Table of Content

Volume 13 Issue 10
26 October 2008

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Consideration of research on some basic problems of clinical pharmacology

WEI Wei

2008, 13(10):  1081-1085. 

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Clinical pharmacology is a subject to study the interactions and rules between drugs and the body .Principles of clinical pharmacology have made significant progress in many aspects, such as clinical trials, and evaluation of new drugs adverse drug reaction monitoring .Much importance should be attached to the study of common, critical and advanced questions in clinical pharmacology .Besides doing the rou-tine service of clinical pharmacology, exploration on academic research should also be strengthened to provide theoretical support to ensure the safety, effectiveness and rationality of clinical drug application .Study on drug interaction, multidrug resistance, pharmacogenetics, pharmacogenomics, PK/PD model, sex phar-macology, pharmacodynamics and molecular mechanism of drug based on pathological histiocyte of human body have attracted people' s attention.Consideration of research on some basic problems of clinical pharmacology were reviewed in this article .

CPU0213, an endothelin receptor antagonist, alleviates diabetic car-diomyopathy through suppressing NADPH oxidase in rats

XU Ming , JI Hui, DAI De-zai, SHI Yan-ping, DAI Yin

2008, 13(10):  1086-1090. 

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AIM: To study the activation of NAD-PH oxidase in diabetic cardiomyopathy participates in myocardial injury that is likely reversed by an endothe-lin receptor antagonist CPU0213.METHODS: Male SD rats were administrated STZ (60mg^。kg^{-1 。}d^-1,i.p.) to develop diabetes mellitus for 8 weeks. CPU0213 (100 mg/kg, p.o .) and aminoguanidine (AMI, 100 mg/kg, p.o .) were applied for 4 weeks. RESULTS: CPU0213 and AMI could significantly al-leviate myocardial hypertrophy, reduce the level of ET-1 and oxidative stress except blood glucose in diabetic rats.Over-expression of mRNA and protein of p22phox and p67phox in neonatal SD rats myocytes incubated with high glucose was suppressed by both CPU0213 and AMI.CONCLUSION: Endothelin receptor antagonist CPU0213 and AMI alleviated diabetic cardiomyopathy in rats, mediated by suppressing over-expression of NADPH oxidase in the myocardium .

Reactivation of neuronal α4β2-nicotinic acetylcholine receptors following desensitization induced by agonist was blocked by benthiactzine

LUO Wang-qian, CUI Wen-yu, WANG Hai

2008, 13(10):  1091-1094. 

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AIM: To investigate the reactivation of neuronal α4β2-nicotinic acetylcholine receptors following desensitization induced by agonist and the antagonism of benthiactzine against it .METHODS: The whole cell recording configuration of patch-clamp technique and the rapid application of nicotine were performed in α4β2-nAChRs heterologously expressed in cultured SH-EP1 cells. RESULTS: An inward current was elicited by rapid application of 1 mmol/L nicotine in SH-EP1 cells.This current reached peak rapidly and then desensitized fast when the application of agonist was prolonged. However, after the removal of nic-otine, an additional inward current reoccurred. This rebound current can be blocked by benthiactzine, a new antagonist of cholinergic receptors. CONCLUSION: Neuronal α4β2-nicotinic acetylcholine receptor heterologously expressed in the SH-EP1 cell line can be desensitized by prolonged agonist application, and be reactivated after the removal of agonist .This reactivat-ed current can be blocked by benthiactzine, a new an- tagonist of cholinergic receptors.

Protective effects of artesunate on mouse sepsis induced by cecal liga-tion and puncture

WANG Li, LIU Xing, ZHOU Hong, CAO Hong-wei, LI Bing, LU Yong-ling, ZHENG Jiang

2008, 13(10):  1095-1098. 

