Risk stratification in Brugada syndrome.
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Arrhythmias, Cardiac↗
Biomedical subjects
Qing Wang
Publications and source records attributed to Qing Wang.
Expression of multiple drug resistance conferring proteins in normal Chinese and Caucasian small and large intestinal tissue samples.
Multidrug resistance conferring proteins (MDRCP) are ATP-binding cassette (ABC) transporters known to significantly influence the absorption, distribution, metabolism, and elimination (ADME) and toxic behavior of many therapeutic agents. Research in the pharmacogenomics area has suggested that mutations and variable expression patterns of these MDCRPs may exist in tissue samples from different ethnic groups. The goal of this study was to examine the expression of P-glycoprotein (PGP), sister of PGP (S-PGP), multidrug resistance protein 3 (Mdr3), multidrug resistance like proteins 1-5 (MRP 1-5), and lung resistance associated protein (LRP) in tissue slides and protein lysates derived from normal adult small or large intestines of Caucasian or Chinese origin. Our results demonstrated ubiquitous expression of PGP, MRP 1, MRP 4, and LRP in the small and large intestinal epitheliums originating from both Caucasian and Chinese origin. S-PGP, Mdr3, MRP 2, and MRP 3 exhibited variable expression in the tissue slides and protein lysates derived from the Chinese and Caucasian small and large intestines. MRP 5 was not observed in any of the samples studied. The results suggest that MDCRPs may have distinct expression profiles in the small and large intestines that potentially vary with genetic background. These studies provide a foundation for further investigations to verify these findings across a wider number of patients of different ethnic backgrounds.
ATP Binding Cassette Transporter, Subfamily B↗
Transport and metabolism of gibberellins in relation to flower bud differentiation in Norway spruce (Picea abies).
A mixture of tritiated and deuterated gibberellin A(4) (GA(4)) was injected into the xylem of Norway spruce (Picea abies (L.) Karst) propagules, below an elongating shoot, or applied directly on the needles of an elongating shoot. The distribution of [(2)H(2)]GA(4) and [(3)H]GA(4) in the needles, stems and buds was determined after 4, 12 and 24 h. After 4 h, most of the xylem-injected GA(4) was found in the needles, whereas after 24 h, most of the GA(4) was found in the stem, with a small portion in the lateral buds. Of the GA(4) applied to the needles, 51% of the radioactivity recovered after 24 h was found in the stem and 2% in the lateral buds. Mixtures of tritiated and deuterated GA(4) and GA(9) were injected into elongating shoots of one abundant-flowering family and one limited-flowering family, grown either under conditions inductive for flowering (hot and dry, HD) or under noninductive conditions for flowering (cool and wet, CW). Shoots of both CW- and HD-treated propagules converted [(2)H(2)]GA(9) to [(2)H(2)]GA(51), [(2)H(2)]GA(4), [(2)H(2)]GA(34) and [(2)H(2)]GA(1), whereas [(2)H(2)]GA(4) was converted to [(2)H(2)]GA(34), [(2)H(2)]GA(1) and [(2)H(2)]GA(8). In shoots of both CW-treated clones, the main metabolite of [(3)H]GA(9) was in the GA(51) region. The HD-treated propagules converted more [(3)H]GA(9) to putative GA(4) than the CW-treated propagules. The main metabolite of [(3)H]GA(4) was in the GA(34) region. Radioactive metabolites were also found in the GA(1) and GA(8) regions.
Journal Article↗
Glucuronidation and sulfation of 7-hydroxycoumarin in liver matrices from human, dog, monkey, rat, and mouse.
Uridine 5'-diphospho-N-acetylgalactosamine glycosyltransferases (UGTs) and sulfotransferases (SULTs) are 2 phase II enzymes that are actively involved in detoxification processes as well as in drug metabolism. Compared with cytochrome P450 enzymes, the role of UGTs and SULTs in drug metabolism has received little attention. Liver microsomes, S9 fractions, and cryopreserved hepatocytes from human, dog, cynomolgus monkey, mouse, and rat were used as matrices in the study. Single compound, 7-hydroxycoumarin (7-HC), along with necessary cofactors was dosed into the matrices and incubated at 37 degrees C; formation of two metabolites, 7-HC-glucuronide and 7-HC-sulfate, was determined with liquid chromatography with tandem mass spectrometry. Within the same species, the UGTs activities in microsomes and S9 fractions were comparable. In addition, UGTs activities in cryopreserved hepatocytes were lower than in the other matrices. Also, the SULTs activities were much higher in S9 fractions than in cryopreserved hepatocytes and microsomes. Species differences on UGTs and SULTs activities were also observed. The results indicated that S9 fractions, microsomes, and cryopreserved hepatocytes might be useful for UGTs metabolism study, whereas S9 fractions appear to be the most appropriate matrix for both UGTs and SULTs metabolism. Species differences with respect to phase II metabolism also need to be taken into consideration when selecting an in vitro system to evaluate various aspects of drug metabolism.
Animals↗
Cryopreserved human hepatocytes as alternative in vitro model for cytochrome p450 induction studies.
Induction of cytochrome P450 (CYP) by drugs is one of major concerns for drug-drug interactions. Thus, the assessment of CYP induction by novel compounds is a vital component in the drug discovery and development processes. Primary human hepatocytes are the preferred in vitro model for predicting CYP induction in vivo. However, their use is hampered by the erratic supply of human tissue and donor-to-donor variability. Although cryopreserved hepatocytes have been recommended for short-term applications in suspension, their use in studies on induction of enzyme activity has been limited because of poor attachment and response to enzyme inducers. In this study, we report culture conditions that allowed the attachment of cryopreserved human hepatocytes and responsiveness to CYP inducers. We evaluated the inducibility of CYP1A1/2 and CYP3A4 enzymes in cryopreserved hepatocytes from three human donors. Cryopreserved human hepatocytes were cultured in serum-free medium for 4 d. They exhibited normal morphology and measurable viability as evaluated by the reduction of tetrazolium salts (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) by cellular dehydrogenases. Treatment with beta-naphthoflavone (10 microM) for 3 d increased ethoxyresorufin-O-deethylase activity (CYP1A1/2) by 6- to 11-fold over untreated cultures and increased CYP1A2 messenger ribonucleic acid (mRNA) expression by three- to eightfold. Similarly, treatment of cryopreserved human hepatocytes with rifampicin (25 microM) for 3 d increased testosterone 6 beta-hydroxylase activity (CYP3A4) by five- to eightfold over untreated cultures and increased CYP3A4 mRNA expression by four- to eightfold. The results suggest that cryopreserved human hepatocytes can be a suitable in vitro model for evaluating xenobiotics as inducers of CYP1A1/2 and CYP3A4 enzymes.
Adult↗