Table of Content

Volume 9 Issue 5
26 May 2004

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Immunogenicity of biotechnology-derived pharmaceticals in preclinical safety evaluation

QIAN Bo-Chu, LU Yan-Ping, XUAN Yao-Xian

2004, 9(5):  481-484. 

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Biotechnology-derived pharmaceuticals is a special class of drug manufactured by biotechnology.In this paper, the immunogenicity of biotechnology-derived pharmaceuticals was discussed, including the strain specificity of animal, humour and cell-derived immunocompetence, and reaction of combination administration in preclinical safety evaluation.

Group Ⅱ and Ⅲ metabotropic glutamate receptors agonists reverse 1-methyl-4-phenylpyridinium-induced glutamate uptake inhibition

WANG Fang, YAO Hong-Hong, HU Gang

2004, 9(5):  485-489. 

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AIM: To study the effects of group Ⅱ and Ⅲ metabotropic glutamate receptors (mGluRs) agonists on 1-methyl-4-phenylpyridinium (MPP +)-induced glutamate uptake inhibition. METHODS: The glutamate uptake into astrocytes was measured by using radio-ligand binding assay method, and the viability of astrocytes was investigated by MTT method. RESULTS: It was shown that MPP + (150, 200 μmol·L^-1) inhibited glutamate uptake into astrocytes, but produced no effect on the viability of astrocytes, and the inhibition rates were 58.3 % and 70.1 %, respectively.Group Ⅱ mGluRs agonist (2' S, 2' R, 3' R)-2-(2', 3'-dicarboxycyclopropyl) glycine (DCG-IV) (0.1, 1, 10, 100 μmol·L^-1) and Group Ⅲ mGluRs agonist L (+)-2-amino-4-phosphonobutyric acid (L-AP4) (1, 10, 100 μmol·L^-1) significantly reversed MPP +-induced glutamate uptake inhibition. CONCLUSION: MPP + directly inhibits the function of glutamate transporters, and group Ⅱ and Ⅲ mGluRs agonists produce neuroprotective effects by enhancing the activity of glutamate transporters.

Effects of diazoxide on membrane potential and respiration function of rat cardiac mitochondria

ZENG Yuan, LONG Chao-Liang, MU Shao-Feng, LI Yan-Fang, WANG Hai

2004, 9(5):  490-493. 

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AIM: To study the effects of selective mitoKATP opener diazoxide on the isolated mitochondria from rat hearts and to discuss its cardioprotective mechanism. METHODS: Using Rhodamine123 (Rh123)as fluorescent prober to measure mitochondrial membrane potential and to record mitochondrial respiratory parameters with a Clark electrode, the effect of diazoxide on mitochondrial membrane potential and mitochondrial respiration were investigated. RESULTS: 50 μmol·L^-1 diazoxide could induce mitochondrial membrane depolarization and this effect was abolished by application of a KATP channel blocker.It could decrease R3 and R4 while oxidizing FAD-dependent substrates (succinate)but did not affect respiratory control ratio (RCR). CONCLUSION: Modulation by diazoxide on functions of rat cardiac mitochondria is associated with its anti-ischemic efficacy.

Effects of prenatal exposure to phenytoin and melatonin on the development of reflex function and locomotive activities of rat pups

WU Chun-Qi, WANG Ai-Ping, LIAO Ming-Yang, WANG Zhi-Qiao

2004, 9(5):  494-499. 

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AIM: To explore the relationship between the developmental neurotoxicity (DNT) induced by prenatal phenytoin(DPH) exposure and free radicals and oxidative stress initiated in the embryonic brain. METHODS: PregnantWistar rats were administered DPH by gavage on gestation days (GD) 11-14 in doses of 0, 100, 200 mg·kg^-1 and or 40 mg·kg^-1 MT (melatonin). RESULTS: DPH treated dams showed a dose related decrease in weight gain throughout the treatment period. Offspring had significantly lowered birth weight along with increased mortality.During the neonatal period, the pups exposed in uterus to DPH showed a significant increase in pivoting locomotion, and delayed in air righting reflex and swimming development.As adults, these pups showed an increased ambulation, rearing, stereotype events and rotational behavior.Furthermore, prenatal DPH exposure resulted in a dose-response shift to the left for locomotor activity of F1 DPH pups after stimulated by 0.2 and 2.0 mg·kg^-1 apomorphine. CONCLUSION: Co-administration of MT and DPH to dams significantly antagonized or protected most of the postnatal adverse effects induced by prenatal DPH exposure in F1 pups, which suggest that DNT induced by prenatal DPH exposure may be evoked and mediated via oxidative stress.

Study on hepatic cytochromes P450 methodology in Wistar rats

ZHU Man, WANG Rui, ZHANG Yong-Qing, CHEN Kun

2004, 9(5):  500-503. 

