Table of Content

Volume 17 Issue 2
26 February 2012

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Evidence of caspases-mediated human stomach carcinoma MGC-803 cells apoptosis induced by L-amino acid oxidase from Naja atra venom

QI Yuan-lin, ZHANG Ming-fang, ZHAO Rong, LIN Jian-yin

2012, 17(2):  121-125. 

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AIM: To investigate the effects and the molecular mechanisms of Naja atra L-amino acid oxidase (NA-LAAO) on the proliferation and cell apoptosis of human stomach cancer MGC-803 cells.METHODS: MGC-803 cells were exposed to different concentrations of NA-LAAO and the cytotoxicity was measured using a CCK-8 kit. The apoptosis-inducing activities of NA-LAAO were examined by propidium iodide staining and Annexin V/PI assay in flow cytometry. The enzyme activity of caspase-3 was measured by a colorimetric assay. The cleavage of PARP-1 was analyzed by Western-blot.RESULTS: NA-LAAO exhibited cytotoxicity on MGC-803 in a dose- and time-dependent manner. The half maximal inhibitory concentration (IC₅₀) values of NA-LAAO were (2.48±0.41), (1.74±0.27) and (0.83±0.19) mg/L in MGC-803 cells at 6 h, 12 h and 24 h, respectively. NA-LAAO induced apoptosis accompanied DNA hypodiploidy, phosphatidylserine exposure, activation of caspase-3, and PARP cleavage.CONCLUSION: NA-LAAO inhibited cell proliferation by inducing a caspase-mediated cell apoptosis.

Pharmacokinetics and bioavalibability of catalpol in rats

WU Li-nan, LU Rong, GU Yuan, LIU Chang-xiao, SI Duan-yun

2012, 17(2):  126-130. 

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AIM: To study the pharmacokinetics and bioavailability of catalpol in rats.METHODS: LC-MS/MS method was established for the quantitation of catalpol.The plasma concentration of catalpol after i.g. administration of 50, 100 and 200 mg/kg dose of catalpol to six rats was calculated by peak area ratio of the determinated (catalpol) and the internal standard (aucubin) obtained by Xcalibur 1.4 program. The main pharmacokinetic parameters were obtained by DAS 2.0 program. The figures were checked by t text method, and calculated for bioavailability.RESULTS: The plasma concentration-time curve of catalpol conformed to two compartment model.After i.g. administration of 50, 100 and 200 mg/kg dose of catalpol, AUC_0→∞ values increased in proportion to dose. t_1/2 appeared to be independent of dose. Mean AUC_0→∞ was (70±23) and (104±11) μg·h·mL^-1 respectively after i.g. and i.v. administration of 50 mg/kg dose,the extent of bioavailability of catalpol was 66.7%.CONCLUSION: The results of the pharmacokinetic study of catalpol showed that it exhibited first order kinetic characteristics and the bioavailability was satisfied.

In vitro inhibition of Huanglianjiedu Decoction on 6 cytochrome P450 isoforms in human liver microsomes

LI Dan, HAN Yong-long, YU Tao, Fu Yao, MENG Xiang-le, YU Qi, GUO Cheng

2012, 17(2):  131-136. 

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AIM: To predict the herb-drug interactions in clinical application, Huanglianjiedu Decoction was evaluated for its in vitro inhibition effect on 6 cytochrome P450 isoforms (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in human liver microsomes.METHODS: Seven metabolites of cytochrome P450 probe substrate (including Paracetamol for CYP1A2, 6α- Hydroxypaclitaxel for CYP2C8, 4-Hydroxydiclofenac for CYP2C9, 4-Hydroxymephenytoin for CYP2C19, Dextrorphan for CYP2D6, 6β-Hydroxytestosterone and 1-Hydroxymidazolam for CYP3A4) were simultaneously measured by LC-MS/MS. Huanglianjiedu Decoction was incubated with human liver microsomes in the presence of seven probe substrates of CYP450 isforms, and the inhibitory effect were evaluated with IC₅₀ values.RESULTS: IC₅₀ value of Huanglianjiedu Decoction on CYP2D6 and CYP1A2 were 3.54 and 10.8 μg/mL, and the other IC₅₀ values were 67.7, 299, 530, 199 and 607 μg/mL with respect to CYP2C8, CYP2C9, CYP2C19, CYP3A4_T and CYP3A4_M isoforms.CONCLUSION: Huanglianjiedu Decoction shows inhibitory effect on CYP2D6 and CYP1A2, but minor inhibitory effects on CYP2C8, CYP2C9, CYP2C19 and CYP3A4.

