Table of Content

Volume 3 Issue 3
26 September 1998

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Enhancement of antitumor activity of nitrogen mustard and cyclophosphamide by buthionine sulfoximine in several cancer cell lines

ZHANG Xue-Feng, YAO Ming-Hui

1998, 3(3):  161-164. 

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Aim To examine the effects of buthionine sulfoximine (BSO), a specific inhibitor of glutathione (GSH) synthesis, on the cytotoxicity of two alkylating agents nitrogen mustard (HN₂) and cyclophosphamide (CTX) in three cancer cell lines in vitro and in vivo. Methods The cytotoxicity of drugs in vitro and in vivo was assessed by modified MTT assay and tumor-weight reduction respectively. Results In human leukaemia HL-60 cells，BSO (50 μmol·L^-1) pretreatment resulted in marked depletion of cellular GSH (by 87% of control ofter 24 h) and enhanced cytotoxicity of HN₂ (0.1 ~ 0.5 mg·L^-1)，with dosemodifying factor (DMF) of 9.19 observed. BSO (400, 500 mg·kg^-1×7, po) and CTX (15, 17.5 mg·kg^-1×7，ip) combination produced higher responses compared to CTX alone，with the growth inhibition rate increased from 22.6% to 32.3%, and from 26.1% to 51.1 % in Lewis- and Hepa A - tumoi-bearing mice respectively. Conclusion The cytotoxicity of HN₂ and CTX can be enhanced by BSO in vitro and in vivo suggesting the clinical applicability of BSO as a new chemosensitizin agent.

Bioavailability study of a new diclofenac slow release tablet in 12 healthy volunteers

GAO Lian-Yong, LI Quan-Sheng, WEI Guang-Li, XIAO Shu-Hua, LIU Chang-Xiao

1998, 3(3):  165-170. 

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Aim The comparative bioavailability of two diclofenac slow release tablets was studied after a single and repeated oral administration in 12 healthy male volunteers. Methods HPLC method with UV detection was used to determine the serum drug concentrations. Results The pharmacokinetic parameters obtained after single oral administration of the two formulations to the subjects in cross-over design showed that there was not significant difference between the two formulations in maximum concentration (C_max) and the area under the time-concentration curve (AUC) (P>0.05) whereas the time to reach the CC_max of the test tablets (TT) was shorter than that of the reference tablets (RT), with a significant difference between them. The relative bioavailability of TT was 98.11%. The result of the study on the repeated oral doses in 12 subjects indicated that there was no significant difference between the two tablets in C_max, C_min, C_ave, r and DF (P＞0.05). The duration of the minimum effective therapeutic drug level (T_mec) and the serum drug concentration peak-trough fluctuation of TT and RT in steady state were similar. Both TT and RT possessed good sustained release property. Conclution The two slow release tablets are bioequivalent formulation, with small difference between the two tablets in C_max and C_min. T_peak of TT in both single and repeated oral doses is significantly shorter than that of RT.

Effect of compound 861 on hepatic stellate cell poroliferation and collagen synthesis

MA Hong, WANG Bao-En, MA Xue-Mei, JIA Ji-Dong

1998, 3(3):  172-174. 

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Aim The effect of compound 861 (Cpd 861) on rat hepatic stellate cell(HSC) proliferation and collagen synthesis in vitro was observed. Methods The second passage of HSC was exposed to Cpd 861 at a concentration of 1.56 ~ 100 mg/ ml for 48 hours. MTT colorimetric assay was used to evaluate the effect of Cpd 861 on HSC proliferation. After incubation with Cpd 861 for 48 hours, HSC was harvested to determine collagen type I, III, IV mRNA by dot blot hybridization and cell culture medium was used to detect collagen secretion by ELISA method. Results Cpd 861 (through 0.45 μm filter membrane) could reduce MTT transforming rate and the inhibitory effect had a positive relation with the concentration of Cpd 861 in the cultured medium. Type I, III, IV collagen and TGF(β1 productions, were inhibited by Cpd 861 at a concentration of 10 mg/ml. Conclusion The antifibrotic mechanism of Cpd 861 was partly due to its inhibition of HSC proliferation and collagen production, which would reduce deposition in the liver.

