Chinese Journal of Clinical Pharmacology and Therapeutics

General considerations on adaptive designs for clinical trail and drug evaluation

ZHAO Chao

2008, 13(1): 1-5.

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Adaptive design is a trial design that allows modifications to some aspects of the trial after its initiation without undermining the validity and integrity of the trial. Adaptive design makes it possible to discover and rectify inappropriate assumptions in trial designs, reduce development costs and the time to market. It has been very attractive to the pharmaceutical industries. In this paper, it is not focused on adaptive designs for clinical trials with multiple endpoints studied using computer simulations, but is to clarify our evolution, which is taken into consideration in a trial adaptive design at present, if need modifications.

Physiological action of peroxisome proliferator activated receptor γcoactivator-1 and its relationship with type 2 diabetes

ZHANG Ke-han, LIU Zhao-qian

2008, 13(1): 6-10.

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Peroxisome proliferator activated receptorγcoactivator-1 (PGC-1) is one of the coactivators which binds to nuclear receptors or non-nuclear receptor transcription factors and coactivates the transcription and expression of target genes. Some target genes mediated by PGC-1 are vital genes for energy and glucose lipid metabolism and they play very important role in regulation of normal energy balance in human body. Recently, some studies showed that the genetic polymorphisms of PGC-1 were associated with the development of type 2 diabetes, which possibly makes it as a new candidate target gene in the treatment of patients with type 2 diabetes.

Metabonomics technology and its applications in disease diagnosis

GUAN En-ze, ZHU Xuan-xuan, WANG Guang-ji, HAO Hai-ping, DING Yang

2008, 13(1): 11-15.

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Metabonomics is the scientific technology to study the regularity of metabolic products in metabolic proceeding and to reveal the essence of vital movement. Metabonomics technologies are introduced in the following aspects: the concepts, characteristics, research direction and approaches. Metabonomics technology and its applications in disease diagnosis are reviewed in this paper.

Advancement of perioperative application of lornoxicam

CHEN Xiao-fei, GUO Jian-rong

2008, 13(1): 16-20.

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Lornoxicam is a new non-steroidal anti-inflammatory drug, it can inhibit the activity of cyclooxygenases and the immunologic injury after operation. Its efficacies on preoperative, operative period and postoperative analgesia are similar to those of opioid. Lornoxicam can decrease the dosage of opioid drugs and has the good qualities of short half-life, few adverse effects and satisfactory tolerance. Lornoxicam can provide rapid and stable analgesic effect in perioperative phase.

Discussion and considerations on the mutant prevention concentration and mutant selective window

HUANG Han, LIU Shi-kun

2008, 13(1): 21-24.

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The mutant prevention concentration (MPC) and mutant selective window (MSW) were new conceptive theories of resistance mutantion preventation which were raised by Zhao X and Drlica K et al. In this paper, the conceptions of MPC and MSW and some could related issues were discussed. Finally how to prevent resistance mutantion was reviewed.

Progress the in etiology and treatment of panic disorder

WANG Xin, LIU Xin-min

2008, 13(1): 25-30.

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Panic disorder is one of the clinical common mental disorder which impairs the quality of patients'life. Its pathogenesis has not yet been fully understood, and the treatment has not been fully developed. This article reviews the advancement of etiology and therapy. The pathogenesis of this disorder is correlated with biological, psychological and social factors. The main treatments are pharmacotherapy, cognitive behavior therapy and combined therapy.

Reversal of antibiotic resistance methicillanin-resistant staphylococcus aureus by polyethyleneimine-phosphothioate oligodeoxynucleotide nanometer particle

WANG Hui, MENG Jing-ru, CHEN Tao, JIA Ming, HE Gong-hao, MA Xue, LUO Xiaoxing

2008, 13(1): 31-35.