Differentiation of rat bone marrow stromal cells into neurol cells induced by mouse nervous growth factor

CHEN Zai-feng, XU Xin-long, WEI Xiao-jie, FU Xiao-jun, PAN Hong-song, XIE Qin-song

2012, 17(2):  137-140. 

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AIM: To observe the effect of mouse nervous growth factor(mNGF) on differentiation of rat bone marrow stromal cells into neurol cells.METHODS: 60 4-week-old healthy clean SD rats were equally randomized into divided into treatment group(n=30)and normal control group(n=30). The treatment group received 0.1 μg/mL mNGF as induction medium. The rats BMSCs of passage 3 were cultured in the medium with or without previous brain tissue extracts. The expressions of neuron specific encolase (NSE) were detected after 3 days by immunocytochemistry.RESULTS: There were a few NSE in the normal control group. The expression of NSE of treatment group were significantly higher than normal control group(P＜0.01).CONCLUSION: mNGF can induce BMSCs into neural cells.

Study on mechanisms of Agkistrodon halyx pallas venom PCA to improve heart function in rats with acute myocardial infarction

LI Shu, ZHANG Gen-bao, HONG Yun, LU Xiao-hua

2012, 17(2):  141-146. 

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AIM: To explore the effect of protein C activator(PCA) from Wannan Agkistrodon halyx pallas venom on heart function in rats with acute myocardial infarction and its mechanism.METHODS: Sixty SD rats were randomly divided into sham operation (SH)group, myocardial infarct(MI)group, low dose, medium dose and high dose of PCA groups (0.5,2,8 mg/kg) and aspirin group (5 mg/kg), and ten in each group. Through ligating of the anterior descending coronary artery to establish AMI,the cardiac muscle samples were obtained 12 hours after AMI. Medlab bio-signal processing system monitored hemodynamic changes in rat heart. The expression of myocardial MMP-9 was detected by Western blot.Myocardial cell and interstitial tissue were observed by microscope.RESULTS: Compared with myocardial infarct group rats, high dose and medium dose PCA significantly increased LVDP, LVEDP, significantly increased +dp/dt_max and -dp/dt_max and reduced levels of MMP-9 protein expression (P <0.05). Cardiac histological detection showed that PCA significantly reduced in infiltration of inflammatory cells and infarct size compared with AMI group.CONCLUSION: Agkistrodon halyx pallas venom PCA can limit the expansion of early myocardial infarction, improve cardiac hemodynamics, inhibit expression of MMP-9, so it would have a certain intervention effect on ventricular remodeling after acute myocardial infarction.

Efficacy of the Gurc-OEG on rat liver fibrosis induced by CCl₄

DENG Yan-hong, SHEN Neng, LING Ning, HU Peng, REN Hong, TANG Hua-dong, PENG Ming-li

2012, 17(2):  147-153. 

