Table of Content

Volume 11 Issue 10
26 October 2006

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Research progress of xanthine oxidoreductase in biological functions and its inhibitor development

ZHU Shen-yin, ZHOU Yuan-da, DU Guan-hua

2006, 11(10):  1081-1086. 

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xanthine oxidoreductase(XOR)is a member of the molybdoenzyme family and best known for its catalytic role in purine degradation , metabolizing hypoxanthine and xanthine to uric acid with concomitant generation of superoxide and hydrogen peroxide.In addition to its role in the pathophysiology of hyperuricaemia and gout , the role for XOR beyond purine metabolism was first suggested in ischaemia-reperfusion injury , there is growing evidence that it also participates in endothelial dysfunction,hypertension and heart failure.Importantly , the XOR inhibitor attenuates dysfunction especially in heart failure caused by XOR in these disease states.Attention to the broader range of XOR bioactivity in the cardiovascular system has prompted strong interest based XOR drug development by pharmaceuticals company.

Recent advances in study of endothelium-dependent hyperpolarizing factor

FAN Yi-fei, KONG De-hu, CHEN Zhi-wu, GAO Shan

2006, 11(10):  1087-1091. 

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Besides cyclooxygenase and nitric oxide synthase, another distinct endothelial pathway, endothelium-dependent hyperpolarization factor (EDHF) , is involved in relaxation of the vascular smooth muscle cells.EDHF has been demonstrated unequivocally in various blood vessels from different species, including human,and is likely to play an important role in cardiovascular physiology and pharmacology.

Latest clinical application and development of gene medicine

XU Rui-an, DIAO Yong, XIE Hai-tang

2006, 11(10):  1092-1097. 

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The clinical trials of gene and cell therapies for diseases, which are difficult to treat by current medical methods, at are an active stage.The novel clinical practice, progress of gene and cell therapy in cancer and nerve system disorder, the safety concerns and the gene express duration exploration are reviewed here.New strategy such as developing new cancer targeted vector,optimization of gene delivery route, and combination with stem cell technology are discussed.

Expression of intracellular adhesion molecule-1 in endothelial cells following experimental subarachnoid hemorrhage and effect of ecdysterone

CHEN Zhi, LIU Zhi, TANG Wei-hua, ZHU Gang, WANG Xian-rong, FENG Hua

2006, 11(10):  1098-1101. 

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AIM: Artificial bloody cerebrospinal fluid(BCSF) was used as pathogeny on human umbilical vein endothelial cells (HUVECs) to mimic SAH status in vivo.We tried to explore expression of ICAM-1 in HUVECs and the effect of ecdysterone (EDS).METHODS: HUVECs were used for study.BCSF was added into the culture with or without ecdysterone (200 mg·L^-1) for 24 h,and then immunocytochemistry and RT-PCR were used to observe ICAM-1 expression in HUVECs.RESULTS: Following BCSF stimulation, both of immunocytochemistry and expression of ICAM-1 mRNA increased in HUVECs.EDS could reduce the expression of ICAM-1 in HUVECs following BCSF stimulation.CONCLUSION: ICAM-1expression in HUVECs could be activated directly by BCSF and reduced by EDS.EDS is possible to be a valid candidate medicine in therapy of CVS.

A simple and repeatable orthotopic model of the A549 cell line in nude mice

KANG Kai, MA Bing-liang

2006, 11(10):  1102-1105. 

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AIM: To establish a simple and repeatable orthotopic animal model of the A549 cell line.METHODS: A549 cells in matrigel were inoculated into left lung or right flank of nude mouse.The growth pattern of A549 tumors and the chemotherapeutic efficacy of carboplatinum were studied.RESULTS: Tumors generated and dispersed widespreadly to contralateral lung.Tumors in lung were less susceptible to carboplatinum than those growing in flank.CONCLUSION: A simple and repeatable orthotopic animal model of the A549 cell line was presented,this allows researchers to evaluate novel compounds and new drugs for treatment of human lung cancer.

Effect of ischemic postconditioning on neurocyte apoptosis and expression of eNOS and iNOS protein in cerebral ischemic reperfusion injury rats

FANG Fang, WANG Wan-ling, YU Shu-yi, ZHANG Hui, XIE Li-xin, FANG Yun-xiang

2006, 11(10):  1106-1109. 