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AIM: This study used polyethyleneimine (PEI) and phosphothioate oligodeoxynucleotide (PS-ODNs) to prepare PEI-ODNs nanometer particle and transmit it into methicillin resistant staphylococcus aureus (MRSA) in vitro by pharmacodynamic evaluation. METHODS: The PEI-ODNs nanometer particle was prepared and its diameter was analyzed. The PEI and PS-ODNs binding rate by fluorospectrophotometer was evaluated. The total colony forming unit (CFU) was counted. The cell growth curve was drawn by measuring A630 nm at different time points with microplate reader. The minimal inhibitory concentration (MIC) was determined by fluid dilution method. RESULTS: The diameter of PEI-ODNs nanometer particle was (85±22) nm and the highest binding rate was (97.3±1.1) %. In M-H agar plate(including 6 μg/mL oxacillin), the number of MRSA colonies was 6.4×108 mL in 30 μg/mL PEI-ODNs nanometer particle treated group, while the number of MRSA colonies in blank control was 3.3×109 mL. The number of MRSA colonies was significantly decreased in PEI-ODNs nanometer particle treated group (P<0.01), while CFU of MRSA was not influenced in control group (P >0.05). Significant growth inhibition of cells treated with PEI-ODNs nanometer particle was observed as compared with those cells in control. The MIC of oxacillin to MRSA was decreased from 1 024 μg/mL to 16 μg/mL when treated with 30 μg/mL PEI-ODNs nanometer particle. CONCLUSION: PEI binds PS-ODNs with high binding rate and has little diameter. The susceptibility of MRSA to β-lactam antibiotics is significantly restored. The results indicate that the PEI can transmit PS-ODNs into MRSA and it is considered as a new vector for PS-ODNs into bacteria.

Therapic effects of CPU0213, a novel endothelin receptor antagonist, on isopreterenol induced cardiomyopathy

TANG Xiao-yun, WANG Qiu-juan, DAI De-zai, DAI Yin

2008, 13(1): 36-41.

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AIM: The present study was focused on the effects of isoproteronol induced cardiomyopathy, and the expression of sarcoplasm reticulum Ca2 + handlingprotein, sarco-endoplasmic reticulum ATPase 2a(SERCA2a). The therapeutic effects of CPU0213, a novel endothelin receptor antagonist were evaluated. METHODS: Male SD rats were administrated isoproterenol (2 mg·kg^-1 ·d^-1,s.c.) for 10 days. A subset of the rats were administrated CPU0213 (30mg·kg^-1 ·d^-1, s. c.) from d 6 to d 10.All the animals were subjected to cannulation through left carotid artery to measure LVSP, LVEDP, and±dp dtmax Expressions of SERCA2a were measured by reverse transcription polymerase chain reaction (RT-PCR) and western blotting assays. RESULTS: Isoproteronol caused a significant decline of SERCA2a expression in both mRNA and protein levels(P<0.05), in conjunction with decreased LVSP,±dp dt max, and elevated LVEDP(P<0.05). And CPU0213 recovered all these alterations partially. CONCLUSION: Blockade of endothelin receptors by CPU0213 is beneficial to isoproterenol caused impairment of cardiac function, in which process endothelin system probably mediates the adverse effects of excessive β-receptor activation.

Research on correlations between cytotoxicity and acute toxicity of seven compounds

LIU Mi-feng, PENG Shuang-qing, SHENG Zhi-guo, XIE Yue-hua, DONG Yan-sheng, YANG Haiying, HAN Gang, YAN Chang-hui

2008, 13(1): 42-45.

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AIM: The study was undertaken to estimate acute toxicity in vivo using cytotoxicity data in vitro, in order to reduce animal usage in acute toxicity testing. METHODS: The basal cytotoxicity of seven compounds in Chinese hamster lung cell(CHL)cells were analyzed by MTT test, the LD50 values of acute toxicity were estimated by Registry of Cytotoxicity prediction model and validated by up-down method in mice. RESULTS: The IC50 values of compounds 1-7 in CHL cells were 0.43, 0.49, 0.18, 0.67, 3.03, 1.68 and 1.79 mg/mL, respectively. The predictive values of LD50 for compounds of 1-7 were 2376. 4, 2478. 3, 1574. 8, 2087.6, 4897.3, 3331.8 and 3300.7 mg/kg, respectively. The LD50 values for all compounds detected by up-down method were more than 2000.0 mg/kg except compound 4 with 1634. 0 mg/kg in female mice. Compared with the chemicals'toxicity classification based on predictive values and true values of LD50, the results indicated that toxicity classification of all compounds were basically at equal pace except compounds 3 and 4. CONCLUSION: The cytotoxicity data in vitro may be helpful in predicting acute toxicity in vivo and reducing the usage of laboratory animals.

