ABSTRACT
OBJECTIVE To investigate the effects of Compound troxerutin and poreine cerebroside injection on the activity of cytochrome P450 （CYP450） enzyme in vivo and in vitro. METHODS Human liver microsomes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） and the specific probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 for 30 min. The production of corresponding metabolites was detected by ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and the half inhibitory concentration （IC50） was calculated. The relative mRNA expression （i.e. induction multiple） of CYP450 enzyme was determined by real-time fluorescence quantitative PCR after human primary hepatocytes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） or 3 positive inducers of CYP1A2， CYP2B6， CYP3A4 for 48 hours. Male SD rats were randomly divided into control group （normal saline+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10， 10， 8 mg/kg） and experimental group （Compound troxerutin and poreine cerebroside injection 0.9 mL/kg+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10，10， 8 mg/kg）， with 6 rats in each group. The pharmacokinetic parameters of probe substrates were detected by UPLC-MS/MS and Cocktail probe drug method. RESULTS After the lzqpharm@126.com treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the activities of CYP2B6， CYP2C8 and CYP2C19 in human liver microsomes had no significant change， and IC50 could not be fitted； IC50 of CYP1A2， CYP2C9， CYP2D6 and CYP3A4 were 419.90%， 97.78%， 176.00%， 19.42%， respectively. After the treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the average induction multiple of CYP3A4 mRNA in human primary hepatocytes （No. MHK） was 4.88 （and the average induction multiples of 2 concentration points were higher than 2）. After the treatment of Compound troxerutin and poreine cerebroside injection， AUC0－t and AUC0－∞ of CYP2C8， CYP2C9 and CYP2C19 substrates were increased significantly， CL of CYP2C8 and CYP2C19 substrates were decreased significantly， while t1/2 of CYP2C9 substrate was prolonged significantly （P＜0.05）. CONCLUSIONS Compound troxerutin and poreine cerebroside injection has no obvious inhibitory effect on CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 in human liver microsomes in vitro， but can induce the mRNA expression of CYP3A4 in human primary hepatocytes in vitro， and can inhibit the activities of CYP2C8， CYP2C9 and CYP2C19 in rats in vivo.
ABSTRACT
The safety of TCM injection triggered attentions and hotspots in recent years in China.The centralized monitoring of TCM injection provided important evidence for analyzing the safety risk of TCM injections,recognizing adverse reactions and contraindications and perfecting the instructions.This study aimed at exploring the ethical problems on centralized monitoring.In this paper,we retrieved and screened the ethical issues of TCM injections over hospital centralized monitoring in China National Knowledge Infrastructure (CNKI,1979-Ju1.,2016).Issues over it were put forward and addressed.It is found that the current ethical issues related to hospital centralized monitoring lacks sufficient attentions,corresponding norms and requirements.Based on the ethical issues reflected from the literatures,suggestions should be pressed ahead with the ethical review of centralized surveillance,signing of informed consents,registration of research programs,data statistics and reporting stages,for the better protection of the rights and interests of subjects and improvement of research quality.
ABSTRACT
OBJECTIVE:To investigate the regularity and characteristics of adverse drug reactions (ADR) induced by Xianling gubao capsule,and to provide reference for rational drug use in the clinic.METHODS:ADR induced by Xianling gubao capsule were retrieved from CJFD,CBM,Wanfang database,VIP during Jan.2007-Oct.2016.The related information of 185 ADR cases were statistically analyzed.RESULTS:Among 185 patients,primary disease was mainly osteoporosis (63 cases,34.05％).The incidence of ADR induced by drug combination (70.81％) was higher than single drug (29.19％).ADR mostly occurred within 90 d after medication (67.03％).Main clinical manifestation was digestive system damage (82.68％).Most patients (61.62％) did not need treatment,symptomatic treatment or drug withdrawal to relieve ADR symptoms.CONCLUSIONS:The monitoring for ADR induced by Xianling gubao capsule should be strengthened in clinic,especially for ADR of liver fuction,soas to promote rational drug use.
ABSTRACT
OBJECTIVE:To investigate the regularity and characteristics of adverse drug reactions (ADR) induced by Xianling gubao capsule,and to provide reference for rational drug use in the clinic.METHODS:ADR induced by Xianling gubao capsule were retrieved from CJFD,CBM,Wanfang database,VIP during Jan.2007-Oct.2016.The related information of 185 ADR cases were statistically analyzed.RESULTS:Among 185 patients,primary disease was mainly osteoporosis (63 cases,34.05％).The incidence of ADR induced by drug combination (70.81％) was higher than single drug (29.19％).ADR mostly occurred within 90 d after medication (67.03％).Main clinical manifestation was digestive system damage (82.68％).Most patients (61.62％) did not need treatment,symptomatic treatment or drug withdrawal to relieve ADR symptoms.CONCLUSIONS:The monitoring for ADR induced by Xianling gubao capsule should be strengthened in clinic,especially for ADR of liver fuction,soas to promote rational drug use.
