Table of Content

Volume 14 Issue 9
26 September 2009

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Method of control selection and margin choice in non-inferiority trials

MA Yu-quan, ZHOU Jun, ZHOU Ai-ping, YIN Ping

2009, 14(9):  961-965. 

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Non-inferiority trial is a type of design which can show that the clinical effect of the experimented medicine is no worse than the active control medicine. In the recent years, owing to the ethical limit of placebo-controlled trail and existence of many active medicines, non-inferiority trial designs have been widely used. Unfortunately, some non-inferiority trial designs have many flaws because of the lack of the golden rules, including disaccord to the applied condition, incorrect selection of the active control, irrationality of the margin conformation and etc. In this paper, control selection and margin choice are discussed and summarized mostly, combining with many overseas researches, in order to provide some suggestions to the design and practice of non-inferiority trial in our country.

Study on the CYP2C9 and CYP2C19 genetic polymorphism in Chinese subjects by using 3-dimense polyacrylamide gel-based microarray platform

MA Jing-jing, LI Jin-heng, CHENG Lu

2009, 14(9):  966-973. 

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AIM: To study the genetic polymorphisms of CYP2C9 and CYP2C19 by using 3-dimense polyacrylamide gel-based microarray method in healthy male Chinese subjects, providing original technology and research method for clinical rational administration. METHODS: 207 healthy male Chinese volunteers were recruited and their genomic DNA were isolated. The genomic fragments containing CYP2C9 ^* 3, ^* 13 and CYP2C19 ^* 2, ^* 3 polymorphic sites were amplified respectively to prepare 3-dimense polyacrylamide gel-based microarrays. After hybridized by fluorescent labeling probes, the microarrays were scanned to obtain genotyping results of CYP2C9 and CYP2C19.The analytic results were confirmed by direct sequencing. RESULTS: In 207 volunteers, the number of subjects with CYP2C9 ^* 1/^*3, CYP2C9 ^* 1/^* 13 and CYP2C9 ^* 3/^* 3 genotype were 11, 1, and 1, respectively. The frequencies of CYP2C9 ^* 3 and CYP2C9 ^* 13 alleles were 2.90 %and 0.24 %, respectively. The incidence of CYP2C9 poor metabolizers was 0.48 %. With regard to CYP2C19, heterozygous variants were 97 and homozygous variants were 26.The frequencies of CYP2C19 ^* 2 and CYP2C19 ^* 3 alleles were 32.85 % and 3.62 %, respectively. The incidence of CYP2C19 poor metabolizers was 12.56 %.The distribution of the four alleles were all coincident with Hardy-Weinberg law. CONCLUSION: 3-dimense polyacrylamide gelbased microarray method could serve as an advanced platform for clinical genotyping. The polymorphisms of CYP2C9 and CYP2C19 are frequent in Chinese population. Detecting the Genotyping CYP2C9 and CYP2C19 gene before administration could optimize related clinical drugs therapy, with the purpose of high efficiency and low incidence of adverse reactions.

Study on the rule of buccal absorption in human and the release discipline of borneol and menthol in Qingyan drop pills

XU Xue-fang, WANG Yang, CHEN Zhi-juan, HAJI Juma, ZHANG Yan-jun, HE Xin

2009, 14(9):  974-978. 

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AIM: Due to small amount of medicaments contained in the drop pills of Chinese herbal medicine, the study of drop pills has been restricted, therefore, the aim of the study was to investigate the dissolution and human buccal absorption characteristic of borneol and menthol in Qingyan drop pills in vitro. METHODS: The gas chromatograph (GC)method was established for simultaneous determination of borneol and menthol in Qingyan drop pills. The in vitro dissolution experiment of borneol and menthol was investigated with the instrument of drug dissolution, the human buccal absorption characteristic of borneol and menthol was performed in 5 healthy volunteers. The correlation between the cumulative human buccal absorption rate and the in vitro cumulative dissolution rate of borneol and menthol were analyzed. RESULTS: The in vitro dissolution experiment indicated that the maximum cumulative dissolution rates of borneol and menthol were 84.3 %, 79.7 % in 10, 20 min respectively, and the human buccal absorption experiment indicated that the maximum cumulative absorption rates of borneol and menthol were 90.3 %, 94.6 % in 45, 30 min respectively. The correlation between in vivo and in vitro experiment was good, and the correlation coefficients were 0.890, 0.907 respectively. CONCLUSION: A rapid, sensitive, and precise GC method has been established for the simultaneous determination of borneol and menthol in Qingyan drop pills. The results demonstrated that borneol and menthol, the main components of Qingyan drop pills, have the characteristic of rapid dissolution, fast release and absorption, which can meet the clinical demands of drop pills and provide theoretical basis for clinical medication.