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AIM: To investigate the protective ef-fects and related mechanisms of artesunate on mouse model of sepsis induced by cecal ligation and puncture(CLP).METHODS: The septic mouse models were established by CLP .Artesunate was administrated in-tramuscularly at 0, 4, 24 and 48 h after CLP .Mortali-ty of CLP mice was observed in the next 7 days.Blood samples were collected at 4,8 h after CLP and the lev-els of LPS , TNF-αand IL-6 were detected by kinetic turbidimetric limulus test or ELISA, respectively .The morphological changes of lung tissues were observed with light microscope at 8 h after CLP.RESULTS: Artesunate degraded obviously the mortality of CLP mice (P <0.05), attenuated the levels of LPS, TNF-αand IL-6 at 4, 8 h after CLP (P<0.05 or P<0.01), and the lung tissues were also less injured in artes unate treatment group .CONCLUSION :Artesu-nate has a significantly protective effect for CLP mice which may be related to attenuating the LPS level , in-hibitting the release of proinflammatory cytokines TNF-α、IL-6 and reducing organ tissue injury .

Apoptosis in K562 cells induced by arsenic trioxide via JNK signaling pathway

ZHANG Sheng-hui, HAN Yi-xiang, WU Jian-bo, YE Ai-fang, YIN Li-hui, TAN Ying-xia

2008, 13(10):  1099-1103. 

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AIM: To investigate the role of c-jun N-terminal kinase (JNK) signaling pathway in the ap-optosis of human chronic myelogenous leukemia cell line K562 induced by arsenic trioxide and the possible mechanisms.METHODS: K562 cells were pre-incu-bated with SP600125 for 3 h prior to exposure to ar-senic trioxide at 4 μmol/L and for different time .The cell morphological changes were observed by inverted phase contrast microscopy .The cell growth inhibitory rate was detected by MTT colorimetric assay .The ap-optosis rate was analyzed by Annexin V/PI fluorescence staining together with flow cytometry .Changes in ex-pression of phospho-JNK protein were examined by ELISA.The mutant P53 expression was assayed by flow cytometry.RESULTS: Arsenic trioxide could significantly inhibit the proliferation of K562 cells and induce their apoptosis.The results of ELISA showed that the protein expression of phospho-JNK was in-creased in K562 cells after stimulated by Arsenic triox-ide.SP600125 remarkablely decreased the protein ex-pression of phospho-JNK as well as the apoptosis rate and the cell growth inhibitory rate, but the mutant P53 expression increased in K562 cells induced by arsenic trioxide as compared with those treated with only ar-senic trioxide.CONCLUSION: JNK signaling path-way may play an important role in the apoptosis of K562 cells induced by arsenic trioxide.

Anti-proliferation effect of troglitazone on NB4 cells and its mecha-nisms of action

XU Yan, HU Ting, WANG Chun-zhi, LIU Pei-qing, LIN Dong-jun, XIAO Ruo-zhi, LIU Jia-jun

2008, 13(10):  1104-1108. 

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AIM: To investigate the anti-prolifera-tion effect of peroxisome proliferator-activated receptor γ(PPARγ) agonist troglitazone (TGZ ) on leukemic NB4 cells and its mechanisms of action.METHODS: NB4 cells in culture medium in vitro were given differ-ent concentrations of TGZ (0-80 μmol/L) for 24, 48 and 72 h .The inhibitory rate of the cells were mea-sured by MTT assay .Cell apoptosis were observed by flow cytometry (FCM) and DNA fragmentation was as-sayed by agarose gel electrophoresis.Bcl-2 and Bax as well as Caspase-3 and poly(ADP-ribose) polymerase (PARP) expressionwere detected by Western blotting . RESULTS: TGZ (over 20 μmol/L) could inhibit the growth of NB4 cells and cause apoptosis remarkably . Furthermore, the suppression was both in time-and dose-dependent manner.DNA ladder was observed af-ter the cells treated by TGZ for 72 h, and marked mor-phological changesof cell apoptosis such as condensati-on of chromatin was clearly observed by Hoechst stain-ing .Western blotting showed cleavage of the Caspase-3 zymogen protein (32000) , with the appearance of its 20000 subunit, and a cleaved 89000 fragment of 116000 PARP was also found.Furthermore, western blotting also showed that anti-apoptotic protein Bcl-2 was decreased remarkably while pro-apoptotic protein Bax increased significantly after the cells were treated by TGZ for 48 h.CONCLUSION: TGZ can inhibit cell growth and induce apoptosis of NB4 cells via acti-vation of Caspase-3 as well as downregulation of Bcl-2 and upregulation of bax expression in NB4 cells.The results indicate that TGZ might be an important poten-tial anti-leukaemia reagent .