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AIM: To evaluate the efficacy of Curc-OEG in preventing CCl₄-induced hepatic fibrosis and to study the effects of that on expression of MMP-13 mRNA,TIMP-1 mRNA and CollagenⅠ.METHODS: Liver fibrosis in rats was induced by CCl₄. Rats were assigned into control group(A),model group(B),low-dose group(C),medium-dose group(D), high-dose group(E) and colchicin group(F).All rats except those in group A were given subcutaneous injection of CCl₄ and olive oil mixture,twice a week for 10 weeks. After 4 weeks, those in group B were treated with normal saline by intravenous injection,those in group C,D and E were treated with Curc-OEG for 25,50,100 mg·kg^-1·d^-1 by intravenous injection, those in group F were treated with colchicin for 0.1 mg·kg^-1·d^-1 by gavage as positive control.At the end of the tenth week, the serum levels of ALT, AST and cotent of hydroxyproline in homogenate were determined. The extent of liver inflammation and fibrosis was evaluated with HE and Sirus staining. The expressions of MMP-13,TIMP-1 and CollagenⅠwere observed with RT-PCR and Western Blot respectively.RESULTS: Compared with model group,medium and high dose of curcumin derivative could obviously decrease the content of hydroxyproline in liver tissue(P<0.05) and levels of ALT, AST in serum(P<0.05) and expression of CollagenⅠ(P<0.05), and it also reduced inflammation destruction of liver architecture and collagen accumulation. Further study showed that MMP-13 mRNA was up-regulated(P<0.05) and TIMP-1 mRNA was down-regulated(P<0.05) after Curc-OEG treatment.CONCLUSION: Curc-OEG could ameliorate the progress of liver fibrosis induced by CCl₄.

γ-Amino butyric Acid in peri-implantation mouse uterine contents and its significance

LUO Wen-ping, ZHAO Hai, LIU Zhen-zhen, TAN Dong-mei, TAN Yi

2012, 17(2):  154-158. 

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AIM: To identify the content of GABA in peri-implantation mouse uterine and its effects on decidualization by intraperitoneal injection different concentration of GABA.METHODS: The contents of GABA in peri-implantation mouse uterine from day 1 to day 8 were measured by chromatometry. From day 5, 0.05 g/kg,0.5 g/kg,5 g/kg concentrations of GABA were injected by abdominal cavity until day 8. Decidual tissues were weighted and then made paraffin section followed by HE staining. Areas of decidual were measured by Image J software.RESULTS: The contents of GABA in the pregnancy of D3 utrerine upregulated followed decreased in D4 utrerine but the highest content of GABA was occurred in D5 implantion sites uterine compared with that of in D1 utrerine. The content of GABA from D6 to D8 utrerine in iner- implantion sites were higher than implantion sites. Both 0.05 g/kg GABA and 5 g/kg GABA could reduced the number of deciduum, while both 0.5 g/kg GABA could down-regulated the weight of deciduum. Both 0.05 g/kg GABA and 0.5 g/kg GABA could reduce the area of decidual region.CONCLUSION: The contents of GABA showed dynamic change in peri-implantation mouse uterine which may be invloved in inhibited decidualization.

Protective effects of ERK1/2 inhibitor PD98059 on multiple organ dysfunction in disseminated- intravascular-coagulation rat

ZHU Hai-long, ZHANG Gen-bao, LI Wei, ZHANG Cui

2012, 17(2):  159-163. 

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AIM: To investigate the protective effects of extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 on multiple organ dysfunction in endotoxin-induced disseminated-intravascular- coagulation (DIC) rat.METHODS: Sprague-Dawley rats were divided randomly into 3 groups: control group, DIC group and inhibitor group. The endotoxin-induced DIC rat model was established with LPS (6 mg/kg) by intraperitoneal injection. Inbibitor group were injected with LPS (6 mg/kg) and PD98059 (10 mg/kg). The blood sample was taken after 5 h to detect APTT, FIB, LDH, ALP, ALT, AST, BUN and Cr by MC-2000 coagulation autoanalyzer and Olympus biochemical autoanalyzer; and then take out the heart, liver, kidney and observe pathology change of the tissue section.RESULTS: Compared with control group: experimental data from DIC group indicated that APTT, LDH, ALP, ALT, AST, BUN and Cr obviously extended or increased (P＜0.01), while FIB reduced (P＜0.01). Heart, liver and kidney biopsy showed vascular engorgement. Except for Cr, all the laboratory indexes ameliorated among inhibitor group than DIC group (P＜0.01), while pathological change was alleviated in heart, liver and kidney.CONCLUSION: This study shows that PD98059 can attenuate multiple organ dysfunction in the pathogenesis in endotoxin-induced DIC rat, and the mechanism involves ERK1/2 inhibition.

