Drugs online research references
J Pharmacol Exp Ther. 2002 Oct;303(1):412-23.
A cell-based reporter gene assay for determining induction of CYP3A4 in a high-volume system.
Raucy J, Warfe L, Yueh MF, Allen SW.
Puracyp, Inc., San Diego, California 92121, USA.
Assessing the inducibility of CYP3A4 by various xenobiotics can predict potential drug interactions. In the present investigation, human hepatoma cells were stably integrated with either the CYP3A4 enhancer region and a luciferase reporter gene or the CYP3A4-luciferase construct and the human pregnane X receptor (PXR). Several colonies containing one to three copies of luciferase per cell were identified by Southern blot analysis. Those transformants producing high luciferase activity in response to rifampicin were used to standardize a 96-well plate screening system with minimal inter- and intraplate variability. Standardization also consisted of assessing viability of cells cultured in medium containing various serum concentrations. In cells maintained for 48 h in medium with less than 5% serum, a significant (p < 0.01) decline was observed in viability accompanied by altered induction. A defined serum-free medium also produced less viable cells but did not alter the inductive response. Treatment of transformants with various concentrations of rifampicin produced a dose-response curve with maximal induction at 10 microM (5.6 +/- 0.18- and 2.1 +/- 0.3-fold above dimethyl sulfoxide (DMSO)-treated cells in transformants with and without PXR, respectively). Of additional agents examined for their ability to induce CYP3A4, omeprazole (200 microM) was the most potent inducer (12.8 +/- 1.9- and 2.4 +/- 0.2-fold above DMSO-treated cells in transformants with and without PXR, respectively). Mifepristone and mevastatin produced modest induction (approximately 3-fold) in the cell line containing exogenous PXR, but produced less than 1.2-fold increases in cells lacking PXR. Thus, only potent inducers can be identified in the cell line without PXR. In contrast, cells containing the receptor can be used to rank CYP3A4 induction. Because a high volume of chemicals can be readily and accurately screened for their ability to induce CYP3A4 with this format, such a system could be valuable in the initial stages of preclinical drug development.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12235278&dopt=Abstract
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J Int Med Res. 2002 Jul-Aug;30(4):413-21.
Polymorphism of CYP2C19 and gastric emptying in patients with proton pump inhibitor-resistant gastric ulcers.
Wada F, Murase K, Isomoto H, Soda H, Takeshima F, Omagari K, Mizuta Y, Tsukamoto K, Murata I, Kohno S.
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
The aim of the present study was to investigate whether CYP2C19 polymorphism status and gastric emptying are related to healing in patients with gastric ulcers. We studied the CYP2C19 status in seven patients with proton pump inhibitor (PPI)-resistant ulcers, 21 with PPI-sensitive ulcers and 46 healthy volunteers using polymerase chain reaction restriction fragment length polymorphism to detect CYP2C19m1 mutation in exon 5 and CYP2C19m2 mutation in exon 4. Gastric emptying was evaluated using the 13C-acetate breath test. The frequency of phenotypes, indicated by genotypes, did not differ significantly between the three patient groups. The peak time of 13C excretion in patients with PPI-resistant ulcers was significantly longer than that of patients with PPI-sensitive ulcers and healthy volunteers. Our results suggest that rate of gastric emptying, but not CYP2C19 polymorphism, is likely to be an important factor in the delayed healing of patients with PPI-resistant gastric ulcer.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12235924&dopt=Abstract
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med.osaka-cu.ac.jp
BACKGROUND/AIMS: Eradication of Helicobacter pylori is known to reduce ulcer recurrence in patients with peptic ulcer disease, however, other long-term effects after eradication therapy are not well known. The aim of this study is to examine the long-term effect of H. pylori eradication on clinical symptoms, quality of life, body mass index, newly emerging symptoms, and newly developed diseases. METHODOLOGY: One hundred and ninety-two Japanese patients with peptic ulcer disease who received H. pylori eradication therapy at Department of Gastroenterology, Osaka City University Hospital between 1993 and 1995 were asked to fill in specially a prepared questionnaire. RESULTS: One hundred and fourteen patients returned the questionnaires; out of them 98 could be analyzed in this study. Successful eradication (n = 88) resulted in alleviation of symptoms, improvement of quality of life and increase of body mass index while failure of eradication (n = 10) had much less or no effects. A relatively high incidence of hyperlipidemia (25.0%) was observed in patients with successful H. pylori eradication. Development of hyperlipidemia was associated with significant improvement of quality of life especially the item concerning eating and drinking habits but not with increased body mass index. In the elderly, no significant change in body mass index was observed, however, post-eradication body mass index was significantly higher in patients with hyperlipidemia than those without. CONCLUSIONS: Cure of H. pylori infection alleviates symptoms and improves quality of life of treated patients, but might be associated with an increased incidence of hyperlipidemia.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12239930&dopt=Abstract
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