Table of Content

Volume 10 Issue 11
26 November 2005

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Progresses in studies on anti-epileptic drugs

HONG Gang, ZHANG Jiang-sheng, WANG Lin-hui

2005, 10(11):  1201-1209. 

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Epilepsy is a common serious brain disor-derand comprises a wide range of symptom induced by varying etiologies.As more and more knowledge of mech-anisms underlying seizure propagation of epilepsy gained,much more new antiepileptic-drug has been developed.In this article,we reviewed some kinds of new antiepileptic drugs used orresearched in recent years.

Biological actions of human urotensin II on cardiovascularsystem

DING Bo, GAO Shan, CHEN Zhi-wu

2005, 10(11):  1210-1214. 

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Urotensin II(U-II),a cyclic peptide has been initially identified as a neuropeptide of teleost fish.Subsequently,U-II has been characterized in the brain of the Europeangreen frog and has also been cloned from the human genome.Human U-II(human U-II,hU-II),composed of 11 amino acid residues is rich in cardiovas-cularand nervous system.As an endogenous ligand forUT receptor,hU-II exerts a broad spectrum of biological actions,such as vasoconstriction and vasorelaxation,fa-cilitating proliferation of cardiac cells,regulating the car-diac function and playing an important role in pathogene-sis of some cardiovasculardiseases such as coronary heart disease and cardiac failure.The effects of hU-II on card-iovascularsystem were briefly reviewed as follows.

Risk management in clinical trails

HUANG Yu-hong, WANG Bao-he, ZOU Shu-xuan, SUN Zeng-tao, SHANG Hong-cai, ZHANG Bo-li

2005, 10(11):  1215-1218. 

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This paperintroduces the international ex-periments of risk management in clinical trails,responsi-bility of sponsor,responsibility of investigatorand respon-sibility of otherparticipators and to helPto improve ourmanagement level of clinical trails.

Pharmacokinetics of 9-nitro-camptothecin in Beagle dogs

YAN Jing-chao, MA Yue-ming, WANG Tian-ming, ZHANG Fang, YAN Dong-ming, Tan Bo, XIE Hua, Zhang Xiao-chen, YU Tie-liu

2005, 10(11):  1219-1224. 

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AIM: To study the pharmacokinetics of 9-nitro-camptothecin(9-NC)in dogs.METHODS: Each Beagle dog was given a single dose of 9-NC by iv orig administration.The concentrations of 9-NC in plasma were detected by HPLC and HPLC-MS.Pharmacokinetic parameters were determined from the plasma concentra-tion-time data with the 3P97 software package.The rela-tionships betweenAUC,C max orke and dose were evaluat-ed by linearregression.RESULTS: Afteriv administra-tion of 9-NC at the dose of 0.5,1,and 2 mg·kg^-1,the t_1/2values of 9-NC were 2.2±2.2,1.8±1.7 and 0.8±0.6 h,respectively,and AUC_0-twere 105±71,272±81 and 396±93 ng·h·ml^-1,respectively.Afterig ad-ministration of 9-NC at the dose of 1,2,and 4 mg·kg^-1,9-NC was rapidly absorbed,reaching C_maxof 9.3±8.2,42±36 and 64±6 ng·ml^-1at T_maxof 0.3±0.1,0.2±0.1,0.4±0.1 h,respectively,the t_1/2values of 9-NC were 1.9±1.3,1.0±0.6 and 2.8±1.5 h,respective-ly,and AUC_0-twere 8.9±7.2,16±12 and 60±26ng·h·ml^-1,respectively.The values of t_1/2and ke of 9-NC were independent of dose(P>0.05).The absolute oral bioavailability of 9-NC was less than 6%.CONCLUSION: Afteriv orig administration of 9-NC,the time course of plasma concentration in dogs complieswith a two-compartment model.The kinetic process of 9-NC in dogs is linearin the range of the experimental dosage.9-NC is absorbed rapidly afterig administration and the oral bioavailability is poor.

Statistical methods of Meta-analysis

YANG Juan, ZHENG Qing-shan

2005, 10(11):  1225-1235. 

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Meta-analysis is a statistical method to systematically combine and evaluate several relevant tri-als.It is applied generally in medical literatures,and it' s statistical methods are developing.The aim of this paperis to introduce several widely-used statistical methods of Meta-analysis.