Effects of Ciwujia Injection on four cytochrome P450 isoforms in rat liver microsomes in vitro

ZENG Chao, LIU Yan, LIU Gao-feng, LI Xiang

2012, 17(2):  164-170. 

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AIM: To investigate the effects of Ciwujia Injection on CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in rat liver microsomes in vitro, providing references for clinical rational use of drug combination therapy.METHODS: Probe drugs of tolbutamide(TB), dextromethorphan(DM), chlorzoxazone(CLZ) and testosterone(TS) as well as Ciwujia Injection of different concentrations were added to incubation systems of rat liver microsomes in vitro, the concentrations of metabolites of the probe drugs in blank control, low, medium and high dose of Ciwujia Injection groups were determined by HPLC after incubation, and the differences of metabolic rates were compared to evaluate the effects of Ciwujia Injection on the activities of the four subtypes.The strength of inhibition (IC₅₀ and K_i values) was further determined if the activity in the medium dose group significantly decreased.RESULTS: Compared with the blank control group, the effects on CYP3A4 activity were statistically significant in low, medium and high dose groups of Ciwujia Injection (P<0.01), and the inhibition rates were 10.22%, 19.00%, 30.29%, with the IC₅₀ and K_i values were 3.96% and 2.74%(V/V); the activities of CYP2D6 were not statistically significant in low, medium and high dose groups (P>0.05); the activities of CYP2C9, CYP2E1 were not statistically significant in low dose groups (P>0.05), meanwhile the inhibitory effects on the two subtype activities in medium and high dose groups were statistically significant (P<0.05), but the rates of inhibition were less than 8.50% in the medium dose groups and less than 12.00% in the high dose groups.CONCLUSION: Ciwujia Injection exhibited inhibition against the activity of CYP3A4 in rat liver microsomes in vitro, with mixed inhibition model, and weak inhibition on CYP2C9, CYP2E1, but no effect on CYP2D6.

Effect of Wedelolactone on COX-2, NO and TNF-α expression in lipopolysaccharide induced RAW264.7 cells

CHEN Jie, LI Rui-ming, XU Jing, GUAN Bi-qiong, LUO Zi-ling

2012, 17(2):  171-174. 

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AIM: To study effect of Wedelolactone on COX-2, NO and TNF-α expression in lipopolysaccharide (LPS) induced RAW264.7 cells.METHODS: The contents of PGE₂, TNF-α, NO were detected by ELISA methods, expression of COX-2 protein in RAW264.7 cells was measured by MTT assay, in the presence or absence of 10 μg/mL lipopolysaccharide (LPS) or Wedelolactone (0.2, 2, 20 μmol/L).RESULTS: The expression of COX-2 protein was significantly induced by LPS, Wedelolactone inhibited the expression of COX-2 protein significantly elicited by LPS in RAW264.7 cells; LPS-induced PGE₂, TNF-α, NO was significantly inhibited by Wedelolactone in RAW264.7 cells, in dose dependent manners.CONCLUSION: The anti-inflammatory mechanisms of TGA may suppress production of PGE₂ through inhibiting COX-2 gene expression, and inhibit activity of NO and TNF-α.

Effects of tectorigenin on the secretion of extracellular matrix in Hepatic stellate cells

WANG Zhi-yong, WU Jun-hua, WANG Yu-rong, YU De-cai, DING Yi-tao

2012, 17(2):  175-180. 

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To investigate the effect of tectorigenin on the secretion of extracellular matrix (ECM) in Hepatic stellate cells.METHODS: HSC-T6 cells were incubated with tectorigenin at different concentrations, the mRNA expression of α-SMA, pro-collagen-α₁(Ⅰ), MMP-13 and TIMP-1 were detected by real-time PCR.RESULTS: Tectorigenin significantly decreased the expression of α-SMA in HSC-T6, as well as the mRNA expression of pro-collagen-α₁, and tectorigenin significantly elevated the mRNA expression of MMP-13, while decreasing the mRNA expression of TIMP-1.CONCLUSION: Tectorigenin could reduce the synthesis and secretion of type Ⅰ collagen in HSC, thereby reducing the deposition of extracellular matrix; the other hand, tectorigenin could promote the degradation of extracellular matrix, so as to have anti-fibrosis potentials.