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AIM: To investigate the effects of postconditioning on neuron apoptosis and expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) protein in local cerebral ischemic reperfusion rats via middle cerebral artery occlusion(MCAO).METHODS: Fifty male Sprague-Dawley rats were randomized into five groups (n =10, each group) ,sham-operated group, MCAO group, preconditioning combined MCAO group, postconditioning combined MCAO grouPand nimodipine combined MCAO group.In the preconditioning groups animals were subject to 2 cycles of 2-min ischemia and 20-min reperfusion of the bilateral carotid arteries 24 h before middle cerebral artery occlusion.In the postconditioning groups animals were subject to 3 cycles of 20-second ischemia and 20-second reperfusion of the MCAO before reperfusion.At the 24^th hour after reperfusion, the rat brains were obtained for detecting eNOS and iNOS protein expression by immunohistochemistry method.RESULTS: In the postconditioning groups, the apoptotic cells were significantly decreased(P<0.05) ;the expression of eNOS protein was significantly increased (P<0.05) ;on the contrary, that of iNOS protein was significantly decreased (P<0.01).CONCLUSION: The postconditioning can prevent apoptosis in local cerebral ischemic reperfusion model rats due to the enhanced expression of eNOS protein and decreased expression of iNOS protein.

Lomerizine inhibits activity of P-glycoprotein in primary cultured brain microvessel endothelial cell monolayers

LI Yun-man, KANG Kai, FANG Wei-rong

2006, 11(10):  1110-1114. 

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AIM: To study the effect of Lomerizine on the activity of P-glycoprotein (P-gp)in the bloodbrain barrier(BBB)and search for novel effective P-gPinhibiting agent against multidrug resistance.METHODS: Rhodamine123 (Rh123)was used to examine the activity of P-gPand RT-PCR to study the mdr mRNA expression in cultured rat brain microvessel endothelial cells (RBMECs).RESULTS: Lomerizine could increase the cellular Rh123 in RBMECs in a concentration-dependent manner.RT-PCR indicated that lomerizine could not down-regulate the expression of mdr mRNA.CONCLUSION: Lomerizine can reverse multidrug resistance in the blood-brain barrier by inhibiting the activity of P-gp.

Effect of salvia miltiorrhiza on cardiomyocyte apoptosis in spontaneously hypertensive rats

YANG Hai-bo, DENG Jie, WANG Ming-ming, ZHENG Zhi

2006, 11(10):  1115-1118. 

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AIM: To observe the effect of salvia miltiorrhiza on cardiomyocyte apoptosis in spontaneously hypertensive rats (SHR).METHODS: 18 male SHR were divided into 3 groups at random (n =6, each):the base group, in which rats were killed in the 8th week ;the salvia group, in which salvia miltiorrhiza (1g·kg^-1·d^-1) was injected intraperitoneally from the 8^th week to the 18th week ;the control group, in which the same volume of vehicle was injected in the same manner.Systolic blood pressure (SBP) and left ventricular mass index (LVMI) were measured.The TUNEL method was employed to evaluate cardiomyocyte apoptosis, and the immunohistochemistry method was applied to detect the protein expression of Bcl-2.RESULTS: Compared with the base group, the SBP, LVMI and apoptosis index increased markedly in control grouP(P<0.05).Simultaneously,the positive expression index of Bcl-2 protein decreased significantly in control grouP(P<0.05).Treated with salvia miltiorrhiza, the LVMI and cardiomyocyte apoptosis decreased.Simultaneously, the positive expression index of Bcl-2 protein increased, whereas SBPchanged slightly but significantly (P<0.05).CONCLUSION: The study shows that chronic use of salvia miltiorrhiza can upgrade the protein expression of Bcl-2 gene, decrease the cardiomyocyte apoptosis and inhibit the development of left ventricular hypertrophy in spontaneously hypertensive rats.

Effect of dexamethasone on eosinophil apoptosis and expression of interleukin-5 mRNA and interleukin-10 mRNA in bronchoalveolar lavage fluid of asthmatic guinea pig

LUO Guang-wei, SUN Jie-min, CHEN Jing

2006, 11(10):  1119-1121. 

