Effect of MDR1 polymorphic expression on oral disposition of cyclosporine A / 药学学报

<p><b>AIM</b>To determine the relationship between C3435T mutation in exon 26 of the human multidrug resistant 1 gene and cyclosporine (CsA) pharmacokinetic (PK) parameters among healthy Chinese volunteers by nonlinear mixed effect model (NONMEM).</p><p><b>METHODS</b>Twenty healthy subjects were given orally a single dose of 500 mg CsA in microemulsion solution. Blood CsA concentrations were measured with HPLC and the genotype for the C3435T polymorphism of MDR1 gene was determined with the PCR and restriction fragment length polymorphism. The results were further confirmed by sequencing. NONMEM was performed to assess the effect of genotype on CsA PK profile.</p><p><b>RESULTS</b>MDR1 C3435T genotype was identified as the best predictor of CsA systemic exposure. The relative bioavailability of CsA was 40% higher in subjects who carried at least one 3435C allele compared to that of TT type individuals in the study population.</p><p><b>CONCLUSION</b>The MDR1 C3435T genotype offers a potential basis of mechanism to explain inter-subject differences in CsA oral bioavailability.</p>

Changes of alkaline phosphatase sugar chains in hepatocellular carcinoma tissue / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the changes of sugar chain structures of alkaline phosphatase (ALP) in hepatoma tissue and its relation to the invasiveness of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>The binding ratios of ALP from 9 normal liver tissues, 16 hepatoma tissues and 16 noncancerous tissues surrounding hepatoma were analysed by affinity chromatography on various lectin columns including leukoagglutinating phytohemagglutinin (L-PHA), lentil lectin (LCA), Datura stramonium agglutinin (DSA), erythroagglutinating phytohemagglutinin (E-PHA) and Sambucus nigra bark agglutinin (SNA).</p><p><b>RESULTS</b>The binding ratios of ALP on L-PHA (22.94%+/-5.30%), DSA (55.97%+/-13.72%), LCA (38.16%+/-8.87%), E-PHA (11.56%+/-4.81%) and SNA (69.80%+/-13.71%) in HCC tissues were significantly increased (P<0.01) compared with that in normal liver tissues (L-PHA 5.89%+/-2.75%, DSA 36.20%+/-11.58%, LCA 17.90%+/-6.71%, E-PHA 5.38%+/-2.20%, SNA 57.32%+/-11.27%), respectively. t values between the two groups were 8.94, 3.64, 5.94, 3.62 and 2.32, respectively. L-PHA-binding ratio (25.84%+/-4.67%) of ALP in HCC with invasiveness was significantly higher than that (18.10%+/-3.64%) without invasiveness (t=3.71, P<0.01).</p><p><b>CONCLUSION</b>The changes of ALP sugar chain structures occur in HCC tissue. b1-6 branching sugar chain structure of ALP is related to the invasiveness of HCC.</p>