Effects of Shenmai injection on the regulation of heart CYP450 isozymes in rats / 中国药理学通报

Aim To investigate the influence of Shen-mai injection ( SMI ) on the expression of cytochrome P450(CYP450) system in rat′s hearts. Methods Rat hearts were prepared after a fourteen-day continuous administration of SMI. The expression of several CYP genes, ANP, BNP and EPHX2 were measured by qPCR. Results SMI induced the increase in the ex-pression of other CYP genes except CYP2 B1、CYP4 A3 and CYP4 F6;HSI caused an induction of CYP2 E1 , CYP4A3,CYP4F1 and EHPX2 as compared with the control. In addition, there was a significant induction of ANP, BNP and EHPX2 and a significant inhibition of CYP2B1 and CYP2C11 after treated with MDI. Conclusion Although there is no significant change in the gene expression of CYP2 B1 after the treatment with SMI, but there is a general trend of induction, and MDI shows a significant inhibition of CYP2 B1 , therefore HSI has greater effect on CYP 2 B 1 than MDI . SMI causes a significant induction of CYP2 E1 , CYP4F1 and EHPX2 , similarly there is an induction of CYP2E1,CYP4F1 and EHPX2 by HSI and MDI, indi-cating that Hongshen and Maidong are both involved in the induction. MDI has a greater inductive effect than HSI on ANP and BNP. SMI is widely used for the treatment of cardiovascular diseases due to its regula-tion of CYP2J3、ANP and BNP mRNA expression.

Relationship between the CYP2C19 polymorphism and the efficacy of triple therapy with lansoprazole onHelicobacter pylori infection in elderly patients / 实用医学杂志

Objective To investigate the Relationship between the CYP2C19 polymorphism and the efficacy of triple therapy with lansoprazole on Helicobacter pylori infection. Methods 125 elderly patients diagnosed with H.pylori infection were treated with triple therapy. Polymorphism of CYP2C19 was measured by AS-PCR. 105 young patients were selected as control group. The relationship between the polymorphism and eradication rate were analyzed. Results Among the 125 patients,eradication rate of extensive metabolizer group,internal metabolizer group and poor metabolizer groups was 85.29%,76%and 89.39%, respectively. There was no significant difference between groups (P > 0.05). Eradication rate showed no difference between experimental and control group either (P>0.05)(P>0.05). Conclusion The results suggests that the CYP2C19 polymorphism has no correlation with the eradication rate of Helicobacter pylori infection by triple therapy with lansoprazole in elderly patients.

Advances in Study on Immunological Factors in Drug-induced Liver Injury / 胃肠病学

The pathogenesis of drug-induced Iiver injury( DILI)remains uncIear. AccumuIating evidences in recent years showed that immunoIogicaI factors pIay important roIe in the pathogenesis of DILI. In this articIe,we summarized recent studies on immunoIogicaI factors invoIved in pathogenesis of DILI and compared the immunity mediated DILI with drug induced autoimmune hepatitis. The advances in study on immunoIogicaI factors in DILI wiII have significant impact on prevention and treatment of DILI and autoimmune hepatitis.

Relationship between CYP1A1 polymorphisms and invasion and metastasis of breast cancer

OBJECTIVE@#To investigate the relationship between CYP1A1 genetic polymorphisms and the invasion and metastasis of breast cancer.@*METHODS@#The CYP1A1 gene polymorphism (an T-C transversion at nucleotide position 3801) was detected by the polymerase chain reaction and restriction fragment length polymorphism in 80 cases with breast cancer and 60 samples of normal breast tissue. The difference in genotypic distribution frequency between the groups, the correlation between the genotypes and the factors related to prognosis were analyzed.@*RESULTS@#The incidence of homozygous and variant genotypes had no difference between the breast cancer group and controls group (P=0.746). The proportion of variant genotype increased as clinical stage (P=0.006) advanced, as well as with increased numbers of lymph node metastases (P=0.010).@*CONCLUSIONS@#In patients with breast cancer there is a correlation between the CYP1A1 CC allele and some factors indicating poor prognosis, including more lymph node metastases as well as a more advanced clinical stage.

Influence of the Cytochrome P450 Polymorphism on Clinical Response to Aripiprazole in Patients with Schizophrenia / 대한정신약물학회지

OBJECTIVE: Aripiprazole is an atypical antipsychotic drug metabolized partly by the hepatic cytochrome P450 enzyme, CYP2D6. The aim of this study was to investigate the influence of the CYP2D6 polymorphism on the pharmacokinetics of and clinical response to aripiprazole. METHODS: The study followed a prospective, multicenter, single-medication group design and involved a 26-week study of aripiprazole treatment in Korean patients with schizophrenia. Eighty-nine patients with schizophrenia were recruited and divided into 4 groups according to CYP2D6 genotype: homozygous extensive metabolizer (EM), heterozygous EM, intermediate metabolizer (IM), and poor metabolizer (PM). During the 26 weeks of the study, the pharmacokinetics of the blood samples was analyzed at week 3 and week 8 of drug administration. We used the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Barnes Akathisia Scale (BAS) for akathisia, the Simpson Angus Scale (SAS) for Par-kinsonism, the Abnormal Involuntary Movement Scale (AIMS) for tardive dyskinesia, and metabolic profiles as clinical measures. RESULTS: The sample was divided into 4 schizophrenia subgroups (homozygous EM, n=15; heterozygous EM, n=47; IM, n=22; PM, n=5). Pharmacokinetics analyses showed that patients with poorer functional alleles (PM) had smaller clearance and more than twice as long half-lives compared to those with homozygous EMs characterized by two functional alleles. PMs tended to show higher AUCs than EMs. Over the 26-week treatment period, however, no significant differences in the clinical responses (changes in the PANSS scores) were observed. The prevalence of extra-pyramidal symptoms (Parkinsonism, tardive dyskinesia, akathisia) did not differ among these groups despite the pharmacokinetic differences. CONCLUSION: Despite its relatively small sample size, this study suggested that the CYP2D6 polymorphism might not constitute the major factor contributing to the clinical response to and adverse effects of aripiprazole.