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B Q Xu

Publications and source records attributed to B Q Xu.

11 recordsLinked to original sources
PubMed2004

Bacterial diversity in Malan ice core from the Tibetan Plateau.

Three ice core samples were collected from the Malan ice core drilled from the Tibetan Plateau, and three 16S rDNA clone libraries by direct amplification from the ice-melted water were established. Ninety-four clones containing bacterial 16S rDNA inserts were selected. According to restriction fragment-length polymorphism analysis, 11 clones were unique in the library from which they were obtained and used for partial sequence and phylogenetic analysis, and compared with 8 reported sequences from the same ice core at depth 70 m. Differences among the samples were apparent in clone libraries. The phylotypes were dominated by the Proteobacteria group, Acinetobacter sp. and Cytophaga-Flavobacterium-Bacteroides (CFB) group. They accounted for 92.5% (Proteobacteria), 100% (Acinetobacter sp.), 34.4% (CFB) and 100% (beta-Proteobacteria) in the clone libraries from the samples at ice depths 35, 64, 70, and 82 m, respectively. The Acinetobacter sp. was only found in the deposition at ice depth 82 m and closely clustered with gamma-Proteobateria. Two members (Malan A-21 and 101) of alpha-Proteobacteria from the sample of 35 m and two (Malan B-26 and 48) of beta-Proteobacteria of 64 m were loosely clustered (< 95% similarity) with known bacteria, represented new genera in ice bacteria.

Bacteria↗
PubMed2001

[Expression of bcl-2 protein in uterine leiomyomas and normal myometrium].

OBJECTIVE: To study the expression of the apoptosis regulatory protein bcl-2 in the uterine leiomyomas and in the normal myometrium. METHODS: The expression of bcl-2 protein was examined by immunohistochemical ABC staining in 40 cases of uterine leiomyomas and normal myometrium. RESULTS: bcl-2 expression was higher in the uterine leiomyomas than that in the normal myometrium, both in the proliferative phase and in the secretory phase of the menstrual cycle (P < 0.01); bcl-2 expression in leiomyomas in the secretory phase was stronger than that in the proliferative phase of the menstrual cycle (P < 0.01). CONCLUSIONS: The increase of apoptosis inhabiting gene bcl-2 may play an important role in the growth of the uterine leiomyomas. This action may be regulated by progesterone.

Adult↗
PubMed2001

Interaction of plasma proteins with cytochromes P450 mediated metabolic reactions: inhibition by human serum albumin and alpha-globulins of the debrisoquine 4-hydroxylation (CYP2D) in liver microsomes of human, hamster and rat.

The effect of human serum albumin (HSA), alpha1-acid glycoprotein (alpha1-AGP), and alpha- and gamma-globulins on the in vitro metabolism of debrisoquine in human, hamster and rat liver microsomes was studied. Interaction of albumin with cytochrome P450 mediated phenytoin metabolism has been reported. Since plasma protein binding of phenytoin is high, in the present study a weakly protein bound drug, debrisoquine, was studied. Debrisoquine is a substrate of CYP2D6. The debrisoquine 4-hydroxylation was measured using a radio-TLC method. Among the four plasma proteins, alpha-globulins had the strongest inhibitory effect on the debrisoquine 4-hydroxylase activity. The inhibition with 2% alpha-globulins was 42+/-18% for human and higher for hamster and rat liver microsomes (65-71%). HSA had less effect than alpha-globulins. In the presence of HSA, the decrease in activity was between 18 and 35% for all liver microsomes studied. The debrisoquine 4-hydroxylase activity was not significantly changed by alpha1-AGP or gamma-globulins. Using an ultra-filtration method, the protein binding of debrisoquine to 4% HSA, 0.5% alpha1-AGP, 2% alpha-globulins and 2% gamma-globulins was found to be 22, 20, 22 and 5%, respectively. Since the observed inhibition is inconsistent with level of protein binding, it appears, particularly in the case of alpha-globulins, that the plasma proteins interact with CYP2D directly.

Adrenergic Agents↗
PubMed1997

Evidence for CYP2D1-mediated primary and secondary O-dealkylation of ethylmorphine and codeine in rat liver microsomes.

