Table of Content

Volume 12 Issue 9
26 September 2007

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In vitro-in vivo correlation (IVIVC):perspectives from CDE reviewer

HUANG Qin, MA Yu-nan

2007, 12(9):  961-964. 

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The in vitro-in vivo correlation (IVIVC) model is often established for the oral solid extended release drug product development in order to predict accurately and precisely the expected bioavailability characteristics for the product from dissolution profile characteristics study.In the past several years, CDE occasionally received IVIVC documents for applying waiver of in vivo bioequivalence study when it is necessary to document bioequivalence because of post-approval changes (e.g., formulation, strength, manufacturing site changes, etc.).This paper discussed the key points in the IVIVC development program and introduced the considerations from CDE perspective in reviewing these applications.

Therapatic potential of cholinergic drugs in treatment of asthma associated with gastroesophageal reflux

KUANG Xiao-dong, CUI Yong-yao, WANG hao, CHEN Hong-zhuan

2007, 12(9):  965-969. 

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Gastroesophageal reflux (GER) has a close association with asthma through vagal nerve.Cholinergic nerve and cholinergic receptors might play an important role in the development of GER-induced asthma, indicating that anti-cholinergic drugs may have therapatic potential in the treatment of asthma induced by gastroesophageal reflux.

Advancement of mammalian CYP450s expression in E.coli

ZHANG Che, ZHANG Zhi-quan, ZHOU Hong-hao

2007, 12(9):  970-973. 

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Cytochrome P450(CYP450) is one of most important enzymes to metabolize endogenous and exogenous substrates in vivo.With the development of molecular biology and recombinant technology, the manipulating and heterogeneous expression of CYP450 cDNA become possible.Many kinds of heterogeneous expression systems have been generally operated nowadays, of which there are advantages and disadvantages respectively.It is usual to express mammalian CYP450s using E.coli as host in Lab, but different protein production and enzyme activity are brought by different expression systems and purification procedures.The present application of different expression modes using E.coli for mammalian CYP450 cDNA will be introduced as well as their advantages and the limits respectively.

Advance in research of orphan nuclear receptor-mediated regulation of UDP-glucuronosyltransferases

ZHANG Li, ZHOU Hong-hao

2007, 12(9):  974-979. 

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UDP-glucuronosyltransferases (UGTs) belong to the Phase II drug metabolizing enzymes.UGTs mediate transformations of glucuronic acid to xeno- and endobiotic chemicals, and it is the most important type of enzymes which involved in biotransformation of phase Ⅱ. More and more evidences have demonstrated that orphan nuclear receptors, such as pregnane X receptor (PXR), constitutive androstane receptor (CAR) and other transcriptional factors can regulate UGTs, differences of the factors above in distribution and activity can induce diversity of expression and activity of UGTs.Besides, researches indicated that the NR-mediated regulations of UGTs may contribute to variations of internal metabolism of compounds.In light of the expression of UGTs correlated to hormone homeostasis, therapeutic and side effects of medicine, incidence and prognosis of tumors and other diseases closely, therefore, elucidating UGT regulation by nuclear receptors has broad significance in drug interactions prediction and rational administration, human disease prevention and so on.

Advances in diagnosis and treatment on human granulocytic anaplasmosis

YU Yan-lin, YANG Jin-sun, RUI Jing

2007, 12(9):  980-983. 

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Human granulocytic anaplasmosis (HGA) is an emerging tick-borne natural focal disease caused by Anaplasma phagocytophilum.Its clinical characters mainly include symptoms of febrile illness, digestive tract and blood system.A few severe patients die with multiple system organ failure.The cases of HGA were recently reported in America, Europe and Africa, and also found in our country.The disease has attracted more attention.The advances of diagnosis and treatments on HGA is reviewed in this article.

Research progress of snake venom disintegrin in treatment of tumor

ZHANG Ye, RUI Jing

2007, 12(9):  984-988. 