Establishment of an acetaminophen-induced hepatotoxicity model of precision-cut liver slices and the regulation of cytochrome P450 2E1

LI Jing-ting, WANG Hui, PAN Xiao-liang, YAN You-e, GUO Yu, ZHANG Ben-jian

2008, 13(1): 46-50.

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AIM: To establish an acetaminohpheninduced hepatotoxicity model using precision-cut liver slice (PCLS) technique and observe the regulation of cytochrome P4502E1 (CYP2E1) so as to provide experimental basis on investigating and screening new potential hepatoprotective drugs. METHODS: (1) The PCLS was prepared by the vibratome and co-incubated with 500 μmol/L acetaminophen for 0, 2, 4 and 6 h. The activities of glutathione S-transferase (GST) and lactic acid dehydrogenase (LDH) were measured in the medium and slices. (2) The rats were intragastrically administrated with ethanol in different dosages (0.25, 0.5, 1.0 g/kg) once a day for three days consecutively, then they were at sacrificed 8 h after the last administration and the slices were prepared. And the slices were co-incubated with 500 μmol/L acetaminophen for 6 h and then the activities of ALT and LDH were detected in the slices and medium. (3) Replace the medium after 1 h pre-incubation, the slices were co-incubated with 500 μmol/L acetaminophen and diethyldithiocarbamate(DDTC) (5, 10, 20 μmol/L) for 6 h and the activities of ALT and LDH in the slices and medium were assayed. RESULTS: Compared with regular culture group, the leakage rates of GST and LDH in acetaminophen co-incubated for 4 and 6 h groups were significantly increased (P<0.01). Compared with those in acetaminophen model group, the leakage rates of LDH of ethanol at the dosages of 0.5, 1.0 g/kg and the leakage rates of ALT of ethanol at the dosages of 0.25, 1.0 g/kg increased significantly (P<0.01, P<0.05). Moreover, the leakage rates of ALT in all concentrations of DDTC decreased remarkably (P<0.05). CONCLUSION: Co-incubation PCLS with 500 μmol/L acetaminophen for more than 4 h is a successful way to establish hepatotoxicity in vitro model. The reduction of CYP2E1 activity might protect the slices from acetaminophen-induced hepatotoxicity, while the increase of CYP2E1 activity might aggravate it.

Protective effects of sodium oxybate on hypoxia reoxygenation injury of hippocampal slices in rats

YOU Wen-bin, JIANG Xin-ying, MA Xing, GU Shu-ling, DAI Ti-jun

2008, 13(1): 51-56.

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AIM: To study the protective effects of sodium oxybate(SO) on hypoxia reoxygenation injury of hippocampal slices of rats and investigate its protective mechanism SO to ischemic cerebral injury. METHODS: Experimental model of hypoxia reoxygenation injury of hippocampal slices of rats was adopted. Slices were equally divided into seven groups: control group, hypoxia reoxygenation (H R) group, SO1, 10, 100μmol/L group, NCS-382 [γ-hydroxybutyric acid(GHB) receptors antagonist] 100 μmol/L combined with SO100 μmol/L (NCS-382 +SO100) group, NCS-356 (GHB receptors agonist) 100 μmol/L group. LDH release rate and gamma-aminobutyric acid (GABA) and glutamate (Glu) content in incubation fluid of hippocampal slices were measured. Tissue injury in slices was detected by TTC staining method. The Changes of histomorphology by HE staining were observed as well. Changes of intracellular calcium by flow cytometry and the expression of nitric oxide synthase by enzymohistochemistry method were studied. RESULTS: Hypoxia reoxgenation caused an increase in LDH release rate, a decrease in TTC staining, a decline of GABA Glu ratio and tissue injury obviously, while pretreatment with SO was able to reverse the indexes mentioned above(P<0.01). Fluorescence intensity of intracellular calcium and the number of NOS positive neurons in H R group were higher than those in the control group (P<0.01). However, fluorescence intensity of intracellular calcium (P<0.01) in SO100 and NCS-356 groups was lower than that in H R group, were the number of NOS positive neurons was reduced obviously (P< 0.01). Using SO after GHB receptors antagonist NCS-382, fluorescence intensity of intracellular calcium and the number of NOS positive neurons were similar to HR group. CONCLUSION: SO can protect hippocampal slices subjected to hypoxia reoxygenation injury significantly in rats. The protective mechanism of SO may related to the increase of GABA Glu ratio, the reducing of calcium reflux and decrease of NOS activity by activating GHB receptors.

