Table of Content

Volume 15 Issue 6
26 June 2010

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Studies on the metabolism and effect on the CYP450 of CH330331 in rat liver microsomes

SUN Hai-yan, HE Fan, BI Hui-chang, HUANG Wen-lin, HUANG Min

2010, 15(6):  607-612. 

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AIM: To study the metabolic kinetics of CH330331 in rat liver microsome, and its inhibition on CYP450 subtypes in the “cocktail” models. METHODS: The incubation parameters in rat liver microsome were optimized and were the Michaelis-Menten parameters K_m and V_max estimated the component of probe inhibitors in “cocktail” models were also confirmed and the effect of CH330331 on main subtypes of cytochrome P450 studied. RESULTS: The K_m and V_max of CH330331 were 18.96 μmol/L and 2.08 μmol/(min·mg protein), respectively. CH330331 had a weakly inhibition to the activity of CYP1A2, CYP2D6 and CYP2C9 but had no effect on CYP2C19, CYP2E1, and CYP3A4. CONCLUSION: CH330331 can increase the blood concentration of those drugs that are metabolized mainly by CYP1A2, CYP2D6 and CYP2C9.

Research on the functional difference among different species of Chuan Fritillaria in relieving cough and resolving phlegm

ZHOU Yi, DING Hong, YAN Bo-hua, LI Ji-shu, LIU Song-shan, LI Ming-quan, WANG Shuai, FENG Fen, HUANG Xiao-yan

2010, 15(6):  612-616. 

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AIM: To study the effect of relieving cough and resolving phlegm among different species of Chuan Fritillaria. METHODS: (1)70 Healthy guinea pigs had been randomly divided to 7 groups: the Control group, the coughing model group, the Positive control group, the Fritillaria unibracteata Hsiao et K.C.Hsia group, the Fritillaria delavayi Ftanch group, the Fritillaria cirrhosa D.Don group and the Fritillaria przewalskii Maxim group. Continuously gave them herbs for 3 days. 60 s Citrate had been inhalated about 30 min after the last time of delivery. The Latency of cough and frequency of cough within 5 min were recorded.(2)60 Healthy mice had been randomly divided to 6 groups: the control group, the positive control group, the Fritillaria unibracteata Hsiao et K.C.Hsia group, the Fritillaria delavayi Ftanch group, the Fritillaria cirrhosa D.Don group and the Fritillaria przewalskii Maxim group. Continuously gave them herbs for 3 days. 30 min after the last time of delivery, 0.5 mL of 0.5% Phenol red solution had been intraperitoneally injected for each mouse. The mice were killed after 30 min. Mice's trachea had been separated and douched; 0.1 mL of 5% NaHCO₃ was added. After centrifuge manipulation, the supernatant had been divided. Enzyme labeling had been applied to measure the OD and eliminating phlegm index. RESULTS: (1) Compared with Fritillaria cirrhosa D. Don group, Fritillaria unibracteata Hsiao et K.C.Hsia group and the Fritillaria cirrhosa D.Don group could both prolong the latency of cough (P<0.05). (2) Compared with Fritillaria delavayi Ftanch group, Fritillaria cirrhosa D. Don group, Fritillaria przewalskii Maxim group and Fritillaria unibracteata Hsiao et K.C.Hsia group could increase the OD value of Phenol red excretion for mice's trachea(P<0.05, P<0.01). CONCLUSION: The Fritillaria unibracteata Hsiao et K.C.Hsia may have a better effect of resolving phlegm compared with Fritillaria delavayi Ftanch, Fritillaria cirrhosa D.Don and Fritillaria przewalskii Maxim. The Fritillaria unibracteata Hsiao et K.C.Hsia and Fritillaria delavayi Ftanch may have a better effect of relieving cough compared with Fritillaria cirrhosa D.Don and Fritillaria przewalskii Maxim.

Study on therapeutic effect of LITONG on atherosclerosis rats

LI Jie, WANG Fu-wen, SUN Min-yao, ZHANG Qiang, TANG Wen-zhao, MU Yan-ling

2010, 15(6):  617-621. 