ABSTRACT
Subject recruitment is an important part of clinical researches. It should follow the ethical principles of fairness and representativeness. The recruitment process should pay attention to protecting the privacy of sub-jects. Various recruitment materials must be approved by the ethics committee before use. Whether could recruit el-igible subjects during Phase I clinical trials will have a significant impact on the results, which should attract the relevant persons′attention including the ethics committee, researchers, clinical research associate and the sponsor.
ABSTRACT
At present,the various levels of safety evaluations of traditional Chinese medical (TCM) injections were in force in post-marketing clinical researches,while the process quality is guaranteed with difficulty.Therefore,it is requisite to call for technical guidance.By drawing lessons from the international experience of drug marketing safety evaluation and the related methods,we proposed the key techniques of quality control for clinical safety evaluation of TCM injections from the three aspects:preparation,implementation and summarization of researches,combining with the characteristics of TCM injections.The key techniques contained some scientific problems,ethics,publicity,data management,statistical analysis,specification report,etc.This paper comprehensively introduced the requisite technologies and methods over research quality,laying a foundation for the studies of post-marketing clinical safety evaluation of TCM injections.
ABSTRACT
Objective: To study the e ects of Heying Anxin Fang on cardiac function and intracellular Ca2+ concentration in cadiocyte of chronic congestive heart failure rats. Methods: Animal models of heart failure were induced by subcutaneous injection of a large dose of ISO, and were randomly divided into model group, Shenmai injection group, captopril group, high, middle and low dosages of Heyinganxin Fang group and normal group with 9 in each group. To determine the indexes of LVSP, LVEDP, +dp/dtmax ,-dp/dtmax and heart weight, and determine Ca2+ concentration in cardiomyocytes by ow cytometer. Results: Compared with normal group, the indexes of heart weight, Ca2+ concentration and LVEDP in model group increased, but indexes of LVSP, +dp/dtmax, -dp/dtmax decreased obviously(P
ABSTRACT
This paper introduces the international experiments of risk management in clinical trails, responsibility of sponsor, responsibility of investigator and responsibility of other participators and to help to improve our management level of clinical trails.
ABSTRACT
The present study investigated the effects of the serum-free conditioned media of the bone marrow endothelial cells on CFU-F for potential mechanisms upon which hematopoiesis may be regulated by them within the bone marrow microenvironment. After obtaining the serum-free conditioned media of human and murine purified bone marrow endothelial cells (hBMEC-CM and mBMEC-CM) in vitro, MW > 10 kD, 3 - 10 kD and < 3 kD components were sifted out from these media by means of serial ultrafiltration. Assays of CFU-F were performed to test the effects of BMEC-CM and their ultrafiltrated components. The results showed that every one of hBMEC-CM, mBMEC-CM and their MW < 3 kD components exerted a suppressive effect on the proliferation of corresponding CFU-F but MW > 10 kD and 3 - 10 kD components. The BMEC-CM and MW < 3 kD components decreased the number as well as the size of CFU-F. There were the markedly negative concentration-dependent relations between the concentrations of MW < 3 kD component and the numbers of CFU-F. These findings suggested that bone marrow endothelial cells in culture could secrete at least a humoral factor (molecular weight less than 3 kD) which has an inhibitory effect on the growth of CFU-F.
ABSTRACT
Objective This study was designed to assess whether Bushen Tongluo Fang(BSTLF),a Chinese materia medica formula,can ameliorate the hypercoagulable state in rats with membranous glomerulonephritis(MGN)induced by cationized bovine serum albumin(C-BSA)in order to gain an insight into the mechanisms responsible for its therapeutic effect.Methods Seventy-two male Sprague-Dawley rats were randomly separated into six groups:the normal control group,the MGN model group,the prednisone-plus-aspirin treatment group,and the low-,moderate-,and high-dose groups of BSTLF.The model of MGN was induced by sc(preimmunization)and iv injections of C-BSA in the latter five groups.After the development of MGN model,the decoctions of BSTLF and the prednisone-plus-aspirin solution were ig administered to the treatment groups respectively twice daily for four weeks.The rats in the model group received their drinking water as vehicle controls.Urinary albumin excretion for 24 h was measured using a rat albumin ELISA kit.The platelet aggregation was analyzed by turbidimetry.The plasma level of fibri-nogen(Fib)was determined by the von Clauss assay.Radioimmunoassay was used to examine thromboxane B2(TXB2)and 6-keto-prostaglandin F1?(6-keto-PGF1?)of the renal cortex.Results Urinary albumin excretion for 24 h,maximal platelet aggregation,plasma Fib level,and TXB2 production of renal cortex in the MGN model group were significantly higher than those in the normal control group,respectively.Compared with the MGN model group,these four measurements were decreased significantly in BSTLF-treated groups.The 6-keto-PGF1? production of renal cortex in the MGN model group was subnormal but no statistically significant differences were observed between the model group and BSTLF groups.Conclusion The results of this study suggest that the administration of BSTLF could attenuate platelet aggregability,lower plasma level of Fib and reduce thromboxane A2 production by renal cortex in the rats with MGN,so that their hypercoagulable state is corrected at least partly and glomerular microthroimbosis is prevented in several ways.These effects may contribute considerably to the mechanisms of BSTLF efficacy for chronic nephritis.