Effects of tanshinone ⅡA on the expression of glutathione-s-transferaseμ2 in spontaneously hypertensive rats

ZHOU Si-gui, WANE Ping, WANG Zhao-he, PAN Xue-diao, LIU Pei-qing

2008, 13(1): 57-61.

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AIM: To observe the effects of tanshinoneⅡA on the expression of glutathione-s-transferaseμ2 (GSTμ2) in spontaneously hypertensive rats, and to investigate the mechanism of the reversal of left ventricular hypertrophy by tanshinone ⅡA. METHODS: There are 3 groups in the experiment: control, spontaneously hypertensive rats(SHR), SHR treated by tanshinoneⅡA. At the endpoint of the experiment, hemodynamic parameters were measured. Then the rats were sacrificed, body weight (BW) and left ventricular weight (LVW) were measured, and the LVW BW ratios were calculated. The oxidative fluorescence dye dihydroethidium was determined by laser confocal fluorescent microscopy to evaluate in situ O2^-generation in the left ventricles. The expression of GSTμ2 was investigated by western blotting. RESULTS: Compared with control, the systolic blood pressure and LVW to BW ratios of SHR elevated markedly, the left ventricular function was decreased. The left ventricular hypertrophy was significantly reversed by tanshinone ⅡA treatment, but tanshinone ⅡA didn't decrease the systolic blood pressure of SHR. O2^-generation increased in SHR significantly, and it was decreased by tanshinone Ⅱ A. The expression and activities of GSTμ2 in left ventricular significantly decreased in SHR, however that was reversed by tanshinone ⅡA. CONCLUSION: Tanshinone ⅡA can significantly reverse the left ventricular hypertrophy in SHR, that might be associated with up-regulation of GSTμ2, decrease of O2^-and elimination of oxidative stress.

Effects of soy isoflavones on serum lipids and the antioxidative effects in vivo and in vitro

PANG Xiao-yun, SHEN Jin-fang, GONG Qin-yan

2008, 13(1): 62-67.

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AIM: To observe the effects of soy isoflavones (SI) on serum lipids, malondialdehyde(MDA)and superoxide dismutase (SOD)of blood and liver in rats fed with high cholesterol diet, and the protective effects of genistein on H2O2 injured ECV304 cell in vitro. METHODS: According to serum cholesterol(TC)level, fifty male Wistar rats were divided into 5 groups, normal control group (NC), high cholesterol control group (HC) and three SI treatment groups. three SI treatment groups were administrated with SI 30, 60, 120 mg/kg intragastrically (ig), and the two control groups were administrated with solvent for 9 weeks. At the end of 2, 4, 9 weeks, serum TC, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein(LDL)were measured. At the end of treatment, SOD activities in RBC and liver, serum and hepatic MDA levels were measured. Hepatic pathological changes were also observed. We also detected survival rate of ECV304 on H2O2 injure after incubated with different concentrations of genistein with MTT assay. RESULTS: SI 30, 60, 120 mg/kg could not reduce serum lipids levels. Hepatic pathological results were also in consistent with serum lipids. But SOD activities in RBC and liver were improved and serum and hepatic MDA levels were decreased in SI treatment groups (P<0.05, P<0.01). In our study, we also observed that genistein 25, 50, 100μmol/L could protect ECV304 cells injured by H2O2 dose-dependenly. CONCLUSION: Soy isoflavones could not improve serum lipids and prevent hepatic fatty degeneration in cholesterol-fed rats. However, they have antioxidative effects both in vivo and in vitro.

Study on indexes of poisoning related acute mucosal lesion in rats

FAN Xiao, ZHANG Hong-liang, XU Yang

2008, 13(1): 68-73.

