Table of Content

Volume 11 Issue 12
26 December 2006

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Sequelae of hypergastrinemia due to long-term administration of proton pumPinhibitors and its management

SHEN Jian, WU Jian-xin, LI Ding-guo

2006, 11(12):  1321-1325. 

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Proton pumPinhibitor (PPI) is considered as the standard treatment for acid-related disorders.However,its long-term use, especially in patients with gastroesophageal reflux disease, would cause potential risks,such as hypergastrinemia along with reduced gastric acidity,hyperplasia of enterochromaffin cells (ECL), gastric neoplasms, rebound gastric acid hypersecretion when PPI treatment is stopped, increased oxyntic gastritis in patients with H.pylori infection, and the possible stimulation of growth of non-gastric tumours due to hypergastrinaemia.Each of these trends has led to numerous studies and evaluations on the potential risk-benefit ratio of the long-term use of PPIs, and countermeasures are being proposed for these problems.

Research advances in pharmacogenomics of warfarin

YANG Jian, MIAO Li-yan

2006, 11(12):  1326-1331. 

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Warfarin is widely used as one of the coumarins anticoagulation drugs in the clinical.Every physician has been disturbed by its narrow therapic index and bleeding complications.It is a difficult thing for the doctor to use it rationally.However, recently, with the rapid development of molecule biology, some research find that gene polymorphism of pharmacodynamics and pharmacokinetics cause the individual variability in drug response.In this review,we focus on the latest development in pharmacogenomics of warfarin at home and abroad in order to give some suggestions for the individual use of warfarin.

Researeh progress for tumor ache

JIANG Shou-yang, YUAN Sheng-tao

2006, 11(12):  1332-1335. 

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Pain is a major symptom in patients suffering from cancer and also the most important factor which affects the quality of patients' lives.Cancer pain has unique mechanism from that of other kinds of pain.Recent years, there have established sorts of cancer pain models in rats and mice and modeled clinical pains caused by tumor intruding nerves or osseous metastasis, or pain of chemotherapy-induced peripheral neuropathy, and they have been used in evaluations of cancer pain treatment drugs.With the development of molecular biology technology and comprehend of pain mechanisms, relieve pain treatments in cell and gene levels as a new method have become an effective addition to traditional 3-stePanalgesic ladder.

Experimental study on antipyretic, analgesic and anti-inflammatory actions of cinnamaldehyde

MA Yue-ying, LI Cang-hai1, LI Lang-fang, ZHO Bao-sheng, GUO Shu-ying, HUO Hai-ru

2006, 11(12):  1336-1339. 

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AIM: To observe the antipyretic-analgesic and anti-inflammatory effects of cinnamaldehyde.METHODS: Febrile model of rats was induced by injecting fresh yeast subcutaneously.The pain models were established by acetic acid and hot plate in mice.The mice inflammatory models were applied by dimethylbenzene(auricle smearmethod)and HAc-induced peritoneal capillary permeability, respectively.RESULTS: Cinnamaldehyde depressed the fervescence by yeast effectively in rats, inhibited the pain evidently caused by acetic acid and hot plate in mice.At the same time, it was found that the mouse' s ear edema induced by dimethylbenzene and the capillary permeability were significantly suppressed by cinnamaldehyde.CONCLUSION: Cinnamaldehyde has remarkable antipyretic-analgesic and anti-inflammatory effects.

Establishment of in situ perfused rat intestine-liver model for evaluation on chlorogenic acid metabolism

WANG Su-jun, ZHANG Zhi-wei, ZHAO Yan-hong, ZHANG Zhen-qing, XIE Hai-tang, RUAN Jin-xiu

2006, 11(12):  1340-1344. 

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AIM: To establish a model of in situ perfused rat intestine-liver preparation and HPLC-MS method in the determination of chlorogenic acid, caffeic acid,hippuric acid and ferulic acid in perfusate, and investigate chlorogenic acid metabolism in intestine and liver of rats by the model.METHODS: Chlorogenic acid and its metabolites (caffeic acid, ferulic acid and hippuric acid)were detected by HPLC-MS from samples of in situ perfused rat intestine-liver model.RESULTS: Main active metabolite of chlorogenic acid is ferulic acid in in situ perfused rat intestine-liver model after intraduodenal injection to rats, and trace caffeic acid and abundant hippuric acid were also found in perfusate.CONCLUSION: In situ perfused rat intestine-liver models are suitable for the study of metabolism of chlorogenic acid in intestine and liver of rats.Chlorogenic acid was extensively metabolized in rat intestine.