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AIM: To observe the therapeutic effect of LITONG on atherosclerosis rats. METHODS: The atherosclerosis rat models were induced by feeding high fat diet. After 8 weeks, 60 rats were selected and were randomly divided into six groups: 300 mg/kg, 150 mg/kg, 75 mg/kg of LITONG, positive drug control(Fenofibrate), model control and normal rat control. The rats in model groups were introgastricly administrating distilled water and were fed high fat diet, and the rats in normal group were introgastricly administrating distilled water. After 60 days, the levels of serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol were detected by blood samples. In addition, the aorta pathology alteration and cell apoptosis of arterial wall endothelial were also examined. RESULTS: Significant differences were seen in the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol and cell apoptosis ratio in LITONG groups ( 300 mg/kg, 150 mg/kg ) compared with those in model group(P<0.05). In addition, the number of foam cells in rat aortic wall and the extent of elastic fiber damage reduced significantly in high-and low-dose groups of LITONG compare with those in model group. CONCLUSION: These studies suggest that LITONG has satisfactory pharmacologic effects on atherosclerosis and can improve elastic fiber damage of rats.

Protective effects of 13-MTD on injury of SH-SY5Y neuroblastoma cells induced by hydrogen peroxide

YU Juan, HU Gui-fang, WENG Sheng-mei

2010, 15(6):  622-626. 

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AIM: To investigate the protective effects of 13-methyltetradecanoic acid(13-MTD) on the injury of cultured SH-SY5Y neural cells induced by hydrogen peroxide(H₂O₂). METHODS: The injury of cultured SH-SY5Y cells was made in vitro by H₂O₂. Microscope was used to detect the morphology of cells. Sulforhodamine B assay was applyed to detect the cell viability. Acridine orange/ethidium bromide (AO/EB) double staining was adopted to observe the apoptotic morphology. MTT assay was employed to detect the mitochondrial reducibility. RESULTS: The cells apoptosis rate was increased, the cells viability and mitochondrial reducibility were decreased significantly in group model of H₂O₂ injury compared with the group control (P<0.01). 13-MTD 10, 20, 40 μg/mL increased cell survival and 13-MTD 5, 10, 20 μg/mL reduced the apoptosis rate as well as 13-MTD 5, 10, 20, 40 μg/mL increased the cell MTT metabolic rate compared with the group model of H₂O₂ injury(P<0.01), there are some dose-dependent relationship (P<0.05, P<0.01). CONCLUSION: Different doses of 13-MTD shows the neuroprotection effects and can protect SH-SY5Y cells from the injury induced by H₂O₂.

Protective effects of Omeprazole on the toxic acute gastric mucosal lesion in rats

FAN Xiao, XU Yang, ZHANG Hong-liang

2010, 15(6):  626-630. 

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AIM: To study the protective effects of different doses Omeprazole on the toxic acute gastric mucosal lesion in rats. Meanwhile, the protective effects were investigated. METHODS: Forty rats were separated into blank control group, acute intoxication control group, low dose omeprazole treatment group, high dose omeprazole treatment group. Ulcer index was calculated, plasma ET, serum TNF-α and cholinesterase activity were measured.With gastric mucosa HE staining, gastric mucosa pathological changes were observed also. RESULTS: A toxic acute gastric mucosal lesion model were established on rats. Omeprazole could prevent rats from acute gastric mucosal lesion induced by poisoning, improve related indexes and pathological states as well; large dose omeprazole could be more beneficial for acute gastric mucosal lesion induced by poisoning. CONCLUSION: Administration of Omeprazole could improve the acute gastric mucosal lesion induced by orgnaophosphorus pesticide orally in rats, and large dose Omeprazole could be more beneficial;ET and TNF-α in serum could be considered as the surrogate for treatment of acute poisoning gastric mucosal lesion induced as well as index for early detection.

Study on compatibility ratio of anti-oxidative effects of Radix Angelica and Rhizoma Ligusticum with different preparation methods

MA Hong-yue, LI Wei-xia, SHANG Er-xin, TANG Yu-ping, DUAN Jin-ao, JIANG Hao-wen

2010, 15(6):  631-635. 