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AIM: To explore the the value of endothelin, tumor necrosis factor and cyclooxygenase-2 in poisoning related acute mucosal lesion in rats. METHODS: 24 healthy SD rats were randomly divided into four groups as below. the blank control group, the acute methamidophos poison group, the acute methamidophos poison group cured with Omeprazole of normal dose (10 mg/kg), the acute methamidophos poison group cured with Omeprazole of large dose (50 mg/kg). The rat's blood was drawn at 4 hours after model was established. The gastric ulcer index was counted and the content of serum cholinesterase, serum endothelin, blood serum tumor necrosis factor and yclooxygenase-2 expression were measured, and correlation analysis were taken. RESULTS: The correlation of gastric ulcer index and the level of serum endothelin and tumor necrosis factorwere established successfully. There was no obvious correlation between cyclooxygenase-2 expression and gastric ulcer index. CONCLUSION: The serum endothelin and tumor necrosis factor-αincrease in acute poisoning related gstric mucosa injury, so they could be used as monitoring indicators for the advancement and improvements of therapy.

Impact of alendronate on bone resorption at the bone-screw interface

GUO Ai, CHEN Liang

2008, 13(1): 74-78.

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AIM: To investigate the impact of alendronate on bone resorption of normal and ovariectomized rats at the bone-screw interface through radiographic and histologic findings. METHODS: Thirtytwo female Wister rats with a mean body weight of 332 g (287-351 g) were divided into four groups at random. Rats in group C and D were ovariectomized. 8 weeks later, the proximal one-third of the left tibia of all rats were inserted into self-drilling mini cortical screws. After operations, alendronate were used in group A and C and saline were given in group B and D. The rats were euthanized at 5 weeks after screws having been attached. Radiographic and histologic findings subsequently were analyzed. RESULTS: Radiographs confirmed that no osteolytic area was present around screws immediately after insertion, whereas 5 weeks after insertion, a wide and low-density area corresponding to the screw hole was evident in the saline groups compared with the alendronate groups. On histologic observation, the width of the fiber membrane and the number of TRAP-positive cells were decreased in the alendronate groups than those in the saline groups, and the difference was statistically significant. CONCLUSION: Alendronate effectly inhibits bone resorption of either normal or ovariectomized rats at the bone-screw interface in rats.

Evaluation of cardiac contractility and relaxation during no-reflow phenomenon by the combination of Doppler tissue imaging with myocardial contrast echocardiography

JIAO Yang, CHEN Li-xin, TAO Hong, ZHU Xiang-ming

2008, 13(1): 79-84.

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AIM: To evaluate the cardiac contractility and relaxation by Doppler tissue imaging (DTI) combined with myocardial contrast echocardiography (MCE) via injection of contrast media, Albunex. METHODS: Nineteen healthy mongrel dogs were conducted 60 min ligation of left anterior descending coronary artery (LAD), followed by reperfusion of 60, 120 and 180min to establish an acute myocardial ischemicreperfused canine model. (1) MCE was performed by bolus injection of Albunex at pre-reperfusion and at post-reperfusion. The perfused defect area defined by MCE at pre-reperfusion was regarded as risk area (RAMCE), while perfused defect area at post-reperfusion was regarded as no-reflow area (NRAMCE). When the ratio of NRAMCE to RAMCE exceeded 25 %, myocardial reperfusion was considered incomplete, i. e. , no-reflow group ;If the ratio was<25 %, myocardial reperfusion was considered adequate, i. e. , reflow group. (2) Left ventricular ejection fraction (LVEF) and wall thickness ratio (ΔT %) of LV anterior wall were determined. (3) S-wave, e-wave and awave velocities at the LV anterior wall were determined by DTI. The e a ratio was measured. RESULTS: The results of MCE showed 7 dogs in reflow group and 10 dogs in no-reflow group. (1) LVEF in reflow group gradually increased with time course after myocardial reperfusion, and in no-reflow group, however, LVEF increasingly declined with ongoing myocardial reperfusion. At the same reperfusion time point, LVEF of noreflow group was significantly lower than that of reflow group. (2) ΔT %in reflow group improved gradually, and however, it cannot come back to that of baseline at 180-min reperfusion. ΔT % in no-reflow group had no signal of recovery with progressive reperfusion. (3) S-wave, e-wave velocities measured by DTI significantly declined after ligation of LAD, and a-wave velocity increased, leading to decline of e a. After myocardial reperfusion, s-wave, e-wave velocities and e a in reflow group gradually increased at post-reperfusion, and a-wave velocity somewhat declined. In no-reflow group, on the other hand, s-wave, e-wave velocities and e a progressively declined and a significant difference was present between reflow group and no-reflow group (P<0.05). CONCLUSION: Cardiac contractility and relaxation cannot be recovered during myocardial microvascular impairment. This change may be further deteriorated with size enlargement of no-reflow area. DTI may provide a sensitive, reliable method for quantifying cardiac contractility and relaxation.