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AIM: To investigate the effect of dexamethasone on eosinophil apoptosis and expression of interleukin-5 mRNA and interleukin-10 mRNA in bronchoalveolar lavage fluid (BALF) of asthmatic guinea pig.METHODS: 30 Hartley male guinea pigs were divided into 3 groups randomly:dexamethasone group, asthma grouPand control group.The EOS apoptosis, IL-5mRNA and IL-10 mRNA expressions were measured by the techniques of TUNEL and RT-PCR.RESULTS: The EOS in BALF of dexamethasone grouPdecreased prominently compared with the asthma grouP(P<0.01) ;the EOS apoptosis increased (P<0.01) significantly.The level of IL-5 mRNA was prominently lower than that of the asthma grouP(P<0.05).The level of IL-10mRNA increased markedly compared with the asthma grouP(P<0.05).CONCLUSION: Dexamethasone can restrain the EOS ascending, increase EOS apoptosis effectively through reducing the expression of IL-5 mRNA and increasing the expression of IL-10 mRNA in asthmatic guinea pigs'respiratory passage.

Effect of iptakalim hydrochloride on extracellular matrix of kidney in spontaneously hypertensive rats

XUE Hao, GAO Min, LIU Guo-shu, WANG Hai

2006, 11(10):  1122-1128. 

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AIM: To investigate the effects of iptakalim hydrochloride (Ipt) on extracellular matrix in SHR renal tissue.METHODS: SHRs at the age of 12-week-old were treated ig with Ipt 1, 3, 9mg·kg^-1·d^-1 ,benazepril 3 mg·kg^-1·d^-1 once a day for 12 weeks.Age-matched WKY rats were used as normal control.The effects of iptakalim on collagen-Ⅳ, MMP-9, TIMP-1 and TGF-β1 expression in SHR kidneys were measured by immunohistochemistry and RT-PCR.RESULTS: After 12 weeks treatment with iptakalim, the expression of MMP-9 mRNA and protein were up-regulated, and those of TGF-β1 , TIMP-1, and Col-Ⅳwere down-regulated in the SHR kidney compared with the untreated controls.CONCLUSION: Iptakalim protects the kidney from hypertensive damage partly by inhibiting TGF-β1 expression and regulating MMP-9 TIMP-1 unbalance in renal tissue, thus promoting ECM degradation, decreasing ECMaccumulation.

Setting uPthe screening model for glucagon receptor antagonists

LIU Jun, ZHANG Lu-yong

2006, 11(10):  1129-1132. 

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AIM: To set uPthe screening model for glucagon receptor(GR) antagonist.METHODS: Rat liver glucagon receptor was prepared by centrifugation.The binding characteristics of GR ligand (¹²⁵I-Glucagon) were studied by radioligands binding in saturation binding experiments and followed by competition binding experiments with a variety of new synthesized compounds.In order to further study the method for screening GR antagonists,GR cDNA was transiently transfected into CHO cells, and then fluo-3 was loaded into the cells.The most important properties of fluo-3 are an absorption spectrum compatible with excitation at 506 nm by argon-ion laser sources and very large fluorescence intensity increase in response to Ca²⁺binding.In the studies, transfected CHO cells were loaded with both fluo-3 and compounds,and then fluorescence intensity was measured to identify GR antagonists.RESULTS: The Kd and Bmax of¹²⁵IGlucagon to GR were 9.38 nmol·L^-1 and 4.33nmol·L^-1 , respectively.Competition binding experiments revealed that compounds ZM102849, ZM102850,ZM102854 and ZM102855 displayed much higher affinity for the GR.When compound ZM102850 was added to the transfected cells, the fluorescence intensity decreased.Therefore, compound ZM102850 was identified as a glucagons antagonist.CONCLUSION: Combining radioimmunoassay and measuring the fluorescence intensity methods can be used to identify GR antagonists.

Effect of combination of ACEI and ARB on left ventricle in pressure-overloaded hypertrophy rats

LIANG Xu-guo, ZHANG Xiu-mei

2006, 11(10):  1133-1136. 

