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  • HMG-CoA reductase inhibitor  (1)
  • Polyether ionophore  (1)
  • 1
    Electronic Resource
    Electronic Resource
    CP-60,993, a new dianemycin-like ionophore produced byStreptomyces hygroscopicus ATCC 39305: fermentation, isolation and characterization (1990)
    Springer
    Journal of industrial microbiology and biotechnology 5 (1990), S. 365-374 
    Details
    ISSN: 1476-5535
    Keywords: CP-60,993 ; 19-Epi-dianemycin ; Polyether ionophore ; Anticoccidial agent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary CP-60,993, 19-epi-dianemycin, is a novel polycyclic ether antibiotic produced byStreptomyces hygroscopicus ATCC 39305. Fermentation recovery, purification and crystallization were achieved using standard procedures. CP-60,993 was characterized as a monocarboxylic acid. Elemental analysis suggested a molecular formula of C47H78O14 for the free acid and C47H77O14 Na for the sodium salt. Crystalline form CP-60,993 sodium salt shows the following properties: m.p. 193∼205°C, E 1 cm 1% =157 at 232 nm, [α] D 25°C +11.0 (c 1, methanol). The structure, determined by MS, PMR and CMR, differs from dianemycin only in the stereochemistry at position 19. This was confirmed by X-ray crystallography carried out on the rubidium salt of CP-60,993. It exhibited activity in vitro against Gram-positive and anaerobic bacteria, efficacy againstEimeria coccidia in vivo in poultry, and stimulation in vitro of rumen propionic acid production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01578095
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  • 2
    Electronic Resource
    Electronic Resource
    Proton-Cotransport of Pravastatin Across Intestinal Brush-Border Membrane (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1727-1732 
    Details
    ISSN: 1573-904X
    Keywords: pravastatin ; intestinal absorption ; active transport ; pH-dependent transport ; HMG-CoA reductase inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of the present study is to clarify the intestinal brush-border transport mechanism of a weak organic acid, pravastatin, an HMG-CoA reductase inhibitor. Methods. The transport of pravastatin was studied by using intestinal brush-border membrane vesicles prepared from rabbit jejunum, and uptake by the membrane vesicles was measured using rapid filtration technique. Results. The initial uptake of [14C]pravastatin was markedly increased with decreases in extravesicular pH and showed a clear overshoot phenomenon in the presence of a proton gradient (pHin/out = 7.5/5.5). A protonophore, carbonylcyanide p-trifluoromethoxyphenylhydrazone, significantly reduced the uptake of [14C]pravastatin. In addition, an ionophore for sodium, potassium and proton, nigericin, stimulated the uptake of [14C]pravastatin in the presence of a potassium gradient ([K + ]in/[K+ ]out = 0/145 mM). On the other hand, neither the imposition of an inwardly directed sodium gradient nor an outwardly directed bicarbonate gradient stimulated the uptake of [14C]pravastatin. In the presence of a proton gradient (pHin/out = 7.5/5.5), the initial uptake of pravastatin was saturable with the apparent Kt of 15.2 ± 3.2 mM and Jmax of 10.6 ± 1.21 nmol/mg protein/10 sec. The uptake of pravastatin was significantly inhibited by monocarboxylic acid compounds such as acetic acid and nicotinic acid in a competitive manner but not by di- or tri-carboxylic acids, or acidic amino acid. Conclusions. It was concluded that a pH-dependent transport of pravastatin across the brush-border membrane occurs by a proton-gradient dependent carrier-mediated mechanism rather than by simple diffusion of its unionized form.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016269806840
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