Effects of propyl gallate on BDNF expression after cerebral ischemia-reperfusion in rats

LIN Min, LIN Zhi-ying, CHEN Xiao-chun, ZHENG Guan-yi, HUANG Jun-shan, ZHENG Jian-ming, ZHANG Jing, ZHOU Yi-can

2008, 13(10):  1109-1115. 

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AIM: To explore the effect of propyl gallate on neurological dysfunction with injury after ce-rebral ischemia-reperfusion, and the effect on neuronal apoptosis and BDNF expression.METHODS: Middle cerebral artery occlusion models of rat transient focal ischemia were induced by inserting a filament through right internal carotid artery for 1 h .Rats were grouped as follows:control, sham operation, model, vehicle, PG 23.5 μmol/kg, PG 47 μmol/kg, PG 94 μmol/kg. Rats received intraperitoneal injections of PG immedi-ately after reperfusion, and the same volume physiolog-ical saline for vehicle group.Neuronogical behavior was evaluated by Longa's scoring method .Each rat re-ceived an injection every day and coronal brain sections were collected after l d, 2 d, 4 d, 7 d of reperfusion. Neuronal apoptosis in the boundary zone of the infarcts was evaluated by TUNEL staining .The expression of BDNF was investigated by immunohistochemistry and Western-blot with corresponding antibodies. RESULTS: Neurological deficits of model group and TUNEL positive neurons were observed at each time point and peaked at 1 d (P<0.01 compared to 2 d, 4 d, 7 d) .BDNF immunoreactivity increased to its peak at l d (P<0.01 compared to 2 d, 4 d, 7 d) and then decreased gradually in the boundary zone of the in-farcts.PG 47 μmol/kg and PG 94 μmol/kg could re-duce those damage and neurological deficits significant-ly (P<0.01) ;Furthermore, PG 47 μmol/kg and PG 94 μmol/kg markedly reduced the number of TUNEL positive neurons and increased the immunoreactivity of BDNF at 1d (P<0.01 compared to model) .Dose of 94 μmol/kg PG was more effective .CONCLUSION: The increasing expression of BDNF after cerebral isch-emia-reperfusion injury possibly affect the recovery of the boundary zone of the infarcts;the possible mecha-nism of propyl gallate could protect neurons from isch-emia-reperfusion injury may involve its upregulation of BDNF.

Effects of roxithromycin on myofibroblast, TGF-β₁ and IFN-γin rats asthma airway remodeling

LIN Jie, DAI Yuan-rong, ZHAO Chu-huan, WENG Hai-xia, XIA Xiao-dong, HE Jian-bo

2008, 13(10):  1116-1121. 

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AIM: To explore the effects of myofi-broblast, TGF-β₁ and IFN-γon asthma airwy remodel-ing and observe the influence of roxithromycin on asth-ma airway remodeling .METHODS: In the experi-ment, thirty SD rats were randomly divided into the asthma group(group A, n =10) , the sodium chloride control group (group C, n =10) and the roxithromycin group(group R, n =10) .The rats were sensitized and stimulated with ovalbumin/Al(OH)3 and OVA atomiza-tion inhalation respectively to establish the asthma mod-el.The α-smooth muscle actin(α-SMA) expression of tracheal subepithelium myofibroblast were determined by immunohistochemistry .The integral optical density (IOD) were quantitatively analysed by image analysis technique .The concentration of TGF-β₁ and IFN-γin bronchoalveolar lavage fluid(BALF) were measured by ELISA .RESULTS: The IOD value suggested that the α-SMA expression of tracheal subepithelium myofibro-blast were increased compared with group C (P<0.01) , and the expression in group R were decreased comparedwith group A (P<0.05) .The expression of TGF-β₁ in BALF in groupA were increased than that in group C(P<0.01) , and TGF-β₁ expression in group R were decreased than that in group A(P<0.01) , but were still higher than that in group C(P<0.05) .The expressions of IFN-γin BALF in group A were de-creased than that in group C(P<0.01) , and IFN-γ expression in group Rwere increased than that in group A(P<0.01) , but were still lower than that in group C(P<0.05) .CONCLUSION: Myofibroblast plays an important role during airway remodeling .Roxithro-mycin may decrease the expressions of TGF-β₁ and in-crease the expressions of IFN-γ that inhibits the prolif-eration and expression of myofibroblast .So roxithromy-cin may be effective drugs in inhibitting asthma airway remodeling.