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The function of cellular membrane receptor has been paid more attention inmany dieases.Integrin is one of them.The major function of integrin is maintaining the proper structure of tissues by organization of cellcell and cell-extracelluar matrix tethering.The initiation and prolongation of many diseases are promoted by these receptors.Disintegrin is one important component of the snake venom.It inhibit the adhesive attraction of integrin particularly.This review summarizes the types and the biological activities of snake venom disintegrins, as well as discusses there potential clinical application of the study, such as anti-tumor, anticoagulation, and various human diseases.

Correlation of levofloxacin pharmacokinetic/pharmacodynamic parameters with selection of staphylococcus aureus resistance

CUI Jun-chang, LIU You-ning, WANG Rui, TONG Wei-hang, LIANG Bei-bei

2007, 12(9):  989-992. 

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AIM: To study the correlation of levofloxacin pharmacokinetic/pharmacodynamic parameters with selection of staphylococcus aureus resistance.METHODS: Tissue cage infection model with staphylococcus aureus was established in rabbits, and the infected animals were given levofloxacin intragastrically at various doses.Changes in levofloxacin concentration, levofloxacin susceptibility of bacteria were monitored at the site of infection.RESULTS: AUC₂₄/MIC, AUC₂₄/MPC, C_max/MIC, C_max/MPC, time above MPC and T_msw showed a statistically significant correlation with selection of staphylococcus aureus resistance, and time above MIC did not (MIC :minimal inhibitory concentration, MPC :mutant prevention concentration, MSW :mutant selection window). Loss of bacterial susceptibility occurred easily when AUC₂₄/MIC was between 20 h and 150 h, and keeping AUC₂₄/MPC above 25 h could restrict selection of resistance.The upper boundary of the selection window in vivo was estimated as an AUC₂₄/MPC value of 25 h, and the lower boundary was estimated as an AUC₂₄/MIC value of 20 h.CONCLUSION: AUC₂₄/MPC, C_max/MPC and time above MPC may be the parameters for predicting resistance.

Anti-apoptotic effect of S-8300 beta cells of islet and renal glomeruli cells in alloxan-diabetes mice

HUANG Feng-jie, QIAN Jing, WU Wu-tong

2007, 12(9):  993-997. 

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AIM: To evaluate the effect of active peptide from shark livers, S-8300, on beta cell of islet and renal glomeruli cells in alloxan induced diabetic mice.METHODS: The anti-apoptotic effect of S-8300 on diabetic mice was investigated by observing pancreas and kidney cells under electron microscope and DNA electrophoresis.The changes of NO and NOS in serum were also been deteced.RESULTS: The ultrastructural apoptosis lesions in pancreas and kidney cells in S-8300 groups were obviously alleviated and significant decrease of NO and NOS in serum was observed in diabetic mice treated with S-8300.CONCLUSION: The hypoglycemic effects of S-8300 was related with its protective activity against the apoptosis.

Endothelin receptor antagonist CPU0213 improves pulmonary injury and fibrosis induced by bleomycin and oleic acid in mice

LI Na, WANG Qiu-juan, DAI De-zai, HE Hai-bo, FENG Yu, DAI Yin

2007, 12(9):  998-1003. 

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AIM: Pulmonary fibrosis (PF) is closely related to progression of pulmonary artery hypertension. The study is aimed to investigate the effects of endothelin receptor antagonist CPU0213 on PF induced by bleomycin or oleic acid in mice.METHODS: Mice were divided into control, PF model, nifedipine treated (p.o.10 mg·kg^-1 ·d^-1), and CPU0213 (p.o.50 mg ·kg^-1 · d^-1), CPU0213(p.o.100 mg·kg^-1·d^-1), CPU0213 (p.o.200 mg·kg^-1 ·d^-1) treated groups (n=10).In bleomycin-induced PF model, the lung weight index, recovery of bronchioalveolar lavage fluid (BALF), leukocytes in BALF and biochemical assay of malondialdehyde (MDA) and hydroxyproline were delected.In oleic acidinduced acute lung injury model, mice received intravenous injection of Evan's blue, and 4hr later the content of Evan's blue in lung were measured.RESULTS: CPU0213 and nifedipine were effective in decreasing lung weight, suppressing inflammatory reactions, oxidative stress, and the accumulation of hydroxyproline in bleomycin- induced PF model.In acute lung injury model, the content of Evan's blue in lung was reduced by CPU0213 and nifedipine.The improvement made by CPU0213 200 mg/kg was better than nifedipine 10 mg/kg.CONCLUSION: Endothelin receptor antagonist CPU0213 showed favorable ability to reverse changes developed in PF. CPU0213 may be promising in the treatment of pulmonary artery hypertension in clinical settings.