Pharmacokinetic and pharmacodynamic studies on repaglinide in healthy Chinese volunteers

TAN Hong-yi, SONG Min, YANG Guo-ping, HUANG Zhi-jun, LIU Chang, YANG Li, XIANG Hong, FU Zhi-min, HUANG Yuan-yuan

2009, 14(9):  979-983. 

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AIM: To study the pharmacokinetics and pharmacodynamics of repaginide in healthy volunteers. METHODS: 19 healthy male volunteers in single oral dose of repaglinide tablets 4 mg. The plasma concentrations of repaglinide were determined by HPLC-MS-MS. The glucose levels of fingertip blood were measured by blood glucose monitoring system. The pharmacokinetic parameters were obtained by statistical analysis of DAS Ver 2.0.RESULTS: Plasma concentration-time curve conformed to one-compartment open model. The main pharmacokinetic parameters: C_max, t_max, AUC_0-88 and t_1/2 were (83.1±23.6) μg/L, (0.71±0.21)h, (97.1±37.8)μg·L-1·h, (1.6±0.7)h. The level of blood concentration was increased and blood glucose was decreased and reached its lowest value (3.0±0.65)mmol/L 1 h after administration of repaglinide. CONCLUSION: Repaglinide is characterised by fast-acting and short effects on insulin secretion. It is a prandial glucose regulator for treatment of type 2 diabetes mellitus that is not controlled by exercise and diet.

Study on essential metabolites of azithromycin in human urine by liquid chromatography-mass spectrometry

SUN Lu, HU Yan-ling, YANG Ya-nan, BAO Kai

2009, 14(9):  984-989. 

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AIM: To investigate the essential metabolites of azithromycin in human urine. METHODS: The urine samples of the volunteers after an oral administration of 500 mg azithromycin tablets were collected for 0-144 h, the samples were purified and separated through Strata C₁₈-E solid-phase extraction column and analyzed with liquid chromatography-mass spectrometry. The potential metabolites were analyzed through comparing the TIC and SIM chromatograms of the blank urine and sample urine, and the structure of the metabolites were identified through the correlation of the full scan MSn spectra of azithromycin and the metabolites. RESULTS: Eight metabolites were found in human urine, 4 metabolites were identified, the major metabolic pathways of azithromycin in human were Odemethylation, N-demethylation, N-desmethyl descladinose and hydroxylation. CONCLUSION: The research is possible to supply a reliable reference for further study on the metabolites of azithromycin.

Effects of genetic polymorphism of OATP1B1 on pharmacokinetics of repaglinide

YANG Guo-ping, SONG Min, TAN Hong-yi, LIU Chun, HUANG Zhi-jun, LIU Chang, YANG Li, XIANG Hong, FU Zhi-min, HUANG Yuan-yuan

2009, 14(9):  990-994. 

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AIM: To investigate the effects of the genetic polymorphism of organic anion transporting polypeptide 1B1 (OATP1B1) on the pharmacokinetic profile of repaginide in Chinese subjects. METHODS: The common haplotypes of SLCO1B1 (the coding gene of OATP1B1), which were reported as SLCO1B1 ^* 1a, ^* 1b, ^* 5 and ^* 15, were determined in 16 healthy male volunteers with the genotypes of ^* 1b/^* 1b, ^* 1a/^* 1a or ^* 1a/^* 1b, ^* 1a/^* 15 or ^* 1b/^* 15.A single dose (4 mg) of repaglinide tablets was given orally. The plasma concentrations of repaglinide were determined by HPLC-MS-MS method. The pharmacokinetic parameters were obtained by DAS Ver 2.0.The statistical differences of the pharmacokinetic parameters were assessed by SPSS 12.0.RESULTS: The values of AUC_{0-8 h} of SLCO1B1 ^* 1b/^* 1b, SLCO1B1 ^* 1a/^* 1a or ^* 1a/^* 1b and SLCO1B1 ^* 1a/^* 15 or ^* 1b/^* 15 three groups were (63±20), (70±26) and (82±24) μg·L^-1 ·h respectively. The values of C_max were (56± 16), (52±17) and (58±34) μg/L respectively. There were no significant differences between any two groups. CONCLUSION: The pharmacokinetic profile of repaglinide was affected by the genetic polymorphism of OATP1B1, but the difference from this experiment is not large enough to affect clinical drug safety and effectiveness.