The purpose of the present study was to investigate the role of specific CYPs responsible for the O-dealkylation of ethylmorphine (EM) and codeine (CD) to morphine (M), as well as that of norethylmorphine (NEM) and norcodeine (NCD) to normorphine (NM) in rat liver microsomes. Liver microsomes metabolize EM and CD to M, and NEM and NCD to NM, in the presence of an NADPH-generating system. The metabolites of EM and CD were determined by HPLC with UV and electrochemical detection. In the present study, the role of CYP2D1 in O-dealkylation of EM/NEM and CD/NCD was investigated by use of specific antiCYP antibodies. When testing rabbit antirat CYP2D1, 2E1, 2C11, and 3A2 antibodies, only the antiCYP2D1 antibody inhibited the EM/NEM and CD/NCD O-dealkylase activities significantly. The maximum inhibition achieved was approximately 80% at a protein ratio (IgG to microsomes) of 10:1, p = 0.001. The contribution of CYP2D1 to the O-dealkylation of EM/NEM and CD/NCD was further confirmed by use of the specific CYP2D1 inhibitors quinine and propafenone. Five microM of quinine inhibited the EM/NEM and CD/NCD O-dealkylase activities by approximately 80%. The CYP3A inhibitor troleandomycin (TAO) failed to inhibit the CYP2D1 catalyzed reaction, but did inhibit the N-demethylation of EM and CD. The O-dealkylation of NEM and NCD was also impaired in Dark Agouti rat (DA) liver microsomes. Taken together, the immunoinhibition and chemical-inhibitor studies of rat liver microsomes provided convincing evidence for the involvement of CYP2D1, the rat counterpart of human CYP2D6, in the metabolism of EM/NEM and CD/NCD to the corresponding O-dealkylated metabolites.

Animals↗
PubMed1997

Effects of ethanol on ethylmorphine metabolism in isolated rat hepatocytes: characterization by means of a multicompartmental model.

Hepatic cytochrome P-450 enzymes mediate at least two important biotransformation pathways of codeine and ethylmorphine starting with either N-demethylation or O-dealkylation, producing polar metabolites which are then subsequently glucuronidated. The present study was designed to characterise the acute effects of ethanol on the metabolism of ethylmorphine and to compare it with the effects on codeine in suspensions of freshly isolated rat hepatocytes. Isolated rat hepatocytes from male Wistar rats were prepared by a collagenase perfusion method. Ethylmorphine, codeine and their metabolites were quantified by HPLC with UV detection. The total ethylmorphine elimination rate was reduced by 12% at 5mM and 38% at 100 mM ethanol. The corresponding percentages for codeine were 16 and 43%. In the presence of ethanol the concentrations of several intermediate and end products of ethylmorphine and codeine changed markedly from the control situation. The experimental data were applied to a mathematical compartmental linear model to estimate the influence of ethanol on the separate reaction rates in the two main metabolic pathways. The ratios between reaction rate constants in the ethylmorphine experiments at 100 and 0 mM ethanol were 0.65 for ethylmorphine-->norethylmorphine, 0.63 for norethylmorphine-->normorphine, 0.56 for ethylmorphine-->morphine, 0.49 for morphine-->normorphine, 0.31 for normorphine-->normorphine-3-glucuronide and 0.49 for morphine-->morphine-3-glucuronide. Almost similar effects of ethanol on codeine metabolism were found. In additional experiments, norethylmorphine or norcodeine (50 microM) was incubated with 5 mM to 100 mM of ethanol and the metabolism of both norethylmorphine and norcodeine was found to be inhibited by ethanol in a concentration-dependent manner. The glucuronidation of morphine and normorphine added in separate experiments was also inhibited by ethanol, from 22 to 36% for morphine-3-glucuronide and 30 to 60% for normorphine-3-glucuronide, respectively, in the presence of 5 mM to 100 mM of ethanol. It was concluded that all steps in the metabolism of ethylmorphine (and codeine) leading to the end products morphine-3-glucuronide and normorphine-3-glucuronide were inhibited by ethanol, and that the glucuronidation process were the ones most affected by ethanol.

Animals↗
PubMed1995

Ethylmorphine O-deethylation in isolated rat hepatocytes. Involvement of codeine O-demethylation enzyme systems.