Effects of N-n-butyl haloperidol iodide on ischemia and reperfusion-induced ventricular arrhythmias in rat heart

GAO Fen-fei, SHI Gang-gang, LI Hai-qing, HUANG Zhan-qin, ZHANG Yan-mei, ZHOU Yan-qiong

2007, 12(9):  1004-1008. 

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AIM: To study the antiarrhythmic effects of N-n-butyl haloperidol iodide (F₂) on ischemia- and reperfusion-induced ventricular arrhythmias.METHODS: Using the Langendorff-perfused rat heart model, the ventricular arrhythmias were induced by ligating the left anterior descending coronary artery for 20 minutes before the release of the ligature.Each concentration of F₂ was administered 5 min prior to the induction of regional ischemia.The effects of F₂ on arrhythmias during periods of ischemia and reperfusion and the effects on PR, QT, RR intervals were investigated.When rat hearts were paced (5 Hz) via the right atrium to prevent bradycardia, the antiarrhythmic effects and the effect on PR interval of 1 μmol/L F₂ were observed.RESULTS: F₂ reduced ischemia- and reperfusion-induced ventricular arrhythmias in concentration-dependent manner, and widened PR, RR intervals.The same effects were observed even in paced rat hearts.CONCLUSION: F₂ could reduce ischemia- and reperfusion-induced ventricular arrhythmias directly in the isolated rat hearts.

Inhibitory effect of histone deacetylase inhibitor FK228 on LNCaP prostate cancer cells

SUN Sheng-kun, HONG Bao-fa, LI Xiu-shen, HOU Chun-mei, XIAO Xu-ren, YU Xiao-dan

2007, 12(9):  1009-1012. 

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AIM: To investigate the mechanisms underlying the antitumor effect of histone deacetylase inhibitor FK228 on LNCaP prostate cancer cell line.METHODS: Proliferation of LNCaP cells exposed to FK228 was detected by MTT assay.Cell apoptosis was assayed by hoechst 33342 nuclei staining.Cleaved PARP, an apoptosis marker protein, was assayed by western blotting after FK228 exposure.The expression of the androgen receptor (AR) was performed by confocal laser scanning microscope.RESULTS: FK228 killed LNCaP cells with an EC₅₀ value of 7.4 ng/mL within 48 hours exposure as well as inducing cell apoptosis.FK228 could deplete AR in the nucleus.CONCLUSION: FK228 exhibits significant antitumor effect against LNCaP cells through depletion of AR.

Effects of HECCM and DDPH on the expression of osteopontin gene and α-SM-actin in PASMC

DU Bing, CHEN Pei-pei, WANG Xi-ming, DUAN Qiu-hong, HE Shan-shu

2007, 12(9):  1013-1017. 

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AIM: To study the effects of hypoxial endothelia cell conditional medium(HECCM) and DDPH on the expression of osteopontin(OPN) gene and α-SM-actin in pulmonary arterial muscle cell (PASMC), and the reverse effect of DDPH on proliferating PASMC induced by HECCM.METHODS: Hypoxial endothelia cell model was established in PASMC of swine.MTT assay and Immunocytochemistry was used to test cell proliferation, the expression of α-SM-actin.Reverse transcription polymerase chain reaction(RT-PCR) was used to detect the expression of OPN gene.RESULTS: (1) HECCM decrease the level of α-SM-actin and up-regulate the expression of OPN gene in PASMC;(2) DDPH increase the level of α-SM-actin and down-regulate the expression of OPN gene in PASMC.CONCLUSION: DDPH could reverse the phenotype transformation of PASMC exposed to HECCM, and transform PASMC from synthetic phenotype to normal contractile phenotype.

