ABSTRACT
Objective:To evaluate the correlation of inter-individual variation of cyclosporine dosage and blood concentration and CYP3A4 and CYP3A5 polymorphism in renal transplant recipients. Methods:Two hundred and twenty-one renal transplant recipients treated with cyclosporine were genotyped for CYP3A4 rs4646437C>T and CYP3A5 6986G>A using ligase detection reactions. The effects of genetic polymorphisms of CYP3A4 and CYP3A5 on cyclosporine trough concentration (C0/D) and 2 h post-dose concentra-tion (C2/D) during the period of 6 months, 6-24 months and above 24 months after renal transplant were studied. Results:CYP3A5 6986G>A genotype affected C0/D during the period of 6 months, 6-24 months and beyond 24 months (PGA>AA. CYP3A4 rs4646437C>T and CYP3A5 6986G>A genotype affected C2/D during the period above 24 months (PCT>TT and CYP3A5 6986GG>GA>AA. Conclusion: CYP3A5 6986G>A genotype affects C0/D and C2/D of cyclosporine, and CYP3A4 rs4646437 C>T genotype affects C2/D of cyclosporine. The effects of genotypes are varied in different stages.
ABSTRACT
AIM To investigate the activation of p38 protein kinase in alveolar macrophages(AMs) stimulated with lipopolysaccharide(LPS) and the effects of dexamethasone(DEX) and N acetylcysteine(NAC) on the process. METHODS AMs isolated and purified from normal rats were divided into four groups:Control group, LPS stimulated group ,DEX group and NAC group. The activation of p38 protein kinase in nuclear protein extract from the AMs and the concentration of TNF ? and IL 8 in supernatant were measured by Western blot and radioimmunoassay, respectively. RESULTS The activation of p38 protein kinase and the concentration of TNF ?, and IL 8 in LPS stimulated group were significantly higher than those in control group( P