Study of hemostatic effect and biocompatibility of RT-Q-remedial biomembrane

CHEN Zhong-hua, CHENG Wei-bo, YIN Zong-ning, TIAN Juan, CHEN Guo-jing

2006, 11(12):  1345-1349. 

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AIM: To investigate the hemostatic effect and biocompatibility of RT-Q-remedial biomembrane.METHODS: There were control, excipient, Shunkang and RT-Q grouPin topical bleeding experiment and control, excipient, and RT-Q grouPin topical biocompatibility experiment, in order to study the hemostatic effect on jugular vein of rat, and to observe the biodegradability and histocompatibility of RT-Q in muscle of rat legs.RESULTS: The hemostatic effect is significant compared with control grouPand excipient grouP(P<0.01), but there is no significant difference compared with Shunkang grouP(P>0.05).The biological evaluation for the biocompatibility is excellent.CONCLUSION: The significant hemostatic effect and good biocompatibility have been proved in topical bleeding of RT-Q.

Studies on correlation between pharmacodynemics and pharmacokenitics characteristics of baicalin using serum pharamoclogical test in rats

SONG Jue, LU Tong, XIE Lin, WANG Guang-ji, LIU Xiao-dong

2006, 11(12):  1350-1354. 

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AIM: To study the correlation between pharmacodynemics and pharmacokenitics characteristics of baicalin using serum pharamoclogical test in vitro.METHODS: After administration of baicalin in rats, the drug-contained serum was obtained at different time and each sample was divided into two portions.One portion was respectively added into the cultured PC12 cells,which had been treated with H2O2, and the viability was determined by MTT colormetric microassay.The otherwas used to determine the concentration of baicalin in each serum sample.Then the relationshiPamong concentration,time and effect could be established.Furthermore, the relationshiPof concentration-effect of bacalin solution was also investigated in vitro.RESULTS: Exact antioxidant effects of baicalin solution and drug-contained serum could be shown in vitro test.The curves of time-effect and time-concentration were both peaked at 15 min after oral administration.CONCLUSION: The protection rate of the baicalin-contained serum had a positive correlation with the AUC of baicalin in serum.

Effect of atorvastatin on intracellular cholesterol content and efflux of macrophages separated from diabetic hamster

ZHU Ying, YAN Xiao-wei, CHEN Lian-feng, WANG Jing-feng, FANG Quan

2006, 11(12):  1355-1359. 

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AIM: To examine the effect of atorvastatin on the intercellular cholesterol content and efflux of diabetic golden hamster models, and to further explore the mechanism about inhibition of atorvastatin on progress of atherosclerotic score.METHODS: We established diabetic golden hamstermodels.Peritoneal macrophages were isolated, purified and cultured in vitro.Then macrophages were incubated with atorvastatin of different concentrations in vitro.Intracellular cholesterol content was determined with combination of enzymatic method and HPLC before and after atorvastatin treatments.RT-PCR was carried out to examine the expression of ABCA1mRNA in macrophages.RESULTS: Atorvastatin, by cooperation with apoA1, can promote intracellular cholesterol efflux significantly, which may be mediated by activation of cholesterol ester hydrolase and by promotion of ABCA1 expression in macrophages.CONCLUSION: Atorvastatin can increase ABCA1 mediated intracellular cholesterol efflux.

Effect of phagotrophic ability of marcophage on pseudomonas aeruginosa

GU Xiao-hua, SHEN Ce

2006, 11(12):  1360-1363. 

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AIM: To observe the effect of phagotrophic ability of macrophage on pseudomonas aeruginosa which was cocultured with low concentration of erythromycin.METHODS: The pseudomonas aeruginosa ATCC 27853 was cultured in LB both with low concentration of erythromycin (GrouPA) and without erythromycin (GrouPB) for 18 h separately, then incubated with macrophage from murine abdominal cavity for 2 h.The ratio of phagocytosis of macrophage was determined by microscope detection.RESULTS: The ratio of phagocytosis of grouPA in which erythromycin was added was higher than the grouPB, and the pseudopodia of macrophage were increased in the grouPA under electron microscope.CONCLUSION: Low concentration of erythromycin may enhance the phagocytosis ability of macrophage in vitro by influencing the virulent factors of PA.