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AIM: To study the methodology of hepatic cytochromes P450 in Wistar rats. METHODS: After the Wistar rats were administered with gatifloxacin and ciprofloxacin once daily for 7 days, and liver microsome was distilled by different velocity centrifugation.The Lowry method was used to measure the concentration of protein in liver microsome, and the activities of gatifloxacin in hepatic microsomal enzymes (CYP450)of rats were studied by spectrophotometer. RESULTS: The linearity range of ox blood serum albumin standard curve was 25-250 mg·L^-1 with the detection limits 25 mg·L^-1 and correlation coefficient 0.9988.The contents of cytochromes P450 and cytochromes b5 and the activity of NADPH-cytochrome C reductase indicated that ultraviolet spectrophotometer method was sensitive.The linearity range of formaldehyde standard curve, which was used to measure the activities of aminopyrine-N-demethylase and erytheomycin-N-demethylase was 0.05-0.5 mmol ·L^-1 with the detection limits 0.05mmol·L^-1 and correlation coefficient 0.9998.The linearity range of resorufin standard curve, which was used to measure the activity of Coumarin 7-hydroxylation was 1-8 μmol·L^-1 with the detection limits 1 μmol·L^-1 and correlation coefficient 0.9998. CONCLUSION: The methods of measuring the contents and activities of the six hepatic microsomal enzymes are sensitive and credible in Wistar rats by ultraviolet and fluorescence spectrophotometer.

Inhibition of prodigiosin on multiplication of human malignant pancreas cancer cells

SHEN Ya-Lin, LIU Jian-Wen, WEI Dong-zhi, TAO Jin-Li, LI Ke, ZHANG Jing

2004, 9(5):  504-509. 

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AIM: To investigate the inhibitive effects of prodigiosin on the multiplication of human malignant pancreas cancer cell 8898, and its mechanism. METHODS: MTT assay was used to measure the rate of viability and inhibition of 8898 cells;the change of cell cycle and the percent of apoptosis were analyzed by FCM;the concentration of prodigiosin in 8898 cells was measured HPLC;and the fragmented DNA was analyzed by agarose gel electrophoresis. RESULTS: In the culture medium containing 5 mg·L^-1 prodigiosin, 8898 cells appeared the morphological character of early stage of apoptosis.Half inhibition concentration (IC50) was 30 mg·L^-1.But to 3T3 cells the drug had no obvious effect.The inhibitive effect of prodigiosin on multiplication of cancer cells was related to the inhibiting of DNA replication in S stage and regulating of cell cycle.The results of HPLC showed that pharmacological effect of prodigiosin dependent on drug concentration in cells. CONCLUSION: Prodigiosin can enter cells and inhibit the multiplication of cells.The mechanism may be related to inducing apoptosis and regulating cell cycle.

Study on absorption mechanism of ginsenoside Rg1 using rat everted gut sac

LI Hao, SUN Jian-Guo, XIE Hai-Tang, WANG Rui, LU Hua, WANG Guang-Ji

2004, 9(5):  510-513. 

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AIM: To develop an accurate, sensitive and reliable HPLC MS detection method for the ginsenoside Rg1, and to study the absorption characteristics of Rg1 in different intestinal sections (ileumand jejunum) and the influence of p-glycoprotein on the absorption rate. METHODS: Rat everted gut sac system was used. Sac containing drug free Krebs solution was immersed into the Krebs solution containing 20 mg·mL^-1 Rg1.The solution inside the sac was collected and drug concentration was determined by validated ESI-HPLC-MS method.Verapamil, a p-glycoprotein inhibitor, was used to study the influence of p-glycoprotein on the absorption of Rg1. RESULTS: The Rg1 concentration in the sac was increasing according to the time and there is no difference of the absorption rate between ileum and jejunum.Verapamil had no effect on the absorption of Rg1 in sac system. CONCLUSION: There is no difference for Rg1 absorption between ileum and jejunum of rat.Rg1 might not be the substrate of p-glycoprotein.

Evaluation of release kinetics of serum creatine kinase isoenzyme MB and cardiac troponin I during no-reflow phenomenon determined by administration of Albunex

CHEN Li-Xin, WANG Xin-Fang1, XIE Ming-Xing1, ZHU Xiang-Ming2, WU Ying

2004, 9(5):  514-518. 

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AIM: To validate the relationship between the release kinetics of serum creatine kinase isoenzyme MB (CK-MB) and cardiac tropnin I (cTnI) and myocardial microvascular impairment during the development of no-reflow phenomenon by measurement of serum CK-MB and cTnI in combination with administration of Albunex. METHODS: 19 dogs underwent 60 min myocardial ischemia, followed by reperfusion of 60 min (n=6), 120 min (n=6) and 180 min (n=7), respectively.Myocardial contrast echocardiography (MCE) was performed by a bolus injection of Albunex.The measurement of peripheral blood concentrations of CK-MB and cTnI at baseline, 60 min ischemia (T0) and 60 min reperfusion (T60) were initiated, and then the increase slope (T60-T0 60) and relative increase value (T60-T0/T0) were calculated at 60 min reperfusion. RESULTS: The concentrations of serum CK-MB and cTnI were markedly higher at 60 min myocardial ischemia than those at baseline (P <0.01).At 60 min reperfusion, a significant difference in the levels of CK-MB and cTnI was observed between ref low group and no-reflow group (P < 0.01).There was a marked difference in the levels of CK-MB and cTnI between reflow group and no-reflow group, too (P <0.01).An extremely significant difference in the increase slope and relative increase value at 60 min reperfusion between two groups was found (P < 0.001). CONCLUSION: These findings show that damaged microvarculature may profoundly influence the release kinetics of serum CK-MB and cTnI.