Agmatine inhibits inflammatory pain induced phosphorylated extracellular signal-regulated protein kinase up-regulation in spinal dorsal horn

QIN Xiao-hui, WU Ning, SU Rui-bin, ZHANG Hong, LI Jin

2007, 12(9):  1018-1022. 

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AIM: To evaluate the analgesic effect of agmatine on the model of formalin-evoked nociception;To investigate the changes in the expression of phosphorylated extracellular signal-regulated protein kinase (pERK) in the spinal dorsal horn of the formalin-induced inflammatory pain and the effect of agmatine on the pERK expression.METHODS: Male SD rats weighing 180-220 g were randomly classified into saline control group, formalin group, and agmatine group n=20.Rats were injected subcutaneously with 50 μL of 5% formalin solution into the plantar surface of the right hind paw.During the next 60 min, the weighted pain score was recorded in 5-min intervals for 12 rats group.Another 8 rats group were decapitated at 8 min after intraplantar injection and L_4,5 spinal cords were dissected and coronal sections were cut. Immunohistochemistry was used to observe the changes of pERK expression in the dorsal horn of spinal cord.RESULTS: Intraplantar injection of formalin produced a typical biphasic nociceptive response.Intraperitoneally pretreatment with agmatine inhibited the nociceptive and hyperalgesic response.Injection of 5% formalin subcutaneously in the hindpaw of rats induced an increase in pERK expression in neurons in the superficial dorsal horn on the ipsilateral side of the L_4,5 spinal cord.Pretreatment with 160 mg/kg agmatine significantly inhibited formalin-induced spinal pERK expression.CONCLUSION :Agmatine induces analgesia in the formalin-induced nociception.pERK activation may underlie spinal nociceptive processing and secondary hyperalgesia after formalin inflammation and may contribute to the analgesic effects of agmatine.

Therapeutic effects of total flavones of bidens pilosa L on hepatic fibrosis in murine schistomiasis

CHEN Fei-hu, LU Yuan-qing, SHEN Ji-jia, REN Cui-ping, YUAN Li-ping, LI Jun

2007, 12(9):  1023-1027. 

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AIM: To observe the therapeutic effect of total flavones bidens pilosa L (TFB) on experimental schistosoma japonicum hepatic fibrosis in mice.METHODS: 50 mice infected with schistosma japonicum cercariae percutanoeusly were divided into 5 groups :model group, TFB 57.5, 115, 230 mg/kg group and Colchicines 0.15 mg/kg group and other 10 normal mice were used as control group.After treatment with TFB for 8 weeks, the spleen and liver were removed and weighed. The contents of ALT, AST, albumin(ALB) and total proteins (TP) in serum were assayed using the corresponding kits.Moreover, histopathological changes in hepatic tissues were examined and the degree of liver fibrosis was scored.RESULTS: The mice that infected with schistosoma japonicum, had a featuring increment in spleen and liver weights, serum ALT, AST and EPG contents, decrease in serum ALB and TP contents.TFB (230 mg/kg) treatment significantly reduced serum ALT, AST and EPG contents (P<0.01).In addition the hepatic histopathology was also improved in TFB treatment group (115, 230 mg/kg) (P<0.01).CONCLUSION: TFB has significant therapeutic effect on schistosoma japonicum-induced liver fibrosis in mice.

Effect of mistletoe lectins on proliferation and apoptosis in HT-29 colon cancer cell

WANG Shao-min, YE Meng, NI Shu-ming

2007, 12(9):  1028-1031. 

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AIM: To study the effect of mistletoe lectins on cell proliferation and apoptosis in HT-29 human colon cancer cell.METHODS: The effect of mistletoe lectins on cell viability in HT-29 cell was evaluated by MTT assay.Cell apoptosis was observed by DNA ladder analysis and Tunel.RESULTS: Mistletoe lectins (eg., 1-4 mg L) inhibited cell growth in a dose and time dependent way in HT-29 cells.HT-29 cells apoptosis can be induced when exposed to mistletoe lectins(eg., 1-4 mg L).CONCLUSION: Mistletoe lectins can inhibits proliferation and induces apoptosis in HT-29 cells in vitro.