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AIM: To study the anti-oxidative effects of Radix Angelica and Rhizoma Ligusticum with different ratio extracted by water, ethanol, alcohol-water. METHODS: Hydroxyl radical generated in Fenton reaction system and oxidative insult in HUVEC induced by H₂O₂ were used in the present study. RESULTS: Water preparation exhibited the strongest scavenging activity against OH generated in a Fenton reaction system. Ethanol preparation had the weakest activity against OH, while exerted strongest activity on damaged HUVEC. Water preparation (1∶1), ethanol preparation (1∶1.5) and alcohol-water preparation (2∶1) were found to be the most potent. CONCLUSION: Radix Angelica and Rhizoma Ligusticum with different ratio exert markedly different anti-oxidative activities. The most reasonable ratio may appear 1∶1 for water preparation and be consistent with clinical ratio in si-wu-tang, a famous TCM fomulae.

Determination of L-carnitine and its active metabolites in rabbit plasma and hepatic tissue by precolumn derivatization HPLC

LUAN Hai-yun, LI Jin-lian, WANG Shao-hua, ZHONG Wei-zhen, HAN Yan-tao

2010, 15(6):  636-640. 

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AIM: To establish a method to determine the concentrations of L-carnitine (LC) and its active metabolites in plasma and hepatic tissue of rabbit by precolumn derivatization HPLC. It was detected the content that the LC and its active metabolites of endogenous and after a single dose by intragastrical administration. METHODS: A single dose of 1 mL/kg that LC was taken orally to New Zealand rabbits with big ears. The plasma and hepatic tissue samples were taken before and after administration respectively. The concentrations of LC and its active metabolites in plasma and hepatic tissues were measured using pre-column derivatization HPLC. RESULTS: The method showed good linear response over the selective concentration range of 2-200, 0.2-40 and 0.1-8 μmol/L for LC, acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC), respectively. The intra-day and inter-day validations were less than 4.12% for three agents; The average methods recoveries of assay were 80%-95%. The plasma concentrations of LC, ALC and PLC in blank rabbits were 15.78, 2.15 and 0.47 μmol/L,respectively, and their concentrations in hepatic tissue were 24.83, 4.61, and 2.08 μmol/g,respectively. After administration for 7 h to rabbits, the concentrations of LC and its active metabolites have a significant change in plasma and hepatic tissue. CONCLUSION: This method is simple, reliable and accurate. These results show that in the absorption process of LC in vivo, LC is acetylated and propionylated, and transformed to active metabolites ALC and PLC. In hepatic tissue, concentrations of LC and its active metabolites are significantly higher than in plasma, indicating that LC and its active metabolites distributied are transfer from plasma to hepatic tissue quickly.

Effect of Helicid on the behavior in chronically stressed mice

TONG Jiu-cui, XIE Hai-tang, YANG Bin, CHEN Ai-dong, LI Hai-gang, PAN Hang-shan, JIA Yuan-wei, ZHONG Min, JIANG Si-yan

2010, 15(6):  641-645. 

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AIM: To study the effect of Helicid on the behavior in chronically stressed mice. METHODS: Mice were exposed to chronic mild stress(CMS) and isolated breed for 28 consecutive days with coadministration of Helicid (40,20,10 mg/kg, i.g. ) or Fluoxetine (2.6 mg/kg, i.g.).The open field test, sucrose preference test and emotional behavior score were applied to assess the behavior efficacy. RESULTS: Helicid or Fluoxetine treatment reversed depression-like behaviors such as deficient locomotory, reduced sucrose preference, emotional behavior score and weight. CONCLUSION: Helicid has an obviously antidepressant effect in chronically stressed mice.

Thrombolysis activities of desmoteplase and mutants expressed in yeast Pichia methanolica

YAN Shou-sheng, GONG Xin-jiang, GUO Yong-qi, LI Jian-feng, WU Guo-dong, WANG Qing-min, SUN Li-xia, YANG Qing-min, WANG Jing-yi

2010, 15(6):  645-650. 