Clinical evaluation of micronised fenofibrate in the treatment of primary hyperlipidemia in the elderly

QIN Shu-Cun, ZHANG Wei-Qiang, QI Peng, ZHAO Mei-Ling, DONG Zhen-Nan, FANG Pin-Fang, ZHANG Jin, LIN Yu-Zhen, XU Xiao-Man, LI Yong-Chang, FANG Xin, FU Lei

1998, 3(3):  176-180. 

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Aim To evaluate the curatice effect of micronised fenofibrate on primary hyperlipidemia in the elderly patients. Methods Fifty two old patients aged from 60 to 76 years with primary hyperlipidemia with total serum cholesterol (TC) greater than 5.20 m mol/L(200 mg/dl) and / or triglyceride (TG) ranging from 2.0 to 5.7 m mol/L (180 ~ 500 mg/dl), were randomly allocated into the fenofibrate or the placebo group. Each case was given oral 200 mg micronised fenofibrate or placebo per day for eight weeks. Results After treatment for four weeks, the serum levels of TC, TG, low density lipoprotein cholesterol (LDLC), and the ratio of [TC-high density lipoprotein cholesterol (HDLC)/ HDLC were more significantly lowered, and the level of HDLC was more significantly increased, in the micronised fenofibrate group than in the placebo one, respectively (P ＜0.01 or P ＜0.05) After treatment for eight weeks the similar effects were observed and the lowering range of the serum levels of TC, TG, LDLC, and the ratio of (TC-HDLC)/HDLC in the fenofibrate group were separately 32.9%, 53.7%, 29.4% and 41.9%, which much higher than these in the placebo group (P ＜0.01 or P ＜0.05). The drug was well-tolerated by all patients and no significant side effect was observed. Conclusion The micronised fenofibrate is highly effective in lowering serum TG as well as effective in lowering TC and LDLC. This agent is safe and tolerable in the elderly patients with hyperlipidemia

Culture of epidermal cells and inhibition effect of cyclosporin A on cell proliferation in infant mice

YANG Yan, WU Tie, LIU Gang, HE Kang

1998, 3(3):  181-183. 

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Aim The growth characteristic of cultured epidermal cell and the inhibition effect of cyclosporin A (CSA) on cell proliferation at the doses of l μg/ml, 3 μg/ml and 6 μg/ml were observed. Methods The single epidermal cells of infant mice were cultured without EGF (eidermal growth factor). Growth curve was descriped by numbering the alive cells in different times. The inhibition rate of CSA on cell proliferation was calculated. Results Epidermal cells might be survived for about 15 days without EGF. Cells would attach to the wall of bottle in 24 h. The growth top time was in 5 ~ 7 days. There were some hollows in cytoplasm after 10 days. There was no inhibition effects of CSA on cell proliferation when cells were cultured for 24 h and 48 h at the dose of 1 μg/ml but a weak inhibition effect was seen in 72 h with the inhibition rate being 15% when cells were cultured with 3 μg/ml CSA for 48 h and 72 h the inhibition rates were 18% and 30%. There was no inhibition effect in 24 h still. When cells were cultured with 6 μg/ml for 24 h 48 h and 72 h the inhibition rates were 16%, 40% and 65% respectively. Conclusion CSA inhibit cell proliferation in a dose and time dependent manner.

Protective effects of liqustrazin on myocardial ischemia-reperfusion injury in rats

WAN Fu-heng, ZHAO Xiao, Man LIU, Bo LI Jin-heng

1998, 3(3):  184-186. 

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Aim The effect of liqustrazin on myocardial ischemia leperfusion injury in rats was observd. Methods The rat model of myocardial ischemia tepeifusion was established by ligating coro-nary artery. The rats were randomly divided in the control, model and liqustrazin treated groups. The activities of SOD, GSH · PX, Ca²⁺-ATPase, K⁺, Na⁺ ATPase and contents of MDA and Ca²⁺ were observed respectively. Results In the liqustrazin treated group as compared with those of the model, the activities of SOD, GSH · PX, Ca²⁺ ATPase, K⁺, Na⁺ -ATPase in the myocardial membrane increased significantly (P ＜0.01 or P ＜0.05) w hile contents of MDA and Ca²⁺ decreased (P ＜0.01) significantly. Activities of SOD and GSH · PX in the mitochondria was also increased (P ＜0.01) and MDA content decreased (P ＜0.01). Conclusions Liqustrazin has notable protective effects on myocardial-ischemia leperfusion injury in rats, which is due to its scarenging oxygen free radicals and anti ipid peroxydation reaction.