Alterations of maternal hepatic drug-metabolizing and antioxidative enz-ymes in tobacco-induced intrauterine growth retardation in rats

WANG Ting, WANG Hui, TANG Hong-bin, YAN You-e, ZENG Han-gao

2005, 10(11):  1236-1239. 

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AIM: To evaluate the alterations of ma-ternal hepatic drug-metabolizing enzymes and antioxidative function in tobacco-induced intrauterine growth retardation(IUGR).METHODS: Pregnant rats were assigned to control grouPand tobacco group.IUGrmodel was pro-duced by smoking from gestational days(GD)9 to GD 20.Fetuses were removed by laparotomy on GD 21.The fetal development parameters such as fetal body weights,littersize and placental weights were recorded.Subcelluarfractionsof liverwere prepared by differential centrifuga-tion.Activities of drug-metabolizing and antioxidative enzymes were monitored.RESULTS: In the tobacco ex-posure group,fetal body weights,littersize and placental weights were significantly reduced(P<0.01).The levels of cytochrome P450(CYP)1A1 in hepatic micro-somes increased by 37.9%,and the activities of CYP3A and glutathione S-transferase(GST)decreased to 73.3% and 86.5%when compared to control group.Meanwhile,the activities of superoxide dismutase(SOD)and catalase(Cat)decreased to 81.0% and 79.7%,respectively,whereas the activity of glutathione peroxidase(GSH-Px)increased in comparison with control group.CONCLUSION: Tobacco exposure in pregnancy results in the alter-ations of partial drug-metabolizing enzymes and antioxida-tive function in maternal liver,and these changes may play an important role in inducing IUGR.Meanwhile,to-bacco exposure in pregnancy may change the drug efficacy and increase the drug toxicity.

Screening of anti-inflammatory Chinese traditional herbs targeted CpG ODN using biosensortechnology

CHENG Juan, ZHENG Jiang, ZHOU Hong, JIANG Dong-neng, WU Chong, CHEN Yi-guo, ZHANG Xiang-wu, YAO Jie

2005, 10(11):  1240-1244. 

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AIM: To screen anti-inflammatory Chi-nese traditional herbs targeted CpG ODN using biosensortechnology.METHODS: Firstly,CpG ODN was immo-bilized on surface of biotin cuvette.Aqueous extractions of seventy-eight traditional Chinese herbs were tested us-ing affinity biosensortechnology.Then aqueous extrac-tions of the herbswith high affinity for CpG ODN were in-cubated with CpG ODN(33μg·ml^-1)at 37 ℃ for30 min,subsequently the mixtures were tested using affinity biosensortechnology.RESULTS: Among the seventy-eight Chinese traditional herbs,fourteen herbs such as ra-dix paeoniae rubra,rhubarb,and terminaliae immaturus possessed the higherbinding activity to CpG ODN,and nine herbs such as Java Brucea fruit,radix paeoniae rubra,and radix sanguisorbae possessed largeramount of effective binding-CpG ODN components.CONCLUSION: Nines kinds of Chinese traditional medicines pos-sess the highly content components with highly specifically affinities to CpG ODN and it provides experimental base forfurtherseparation anti-inflammatory component from Chinese traditional medicine.

Alterations of maternal hepatic drug-metabolizing and antioxidative enz-ymes in tobacco-induced intrauterine growth retardation in rats

WANG Ting, WANG Hui, TANG Hong-bin, YAN You-e, ZENG Han-gao

2005, 10(11):  1245-1248. 