Pharmacokinetics and distribution of amphotericin B liposome in animals

XU Zhi-ru, QIN Yan, MAO Wen-xue, LIU Quan-hai

2009, 14(9):  995-999. 

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AIM: To determine amphotericin B concentrations in plasma and tissues and to compare the pharmacokinetic profile in dogs and distribution profile in SD rats main tissues of test and reference amphotericin B liposome. METHODS: Six dogs were intravenously administered of 5 mg/kg test and reference preparations in an randomized cross-over study. Blood samples were collected at various time-points after drug administration. Rats were intravenously administered of 5 mg/kg test and reference preparations, tissues were collected at various time-points after drug administration. Analytical method based on HPLC method was established to determine the plasma and tissue concentration. The pharmacokinetic evaluation was carried out using the DAS 2.0 program. RESULTS: Six dogs were intravenously administered of 5 mg/kg amphotericin B liposome, and an open two compartment model best described the concentration-time profiles for amphotericin B liposome. The main pharmacokinetic parameters were t_1/2β(53.6±2.2)h, AUC(18.7±3.2)mg·L^-1·h ; CL(0.23±0.05) L·h^-1 ·kg^-1, V₁ (11.6±2.8) L/kg for the test preparation and t_1/2β(52.8±0.9)h, AUC(19.6±2.2)mg·L^-1·h, CL (0.22±0.03) L·h^-1 ·kg^-1, V₁(10.6±2.9)L/kg for the reference preparation. CONCLUSION: The statistics analysis shows that there are no significant differences(P > 0.05)between the test and reference preparation in major pharmacokinetic parameters in dogs and tissue distribution in rats.

Anti-inflammatory effect and mechanism study of total flavonoids in Chrysanthemum morif olium Ramat

WU Xiao-ning, YU Chen-huan, BAO Qi-nian

2009, 14(9):  1000-1003. 

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AIM: To study the anti-inflammatory effect of total flavonoids in Chrysanthemum morif olium Ramat and the mechanism. METHODS: The auricle edema was induced by dimethylbenzene, the abdominal cavity capillary permeability was increased by HAc, the edema in feet was induced by carrageenan in mice, and the air-pouch acute inflammation induced by carrageenan in rats were applied in anti-inflammatory experiments. The anti-inflammatory effect of total flavonoids in different models were observed, then the content of the protein, the amount of white blood cell(WBC), prostaglandin E₂ (PGE₂)and malonaldehyde (MDA) and the activity of superoxide dismutase (SOD)were determined. RESULTS: Total flavonoids could inhibit the capillary permeability and the engorgement of inflammatory texture, decrease the total protein content in efflusion and the amount of WBC, reduce PGE₂ and MDA contents and increase SOD activity. CONCLUSION: The mechanisms of anti-inflammatory action of total flavonoids are related to the depression of vasopermeability, reduction of inflammatory mediators and augmentation of oxygen free radical scavenging capacity and anti lipid peroxidation.

Effects of synthetic musk on clotting-time and platelet aggregation rate in acute blood-stasis model rats

LI Hai-tao, LI Jie, CHEN Tao, JI Shui-ling

2009, 14(9):  1004-1007. 

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AIM: To study the effects of synthetic musk on clotting-time and platelet aggregation rate in acute blood-stasis model rats. METHODS: The acute blood-stasis model rats were made by soaked ice water after injection of adrenalin hydrochloride in a major dose. Compound salvia tablet was intragastrically administered in positive control group. After management, the clotting-time and platelet aggregation rate were observed. RESULTS: Compared with the model group, after administration of synthetic musk the maximum percentage of platelet aggregation was palliated significantly(P <0.01 or P <0.05).Compared with the model group, after administration of high dose synthetic musk the TT, PT and APTT (indexes of clottingtime) were prolonged significantly(P <0.05). CONCLUSION: Synthetic musk can inhibit the platelet aggregation, prolong the clotting-time and ameliorate the abnormality in hemorheology.

Effect of budesonide on the expression of inducible nitric oxide synthase at blood heterophil granulocyte in asthma rats

YE Hui, YING Xiao-ming, TONG Xia-sheng, CHEN Li-zhong, ZHAO Bei

2009, 14(9):  1008-1012. 