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AIM: To study the thrombolysis activities of wide type Desmodus rotundus Salivary Plasminogen Activivator (DSPAwt) and its mutations F195 and QNRR expressed in yeast Pichia methanolica. METHODS: The rat model of artery-vein bypass thrombosis was used to measure the thrombolysis activities of DSPA^wt, F195 and QNRR, in which indexes such as weight of thrombus, bleeding time (BT), thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimer were investigated. DSPA was expressed in CHO cells (DSPAαl) and the launched thrombolytic drug rt-PA were used as positive controls. RESULTS: Positive controls as well as DSPA^wt, F195 and QNRR at doses of 0.7 mg/kg and 1.5 mg/kg individually showed thrombolysis potency, which decreased the weight of thrombus, delayed the levels of BT, TT, PT, APTT and elevated the level of D-dimer. F195, QNRR and DSPAαl had the similar higher activities, while DSPA^wt possessed limited thrombolysis effects. CONCLUSION: The results suggest a novel method to express DSPAs for further development as a novel type of drug for treatment of thrombotic diseases such as acute ischemic stoke.

Sibutramine versus orlistat for obesity: A Meta-analysis of randomized controlled trials

TIAN Hong-liang, GE Sai, YUAN Hao, TANG Zhen, ZHANG Li-han, TIAN Jing-hui, YANG Ke-hu

2010, 15(6):  651-656. 

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AIM: To compare the efficacy and investigate the clinic value between sibutramine and orlistat for obesity. METHODS: The database was retrieved from PubMed, EMBASE, SCI, the Cochrane Library, Chinese Biomedical Literature Database, China Journal Full Text Database, Chinese Medical Association Journals, and references of the included studies up to December 2009. Randomized control trials (RCT) of sibutramine versus orlistat for obesity were included. The quality of the included studies was evaluated by Handbook recommend standard. Data were analyzed by RevMan 5.0 from the Cochrane Collaboration. RESULTS: Five RCTs were included. Meta-analysis showed that there were no differences between sibutramine and orlistat for obesity in weight loss, body mass index(BMI) decrease, waist circumference decrease and LDL-C change. Although there were fewer adverse events in the two groups, the form of adverse events were different because of the different mechanism of two drugs. CONCLUSION: Sibutramine and Orlistat have significant effects in the treatment of obesity. Meanwhile, there is no significant difference between two drugs, while the performance of two groups of drug adverse events is different.

Physiologically based gastrointestinal models for the prediction of oral drug absorption

LI Guo-fu, YANG Jin, ZHANG Xue-ying, ZHAO Hao-ru

2010, 15(6):  656-662. 

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Oral drug absorption is influenced by different physiological factors, such as composition of gastrointestinal fluid, pH, transit, transport and metabolism. The ability to accurately predict the oral drug absorption only depended on in vitro results, before preclinical or clinical researches will improve the efficient of drug development. Various physiologically based gastrointestinal models based on the profound understanding of oral absorption process provide an opportunity to assess in vivo oral absorption. These physiological models can link to classical pharmacokinetic models to predict the rate and extent of oral drug absorption. This paper reviews the principle and new application of these physiological models, then compare and discuss with those.

Comparison of the pharmacokinetics of BAPTA-AM liposome injection in rats and Beagle dogs

ZHENG Feng, LIU Wen-ying, WEI Wei

2010, 15(6):  663-667. 

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AIM: To compare the pharmacokinetics of BAPTA-AM liposome injection in rats and Beagle dogs. METHODS: The concentration of BAPTA-AM in plasma was quantified by LC-MS/MS after intravenous injection. The pharmacokinetic parameters were calculated by the non-compartment model. RESULTS: The elimination half-life in rats after intravenous injection 1.5, 3.0 and 6.0 mg/kg BAPTA-AM liposome were (255±140), (290±260)and (376±257)min respectively, and the AUC_0-∞ were(831±251), (1467±528)and(3650±1664) μg·L^-1·min, respectively. The elimination half-life in dogs after intravenous injection 0.5, 1.0 and 2.0 mg/kg BAPTA-AM liposome were (362±305), (347±278)and (432±292)min respectively, and the AUC_0-∞ were (400±118), (569±139)and (1185±640) μg·L^-1·min, respectively. CONCLUSION: After intravenous injection, BAPTA-AM liposome is metabolized rapidly and distributed abroad in rat and Beagle dog. There is no difference in the pharmacokinetic between rats and dogs.