Pharmacokinetic study of glipizide effected by roxithromycin in rabbits

ZHOU Peng, SUN Yuan, ZHANG Shu-xia, XIA Ai-xiao, CHEN Sai-zhen, DU You-gong

2012, 17(2):  181-184. 

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AIM: To study the influence of roxithromycin on the pharmacokinetics of glipizide capsule in healthy and diabetic rabbits METHODS: Glipizide (5 mg) was taken orally once to every rabbit. After 2 weeks of clearing stage, roxithromycin (50.0 mg) was administered daily by intra peritoneal injection bid for 3 d,then glipizide was taken orally at the same dosage on the 4 d. The blood was drawn from ear vein before and at 0.5, 1.5, 3, 5, 7, 9, 11,24 and 35 h after administering glipizide in every rabbit. Then the blood concentration of glipizide was measured by HPLC. The pharmacokinetic parameter was calculated with pharmacokinetic software DAS2.0. The pharmacokinetics of glipizide in rabbits administered with or without roxithromycin were analyzed by auto-control.RESULTS: The concentration time-curves were fit to the one-compartment model. In healthy rabbits administered with glipizide, the t_1/2, C_max, AUC values were (2.9±0.4) h , (5815±940) μg/L, (58919±860)μg·h·L^-1. In healthy rabbits administered with glipizide and roxithromycin, the t_1/2, C_max, AUC values were (3.5±0.9) h, (6165±764)μg/L , (76515±1830) μg·h·L^-1.In diabetes rabbits administered with glipizide, the t1/2, C_max, AUC values were (1.7±0.4) h, (4307±580) μg/L, (32469±786)μg·h·L^-1. In diabetes rabbits administered with glipizide and roxithromycin, the t_1/2, C_max, AUC values were (3.2±1.5)h,(8531±1479) μg/L,(76489±1588) μg·h·L^-1. There were notable differences on t_1/2, C_max, AUC values of glipizide in rabbits administered with or without roxithromycin.CONCLUSION: Roxithromycin shows significant inhibition on the pharmacokinetics of glipizide. The two drugs in clinical share requiring attention adjustment dose in order to avoid hypoglycemia hazards.

Relationship between the angiotensin Ⅱ type 2 receptor A1675G polymorphism and antihypertensive effect of valartan

LI Gang-qiang, YAN Wei, CHAO Sheng-wu, FAN Ji-hai

2012, 17(2):  185-188. 

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AIM: To study the relation of single nucleotide polymorphism of angiotensin Ⅱ receptor 2(AGTR2) A1675G with essential hypertension(EH) and antihypertensive response to valsartan.METHODS: Eighty case essential hypertension patients were received valsartan once daily for four weeks. Direct DNA sequencing was performed to detect the signgle nucleotide polymorphisms in eighty patients with essential hypertension and fourty normal blood pressure controls.RESULTS: There were significant differences of A1675G allele frequency between hypertensive group and normal controls(P<0.05).Treated with valsartan, patients with A allele had greater reduction in blood pressure (P<0.05).CONCLUSION: The results indicates that the AGTR2 A1675G single nucleotide polymorphisms might involved the development of essential hypertension and it is associated with antihypertensive predictor of valartan.

Pharmacokinetic interaction between warfarin and aspirin in rats

HUANG Xiao-hui, WANG Xia-qin, TANG Hai-qin, WANG Qin, CHEN Yun, LI Jing, LI Jun

2012, 17(2):  189-194. 