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AIM: To observe the effect of budesonide on the expression of inducible nitric oxide synthase (iNOS) at blood polymorphonuclear leukocyte (PMN) in asthma rats. And to approach the pathogenesis of PMN in asthma inflammation. METHODS: The model rats of asthma were induced by OVA and Al (OH) 3.The blood PMN was isolated and purified. The expressions of iNOS protein at blood PMN were detected by immunohistochemical method. The concentration of nitric oxide (NO) at bronchoalveolar lavage fluids (BALF) were detected by colorimetric method. RESULTS: Expressions of iNOS protein at PMN in asthma group were significantly higher than those in control group (P <0.01). And the expressions of iNOS protein at PMN in budesonide treated group were significantly lower than those in asthma group (P < 0.01). The expressions of iNOS protein at bronchial wall in asthma group were significantly higher than those in control group (P <0.01). And the expressions of iNOS protein in budesonide treated group were significantly lower than those in asthma group, but higher than those in control group (all P <0.01). Concentrations of NO at BALF in asthma group were significantly higher than those in control group (P < 0.01). Concentrations of NO at BALF in budesonide treated group were significantly lower than those in asthma group. There was significant positive correlation between the expressions of iNOS protein at blood PMN and NO concentration at BALF(n =29, r =0.754, P <0.01). And there was significant positive correlation between the expressions of iNOS protein at bronchial wall and NO concentration at BALF (n =29, r = 0.760, P <0.01). CONCLUSION: The levels of iNOS protein synthesized by PMN are increased in asthma rats. PMN may be implicated with asthma pathogenesis via iNOS, but this function of PMN can be partly inhibited by budesonide.

Effects of p21 gene transfection in human arterial smooth muscle cells

LIN Bing-lai, JIANG Lan-lan, FANG Wu-wang

2009, 14(9):  1013-1017. 

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AIM: To find a new way for the treatment of restenosis after coronary artery inserted stent, the effect of p21 gene transfection in human arterial smooth muscle cells (HASMCs) was investigated and its antagonistic effect of restenosis after coronary artery inserted stent was studied. METHODS: P21 gene was transfected into HASMC via Lipofectamine 2000 liposomes and the expression of its encoded protein in HASMCs was detected by immunohistochemistry. The effects of p21 gene transfection on the growth, proliferation and apoptosis of HASMCs were described by cell growth curves, the WST-1 assay and flow cytometry (FCM) analysis respectively. RESULTS: Immunohistochemical result indicated that the protein encoded by p21 gene was highly expressed in the cytoblast of HASMCs. The expression of p21 gene significantly inhibited the growth and proliferation of HASMC and remarkably promoted its apoptosis. Compared with the control group, the difference was statistically significant. CONCLUSION: These results demonstrate that the encoded protein of the p21 gene transfected into HASMCs may be involved in inhibiting cell growth and inducing apoptosis, suggesting that the technology of p21 gene transfected into HASMCs can be a new strategy to prevent and treat restenosis after coronary artery inserted stent.

Expression and significance of signal transducer and activator of transcription 6 and prostate-specific antigen proteins in prostatic carcinoma

CHEN Rong-sheng, LUO Dong-jiao, CHEN Li, TONG Xia-sheng, CHEN Hao, WANG Enzhi

2009, 14(9):  1018-1022. 

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AIM: To observe the expressions of signal transducer and activator of transcription (STAT)- 6 and prostate-specific antigen(PSA) proteins in prostatic carcinoma, and approach the pathogenesis and early diagnosis methods of prostatic carcinoma. METHODS: All patients were operated during January 2005 to May 2008 including 20 cases of prostatic carcinoma and 36 cases of benign prostatic hyperplasia. The expressions of STAT-6 and PSA proteins were detected by immunohistochemical methods in prostate tissue. The concentration of totall PSA(tPSA) and free PSA(fPSA) in serum were detected by electrochemiluminescence. The prostate volume was measured by color doppler ultrasound. The ratio of f/ t value and prostate specific antigen density (PSAD) were calculated. RESULTS: The expressions of STAT-6 and PSA protein were significantly higher in prostatic carcinoma group (Optical Density: 0.24±0.08 and 0.31±0.09, respectively) than those in benign prostatic hyperplasia group(Optical Density: 0.12±0.06 and 0.20±0.07, respectively) (all P <0.01). The concentrations of tPSA and fPSA in serum and PSAD were significantly higher in prostatic carcinoma group [(43±26) ng/mL, (3.8± 2.2) ng/mL and (0.88±0.66) ng·mL^-1·cm^-3, respectively] than those in benign prostatic hyperplasia group[(6±4) ng/mL, (1.2±0.8) ng/mL and (0.12±0.09) ng·mL^-1 ·cm^-3, respectively] (all P <0.01). There were no statistically differences in the f/t value and prostate volume between prostatic carcinoma group[(0.14±0.10), (61±35) cm³, respectively] and benign prostatic hyperplasia group(0.31± 0.48, 47±24 cm³, respectively) (all P >0.05). CONCLUSION: STAT-6 and PSA may participate in the development of prostatic carcinoma. The concentrations of tPSA and fPSA in serum and PSAD can be applied as effective screening targets for prostatic carcinoma diagnosis.