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AIM: To explore the effect of the combination of ACEI and ARB on left ventricle in pressureoverloaded hypertrophy rats, and also the relationshiPbetween left ventricular hypertrophy (LVH) and cytokines,matrix metalloproteinases, apoptosis, and apoptosis genes.METHODS: IL-6, IL-10, MMP-2 and MMP-9 were evaluated by ELISA method.TNF-alpha was measured with radioimmunoassays.Flow cytometer was used to measure the apoptosis ratio and the expression of Fas,Bcl-2 and Bax.RESULTS: 6 weeks after abdominal aortic coarctation operation, the weight of the left ventricle(0.983 ±0.316 g) and heart weight body weight (0.382±0.154) were significantly increased in control grouPcompared with the sham operated group.And also IL-6(208.71 ±84.51 pg·ml^-1) , TNF-α(1.983 ±0.842ng·ml^-1) , MMP-2 (74.63 ±37.62) , MMP-9 (57.74 ±25.61) , apoptosis ratio (8.47 ±4.18) and apoptosisgenes (fas, bax, bcl-2, bcl-2/bax) expression were increased,but IL-10 (86.23 ±40.13 pg·ml^-1) was decreasedcompared with sham operated group.The 3groups with drugs (CP, LT, CP+LT) decreased the increasing weight of LV and ventricular weight body weight and inhibited the changes of influencing factors (IL-6,IL-10, TNF-α, MMP-2, MMP-9, apoptosis ratio and apoptosis genes expression) , especially in the grouPof combination of 2 drugs.CONCLUSION: LVH might be related with many influencing factors.ACEI and ARB may have the positive importance in the treatment and prevention of LVH.

Effects of bioactive compounds from paecilomyces tenuipes on lipid peroxidation of brain in chronic stress rats and its acute toxicity

YIN Yan-yan, LI Chun-ru, KAN Hong-wei, ZHENG Li-fang, MING Liang

2006, 11(10):  1137-1139. 

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AIM: To study the acute toxicity of bioactive compounds from paecilomyces tenuipes (BCPT) and the effect of BCPT on lipid peroxidation of brain in chronic stress model (CMS) of depression in rats.METHODS: The depression animal model was induced by chronic unforeseeable stress (CUS).The maximally tolerated dose (MTD) was used to detect the acute toxicity of BCPT.UV spectrophotometer analysis technique was used to detect the activity of SOD, GSH-PX and CAT,and content of MDA and NO in rat's brain.RESULTS: The MTD of BCPT was 9 g·kg^-1.BCPT could obviously enhance the activities of SOD, GSH-PX and CAT, and also significantly inhibit the increase of MDA and NO content in brain in CMS rats.CONCLUSION: BCPT has little toxicity and produces an antidespressant-like effect in antioxidation in CMS rats.

Alteration of pain related factors levels after Yunke and¹⁵³Sm-EDTMPtreatment in patients with painful skeletal metastases

CHENG Guang-hua, DAI Yun-hai, YANG Jun

2006, 11(10):  1140-1143. 

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AIM: To comparatively analyze the pain related factors levels and therapeutic response in patients treated with⁹⁹Tc-MDPand¹⁵³Sm-EDTMPfor painful skeletal metastases.METHODS: Plasma endothelin (ET), calcitonin gene-related peptide (CGRP), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α(6-k-PGF1α)levels were analyzed in 93 patients with painful skeletal metastases prior and 3 months after treatment.55 cases were just treated with¹⁵³Sm-EDTMP(grouPA);19 cases were treated only with⁹⁹Tc-MDP(grouPB);and 19 cases were treated with both¹⁵³Sm-EDTMPand⁹⁹Tc-MDP(grouPC).RESULTS: 69.1%, 73.7% and 89.5% of the patients were experienced pain relief 3 months after treatment in groups A , B and C , respectively.Comparative analysis shows that:ET and 6-k-PGF1αlevels increased significantly 3 months after treatment in all patients (P<0.01);CGRPlevels decreased significantly 3 months after treatment (P<0.05)in patients of groups B and C.No significant changes of CGRPand TXB2 levels were observed prior and after treatment in grouPA , nor do TXB2 levels in patients of groups B and C.CONCLUSION: Combined treatment with⁹⁹Tc-MDPand¹⁵³Sm-EDTMPwere found more efficient in patients with skeletal metastases than just treatment with¹⁵³Sm-EDTMP.The therapeutic response of⁹⁹Tc-MDPand¹⁵³Sm-EDTMPfor painful skeletal metastases may be closely related to the alteration of plasma ET , 6-k-PGF1αand CGRPlevels.