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AIM: To evaluate the alterations of ma-ternal hepatic drug-metabolizing enzymes and antioxidative function in tobacco-induced intrauterine growth retardation(IUGR).METHODS: Pregnant rats were assigned to control grouPand tobacco group.IUGrmodel was pro-duced by smoking from gestational days(GD)9 to GD 20.Fetuses were removed by laparotomy on GD 21.The fetal development parameters such as fetal body weights,littersize and placental weights were recorded.Subcelluarfractionsof liverwere prepared by differential centrifuga-tion.Activities of drug-metabolizing and antioxidative enzymes were monitored.RESULTS: In the tobacco ex-posure group,fetal body weights,littersize and placental weights were significantly reduced(P<0.01).The levels of cytochrome P450(CYP)1A1 in hepatic micro-somes increased by 37.9%,and the activities of CYP3A and glutathione S-transferase(GST)decreased to 73.3% and 86.5%when compared to control group.Meanwhile,the activities of superoxide dismutase(SOD)and catalase(Cat)decreased to 81.0% and 79.7%,respectively,whereas the activity of glutathione peroxidase(GSH-Px)increased in comparison with control group.CONCLUSION: Tobacco exposure in pregnancy results in the alter-ations of partial drug-metabolizing enzymes and antioxida-tive function in maternal liver,and these changes may play an important role in inducing IUGR.Meanwhile,to-bacco exposure in pregnancy may change the drug efficacy and increase the drug toxicity.

Depletion of androgen receptorin LNCaPprostate cancercell line by tri-chostatin A

SUN Sheng-kun, LIU Bing, LI Xiu-shen, HOU Chun-mei, HONG Bao-fa, YU Xiao-dan

2005, 10(11):  1249-1252. 

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AIM: To investigate the mechanisms un-derlying the antitumoreffect of trichostatin A(TSA)on LNCaPprostate cancercell line.METHODS: Prolifera-tion of LNCaPcells exposed to TSA was detected by MTT assay.Cell apoptosis was assayed by Hoechst 33342 nu-clei staining.Western blotting was performed to analyze the expression of the androgen receptor(AR)afterTSA exposure.Semi-quantitative RT-PCrwas used to assay the transcription changes of AR.RESULTS: TSA kills LNCaPcellswith an ED 50 value of 125.9 nmol·L-1 with-in 48 hours exposure.TSA inhibited LNCaPcell prolifer-ation aswell as inducing cell apoptosis.TSA depleted Arboth in a dose and time dependent manner.Moreover,the expression of cell cycle-dependent kinase inhibitor,p21,was induced.The decreasing of Aroccurred at the protein level instead of transcription suppression.CONCLUSION: TSA exhibits significant antitumoreffect against LNCaPcells through depletion of AR.

Comparison of drugs effect on MHV-A59 virus by established DBT cell model

FU Hong-yan, Xu Bo, WANG Hong-jun, GONG Ze-hui

2005, 10(11):  1253-1256. 

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AIM: To establish sensitive DBT cell model to MHV-A59 by virology method,and develoPse-lective method of anti virus drugs in cell level.METHODS: Test 50% percent tissue culture infective dose(TCID₅₀)by cytopathetic effect(CPE)and plaque meth-ods.Preparation of antibody against virus by partially pu-rified virus immunized animal.Selective anti virus drug adding 100 fold of TICD50virus dose infected DBT cell as positive results by protesting lower50%CPE,and tested drugs lowest virus inhibit concentration.RESULTS: Pre-pared antibody has specificity reverse virus action,and new synthesized drugs had various degree protective ac-tions to virus infective.CONCLUSION: The DBT cell model sensitive to MHV-A59 can select anti coronaviruses drug.

Comparison of affinity of mannose receptorof peritoneal macrophage and alveolarmacrophage and its ligands in rats

LV Zheng-guang, LIU Li, MEI Qi-bing, CAO Wei, WANG Zhi-peng, LIU Xin-you, YU Lu

2005, 10(11):  1257-1265. 

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AIM: To evaluate the affinity of the man-nose receptorof peritoneal macrophage and pulmonary macrophage and theirligands.METHODS: Two kinds of macrophage were acquired through Irrigation of peritoneal cavity and bronchoalveolarlavage(BAL).Afterpurifica-tion and identification,macrophage were incubated with fluorescent isothiocyanate(FITC)-labeled mannosylated albumin(M-FITC-BSA,Sigma A7790)for20 minites,the affinity of Mrand its ligands are measured by flow cytometry(FCM)and fluorescene microscope.RESULTS: There existed Mrin macrophage.The binding of Mrand its ligandswas calcium dependent,which was inhibited by the existence of D-mannose and EDTA,but not by D-galactose.The affinity of peritoneal macrophage Mrand its ligands were greaterthan that of the pulmo-nary macrophage Mrand its ligands.CONCLUSION: The affinity of peritoneal macrophage Mrand its ligands are greaterthan that of the pulmonary macrophage Mrand its ligands.