Effects of dexamethasone on toll-like receptor 4 mediated signaling pathways in mice dendritic cells

WU Xiang-ling, HE Xiao-kui, LI Bo, HU Yong-xiu

2009, 14(9):  1023-1027. 

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AIM: To observe the effects of dexamethasone on the expression of toll-like receptor 4 (TLR4) and the activation of NF-κB of dendritic cells (DC), and investigate the mechanism of dexamethasone suppressing differentiation, maturation, and function of DC. METHODS: DC generated from C57BL/6 murine bone marrow cells were induced by GM-CSF and IL-4.Dexamethasone was added in the DC's culture system, the cells were analyzed by flow cytometry (FCM) to determine the expression of TLR4 &CD11c, and by electrophoretic mobility shift assay (EMSA) to verify the activation of transcription factor NF-κB of DC. RESULTS: Dexamethasone could suppress the expression of CD11c and the activation of NF-κB with a dose-effect relationship in DC, but it could not suppress the expression of TLR4 of DC. CONCLUSION: The mechanism of dexamethasone involved in inhibition of differentiation, maturation, and function of DC is perhaps related to suppression of NF-κB activation.

Experimental study on Shu Dan Tong granules in prevention and frecatment effects of cholelithiasis

LU Hong, ZHANG Xin-yue, LIU Fang-fang, LIU Ping, JIN Shao-sheng

2009, 14(9):  1028-1031. 

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AIM: To observe the prevention and cure effects of Shu Dan Tong granules(SDT) on experimental cholelithiasis in guinea pigs. METHODS: 62 DHA guinea pigs were randomly divided into normal group, model control group, positive control group, as well as SDT 5, 10, 20 g (crude drug, the same below)/ kg dose group, feed with high cholesterol and low protein lithogenic diet in addition to the normal group, and all guinea pigs in different group were given corresponding drugs simultaneously by gavage administration for 70 days, and the general condition, stone formation, bile secretion and composition, blood biochemistry were observerd or detected. RESULTS: SDT can significantly improve the general condition of cholelithiasis in guinea pigs, lower lithogenesis rate and improve total bile acid (TBA) content in doses of 5, 10, 20 g/kg, and can significantly improve the bile secretion and plasma cholecystokinin (CCK) levels, lower serum total cholesterol (TC) levels in doses of 10, 20 g/kg. CONCLUSION: SDT has the prevention and cure effects on cholelithiasis modle of guinea pigs.

Effects of valsartan on BKCa of hypoxic pulmonary hypertensive rats

WANG Xin, YANG Yu-wen, WANG An-cai, KONG Xiang-quan

2009, 14(9):  1032-1035. 

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AIM: To observe the effects of valsartan on the large-conductance calcium-activated potassium channel (BKCa)of smooth muscle cells isolated from hypoxia-pulmonary artery hypertension (PAH) rats. METHODS: Thirty second-grade healthy SD male rats aged 7 weeks were selected, and divided randomly into 3 groups: Group A was control group, Group B was PAH group and Group C was valsartan intervention group with 10 rats in each group. The mean pulmonary artery pressure(PAMP)was measured in 3 groups. The arteria mesenterica smooth muscle cell capacitance of membrane(Cm), potassium current, and the current after BKCa was blocked by tetraethylammonium(TEA)were recorded by whole cell patch clamp and the BKCa current and the BKCa current density were calculated. The BKCa protein expression was measured by immuno-histochemical stain. RESULTS: Compared with Group B, the PAMP was lower than that in Group A or Group C(P <0.01), the membrane capacitance, BKCa current, current density and iOD value in Group A were higher(P <0.05), the BKCa current, BKCa current density were increased at different degrees in Ggroup C (P <0.05), but there was no change in iOD value. CONCLUSION: Valsartan can effectively reduce pulmonary pressure in hypoxia- pulmonary artery hypertension rats. The mechanism was probably the BKCa was activiated by valsartan.