The O-dealkylation of ethylmorphine (EM) and codeine (CD) to morphine (M) co-segregates with debrisoquine/sparteine genetic polymorphism in man. CD O-demethylation is catalysed by cytochrome P450 2D1 (CYP2D1) in rats. In the present study, the O-deethylation of EM was examined and compared with that of CD in suspensions of freshly-isolated hepatocytes prepared by a collagenase method from Wistar rats with and without CYP2D1 inhibitors. Isolated hepatocytes were also prepared from Dark Agouti (DA) rats deficient in CYP2D1, and were incubated with EM or CD. EM, CD and their metabolites were quantified by HPLC with UV detection. EM had a similar pattern of metabolism to that of CD in suspensions of hepatocytes from Wistar rats. Both EM and CD were O-dealkylated to form M plus morphine-3-glucuronide (M3G) and N-demethylated to form norethylmorphine (NEM) or norcodeine (NCD), respectively, which were further metabolized to normorphine (NM) and finally glucuronidated to normorphine-3-glucuronide (NM3G). As compared to hepatocytes from Wistar rats, DA rats were characterized by a markedly decreased formation (70 approximately 75% reduction) of M plus M3G from both EM and CD. Quinine, quinidine, propafenone and sparteine all inhibited EM O-deethylation as well as CD O-demethylation. Quinine was the most potent inhibitor of both these O-dealkylations (Ki = 0.2 microM for both EM and CD, respectively). Quinine as well as the other inhibitors inhibited both EM and CD O-dealkylation competitively and with small differences in Ki versus EM and CD, respectively. The metabolism of EM to M plus M3G and that of CD to M plus M3G was highly correlated when results from the various separate cell suspensions were plotted. In conclusion all findings indicated that the enzyme responsible for O-demethylation of CD, CYP2D1 was also responsible for the O-deethylation of EM to M.

Animals↗
PubMed1995

Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.

1. The pharmacokinetics of ethylmorphine after administration of a single dose of the cough mixture Cosylan were investigated in 10 healthy subjects. 2. The median urinary recovery of ethylmorphine and measured metabolites was 77% over 48 h. The median tmax of unchanged ethylmorphine was 45 min, and the terminal elimination t1/2 was 2 h. Ethylmorphine-6-glucuronide was found to be the major metabolite. 3. Two subjects had significantly lower urinary recovery (0.48 h) of morphine and morphine-glucuronides than the remainder. Furthermore, these two had urinary metabolic ratios (MRO) and partial metabolic clearances (CLmO) for O-deethylation of ethylmorphine tentatively classifying them phenotypically as poor metabolisers of the debrisoquine/sparteine type. 4. Genotyping for cytochrome P450 (CYP) 2D6 alleles revealed five homozygote (wt/wt) and five heterozygote subjects. Two subjects phenotypically classified as poor metabolisers were genotypically CYP2D6A/wt and CYP2D6D/wt, respectively. 5. Serum and urine samples taken more than 8 and 24 h after administration of ethyl-morphine respectively, contained morphine and morphine-glucuronides, but no ethylmorphine, ethylmorphine-6-glucuronide or (serum only) norethylmorphine. Norethylmorphine could be detected after hydrolysis of urine samples in all subjects. The urinary recovery of the active metabolites morphine and morphine-6-glucuronide after administration of ethylmorphine varied by a factor of 9 between individuals. 6. The wide variation in recovery of morphine and morphine-glucuronides after oral administration of ethylmorphine could not be explained simply by a difference in CYP2D6 genotype. Constitutional variation in other enzymatic pathways involved in ethylmorphine metabolism is probably crucial. Ratios of morphine to parent drug cannot be used to distinguish the source of morphine after administration of ethylmorphine. Norethylmorphine should be included in urine assays for opiates in forensic toxicology, and no firm conclusions about the source of morphine are possible based on serum samples obtained more than 24 h after drug administration.

Adult↗
PubMed1993

Ethylmorphine metabolism in isolated rat hepatocytes.

The metabolism of ethylmorphine has been studied in suspensions of isolated rat hepatocytes. Early during incubation, the two major metabolic intermediates detected were morphine and norethylmorphine following N- and O-dealkylation of ethylmorphine, respectively. During subsequent incubation the concentration of the second metabolic intermediate, normorphine increased, before the concentration peaked at approximately 20 microM (100 microM ethylmorphine). Both morphine and normorphine were glucuronidated to form morphine-3-glucuronide and normorphine-3-glucuronide, respectively, which appeared to be the major metabolic end products. The percentage of ethylmorphine metabolized to morphine-3-glucuronide was found to be dependent on the initial concentration of ethylmorphine. With increasing initial ethylmorphine concentration the relative formation of morphine-3-glucuronide was reduced (29 +/- 10% at 5 microM, 18 +/- 5% at 20 microM, and 15 +/- 4% at 100 microM mean +/- S.D., n = 10). The concentrations of ethylmorphine and its metabolites were found to be higher in liver cells than in medium. Thus the ratios between the intra-/extra-cellular concentrations of ethylmorphine increased somewhat from an initial value of 4 during the period for which ethylmorphine could be detected intracellularly. The drug metabolites all exhibited ratios above 10 for the initial 100 min. of incubation. With time these ratios showed a decline, but even for prolonged incubation the ratios were 5 or higher for the end products. Thus considerable drug concentration gradients existed across the cell membrane of isolated rat hepatocytes.

Animals↗