Table of Content

Volume 9 Issue 8
26 August 2004

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Progress on the drugs for regulating high-density lipoprotein

LI Qin-Kai, YIN Wei-Dong

2004, 9(8):  841-844. 

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Atherosclerosis (AS) is pathologically important basis of many kinds of coronary atherosclerosis disease (CAD).It can be substantially protected by raising high-density lipoprotein (HDL).In view of mechanism, drugs for raising HDL include:cholesterol ester transfer protein inhibitors, peroxisomal proliferator-activated receptor agonists, liver X-activated receptor agonists, farnesoid X receptor antagonists or agonists, lipoprotein lipase activators, niacin, and phenytoin and lecin:cholesterol acyltransferase activators, etc.This review aimed to the progress of drugs for regulating highdensity lipoprotein and their mechanism, in view of clinical and preclinical aspects.

Proliferation of vascular smooth muscle cells in cardiovascular diseases and drug research and development

MA Bing-Liang, WU Yu-Lin

2004, 9(8):  845-850. 

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The proliferation of vascular smooth muscle cells plays an important role in the initiation and aggravation in cardiovascular diseases such as hypertension, arteriosclerosis, restenosis.This article reviewed the progress in the studies on extracellular influencing factors, intracellular signal transduction, cell cycle of vascular smooth muscle cells and the relative drug research and development.

Phytoestrogens and progress of protective effects researching on central nerve system

YU Juan, NI Xiu-Shi, XU Yun

2004, 9(8):  851-854. 

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Phytoestrogen is a kind of plant element which is similar to animal estrogen.Phytoestrogens can prevent progreator system cancer, cardiovascular disease and osteoporosis.Recently more and more researches are reported on the protection of phytoestrogens on central nerve system.

Immunotoxicology applied in new drug safety assessment

WU Nan, WANG Ai-Ping

2004, 9(8):  855-858. 

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Studies on immunotoxicology in developing new drugs are very important and popular.This paper summarizes the side effects, and the methods for checking and notices of new drugs.

Effects and significance of growth and development on drug metabolism in infants and children

JU Rui-Xiu, WANG Shen-Tian

2004, 9(8):  859-862. 

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Infants and children are far from adults in terms of medications.The growth and developmental changes profoundly affect the absorption, distribution and metabolism of drugs and the response to medications.The dosage and interval of drugs change along with growth and development, so it is needed those age-dependent adjustments in infants and children.

Potential effect and mechanism of IFNγon tumor angiogenesis

CAO Qi-Zhen, LIN Zhi-Bin

2004, 9(8):  863-867. 

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AIM: To study the effect and potential mechanism of IFNγon tumor angiogenesis.METHODS: Human umbilical cord vascular endothelial cell (HUVEC) was cultured in vitro.The effect of IFNγ(10, 100, and 1000 unit·ml^-1)on proliferation of HUVEC was detected by MTT assay in vitro.HUVEC pretreated with IFNγ(10, 100, and 1000 unit·ml^-1)was stained with PI and detected by flow cytometry (FCM).The mRNA expression of apoptosis relative gene Bcl-2 and Bax of HUVEC treated with IFNγ(100, and 1 000 unit·ml^-1)were detected with semi quantitative reverse transcription-polymerase chain reaction (RT-PCR).IFNγ(30, 300, and 3 000 unit·ml^-1)on VEGF secretion and expression in human lung carcinoma cell PG in hypoxia were detected by ELISA assay.CONCLUSION: The key attributes of IFNγon tumor angiogenesis possible directly inhibit vascular endothelial cells or indirectly inhibit growth factors secretion and expression in tumor cells.

Study on quantitative structures-pharmacokinetic relationship of dipyridines calcium ion antagonists

LIU You-Ping, SONG Nai-Ning, LIU Chang-Xiao

2004, 9(8):  868-871. 

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AIM: To study on the quantitative structures-pharmacokinetic relationship of dipyridines calcium ion antagonists to provide the theoretic method to screen new drugs in early period.METHODS: The structures of calcium ion antagonists were conversed from two to three dimensional structure by Insight Ⅱ Program. The conversed structures were optimized to the minimum energy by the steepest descent and conjugate gradient methods. The physico-chemical parameters of the optimized structures, including Log P, surface area, volume, hydration energy, refractivity and polarizability, were calculated by HyperChem Program.The interrelation between structures and pharmacokinetic parameters for calcium ionantagonists was analyzed.RESULTS: There was a good correlation between the hydrophobicity constants (Log P) and the reached peak time (Tmax) after extravenous administration of the calcium ion antagonists to the subjects. The correlation coefficient was over 0.9.CONCLUSION: The correlation between the chemical structure and its pharmacokinetic parameters can provide instructions to new drug design for calcium ion antagonists.