Effects of the erigeron injection on liver microsomal cytochrome P450 system in mice

XU Li-jun, JU Wen-zheng, CHEN Wei-kao, TAN Heng-shan

2008, 13(10):  1122-1126. 

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AIM: To investigate the effects of eri-geron injection on liver microsomal cytochrome P450 (CYP450) system in mice .METHODS: Mice were divided into control group (CG) , positive control group, normal-dosage group (NG) and high-dosage group (HG) .The mice of control group were given sa-line only and the mice of positive control group were given Phenobarbital sodium injection (PBN) at 80 mg/kg by peritoneal injection (i .p.) , once daily for seven days.The remaining two groups were i .p.with 10 mg/kg (normal-dosage group) and 30 mg/kg (high-dosage group) erigeron injection, respectively, once daily for two weeks.Then the total content and activi-ties of CYP450 of mice were determined by spectropho-tometer .RESULTS: The study showed that the cont-ent of CYP450 and protein in mice of normal-dosage group and high-dosage group were higher than those in control group, except liver indexes.In terms of the eri-geron injection effects on Erythromycin-N-demethylase and aminopyrine-N-demethylase, the normal-dosage group and high-dosage group can decrease the activity of Erythromycin-N-demethylase (P <0.01) , but had no effect on aminopyrine-N-demethylase (P >0.05) . Phenobarbital sodium can increase the levels of liver indexes, the content of CYP450 and protein(P < 0.05) , Erythromycin-N-demethylase and aminopyrine-N-demethylase (P <0.01) .CONCLUSION: The erigeron injection had no effect on the liver indexes and the levels of aminopyrine N-demethylase in mice. However, the content of CYP450 and protein, and the levels of Erythromycin N-demethylase were affected. The erigeron injection may be an inhibitive agent to CYP3A.

Determination of proteasome activities with fluorescence kinetic assay and its application in screening proteasome inhibitors

ZHOU Yong-lie, LV Ya-ping, XU Wu-lin, HU Wei-xiao

2008, 13(10):  1127-1133. 

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AIM: To establish a method for the determination of proteasome activities with fluorescence kinetic assay and evaluate the application in screening proteasome inhibitors.METHODS: The proteasome activities of chymotrypsin-like(CT-L) , trypsin-like (T-L) and peptidyl glutamyl peptide hydrolysing-like (PG-PH-L) were measured with specificity fluorescence peptide substrate Suc-Leu-Leu-Val-Tyr-AMC (Suc-LLVT-AMC) , Z-Val-Val-Arg-AMC (ZVVA-AMC) , Z-Leu-Leu-Glu-βNA (ZLLG-βNA) .The conditions of enzyme reaction had been optimised and the technolo-gies were evaluated .The inhibition of the CT-L, T-L and PGPH-L activities of purified 20S proteasome ac-tivity of proteasome extracts were prepared from B16 and Namalwa cells by PS-341 and ZGDHu-1were mea-sured. RESULTS: The optimum pH of enzyme reac-tion was 8.2.The addition of 0.3 g/L SDS buffer only to the assay was required to activate the CT-L of pro-teasome .The K m of CT-L, T-L and PGPH-L activities of proteasome were 3.55, 4.12, 4.88 μmol/L respec-tively and the linearity of reaction curve was up to 20 min.When purified 20S proteasome was used, the as-say for detecting CT-L, T-L and PGPH-L activities was linearly dependent on total protein 100, 120, 100 μg/L in 2 mL assay volume respectively .When the extracts of B16 cell proteasome were detected, the proteinum concentrations were 200 mg/L .The degree of precision in within-run and between-run CVs were (2.25-5.78) %and (3.75-8.42) %respectively .The IC 50 values of the PS -341 and ZGDHu-1 for inhibtion of the CT-L, C-L and PGPH-L activities of purified 20S proteasome were 12.36, 12.42, 24.40 nmol/L and 2.24, 0.92, 0.51 μmol/L respectively.CONCLUSION: The assay provides a reliable and effective method for studying the screen of proteasome inhibitors and it is an useful index in clinical trials with protea-some inhibitors.

siRNA targetgene c-myc downregulates human telomerase reverse tran-scriptase gene and telomere lengths in human colon cancer Colo320 cells

HUANG Hao, LI Xiu, XIAO Hong, FU Lei, YU Nan-cai, LIN Shi-he, YI Yan-dong

2008, 13(10):  1134-1138. 

