. In Belfast, although not statistically significant, the Apo B signal peptide polymorphism had a similar effect on Apo-B-related parameters as seen in Strasbourg. No significant associations were observed in the Haute-Garonne population where the risk of myocardial infarction is three times lower than in Belfast. In all three populations, the average Lp(a) levels were consistently different among Apo B signal peptide genotypes. These data implicate the Apo B signal peptide in determining some of the risks of myocardial infarction in these populations. Regardless of the exact mechanism, the Apo B signal peptide is an important candidate locus for the study of potentially atherogenic lipid variants.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Dextromethorphan ; ELISA ; polymorphism ; population study ; French Caucasians
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Simple, sensitive and selective enzyme immunoassays (ELISA) for monitoring urinary dextromethorphan and its major metabolite, dextrorphan, were developed. Dextromethorphan and dextrorphan hemisuccinates were linked to bovine serum albumin and specific antisera against each immunogen were raised in rabbits. The sensitivity of the ELISA was high (limit of detection 740 and 600 pg·ml−1 for dextromethorphan and dextrorphan, respectively). Intra- and interassay variation was 〈10%, and cross-reactivity between the two compounds was 〈1%. The ELISA was employed to phenotype 216 French subjects. The frequency of poor metabolizers was 5.1%.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: Clofibryl glucuronide ; fenofibryl glucuronide ; Genetic polymorphism ; clofibrate ; fenofibrate ; oral contraceptives ; smoking ; alcohol ; enzyme induction ; drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possible polymorphism of the glucuronidation reaction in man has been investigated using two hypolipidaemic compounds, fenofibrate and clofibrate, as the test probes. The formation of fenofibryl and clofibryl glucuronides was identified by their susceptibility to hydrolyses by β-glucuronidase. The urinary excretion of the glucuronides was measured in 72 healthy volunteers after a single dose of fenofibrate, and in 104 subjects given a single dose of clofibric acid. Fenofibrate was excreted at a lower rate than clofibrate, since 13.94% and 26.55% of the doses of fenofibrate and clofibrate respectively, were recovered in urine in 8 h. Correlation analysis indicated that sex and body mass index significantly influenced the formation of fenofibryl glucuronide, whereas age and oral contraceptives affected the excretion of clofibryl acid glucuronide. The 8-hour urinary excretion patterns of clofibryl glucuronide and of clofibric acid presented a Gaussian distribution, whereas those of fenofibryl glucuronide and fenofibric acid showed 2 populations. When the metabolic ratio free fenofibric acid/glucuronide was considered, 84.7% of subjects presented the ratio 0.147, and 15.3% had the 3-fold higher ratio of 0.421. The study has shown, in the human population studied, that the glucuronidation of fenofibric acid but not that of clofibric acid may present a polymorphism.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Glutathione ; o-Phthalaldehyde ; Post-column derivatization ; Plasma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A method for the assay of various forms of glutathione in human plasma has been developed. The reduced form was measured after direct injection of deproteinized plasma with perchloric acid. The unbound oxidized forms were assayed in deproteinized plasma after reduction with dithiothreitol. The total amount of glutathione was determined by reduction before protein precipitation. Separation of reduced glutathione from other endogenous thiols was by ion-pair, reversed-phase, high-performance liquid chromatography. Post-column derivatization withortho-phthalaldehyde made the assay more selective than when using pyrenemaleimide as thiol fluorogenic reagent. The linear range was 0.02 to 2.0 μg mL−1 with good repeatability (relative standard deviation less than 5% for the lowest concentration measured).
    Type of Medium: Electronic Resource
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