Clinical comparison of the efficacy and safety of epidural ropivacaine mesylate and ropivacaine hydrochloride

XU Jian-Qing, ZHU Bo, YE Tie-Hu, WU Xin-Min, QIN Xiang, WANG Geng, XU Xing, YU Bu-Wei, LI Yi-Liang, ZHOU Jing-Fang, WANG Yu-Ping

2004, 9(8):  872-875. 

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AIM: To compare the efficacy and security of epidural ropivacaine mesylate clinically with ropivacaine hydrochloride in a randomized double-blind multicenter study.METHODS: One hundred and twenty-four elective patients from three centres, undergoing lower epidural anesthesia for intraperitoneal hysterectomy, partial cystectomy and so on, were randomly assigned to two equal groups received 15 ml of either 0.75 % ropivacaine hydrochloride or 0.894 % ropivacaine mesylate.RESULTS: There were no significant differences found in the onset, extent, and duration of sensory and motor block, and also in the hemodynamic stability.When ropivacaine mesylate was clinically compared with ropivacaine hydrochloride.No serious adverse events were found in this study.CONCLUSION: Epidural ropivacaine mesylate is similar to ropivacaine hydrochloride in both efficacy and safety.

Inhibitory effects of leuprolide acetate microsphere on experimentally induced endometriosis in rats

XU Xin-Hong, YU Rong, GONG Qin-Yan, YAO Ming-Hui

2004, 9(8):  876-879. 

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AIM: To study the inhibitory effects of domestic leuprolide acetate microsphere (LE-ms)on the growth of explanted endometrium in the rat models of EMT and its possible mechanisms.METHODS: The 60 rats models of EMT were induced surgically by the Jones method.Then the animals were treated with LE (20μg·^-1 ·d^-1, 28 d, sc), enanton(20 μg·^-1·d^-1, sc)and domestic LE-ms (2, 20, and 200 μg㎏^-1 ·d^-1, sc), respectively;another 30 rats were divided into sham group(N.S, 1 ml·kg^-1·d^-1, 21 d, sc), EMT + LE group(100 μg·kg^-1·d^-1, 21 d, sc)and EMT group(N.S, 1ml·kg^-1·d^-1, 21 d, sc).At the same time, estrous cycle was monitored daily by examination of vaginal cytologic smears.After 3 weeks, blood was drawn and the serum estradiol concentration was assayed.The volume of endometrial implant was assessed.Lateral uterus, bilateral ovary, thymus and spleen were weighed.The NK cell cytotoxicity in the spleen was evaluated with lactate dehydrogenase (LDH)release assay.RESULTS: Implants in control group continued to grow, while those in groups treated with the drugs showed remarkable atrophy.The inhibitory rates were 87.2 %, 78.3 %, 57.3 %, 89.0 % and 94.7 %, respectively.The regular estrous cycle of the model rats was abolished and serum estradiol reduced(P<0.05);the lateral uterine weight was reduced significantly(P<0.001);the thymus weight was increased(P<0.05);the spleen weight did not change significantly(P>0.05);and the NK cells activity was enhanced(P<0.05).CONCLUSION: Ectopic endometrium can be inhibited significantly with the treatment of domestic leuprolide microsphere, and its mechanism may be related to reduce estrogen level, which is important for both the growth of the ectopic endometrium and the enhancement of immune function.

Effects of atorvastatin on ventricular remodeling in spontaneously hypertensive rats

WANG An-Cai, CHENG Bei, XIE Xiao-Jing, XU Hao

2004, 9(8):  880-884. 

