The aim was to investigate the effect of UGT1A9, UGT1A8, UGT2B7 and ABCC2 polymorphism on the pharmacokinetics of mycophenolic acid (MPA) and its metabolites phenolic glucuronide (MPAG) and acyl glucuronide (AcMPAG) in Chinese renal transplant recipients. Single nucleotide polymorphisms (SNP) in UGT1A9-118(dT)(9)/(10), UGT1A9 T-440C/C-331T, UGT1A8*3, UGT2B7 G211T, UGT2B7 C802T, ABCC2 C-24T, and ABCC2 G1249A were detected. A total of 46 recipients were enrolled in the pharmacokinetics study at day 30 after kidney transplantation. Differences in the MPA pharmacokinetic profiles confirmed large inter-patient variation of MPA exposure. A statistical significant increase in the dose-adjusted AUC(6-12) level of MPA was found in patients bearing the -118(dT)(10) allele of the UGT1A9 gene (T(9) = 7.34 +/- 4.11 mg h ml(-1) g(-1); T(9)/T(10) = 11.54 +/- 7.62 mg h ml(-1) g(-1); and T(10) = 11.89 +/-8.76 mg h ml(-1) g(-1), p = 0.041). A similar trend was also observed for the dose-adjusted AUC(0-12) and AUC(6-12) of MPAG. Patients carrying the heterozygous mutant alleles of ABCC2 G1249A exhibited higher AUC(6-12)/D of AcMPAG than those with wild-type genotype (p = 0.016). The other SNPs that were genotyped did not cause any significant variation in MPA and MPAG pharmacokinetic parameters. In conclusion, the enterohepatic recirculation of MPA in the patients seems to be more extensive in UGT1A9-118(dT)(10) allele carriers, and the exposure of AcMPAG is higher in patients carrying ABCC2 G1249A genotype than those with wild-type genotype.
In this work, two Cu(II)-based coordination polymers with the chemical formulae of [Cu(333cptpy)2]n·2nH2O (1, H333cptpy = 4'-(3-carboxyphenyl)-3,2':6',3''-terpyridine) and [Cu(233cptpy)2(H2O)2]n (2, H233cptpy = 4'-(2-carboxyphenyl)-3,2':6',3''-terpyridine) are hydrothermally synthesized using two positionally isomeric pyridyl-carboxylate ligands. The two as-prepared complexes are studied via X-ray single crystal diffraction along with the elemental analysis. Furthermore, the protective effect of compounds 1 and 2 against neonatal sepsis is evaluated. Firstly, ELISA is performed to detect the content of the C-reactive protein (CRP) in the serum of newborns after treatment with compounds 1 and 2. Next, the inflammatory level in the body is detected by the RT-PCR measurement of nf-κb and tnf-α.
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