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AIM: To study transfected shRNA of c-myc as therapeutic agents into target cell Colo320 which expressed more tolomerase activity to investigate the effect of inhibition on telomerase activity and te-lomere lengths and tumor cell growth. METHODS: A plasmid-based polymerase III promoter system was used to deliver and express short interfering RNA (siRNA) targeting c-myc in Colo320 cells.The c-myc and hu-man telomerase reverse transeriptase (hTERT) mRNA level was monitored by fluorescence real time reverse transcription-polymerase chain reaction, the protein level of c-myc, hTERT were examined by western blot analysis. Meanwhile, telomere lengths and telomerase activity were measured by Southern analysis of telomere restriction fragment (TRF) length and PCR-ELISE. We also assessed the effects of c-myc silencing on tu-mor growth by DNA synthesis (³H-thymidine).RESULTS: The data showed that expression of c-myc and hTERT decreased in shRNA-transfected cells, down-regμlation of c-myc and hTERT inhibited cell growth, reduced cell telomere lengths and telomerase activity . CONCLUSION: shRNA of c-myc had the ability to inhibit telomerase activity and telomere lengths and cell growth and was dose dependent .

Influence of traditional Chinese medicine on PCOS rat model serum sex hormone T, FSH, LH, and Leptin

DENG A-li,ZHOU Zhong-ming, XIANG Nan, JIANG Hui-zhong, ZHANG Ya-bing, JING Jing, YU Nian, CHEN Lu

2008, 13(10):  1139-1143. 

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AIM: To observe the changes of serum sex hormone T, FSH, LH and Leptin, and explore the influence of traditonal Chinese medicine complex on the reproduction endocrine system in PCOS rat model. METHODS: PCOS rat model was established by Poresky method, the changes of the rats weight, serum sex hormone T,FSH, LH and Leptin were observed af-ter the treatment with traditional Chinese medicine, western medicine (rosiglitazone) , united medication, respectively, and the correlations of serum Leptin levels with FSH, LH, LH/FSH, T, Weight were analyzed. RESULTS: The traditional Chinese medicine group could decrease serum sex hormone T, LH, Leptin level and the LH/FSH, Leptin level and LH, T were positive correlated in model rats. CONCLUSION: The traditional Chinese medicine can improve reproduction en-docrine system functoins and decrease serum Leptin levels on PCOS rat model.

Effects of rosiglitazone on the production and degradation of extracel-lular matrix of glomerular mesangial cells incubated with high concen-tration of glucose

NI Lian-song, JIN Jie-na, ZHENG Jing-chen, SHEN Fei-xia

2008, 13(10):  1144-1148. 

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AIM: To investigate the protection mechanisms of rosiglitazone on diabetic nephropathy. METHODS: Rat mesangial cells(MC) were incubated in media containing 5.5 mmol/L normal control glu-cose, 25 mmol/L high concentration glucose, 25 mmol/L glucose +20 μmol/L rosiglitazone maleate. Cells proliferation were assessed by CCK-8.Synthesis of fibronectin (FN) , type Ⅳ collagen (Col-Ⅳ) , transforming growth factor-β₁ (TGF-β₁ ) and matrix met-alloproteinase inhibitor-1(TIMP-1) in supernatant were determined by ELISA method, the activities of matrix metalloproteinase-2, 9 (MMP-2, 9) in supernatant were determined by gelatinase zymography .RESULTS: Compared with control group, MC cultured with high concentration glucose showed a high growth rate and in-creased synthesis of Col-Ⅳand FN, decreased the activities of MMP-2 and MMP-9, and increased secretion of TGF-β₁ and TIMP-1.Compared with high glucose group, these changes could be reversed by rosiglitazone intervention .CONCLUSION: Rosiglitazone could in-hibit high concentration glucose-induced proliferation of mesangial cells, decrease synthesis of extracellular matrix, and increase degradation of extracellular matrix.

