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  • 1
    ISSN: 1432-0738
    Keywords: Hepatocyte primary culture ; Serum-free ; DNA synthesis ; Mitosis ; Cyproterone acetate ; Epidermal growth factor ; Cytotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to elucidate whether serum-free conditions could be found in primary hepatocyte cultures under which the growth inducing properties of xenobiotics and hormones could be tested. Cyproterone acetate (CPA), a steroid with anti-androgenic and progestogenic activity, was chosen as a model compound because of its known strong mitogenic properties in rat liver in vivo. EGF served as a positive control. Induction of DNA synthesis was studied by [3H]-thymidine labeling and autoradiography. Mitoses were counted in hematoxylin stained specimens. The main steps which led to an efficient stimulation of DNA synthesis by CPA were (i) reduction of hormone concentrations to levels approaching (approx. 10 x) physiological concentrations better than the previously used pharmacological ones (up to 2500 x); (ii) supplementation with glucocorticoid (most effective at 10–100 nM dexamethasone); (iii) selection of the interval for cumulative labeling with thymidine at 44–68 h; (iv) lowering of cell density at seeding to 50 000 cells/cm2 (subconfluency); (v) treatment with concentrations of 10–100 μM CPA. With these conditions CPA labelling was 13–20% (increase 4-to 9-fold). Mitotic incidence was 0.56% (CPA) versus 0.08% in controls. From a dose response study (0.1–100 μM) a no-effect-level for induction of DNA synthesis was found in the range of 0.1–1 μM. None of the high concentrations of CPA did cause cytotoxicity as estimated by morphological observations or release of lactate dehydrogenase into the medium. This work demonstrates that CPA under appropriate, defined culture conditions induces DNA synthesis and mitosis. The findings suggest that CPA action on the liver in vivo is at least in part a direct one. The extent of induction was in the same range as found in vivo. The effective concentrations were almost equivalent to CPA liver concentrations after treatment in vivo. Thus the present culture conditions appear to simulate quite well in vivo liver growth control mechanisms. This stresses the versatility of primary hepatocyte cultures as a tool in toxicology for the study of normal and drug-induced growth responses.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0738
    Keywords: Key words Peroxisome proliferator ; Nafenopin ; Fat ; Oxidative stress ; Lipid peroxidation ; Rat liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Oxidative stress is discussed as a possible hepatocarcinogenic mechanism of peroxisome proliferators (PP) in rodents and is suggested to result from the induction of peroxisomal β-oxidation (PBOX) by PP. The induced PBOX is assumed to produce excessive H2O2 from the degradation of fatty acids, ultimately leading to oxidative stress and lipid peroxidation. In the present short term-study, we attempted to stimulate lipid peroxidation in male Wistar rats by (1) inducing PBOX enzymes with the peroxisome proliferator nafenopin at 90 mg/kg body weight per day in the diet for 10–11 days, and (2) by supplying the induced PBOX with an abundant amount of fatty acid as substrate, using a corn oil gavage at 20 ml/kg body weight. The corn-oil gavage alone, i.e. without preceding nafenopin treatment, enhanced liver triacylglycerol nine- to tenfold and hepatic lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS), was increased 50% compared with controls. Both observations were made after 18 h when the peak elevations occurred. Upon pretreatment with nafenopin, asssociated with a sevenfold induction of PBOX, the corn oil gavage however caused only a threefold maximal increase in hepatic triacylglycerol, also at the 18 h time-point; TBARS remained almost at control levels, as monitored at seven time points over 24–25 h. These results suggest that nafenopin reduces rather than enhances lipid peroxidation, despite the provision, in a short term study, of high doses of substrate to the induced enzyme system that is hypothetically causing oxidative stress in the liver.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 113 (1980), S. 1931-1944 
    ISSN: 0009-2940
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Antibiotic Models, 2. The Ring A of Daunomycinone  -  Stereospecific Synthesis of Derivatives of (1S,3S)-1-Acetyl-4-cyclohexene-1,3-diol from Quinic AcidStarting with quinic acid (4) stereospecific syntheses of the protected rings A (17 and 25, resp.) of 7-epidaunomycinone and of daunomycinone were developed. The configuration of the intermediate 10 was established by x-ray structure analysis.