Changes of intracellular reactive oxygen species and Ca²⁺levels of K562 cells in process of apoptosis induced by simvastatin

HUANG Wen-fang, ZENG Ya-li, LIU Hua, YANG Yong-chang, ZHOU Ding-an

2006, 11(12):  1364-1368. 

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AIM: To investigate the changes of reactive oxygen species (ROS) and Ca^{2 +}levels in K562 cellsinduced by simvastatin to predict the mechanism of apoptosis.METHODS: K562 cells cultivated in routinemethod were treated with 20 μmol·L^-1simvastatin.Themorphology change was observed under light microscope after 24 h.Flow cytometry assay was used to detect the apoptotic ratio, the ROS and the Ca2⁺levels.RESULTS: 24 h after K562 cells had been treated with 20μmol·L^-1simvastatin, there were some morphological changes of the cells such as karyopyknosis, nuclear fragmentation and apoptotic body emerged.AnnexinV-FITC/PI was used to detect the apoptic ratio of K562 cells, the apoptotic ratio of treated groups was markedly increased compared with the control groups in a time-dependent manner.ROS, which was detected by 2', 7' -dichloro fluorescein diacetate (DCFH-DA), was markedly increased in treated groups compared with the control groups at different time points (12, 24, 48, 72 h), and the level ROS got its peak time after 24 h.The Ca^{2 +}, which was detected by Fluo-3AM, was markedly increased in treated groups compared with the control groups at different time points, and the level ROS got its peak time after 12 h.CONCLUSION: K562 cells can be induced toapoptosis by simvastatin.The potential mechanism of apoptosis might be related to the increase of ROS and Ca²⁺level.

Protective effect of total flavones of Bidens pilosa L on experimental liver ibrosis in rats

CHEN Fei-hu, YUAN Li-ping, ZHONG Ming-mei, XIA Li-juan, LI Jun

2006, 11(12):  1369-1374. 

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AIM: To observe the curative effect of total lavones of Bidens pilosa L (TFB) on experimental liver ibrosis in rats.METHODS: Rat liver fibrosis model as established by subcutaneous injection (s.c.) of 50 % Cl4 twice a week lasting for 18 weeks.TFB (160, 80,40 mg·kg^-1) was treated gastrogavage (i.g.) daily since he 9th week.The spleen and liver weights were eighed. The contents of alanine aminotransferaseALT), aspartate aminotransferase (AST), hydroxyproline(Hyp), malondialdehyde (MDA) and glutathione eroxidase (GSH-Px) in liver tissue were assayed using he corresponding kits.The hyaluronic acid (HA), procollagen II (PC Ⅲ) and C Ⅳcontents in serum were also ssessed by radioimmunoassay.Liver samples collected fter experiment were stained with hematoxylin-eosinHE) and Masson and scored.Moreover, electron microscope as used to observe ultramicrosrtucture of the cells n livers.RESULTS: CCl4 caused liver fibrosis, featuring ncreases in spleen and liver weights, serum ALT,AST, HA, PC Ⅲ, C Ⅳ, and liver MDA and HyPcontents,a decrease in liver GSH-Px activity.Compared with odel group, TFB (160, 80 mg·kg^-1) treatment significantly educed spleen and liver weight, serum ALT,AST, HA, PC Ⅲ, C Ⅳ, liver MDA andHyPcontent (P<0.01).Moreover, TFB 160 or 80 mg·kg-1 could increase iver GSH-Px activity (P<0.01).Fibrosis changes f liver histology was also improved in TFB (80, 160 g·kg^-1) -treated rats (P<0.05).CONCLUSION: TFB significantly reduced CCl4-induced liver fibrosis in ats, probably through exerting a protective effect by its ree-radical scavenging ability.

Reactive oxygen species play an important role in arsenic trioxide-induced apoptosis of multi-drug resistant K562/ADM cells

ZHANG Ya-li, WEI Hu-lai, GUO Lu

2006, 11(12):  1375-1379. 