Association between genetic polymorphism of CYP3A5 and blood con-centration/dose ratio of cyclosporine combined with calcium channel blockers in renal transplant patients

SHI Dao-hua, LIN Zhi-jie

2008, 13(10):  1149-1153. 

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AIM: To study the relationship be-tween the genetic polymorphism of CYP3A5 gene and the blood concentration/dose ( C/D) ratio of cyclospo-rine combined with calcium channel blockers ( CCBs) in renal transplant patients.METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was applied to determine the genotype of CYP3A5 in 69 renal transplant patients. The blood concentration/dose (C/D) ratio of cyclospo-rine was compared in patients coadministrated of CCBs with different genetic polymorphism of CYP3A5.RE-SULTS: The cases of genotype of CYP3A5 ＊1/＊1, CYP3A5＊1/＊3 and CYP3A5 ＊3/＊3 were 8,23 and 38, respectively .The mutation rate of CYP3A5＊ 3 in renal transplant patients was 71.74%.The CsA C/D ratio of patients of CYP3A5＊1/＊1 and CYP3A5 ＊1/＊3were 1 .73 and 2.43 times higher than that in patients of CYP3A5 ＊3/＊3.The CsA C/D ratio of patients ( CYP3A5 ＊1/＊1, CYP3A5 ＊1/＊3) com-binedwith CCBs had been obviously elevated ( 19.90 ±7.66 vs 36.01±8.18, 34.33 ±7.87 vs 46.16± 9.63 ng·mL^-1 per mg·kg^-1 ;P <0.01, P <0.05) , and that of patients with CYP3A5 ＊3/＊3 genotype showed no significant changes ( 48.27 ±10 .60 vs 46.42 ±9.24 ng·mL^-1 per mg·kg^-1 ).CONCLUSION: The CsA C/D ratio is related to the genetic polymorphism of CYP3A5 gene in renal transplant pa-tients combined with CCBs.

Finding and analysis of CYP3A4 new genotype from Chinese Han pop-ulation in East China

ZHANG Ping-hu, ZHANG Juan, GAO Yi-xiang, ZHONG Min, SHANG Jing, ZHANG Lu-yong

2008, 13(10):  1154-1157. 

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AIM: To explore the genotype differ-ence of CYP3A4 gene from Chinese Han population in East China .METHODS: The CYP3A4 gene cDNA of six samples of adult human liver tissues from Chinese Han population were amplified and identified by RT-PCR and DNA sequencing .RESULTS: One new geno-type of CYP3A4 was identified from six samples.There are three amino acids mutations, i .e .V (GTG) →A (GCG) at 71st amino acid site ;V(GTC) →I(AIC) at 225th amino acid site;W(TGG) →V(GTG) at 393rd amino acid site, and three nucleotide acids lack, i .e . CAG from 671st to 673rd nucleotide acid site. CONCLUSION: one new genotype of CYP3A4 gene is dis-covered for the first time from Chinese Han population in East China.

Pharmacokinetics of icotinib in Beagle dog studied by using LC/MS/MS method

GUAN Zhong-min, CHEN Xiao-yan, ZHONG Da-fang, WANG Yin-xiang

2008, 13(10):  1158-1162. 

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AIM: To develop an LC/MS/MS meth-od for the determination of icotinib in dog plasma and study the pharmacokinetics of icotinib.METHODS: Icotinib was administered to 32 Beagle dogsvia intrave-nous bolus (10 mg/kg) or oral dosing (10, 20 or 40 mg/kg) administration after randomly dividing into 4 groups.The concentrations of icotinib in dog plasma were detected by using LC/MS/MS method, and the pharmacokinetic parameters were calculated.RESULTS: The linear calibration curves were obtained in the concentration range of 0.5 -10000 ng/mL .The relative standard deviation (RSD) of intra-day and in-ter-day was less than 10%.The value of area under the curve (AUC_0-t ) was (27.3 ±15.3) μg^。mL^-1。h after intravenous bolus administration.The values of AUC_0-t were (7.47 ±3.30) , (23.5 ±11.5) and (54.5 ±24.9) μg^。mL^-1。h after oral dosing for the three groups, respectively .The absolute bioavailability of icotinib in dog was 27.4%.CONCLUSION: The method is sensitive, selective and proved to be suitable for preclinical investigation of icotinib pharmacokinet-ics.