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AIM: To explore the pharmacokinetic interaction between warfarin and aspirin in rats at non-steady-state and steady-state.METHODS: Three groups of six rats each were used according to a parallel study. Group I (warfarin) received daily repeated 0.2 mg/kg intragastric administration. Group II (aspirin) received daily repeated 10 mg/kg intragastric administration. Group III (warfarin plus aspirin) was administered as drug combination, namely daily oral dose of 0.2 mg/kg warfarin and 10 mg/kg aspirin. The rats received once daily repeated oral administration for 6 days. Plasma drug concentrations were obtained at scheduled time points on the first and the 6th day after dosing. The pharmacokinetic profiles and calculated parameters were analyzed and compared.RESULTS: The pharmacokinetics of warfarin and aspirin were best fitted to a two-compartment and one compartment model, respectively. At non-steady-state, the concentration-time course and related parameters of warfarin and aspirin was not changed by each other. At steady-state, the pharmacokinetic characteristics of warfarin were also not changed by aspirin. However, after multiple doses, Aspirin increased the peak plasma concentration and area under the curve of warfarin at steady-state.CONCLUSION: At steady-state after multiple dosing, aspirin increased the exposure of warfarin, which indicates that the combination therapy may increase the bleeding risk. This increase may represent a safety concern. The results suggest some differences of pharmacokinetic properties between warfarin and aspirin combinations at steady state, which indicates that when warfarin and aspirin are administered together, therapeutic drug monitoring should be enhanced.

Meta analysis on Pule'an for treating benign prostatic hyperplasia

LV Shen, CAO Ting-wei

2012, 17(2):  195-198. 

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AIM: To evaluate the efficacy of Pule'an for treating benign prostatic hyperplasia(BPH).METHODS: The data of randomized controlled trials(RCT) of Chinese studies on Pule'an for the treatment of BPH all over China were retrieved from CNKI, Wanfang Data and VIP. The data were extracted by using designed extraction form. Data were processed by Stata 11.0.RESULTS: Five studies involving 361 men met the inclusion criteria, which were included in the Meta analysis. The baseline of patients' characteristics was comparable in all the studies.CONCLUSION: By comparing the five common criteria, it was found that Pule'an was effective for improving IPSS, Q_max and QOL. More high quality trials with large samples and longer follow-up will be better for understanding the effects of Pule'an in BPH.

LC-MS/MS determination of torasemide in Beagle dog plasma and bioavailability evaluation

LI Rui-xing, FAN Hui-rong, WEI Guang-li, REN Xiao-wen, SI Duan-yun, LIU Chang-xiao

2012, 17(2):  199-205. 

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AIM: To establish an LC-MS/MS method for the determination of torasemide in Beagle dog plasma,and study the relative bioavailability of the torasemide sustained release tablets.METHODS: A reversed phase HPLC column of Waters Symmetry-C₁₈ (100 mm×4.6 mm, 5 μm) was used in the experiment.Acetonitrile-20 mmol/L ammonium formate (65∶35,V/V) was used as mobile phase at the flow rate of 0.4 mL/min, the column temperature was set at 30 ℃. A single oral dose of 5 mg torasemide release tablets or reference tablets were given to 6 Beagle dogs in an open randomized two way crossover design.The concentrations of plasma samples collected at the different time were determined by LC-MS/MS method.RESULTS: With the linear range of 0.02-5 μg/mL and the lower limit quantification of 0.02 μg/mL, the LC-MS/MS method had high sensitivity, stability and specificity. The main pharmacokinetic parameters of test sustained release tablets and reference tablets were as follows:the C_max were (2.6±0.5) μg/mL and (3.0±0.6) g/mL,the t_max were (3.3±1.4) h and (1.2±0.8) h,the AUC_{0-48 h} were (36.1±11.0) μg·h·mL^-1 and (32.1±13.1) μg·h·mL^-1. Compared to regular tablets,the bioavailability of sustained release tablets was (118.0±28.3)%.CONCLUSION: The method is simple, accurate and robust for the determination of torasemide in Beagle dog plasma, and successfully applied it to the bioavailability evaluation of torasemide sustained release tablets given to Beagle dogs.

Quantitative determination of Indapamide in human plasma by high performance liquid chromatography-tandem mass spectrometry

XU Shan, LIANG Yu-guang, QU Heng-yan, LI Yuan-yuan, GAO Hong-zhi, HAO Guang-tao

2012, 17(2):  206-210. 