Nitric oxide-induced PC12 cells apoptosis and protective effect of paeoni-florin

SUN Rong, WU Dong-dong, LIU Guo-qing

2005, 10(11):  1266-1274. 

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AIM: To explore the possible mechanism of nitric oxide-induced PC12 cells apoptosis and the pro-tective effect of paeoniflorin.METHODS: Cell survival was detected by MTT and lactate dehydrogenase detec-tion.DNA fragmentation was observed by gels electro-phoresis.Apoptotic cells and mitochondral transmembrane potentiall were observed by flow cytometry in PC12 cells.RESULTS: 500μmol·L^-1of SNPinduced PC12 cells apoptosis.Paeoniflorin decreased nitric oxide induced PC12 cells apoptotic rate and increased mitochondrial transmembrane potential.CONCLUSION: Paeoniflorin can inhibit nitric oxide-induced apoptosis in PC12 cells.The mechanism is related to preventing loss of MMPin PC12 cells.

Analysis of T-type correlation degree between bone mineral contents and histomorphometry of lumbarvertebrae body in ovariectomized rats

XU Bi-lian, CUI Liao, WU Tie, LIU Yu-yu, ZOU Li-yi

2005, 10(11):  1275-1278. 

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AIM: To study the correlative changes of bone mineral contents and histomorphometry of lumbarvertebrae in ovariectomized rats by analysis of T-type cor-relation degree.METHODS: Forty 10.5-month-old vir-gin female Sprague-Dawley rats were randomly divided in-to five groups:(1)Basal:at 10.5 mon of age;(2)sham-1:sham-operated at 13 mon of age;(3)OVX-1:ovariectomized at 13 mon of age;(4)sham-2:sham-op-erated at 16 mon of age;(5)OVX-2:ovariectomized at 16 mon of age.Afterovariectomy,all rats were treated orally with NS at 5 ml·kg^-1·d^-1.At the end-point of study,the undecalcified longitudinal fourth lumbarverte-bra(LV4)sections were cut and stained with Goldner' s Trichrome forbone histomorphometric analyses.The fifth lumbarvertebra(LV5)was dried with temperature and digested with acid fortesting of bone mineral content.Then the effects of bone mineral contents on bone histo-morphometry were assessed by analyzing the T-type corre-lation degree in the Grey system.RESULTS: All degrees of correlation between bone mineral contents and static histomorphometric parameters(trabecularbone volume)(BV/TV),trabecularthickness(Tb.Th)were positive,but fordynamic histomorphometric parameter(BFR/BV),the correlation degrees were negative.The effect of cont-ents of calcium(Ca)and phosphorus(P)on histomor-phometric parameters of lumbarvertebrae was much great-erthan that of the otherbone mineral contents.CONCLUSION: Analysis of T-type correlation degree can evaluate the correlative changes of bone mineral contents and histomorphometry of lumbarvertebrae in ovariecto-mized objectively and fairly.

Setting uPpopulation pharmacokinetics/pharmacodynamics model of VPA n children with epilepsy by NONMEM software

JIANG De-chun, WANG Li, LU Wei

2005, 10(11):  1279-1289. 