Effects of reduced glutathione hormone against ototoxicity of amikacin in guinea pigs

WANG Ju-xiang, ZHU Xin-bo

2008, 13(1): 85-88.

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AIM: To observe the protective effects of reduced glutathione hormone (GSH) against ototoxicity of amikacin in guinea pigs. METHODS: 56 adult guinea pigs were divided into four groups randomly: amikacin group, GSH group, combination group and sodium chloride group. Each group was intramuscularly injected with amikacin, GSH, amikacin +GSH and sodium chloride respectively. After the observation, the activities of reactive oxygen species(ROS), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and catalase (CAT) were measured. The number of deeply stained cuticular plate was counted with surface preparation technique of the cochlea. The change of cell organ of outer hair cells was monitored by scanning electron microscope. RESULTS: The activities of SOD, CAT and GSH-Px were significantly decreased and the content of ROS was increased in amikacin group (P<0.05). However, GSH could significantly inhibit these changes among the animals in treating group. Outer hair cells of GSH group were arranged tidily in three rows and showed characteristic V-arranged stereocilia. Stereocilia of outer hair cells in amikacin group failed off markedly in a disarranged pattern and the number of deeply stained cuticular plate increased significantly. In combination group, the changes of the number of deeply stained cuticular plate showed significant difference as compared with those in amikacin group (P<0.01). In GSH group and combination group showed no significant difference. In amikacin group, the phenomenon of karyopyknosis appeared, the quantity of mitochondrion decreased and most of them had vacuolar degenerated. The cells of GSH group and sodium chloride group changed slightly. The mitochondrion in combination group was deeply stained and light swelling. CONCLUSION: These results suggest that co-administration of GSH and amikacin can attenuate the ototoxicity of amikacin.

Effects of scopolamine on expression of p-CREB and c-Fos in amygdala nucleus in rats with recurrence of conditioned place preference induced by morphine

ZHAO Yong-na, LI Xiao-hong, FANG Zheng-mei, LI Shun-ying, SHAO Xiao-xia

2008, 13(1): 89-93.

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AIM: To dectect the effects of scopolamine on expression of phospho-cAMP response element binding protein (p-CREB) and c-Fos in amygdala nucleus (Amy) in rats with recurrence of conditioned place preference(CPP) induced by morphine. METHODS: Morphine was administered by subcutaneous injection at gradually increasing dose(from 10 mg/kg to 60 mg/kg) for 6 days to establish CPP model. From d 7, the rats were administered saline instead of morphine for 10 days to induce CPP extinction. The rats were given a single priming injection of morphine (4 mg/kg) to reinstate the CPP model, some rats were treated by i. p. scopolamine (1, 2, 3 mg/kg) prior to priminging injection of morphine. The expression of p-CREB and c-Fos in Amy were assayed by immunohistochemistry in the phase of reoccurrence of CPP. RESULTS: After priming injection of morphine 4 mg/kg, the time spent on the drug paired side was significantly reduced because of the treatment with scopolamine, compared with that in the morphine group(P<0.05). Compared with the morphine group, scopolamine decreased the expression of p-CREB and c-Fos of Amy in rats (P<0.05). CONCLUSION: The effects of scopolamine inhibiting morphine CPP reccurrence were probably related to its inhibitory effect on p-CREB and c-Fos expression of Amy in rat.