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AIM: To investigate the effects of atorvastatin on ventricular remodeling in spontaneously hypertensive rats (SHR).METHODS: SHRs (n=24)were randomly divided into four groups (n=6):SHR control group, 50 mg atorvastatin group (50 mg·kg^-1·d^-1), 10mg atorvastatin group (10 mg·kg^-1 ·d^-1)and valsartan group (20 mg·kg^-1 ·d^-1).Six male Wistar-Kyoto rats were selected as normal control group (WKY group). Systolic blood pressure (SBP)was measured before and after treatment with atorvastatin every 2 weeks.Plasma concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C)and Ang ,and myocardial Ang Ⅱ, hydroxyproline and collagen levels were measured.Heart weight (HW), left ventricle mass (LVM)and left ventricle mass index (LVMI)were gauged.Myocardial ultrastructure was observed by transmission electron microscopy.RESULTS: SBP in all SHR groups was much higher than that in WKY group beforeexperiment (P<0.01).SBP significantly decreased in 50 mg atorvastatin group at 4 weeks and 6 weeks (P< 0.01).Compared with SHR control group, there was a significant descent in serum TC, TG and LDL-C concentrations in 50 mg atorvastatin group (P<0.05, or P <0.01).The level of LDL-C decreased merely in 10 mg atorvastatin group (P<0.05).There was no difference in plasma Ang Ⅱ level among WKY group and SHR groups.But myocardial Ang Ⅱ level in SHR group was significantly higher than that inWKY group (P<0.05). After 6 weeks, plasma Ang Ⅱ level among atorvastatin groups and valsartan group was markedly higher than that in SHR control group (P<0.01), and myocardial Ang Ⅱ level was significantly lower than that in SHR group (P<0.05).Myocardial hydroxyproline and collagen level in SHR group was significantly higher than that in WKY group (P<0.01).After treatment of 50 mg atorvastatin, it was markedly lower than that in SHR control group (P<0.05).Compared with WKY group, HW, LVM and LVMI were significantly increased in SHR group (P<0.01).After treatment of 50 mg atorvastatin, HW, LVM and LVMI were significantly lower than those in SHR control group (P<0.05).The changes of myocardial ultrastructure in atorvastatin and valsartan groups were significantly improved.CONCLUSION: Atorvastatin can significantly improve ventricular remodeling in SHR, and decrease blood pressure and myocardial Ang Ⅱ level which may be one of its mechanisms.

Effects of puerarin on GLUT4 in adipocyte of rats with insulin resistance

LI Juan-Juan, BI Hui-Min

2004, 9(8):  885-888. 

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AIM: To investigate the effects of puerarin on expression and translocation of glucose transporter 4 (GLUT4) in adipocyte of rats with insulin resistance induced by diets.METHODS: Experimental rats were divided into three groups:control group (n=10), model group (n=10) and puerarin group (n=10) randomly. Animals in model group and puerarin group were fed with the diets enriched with sucrose (20 %, w w), lard (10 %, w w), cholesterol (2.5 %, w w) and cholic acid (1 %, w w) to induce insulin resistance. Puerarin group were treated with puerarin (100 mg·kg^-1 body weight, ip) every day for 6 weeks.After the plasma membranes and the intracellular membranes of adipocyte were prepared and separated, GLUT4 protein was detected by Western blot analysis.Body weight, serum triglyceride and cholesterol, fasting plasma glucose and serum insulin concentration were detected termly.And the insulin sensitivity index was also calculated.RESULTS: Western blot analysis showed that intracellular membranes GLUT4 protein in adipocyte of model group rats decreased by 38.72 % (P<0.05) and plasma membranes GLUT4 protein decreased by 21.91 % (P<0.05) as compared with rats of control group.After 6 weeks of treatment of puerarin, intracellular membranes GLUT4 protein of purarin group rats did not change and plasma membranes GLUT4 protein increased 21.46 % (P<0.05) as compared with rats of model group.CONCLUSION: Puerarin can increase the amount of GLUT4 protein in adipocyte of rats with insulin resistance and ameliorate translocation of GLUT4, which may increase the uptake and utilization of glucose.

Evaluation of efficacy and safety of depot medroxyprogesterone acetate in treatment of patients with recurrent pain of postoperative endometriosis

ZHOU Jie, LEI Zhen-Wu, XU Xiao-Wen, LV Jie-Qiang, SUN Jing,WANG Fang

2004, 9(8):  889-892. 

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AIM: To evaluate the efficacy and safety of depot medroxyprogesterone acetate in the treatment of patients with recurrent pain of postoperative endometriosis.METHODS: 48 women suffering from recurrent pain of postoperative endometriosis were randomized into either of the following two groups:25 cases in the group of DMPA received intramuscular depot medroxyprogesterone acetate 150 mg every 28-30 days for 24 weeks; 23 cases in the other group of danazol took danazol 400-600 mg everyday for 24 weeks.Symptoms and signs were recorded before and after the treatment, and the menstrual and weight changes were also recorded.The levels of the liver and renal function, and sex hormone were examined at the same time.RESULTS: Total subjective symptoms scores of DMPA showed the decrement of 82.5 % after 12-week and 92.5 % after 24-week treatment.The size decreased 41.5 % in ovarian endometriooma after 12-week treatment and 56.2 % after 24-week treatment, respectively (P<0.05), The total snbjective symptoms scores were decreased 84.1 % and 95.1 % respectively after 12-week and 24-week treatment in the group of receiving danazol. Reductions of 34.4 % and 52.2 % in ovarian endometriooma were observed after 12 weeks and 24 weeks treatment, respectively (P<0.05).Serum E2 remained on the levels of early follicular phase in two groups.The main side effects of DMPA were irregular bleeding or spotting, delaying of ovulation and weight gaining.A longterm use of DMPA typically results in amenorrhea.Liver functional lesion and anabolic androgenic side effects of weight gainning and acne were more common in the group of receiving danazol. CONCLUSION: Depot medroxyprogesterone acetate is an effective agent in treatment of patients with recurrent pain of postoperative endometriosis because of its convenience, low-cost and good compliance with little side effects.It can be used repeatedly over a long period of time.