Study on protection of acanthopanax senticosus injection to focal cerebral ischemia in rats

GUAN Li-xin, ZHAI Feng-guo, YI Xin, SU Yun-ming

2007, 12(9):  1032-1036. 

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AIM: To investigate the protective mechanism of acanthopanax senticosus injection (ASI) on focal cerebral ischemia injury in rats.METHODS: Wistar rats were randomly divided into sham operated group, model control group and two ASI groups, to which ASI of 45 and 90 mg/kg was intraperitoneally administered for 7d, and then subjected to cerebral ischemia injury induced by middle cerebral artery occlusion (MCAO) in rats, via string ligation of arteria carotis interna.The content of maleic dialdehyde (MDA) was determined by thibabituric acid (TBA) test and the activity of superoxide dismutase (SOD) was detected by chemical colorimetry test in cerebral tissues.Apoptosis in cortex region was measured with TUNEL method.Bcl-2, bax and caspase-3 protein expression of neurons was detected with immunohistochemistry staining in cortex region.RESULTS: ASI (45, 90 mg/kg) could significantly decrease the content of MDA and increase the activity of SOD, and inhibit the neuronal apoptosis.ASI (45, 90 mg/kg) could increase the expression of bcl-2 protein, and reduce the expression of bax and caspase-3 protein significantly.CONCLUSION: The protective mechanism of ASI on focal cerebral ischemia injury may be related to anti-free radical effect and inhibition of neuron apoptosis.

Role of cytochrome P450 on the metabolism of injection bupleuri

WANG Jing, YU Hui-yan, GUO Lei, LIU Yan, ZHU Da-ling

2007, 12(9):  1037-1041. 

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AIM: To identify the effects of injection bupleuri.on activity of CYPs subgroups.METHODS: The activity of CYP1A2 was determined by measuring the ratio of caffeine and its metabolite in whole blood in vivo by HPLC and the ratio of phenacetin and its metabolite in liver microsomes in vitro.The expression of CYP1A2、 3A4、4A1 in three groups were examined by Western blotting.RESULTS: There were no significant difference between probes metabolic rates among groups in vivo and in vitro(P>0.05).Also there were similar expression of CYP1A2 in rat liver microsomes from control and treated groups.The expression of CYP3A4 increased in the high dose bupleuri.group.the expression of CYP4A1 obviously decreased in bupleuri.groups.CONCLUSION: Injection bupleuri can inhibit CYP4A1 and induce CYP3A4 expression in rat livers.however it does not effect rat CYP1A2 in vivo or in vitro obviously.

Study on mechanisms of κ-opioid receptor agonist affects neonatal rat myocardial hypertrophy induced by isoproterenol

CUI Lei, WANG Hong-xin, ZHAO Min

2007, 12(9):  1042-1046. 

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AIM: To study the mechanisms of effects of the κ-opioid receptor (κ-OR) on neonatal rat hypertrophic myocardial cells induced by isoproterenol (ISO). METHODS: Myocardial cells of neonatal rats were cultured in vitro.The total protein content was detected by the Lowry's assay.The volume of myocardial cell was measured by computer photogragh analysis system and the protein synthesis was assayed with [³H] leucine intake method.The degree of extracellular signal-regulated kinase (ERK) phosphorylation was determined by western- blotting.RESULTS: U0126(an inhibitor of ERK) decreased the total protein content, the cell size, the[³H] leucine incorporation and the ERK phosphorylation degree in hypertrophic myocardial cells induced by ISO.1 μmol/L U50, 488H(a κ-opioid receptor antagonist) could decrease the total protein content, the cell size, the[³H] leucine incorporation and the degree of ERK phosphorylation.But these effects could be diminished when incubated with U0126. CONCLUSION: κ-opioid can abolish the hypertrophic response induced by ISO of cardiac myocytes, which was associate with ERK pathway.The inhibitor of ERK significantly inhibits the ISO-induced hypertrophied effect.