Effect of taurine on the content of tumor necrosis factor alpha and angiotensin Ⅱ in plasma and myocardium of the rats following severe burns

WAN Fu-Sheng, WAN Yi-Fu, LI Guo-Hui

2004, 9(5):  519-522. 

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AIM: To investigate the effect of taurine on myocardial injury in rats with severe burns. METHDOS: 110 healthy adult Wistar rats were randomly divided into 3 groups:the normal control (n=10, without burns), the burn group (n=50, subjected to a 30 % total body surface area III degree scald injury), and the group treated with taurine (n=50), by abdominal cavity injection taurine (400 mg·kg^-1) after scald injury immediately.Levels of tumor necrosis factor alpha (TNF-α), troponin (cTnT) and angiotensin Ⅱ (Ang Ⅱ) in plasma and content of TNF-α, Ang Ⅱ in myocardiumwere assayed at 1, 3, 6, 12 and 24 h postburn. RESULTS: Plasma cTnT increased markedly at 3h postburn, peaking at 12 h, and it was still higher than that of the control at 24 h postburn.TNF-αin plasma and myocardium also increased markedly at 6 h postburn, peaking at 12 h postbrun, and decreased somewhat at 24 h postburn, but it was still higher than that of the control group.Plasma Ang Ⅱ increased significantly at 1 h postburn, peaking at 6 h postburn, and it was also higher than that of the control in plasma and myocardium at 24 h postburn.After treated with taurine, however, levels of cTnT, TNF-αand Ang Ⅱ in plasma and myocardium decreased significantly compared with that of the burn group.Additionally, the levels of TNF-αand Ang Ⅱ in plasma were correlated with cTnT levels. CONCLUSION: Taurine can protect myocardium from injury following severe burns.

Effects of probenecid on pharmacokinetics of cefaclor in rats

ZHANG Xiu-Hong, MA Zhang-Qing, GUI Chang-Qing, SONG Jian-Guo

2004, 9(5):  523-526. 

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AIM: To investigate the effect of concurrent probenecid administration with different dosages on pharmacokinetics of cefaclor in rats. METHODS: Cefaclor (100 mg·kg^-1, ig) was given alone or in the presence of probenecid (300, 600 and 900 mg·kg^-1, ig) to rats.Serial blood samples were drawn according to the exact time schedule and concentrations of cefaclor were determined by HPLC method. RESULTS: Under the dosages of probenecid ranged from 300 to 600 mg·kg^-1, Cmax and AUC of cefaclor increased, while Vd/F and Cl/F of cefaclor decreased.However, when a still higher dosage (900 mg·kg^-1) of probenecid was used, Cmax of cefaclor decreased, while AUC, Vd F and Cl/F maintained at the levels of those with probenecid 600 mg·kg^-1. CONCLUSION: Probenecid can markedly alter pharmacokinetics of cefaclor and the influential magnitude for each parameter is dependent on the dose of probenecid used in the trial.The Cmax of cefaclor increases with proper dosage of probenecid, while decreases with over dose of probenecid, and this phenomenon may be related to the inhibition of cefaclor intestinal absorption attained with over dose of probenecid.

Effects of glucagon-like peptide-1 (7-36) on decreasing blood glucose in normal animals

LE Jia-Jing, LI Zhan-Jun, QU Cai-Rong, GONG Ze-Hui, XU Kang-Sen

2004, 9(5):  527-531. 

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AIM: To observe the effects of glucagonlike peptide-1 (rhGLP-1) (7-36) on decreasing blood glucose and stimulating the insulin secretion in mice and rabbits, and how the actions depend on the glucose levels. METHODS: After subcutaneous injection of rhGLP-1(7-36) at different doses in different animal models, the serum was collected and the values of blood glucose and insulin were measured. RESULTS: After subcutaneous injection of rhGLP-1 (7-36) at different doses in normal C57 mice and rabbits, no obvious changes of the levels of blood glucose and insulin secretion was found, which suggested rhGLP-1 (7-36) did not affect the levels of blood glucose and the action of insulin secretion.For the mice and rabbits given doses of glucose 2 and 3 g·kg^-1 respectively, rhGLP-1 (7-36) had the effects of increasing insulin secretion, and lowering the level of blood glucose strongly, which suggested rhGLP-1(7-36) had obvious effect of increasing insulin secretion depending on the level of glucose.In the glucose tolerance test (GTT), rhGLP-1 (7-36) of 16 μg·kg^-1 increased the insulin secretion of rabbit given glucose, and had the effect of lowering the glucose curve obviously, which showed the rhGLP-1(7-36) could improve the tolerance to glucose of rabbits. CONCLUSION: rhGLP-1 (7-36) has the effect of lowering the levels of glucose.However, it has no effect on the normal level of glucose.