Effects of propofol on ATP content ,ATPase activity and lipid peroxidation of hippocampus mitochondrial following global ischemia-reperfusion in rats

GUO Jian-Rong, CUI Jian-Jun, DING Jie-Qing, REN Li-Yuan, YU Lei-Ting

2004, 9(8):  893-898. 

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AIM: To investigate the effects of propofol on the ATP content, ATPase activity, lipid peroxidation and ultrastructure in hippocampus mitochondrial in rats following global ischemia-reperfusion.METHODS: Global ischemia-reperfusion was induced by the use of 4-vessel occlusion method in a rat model.30 male Wistar rats were randomly divided into three groups:sham operation group (n=10), ischemia-reperfusion control group(n=10), and propofol treated group, 100 mg·kg^-1 propofol before ischemia (n=10).After global ischemia 10 min and reperfusion 60 min, rats were decapitated and the brains removed.The contents of ATP and MDA, activities of Na⁺-K⁺-ATPase, Ca²⁺-ATPase, SOD and GSH in hippocampus mitochondrial were measured, and mitochondrial structure was observed by electron microscope.RESULTS: The content of ATP, activities of Na⁺-K⁺-ATPase, Ca²⁺-ATPase, SOD and GSH decreased significantly, and the content of MDA increased obviously in the hippocampal mitochondrial after ischemia-reperfusion. Propofol significantly improved the decrement levels of ATP, Na⁺-K⁺-ATPase, Ca²⁺-ATPase, SOD and GSH, and inhibited the content of MDA increased in hippocampal mitochondrial.Electron microscopic examination also showed that mitochondrial damage was milder in propofol treated group than that in ischemia-reperfusion control group. CONCLUSION: Neuroprotective effects of propofol may be related to the inhibited mitochondrial lipid peroxidation, the integrality protected in mitochondrial structure, and the improved mitochondrial energy metabolism and ATPase activity after global ischemia-reperfusion.

RP-HPLC assay for plasma concentration of itopride hydrochloride granule and its pharmacokinetcs and bioequivalence in healthy volunteers

LI Qing-Zhong, GU Shi-Fen, WU Ji, CHEN Hui

2004, 9(8):  897-900. 

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AIM: To determine the plasma concentration of itopride hydrochloride granule and study its pharmacokinetics and bioequivalence in healthy volunteers. METHODS: A reversed-phase high performance liquid chromatography (RP-HPLC)method was established for the determination of itopride hydrochloride in human plasma after a single oral dose administration of 100 mg itopride hydrochloride granule (test preparation) and itopride hydrochloride tablet (reference preparation) in a crossover design.RESULTS: The main pharmacokinetic parameters after a single oral dose administration of 100 mg itopride hydrochloride granule and tablet were as follows:C_max 594.8 ±152.3 and 628.6 ±261.4 μg·L^-1 ,T_max 0.766 ±0.213 and 0.900 ±0.392 h, T_12ke 3.21 ±0.86 and 3.49 ±0.77 h, AUC_0-152266.0 ±1340.9 and 2339.4 ± 1831.7 μg·L^-1 ·h^-1, respectively.CONCLUSION: The relative bioavailability of itopride hydrochloride granule is 106.9 %±27.3 %.The results of statistical analysis for C_max, AUC_0-15 and AUC_0-∞ show that itopride hydrochloride granule and itopride hydrochloride tablet are bioequivalent.

Effects of amlodipine on expression of nitric oxide synthase in myocardial ischemia reperfusion model in hypercholesterolemia rats

LI Jing-Rong, XIONG Shu-Dao, LI Yu-Guang, ZHANG Yuan-Chun

2004, 9(8):  901-905. 