Pharmacokinetics and bioequivalence of piracetam tablets in healthy volunteers

ZHANG Zhi-tao, HUO Qiang, ZHAO Huai-qing

2006, 11(10):  1144-1147. 

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AIM: To study the bioequivalence of piracetam tablets in Chinese healthy volunteers.METHODS: Twenty volunteers were randomly divided into two groups (test and reference), with double cross-over design and single-dose oral administration.The concentration of piracetam in serum was determined by HPLC.The main pharmacokinetic parameters were calculated and the bioequivalencewas evaluated with DAS2.0 practical pharmacokinetics program.RESULTS: The pharmacokinetic parameters of piracetam tablets were as follows:t_1/2 were 5.50 ±1.48 and 4.29 ±1.00 h , C_max were 21.47 ±6.27 and 20.96 ±5.10 mg·L^-1 , T_max were 0.70 ±0.46 and 0.66 ±0.36 h , AUC_0-24h were 93.44 ±16.61 and 96.67 ±18.50 mg·h·L^-1.The relative bioavailability of the test preparation was 99.8%±22.7%.CONCLUSION: The test and reference preparations were bioequivalent and may be prescribed interchangeably.

A rapid and sensitive method for determination of escitalopram in human plasma and its application in pharmacokinetic study by liquid chromatography-tandem mass spectrometry

YANG Qian, LIU Wen-ying, ZHENG Feng, XU Ji-hua, RAO Jin-hua, SUN Di, GAO Shu

2006, 11(10):  1148-1153. 

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AIM: To determine the concentration of escitalopram in human plasma by HPLC-MS MS and investigate the pharmacokinetics of escitalopram.METHODS: The method involved protein precipitation with methanol.The chromatographic separation was achieved within 6.0 min by using methanol-water with 15 mmol·L^-1ammonium acetate-formic acid (72 ∶28 ∶0.1, v/v/v) as mobile phase and a Lichrospher CN 150 mm ×4.6 mm analytical column.The analytes were detected using an electrospray ionization tandem mass spectrometry in SRM mode.Detection of the ions was performed by monitoring the transitions of m/z 325.0 to 234.0 for escitalopram and m/z 409.1 to 238.1 for amlodipine(internal standard) , respectively.RESULTS: The standard curve was linear (r =0.999) over the concentration range of 0.20 -50.00 ng·ml^-1.Accuracy and precision were below the acceptance limits of 15%.The recoveries of escitalopram ranged from 96.0% to 103.6%.The lower limit of quantification for escitalopram was 0.20 ng·ml^-1 using 200 μl plasma sample.The pharmacokinetic parameters of escitalopram after a single oral dosing of escitalopram oxalate tablet (10 mg)to ten healthy male volunteers were achieved.The C_max ,T_max , AUC_{0 -t} , AUC_{0 -∞}, t_{1 2}and K e of escitalopram were 9.21 ±2.10 ng·ml^-1 , 3.75 ±1.04 h, 514.6 ±152.3 ng·h·ml^-1 , 540.5 ±162.3 ng·h·ml^-1 , 34.06 ±7.71 h and 0.021 ±0.004 h^-1 , respectively.CONCLUSION: The determination of concentration of escitalopram in human plasma by HPLC-MS MS method was rapid, sensitive and reliable.It can be used for clinical pharmacokinetic study of escitalopram.

Esomeprazole for gastroesephageal reflux disease:a systematic review

ZHONG Li-chun, JIA Hong, LI Chang-ping, ZHOU Yi-jun

2006, 11(10):  1154-1159. 

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AIM: To evaluate the efficacy of esomeprazole in the treatment of gastroesephageal reflux disease(GERD) when compared to the other PPI.METHODS: We were searching RCT researchers contacted.The quality evaluation of studies and data analysis were conducted by the methods of the Cochrane Collaboration.RESULTS: Fourteen RCTs met the inclusion criteria.In patients with NERD symptom relief rate esomeprazole had significant effect when compared with pantoprazole.In patients with EE symptom relief rate esomeprazole had significant effect comparing with the other PPI.CONCLUSION: Esomeprazole was better than pantoprazole in patients with NERD symptom relief rate.In patients with EE symptom relief rate esomeprazole was better than the other PPI.