Pharmacokinetics of Huperzine A substain-release tablets after multiple doses in healthy volunteers

WEI Zhen-man, DING Jin-biao, HU Lin, CHEN Hong-ge, WU Rong-rong, LIU Wan-hui, SHA Chun-jie

2010, 15(6):  668-672. 

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AIM: To evaluate the pharmacokinetics of Huperzine A sustained-release tablets after multiple doses in Chinese healthy volunteers. METHODS: In a randomized crossover trial, 24 healthy subjects received multiple oral doses of either Huperzine A sustained-release tablets or a common Huperzine A tablet for 7 days. The plasma concentrations were determined by LC/MS/MS. Pharmacokinetic parameters were obtained using DAS program. RESULTS: The major pharmacokinetic parameters of test and reference Huperzine A tables were as follows: C_{ss min} were (0.54±0.21) and (0.79±0.20)ng/mL,C_{ss max} were (1.65±0.45)and (1.83±0.37)ng/mL,C_ss were (1.05±0.28) and (1.22±0.28)ng/mL,t_max were (3.5±1.9) and (1.1±0.4) h,AUC_0-t(ss) were (31±8) and (35±9)ng·mL^-1·h,AUC_0-∞(ss) were (37±10)and (41±11)ng·mL^-1·h,AUC_ss were (25±7)and (15±3)ng·mL^-1·h,respectively. The relative bioavailability of test tablet as estimated by AUC_0-t(ss) was (88±12) %. There was significant difference in t_max between two tablets. CONCLUSION: The results show that the Huperzine A substain-release tablets clearly have the characteristic of slow releasing properties.

Efficacy and plasma concentration analysis of Vancomycin in the treatment of methicillin-resistant Staphylococcus aureus infection

HUA Jun-yan, TIAN Wei-qiang, ZHU Ya-yan, YU Hui-kang

2010, 15(6):  673-677. 

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AIM: To investigate the relationship of clinical efficacy, blood trough concentration and adverse reavtion, which in the treatment of methicillin-resistant Staphylococcus aureus infection with Vancomycin. METHODS: The clinical data of 82 hospital patients who were infected by methicillin-resistant Staphylococcus aureus and treated with Vancomycin from January 2008 to October 2009 were retrospectively analyzed the clinic efficacy, bacteriological treatment, adverse reaction were observed, and the blook trough concentration was detected. RESULTS: The treatment effective rate of Vancomycin-blood trough concentration which was less than 5 μg/mL, in the range of 5-10 μg/mL, and greater than 10 μg/mL were 68.75%, 72.73% and 81.82%. The bacterial clearance rates were 62.50%, 68.18% and 72.73%. One case of blood trough concentration of 14.6 μg/mL in patients with renal toxicity. CONCLUSION: Increasing the blood trough concentration of Vancomycin can improve the treatment of methicillin-resistant Staphylococcus aureus infection in the efficacy and bacterial eradication rates, but the probability of renal toxicity adverse reactions will also increase accordingly.

Evaluation of co-detection of ischemia modified albumin and treadmill exercise test in the diagnosis of silent myocardial ischemia

WU Ming, LI Xiang-dong, ZHA Chun-guang, WANG An-cai

2010, 15(6):  678-681. 