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AIM: To assess the influence of amlodipine on the expression of eNOS and iNOS on coronary vessels in myocardial I R model in hypercholesterolemia rats. METHODS: 64 healthy male Wistar rats were randomly divided into 4 groups:pure hypercholesterolemia group (Con), amlodipine group (AM), amlodipine +L-NAME group (AL), and amlodipine +sham group (Sham).Rats were fed with 3 %-4 % cholesterol and 15 %-20 % lard diet for 6 weeks.As dissecting thorax, the left coronary artery (LCA) was ligated for 30 minutes, and then followed a relaxation for 20 minutes or 2 hours.The expression of iNOS and eNOS was observed by immunohistochemical ABC method on endothelium of coronary vessels. RESULTS: Expression of eNOS and iNOS on endothelium of coronary vessels were marked positive, downregulated after ischemia 30 minutes, apparently increased after reperfusion 20 minutes, and reached the peak after reperfusion 2 hours in Con group.However, the effects were reversed partly by amlodipine.In AM group, the expression of NOS especially iNOS was downregulated significantly before ischemia (P<0.01), and then the expression of eNOS increased (P<0.01) while iNOS decreased (P>0.05) after ischemia 30 minutes.Both the expression of eNOS and iNOS was downregulated at the point of reperfusion 20minutes, followed an increase oparently but weaker than that in Con groups at 2 hours.In combined with L-NAME, the effect of amlodipine on eNOS and iNOS was partly prevented.CONCLUSION: Amlodipine is effective on hypercholesterolemic, myocardial postischemic and early reperfusion damage reduction, and most probably nitric oxide plays a determinant role in this effect.

Effects of aspirin and sulindac on expression of cyclooxygenase-2, vascular endothelial growth factor, laminin receptor, and CD₄₄V₆ in 3AO cells

GAO Xue-Qin, HAN Jin-Xiang, ZHANG Wei-Dong, SONG Shou-Qin, ZHU Bo

2004, 9(8):  906-910. 

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AIM: To investigate the effects of aspirin and sulindac on the expression of cyclooxygenase-2(COX-2), vascular endothelial growth factor (VEGF), CD₄₄V₆ and laminin receptor (LN-R) in 3AO cells. METHODS: The growth inhibition effects of aspirin and sulindac in 3AO cells were tested by MTT assay.The expression of COX-2, VEGF, LN-R and CD₄₄V₆were evaluated by immunocytochemistry.RESULTS: Aspirin and sulindac significantly inhibited the growth of 3AO cells whether added before or after cells adhered.When the pH was adjusted with sodium bicarbonate, the inhibition had a little decrease.Aspirin and sulindac also inhibited the expression of COX-2 and VEGF.But there were no effect on the expression of LN-R and CD₄₄V₆.CONCLUSION: Inhibited expression of COX-2 may down-regulate the expression of VEGF, and inhibit the angiogenesis of tumor.Aspirin and sulindac may exert their chemopreventive and anticancer effects by inhibiting the expressions of COX-2 and VEGF.

Establishment of precision-cut fibrotic liver slice technique

GUO Yu, WANG Hui

2004, 9(8):  911-913. 

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AIM: To establish the technique of precision-cut fibrotic liver slice (PCLS) and grope the optimal cultural conditions for researching the liver xenobiotic metabolism in vitro and the drug interaction.METHODS: Complex factors (higher fat diet, alcohol and CCl4) were used to make the animal model of liver fibrosis.Fibrotic liver slices were prepared and cultivation system was established. Lactate dehydrogenase (LDH) leakage, glutathione S-transferase (GST) activity and 3[ 4, 5-Dimethythiazole-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) reduction were chosen as indexes to assess the viability of the slice in different thickness, medium pH and cultural time.RESULTS: Rats were in earlier hepatic fibrosis after administration for 3 weeks.When the thickness of slices was 300 μm and medium pH was 7.0, the LDH leakage, GST activity and MTT reduction could maintain on a steady level in 6 h.CONCLUSION: A 300 μm of thickness, 7.0 of medium pH and 6 h of cultural time are the optimal slicing and culturing conditions for fibrotic liver slice.

Effects of valsartan and benazepril on glomerulosclerosis in rats with 5/6 nephrectomy

YANG Li-Cai, ZHANG Dao-You, ZHANG Hui, ZHU Gui-Lan, GAO Chao-Qing

2004, 9(8):  914-918. 

