In recent years,a large number of drugs have been withdrawn from the market because of torsade de pointes(TdP) and sudden cardiac death,which pose great risks in drug application.Therefore,the different models have been developed to detect TdP liability during the early stage of drug development.In this paper,the principles and characteristics of these screening models are reviewed to give props for preclinical safety assessment.

AIM To investigate if the beneficial effects of β-aescin on ischemia/reperfusion (I/R) induced cerebral injury are related to the inhibition of expressions of pro-inflammatory cytokines. METHODS Rats were pretreated ig with β-aescin for 7 d and then subjected to cerebral I/R injury induced by a middle cerebral artery occlusion. The infarct volume and the neurological deficit were determined by the method of TTC staining and the Longa's score. The permeability of the blood-brain barrier was evaluated by measurement of the Evans blue (EB)content in the brain with spectrophotometer. The serum contents of interleukin-8 (IL-8) and tumor necrosis factor-α(TNF-α) protein were determined by radioimmunoassay and ELISA assay. The expression of nuclear factor-κB (NF-κB) was evaluated with Western blot. RESULTS β-Aescin significantly reduced infarct volume (P<0.05 or P<0.01), ameliorated the neurological deficit and reduced the permeability of blood-brain barrier (P<0.05). Pretreated with β-aescin 30 and 60 mg·kg-1, the serum content of IL-8 and the expressions of TNF-α and NF-κB protein in brain tissue were significantly decreased (P<0.05). CONCLUSION β-Aescin has protective effects on cerebral injury through inhibiting the expression and release of the inflammatory mediators after I/R injury.

Objective To evaluate the efficacy and safety of metoclopramide and ondansetron in preventing nausea and vomiting induced by chemotherapy or operation. Methods Medline database from 1966 to 2002 and CBMdisc database from 1978 to 2002 were used for sources. The studies were set up according to the inclusion/exclusion criteria. The information about trial design, characters of participants and results from the data were independently extracted, and the studies were blindly evaluated by two authors. The studies were tested for heterogeneity of the odds ratio (OR).Results A total of 33 studies were collected (score range of 65-95), of which 19 were high quality for its score(≥85).Ondansetron was more effective than metoclopramide on preventing nausea and vomiting in short term (within one day and three days), and they have similar effects on preventing nausea and vomiting in the long term (more than three days). However, the pooled OR of effective rate of metoclopramide and ondansetron were 0.13-0.70 (P

Aim To investigate the protective effects of breviscapine(Bre) on myocardial hypertrophy and fibrosis induced by isoproterenol (Iso) in rats and its mechanism. Methods Myocardial hypertrophy and fibrosis model of rats were induced by injection of Iso for 7 days(5 mg?kg -1?d -1,sc).From day 2～15,rats were treated with Bre 12.5 and 25 mg?kg -1?d -1 ip,the NS control and Iso model group received saline injection.On day 15,animals were killed by decapitation,monitored in terms of myocardial indexes (heart weight/boday weight, HW/BW and left ventricalar weight/body weight,LVW/BW);the contents of angio- tensin Ⅱ(AngⅡ),nitric oxide(NO) and hydroxyproline and the activity of Na+,K+-ATPase and Ca 2+-ATPase in left ventricle were assayed with radioimmunoassay and spectrophotometry,respectively. Results Compared with the NS control group, the myocardial indexes, the level of AngⅡ and hydroxyproline in left ventricle were markedly increased and NO content, activity of Na+,K+-ATPase and Ca 2+-ATPase in left ventricle were decreased in Iso model group;treatment with Bre 25 mg?kg -1?d -1 significantly reduced the myocardial index and content of AngⅡ and hydroxyproline in left ventricle,increased the NO content ,enhanced the activity of Na+,K+-ATPase and Ca 2+-ATPase.Conclusion Bre can alleviate myocardial hypertrophy and fibrosis induced by Iso in rats.

OBJECTIVE:To provide suggestion and advice for the selection and utilization of essential drug. METHODS:WHO standards for the selection of essential drug and the formulation process of National Essential Drug?Part for Primary Medical and Health Institutions (2009 edition) were analyzed. The significance of theory and methods of pharmacoepidemiology in the selection, utilization and performance evaluation of essential drug were put forward. RESULTS & CONCLUSION:National essential drug should be selected according to evidence-based medicine and pharmacoeconomics based on pharmacoepidemiology, in order to take advantage of a drug epidemiology-based evidence-based medicine and drug selection based on economics, the study concludes. Dialectical thinking about safety and effectiveness of essential drug should be conducted.

AIM To investigate the reativative and protective effect of Neferine (Nef) on the poisoning mice of cholinesterase (ChE) with dichlorves (DDVP) or dipterex (Dip) of LD 100 . METHODS The mice were randomly divided into poisoning group with DDVP or Dip and Nef, Atropine and Pyraloxime methylchloride (PAM Cl) treatment group. Activity of mice blood ChE was determined with Ellmaris method, and acute toxicity experiment was used to determine the protective effect. RESULTS ① Nef (15 mg?kg -1 , ip) exhibited a definite protective effect on poisoning mice, and the mortality of the animals treated with Nef was significantly lower than that of the control group with normal saline ( P 0 05). But Nef and atropine group was significantly lower than that of thePAM Cl group ( P

Addiction diseases make patients dependent on drug abused or some kind of behavior, and seriously impair their physical and mental health . Drug therapy for this kind of disease has got increased attention in recent years besides non drug treatment measures. Dependentless antileptic agents such as carbamazepine and phenytoin show their effective effects on some symptoms like withdrawal syndrome and craving. The mechanisms of addiction diseases and the drug's effects was discussed. Comparative study was made addiction disease and epilepsy.

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.

Dauricine ( Dau ) significantly prolonged monophasic action potential duration of 50% and 90% repolarization ( MAPD50 and MAPD90 ) and functional refractory period (FRP)of the hearts in anesthetized cats in dose-dependent manner. At 9 mg/kg of Dau, MAPD50 was increased from 170?19 ms to 197?20 ms; MAPD90 from 216?16 ms to 249?18 ms; FRP from 177 ? 15 ms to 238 ? 20 ms.Dau 5 mg/kg iv followed by constant perfusion for 30 min could prevent the shortening of MAPD50 in the ischemic boundary area ( BA ) and increased FRP in the non-ischemic area ( NA ) , ischemic central area ( CA ) and BA, and markedly reduced the extent of dispersion of FRP of hearts in anesthetized cats. The results suggest that the antagonizing effect of Dau on the arrhythmias caused by acute myocardial ischemia and reperfusion might be related to its action of prolonging FRP and decreasing the dispersion of FRP in ischemic hearts.

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.