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AIM: To discuss the role of the reactive oxygen species (ROS) and relationshiPbetween ROS and expression of mdr1/P-gPduring apoptosis induced by arsenic trioxide (As₂O₃) in multidrug-resistant human leukemia K562/ADM cells.METHODS: The cell proliferating activity was assessed with MTT assay.The cell apoptosis was determined by annexin Ⅴ/PI staining.ROS was labelled by DCFH-DA and examined by flow cytometry.Expression of mdr1 mRNA and P-gPwere detected by RT-PCR and flow cytometry, respectively.The contents of adriamycin (ADM) were detected by flow cytometry.RESULTS: As2O3 inhibited K562/ADM cells growth effectively, and the apoptosis rate of the cells by Annexin Ⅴ/PI staining was obviously increased.During apoptosis induced by 2 to 5 μmol·L^-1As₂O₃, the level of ROS was markedly decreased;the expression of mdr1 mRNA and P-gPwere significantly down-regulated, and the function of P-gPwas restrained so that the content of ADM increased in the cells.CONCLUSION: As₂O₃inhibits the proliferation activity and reverses phenomena of P-gp-mediated multidrug-resistance and apoptosis resistance in drug-resistant K562/ADM cells.The possible mechanism is down-regulation of mdr1/P-gPexpression via declines of ROS activity.

Effects of silybin-phosphatidylcholine compound on expressions of collagens in fibrotic liver induced by dimethylnitrosamine in rats

ZHU Yue-ke, DUAN Zhong-ping, ZHU Ji-dong, WANG Bao-en, LIU Fang, XIE Xian-chun

2006, 11(12):  1380-1384. 

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AIM: To investigate the effects of silybinphosphatidylcholine compound (SPC) on expressions of collagens type I and III in the fibrotic liver.METHODS: Wistar rats were randomly divided into normal control group, model group, SPC intervened group, model control group, and SPC therapeutic group.The animal models of liver fibrosis were induced by intraperitoneal injection with dimethylnitrosamine (DMN).Liver fibrosis stages were evaluated on the liver tissue sections which were performed with HE and Reticulation' s stain.Semiquantitive RT-PCR was performed to determine mRNA levels of collagens type I and III in liver tissues.Immunohistochemical staining was performed to show the positive expression of collagens type I and III in liver tissues.RESULTS: Compared with model group, liver fibrosis stage in SPC intervened grouPwas obviously lowered.Compared with model control group, the liver fibrosis was significantly relieved after SPC' s therapy.In intervened and therapeutic groups, the liver tissue' s mRNA levels of collagen type I and III were all obviously lower than those in the model and model control groups, respectively.In intervened and therapeutic groups, the positive expressions in liver tissues of collagens type I and III were all much weaker than those in the model and model control groups, respectively.CONCLUSION: Silybin has the positively preventive and therapeutic effects on the experimental liver fibrosis induced by DMN in rats, and inhibiting the expression of collagens type I and III in liver tissues is one of the anti-fibrosis mechanisms of SPC.

Isosorbide dinitrate induces late preconditioning against myocardial infarction in rats

WANG Zhan-qing, WANG Jin-ping, XU Jing-feng

2006, 11(12):  1385-1388. 

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AIM: To determine whether isosorbide dinitrate (ISDN) could induce late ischemic preconditioning in rats.METHODS: SD rats were divided into oral normal saline (control group), oral ISDN (0.2mg·kg^-1, ISDN group), SHAM grouP;oral normal saline combined with ischemia and reperfusion(I/R) (I/R control group), ISDN plus I/R group, ISDN plus Gly plus I/R group, Gly plus I/R control grouPand late ischemic preconditioning grouP(3 cycles of 5-min coronary occlusion 5-min reperfusion, LPC group).24 h later,rats, like other groups with I/R, were underwent a 40 min coronary occlusion followed by 1.5 h of reperfusion.RESULTS: Myocardial infarct size and the levels of creatine kinase (CK) in serum were significantly reduced after pretreated with ISDN +I/R versus I R control group(P<0.05), so was lactate dehydrogenase (LDH) (P<0.01).Nitric oxide and Mn-superoxide dismutase in heart tissue were significantly elevated, while MDA was significantly reduced (P<0.05).The level of induced nitric oxide synthetase (iNOS) in heart tissue was significantly elevated in the ISDN grouPcompared with controls(P<0.01).CONCLUSION: ISDN induces delayed cardioprotection against myocardial infarction similar to that afforded by the late phase of ischemic PC, possibly by up-regulating NO and iNOS, and strengthening antioxidant mechanism.