Effects of serum without immunoglobulin G from patients with systemic lupus erythematosus associated thrombocytopenia on megakaryocyto-poiesis of normal stem cells derived from cord blood

YUAN Guo-long, XU Liang, LI Zhi, CHEN Lan-fang, XUAN Dan, LU Jin-ming

2008, 13(10):  1163-1167. 

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AIM: To explore the contribution of serum without immunoglobulin G from patients with systemic lupus erythematosus (SLE) associated throm-bocytopenia on megakaryocytopoiesis of stem cells de-rived from normal cord blood .METHODS: The im-munoglobulin G was depleted from serum of patients with SLE associated thrombocytopenia by Affinity Chro-matography .The mononuclear cells derived from nor-mal cord blood were cultured in semi-solid culture sys-tem in vitro in presence of thrombopoietin (TPO) . Colony forming units-megakaryocyte (CFU-MK) was quantified by an indirect immunophosphatase alkaline labeling technique using an anti-GP Ⅱb/Ⅲa MoAb. RESULTS: No statistically difference can be found be-tween the number of CFU-MK (69.3 ±19 .4) in nor-mal control(n =10) and the group(n =4) with addit-ional serum from SLE patients with thrombocytopenia or without immunoglobulin G (58.5 ±32.5 vs 73.0 ± 28.3, P >0.05) Suppression of megakaryocyto-poiesis, however, could be observed only in one case after addition of serum, and the suppression did not disappear when immunoglobulin G was depleted from the serum by Affinity Chromatography .Morphological-ly, the large colony could be observed in normal cord blood, while almost all of colony was small after addit-ion of serum of patients (13.9±3 .9 vs 34.0±12.6, P<0.05) or without immunoglobulin G (13.9 ±3.9 vs 43.8 ±15.4, P<0.05) compare to normal con-trol .CONCLUSION: It may suggest that the serum from patients with SLE associated thrombocytopenia could suppress the formation of CFU-MK derived from normal cord blood.The suppression might be indepen-dented on immunoglobulinG .

Clinical efficacy and safety of ornidazole vaginal effervescent tablets in the treatment of bacterial vaginitis

CHENG Su-qing, GAO Hai-yan, XU Ju-fang

2008, 13(10):  1168-1172. 

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AIM: To evaluate the clinical efficacy and safety of ornidazole vaginal effervescent tablets in the treatment of bacterial vaginitis. METHODS: A random, double blind and parallel control trial method was adopted .132 patients with bacterial vaginitis were randomly assigned into trial group ( 67 cases) or control group ( 65 cases) .And patients received ornidazole vaginal effervescent tablets or metronidazole vaginal ef-fervescent tablets once daily for 7 days. Therapeutic effect of two groups were observed in 3-7 days and 28-35 days after treatment .RESULTS: The clinical cure rate, efficacy rate in 3-7 days and 28-35 days after the treatment were 88.52 %, 95.08%, 93.44%, 96.43% respectively, while those for control group were 78.69%, 91 .80%, 85.25%, 90.17%respec-tively .Adverse effect occurrence rate of trial group and control group were 1.5% and 4.9% respectively . There were no significant differences between the two groups( P >0.05) .CONCLUSION: Ornidazole vagi-nal effervescent tablets is a safe and effective agent for the treatment of bacterial vaginitis.

Administration of esmolol during operation decreased the consumption of fentanyl in senile patients and its safety

WANG Er-hua, CAI Ding-qiu, TAO Jia, CUI Shi-he, MA Zheng-liang

2008, 13(10):  1173-1176. 