Study on the pharmacokinetics of astemizole suspensions in healthy volunteers

LIU Jun-Bao, CHEN Xiao-Chuan, CAO Qi, YA NG Guang-De, YANG Yin-Jing

1998, 3(3):  187-189. 

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Aim To compare the pharmacokinetic parameters of the domestic astemizole suspension with those of the imported product in Chinese healthy volunteers. Methods Astemizole and demethylastemizole concentration was measured by radioimmunoassay in a clinical trial of crossover design. Results The main pharmacokinetic parameters of the domestic product calculated by practical pharmacokinetics program 87 were Vd =6.88 ±1.36 L; αT_1/2 =4.24 ±4.06 h; βT_1/2 =170.31 ±73.80 h; CL =0.067±0.023 ng/ml; T_peak =1.00 ±0.53 h; C_max =1.25 ±0.17 ng/ml; AUC =162.97±48.57 ng/ml·h^-1, while the parameters of the i mport ed product were Vd =6.40 ±3.07 L; αT_1/2 =1.31 ±0.91 h; βT_1/2 =156.02 ±120.74 h; CL =0.079±0.045 ng /ml; T_peak =1.00 ±0.53 h; C_max =1.08 ±0.19 ng/ml; A UC =173.46 ±114.66 ng/ml·h^-1. The relative bioavailability of the domestic suspension was 90.5%. Conclusion No significant pharmacokinetic difference has been found between the domestic and the imported as temizole suspensions.

Microbiological turbidimetric method in determination of serum concentrations of ciprofloxaxin

CHEN Qiang, WANG Rui, FANG Yi

1998, 3(3):  190-191. 

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Aim The application of microbiological turbidimetric method to determination of serum concentrations (C) of ciprofloxacin (CPLX) was studied. Methods A series diluted concentrations of CPLX were prepared with blank serum. The solution was put in a research unit with standard bacteria (ATCC 27853) dilution of 10⁷ cfu/ ml and incubated in Avantage analysis system. Absorbance (A) was recorded once every 5 min in a wavelength of 670 nm. Results There was a liner relationship (r =0.9950, n =8) between concentrations of CP LX and absorbance. The regression equation was C =9.4020-22.55 A. The lowest detectable concentration was 0.03 μg /ml. The rate of recovery of the method was 96.5 % ~ 108.0 %. The coefficient of variation within a day was 2.11% ~ 9.13 % while the coefficient of variation in different days was 1.99 % ~ 9.72 %. Conclusion The microbiological turbidimetry is a rapid, convenient and accurate method to determine the concentration of CPLX.

Effects of Shiquandabu bolus on cyclosporinl induced hepatotoxicity in rats

ZHANG Li-Ming, ZHU Li-Qing, WU Xiu-Hua

1998, 3(3):  192-193. 

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Aim The effect of Shiquandabu bolus (SQDB), a preparation of traditional Chinese medicaine on cycloporine (CsA) induced hepatotoxicity in rats was observed. Methods Wistar rats were separated into four groups: CsA (50 mg/kg), CsA(50 mg/kg) +SQDB (0.6 g/kg), CsA (50 mg/kg) + SQDB (0.3 g/kg) and normal saline (2% CMC Na) were separately given to the rats (ig, qd) for seven days, and then the parameters about liver function, glutamic-pyruvic transaminase (GPT) alkaline phosphatase (AKP) superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione strans ferase (GST) in serum, were determined, and pathologieal changes of liver tissue were observed by light microscope. Results In the CsA group, the levels of GPT and AKP in serum were higher significantly, but in the SQDB groups lower than those in the normal. The levels of SOD and GST were decreased more significantly in the three drug groups than in the normal but there was no significant difference in decrease between the SQDB and CsA groups. The levels of MDA in the two SQDB groups were higher but in the CsA group lower than in the normal. Conclusion SQDB has the effect of ferment reduction but no effect of clear an?ti oxidation and removing free radicals on CsA hepatotoxicity in rats.