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AIM: To observe and compare the improvement of glomerul-osclerosis in rats with 5/6 nephrectomy by valsartan and benazepril.METHODS: Thirty Sprague-Dawley male rats were selected and performed five-sixths nephrectomy to produce chronic renal failure model.Two weeks after the surgery, the rats were randomly divided into model group, valsartan group and benazepril group, and established a shame group serving as normal control.The weight, blood pressure, blood uria nitrogen (BUN) and serum creatinine were measured on the sixth week after operation, then the rats were killed to take the kidneys for pathological histological observation. Immunohistochemistry was used to examine the expression of TGF-β₁ protein and fibronectin (FN) and collagen IV in glomeruli.RESULTS: As compared with model group, systolic pressure decreased (P<0.01) and renal function was ameliorated in two treatment groups, as well as the extent of glomerular mesangial proliferation, glomerulosclerosis index (GSI) decreased significantly (P<0.01).Immunohistochemistry staining indicated that there was an decreasing expression of TGF-β₁, FN and collagen IV in glomeruli in two treatment groups compared with model group (P<0.01).CONLUSION: The renoprotective effect of valsartan on chronic experiment renal failure rats is similar as benazepril.valsartan and benazepril can improve glomerulosclerosis by decreasing the expression of TGF-β₁, FN and collagen IV in glomeruli.

Inhibition of octreotide on the proliferation of the in vitro cultured liver cancer cell SMMC-7721

LI Chang-Zheng, WANG Zhi-Qiang, FANG Yi

2004, 9(8):  919-921. 

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AIM: To study the anti-cancer effects of octreotide on the proliferation of liver cancer cells. METHODS: The liver cancer cells SMMC-7721 were cultured in RPMI-1640 media with 10 % fetal bovine serum, 100 U·ml^-1 penicillin and streptomycin.10^-5 ,10^-4, 10^-3 and 10^-2g·L^-1 of octreotide were added and MTT colorimetric assay were used to detect the growth inhibition rate.DNA staining and cell cycle analysis were done at 0, 6, 12, 24 and 36 hours after medication when the concentration of octreotide was 10^-3g·L^-1.RESULTS: MTT colorimetric tests showed that octreotide suppressed the growth of liver cancer cells.48 hours after medication, the cell growth inhibition rate was 9.33 %, 12.70 %, 19.70 % and 20.93 % when the octreotide concentration was 10^-5, 10^-4, 10^-3 and 10^-2g·L^-1 separately.Cell cycle analysis showed that the percentage of G₀-G₁ phase cells increased and the percentage of G₂-M phase cells decreased.CONCLUSION: Octreotide inhibits the cultured liver cancer cells proliferation in vitro, its mechanisms may be related to preventing the G₀-G₁ phase cells from going into G₂-M phase.

Pharmacokinetics of N-n-butyl haloperidol iodide determined by HPLCMS method in rabbits

LIN Chao-Xian, SHI Gang-Gang, LUO Wen-Hong, LI Hui, ZHENG Jin-Hong, GAO Fen-Fei

2004, 9(8):  922-924. 

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AIM: To study pharmacokinetics of N-nbutyl haloperidol iodide (F2) in rabbits.METHODS: Blood samples were collected at different time points after six rabbits were given F2 2.0 mg·kg^-1, iv.Then the plasma concentrations of F2 were detected by HPLC-MS method.And pharmacokinetic parameters were calculated using the 3p97 program.RESULTS AND CONCLUSION: The open two-compartment model can best describe the concentration-time curve of F2.The major pharmacokinetic parameters are listed as following:the half-life of distribution phase T_12α=0.10 h, the half-life of elimination phase Σ_12β=6.4 h, the volume of the central compartment Vc=4 L, the total areas under the concentration-time curve AUC=183 μg·h^-1·L^-1, and the plasma clearance CL=12.9 L·h^-1.HPLC-MS is a sensitive and specific method in this study.

Study of pharmacological effects and mechanism of ethyl ferulate

WANG Ru-Tao, ZHOU Si-Yuan, ZHANG Feng, MEI Qi-Bing

2004, 9(8):  925-928. 

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AIM: To investigate the pharmacological effects and mechanism of ethyl ferulate (EF).METHODS: The platelet congregate rate was observed by congregater TYXN-91 and the platelet intracellular calcium oscillation was observed by laser scanning.The acute liver injury model of mice was made by using the CCl4 156 mg·kg^-1, ip.Then the levels of ALT and AST were determined in serum and the levels of MDA and SOD in the liver.RESULTS: The inhibition rate of the platelet congregate were 26.3 %±3.3 %, 33.4 %±2.4 %, 73.4 %±3.1 %, and 94.9 %±2.7 %(n=8)in different concentration(0.1, 0.5, 1.5, and 3.0 mmol·L^-1)of ethyl ferulate, respectively.It was higher than those in the same concentrations of ferulic acid.The change of the fluctuation of calcium (ΔFI 4.6 ±1.7)in EF group was much lower than the rest level (10.3 ±2.6)(n=8, P <0.01).The levels of AST and ALT in serum andMDA in the liver tissue of EF group were obviously lower than those of the control group.It also showed that EF could significantly enhance the activities of SOD.CONCLUSION: The inhibition of ethyl ferulate on platelet congregation induced by ADP is much better than that of ferulic acid.Ethyl ferulate against the CCl4 acute liver injury is better than that of ferulic acid in mice.