Effects of Salvia miltiorrhiza Bge water extract on prednisone -induced osteoporosis in rats

XIAO Liu-bin, LIU Guo-xiong, WANG hui

2008, 13(1): 94-98.

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AIM: To investigate the effect of Salvia miltiorrhiza Bge water extract on osteoporosis which induced by prednisone in rats. METHODS: Fifty SD rats were randomly divided into control group, prednisone group and Salvia miltiorrhiza Bge high dose group, middle dose group and low dose group, with 10 rats per group. Rats in the control group were treated with dissolvant, the others were treated with prednisone firstly, and then, the rats in prednisone group were treated with dissolvant, the 3 groups were treated with high dose, middle dose or low dose water extract of Salvia miltiorrhiza Bge respectively, once a day. After 8 weeks, the bone histomorphometric analysis of thighbone were performed in undecalcified sections, the content of Ca²⁺ and hydroxyproline (Hyp) were measured, the length and width of the thigh bonewere tested. RESULTS: The bone weight, bone Hyp and bone Ca²⁺ in prednisone group were lower than those in control group. The fat in the marrow, the cholesterin in plasma were increased but ALP and HDL were reduced (P<0.05). Salvia miltiorrhiza Bge water extract could increase the bone weight, reduce the fat in the marrow and increase the ALP and HDL (P<0.05), but the relationship between dose and efficacy was not significant. CONCLUSION: Prednisone can restrain bone growth and induce bone loss, while Salvia miltiorrhiza Bge water extract has good protective effect.

Effects of Yinqu Capsule on blood lipid in rats with experimental hyperlipidemia

LI Li-hua, XU Hui-qin

2008, 13(1): 99-102.

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AIM: To observe the effects of Yinqu Capsule on blood lipid in rats with experimental hyperlipidemia. METHODS: Rats were fed with fatty forage for two weeks to make the model of hyperlipidemia. The rats were randomly divided into five groups: model group, Xuezhikang group and three dosages of Yinqu Capsule groups. The drugs were administered for two weeks consecutively. The levels of T-CHOL, TG, LDL-C and VLDL-C in serum of rats were detected to observe the preventive and therapeutical effects of Yinqu Capsule. RESULTS: Compared with control group, the levels of T-CHOL, TG, LDL-C, VLDL-C and T-CHOL HDL-C of Yinqu Capsule groups were significantly decreased and the content of HDL-C was slightly increased(P<0.05 or P<0.01). CONCLUSION: Yinqu Capsule could modulate blood lipid of hyperlipidemia rats to a certain extent.

Experimental study on anti-tumor effect of chitosan sulfate in mice

HE Kang, FENG You-hui, AI Chun-mei

2008, 13(1): 103-106.

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AIM: To investigate the anti-tumor effects of chitosan sulfate in mice. METHODS: 80 mice were divided into control group, 5-FU treatment group and Chitosan sulfate treatment group (200 mg/kg and 100 mg/kg). Different doses of Chitosan were intraperitoneally injected into mice with sarcoma 180 and EAC cancer respectively for 10 days. The tumor inhibiting rate, the weight index of important organ and life prolongation were calculated. RESULTS: The tumor inhibiting rate of high dose, low dose of Chitosan sulfate and 5-FU were 38. 67 %, 30.19 %, 43. 27 %, life prolongation of high dose, low dose of Chitosan sulfate and 5-FU were 65. 38 %, 69. 23 %, 54. 93 %, Compare with control and 5-FU group, the indexes of thymus in high dose and low dose of Chitosan sulfate were significantly increased (P<0.05). CONCLUTIONS: Chitosan sulfate shows significant anti-tumor effects on sarcoma-180 and can prolong the life of mice with EAC cancer. Such effects may be owe to improvement of body immunity.

Phase Ⅲ clinical trial of Xiaoeryiniao Granule on children with enuresis of kidney-qi deficiency in comparing with meclofenoxate hydrochlorid capsules

HU Si-yuan, MA Rong, LIU Xiao-fan, XIANG Xi-xiong, DING Ying, HUANG Wen-yu, HUANG Zhi-jun, XIAO Fei

2008, 13(1): 107-111.