Comparative study on effects of active ingredients of several traditional Chinese medicines on rabbit platelet aggregation in vitro

WU Yuan, GUO Hong-bao, WANG Tie-jun, WANG Yin-ye

2007, 12(9):  1047-1051. 

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AIM: To compare the inhibitory activities of the active ingredients of several traditional Chinese medicines on platelet aggregation.METHODS: The platelet aggregation was tested with Born's method, which was induced by ADP, PAF and collagen.The effects on platelet aggregation of six ingredients were evaluated to determine their characteristics.RESULTS: Ginsenosides, panax notoginosides and safflor pigment showed significant inhibitory effects on the aggregation induced by the three drugs;ginsenosides showed the most potent inhibitory activity among them.Salvianolic acids and pueraria flavonoids evidently inhibited the aggregation induced by ADP or collagen, but did not influence PAF-induced platelet aggregation.Ophiopogon japonicus saponins significantly inhibited collagen-induced platelet aggregation, but did not obviously inhibit the aggregation induced by ADP or PAF.CONCLUSION: Ginsenosides showed the most potent inhibitory effect on platelet aggregation among these ingredinents.Panax notoginosides, ginsenosides and safflor pigment displayed extensive inhibitory activities on platelet aggregation.These results provide more information for the clinical selection of Chinese materia medica in the treatment of thrombotic diseases and the development of new Chinese medicine.

Methodological study on improving tumor formation rate of xenografted human lung cancer in nude mice

ZHANG Bao-lai, XU Ming-li, GAO Ming-tang, LU Li, WANG Li, CUI Ming-xia, LI Wen-guang, WU Yong-jie

2007, 12(9):  1052-1057. 

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AIM: To improve tumor formation rate of xenografted human lung cancer in nude mice.METHODS: Before xenograftion, human lung cancer SPC-A-1 or GLC-82 cells and their tissue homogenate were diluted with supernatant of mice sarcoma 180 ascites being rich in growth factors.The diluted SPC-A-1 or GLC-82 cell suspensions were injected subcutaneously at right back or armpit of nude mice.The effects of supernatant of mice sarcoma 180 ascites on the tumor growth rate and tumor formation rate were evaluated.RESULTS: Compared with control group, the tumor growth rate and tumor formation rate of human lung cancer SPC-A-1 or GLC-82 in nude mice were significantly improved with the addition of the supernatant of mice sarcoma 180 ascites.CONCLUSION: The supernatant of mice sarcoma 180 ascites can significantly improve the tumor growth rate and tumor formation rate of human lung cancer SPC-A-1 or GLC-82 in nude mice.

Effects of atorvastatin on the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1

WANG Ai-li, CHENG Ling-ling, HU Jian-feng, CHENG Xin-yao

2007, 12(9):  1058-1061. 

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AIM: To investigate the effects of atorvastatin on the proliferation and collagen synthesis of cardiac fibroblasts (CFs) induced by endothelin-1 (ET-1). METHODS: Neonatal rat cardiac fibroblasts were randomly divided into 4 groups :control, ET-1, Atorvastatin, ET-1+atorvastatin (10^-7-10^-4 mol/L).CFs number was measured by MTT assay.Cell cycle distribution was determined with flow cytometer (FCM).[³H]-Proline uptake was evaluated by scinillation counting.Nitric Oxide (NO) was measured by chromatometry.RESULTS: 10^-6 mol/L ET-1 significantly increased the A490 value and [³H]-Pro incorporation, and decreased the secretion of NO compared with the control group (P<0.01).10^-7-10^-4 mol/L atorvastatin inhibited the above effects of ET-1 on CFs in a concentration-dependent manner (P<0.01 vs ET-1).In the ET-1 group, Phase S cell percentage was higher than that of contol, which was inhibited by atorvastatin (P<0.01 vs ET-1 and control).CONCLUSION: Atorvastatin dose-dependently inhibits the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1, which may be partially mediated by NO.

