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Human CYP2C9 is important in the metabolism of numerous clinically used drugs such as the anticoagulant warfarin, the anticonvulsant phenytoin, antidiabetic drugs such as tolbutamide and glipizide, the hypertensive agent losartan, and numerous nonsteroidal anti-inflammatory drugs. Several studies have reported that certain drugs such as rifampicin and(More)
Cytochrome P450 (P450) enzymes play important roles in the metabolism of endogenous and xenobiotic substrates in humans. CYP2C8 is an important member of the CYP2C subfamily, which metabolizes both endogenous compounds (i.e., arachidonic acids and retinoic acid) and xenobiotics (e.g., paclitaxel). Induction of P450 enzymes by drugs can result in tolerance(More)
Time-dependent inactivation (TDI) of human cytochromes P450 3A4 (CYP3A4) is a major cause of clinical drug-drug interactions (DDIs). Human liver microsomes (HLM) are commonly used as an enzyme source for evaluating the inhibition of CYP3A4 by new chemical entities. The inhibition data can then be extrapolated to assess the risk of human DDIs. Using this(More)
CYP2C19 is an important human drug-metabolizing enzyme that metabolizes a number of clinically used drugs including the antiulcer drug omeprazole, the anxiolytic drug diazepam, the beta-blocker propranolol, the antimalarial drug proguanil, certain antidepressants and barbiturates, and the prototype substrate S-mephenytoin. Previous studies show that(More)
In humans, four members of the CYP2C subfamily (CYP2C8, CYP2C9, CYP2C18, and CYP2C19) metabolize more than 20% of all therapeutic drugs as well as a number of endogenous compounds. The CYP2C enzymes are found predominantly in the liver, where they comprise approximately 20% of the total cytochrome P450. A variety of xenobiotics such as phenobarbital,(More)
This paper describes an approach to the evolutionary modeling problem of ordinary differential equations including systems of ordinary differential equations and higher-order differential equations. Hybrid evolutionary modeling algorithms are presented to implement the automatic modeling of one- and multi-dimensional dynamic systems respectively. The main(More)
Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics. No standard treatment has been established. This retrospective study was designed to investigate the clinical and pathological characteristics, diagnosis, treatment, and prognosis of esophageal BSCC. Clinical data were retrospectively analyzed from 26(More)
CYP2C9 is an important human drug-metabolizing enzyme that is expressed primarily in liver. Recent studies in our laboratory have shown that the nuclear receptor pregnane X receptor (PXR) is important in the transcriptional activation of the CYP2C9 promoter by drugs such as rifampicin and that the essential element is a constitutive androstane receptor(More)
OBJECTIVE Immune responses are important in dictating non-alcoholic steatohepatitis (NASH) outcome. We previously reported that upregulation of hedgehog (Hh) and osteopontin (OPN) occurs in NASH, that Hh-regulated accumulation of natural killer T (NKT) cells promotes hepatic stellate cell (HSC) activation, and that cirrhotic livers harbour large numbers of(More)
UNLABELLED Clinicians rely upon the severity of liver fibrosis to segregate patients with well-compensated nonalcoholic fatty liver disease (NAFLD) into subpopulations at high- versus low-risk for eventual liver-related morbidity and mortality. We compared hepatic gene expression profiles in high- and low-risk NAFLD patients to identify processes that(More)