Effect of famotidine on pharmacokinetics of domperidone in healthy volunteers after a single oral administration

LIANG Yan, TIAN Shuo-han, SUN Pei-hong, ZHAO Xia, ZHOU Ying, LIU Yu-wang, CUI Yi-min

2006, 11(10):  1160-1163. 

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AIM: To study the effect of famotidine on the pharmacokinetics of domperidone.METHODS: A single oral dose of domperidone 10 mg was given to 10 healthy volunteers under the condition of untaking or taking famotidine in a randomized, cross-over study.Plasma domperidone concentration was determined by a validated LC/MS/MS method.Pharmacokinetic parameters were calculated by DAS software and compared by t tests.RESULTS: The concentration-time curve of domperidone with untaking or taking famotidine was conformed to a two-compartment model.Under untaking and taking famotidine conditions, the main pharmacokinetic parameters,t max , C_max and AUC_0-tn , were 0.63 ±0.36 and 1.50 ±0.97 h, 9.91 ±5.45 and 4.30 ±5.01 μg·L^-1 , 39.57±10.46 and 32.43 ±9.61 μg·h·L^-1 respectively.The absorption of domperidone was delayed, and the peak concentration and area under curve were reduced significantly when famotidine was taken.CONCLUSION: Famotidine had a significant effect on the pharmacokinetics of domperidone after a single oral dose in healthy volunteer.

Therapeutic effects of survivin and bcl-2 gene combined with antisense oligodeoxynucleotide on human breast cancer transplanted subcutaneously in nude mice

WANG Wen-wu, OU-YANG Xue-nong, ZHANG Xia, JIANG Hao

2006, 11(10):  1164-1167. 

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AIM: To investigate the effects of surviving and bcl-2 combined with ASODN on the treatment of breast cancer xenograft in nude mice.METHODS: The model of xenografts derived from MCF-7 breast cancer cell was established in BALB/c nude mice , then they were randomly divided into a negative control grouPand 5 experimental groups [intraperitoneal injection of liposomesurvivin-SODN , liposome-bcl-2-SODN , liposome-survivin-ASODN , liposome-bcl-2-ASODN , combined ASODN].The tumor growth inhibitory rate and the tumor volume decreased rate were calculated.RESULTS: Survivin and bcl-2 combined with ASODN exhibited potent tumor growth inhibition.The tumor volume inhibitory rate was 78.4%;the tumor weight inhibitory rate was 75.3%;the tumor volume decreased rate was 41.6%for combined grouPpost-experiment of the 6 groups , and there was no significant difference on nude mice weight post-experiment.CONCLUSION: Survivin and bcl-2 combined with ASODN showed potent tumor growth inhibition in vivo.

Clinical evaluation of PLF and PFM regimens in recurrent or metastasis nasopharyngeal carcinona

JIANG Yi, QIU Xi-hui, CHEN Zhi-ming, LIN Dan-xia, YANG Yu-xian

2006, 11(10):  1168-1172. 

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AIM: To evaluate the efficacy and safety of PLF and PFM regimen based on cisplatin plus 5-fluorouracil in recurrent or metastasis nasopharyngeal carcinoma(NPC) , and to explore prognostic factors of advanced NPC by survival analysis.METHODS: Patients with recurrent or metastasis NPC were enrolled in the study.They were nonrandomly assigned to receive a 2-hour infusion of folinic acid 200mg·m^-2 followed by a 5-FU bolus 400 mg·m^-2 and 48-hour infusion 3, 000mg·m^-2 combined with DDP25 mg·m^-2 on day 1 -3 every 3 weeks (PLF) or DDP25 mg·m-2 on day 1 -3,5-FU bolus 400mg·m^-2 on day 1 -5 plus pingyangmycin 5 mg·m^-2 on day 1, 3 and 5 every 3 weeks (PFM).RESULTS: 48 patients were enrolled.The total response rate was 63.83%, and the response rate of PLF 、PFM regimen was 76.92% and 47.62%(P=0.066, respectively.The main side effects include nausea, vomiting,alopecia, bone marrow suppression and mucositis.The DLF regimen was milder than DFM regimen in nauseavomiting(P=0.032).After a median follow-uPof 10 months, the overall median survival was 11.0 months,and the median survival of grouPA and grouPB were 12 and 9 months(P=0.3691) , respectively.A highly significant correlation was noted between poor-prognosis to severe anemia (Hb <10 g·L^-1 , P=0.001) before chemotherapy and the older patients (age ≥65, P=0.030) by Cox Regression analysis.CONCLUSION: The PLF regimen can be recommended for recurrent or metastasis NPC as first-line good treatment because its tolerable and more active.Anemia (Hb <10 g·L^-1) and older age (age≥65) indicate poor prognosis.