Gender difference of nimodipine pharmacokinetics in rats

WANG Xiao-Li, XIE Lin, LIU Xiao-Dong

2004, 9(5):  532-535. 

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AIM: To study gender difference in nimodipine (NMD) pharmacokinetics in rats after oral administration NMD and co-administration erythromycin (Ery). METHODS: NMD concentrations in plasma were determined by HPLC after ig administration of 20 mg·kg^-1 NMD and co-administration of 50 mg·kg^-1 Ery, respectively. RESULTS: Marked gender differences for NMD concentrations in rat plasma were found after oral administration of 20 mg·kg^-1 NMD.In groups of NMD alone, the plasma concentrations of NMD in male rats were significantly (P <0.05) lower than those in female rats.AUC value of NMD in male rats was only about one-fourth of that in female rats.In groups for co-administration of Ery, there also exists gender difference;the concentrations of NMD in male rats also were significantly (P <0.05) lower than those in female rats and AUC value of NMD in female rats was about 3.4-folds of that in male rats.In addition, NMD concentration in plasma was significantly increased after co-administration Ery, which AUC values increased 2.0-and 1.6-folds of those in alone NMD, respectively. CONCLUSION: There are marked gender differences in NMD pharmacokinetics of oral administration in rats, and Ery can increase plasma concentrations of NMD.

Antibacterial activity of cefathiamidine in vitro combined with 6 antimicrobial agents against Staphylococcus epidermidis

ZHOU Xiao-Qing, PEI Fei, CHAI Dong, FANG Yi, WANG Rui

2004, 9(5):  536-539. 

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AIM: To evaluate the antibiotic effects in vitro of cefathiamidine combined with 6 antimicrobial agents against Staphylococcus epidermidis. METHODS: The protocol was designed by checkerboard method, the MICs against 30 strains of Staphylococcus epidermidis were determined by broth dilution method, and the FIC index was calculated according to MIC values. RESULTS: The MIC50 of cefathiamidine alone against Staphylococcus aureus was 16 mg·L^-1 and theMIC50 of cefathiamidine combined with 6 antimicrobial agents was reduced to 0.125, 0.125, 0.125, 0.125, 0.25, 0.125 mg·L^-1, respectively.The MIC90 of cefathiamidine alone against Staphylococcus epidermidis was reduced to 1, 1, 1, 2, 1 mg·L^-1, respectively. CONCLUSION: The synergism and additivity are shown when cefathiamidine combined with 6 antimicrobial agents against 30 strains Staphylococcus epidermidis, and the autonomy and antagonism are not found.

Effects of ecdysterone on injury of endothelial cells following experimental subarachnoid hemorrhage

CHEN Zhi, ZHU Gang, TANG Wei-Hua, LIU Zhi, WU Nan, WANG Xian-Rong, FEN Hua

2004, 9(5):  540-543. 

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AIM: To investigate the effects of ecdysterone (EDS) on injury and proliferation of endothelial cells caused by bloody cerebralspinal fluid (BCSF). METHODS: Rabbit brain microvessel endothelial cells (BmvECs) were divided into control group, BCSF group and EDS group, which were treated with DMEM, BCSF and both of BCSF and EDS (200 mg·L^-1), respectively. Morphological changes, cell counting, MTT assay, and flow cytometric analysis were used to evaluate the cytotoxic effects on BmvECs. RESULTS: BCSF could cause severe morphologic changes in BmvECs, decrease the OD of MTT assay and cell proportion of G0-G1 of BmvECs(P <0.01).EDS could alleviate these changes in BmvECs caused by BCSF. CONCLUSION: EDS has protective effects on the injury of BmvECs caused by BCSF, which suggests EDS may play a role in the therapy of CVS.

Reversal of multidrug resistance by CPUE1 in K562 A02 cells

ZHU Hao-Jie, HOU Yuan-Yuan, LIU Guo-Qing

2004, 9(5):  544-547. 

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AIM: To study the effect of CPUE1 on the reversal of multidrug resistance (MDR) in K562/A02 cells and its mechanism. METHODS: MTT assay was used to determine the influence of CPUE1 on the cytotoxicity of vincrisine (VCR) in K562/A02 cells.The effect of CPUE1 on the apoptosis induced by VCR in K562/A02 cells was detected using DNA analysis and Annexin-Ⅴ PI double stain assay.Flow cytometry was used to investigate the efflux of rhodamine123 (Rh123) by P-glycoprotein (P-gp) in K562 /A02 cells. RESULTS: CPUE1 increased the cytotoxicity and apoptosis induced by VCR in K562 A02 cells.At the concentration of 10 μmol·L^-1, CPUE1 reduced the IC50 value of VCR from 60.54 to 4.17 μmol·L^-1.CPUE1 inhibited the efflux of Rh123 and resulted in the increase of intracellular accumulation of Rh123 in K562/A02 cells. CONCLUSION: CPUE1 has strong reversal effect on MDR in K562/A02 cells by inhibiting P-gp activity.