Comparison of protective effects on H₂O₂-induced PC12 injury from S. miltiorrhiza Bunge injection and S. przewalskii Maxim injection

LUO Hui-ying, CHENG Ti-juan

2009, 14(9):  1036-1039. 

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AIM: To compare the influence of S. miltiorrhiza Bunge injection (SMBI) and S. przewalskii Maxim injection (SPMI) on H₂O₂-induced injury in PC12.METHODS: PC12 cells were cultured in vitro to compare the protective effects of SMBI and SPMI on cell injury induced by H₂O₂. The survival rate was measured by MTT method, and the apoptosis rate of PC12 cells was detected by flow cytometry, the protein expressions of bcl-2 and bax in PC12 cells were detected by immunocytochemistry staining method. RESULTS: When PC12 was damaged by H₂O₂, the rate of cell survival was degraded, and the rate of apoptosis was increased. SMBI and SPMI could alleviate the destroy effectively(P <0.05), they both could strengthen the expression of bcl-2(P <0.05) and lighten that of bax(P <0.05). CONCLUSION: The results suggested that SMBI and SPMI had comparable protective effect on H₂O₂-induced injury in vitro. The main effects of both injections were related to strengthening the expression of bcl-2 and lightening that of bax.

Determination of the median effective dose of rocuronium via tracheal in tubation in different age male patients by sequential experimental method

ZHANG Kai, YUE Xiu-qin

2009, 14(9):  1040-1043. 

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AIM: To determinate the median effective dose (IED₅₀) of rocuronium via tracheal intubation in different ages male patients by sequential experimental method, and study the effect of the age to IED₅₀. METHODS: 40 patients(ASA grade Ⅰ or Ⅱ) scheduled for selective surgical procedure under general anaesthesia were studied. The patients were divided into two groups, young men group(n =20) and older men group(n =20). The tracheal intubation dose was divided into four grades by geometric progression growth, 0.35, 0.42, 0.5, 0.6 mg/kg in the young men group and 0.31, 0.37, 0.44 and 0.53 mg/kg in the older men group. The IED₅₀ and 95 % confidence interval (95 %CI) of rocuronium during intubation in either group was determined by sequential experimental method. RESULTS: IED₅₀ was 0.4502 mg/kg in the young men group, which was 0.4039 mg/kg in the older men group. The IED₅₀ in the older women group was 89.7 % of that in the young women group(P <0.05). The concentration of plasma total protein and albumin in the oldermen group was lower than that in the young men group (P <0.05). CONCLUSION: Sequential experimential method is a simple, efficient and reliable method for the IED₅₀ determination of rocuronium during intubation. The IED₅₀ was lower in the older men group than that in the young men group, which is possibly related to the difference of the concentration of plasma total protein in different ages male patients.

Pharmacokinetics of memantine hydrochloride capsule in Chinese healthy volunteers

ZHANG Kun, QU Ting-ting, YUAN Gui-yan, WEI Chun-min, WANG Ben-jie, GUO Ruichen

2009, 14(9):  1044-1046. 

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AIM: To study the pharmacokinetics of memantine in healthy Chinese volunteers after single and multiple doses of memantine hydrochloride capsule. METHODS: The concentration of memantine in human plasma was determined by HPLC-MS MS method and its pharmacokinetic parameters were calculated by DAS 2.0.RESULTS: The main pharmacokinetic parameters of memantine after single oral dose of 5, 10, 15 mg memantine hydrochloride capsule were as follows: t_max were (5.6±1.2), (5.2±2.0) and (4.9±1.1) h.C_max were(4.4±0.9), (8.9±1.6) and (16.5±2.8) ng/mL, t_1/2 were (47±10), (47± 9) and (51± 9) h, and after multiple oral dose of 10 mg memantine hydrochloride capsule were as follows: t_max was(6.0±1.4) h, C_max was(32±6) ng/mL, t_1/2 (46±8) h. CONCLUSION: A dose relationship of C_max and AUC existed after single oral doses of 5, 10 and 15 mg memantine hydrochloride capsule.There is accumulation after a multiple dose of 10 mg once daily administration.

Effects of remifentanil on heart rate —clinical and experimental research

LI Li-bing, SU Chang, MA Lan, GAO Chang-qing

2009, 14(9):  1047-1052. 

