Adiponectin gene polymorphisms are associated with posttransplantation diabetes mellitus in Chinese renal allograft recipients.

BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is a well-recognized renal transplantation complication that is associated with increased graft loss, morbidity, and mortality. Adiponectin gene polymorphisms are associated with type 2 diabetes. However, it remains unknown whether these polymorphisms increase the risk for development of PTDM. Therefore, the aim of this study was to investigate the association between the adiponectin gene polymorphism and the risk of PTDM among Chinese renal allograft recipients. METHODS: We genotyped 398 unrelated renal allograft recipients without a prior diagnosis of diabetes, including 97 PTDM and 301 without PTDM, for adiponectin gene variants: single nucleotide polymorphisms at position 45 and 276, that is, SNP-45: T/G, SNP-276: G/T, using the polymerase chain reaction-restriction fragment length polymorphism assay. No prisoners or organs from prisoners were used in the study. RESULTS: The G allele of SNP-276 was significantly more frequent in PTDM than non-PTDM subjects (P = .041). For SNP-45 and SNP-276, the incidence of PTDM was significantly higher in patients with the GG genotype than those with the TG and TT genotypes (48.1% vs 21.5% and 23.6% and 30.7% vs 18.5% and 22.8%; (P = .011 and .024, respectively). Even after adjusting for age and sex, the effects of the SNP-45 genotypes for GG compared to TT (odds ratio [OR] = 3.108, P = .009) and GG compared to TG (OR = 3.620, P = .004) as well as for SNP-276 genotypes GG compared to TG (OR = 2.203, P = .002) and body mass index at transplantation (OR = 1.099, P = .024) remained significant. CONCLUSIONS: These data suggested that SNP-45 and SNP-276 of the adiponectin gene were significantly associated with an increased risk for PTDM among Chinese renal allograft recipients.

The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers.

The effects of berberine (BBR) on the pharmacokinetics of ciclosporin A (CsA) were examined in healthy volunteers. Six healthy male volunteers were orally treated with 0.3 g BBR, twice daily for 10 days. Pharmacokinetic investigations on CsA at 6 mg/kg were done both before and at the end of the BBR treatment period. Another six healthy male volunteers were involved in the pharmacokinetic study with 3 mg CsA/kg, in which the subjects orally received the second single dose of 3 mg CsA/kg, followed by a single oral dose of 0.3 g BBR. The blood CsA concentrations were determined by fluorescence polarization immunoassay. In the pharmacokinetic study with 6 mg CsA/kg, BBR caused no significant changes in the pharmacokinetic parameters of CsA. However, in the trial with 3 mg CsA/kg, the average percentage increase in area under the blood concentration-time curve of CsA was 19.2% (P < 0.05) and the mean C12 increased to 123 microg/l from 104 microg/l (P < 0.05), without altering elimination half-life (t(1/2)), maximum blood drug concentration (Cmax), time to Cmax (tmax), apparent oral clearance (CL/F). The present results suggest that BBR can increase the oral bioavailability of CsA at the dosage of 3 mg/kg. The BBR-mediated increase in CsA bioavailability may be partly attributed to a decrease in liver and/or intestinal metabolism through the inhibition of CYP3A4 in the liver and/or gut wall. The BBR-induced increase in emptying time of stomach and small intestine might be another reason for the increase in CsA bioavailability. However, the speculation should be proved by further investigation.

Determination of acrylamide metabolite, mercapturic acid by high performance liquid chromatography.

A HPLC Assay was developed to identify and measure the metabolite of acrylamide, mercapturic acid, N-Acetyl-s-(propionamide)-cysteine (APC) in urine. O-phthalaldehyde (OPA) was utilized as a precolumn derivatizing agent in the assay. This derivative was isolated with a good selectivity by high performance liquid chromatography (HPLC) employing reversed phase ODS columns. The quantitation of the mercapturic acid derivative was reproducible and with a detection limit of 1 pmol. The average coefficient of variation for the runs carried out on the same day was approximately 4.6% at the range of 80-160 mumol.L-1 of APC, and the mean analytical recovery from urine samples was 94%. The metabolite of urine of workers exposed to acrylamide was identified as N-acetyl-s-(propionamide)-cysteine by HPLC chromatography and fluorescence scan and HPLC-Mass spectra. All results were identical with the authentic synthesized compound.