Effects of bifendate on the blood concentration and hepatic toxicity of cyclosporine A in renal transplanted recipients

YU Ai-Rong, WU Xiao-Chun, LI Qing, XIN Hua-Wen, ZHU Min

2004, 9(5):  548-550. 

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AIM: To study the effects of bifendate on the blood concentration and hepatic toxicity of cyclosporine A in renal transplanted recipients. METHODS: 28 cases with renal transplantation in coadministration group were treated with CsA and BFD, and 30 cases with renal transplantation in control group received only CsA.Blood levels of CsA, biochemistry indexes for liver and renal function were determined. RESULTS: Blood concentrations of CsA in patients combined with BFD went down by 17.7 % compared with those before taking BFD and had a significant decrease compared with control group.Blood concentrations of CsA were significantly increased after stopping BFD administration.Mean blood concentrations were increased by 36.3 %.BFD could effectively reduce higher ALT and AST. CONCLUSION: BFD can markedly decrease the blood concentration of CsA in renal transplanted recipients.

Comparation of quetiapine and clozapine in treatment of patients with first-onset schizophrenia

WANG Man, HAN Feng, MA Huan

2004, 9(5):  551-554. 

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AIM: To compare the efficacy and safety between quetiapine and clozapine. METHODS: There were 85 patients with first on-set schizophrenia in this study, 43 patients treated with quetiapine 425 ± 56 mg·d-1 and 42 patients treated with clozapine 350 ± 73 mg·d-1.The study lasted for 8 wk.The Positive and Negative Symptom Scale (PANSS) and Treatment Emergent Symptom Scale (TESS) were used to evaluate therapeutic and side effects. RESULTS: The PANSS scores in both groups decreased significantly after treatment with those two drugs(P <0.05 or P <0.01).The rates of improvement were similar in quetiapine group and in clozapine group (88.4 % vs 83.8 %).The efficient dosages ranged from 375 to 600 mg·d-1 for quetiapine and from 300 to 475 mg·d-1 for clozapine.TESS showed quetiapine had fewer side effects than clozapine. CONCLUSION: Quetiapine has similar efficacy and the time before effect to clozapine in the treatment of schizophrenic with fewer side effects than clozapine.

Effects of adriamycin on cell apoptosis and expression of dephosphorylated RB protein in human breast cancer

WANG Wen-Wu, OU-YANG Xue-Nong, JIANG Hao

2004, 9(5):  555-557. 

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AIM: To investigate the roles that adriamycin (ADR) plays in the expression of dephosphorylated RB protein and inducing apoptosis of human breast cancer cells (MCF-7/S) cultured in vitro. METHODS: MTT colorimetric assay was applied to examine the growth inhibition, and apoptosis rates (AR) were determined by terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL);the expressive levels of dephosphorylated RB protein were detected with immunocytochemistry. RESULTS: ADR inhibited proliferation of MCF-7 S cells in a dose dependent manner, and the 50 % inhibition concentration (IC50) was 0.128 mg·L^-1.Tumor cell AR in ADR group ($x^{-}$=0.261) was significantly higher than that in control group ($x^{-}$=0.045, P < 0.01).The expressive levels of dephosphorylated RB protein in ADR group (MOD ×area=987 ±207) was significantly higher than that in control group (MOD ×area=132 ±32, P <0.01).The dephosphorylated RB was enhanced by ADR in breast cancer cells.There was significant positive correlation between AR and the expressive levels of dephosphorylated RB protein in ADR group (P <0.05). CONCLUSION: ADR inhibits the growth proliferation and induces apoptosis in MCF-7/S cell line, which is possibly related to enhancing dephosphorylated RB protein expression.

Effects of tetramethylpyazine injection on isolated tracheal smooth muscles of guinea pigs

YANG Yan-Qiu, LI Riu-Fa, XU Ji-De, FANG Mao, WU Jie, Huang Wen-Xian

2004, 9(5):  558-560. 

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AIM: To investigate the effects of tetramethylpyazine (TMP) on isolated trachea of guinea pigs. METHODS: The contraction effects were observed from the isolated tracheal smooth muscles. RESULTS: TMP had a significant relaxing effect of concentration-dependent on isolated tracheal smooth muscles and the effect was antagonized by propranolol.It had also obvious synergism to nifedipine in the direct relaxation to the isolated tracheal smooth muscles.Atropine had no effect on the relaxation of the TMP. CONCLUSION: TMP has a significant relaxing effect on isolated tracheal smooth muscles of guinea pigs.The effect is related with β2 receptors and inhibiting calcium inflow.

Clinical study on the six-minute walk test and serumbrain natriuretic peptide levels in patients with chronic heart failure

CHEN Xie-Xing, HONG Hua-Shan, CHEN Liang-Long, ZHENG Guan-Yi1, WANG Yi-Bo, JIANG Qiong, DONG Xian-Feng

2004, 9(5):  561-564. 