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AIM: To establish a simple, sensitive method of high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) for the determination of Indapamide in human plasma.METHODS: Repaglinide calcium was used as internal standard.Indapamide was separated on an Agilent-ZORBAX-C₁₈ column (2.1 mm×150 mm,5.0 μm).The mobile phase consisted of acetonitrile-0.1% formic acid(90∶10).Electrospray ionization(ES1) was applied and operated in the positive multiple reaction monitoring(MRM) mode,used the transitions of [M+H]+m/z 388.4 m/z 247.4 and [M+H]+m/z 384.2 m/z 231.3 to quantify Indapamide and the internal standard respectively.RESULTS: The linear calibration curve was obtained over the concentration range of 0.5-50 ng/mL.The limit of quantification was 0.5 ng/mL.The inter- and intra-day precision (RSD) were less than 15%.The average recovery was between 94.60% and 110.33%.CONCLUSION: The method had been proved to be specific,convenient,sensitive and suitable for the clinical investigation of Indapamide pharmacokinetics.

Cinical study of Keluoxin combined with enalapril in treatment of diabetic nephropathy

LIU Lei, LI Liang-Zhi, HE Xian-Hong, TANG Yue-wu, SHI Ji-hong, LIU Chun-qiu, WU Ze-cheng, WANG Jun

2012, 17(2):  211-214. 

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AIM: To study the clinical curative effect of keluoxin collocystis combined with enalapril in treatment of diabetic nephropathy.METHODS: Forty three patients with early diabetic nephropathy and 37 patients with clinical diabetic nephropathy were randomly divided into enalapril control group and keluoxin combined with enalapril treated group,the tota1 course of treatment was 2 months.RESULTS: After 2 months of treatment,the levels of TC,TG and LDL-C in treated group were decreased obviously (P<0.05,P<0.01),the level of HDL-C was elevated obviously (P<0.05)in treated group,while there were no significant difference of TG, TC, LDL-C and HDL-C in control group.The UAER, α₁-MG、β₂-MG were decreased significantly in both groups in early diabetic nephropathy(P<0.05,P<0.01),but more significant in treated group than that in control group (P<0.05).The urine protein quantitative, urinaryα₁-MG, urinaryβ₂-MG and blood albumin were improved significantly in both groups in clinical diabetic nephropathy(P<0.05,P<0.01),but more significant in treated group than that in control group (P<0.05);the serum creatinine (Scr) in the clinical DN patients of control group was no obvious improvement (P>0.05),but the Scr in treatment group was improved significantly (P<0.05).CONCLUSION: Keluoxin combined with enalapril in treatment of DN patients has better effectiveness in reducing albuminuria and in improving renal function than enalapril alone.The data indicates that the combination of the two drugs can help each other against DN development. Keluoxin combined with enalapril are effective in treatment of diabetic nephropathy.

Efficacy and safety of paliperidone extended-release tablets as substituting medication in acute patients with schizophrenia

XU Ben-jian, CHEN Ju-feng

2012, 17(2):  215-219. 

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AIM: To evaluate the efficacy, safety and effect on personal and social function of paliperidone extended-release tablets (paliperidone ER) as substitution in inpatients experiencing an acute episode of schizophrenia, and unresponsive to prior medications of olanzapine besids.METHODS: Forty-five patients enrolled were assigned to receive paliperidone ER or risperidone for 6 weeks, meanwhile their prior medications of olanzapine were slowly tapered off within first 2 weeks. Positive and Negative Symptom Scale (PANSS) was used to assess the efficacy, Personal and Social Performance Scale (PSP) for social function, Treatment Emergent Symptom Scale (TESS) for tolerability and safety.RESULTS: PANSS total and PANSS factors scores significantly decreased from baseline to end point in paliperidone ER treatment group (P<0.01), moreover, significant improvements in mean PSP scale scores were observed (P<0.01). Paliperidone ER treatment was associated with low incidence of adverse events including insomnia, somnolence, extrapyramidal disorder, increased serum prolactin concentration, which could be well tolerated.CONCLUSION: This study demonstrated that paliperidone ER, as substitution for olanzapine combines consistent efficacy in significantly improving the symptoms of schizophrenia and personal and social functioning with a favorable safety profile, may provide a valuable new alternative for schizophrenia.

