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Jasminder Sahi Ralph H Stern Mark A Milad Kelly A Rose Gordon Gibson Xianxian Zheng Linda Stilgenbauer Nalini Sadagopan Summer Jolley Darryl Gilbert Edward L LeCluyse 《Drug metabolism and disposition》2004,32(12):1370-1376
Avasimibe, an acyl-CoA:cholesterol acyltransferase inhibitor, has been previously shown to be a potent inducer of CYP3A4 and multiple drug resistance protein 1. We have further characterized the drug interaction potential of avasimibe by studying the inductive and inhibitory effect of this compound on major drug-metabolizing enzymes. Enzymes known to be involved in the metabolism of drugs likely to be coadministered with avasimibe, such as CYP1A1/2, CYP2C, and CYP2B6, were evaluated further by microarray analysis, Western immunoblotting, and activity assays, using rifampicin and beta-naphthoflavone as positive controls. No change was observed in CYP1A1/2 mRNA or activity levels after avasimibe treatment. Differential induction of CYP2C9- and CYP2B6-immunoreactive protein and activity was observed depending on drug concentration and donor. Microarray analysis showed a similar increase in CYP2C and CYP2B6 mRNA levels. The inhibition potential of avasimibe on the major drug-metabolizing enzymes was assessed using pooled human liver microsomes. Avasimibe inhibited CYP2C9 (IC50 2.9 microM), CYP1A2 (IC50 13.9 microM), and CYP2C19 (IC50 26.5 microM). A clinical drug interaction study was conducted to determine whether avasimibe might interact with the CYP2C9 substrate warfarin. Volunteers received 750 mg of avasimibe and showed a 54.2% reduction in trough concentrations of S-warfarin and decreased prothrombin times by 12, 15, 19, and 21% on days 6 through 9, respectively. These results demonstrate that avasimibe's inductive spectrum resembles that of rifampin. 相似文献
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Bielinska M Parviainen H Porter-Tinge SB Kiiveri S Genova E Rahman N Huhtaniemi IT Muglia LJ Heikinheimo M Wilson DB 《Endocrinology》2003,144(9):4123-4133
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S K Bansal P C Gautam S P Sahi S K Basu J M Lennox A J Warrington 《Age and ageing》1987,16(5):279-284
Ninety-two consecutive elderly patients suffering from acute gastrointestinal bleeding were studied over a 3-year period. All were admitted to a specially designated Geriatric/Surgical Ward under the care of consultant physicians in geriatric medicine. The nurses were trained to look after acute surgical and geriatric patients. Patients were aged between 65 and 93 years. All were managed jointly by the surgeons and physicians. Only 13 needed emergency surgery which was preceded by urgent endoscopy. The rest were managed conservatively with intravenous cimetidine and blood transfusions as required. The overall mortality was low at 5.4%. It is concluded that in a series of elderly patients with acute gastrointestinal bleeding the mortality was not high in a unit where the management was conservative and there was joint care between geriatricians and surgeons. 相似文献
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Andréa Alessio Fabricio R.S. Pereira Maurício S. Sercheli Jane M. Rondina Helka B. Ozelo Elisabeth Bilevicius Tatiane Pedro Roberto J.M. Covolan Benito P. Damasceno Fernando Cendes 《Human brain mapping》2013,34(1):186-199
We aimed to identify the brain areas involved in verbal and visual memory processing in normal controls and patients with unilateral mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS) by means of functional magnetic resonance imaging (fMRI). The sample comprised nine normal controls, eight patients with right MTLE, and nine patients with left MTLE. All subjects underwent fMRI with verbal and visual memory paradigms, consisting of encoding and immediate recall of 17 abstract words and 17 abstract drawings. A complex network including parietal, temporal, and frontal cortices seems to be involved in verbal memory encoding and retrieval in normal controls. Although similar areas of activation were identified in both patient groups, the extension of such activations was larger in the left‐HS group. Patients with left HS also tended to exhibit more bilateral or right lateralized encoding related activations. This finding suggests a functional reorganization of verbal memory processing areas in these patients due to the failure of left MTL system. As regards visual memory encoding and retrieval, our findings support the hypothesis of a more diffuse and bilateral representation of this cognitive function in the brain. Compared to normal controls, encoding in the left‐HS group recruited more widespread cortical areas, which were even more widespread in the right‐HS group probably to compensate for their right mesial temporal dysfunction. In contrast, the right‐HS group exhibited fewer activated areas during immediate recall than the other two groups, probably related to their greater difficulty in dealing with visual memory content. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc. 相似文献
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