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AIM: To investigate clinical significance of Six-Minute Walk Test (6MWT) and serum brain natriuretic peptide (BNP) levels in evaluating heart function in patients with chronic heart failure (CHF). METHODS: 51 patients with CHF (CHF group) and 30 healthy subjects served as control group were involved in the trials.The distance walked in six-minute and the serum levels of BNP-32 by enzyme-linked immunosorbent assay method were observed.The differences among 6MWT distance, BNP levels and different NYHA classes were analysed. RESULTS: The 6MWT distances in CHF group and control group were 380.3 ±121.7 and 546.8 ± 128.5 m, respectively (P <0.01).The serum levels of BNP in CHF group and control group were 758.3 ±289.5 and 109.3 ±37.6 ng·L^-1, respectively (P <0.01). The 6MWT distances in NYHA class Ⅱand Ⅲ of CHF patients were 425.0 ±105.8 and 335.6 ±126.1 m, respectively (P <0.01).The BNP levels in NYHA class Ⅱ and Ⅲ of CHF patients were 638.5 ±224.5 and 878.0±334.0 ng·L^-1, respectively (P <0.01).BNP levels in CHF patients of 6MWT distances among below 300, 300-374.9, 375-449.9 and above 450 m was 988.9 ±202.6, 768.6 ±217.4, 657.5 ±185.0 and 506.9 ±198.4 ng·L^-1, respectively (P <0.01).The 6MWT distance was inversely correlated to the BNP level (r=-0.752, P <0.01). CONCLUSION: Not only 6MWT distances but also serum BNP levels have an important clinical value in evaluating heart function of CHF.

Effects of berberine chloride and co-administration with cyclosporin on CPY3A1 in rat liver and small intestine

XIN Hua-Wen, WU Xiao-Chun, LI Qing, YU Ai-Rong, ZHONG Min-Yuan, ZHU Min, LIU You-Ying

2004, 9(5):  565-568. 

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AIM: To study the effects of berberine chloride (Ber) and co-administration with cyclosporin (CsA) on CYP3A1 in rat liver and small intestine. METHODS: The rats were randomly divided into 7 groups: control group, 150 mg·kg^-1 ketoconazole, 100 mg·kg^-1 Ber, 200 mg·kg^-1 Ber, 45 mg·kg^-1CsA, 100 mg·kg^-1Ber co-administrated with 45 mg·kg^-1CsA, and 200 mg·kg^-1 Ber co-administrated with 45 mg·kg^-1CsA.The levels of CYP3A1 in rat liver and small intestine were assayed by RT-PCR and Western blot. RESULTS: After administration for 12 d, all drug administration groups, except 100 mg·kg^-1 Ber, had significant inhibitory effects on the mRNA levels of CYP3A1 by RTPCR analysis in the liver.The analysis of Western blot showed that 200 mg·kg^-1 Ber co-administrated with 45 mg·kg^-1CsA for 6d exhibited the inhibitory action on CYP3A1 in the liver.Moreover, 100 mg·kg^-1Ber co-administrated with 45 mg·kg^-1 CsA and 200 mg·kg^-1 Ber co-administrated with 45 mg·kg^-1 CsA for 12 d could markedly inhibit the expression of CYP3A1 by Western blot analysis in both liver and small intestine. CONCLUSION: The mechanism on the increase of CsA concentration by Ber may be that Ber intensifies the inhibitory effects of CsA on CYP3A1 to reduce the metabolism and elimination of CsA in liver and small intestine.

Arsenic trioxide-induced apoptosis in K562/ADM cells and its mechanisms

WANG Dong-Hai, WEI Hu-Lai, SU Yong-Hong, HAO Chun-Yan, LIU Jian-Min

2004, 9(5):  569-572. 

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AIM: To observe the apoptosis of K562/ ADM cells induced by As2O3 and to explore its possible mechanisms. METHODS: MTT assay, Wright-Giemsa staining, DNA agarose gel electrophoresis and cell cycle analysis were used to examine apoptosis in K562/ADM cells.Expression levels of Fas, Bcl-2 and P53 antigens were measured with FCM.Colorimetric assay was employed to detect the activation of Caspase3. RESULTS: As2O3 inhibited growth of K562/ADM cells.Morphological changes typical of apoptosis were observed through light microscopy.Agarose gel electrophoresis showed evident DNA fragmentation.Cell cycle analysis indicated increased Sub-G1 proportion and apoptosis rate, as well as apparent G2 M phase arrest.The expression of Fas and P53 antigens significantly increased after application of As2O3.Caspase 3 was also activated by As2O3. CONCLUSION: As2O3 induces apoptosis in K562/ADM cells by activating Caspase 3 via a Fas-dependent pathway.

Interaction between 5-fluorouracil, mitomycin and epirubicin on human pancreatic carcinoma cell line Aspc-1 and Bxpc-3

ZHOU Jun-Jie, FENG Yao-Liang, SHI Hai-Bing, DAI Chun-Cai

2004, 9(5):  573-576. 