An easy method to establish experimental rabbit endocarditis model

ZHANG Chun-Fen, DONG Hai-Xin, KI Jian-Mei, WANG Qing, LUN Xue-Qing², YAO Lei, LIU Shan-Ting

1998, 3(3):  195-197. 

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Aim To establish the experimental rabbit model of endocarditis caused by α-hemolytic streptococcus. Methods A sterile polythene catherer was inserted through the right carotid artery across the aortic valve into the left ventricle. 24h after the operation the animals were radomly divided into two groups. Control group and infection group. In the infection group into each animal 10⁸ CFU ahemolytic streptococcus was injected through peripheral ear vein, while in the control group I ml of normal saline was injected into each animal. 7 d after injection, all animals were saciified and the vegetations on aortic valve and endocardial wall of the left ventricle were removed, weighted, and the number of organisms in blood and vegetation was counted. Results Each infected animal had cardial valve vegetation and endocardial vegetation there were organisms in blood and vegetation. Conclusion This method maked it easy to establish a rabbit endocarditis model.

Effects of naloxone on human renal postischemic reperfusion in vitro

SUN Cheng-Chun, HAO Jun-Wen, ZHANG Hai-Bin, ZHU Li-Qing, WANG Jing-Xiang

1998, 3(3):  198-199. 

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Aim The effect of naloxone (NAL) on human renal postischemic reperfusion in vitro was observed. Methods Six human kidneys in two groups were reperfused separately by either normal perfusion solution or the solution added by 0.8 μg/ml of naloxone. Malondialdehyde (MDA) and superoxide dismutase (SOD) in the reperfusion solution and Na⁺, K⁺-ATP ase and Ca²⁺-ATPase in the renal tissue were determined. The histopathological structure of kidneys was obseved. Results All the above parameters in the treatment had no significant difference from those in the control group. Conclusion NAL had no obvious effect on human renal postischemic reperfusion in vitro. It was supposed that though NAL had protective effect on renal postischemic reperfusion in vivo, it did not directly affect the kidney.

Study of urokinase combined with magnesium sulfate in the treatment of early acute myocardial infarction

ZHOU Hong-Qing, SUN Ming¹, HU Chan, LI Liu-Nan², LIU Zhi-Xiong³

1998, 3(3):  200-202. 

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Aim To evaluate the efficacy and safety of urokinase (UK) combined with magnesium sulfate (MS) in the treatment of early acute myocardial infarction (AMI). Methods One hundred and fifty-one patients with AMI admitted to hospitals from December 1991 to May 1998 were randomly divided into two groups, 76 cases in UK plus MS (UM) group and 75 cases in UK group. In UM group, MS begen to be used 15 minites before intravenous drip of UK. Dose of UK in both groups was equivalent. The patency of infarct-elated coronary artery within three hours (including delayed patency)was assessed by uniform clinical criteria. Results The recanalization rate was higher in UM group than in UK group, but there was no statistical significance (73.7% vs 65.3%, P ＞0.05) five week mortality was 1.3% and 9.3% respectively. The difference was abvious (P＜0.05). Incidence of reperfusion arrhythmias was dramatically decreased (64.3 vs 87.8%, P＜0.01) in UM group. Moreover frequency of severe arrhythmias after thrombolysis was much lower in UM group than that in UK group (10.5% vs 28.0%, P＜0.01). In comparison with UK group, incidences of left heart failure (11.8% vs 25.3%) early postinfarction angina (3.9% vs 13.3%) reinfarction and infarct extension (2.6% vs 10.7%) were significantly reduced (all P＜0.05) in UM group, and frequency of cardiogenic shock (3.9% vs 8.0%) was lower, but it was not significant (P ＞0.05). Conolusions The efficacy of UK combined with is was superior to that of UK alone, for AMI and MS might be an effective and safe adjunct for thrombolytic therapy