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AIM: To set uPpopulation pharmacoki-netics/pharmacodynamics(PPK/PD)model of valproate(VPA)in children with epilepsy in China,and promote easonable use of antiepileptic drugs(AEDs)in clinical ractice.METHODS: Sparse data of VPA serum con-centrations from 246 pediatric children were collected.These patientswere divided into three groups:PPK-Model rouP(n =146),to calculate PPK parametervalues of PA and set uPa PPK model;PPK-Valid grouP(n =100),to valid the PPK model;and PPD grouP(n =69),to set uPPPK PD model.Based on the data of PK-Model grouPand PPK-Valid group,a PPK model of PA in children with epilepsy in China was successfully et uPby using NONMEM software by ourselves.Now,using the data of 69 patients in PPD grouPwho were on PA monotherapy and this PPK model,we set uPPPK/PD model by NONMEM software.Efficacy of epilepsy treatment was divided into 5 grades according to the per-centage of seizure frequency decreased(PSFD%):grade 1:PSFD%was 100%;grade 2:PSFD%was 75%-100%;grade 3:PSFD% was 50%-75%;grade 4:PSFD% was 25%-50%;grade 5:PSFD%was less than 25%.The quantitive relationshiPbetween the VPA serum concentrations and the probability forits efficacy score was characterized by Logistic regression analysis with NONMEM.RESULTS: Logistic regression analysis showed that,VPA serum concentrations and the proba-bility forits efficacy grades 5,4,3,2,and 1 were(23μg·ml^-1,5,50%),(30μg·ml^-1,4,32.3%),(50μg·ml^-1,3,26.3%),(65μg·ml^-1,2,36.5%),(78μg·ml^-1,1,50%),and(100μg·ml^-1,1,84.2%)respectively.CONCLUSION: A PPK/PD mod-el of VPA in children with epilepsy in China is success-fully established by using NONMEM software,and the probability of efficacy grade forany concentration can be calculated.It will be valuable to facilitate individualized dosage regimen.

Study of carthamus tinctorius extract on left ventricle in pressure-over-loaded hypertrophy rats

WANG Jian-ping, WANG Xiong

2005, 10(11):  1290-1293. 

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AIM: To explore the effect of Carthamus tinctorius extract on left ventricularhypertrophy induced by partly abdominal aortic coarctation operation in Wistarrats and to study the involved mechanism.METHODS: 12 ratswere sham operated when the hypertensive hyper-trophy was inducedwith abdominal aortic coarctation in 40 rats,which were randomly divided into control group,captopril group,Carthamus tinctorius extract grouPone week later.The drugs were given by gastric perfusion once a day for6weeks.The weight of the rat and the left ventricle were measured,cardiac coefficient were calcu-lated and MMP-2,MMP-9 were evaluated by ELISA means.RESULTS: The cardiac coefficient of the control grouPwas significantly increased and the expression of MMP-2,MMP-9wasgreatly enhanced in the control rats.After6weeks treatment with captopril and carthamus tinc-torius extract,cardiac coefficient was significantly attenu-ated as well as the expression of MMP-2,MMP-9 in se-rum respectively.CONCLUSION: Carthamus tinctorius extract can prevent from the remodeling process of ventric-ularmuscles,which might be related with the expressive depression of MMP-2,MMP-9.

Development of cerebellum with 7 months orally phenytoin zinc in child-hood rabbits

PU Qi-song, YANG Jian-quan, LEI Jun, LI Chun-ping, LAN Da-rong, ZHANG Xiang, WU Ti-cheng, CAI Chun-yan

2005, 10(11):  1294-1298. 

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AIM: To investigate developing cerebel-lum with long-term orally phenytoin zinc(PZ)orpheny-toin sodium(PS)in the childhood rabbits.METHODS: One-month-old young rabbits were taken PZ orPS orally for7 months(doses:30 and 10 mg·kg^-1·d^-1).The rab-bits were performed forCT scans before,during and afteradministrated.Taken drugs end,brains were fixed with Brouin' s pourfrom carotid,separated and determined weight and width,length and height of the brain.RESULTS: In the high-dose grouPtreated with PS,at the 4 and 7 months crosscut of cerebellum were decreased by 14.0%(P<0.05)and 32.2%(P<0.01)and crosscut of vermis were decreased by 16.4%(P<0.05)and 30.8%(P<0.01)respectively compared with the control with CT scan analysis.In PZ high-dose grouPonly at 7months,crosscut of cerebellum and vermis were decreased by 16.1%(P<0.05)and 19.7%(P<0.01),respectively compared with the control by CT.In PS high-dose grouPthe width and length of fixed cere-bellum and vermis were more short than control,the wet weight and dehydrated weight with ethanol of the whole brain were decreased than control,the weight of whole brain and cerebellum was decreased by 15.4% and 18.4%respectively compared with control.Nevertheless in PZ grouPabove-mentioned determine were no differ-ence with control.CONCLUSION: Long-term use of PS may cause cerebellaratrophy in child rabbit,while PZ may lowerthe cerebellaratrophy.

Meta-analysis of efficacy of risperidone in combination with antidepressant and single antidepressant in treatment of depression

JIN Wei-dong, CHEN Jiong, TANG Xian-xiang, XING Bao-ping

2005, 10(11):  1299-1303. 