Clinical evaluation of efficacy of simvastatin on exercise-induced myocardial ischemia in patients with stable exertional angina pectoris and hypercholesterolemia

HUO Yong-Jia, CHENG Ying, CHENG Li

2004, 9(8):  929-931. 

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AIM: To evaluate the efficacy of simvastatin on exercise-induced myocardial ischemia in patients with stable exertional angina pectoris and hypercholesterolemia. METHODS: Ninety patients with stable exertional angina pectoris, positive rate of exercise test and hypercholesterolemia were randomly divided into two groups:the therapy group assigned to a 12-week treatment period either diet plus simvastatin (n=45) ;the control group with diet alone (n=45).All the patients underwent exercise testing before and after the treatment period.RESULTS: (1) Simvastatin-treated patients had a significant variation in total cholesterol, triglyccrides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol after treatment (P<0.05), whereas the control group had not.(2) After a 12-week treatment, only 8 patients (18 %) of the therapy group had positive rates in exercise test, whereas 41 patients (91 %) of the control group still had positive rates in exercise test.Exercise tolerance had significantly improved in the therapy group, the time to ST depression of 1.0 mm had prolonged and the severity of ST depression had reduced after treatment (P<0.05).CONCLUSIONS: Besides the cholesterol-lowering effect, simvastatin can relieve exercise-induced myocardial ischemia in patients with stable exertional angina pectoris and hypercholesterolemia.

Clinical evaluation on efficacy of domestic nateglinide tablet in patients with type 2 diabetes mellitus

XIA Li-Bin, LU Mei-Qin, ZHANG Bin-Hua, ZHANG An-Su, CHEN Yue-Ping, HUA Qiang, MAO Guo-Guang

2004, 9(8):  932-934. 

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AIM: To evaluate the efficacy of domestic nateglinide tablet with the treatment of patients with type 2 diabetes mellitus (T2DM).METHODS: Forty-six patients of T₂DM were included in this study.The twentythree patients in nateglinide group took nateglinide tablet, and another twenty-three patients in the repaglinide group took repaglinide tablet.The changes of both fasting blood glucose and hemoglobin A_1C(HbA_1C)levels were assayed. RESULTS: After the treatment of 12 weeks, the levels of fasting blood glucose and HbA1C decreased significantly (P<0.01).After 8th weeks, the levels of fasting blood glucose of repaglinide group on finger-tip decreased significantly than those of the nateglinide group.CONCLUSION: Domestic nateglinide, as an effective and safe agent, can improve the glycometabolism in treating T₂DM.

Effects and mechanism of naloxone on learning and memory in mice being repeatedly cerebral ischemia reperfusion

HUO Zhan-Yang, HUO Xiao-Chen, FU Feng-Ying

2004, 9(8):  935-938. 

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AIM: To observe the effects and mechanism of naloxone being injected intra-cere broventricular on studying and memory in mice with repeatedly cerebral ischemia reperfusion.METHODS: Double-tube was embedded in lateral ventricle of mice, anti-infection was taken for 4 or 5 days to mice after operation, and the repeated cerebral ischemia reperfusion model was made in awakening mice.Behavior of learning and memory was observed by eletic maze test, methylenedioxy (MDA) in brain tissue was detected by TBA, the content of β-Ep in brain tissue and blood plasma was measured by radio-immunity method, and the number of cell was counted in htppcoampal CA1 on section of brain tissue.RESULTS: Naloxone obviously improved the disorder of studying and memory of mice, and inhibited the abnormal increased MDA and β-Ep in brain tissue caused by repeated cerebral ischemia.It also improved the number of cell in htppcoampal CA1.CONCLUTION: Naloxone can protect mice being repeatedly cerebral ischemia reperfusion from the damage of studying and memory, and its mechanism is related to its contradicting β-Ep activity and lowing MDA in brain and increased htppcoampal CA1.

Protective effect of baicalin-mediated on mice spinal ganglion cells against gentamicin-induced ototoxicity

DAI De

2004, 9(8):  939-941. 

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AIM: To study the protective effect of baicalin (BA) against the ototoxicity of gentamicin (GM) of mice spinal ganglion (SG) cells.METHODS: MTT assay was employed to determine the growth inhibition of GM on the SG cells.The activities of superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX), and the content of malondialdehyde (MDA) were measured by UV chromatography in SG cells from mice of different groups.RESULTS: Baicalin reversibly limited the GM-induced growth inhibition of SG cells in a dose-dependent manner.BA increased the activity of T-SOD and GM-induced decreased activity of T-SOD and GSH-PX in SG cells.The compound could also reduce MDA level and limite the GM-induced high content of MDA in SG cells.CONCLUSION: Baicalin mediated neuroprotective effect on SG cells is against gentamicin-induced ototoxicity through anti-oxidant.