    Notes: Aus Chinasäure (4) wurden stereospezifische Synthesen der geschützten Ringe A (17 bzw. 25) von 7-Epidaunomycinon und Daunomycinon entwickelt. Die Konfiguration der Zwischenstufe 10 wurde durch Röntgenstrukturanalyse bestätigt.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The crystal structure of a glycopeptide antibiotic A-40926 aglycone was investigated by X-ray analysis at -120°. A-40926 crystallises in the orthorhombic space group P212121 with two monomers in the asymmetric unit, a = 21.774(4), b = 28.603(7), c = 29.757(4) Å. ‘Conventional’ direct methods approach failed to solve the structure, but a novel iterative real/reciprocal space procedure was successful. Refinement against 11248 F2 data led to R1 = 13.3% for 6770 F 〉 4σ (F). The two monomers of A-40926 have similar conformations and are bound by antiparallel H-bonds to form a ‘chain’ structure of connecting dimers. The antibiotic molecule possesses a ‘binding pocket’ for the C-terminal carboxy group of the cell-wall protein, which is consisten with suggestions based on NMR data and the recently reported crystal structure of ureido-balhimycin. In A-40926 the monomers are polymerically linked by H-bonds, quite unlike the tight dimer formation observed in ureido-balhimycin.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 35 (1952), S. 1524-1527 
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Mit Hilfe von 15N wird gezeigt, dass bei der durch Anilinhydrochlorid hervorgerufenen «Umlagerung» von Diazoamidobenzol in p-Aminoazobenzol ein quantitativer Austausch zwischen den —N·C6H5-Gruppen des Triazenderivates und denen des Anilinsalzes stattfindet. Dagegen wird das mittelständige Stickstoffatom des Diazoamidobenzols von dem Austausch nicht berührt.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 35 (1952), S. 1548-1559 
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 1. Es wird eine Übersicht der Anschauungen gegeben, die zur Stütze der Ring- bzw. Kettenformel organischer Azide vorgebracht worden sind: .
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 35 (1952), S. 400-406 
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Mit Hilfe von 15N wird gezeigt, dass 1Bei der α-Methylindolsynthese nach E. Fischer das kernständige Stickstoffatom des Hydrazons in das Ringsystem eingebaut, das andere N-Atom als Ammoniak abgespalten wird;2bei der Synthese von 2-Aminobenzthiazol aus 1-Phenylthiosemicarbazid ein Zwischenkörper auftritt, der im Sinne der Robinson'-schen Auffassung als ein Diamin formuliert werden muss.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 33 (1950), S. 2128-2134 
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Es wird eine Methode beschrieben, um Konzentrationen der Stickstoffisotope 15N und 14N mit nur 50 γ N2 durch Photometrierung ultravioletter Banden zu bestimmen. Der mittlere Fehler beträgt etwa ± 2% bei Berücksichtigung der Schwärzungsverhältnisse. Die gewöhnlichen Verunreinigungen beeinflussen die Resultate nieht.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1986 (1986), S. 545-550 
    ISSN: 0170-2041
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Antibiotic Models, 6.  -  Preparation and Glycosylation of the Ring-A Model of DaunomycinoneBy mercury salt-mediated solvolysis of the dithiane function compound 1a was transformed into the (3S) derivative 2, which represents the ring-A fragment of daunomycinone. Glycosylation with the α-L-daunosaminyl chloride 4 gave the glycoside 5. HPLC separation yielded the pure α-anomer which completely resembles daunomycin except for the ring elements B, C, and D, and which, correspondingly, should not exhibit intercalation properties.
    Notes: Durch Quecksilbersalz-vermittelte Solvolyse der Dithianfunktion gelingt aus 1a die Darstellung der (3S)-Verbindung 2, dem Ring-A-Modell des Daunomycinons. Glycosylierung mit dem α-L-Daunosaminylchlorid 4 führt zum Glycosid 5, dessen α-Anomer vollkommen einem Daunomycin mit fehlenden Ringen B, C und D entspricht und daher keine Intercalationseffekte aufweisen sollte.
    Type of Medium: Electronic Resource
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