Effect of angiotensin-(1-7) on intimal hyperplasia and blood flow in carotid artery after adventitia removal in spontaneously hypertensive rats

WANG An-cai, LI Jun, CAO Heng, WANG Jun-yuan, CAO Xiao-xia, WU Ming

2006, 11(12):  1389-1394. 

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AIM: To investigate the effect of angiotensin-(1-7) on intimal hyperplasia and blood flow in carotidartery after adventitia removal in SHR.METHODS: Twenty-four spontaneously hypertensive rats(SHR) with right carotid artery adventitia removed were randomly divided into 3 groups (n =8, each):Ang-(1-7), Ang779 and SHR control group.Eight Wistar-Kyoto rats were selected as normal control grouP(WKY group).Adventitia in right carotid artery was removed by mechanical and chemical means.Adventitia in left carotid artery was sham-operated. Ang-(1-7) in saline (25μg·kg^-1·h^-1) was infused intravenously for 14 days.The systolic blood pressure (SBP) was taken.The velocity of carotid artery was detected by electromagnetic rheometer.Plasma and carotid artery angiotensin II (Ang Ⅱ)levels were measured by radioimmunoassay.The intimal hyperplasia was measured by computed video processing.The expression of local angiotensin II type 1 receptor(AT1R) protein in both arteries was determined by immunohistochemistry method.The apoptosis of vascular tissue cell in carotid artery was evaluated by terminal deoxynucleotidyl transferase-mediated DutPnick-end labeling(TUNEL) assay and measured by image analyse system.RESULTS: SBPin Ang-(1-7) grouPwas significantly lower than that in Ang779 and SHR grouP(all P<0.01).Compared with Ang779 and SHR group, the carotid blood flow in no adventitia removal in Ang-(1-7)grouPwas increased significantly (P<0.01).Compared with no adventitia removal, the intimal hyperplasia in adventitia removal was exacerbated significantly (P<0.05), and it was markedly inhibited in Ang-(1-7)grouP(P<0.01).Carotid artery Ang Ⅱlevel in adventitia removal was significantly higher than that in no adventitia removal (P<0.01).Ang-(1-7) had no significantly effect on plasma and local Ang Ⅱlevels (P>0.05).The expression of AT1R protein in adventitia removal was significantly higher than that in no adventitia removal in SHR and Ang779 group.Compared with Ang779 and SHR group, the expression of AT1R protein in Ang-(1-7) grouPwas down-regulated significantly (all P<0.01).Compared with Ang779 and SHR group, apoptotic index in adventitia removal and no adventitia removal in Ang-(1-7) grouPwas increased significantly (all P<0.01).CONCLUSION: Ang-(1-7) can significantly improve intimal hyperplasia and increase blood flow in carotid artery with adventitia removal in SHR, which may be related to the down-regulation of local AT1 R protein.

Simultaneous measurement of magnesium isoglycyrrhizinate and glycyrrhetic acid in plasma of dog by HPLC

LIU Su-yi, WANG Qing-min, CAO Cong, DING Jian-hua, HU Gang

2006, 11(12):  1395-1400. 

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AIM: To quantify magnesium isoglycyrrhizinate(MGL) and glycyrrhetic acid in the plasma of dog by develoPa simple, rapid, sensitive high-performance liquid chromatography (HPLC-UV) method.METHODS: HPLC-UV methods with wavelength 252 nm were used for the quantitation of MGL and GA in plasma.The concentration of MGL and GA were assayed on a Kromasil ODS-1 C18 column with the column temperature 25 ℃.The mobile phase was a gradient system with 0.1 % diethylamine in water (pH 4.60) and acetonitrile at a flow rate of 1.0 ml·min^-1.RESULTS: There was a good linear response range of 0.2 -2.5 mg·L^-1and 2.5 -100 mg·L^-1, while the limit of quantification was 0.2mg·ml^-1.The relative recovery rate of MGL was 94.3 %-101.9 %, GA 96.4 %-101.9 % (n =5);the absolute recovery rate was MGL 78.7 % -87.0 %, GA 77.5 %-87.7 % (n =5).The intra-day and inter-day variations were all less than 15 % (n =5).The plasma samples preserved in refrigerator is stable at -20 ℃ for 14 days, freeze thawing 3 times and at room temperature for 10 h without degradation.CONCLUSION: This method is shown to be specific, sensitive, reliable and suitable for the quantitative determination of magnesium isoglycyrrhizinate following oral administration in biological sample.

