Intestinal CYP3A4-mediated biotransformation and active efflux of absorbed drug by P-glycoprotein are major determinants of bioavailability of orally administered drugs. The expression of CYP3A4 and P-glycoprotein in the intestine is not co-ordinately regulated. However, synergistic actions of CYP3A4 and P-glycoprotein in intestinal drug disposition have been confirmed by in vitro and animal studies. Further understanding of this interaction would be potentially useful to improve oral bioavailability of CYP3A4/P-glycoprotein substrates.

OBJECTIVE:The effects of theasinesin on the immune functions of normal and immunosuppressed nice were studied.METHODS:The immunosuppressed mice were induced by cyclophosphamide(15mg/(kg?d)?4d,ip).The immunom_odulatory effects of theasinesin were measured by delayed type hypersensitivity(DTH),phagocytosing function assay of peritoneal macrophage,cleaning charcoal particles method,and HC50 method.RESULTS:Theasinesin(50,100,200mg/(kg?d)?7d)could significantly intensify DTH caused by DNFB.It could also improve phagocytosing function of peritoneal macrophage and increase production of serum hemolysins in mice immunized with SRBC.The ear swelling,K,? and the level of serum hem_olysin that were lowered by cyclophosphamide were also markedly increased by theasinesin.CONCLUSION:Theasinesin has an enhanced effect on immunofuctions of normal mice ans immunosuppressed mice.

Immunosuppressive drugs used in organ transplantation are highly effective in preventing acute rejection. However,the clinical use of the drugs is complicated by the fact that they display highly variable pharmacokinetics and pharmacodynamics among in-dividual patients. The influence of genetic variation on the interindividual variability in immunosuppressive drug disposition,efficacy and toxicity has been explored in recent years. The review summarized all kinds of immunosuppressants and their relationship with ge-netic polymorphisms,including the SNPs of related enzymes about pharmacokinetics and pharmacodynamics,the SNPs of donor and tar-get site. The review focused on the current situation and progress in the related research areas.

Pregnane X receptor ( PXR) , a member of the nuclear receptor subfamily, plays an important role in the regulation of drug metabolic enzymes and transporters. PXR can regulate the expression of downstream target genes through transforming a large number of exogenous and endogenous chemical substances, and can be activated by a variety of Chinese herbal medicines. The same as PXR, constitutive androstane receptor ( CAR) can participate in the regulation of drug metabolic enzyme CYP450 and become the targets of drug action through combining with exogenous ligands to regulate the expression of CYP2B6, CYP3A4, CYP2C19 and UGT1A1.

Objective:To investigate the correlation of ABCB1 polymorphisms and the synergistic effect of Wuzhi capsules on ta-crolimus. Methods:The ABCB11236C>T(rs1128503), ABCB12677G>T/A(rs2032582) and ABCB13435C>T(rs1045642) genotypes were determined by restriction fragment length polymorphism ( RFLP) analysis. The whole blood levels of tacrolimus in renal transplant recipients were measured by chemiluminescent microparticle immunoassay. Analysis of covariance ( ANCOVA) was per-formed to determine the difference of tacrolimus C0/D among the various groups. Results: Whether co-administeration of Wuzhi cap-sules and tacrolimus or not, tacrolimus C0/D of ABCB11236C>T, ABCB12677G>T/A and ABCB13435C>T genotype and haplo-type was without significant difference. Conclusion:When combined with Wuzhi capsules, ABCB11236C>T, ABCB12677G>T/A and ABCB13435C>T mutation is not associated with tacrolimus C0/D.

Pharmacogenomics does not only bring the connection of genes,medicines and diseases,but also become a powerful tool for clinical pharmacists.Pharmacogenomics is commonly used in clinical practice,especially in the implementation of genetic-test results for guiding rational use of medicines.The genotyping results of genes can provide good individualized medication guidance for patients,which can be confirmed by clinical use of the clopidogrel and warfarin.As a member of the clinical treatment team,clinical pharmacists should take advantage of pharmaceutical and pharmacogenomics information to promote rational use of medicines.

AIM　To investigate the inhibitory effects on the growth of SMMC-7721 human hepatocellular carcinoma cell line and its mechanism by theasinesin. METHODS　MTT assay,colony formation test, 3H-TdR, 3H-Leu incorporation test, determination of the intracellular cAMP and cGMP level, in situ hybridization were used. RESULTS　Theasinesin at 50 mg*L-1 could significantly inhibit the growth and colony formation of SMMC-7721 cells. Theasinesin could strongly inhibit DNA and protein synthesis and increase intracellular cAMP levels. C-myc gene expression was significantly decreased and p53 gene increased strongly in a dose-dependent manner.CONCLUSION　Theasinesin demonstrates significant inhibitory effects on the growth of SMMC-7721 cells. Its mechanisms may involve the inhibition of DNA and protein synthesis ,the elevation of intracellular cAMP levels, inhibition of c-myc gene expression and enhancement of p53 gene expression.

Objective:To discuss the ways to deal with adverse drug reactions in pharmaceutical care. Methods:A case of drug-induced kidney injury was provided to analyze the effect of clinical pharmacist on adverse drug reactions. Results and Conclusion:Good quality of pharmaceutical care, such as reliable drug information, is valuable in clinical practice.

AIM To investigate the inhibitory effects on the growth of SMMC 7721 human hepatocellular carcinoma cell line and its mechanism by theasinesin. METHODS MTT assay,colony formation test, 3H TdR, 3H Leu incorporation test, determination of the intracellular cAMP and cGMP level, in situ hybridization were used. RESULTS Theasinesin at 50 mg?L -1 could significantly inhibit the growth and colony formation of SMMC 7721 cells. Theasinesin could strongly inhibit DNA and protein synthesis and increase intracellular cAMP levels. C myc gene expression was significantly decreased and p53 gene increased strongly in a dose dependent manner. CONCLUSION Theasinesin demonstrates significant inhibitory effects on the growth of SMMC 7721 cells. Its mechanisms may involve the inhibition of DNA and protein synthesis ,the elevation of intracellular cAMP levels, inhibition of c myc gene expression and enhancement of p53 gene expression.

AIM To investigate the mechanism of the anticancer effect of theasinesin. METHODS MTT assay, electronic microscopy technique, DNA gel electrophoresis, flow cytometric analysis with Annexin V Fluos staining,RT PCR and immunocytochemistry were performed for apoptosis and its mechanism. RESULTS After HL 60 cells were treated with theasinesin, HL 60 cells were characterized by condensation of the nuclear chromatin, margination against the nuclear envelope, and apoptotic body formation with scanning and transmission electronic microscopy. A typical DNA ladder was detected by agarose gel electrophoresis of DNA extracted from HL 60 cells. Flow cytometric analysis of HL 60 cells by Annexin V Fluos and propidium iodide double staining demonstrated that theasinesin induced apoptosis had dose effect and time effect relationships, but treatment with high dose or long time would induce cell necrosis principally. RT PCR and immunocytochemistry indicated that bcl 2 gene was reduced strongly in HL 60 cells. CONCLUSION\ Theasinesin induces apoptosis in HL 60 cells. The mechanisms for antitumor activity of theasinesin may involve in induction of apoptosis in cancer cells.