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AIM: To evaluate the influences of perioperative esmolol administration upon the consump-tion of fentanyl in senile patients and its safety . METHODS: Forty ASAⅡ-Ⅲ old patients undergoing joint replacement were randomly assigned two groups of equal size .Rout fentanyl-isoflurane combined anesthe-sia was used in group C patients;Patients in the group E received an i .v.loading dose of esmolol 1 mg/kg be-fore anaesthesia induction and followed by infusion of 25 μg^。kg^{-1 。}min^-1 , MAP, HR were keeped within 20%of the baseline and BIS in 45-60 in both groups ;Observe intraoperative changes of MAP, HR, BIS, note VAS, Ramsay sedation score after extubation, note laryngeal reflex time(LRT) , eyes-opening time(EOT) , extubation time (ET) at resuscitation and follow the in-formation about drug consumption and perioperative complications.RESULTS: T 4 HR, T 2 BIS in group E were less than group C (P <0.05) ;VAS, Ramsay scores were similar between the two groups (P > 0.05) ;LRT, EOT, ET and intraoperative consump-tion of fentanyl in group E were obviously less than those in group C (P <0.05) , the rates of PONV and intraoperative awareness were similar between the two groups (P >0.05).CONCLUTION: Perioperative esmolol administration can reduce the intraoperative consumption of fentanyl during general anaesthesia in senile patients undergoing joint replacement, and that brings about quicker and safe resuscitation .

Comparison of valsartan/hydrochlorothiazide and valsartan in the treatment of hypertension

CAO Dong-ping, LV Jun-e, LIU Yong-xin, YAO Wen-jing, RONG Chun-li, YU Wei

2008, 13(10):  1177-1181. 

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AIM: To compare the T/P ratio and the smoothness index of blood pressure in the treatment of mild to moderate essential hypertension with fixed-dose valsartan/hydrochlorothiazide (80/12.5 mg) and valsartan (80 mg) , and to evaluate the depressurization therapeutic effect of valsartan/hydrochlorothiazide (80/12.5 mg) .METHODS: 84 patients with mild to moderate essential hypertension(SBP≥140 mm Hg and <160 mm Hg, DBP ≥95 mm Hg and <110 mm Hg) had been divided into randomly valsartan hydrochlorothiazide group and valsartan group.The treatment lasted for 8 weeks and the changes of blood pressure and biochemical indicator were observed be-fore and after treatment .RESULTS: The effective rate of depressurization in valsartan/hydrochlorothiazide group and valsartan group were 84.2% , 52.5% re-spectively .The rate of patient reaching goal BP levels were 73.9%, 42.9%respectively .There was statisti-cally significant difference between the two groups(P < 0.001) .The T/P ratio of SBP was 76.7%, the DBP was 71.2%in valsartan/hydrochlorothiazide group, the smoothness index of SBP was 1.14 ±0 .39, the DBP was 1.09±0 .27.The T/P ratio of SBP was 77.6%, the DBP was 71.3%, The smoothness index of SBP was 1.24 ±0.39, the DBP was 1.19 ±0.27.There were no significant difference (P>0.05) between the T/P ratio and smoothness index in the both groups. CONCLUSION: The efficacy of fixed-dose Valsartan Hydrochlorothiazide (80/12.5 mg) was superior to val-sartan(80 mg) monotherapy in the treatment of mild to moderate essential hypertension.

Dose-response and control of adeno-associated viral vectors based preclinical and clinical gene therapy

WANG Qi-zhao, LV Ying-hui, XU Rui-an

2008, 13(10):  1182-1194. 

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Human gene therapy needs to express exogenous DNA at the targeting cells, producing a practical and efficient therapeutic dosage at an approp-riate time (quantitative pharmacology)with a safe man-ner .Recombinant adeno-associated virus(rAAV)vec-tors possess a number of properties and recent progress in rAAV production made it rapidly become the reagent of choice for therapeutic gene transfer.Over 60 clinical trials of gene therapy based on rAAV have been carried out .The dose response reaction between rAAV vectors and gene expression activity or clinical outcome is one of major aspects of these trials.Most studies showed that vector genomes (vg)and gene expression had a concentration-dependent relationship during a certain scope .However, gene expression can be affected by viral serotypes, tissue tropisms, cell targeting , drug regulation, injection route , age and sex , etc .Thus, these aspects should be carefully considered by scienti-sts, pharmacologists and physicians during animal ex-periments or clinical trails.

Relationship between eIF3 subfamily and the development of tumor

HAN Li-fang, LIU Zhao-qian

2008, 13(10):  1195-1200. 

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eIF3 is the largest and most complex eukaryotic initiation factor in mammals, and it plays an important role in the regulation of translation .Some studies showed that the changes of levels of gene and protein expression of many subunits in eIF3 family are associated with the development, progression, and prognosis of human tumors. The relationship between eIF3 subfamily and the tumor development and progres-sion was reviewed in this article.