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AIM: To observe effects of 5-fluorouracil, mitomycin and epirubicin on human pancreatic carcinoma cell line Aspc-1 and Bxpc-3. METHODS: The MTT assay and median-effect principle were used to observe the effects. RESULTS: The effects of the individual or combined drugs were enhanced as drug concentration increased.The interaction between 5-fluorouracil and mitomycin was synergistic at higher concentration (CI <1) and antagonistic at lower concentration (CI >1), but between mitomycin and epirubicin, it was slight antagonistic on Aspc-1.The interactions between 5-fluorouracil and mitomycin, mitomycin and epirubicin were synergistic at lower concentration (CI <1) and antagonistic at higher concentration (CI >1) on Bxpc-3.The interaction between 5-fluorouracil and epirubicin was slight antagonistic on both cell line. CONCLUSION: Increment of the local drug concentration by intraarterial infusion or consecutive arterial infusion through the reserved catheter can improve the chemotherapeutic efficiency of pancreatic carcinoma.The interactions between the drugs are related to the drugs concentration, different drugs and cell line.

Clinical pharmacokinetics and bioequivalence of domestic gatifloxacin in Chinese male volunteers

ZHANG Jing, YU Ji-Cheng, CAO Guo-Yin, SHI Yao-Guo, WU Ju-Fang, CHEN Zhang-Jin, ZHANG Yin-Yuan

2004, 9(5):  577-580. 

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AIM: To evaluate the pharmacokinetic profiles and the bioequivalence of domestic gatifloxacin in Chinese male volunteers. METHODS: 24 healthy male volunteers received a single 400 mg dose of domestic or imported tablet of gatifloxacin in a randomized and twoway crossover design.The drug concentrations in plasma and urine were measured by HPLC method. RESULTS: The pharmacokinetics of gatifloxacin was fitted into twocompartment model after a single oral dose of 400 mg domestic and imported tablet in 24 healthy volunteers.The mean peak concentration (C_max), median peak time (T_max), elimination half-life (T_{1 2β ) and area under the curve (AUC0~∞ ) in plasma were 4.45 ±1.04 and 4.05 ±0.85 mg·L^-1, 0.75(0.5, 3) h and 0.75(0.5, 2.5) h, 6.97 ±1.08 and 7.19 ±0.91 h, 31.99 ±3.80 and 32.11±3.37 mg·h·L^-1, respectively.The cumulative urinary excretion rates within 48 h were (79.47 ± 6.00) %and (79.59 ±5.89) %.Compared with imported tablet, the differences of the main pharmacokinetic parameters were not statistically significant (P >0.05). The relative bioavailability of domestic gatifloxicin tablet was (99.74 ±7.42) %. CONCLUSION: The effective concentration maintained in plasma is longer and the cumulative urinary excretion rate is higher after a single oral dose of domestic tablet of gatifloxacin and it was equivalent to that of imported gatifloxacin.}

Preventive effects of compound danqi on prednisone-induced cerebra in rats

ZOU Li-Yi, WU Tie, CUI-Liao

2004, 9(5):  581-584. 

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AIM: To study the cerebra damaged by long-term administration of prednisone, and investigate the preventive effects of compound danqi (CD) in rats. METHODS: 40 SD rats were randomly divided into 5 groups with 8 rats each group.Group 1 was control (NS group), other groups were oral gavages prednisone (2.7 mg·kg^-1 ·d^-1) first, and then plus vehicle (GC group), or plus CD at dose of 2.5, 5.0 or 10.0 g·kg^-1·d^-1, respectively, once a day for 12 weeks.At the experimental endpoint, animals were drawn blood from right ventricle under anesthesia.The left half cerebrum was milled in 10 % homogenate to test the content of mono-amine oxidase (MAO), superoxide dismutase (SOD) and acetylcholinesterase (AchE).The right half cerebrum was for histological observation. RESULTS: The concentration of SOD and AchE decreased, yet MAO increased significantly in GC group.Moreover, histopathology showed that the structure of cerebrum cortex became thinner and hippocampi was in disorder.Dropsical and necrotic nerve cells were found.Yet CD could prevent the changes of nerve centre in prednisone tats. CONCLUSION: Cerebra damage occurs in four-month-old male Sprague-Dawley rats after prednisone-treated for 12 weeks.The treatment of CD in different dose can prevent the damage.

Antioxidant effects of extract solution of bamboo leaves in mice

MA Shi-Yu, LI Li, WU Ji-Liang, YAO Jing-Qi, LUO De-Sheng

2004, 9(5):  585-587. 