Therapeutic effects of Xuebijing injection on patients with acute respiratory distress syndrome

JIANG Xiao-gan, LU Wei-hua, JIN Xiao-ju, WU Jin-yi, SHENG Guang-gui, WANG Zhen

2012, 17(2):  220-224. 

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AIM: To observe the effect of Xuebijing injection on cytokine, coagulation function, and pulmonary function in patients with acute respiratory distress syndrome (ARDS).METHODS: From February 2008 to February 2010, a clinical study was conducted on consecutive adult patients with ARDS in department of intensive care medicine. The patients were divided into test group (30 patients) and control group (29 patients). Both groups were treated with the routine therapy of ARDS according to the ALI/ARDS guidelines of Society of Critical Care Medicine 2006, and in addition, Xuebijing injection was used in a dose of 50mL three times a day for 7 days in test group. Acute physiology and chronic health evaluationⅡ(APACHE Ⅱ)score,modified lung injury score(MLIS),partial pressure of oxygen(PaO₂),partial pressure of carbondioxide(PCO₂) and oxygenenation index(PaO₂/FiO₂) were recorded, and contents of interleukin (TNF-α,IL-6,IL-8)and prothrombin time(PT), activated partial thromboplastin time(APTT), platelet count (PLT), fibrinogen(FIB), C-reactive protein(CRP) were measured on before and the 1st,4th,7th days after therapy both two groups.RESULTS: A significant improvement of TNF-α,IL-6,IL-8,PT,APTT,PCO₂,CRP,FIB,PLT was observed, compared with that in the control group on 4th,7th days after treatment(P<0.05).The levels of PaO₂ and PaO₂/FiO₂ were higher in the test group than that in the control group on the 7th day after treatment(P<0.05). While the APACHEⅡscore and MLIS score between two groups had no significant difference.CONCLUSION: Xuebijing injection can play an adjuvant therapy role on ARDS by improve coagulation function, pulmonary function and decreasing the contents of TNF-α,IL-6,IL-8 in serum.

Relationship between ABC transporters on the blood-brain barrier and central nervous diseases

NIU Fang, ZHOU Fang, WU Xiao-lan, WANG Guang-ji

2012, 17(2):  225-233. 

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ATP-binding cassette (ABC) transporters are an important type of transporters on the blood-brain barrier, which mediate the efflux of numerous endogenous substances, drugs and neurotoxicants from the brain parenchyma. Various diseases can change the expression and activity of ABC transporters. Up-regulation of ABC transporter expression and activity is a major factor to cause drug resistance in centre nervous system (CNS), while reduction of transporter expression and activity increases the accumulation of neurotoxicants in brain to aggravate the disease. Thus, elucidating the relationship between transporters and CNS diseases is critical for discovering pathogenic mechanism and providing the strategies for improving the therapeutic effects of CNS drugs. This review covers the alterations of ABC transporter expression and activity in CNS diseases, the effects of these changes on CNS diseases and the related signaling mechanisms. Finally, we also propose some strategies for improving neuroprotection and enhancing therapeutic drug delivery to the brain.

Effects of extracellular-signal regulated kinsae signaling pathway on myocardial ischemia/reperfusion injury

CHEN Gao-yong, ZHANG Yan-mei, SHI Gang-gang

2012, 17(2):  234-240. 

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It has been suggested that extracellular-signal regulated kinsae (ERK), an important subfamily of mitogen-activated protein kinases (MAPKs), plays a pivotal role in modulating cell growth, differentiation, stress and death. Multiple studies showed that: during myocardial ischemia/reperfusion (I/R) injury ex vivo and in vivo, ERK becomes activated and plays a key role in inducing cell survival or cell damage, which might be dependent on the type of cell and the degree and duration of I/R. In this review we focus on the role of ERK pathway in myocardial I/R injury.