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AIM: to assess the differences in efficacy and safety between risperidone combing antidepressants and single antidepressant in treatment of depression.METHODS: 10 studies meeting ourcriteria were ana-lyzed by based-evidence medicine,comparing the differ-ence in efficacy,effect size(ES),full remission rate and side effects.RESULTS: Hoterogenity test:(1)efficacy,χ²=7.26,d_f=9,P>0.05;(2)safety,χ²=3.41,d_f=2,P>0.05.Comprehensive test:the comprehensive testing result between two groups at 1st,2nd,4th,6th,8th weekend were as following:Z₁=14.19,P<0.01;Z₂=14.00,P<0.01;Z₄=17.40,P<0.01;Z₆=12.10,P<0.01;Z₈=5.94,P<0.01.3.Effect size(ES):The effect size of two groups at 1st,2nd,4th,·1302·Chin J Clin Pharmacol Ther2005 Nov;10(11)6th,8th weekend are all respectively more than 0.5,and intervening effect size between two groups all more than 0.8.4.Efficacy:The full remission rate and significant effective rate of studying groups by fixed effect model and random effect model were highersignificantly than that of control groups,and ineffective rate were significantly low-erthan that of control groups.4.Side effect:No differ-ence in side effects between two groups was found(Z =0.20-1.15,P>0.05).CONCLUSION: It is a bettertherapy of patients with depression,especially treatment-resistant depression,combining antidepressants with lowerdosage of risperidone.

Effects of non-neuronal AChRs on proliferation of splenocytes of mice

WEN Xiao-ming, ZHANG Ying-li, LIN Xi-min, GUO Shun-xing, WANG Hai

2005, 10(11):  1304-1308. 

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AIM: To examine the effects of non-neu-ronal AChRs on the proliferation of splenocytes.METHODS: The effects of AChRs agonist carbachol on the prolif-eration of mice splenocytes stimulated by concanavalin measured by MTT reduction assay in vitro.RESULTS: The splenocytes responded to carbachol(in the range of 10^-11-10^-9mol·L^-1and 10^-5-10^-4mol·L^-1)byin-creased proliferation which were blocked by the muscarin-ic antagonist atropine(10^-7mol·L^-1).In contrast,car-bachol(10^-7-10^-6mol·L^-1)produced diminished pro-liferation,an effect which were blocked by the nAChRs antagonist mecamylamine(10^-7mol·L^-1).It suggests that mAChRs was sensitive to 10^-11-10^-9mol·L^-1and 10^-5-10^-4mol·L^-1carbachol,resulting in increasing proliferation and nAChRs responses to 10^-7~ 10^-6mol·L^-1carbachol leading to proliferation inhibition.CONCLUSION: Carbachol can elicit two different ef-fects according to different concentrations in splenocytes via non-neuronal mAChRs or nAChRs.

Statistical methods of Meta-analysis

YANG Juan, ZHENG Qing-shan

2005, 10(11):  1309-1314. 

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Meta-analysis is a statistical method to systematically combine and evaluate several relevant tri-als.It is applied generally in medical literatures,and it' s statistical methods are developing.The aim of this paperis to introduce several widely-used statistical methods of Meta-analysis.

Some thoughts on use of randomized controlled in individual patients in TCM researches

XU Wei-hua

2005, 10(11):  1315-1317. 

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This paperdescribed the design model of randomized controlled trial in individual patients(N of 1 RCTs)and the conditions of conducting this study de-sign,and also pointed out the key points to be considered in conducting an N of 1 RCTs in clinical trial of TCM,i.e.the implementation of blindness,selection of the con-trolled drug and effect indices,setting uPof wash-out pe-riod and the generalization of the study findings.

Risk management in clinical trails

HUANG Yu-hong, WANG Bao-he, ZOU Shu-xuan, SUN Zeng-tao, SHANG Hong-cai, ZHANG Bo-li

2005, 10(11):  1318-1320. 

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This paperintroduces the international ex-periments of risk management in clinical trails,responsi-bility of sponsor,responsibility of investigatorand respon-sibility of otherparticipators and to helPto improve ourmanagement level of clinical trails.