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AIM: To study the antioxidant effects of extract solution of bamboo leaves in mice and the effects of scavenging hydroxyl free radical (·OH-) in vitro. METHODS: The mice were treated with extract solution of bamboo leaves (8, 12 g·kg^-1, ig) daily for 30 d.The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in blood and the contents of lipofuscin (LF), malondialdehyde (MDA) and SOD in liver, and brain and heart by biochemical methods were determined.·OH-was induced by ascorbate-Cu 2+reaction system, and the effect of extract solution of bamboo leaves on scavenging ·OH-was estimated by colorimetry. RESULTS: The extract solution of bamboo leaves could significantly increase the activities of SOD and GSH-Px in blood and the activities of SOD in liver, brain and heart in mice, and obviously reduce the contents of LF and MDA in mice tissues.The extract solution of bamboo leaves of 0.05-1.0 g·L^-1 had markedly effects on scavenging ·OH-from 7.8 % to 87.7 % in dose-effect relationship (r=0.976). CONCLUSION: The extract solution of bamboo leaves can obviously inhibit damage of free radical and prevent lipid peroxidation.The mechanisms may associate with directly scavenging ·OH-, and with increasing the activities of antioxidation enzymes in mice tissues.

Effects of xanthotoxol on physiological characteristics of isolated guinea pig atrium

LIU Jian-Xing, ZHOU Qing, ZHOU Li, LIAN Qi-Shen

2004, 9(5):  588-591. 

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AIM: To study the effects of xanthotoxol (XT) on physiological characteristics and its mechanism in isolated guinea pig atria. METHODS: It was determined by the contractile amplitude, excitability and the spontaneous beats in the right atria, respectively. RESULTS: In the experiment of contractile amplitude, after 15 min of administration of XT 20, 40 and 80 μmol·L^-1, the contractile force of left atria was 0.85, 0.68, and 0.48 g, respectively (P <0.05, compared with control group).It showed that XT could decrease the contractile force in concentration-dependent manner significantly.In the experiment of the sinus rates, after 30 min of administration of XT 20 and 40 μmol·L^-1, the fact that the sinus rates decreased from 90.0 min-1 to 60.2 min-1 and 38.7 min-1, respectively (P <0.05 vs solvent group) indicated that XT significantly reduced the sinus rates.In the experiments of the functional refractory period and excitability, no effects of XT were demonstrated. CONCLUSION: XT can decrease the contractile force and the spontaneous beats.The inotropic and chronotropic action of XT may be related to inhibiting Ca²⁺ influx from outside the cells and Ca 2+ release from calcium reservoir inside the cells.

Evaluation of therapeutic efficacy and failure factors of methotrexate in treatment of ectopic pregnancy

LIN Qiong

2004, 9(5):  592-594. 

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AIM: To evaluate the therapeutic efficacy and failure factors in single dose methotrexate intramusculr injection in treatment of ectopic pregnancy. METHODS: The clinical data of 70 successfully treated cases and 10 failed cases were analyzed comparatively, including the duration of menoschesis, serum β-HCG level, diameter of adnexa mass and abdominal pain before treatment as well as the decline rate of serum β-HCG level and change of mass diameter after 3 d of treatment. RESULTS: In succeeded group, the average duration of menoschesis, the mean level of serum β-HCG and average diameter of adnexa mass were 53 ±5 d (14.3 % of patients ≥60 d), 1483 ±216 IU·L^-1 (11.4 %of patients ≥4000 IU·L^-1) and 2.9 ±0.9 cm(7.9 % of patients showed increase of mass diameter ≥25 %), respectively; whereas in failed group, these corresponding figures were 62 ±6.d(40.0 %), 6661 ±126 IU·L^-1 (80.0 %), 4.1 ±0.6 cm (40.0 %), respectively.After 3 d of treatment, 14.3 % of patients in succeeded group revealed a decline rate of serum β-HCG level ≤15 %, while 60.0 % of patients in failed group revealed a similar decline rate. CONCLUSION: Methotrexate is an effective drug for treating ectopic pregnancy in its early stage.The serum β-HCG level before treatment, its decline rate and the change of adnexa mass diameter after 3 d of treatment are closely related to the therapy failure.Presence of fetus heart beating is not a contraindication for drug treatment of ectopic pregnancy.

Technical procedure for design and development of clinical trial data collecting and reporting documents

WANG Yi-Bing, XIONG Ning-Ning, BO Qing-Yan, ZHOU Jian-Dong, JIANG Meng, LIU Fang, FU Wei-Min

2004, 9(5):  595-597. 

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The quality and integrity of the clinical trial data rely importantly on the design and compilation of report documents and the collection of trial data.Therefore, based on practical experiences and with reference to the Good Clinical Data Management, we develop this technical procedure, including designing and printing procedures.

Data and safety monitoring in clinical trials

ZOU Jian-Dong, XIONG Ning-Ning, WANG Xiu-Qin, LIU Fang, JIANG Meng, FU Wei-Min

2004, 9(5):  598-600. 

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The purpose of clinical data and safety monitoring is to insure the safety of participants, the validity of data, and the appropriate termination of studies for which significant benefits or risks have been uncovered or when it appears that the investigation cannot be concluded successfully.All clinical trials require data and safety monitoring plans, or data and safety monitoring board as necessary.The method and degree of data and safety monitoring must be commensurate with the degree of risk involved in participation in the trial and the size and complexity of the trial.The range of monitoring includes the quality of trial execution, safety data and efficacy data, while types of monitoring include continuous and cumulative evaluating trial outcome data and interim analyses