Randomized controlled multicenter clinical trial of cefmenoxime hydrochloride for injection in treatment of acute bacterial infections

XU Ling-yun, XIONG Sheng-dao, LIU Xiao-cheng, YANG Jiong, DING Guo-hua, XU Qi-yong, XU Lian-fang5, YIN Ping, JING Shu-fang, ZENG Fan-dian

2006, 11(12):  1401-1407. 

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AIM: To evaluate the clinical efficacy and safety of domestic cefmenoxime hydrochloride for injection in the treatment of acute bacterial infections.METHODS: A randomized, comparative, single-blind,multicenter clinical trial of domestic cefmenoxime hydrochloride injection (test) and cefmenoxime hydrochloride injection (Bestcall) made in Japan (control) in the treatment of respiratory and urinary tract infections were conducted.The test drug and control drug were administrated intravenously at a dose of 1.0 g bid for 7 to 10 days, re-spectively.Among ITT (intention-to-treat) population,71 patients were enrolled in test grouPand 68 patients in control group.Among PP(per-protocol) population, 68 patients were evaluated in test grouPand 64 patients in control group.RESULTS: All the results were analyzed on the basis of ITT and PPpopulation.The clinical efficacy rates for test and control grouPwere separately 88.7 %(ITT), 92.7 %(PP) and 86.8 %(ITT), 92.2 %(PP).The bacterial eradication rates were 96.7 % and 94.6 %, respectively.The incidences of adverse reaction were 5.6 %and 7.4 %, respectively.There were no significant differences between the two groups (P>0.05).ITT and PPanalysis revealed similar result.CONCLUSION: The domestic cefmenoxime hydrochloride injection has an excellent clinical efficacy and good safety profile in treating patients with acute bacterial infection as the controldrug.

Comparative study of cisplatin plus gemcitabine versus cisplatin plus vinorelbine in patients with advanced stage non-small cell lung cancer

ZHAO Wen-ying, JI Zhao-ning

2006, 11(12):  1408-1411. 

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AIM: To explore the differences of efficacy and side-effects in advanced stage non-small cell lung cancer (NSCLC) patients treated with gemcitabine plus cisplatin or vinorelbine plus cisplatin.METHODS: Eligible patients were randomly assigned to GP(gemcitabine+cisplatin) grouPor NP(vinorelbine plus cisplatin)group.In GPgroup, 36 evaluable patients were treated with gemcitabine 1000 mg·m^-2IV on day 1 and 8 and cisplatin 75 mg·m^-2IV which was divided into 1 -3 days dosing, in a 21 days per cycle manner.In NPgroup, 30 evaluable patients were treated with vinorelbine 25 mg·m^-2IV on day 1 and 8 and cisplatin 80 mg·m^-2IV which was divided into 1 -3 days dosing, 21 days per cycle.All the patients at least received two cycles therapy.The response rate, median survival time (MST), l year survival, and side-effects were observed.RESULTS: The response rates were 41.6 % vs 36.7 %;MST were 10.3 months vs 9.6 months;1 year survival rate were 44.4 %vs 40.0 %(P=0.33) in GPgrouPand NPgroup, respectively.III-IV grade thrombocytopenia toxicity incurred significantly higher in GPgrouPthan in NPgroup, with the occurrence rate being 47.2 % vs 6.6 % (P<0.01).However, III-IV grade granulocytopenia was significantly less incurred in GPgrouPthan in NPgroup, 33.3 % vs 60.0 % (P<0.05).CONCLUSION: Our study demonstrates that GP(gemcitabine +cisplatin) regime and NP(vinorelbine plus cisplatin) regime are equivalent in treating advanced NSCLC, however they have few different toxicities.

Protective effects of nimodipine liposomes for injection on injuries of total cerebral ischemia reperfusion in rats and anoxia in mice

YANG Juan, WANG Qiu-juan, PAN Zhi-wei, ZHU Jia-bi

2006, 11(12):  1412-1415. 

