Search results for "VITRO"
showing 10 items of 2786 documents
Strategies and Molecular Probes to Investigate the Role of Cytochrome P450 in Drug Metabolism
2003
Drug metabolism is the major determinant of drug clearance and, because of polymorphic or inducible expression of drug-metabolising cytochrome P450s (CYPs), is the factor most frequently responsible for interindividual differences in pharmacokinetics. A number of well characterised CYP substrates and inhibitors have been identified that allow precise measurements of individual CYP isoforms. Their use, alone or in combination, facilitates the phenotype characterisation of hepatocytes in vitro and in vivo. Two procedures are used for in vitro investigation of the metabolic profile of a drug: incubation with microsomes and incubation with metabolically competent cells. The major limitation of …
Expression of the human complement C8 subunits is independently regulated by interleukin 1β, interleukin 6, and interferon γ
1998
The eighth component of human complement (C8) is composed of two subunits which are products from three separate genes. The alpha-gamma- and the beta-subunit of C8 are expressed independently, and are part of the membrane attack complex. C8 is primarily synthesized in the liver. It has been shown in previous studies that the human hepatoma cell line HepG2 constitutively expresses C8, and thus is a suitable model system for studying C8 biosynthesis in vitro. Expression is modulated by the cytokines IL-1 beta, IL-6 and IFN-gamma. The effect of the different cytokines on the expression of these subunits was examined using biosynthetical labelling and immunoprecipitation methods. C8 alpha-gamma…
In vivopredictive release methods for medicated chewing gums
2012
Understanding the performance of a drug product in vivo plays a key role in the development of meaningful in vitro drug release methodology. In case of functional chewing gums, the mode and the mechanism of release and the site of application differ significantly from other conventional solid oral dosage forms and require a special consideration to extract meaningful information from clinical studies. In the current study, suitable drug release methodology was developed to predict the in vivo performance of an investigated chewing gum product. Different parameters of the drug release testing apparatus described in the Ph. Eur. and Pharmeuropa were evaluated. Drug release data indicate that …
�ber die Wirkung von Apurins�ure und Apyrimidins�ure auf die enzymatische Desoxyribonukleins�ure-(DNA-) Synthese in vitro
1970
The effect of chemically modified deoxyribonucleic acid (DNA) on enzymatic DNA-synthesis in vitro has been investigated with analogues of DNA prepared without either purine bases (apurinic acid, APA) or pyrimidine bases (apyrimidinic acid, APyA). DNA-synthesis in vitro was studied with the deoxynucleotide polymerizing enzymes purified from calf thymus (replicative and terminal deoxynucleotidyltransferase respectively).
Hemmung von DNA-Synthese und Zellvermehrung durch Apurins�ure und Apyrimidins�ure
1968
Apurinic acid (APA) and apyrimidinic acid (APyA) prepared from deoxyribonucleic acid (DNA) by removing either purine or pyrimidine bases have been reported to inhibit enzymatic DNA-synthesis in vitro (Heicke, 1970). The present paper deals with in vivo effects of APA and APyA on mammalian cells in tissue culture.
Antiasthmatic acetophenones - an in vivo study on structure activity relationship.
1994
The recently isolated acetophenone glucoside androsin, as the major antiasthmatic principle of Picrorhiza kurroa Royle ex Benth. (Scrophulariaceae), was used as a lead compound for detailed structure-activity relationship studies. More than 25 synthesized or commercially available acetophenones with modified substitution patterns were screened in the Plethysmographic guinea pig model using PAF and/or ovalbumin as challenging agents for the generation of bronchial constriction. Whereas the aglycones in most cases were more effective than the corresponding glycosides, substitution patterns in position 3 and 4 of the phenyl ring and the keto function attached to the phenyl ring were found to b…
Fluorescence-based assays for screening nine cytochrome P450 (P450) activities in intact cells expressing individual human P450 enzymes.
2004
In this study we describe a battery of fluorescence assays for rapid measurement in intact cells of the activity of nine cytochromes P450 (P450s) involved in drug metabolism. The assays are based on the direct incubation of monolayers of cells expressing individual P450 enzymes with a fluorogenic substrate followed by fluorimetric quantification of the product formed and released into incubation medium. For each individual P450 activity, different fluorescence probes were examined, and the one showing the best properties (highest metabolic rates, lowest background fluorescence) was selected: 3-cyano-7-ethoxycoumarin for CYP1A2 and CYP2C19, coumarin for CYP2A6, 7-ethoxy-4-trifluoromethylcoum…
Triterpene Saponins from the Roots of Achyranthes bidentata
2001
Three saponins, oleanolic acid-28- O -s-D-glucopyranoside (1), chikusetsusaponin V (2), and 3- O -s-D-glucopyranosyl-oleanolic acid-28- O -s-D-glucopyranoside (3) were isolated from the roots of Achyranthes bidentata Blume (Amaranthaceae). No activity was shown in the granulocyte phagocytosis test nor in the test of the potentiation of the cytotoxicity of cisplatin in human colon cancer cells. This is the first report of compounds 1, 2 and 3 isolated from Achyranthes species. Furthermore, the NMR data of 2 completed the partially published data.
Characterization of a common binding site for basic drugs on human ?2-acid glycoprotein (orosomucoid)
1983
The interaction of chlorpromazine, dl-propranolol, and imipramine with isolated α1-acid glycoprotein is characterized by relatively high association constants and only one binding site per protein molecule. The mutual displacement between the three drugs indicates that all three compounds are bound to the same binding site. Several other basic drugs from different pharmacological and chemical classes also displace chlorpromazine, dl-propranolol, and imipramine with potencies, one would predict from their association constants or from the degree of their plasma binding in humans. It is concluded that displacement phenomena like those observed in this study in vitro are likely to occur also i…
An Aqueous Extract ofWithania somniferaRoot Inhibits Amyloid β Fibril FormationIn Vitro
2011
The ability of an aqueous extract of W. somnifera L. Dunal (Family: Solanaceae) roots to inhibit fibril formation by the amyloid-β peptide in vitro was investigated. W. somnifera is used extensively in traditional Ayurvedic medicine as a nerve tonic with reputed memory enhancing properties. Inhibition of fibrillogenesis measured by transmission electron microscopy and ThT fluorescence assay showed that an aqueous extract of W. somnifera strongly inhibited Aβ fibril formation in a concentration-dependent manner, when compared with control samples. These results suggest that the aqueous extract of W. somnifera root has an ability to inhibit the formation of mature amyloid-β fibrils in vitro, …