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AIM: To investigate the effects of remifentanil on heart rate (HR) and heart rate variability (HRV) in patients and isolated rat hearts, and approach its mechanism of action. METHODS: Clinical research: 40 patients were divided into two groups randomly: remifentanil-only-group(Group R, n =20) and pre-atropine-group (Group A, n =20). Group A were given atropine 0.5 mg (i. m.) 30 min before remifentanil administration. Remifentanil 2 μg/kg was administrated with TCI pump at speed of 1 μg·kg^-1·min^-1. HR and Low frequency High frequency(LF/HF) were observed and recorded before and after administration. Animal experiment: 24 SD rats were divided into three groups randomly (n =8): control group (Group C), 10 ng/mL remifentanil group (Group R10) and 30 ng/mL remifentanil group (Group R30). The isolated rat hearts were perfused with Langendorff apparatus. HR and LVDP were monitored continuously. RESULTS: HR and LF/HF in Group R were decreased significantly (P <0.05) at each observed point after remifentanil administration. But in Group A, the changes of HR and LF/HF were not observed. Compared with Group A, the HR and LF/HF at each observed point were decreased (P <0.05). Between Group R and Group A, HR and LF/HF had significant differences(P <0.05). In animal experiment there was no significant difference of HR and LVDP in the three groups. CONCLUSION: Intravenous injection of remifentanil decreases HR and HRV of patients markedly. The inhibitory effects of remifentanil on heart can be reversed by atropine. Based on animal experiment we conclude that the depression of remifentanil on heart is caused by inhibiting central nervous system or interfereing balance of autonomic nerve system.

Effects of levocarnitine oral solution on the plasma N-terminal probrain natriuretic peptide levels in children with acute lymphocytic leukemia treated by daunorubicin

WANG Ju-xiang, ZHU Xin-bo, ZENG Wei-wei, QIAN Jiang-chao, ZHOU Hai-xia, HUANG Zhen, FANG Xi-min, XU Xia, LI Yuan

2009, 14(9):  1052-1055. 

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AIM: To explore the value of N-terminal pro-brain natriuretic peptide (NT-pro BNP) in diagnosing the myocardiopathy induced by daunorubicin (DNR) and the more effective cardiac-protection drugs by investigating the changes of the NT-pro BNP levels after administrating DNR in children with acute lymphocytic leukemia. METHODS: Twenty-two children with acute lymphocytic leukemia who treated with DNR containing vincristine, L-asparaginase, prednisone, were randomly divided into two groups. The therapy group received L-CN as the cardiac-protection drug and the control group without protecting heart drug during chemotherapy with DNR. The level of NT-pro BNP in plasma was measured by immunoassay before and after using DNR and the cardiac troponin I(cTnI) and cardiac muscle enzyme (LDH1, CPK-MB) and ECG were detected before and after chemotherapy. RESULTS: The level of NT-pro BNP in plasma was increased from (53±11) pg/mL to (162±27) pg/mL (P <0.01) in the therapy group after chemotherapy and which in the control group was increased from (51±10) pg/mL to (194±38) pg/mL (P <0.01). There was no significant difference in the level of NT-pro BNP before chemotherapy between two groups. The level of NT-pro BNP in plasma was lower in the therapy group than that in the control group(P <0.05). The improving condition of the level of NT-pro BNP in the therapy group was better than that in the control group after chemotherapy. There were no significant difference in the ECG and cTnI and LDH1, CPK-MB in two groups before and after chemotherapy. CONCLUSION: NT-pro BNP can be served as a good indicator for DNR-induced myocardiopathy. Compared with control group, the improving condition of NT-pro BNP is obvious treated with levocarnitine.

Effects of Qingrehuayuziyin Fang on lymphocyte apoptosis and expression of Fas and FasL in peripheral blood in the patients with systemic lupus erythematosus

LIANG Wei, JIN lin, GONG Ling, ZHANG Li-ling, LIAO Hui, CAI Ying, TANG Yong-ming

2009, 14(9):  1056-1060. 

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AIM: To investigate the effect of Qingrehuayuziyin Fang on lymphocyte apoptosis and expression of Fas and FasL in peripheral blood in the patients with systemic lupus erythematosus (SLE). METHODS: Eighty patients with SLE were selected and divided randomly into two groups, 40 in the therapy group and 40 in control group respectively. Patients were get the treatment of Qingrehuayuziyin Fang combined hormone (prednisone) as therapy group and get hormone treating only as control group. After treating three months, lymphocyte were collected to be detected the rate of apoptosis by flow cytometer. Meanwhile, the expression of Fas and FasL were analyzed by RT-PCR. RESULTS: After three months treating, the rate of lymphocyte apoptosis was decreased significantly in therapy group compared with that in control group(P < 0.01) and with that in pre-treating (P <0.01). The expression of Fas and FasL, compared with that in control group, was also decreased significantly (P < 0.01). CONCLUSION: Qingrehuayuziyin Fang is useful for treating SLE by suppressing lymphocyte apoptosis, decreasing the level of Fas and FasL in peripheral blood and further modifying the immune status.