Ipriflavone up-regulates mRNA expression of osteoprotegerin in lumbar vertebra of ovariectomized rats

SHANG Min, YANG Xin, LI Ya-zhen, GU Bei, WU Qiong, LIAO Qin-ping

2006, 11(10):  1173-1176. 

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AIM: To build a postmenopausal osteoporotic model in rats and investigate the effect of ipriflavone on the expression of osteoprotegerin (OPG) mRNA in lumbar vertebra of ovariectomized rats, and to analyze its mechanism in the prevention of postmenopausal osteoporosis.METHODS: Forty female rats at 6 months of age were randomly allocated into 4 groups:sham-operated group, ovariectomized grouP(OVX) , OVX combined valerate estradiol group, and OVX combined ipriflavone group.Rats were sacrificed after they had been lavaged for 13 weeks.The fourth lumbar vertebra was dissected out for histomorphology and the second lumbar vertebra for measurement of mRNA level of OPG by way of reverse transcription polymerase chain reaction technique.RESULTS: The trabecular volume was significantly lower in OVX grouPrats than that in sham grouPrats, while osteoid seam was significantly higher.Valerate estradiol and ipriflavone can increase the trabecular volume and reduced osteoid seam significantly in OVX rats.To compare with sham grouPrats, the mRNA level of OPG decreased significantly in OVX rats, and valerate estrodiol and ipriflavone can up-regulate the expression level of OPG mRNA significantly.CONCLUSION: Our experiment built the postmenopausal osteoporotic model successfully.Valerate estradiol and ipriflavone can prevent postmenopausal osteoporosis by its inhibitory effect on bone turnover.OVX-induced bone loss was associated with OPG.Iprif lavone,just like valerate estradiol, perhaps has its antiresorbative effect on bone by the signal of OPG.Estrogen and ipriflavone can up-regulate the mRNA expression of osteoprotegerin in the lumbar vertebra tissue of ovariectomized rats.

Efficacy and safety of Weishuan pellets in treatment of patients with functional dyspepsia

ZHANG Qiong, LI Bao-shuang, LI Zhen-hua

2006, 11(10):  1177-1180. 

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AIM: To evaluate the clinical efficacy and safety of the Weishuan pellets in treatment of patients with functional dyspepsia.METHODS: 409 subjects were involved in a multi-center randomized , doubleblinded, double-simulation , and positive drug parallelcontrolled clinical trail.308 patients were enrolled in the Weishuan-pellets grouP, while 101 cases were enrolled in the control group.RESULTS: The total effective rate and recovery and excellence rate in Weishuan pellets were 95.70% and 63.03%, respectively ;In the control grouP, the total effective rate and recovery and excellence rate were 94.06% and 62.38%, respectively.For the effects on Piman synodrome , the total effective rate and recovery and excellence rate were 92.07% and 62.04%,respectively ;In the control grouP, the total effective rate and recovery and excellence rate were 87.12% and 54.45%, respectively.For effects on gastric emptying function , in the treatment grouP, the total effective rate and recovery and excellence rate were 73.85% and 60.78%, respectively ;In the control grouP, the total effective rate and recovery and excellence rate were 70.37% and 59.26%, respectively.There was no significant difference between the two groups (P>0.05).CONCLUSION: Weishuan pellet is an effective and safe drug in treatment of patients with functional dyspepsia.

Study on pharmacokinetics and bioavailability of sustained-release roxithromycin tablets in beagle dogs

LU Jing-lan, GAO Gui-zhen, FENG Shi-jun

2006, 11(10):  1181-1184. 