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AIM: To evaluate the diagnostic value of co-detection of ischemia modified albumin (IMA) and treadmill exercise test (TET) for silent myocardial ischemia (SMI). METHODS: 80 patients [55 males and 25 females; mean age (54±8) years] with suspected SMI were selected. All patients were examined with TET and coronary arteriongraphy(CAG) in one week. IMA was detected before TET and two hours after TET. All patients were divided into CHD and NCHD groups combined with the results of CAG. Changes in the concentration of IMA were observed of two groups before and after TET. The diagnostic value of co-detection of ischemia modified albumin and treadmill exercise test was evaluated for SMI. RESULTS: Among the 80 patients, it was diagnosed as CHD 33 cases, NCHD 47 cases. There were significant higher levels of IMA after TET in CHD group (P<0.05), but no significant differences in NCHD group (P>0.05). IMA levels were significantly higher in the patients of CHD after TET than those patients of NCHD[(13.3±3.5) vs (4.7±1.8) ng/mL,P<0.01]. But before TET, there were no significant differences between CHD and NCHD groups (P>0.05). The sensitivity value was 81.8％ for IMA after TET, specificity was 76.6%, positive predictive value was 71.1%, negative predictive value was 85.7%. The sensitivity was 93.8% with the co-detection of IMA and TET, specificity was 87.5%, positive predictive value was 83.3%, negative predictive value was 95.5%. CONCLUSION: IMA is a useful biochemical marker for the early myocardial ischemia. There is a high sensitivity and negative predictive value for IMA two hours after TET in thediagnosis of SMI. There is much higher diagnostic value with the co-detection of IMA and TET.

Value of serum ferritin on the diagnosis and prognosis in rheumatic disease

REN Chuan-yong, XU Liang, XUAN Dan, LI Zhi, SHENG Jun, LU Jing-ming

2010, 15(6):  682-685. 

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AIM: To study the value of serum ferritin (SFe) on diagnosis and prognosis in rheumatic disease. METHODS: The clinical data of 156 cases rheumatic disease patients were collected from July 2008 to February 2009,and the same period 20 cases of healthy volunteers as normal control. The levels of serum ferritin(SFe) in disease groups and normal control group were compared.Statistical analysis was performed to correlate each clinical data with the levels of SFe and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (CCP-Ab), complement C₃ in disease groups. RESULTS: The average levels of SFe in adult onset Still's disease (AOSD) group and rheumatoid arthritis (RA)group were (1707±387),(299±228) ng/mL,respectively,which were higher than those in normal control group(143±100) ng/mL,n＝20,P＝0.000, P＝0.028. The average levels of systemic lupus erythmatosus (SLE) group (n=30) were (295±326) ng/mL,there was no difference between the SLE group and normal control group(P=0.050). When SLE patients were divided into two groups by SLE disease activity index (SLEDAI) exceed(338±225) ng/mL, n=12 or less than 10 scores(158±123) ng/mL, n=18 then the average level of SFe of two groups were compared with each other, a statistical difference(t=2.534,P=0.042) was founded.The levels of SFe and CCP-Ab in RA group had significant correlation(r=0.531,P＝0.004), there was no significant correlation to other clinical index. CONCLUSION: The levels of SFe could be helpful for the diagnosis of AOSD, and may be the indicator of morbidity and activity in patients with AOSD and RA.When the activities of SLE is increased,the levels of SFe are significantly increased.

Influence of preemptive analgesia with parecoxib sodium on the balance of Th1/Th2 during radical resection of gastric carcinoma

CHEN Zhong-hua, JIANG Zong-ming, LOU Jing-zhi, ZHENG Xian-he,ZHANG Chang-feng, HU Shuang-yan, FANG Ju-mei

2010, 15(6):  686-690. 

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AIM: To determine the effect of preemptive analgesia with parecoxib sodium on balance of Th1/Th2 during radical resection of gastric carcinoma. METHODS: Fourty patients scheduled for radical resection of gastric carcinoma under general anesthesia were randomly allocated into groupⅠand groupⅡwith 20 cases each. Parecoxib sodium 40 mg was intravenously administered 30 minutes before anesthesia induction in groupⅠ, while in groupⅡ normal saline 5 mL was injected via vein route 30 minutes before anesthesia induction. All patients received intravenous injection of parecoxib sodium 40 mg 10 min before the end of operation and then were attached to a PCIA pump. PCIA with fentanyl 10 μg/kg was added into normal saline 100 mL in two groups. The infusion rate was 2 mL/h, bolus dose was 0.5 mL,lockout interval was 15 min. The plasma concentrations of cortisol, interferon-γ(INF-γ) and interleukin-4(IL-4) were measured before induction of anesthesia(T₁), at the end of operation(T₂), at 24h(T₃) and 72 h(T₄)after operation. RESULTS: Compared with T₁,Cor was higher at T₂ and T₃ in groupⅡand at T₃ in groupⅠ(P＜0.05). Cor levels at T₂ and T₃ were lower in groupⅠthan those in groupⅡ(P＜0.05).IL-4 of groupⅠwas lower at T₃ than that at T₁ (P＜0.05). IL-4 at T₄ was lower in groupⅠthan that in groupⅡ(P＜0.05). INF-γof groupⅠwas higher at T₂,T₃ and T₄ than those at T₁ (P＜0.05), which was higher at T₂ and T₃ than those of groupⅡ(P＜0.05).The ratio of IFN-γ/IL-4 in both groups was significantly higher at T₂,T₃ and T₄ than those at T₁, which at T₃ was higher in groupⅠ than that in groupⅡ(P＜0.05). CONCLUSION: Preemptive analgesia with parecoxib sodium can alleviate the excursion degree of Th1/Th2 and improve immunological suppression after radical resection of gastric carcinoma.