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AIM: To study the protective effects of nimodipine liposomes for injection (NDLI) on injuries of total cerebral ischemia/reperfusion(I/R) in rats and anoxia in mice.METHODS: Acute anoxia in mice was produced by hypoxia under normal pressure and decapitation.In these two models the survival time and persistent time of gasping were observed.Ameliorated pulsinelli four-vessel occlusion method was used to make global brain ischemia model.The EEG, the time of righting reflex recovery and Evans blue content in the homogenate of the brain tissues were recorded.RESULTS: NDLI obviously prolonged the survival time and persistent time of gasping in mice subjected to acute anoxia, remarkably shortened the time of EEG recovery and righting reflex recovery, and reduced Evens blue content in the homogenate.CONCLUSION: NDLI has significantly protective effects on injuries of total cerebral I/R and anoxia.

Efficacy of rabeprazole-based triple therapy in treatment of helicobacter pylori positive patient with portal hypertension gastric disease

PENG Xuan-jie

2006, 11(12):  1416-1419. 

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AIM: To compare the efficacy of rabeprazole-based triple therapy in the treatment of helicobacter pylori (H.pylori)-positive patient with portal hypertension gastric disease (PHG).METHODS: We selected 62 consecutive H.pylori positive patients with portal hypertension gastric disease and randomized them into 2 Chin J Clin Pharmacol Ther 2006 Dec;11(12) groups.The RFA grouPwas treated with rabeprazole 10 mg bid (rabeprazole-group, n =32), and the OFA grouPwas treated with omeprazole 20 mg bid (omeprazolegroup,n =30) for 1 week, all patients were given amoxicillin 1 g bid and furazolidone 100 mg bid for one week meawhile.One month after treatment, the eradication rate of H.pylori was valuated according to result of C¹⁴ureabreath test and helicobacter pylori stool antigen.RESULTS: The eradication rate of H.pylori for patients in RFA grouPand OFA grouPwere 81.3 % % vs 73.3 % by intention to treat analysis and 89.7 % vs 81.5 % by per protocol (P>0.05).Few major severe adverse events were reported.The mild-moderate side effect rate in RFA grouPand OFA grouPwere 28.1 % and 53.3 %,respectively (P<0.05).The levels of serum total bilirubin(STB) and alanine aminotransferase (ALT) after treatment were significantly higher than that before treatment in OFA group.The significant increases of STB and ALT after treatment had not found in RFA group.CONCLUSION: For the patients with portal hypertension gastric disease, there is no significant difference between the two groups in terms of the eradication rate of H.pylori(P>0.05), but RFA grouPis obviously lower than the OFA grouPin the side-effect of drugs, so it is an ideal therapy.

Effects of operation wound on both endothelin and calcitonin gene-related peptide in hematoplasma of patients

ZHU Liang-hong, CHENG Guang-hua, ZHANG Xin-lu

2006, 11(12):  1420-1422. 

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AIM: To investigate the effects of major operation wound on both endothelin (ET) and calcitonin gene-related peptide (CGRP) in hematoplasma of patients.METHODS: We measured both endothelin and calcitonin gene-related peptide in hematoplasma during perioperative period for 30 patients who underwent Ⅲcategory operation and for 15 patients who underwent Ⅳcategory operation.RESULTS: After operation, ET and CGRPin hematoplasma of both groups who underwent Ⅲcategory and Ⅳcategory operation were significantly increased compared with those before operation (P<0.01);ET in hematoplasma after operation was not statistically significant between the two groups.CGRPin hematoplasma after operation in the grouPwho underwent Ⅳcategory operation was increased markedly vs the grouPwho underwent Ⅲcategory operation (P<0.05).CONCLUSION: Operation wound can increase ET and CGRPin hematoplasma, and the extent of increasing CGRPis probably related to that of operation wound.

Determination of oxymatrine concentrations in plasma by RP-HPLC with solid phase extraction method and study on its bioequivalent

HU Min, XU Wen-wei, XIA Chun-hua, XIONG Yu-qing

2006, 11(12):  1423-1426. 

