Assessment of time-dependent inhibition (TDI), especially CYP3A4, is an important parameter for preclinical and clinical development. The use of human liver microsomes (HLM) is the most common in vitro matrix to assess TDI, but this often leads to an overprediction of an actual effect observed clinically. Recently, the use of human hepatocytes has been hypothesized as a more relevant and possib...

PURPOSE Laryngeal squamous cell carcinoma (LSCC) represents one of the most common cancers of the head and neck and the search for molecular markers is required for early diagnosis, prognosis and optimal therapy. The purpose of this study was to investigate the clinical significance of Cyclin D1, FGF3, p16 and p21 protein expression in LSCC and laryngeal dysplasia (LD) and to evaluate the assoc...

Prilocaine and lidocaine are classified as amide-type local anesthetics for which serious adverse effects include methemoglobinemia. Although the hydrolyzed metabolites of prilocaine (o-toluidine) and lidocaine (2,6-xylidine) have been suspected to induce methemoglobinemia, the metabolic enzymes that are involved remain uncharacterized. In the present study, we aimed to identify the human enzym...

AIMS Using the fluconazole-zidovudine (AZT) interaction as a model, to determine whether inhibition of UDP-glucuronosyltransferase (UGT) catalysed drug metabolism in vivo could be predicted quantitatively from in vitro kinetic data generated in the presence and absence bovine serum albumin (BSA). METHODS Kinetic constants for AZT glucuronidation were generated using human liver microsomes (HL...

The metabolism of the carcinogenic mycotoxin aflatoxin B1 (AFB1) was examined in microsomes derived from human lymphoblastoid cell lines expressing transfected CYP1A2 or CYP3A4 complementary DNAs and in microsomes prepared from human liver donors (n = 4). Lymphoblast microsomes expressing only CYPIA2 activated AFB1 to AFBl-8,9-epoxide (AFB1-8,9-epoxide trapped as the glutathione, conjugate) at ...

Prilocaine and lidocaine are classified as amide-type local anesthetics for which serious adverse effects include methemoglobinemia. Although the hydrolyzed metabolites of prilocaine (o-toluidine) and lidocaine (2,6-xylidine) have been suspected to induce methemoglobinemia, the metabolic enzymes that are involved remain uncharacterized. In the present study, we aimed to identify the human enzym...

Gene-environment interaction (GEI) analysis can potentially enhance gene discovery for common complex traits. However, genome-wide interaction analysis is computationally intensive. Moreover, analysis of longitudinal data in families is much more challenging due to the two sources of correlations arising from longitudinal measurements and family relationships. GWIS of longitudinal family data c...