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AIM: To evaluate the effect and safety of Xiaoeryiniao Granule in the treatment of children with enuresis of kidney-qi deficiency. METHODS: A stratified-block randomized, double-blind, doubledummy, parallel-controlled, multicenter trial was designed for clinical study. RESULTS: In treating the syndrome of kidney-qi deficiency of enuresis, the clinical cure rates, the markedly effective rates and the total effective rates in the two groups were 26.33 % vs 21.30 %, 50.30 % vs 50.00 % and 76.63 % vs 71.30 %, respectively. By non-inferior test, the results suggested that the treatment group was non-inferior to the control group in clinical curative effect. Improvements of Chinese mealicine symptoms of two groups were as follows: cure rates, the markedly effective rates and the total effective rates were 20.71 % vs 16.67 %, 41.42 % vs 37.04 % and 62.13 % vs 53.71 % respectively, there was no significant difference between the two groups (P >0.05). But there were significant differences between pretreatment and post-treatment in intra-group comparison on single symptoms, such as times of enuresis, depth of sleep and abnormal tongue and pulse display. And two patients in the control group shown abnormal alanine aminotransferase(ALT) levels (aggravation after treatment with an occurance rate of 1. 75 %). CONCLUSION: Xiaoeryiniao Granules on children enuresis of kidney-qi deficiency not only non-inferior to the control group in clinical curative effect, but also has better safety.

Pharmacokinetic studies of ceptopril in healthy male and female volunteers

TIAN Lei, HUANG Yi-ling, GONG Pei, BIAN Wen-yan, JIANG Wen, LI Yi-shi

2008, 13(1): 112-116.

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AIM: To study the pharmacokinetic profiles of ceptopril, a new ACE inhibitor, in Chinese healthy male and female volunteers. METHODS: 10 healthy volunteers (5 males and 5 females) were en- rolled and 30 mg ceptopril oral dose was given twice daily for 7 days. Another 10 healthy volunteers (5 males and 5 females) were treated with 60mg captopril in the fed and fasted conditions. With the analysis of HPLC for the concentrations of ceptopril in plasma, pharmacokinetic parameters were calculated by Win-Nonlin software. RESULTS: No significant difference was observed between the pharmacokinetic parameters of the 1st dose and the last dose (P >0.05), with values as follows: t_max (1.2±0.5) h and (1.2±0.3)h, C_max (279±100) μg L and (299±101) μg L, AUC0-t (421±107) μg·L^-1 ·h and (461±152)μg·L^-1 ·h, t_1/2 (1.3±0.9) h and (1.3±0.5) h. Compared with those in fasted condition, t_max was prolonged, and AUC and C_max were not significantly changed in fed condition. There was no significant difference between the male and female volunteers. CONCLUSION: There was no accumulation when ceptopril was given with multiple doses. Food affected the absorption rate of ceptopril, but did not decrease its exposure. No sex difference was observed.

A randomized and double-blind clinical trial of venlafaxine hydrochloride sustained release capsules for treating juvenile depression

JI Wei-dong, GUO Tian-you, YANG Chuang, ZHOU Jia-xiu, YAO Jing, HUANG Xiao-qi

2008, 13(1): 117-120.

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AIM: To evaluate the efficacy and safety of venlafaxine hydrochloride (HCl) sustained release capsules in treating juvenile with depressive disorder. METHODS: A randomized, double blind and double dummy clinical trial enrolled 60 adolescent patients with depression, who were randomizedly designed to administer venlafaxine HCl sustained release capsules 150 mg or fluoxetine 20 mg daily for 8 weeks. The efficacies of both treatment groups was evaluated based on the Hamilton Depression Scale and Clinical General Impression Scale pre and post-treatment. RESULTS: The scores of Hamilton Depression Scale at the end of therapy were significantly reduced compared with the baseline in both groups(P<0.01). The effective rate of venlafaxine HCl sustained release capsules versus fluoxetine treatment was 70.0 % and 65.5 %, respectively, the P value showed no statistical difference(P >0.05). The common adverse reactions included dry mouth, insomnia, dizziness, and loss of appetite. CONCLUSION: Venlafaxine HCl sustained release capsules is an effective agent for juvenile with major depression.

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