Clinical trials simulation in drug development

HUANG Ji-han, HUANG Xiao-hui, LI Lu-jin, WANG Qin, WANG Kun, ZHENG Qing-shan

2010, 15(6):  691-699. 

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Clinical trial simulation is playing more and more important role in new drug development, making the drug development more efficient and informative. Clinical trial simulation can be viewed as the abstraction of the clinical trial process. It is used to investigate assumptions and to influence trial design in order to maximize the amount of information gained in drug development. Simulation can be used for modeling variability, estimating the impact of operational factors, evaluating assumptions, comparing trial designs, discriminating between competing drugs. In this review, we describe the motivations and history, general methodology and some examples of clinical trial simulation, including a brief description of current software available for performing such simulations, and finally our view of the current and future impact and directions for this powerful technology in drug development. Simulation is applicable to many areas of the clinical trial process. The focus here centers on the use of simulation with models based upon the pharmacokinetic-pharmacodynamic relationship that reflect the disposition and effect of drugs as observed in clinical trials.

Advancement in research on precursor of brain derived neurotrophic factor

BAI Xian-shu, LIAO Hong

2010, 15(6):  700-704. 

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The neurotrophins are a family of growth factors belong to a class of secreted proteins, which participate in several physiological events of neural system. Recent studies indicate that pro-neurotrophins and their mature forms often have opposite function in biological effects,their receptors and the intracellular signaling pathways. The recent progress of precursor of brain derived neurotrophic factor(proBDNF), especially the distribution, biosynthesis, secretion, bioactivity of proBDNF and the relationship between proBDNF and neural system diseases are reviewed in this article.It is very important to study the function of proBDNF participated in the physiological and pathological conditions for drug researching and developing and for the treatment of nervous system diseases.

Adrancement in pharmacogentics and hypenteasion medicine

SHEN Jie, XIE Hai-tang, LIU Zhao-qian

2010, 15(6):  705-714. 

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Pharmacogenetics is essential for explanation on individual variation of drug responses, and application of personalized medicine. Recently new technological developments draw attentions for their clinical applications in hypertension therapy. This article aims to review the advancements in gene polymorphisms related with hypertension therapy from pharmacokinetics and pharmacodynamics points, as well as their impacts on hypertension therapy, according to ourexperiences in such fields. We conclude that pharmacogenomics advancements such as gene-array would greatly improve personalized medicine of hypertension and other diseases in the future.

Research advancement in effects of gene single nucleotide polymorphism to platinum drugs' chemotherapy sensitivity in NSCLC patients

ZHAO Gang-tao, YANG Fan, DING Yuan-yuan, ZHENG Fei, ZENG Ming, ZHAO Wei-juan, XU Jing-feng

2010, 15(6):  715-720. 

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By Consulting the papers at home and abroad, we summarize the effect of gene single nucleotide polymorphism to platinum drugs in non-small cell lung cancer (NSCLC)patients. The result is there existing huge interindividual variability on the sensitivity of platinum drugs in NSCLC patients. The gene SNP is an important factor to the chemotherapy therapeutic effect of platinum drugs. Better therapeutical effect will show up when taking medicine individually in case of the gene types of NSCLC patients are definite.