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AIM: To investigate the pharmacokinetics of the roxithromycin sustained-release tablets in 8 beagle dogs.METHODS: Microbiological method was used to determine the serum concentration of roxithromycin after normal and sustained-release tablets were orally administrated in 8 healthy beagle dogs.Pharmacokinetic parameters were calculated , and the bioequiverlence was estimated by statistical method.RESULTS: The pharmacokinetic parameters of sustained-release and normal tablets after single oral dose study were as following:the t_max were 4.74 ±1.21 h and 1.21 ±0.64 h , the C_max were 21.08±4.24 μg·ml^-1 , and 28.26 ±5.41 μg·ml^-1 , respectively;the AUC were 164.49 ±28.55 μg·h·ml^-1 and 177.95 ±27.63 μg·h·ml^-1 respectively.Compared to normal tablets , the bioavailability of sustained-release tablets was 93.6%±10.5%.There was much difference for t_max and C_max parameters between the two tablets.CONCLUSION: The results of the present study indicate that the absorption speed was slower for sustained-release tablets than normal tablets , but the extend of absorption for the two roxithromycin tablets was bioequivalent.

Protective effect of α-diammonium glycyrrhizinate phosphatidylcholine complex against acute hepatic injury in mice

YU Feng, LIU Chun, DONG Li-ping

2006, 11(10):  1185-1189. 

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AIM: To investigate the protective effect of α-diammonium glycyrrhizinate phosphatidylcholine complex(DGLL) on chemical liver injury and its possible mechanisms.METHODS: The acute hepatic injury model inmice was induced by D-GalN.We measured the changes of activity of ALT and AST in serum and MDA,XOD, GSH-PX, NO, NOS and iNOS content of liver tissue.The model of chemical liver injury in mice was prepared.In vitro, primary cultured mice hepatocyte was injured by CCl4 , and the level of ALT in medium was measured to study protective effect of DGLL.RESULTS: DGLL could decrease the activities of ALT and AST in serum and the MDA, XOD, NOS and iNOS content of liver tissue, and was able to increase the activities of GSH-PX content of liver tissue.In vitro, it is indicated that GPLL had a notable protective effects on the hepatocyte injured by CCl4 and could suppress the level of ALT.CONCLUSION: DGLL had notable protective effect against acute liver injury in mice.

Key role in clinical trial:clinical research coordinator

BO Qing-yan, XIONG Ning-ning, ZOU Jian-dong, JIANG Meng, LIU Fang, WANG Xiu-qin, GAO Wei-min

2006, 11(10):  1190-1193. 

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Clinical research coordinator (CRC) has been an important role in clinical trial and as a profession for almost 30 years in foreign countries.Most CRCs have professional backgrounds of nurse, pharmaceuticals and other biomedical specialties.CRC's scope of work involves each aspects of clinical trial, including preparation of clinical trial, liaison with IRB and sponsor, and assisting in the operation of trials, such as obtaining informed consent, diseases management education, liaison, consultation and discussion with patients and their families,data collection and CRF transcription, management of clinical examination, adverse event, trial medicine, clinical trial files and other materials, as well as responding to monitor and audit and inspection.CRC plays an important role in guaranteeing the ethic and scientific rationality,and the reliability of data in clinical trial.

Use and limitation of surrogate outcomes in clinical trials

XU Xiao-guo, JIANG Meng

2006, 11(10):  1194-1197. 

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According to the status quo of choosing outcome indexes in Chinese and other countries'clinical trials, propose the concepts of surrogate outcomes and end points and correlation between them, discuss the general methods and present problems of choosing true endpoints.It is emphasized that only the primary outcomes which affect the patients directly can prove the real effectiveness of the interventions.Only when the surrogate ones, such as biological indexes from laboratory and the patients'symptoms or signs, which are proved to have a correlate of the true clinical outcome and fully capture the net effect of treatment on the clinical outcome, can the latter be the substitute for the former.

Approach of compensation to subjects'impairment in clinical drug trial (I)

LIANG Wei-xiong

2006, 11(10):  1198-1200. 

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This issue introduces the existing problems and corresponding countermeasure about the compensation to the subjects'impairment in Chinese clinical drug trial nowadays.It suggests that the corresponding laws of impairment compensation should be perfected.Moreover,during the designation, the inspection of ethics inspection committee, the execution of informed consent and the compensation problem must be clarified.It also appeals the establishment of compensation fund and related accidence insurance, from which the compensation shall be made after the analysis and assessment of professional institute,thus the clinical drug trials can be guaranteed successfully.