Effects of ketamine on cumulative survival in septic mice induced by cecal ligation and puncture

LIU Fen, CHEN Jin-He, LI Sheng-Hua, ZHAO Wen-Hui, AI Yong-Xun

2004, 9(8):  942-944. 

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AIM: To investigate the dose-related effects of ketamine on cumulative survival in mice models of polymicrobial sepsis induced by cecal ligation and puncture (CLP).METHODS: Mice with CLP were divided randomly into four groups, received ketamine injection intraperitoneally of 0, 3, 6, and 12 mg·100 g^-1, respectively, at 1 and 6 h after CLP.The survival rate was observed in each group.RESULTS: No change in mortality was observed after 72 hours among four groups.Ketamine administration was associated with significant improvement of the survival of mice with CLP (P<0.05), especially in 6 mg·100 g^-1 group (P<0.05).CONCLUSION: Ketamine administration dose-independently delays lethality from sepsis in mice with CLP.

Expression of type Ⅰ transforming growth factor β receptor in renal cortex of streptozotocin-induced type Ⅱ diabetic rats and the regulation of valsartan

ZHENG Min, HE Min, XU Ji-Liang, YIN Xiao-Qin

2004, 9(8):  945-948. 

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AIM: To study the expression of typeⅠtransforming growth factor β (TβR-Ⅰ) in renal cortex in streptozotocin-induced type Ⅱ diabetic mellitus and the regulation of valsartan.METHODS: The rat models of type Ⅱ diabetic rats were made.At the end of the 20^th weeks, the kidneys were taken out to measure the expression of TβR-ⅠmRNA by RT-PCR.RESULTS: The expression of TβR-Ⅰ mRNA in diabetic rats without any therapy (0.72 ±0.14) was higher than that in control(0.26 ±0.12) (P<0.01), and the expression of TβR-ⅠmRNA in the diabetic rats treated with valsartan (0.34 ±0.11) was lower than that in the diabetic rats without any therapy (P<0.01).CONCLUSION: The expression of TβR-ⅠmRNA increases significantly in renal cortex of type Ⅱ diabetic rats.Valsartan can decrease the expression of TβR-ⅠmRNA in renal cortex of type Ⅱ diabetic rats.

Statistical approaches to establishing bioequivalence

CHEN Feng, YU Hao, LU Jing-Jing, ZHAO Yang, LIU Yu-Xiu

2004, 9(8):  949-953. 

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The purpose of bioequivalence (BE)trial is to show that the test (T)and the reference (R)products can produce similarity bioavailability, and then show therapeutically equivalence.There are three types of bioequivalence, namely, average bioequivalence (ABE), population bioequivalence (PBE) and individual bioequivalence (IBE).The ABE approach focuses only on the comparison of population averages of a BE measure of interest and not on the variances of the measure for the T and R products.In contrast, the approaches to establish PBE and IBE include the comparisons of both averages and variances of the measure.The PBE approach assesses total variability of the measure in the population.While the IBE approach assesses within-subject variability for the T and R products, as well as the subject-by-formulation interaction, that is, the variation in the average T and R difference among individuals.In present paper ,the principle of the statistical approaches to establish BE ,the way to predetermine criterions and BE limits were introduced, and an example were illustrated.

Standard operating procedures for investigators in institution of clinical trial

CHEN Jiong-Hua, XIONG Ning-Ning, ZHOU Jian-Dong, JIANG Meng, LIU Fang, FU Wei-min

2004, 9(8):  954-957. 

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Standard Operating Procedures (SOP)of clinical investigators are established according to SFDA ,ICH and WHO Good Clinical Practice standards, and experiences of clinical trials practice in our hospital.It includes qualification and competence of investigators, prior to initiation of the study, screening and recruitment of study subjects, obtain informed consent from all trial subjects, protocol compliance, provide medical care for trial subjects, randomization procedures and unblinding, safety reporting, source data document, case report forms, product management, premature termination or suspension of a trial, progress and final reports, and investigator’sfiles.

SAS statistics table of covariance analyses of clinical trial

TONG Xin-Yuan, ZHANG Gao-Kei, YAO Chen

2004, 9(8):  958-960. 

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Four macro SAS instructions of covariance analysis are worked out, and a statistical table of covariance analysis is produced with the operation of macro SAS in this paper.