Effects of orlistat on endothelium-independent vasodilation function in obese subjects with hypertension

LIU Jing, SUN Ning-ling, YANG Song-na, MA Zhi-yi, YANG Jing

2009, 14(9):  1061-1064. 

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AIM: To evaluate the effect of orlistat on blood pressure and arteria brachialis nitroglycerin mediated endothelium-independent vasodilation in obese subjects with hypertension. METHODS: Thirty obese patients with mild hypertension (obese hypertension group)took orlistat 120 mg tid for 12 weeks. The height, body weight, waist circumference (WC)and blood pressure were measured and the body mass index (BMI)was calculated. The degree of nitroglycerin-mediated vasodilation (NMD)of brachial artery was determined by high-resolution ultrasound before and after 12 weeks treatment with orlistat. 15 concurrent blood pressure, age and gender-matched non-obese hypertensive patients served as control. RESULTS: The baseline parameters were comparable between the two groups. There were no differences in NMD between obese hypertension group and no obese hypertension group before treatment, while the BMI and WC were obviously increased in obese hypertension group (P <0.01, respectively). The BMI, WC and blood pressure were decreased significantly (P <0.05 or P <0.01, respectively) after 12 weeks orlistat treatment. Compared with that in before treatment group the NMD was not significantly affected (16.2 % vs 15.5 %, P >0.05). CONCLUSION: Orlistat can decrease the body weight and blood pressure in a short period treatment, but there were no effects on arteria brachialis nitroglycerinmediated endothelium-independent vasodilation in obese hypertension patients.

Clinical observation on puerarin combined buflomedil in the treatment of 60 cases with vertebro basilar artery insufficiency

CHEN Yong, FU Ling, CHEN Yun-qing, FU Heng, ZHENG Zuo-hong

2009, 14(9):  1065-1067. 

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AIM: To observe the clinical efficacy of puerarin combined buflomedil in the treatment of vertebro basilar artery insufficiency and the bleeding and clotting time, the prothrombin time and the average blood flow velocity of vertebral-basilar artery (VBA)by transcranial Doppler (TCD). METHODS: One hundred and twenty patients with vertebro basilar artery insufficiency were randomized into the treatment group (n =60)which were treated with buflomedil alone and control group (n =60)which were therapied by puerarin combined buflomedil. Changes of the clinical efficacy, the bleeding and clotting time, the prothrombin time and the average blood flow velocity of VBA before and after treatment were observed and compared in the two groups. RESULTS: The total effective rate was 90 % in the treatment group and 71.2 % in the control group showing statistically significant difference (P < 0.05).Compared with that before treatment, there was significant difference in improving the blood flow velocity of VBA after treatment in the treatment group(P < 0.05), while no differences in the control group. There were no significant differences between the two groups in the prothrombin, bleeding and clotting times. CONCLUSION: The therapeutic effect of puerarin combined buflomedil in treating patients with vertebro basilar artery insufficiency is superior to that of buflomedil alone.

Study between related factors of hepatocellular carcinoma and ubiquitin proteasome pathway

WANG Shuai, CHU Liang, HU Xiao-wei, YAO Ji-hong

2009, 14(9):  1068-1073. 

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Hepatocellular carcinoma is one of the largest causes of cancer-related deaths worldwide for which there are very limited effective treatment options. The ubiquitin-proteasome pathway (UPP) has rapidly become acknowledged as both critical mechanism for cellular biological function and a latent target of regulation of cancer- related disease. This review focus on the role of ubiquitin-proteasome pathway in hepatocellular carcinoma and its correlation factors (HBV 、P27 、 NF-κB, et al), in order to find novel therapeutic interventions against the genesis and development of hepatocellular carcinoma.

Advance in research for pharmacokinetics on antifugal drug of itraconazole

MIAO Cai-yun, CHEN Jiang-fei

2009, 14(9):  1074-1080. 

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Itraconazole, a triazole broad-spectrum antifungal drug, is notably effective on superficial and deep fungal infection, and widely used with good tolerance. This article reviews the pharmacokinetic characters, interaction and pharmacokinetics in different patient groups of itraconazole in order to promote its rational application in clinical practice.