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AIM: To develoPa reversed RP-HPLC method for the study of pharmacokinetics and bioavailability of oxymatrine in male volunteers.METHODS: 1.0 ml plasma sample was applied to C18 cartridges activated with methanol.After washing, the cartridge was eluted with 2 ml mixed liquor of methanol and chloroform.The elution was evaporated to dryness with nitrogen gas at 60 ℃.The residue was dissolved with 80 μl mobile phase solution, and 20 μl was injected onto a Diamonsil ODS C₁₈column (5 μm, 4.6 mm ×150 mm).The mobile phase was 0.005 mol·L^-1sodium heptanesulfonate (pH=3.5, adjusted with H3PO4) -acetonitrile (80∶20).The flow rate was 1.0 ml·min^-1.An ultraviolet detector was set at 220 nm wavelength to monitor eluted components.A single oral dose of 600 mg of oxymatrine dispersible tablet and oxymatrine capsule was given to each of 18 healthy volunteers in an open randomized two-way crossover design.RESULTS: The linear range was 0.025 -1.600 mg·L^-1, r =0.9999.The limit of determination was 0.025 mg·L^-1.The method recovery was 96.5 %-110.2 %.Within-day precision (RSD) and between-day precision (RSD) were less than 10 %.The main pharmacokinetic parameters obtained showed no statistically significant difference between two preparations.CONCLUSION: The method is sensitive, specific and reproducible for the determination of oxymatrine concentration in human plasma.Two products are bioequivalent.

Effects of Danzhi capsule on endothelial function assessed by Doppler ultrasonograph

NI Ying-qun, FANG Zhao-hui, WANG Fei

2006, 11(12):  1427-1429. 

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AIM: To assess the protective effects of Danzhi capsule (DZC) on vascular endothelial function of type 2 diabetes mellitus by Doppler ultrasonograph.METHODS: 46 patients were randomly divided into two groups, DZC treated grouP(n =24) and western medicine control grouP(n =22).Endothelial function was assessed simultaneously by B mode ultrasonography before and after treatment due to the change in diameter of the brachial artery during reactive hyperemia and in response to taking nitroglycerin sublingually.At the same time,the insulin resistance index, free fatty acid, and fasting blood sugar and change in serum insulin were observed before and after treatment for the two groups.RESULTS: Compared with control group, index of insulin resistance (IR), index of insulin sensitive index, EDVR and NID of DZC grouPwere improved significantly (P<0.05).CONCLUSION: DZC can significantly improve the endothelial function, alleviate IR and delay the occurrence of chronic complication.

Effects of telmisartan on serum uric acid metabolism and microalbuminuria excretion in patients with mild to moderate essential hypertension

ZHU Ji-ji

2006, 11(12):  1430-1432. 

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AIM: To observe the effects of telmisartan on serum uric acid metabolism and microalbuminuria excretion in patients with mild to moderate essential hypertension.METHODS: 88 patients with mild to moderate essential hypertension were randomly divided into reatment grouP(n =44)and control grouP(n =44).Patients of the treatment grouPreceived telmisartan 40 mg.o.q.d.for 2 weeks, and those of control grouPreceived elodipine 5mg p.o.q.d.for 2 weeks, then, followed y a doubling dose for another 2 weeks in those patients ith seated diastolic blood pressure ≥90 mmHg or ystolic blood pressure ≥140mmHg.Before and after the herapy of telmisartan or felodipine, blood pressure, serum ric acid and microalbuminuria of the patients were easured.RESULTS: Both SBPand DBPdecreased in wo groups after the treatment.In telmisartan grouPdecreasing erum uric acid level was better than that in felodipine rouP(P<0.01).Rate of decrease of excretion ate of urinary albumin in telmisartan grouPwas much etter than that in felodipine grouP(P<0.01).CONCLUSION: Telmisartan can not only reduce blood pressure but also decrease the level of serum uric acid, as well as the excretion of urinary albumin.

Simply introduced the application of grouPsequential design in clinical test

LI Xian-tao, LIANG Wei-xiong, ZHANG Bo-li

2006, 11(12):  1433-1436. 

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In clinical trials, interim analyses are usually performed for ethical or economical reasons.GrouPsequential design was the method of interim analysis recommended by ICH-GCP.The principle of grouPsequential design and its several questions:times of interim analysis, the value of statistic test, the sample estimate,selection of endpoints and others were introduced in this article.

Item charge and the accounting management of bioequivalent trial in human

XIAO Da-wei

2006, 11(12):  1437-1440. 

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The bioequivalent test in human belongs to clinical trial range.The medical institutions should strictly carry out the state laws and obey rules and regulations,the good clinical practice, and the interrelated clinical trial international laws.In technology, all clinical activity should try its best to the demand of standard operation procedure and to accord with the different principle of technique guidance and the standards.The items of charge and accounting management should be specification and reasonable.The prices gradually tend to its perfecting system.