Prediction of the AUC and the comparison of approaches for validation

XU Ling, LV Ying-hua, YANG Juan, HE Ying-chun, LIU Hong-xia, SUN Rui-yuan, ZHENG Qing-shan

2007, 12(9):  1062-1067. 

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AIM: To predict the AUC with an example by the limited sampling strategy (LSS)and compare the performance of three approaches for internal validation.METHODS: Twenty healthy subjects received 200 mg tiopronin po.A multi-linear regression analysis of the AUC against the tiopronin concentration was carried out to estimate AUC by LSS.According to the values of rmse and Pe, the regressionmodel was validated by the simulation, Bootstrap method and Jackknife method.RESULTS: The model (AUC_0-48=9.36+1.81C₃+23.28 C₈)was accurately validated by the simulation data.The parameters obtained from the simulation, Bootstrap method and Jackknife method were that Intercept=17.58, 9.33, 9.84;M₁=1.01, 1.76, 1.84;M₂=6.17, 23.14, 21.36;and rmse=3.87, 1.94, 2.23.CONCLUSION: The simulation can evaluate the multi-linear regression model by the estimated AUC, and not by the estimated regression model parameters.The Bootstrap and the Jackknife are appropriate approaches as internal validation of the model.

Relative bioavailability of three formulations of citalopra hydrobromide in Chinese healthy volunteers

NI Li, CAO Xiao-mei, LI Jin-heng, CAI Ming-hong

2007, 12(9):  1068-1071. 

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AIM: To study the pharmacokinetics and relative bioavailability of citalopra hydrobromide in human plasma.METHODS: The citalopra hydrobromide concentrations in plasma were determined by HPLC-UV.The column was Lichrospher ODS (5 μm, 250 mm×4.6 mm).The mobile phase was acetonitrile-0.1 mol/L KH₂PO₄ buffer-triethylamine (35：65：0.3, v/v/v).The flow rate was 1 mL/min.The detection wavelength was 240 nm.The test and reference formulations of citalopra were given to 18 healthy male volunteers.RESULTS: The calibration curve was linear within the range of 2- 128 μg/L, r=0.9992.The minimum detection limit was 1 μg/L.The recovery was 80%-88%, the RSDs of inter- day and intra-day were not more than 15%.After a single oral dose of 20 mg citalopra hydrobromide was given, the main pharmacokinetic parameters tmax were (4.6±1.0), (4.4±1.4) and (4.0±1.4) h;C_max were (70±19), (71±17) and (66±21) μg/L;and t_1/2 were (37±9), (37±6) and (36±6) h respectively.CONCLUSION: No significant difference exists among the pharmacokinetic parameters of the three formulations. They are bioequivalent.

Study on bioequivalence of irbesartan tablets produced by two companies

REN Xiu-hua, LIU Dong, YU Yang, LIU Yu, LI Fei-e, ZHANG Dong-lin

2007, 12(9):  1072-1075. 

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AIM: To study the pharmacokinetics and relative bioavailability of irbesartan tablets.METHODS: A single oral dose of 300mg irbesartan of reference or test tablet was given to each of 18 male healthy volunteers according to an open randomized crossover design.The concentrations of irbesartan in plasma were determined by HPLC.RESULTS: The main pharmacokinetic parameters of irbesartan showed that C_max were (3147±922) and (2856±652) ng/mL, tmax were (1.6±0.7) and (1.9±1.1) h, AUC_0→t were (17559±7482) and (17366± 5498) ng°mL^-1°h, AUC_0→∞ were (18276±7710) and (18284±5336) ng°mL^-1°h for reference or test tablet respectively.There was no significant difference between the parameters of two tablets.CONCLUSION: The relative bioavailability of test tablet to reference tablet is 101%±32%.The results of statistical analysis show that two formulations are bioequivalent.

Effects of Vit A on the immunologic status of infants with bronchiolitis

LIU Ya-li

2007, 12(9):  1076-1078. 

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AIM: To observe the concentration of serum vitaminA and discuss the effects of vitamin A on the immune function in infants with acute bronchiolitis in vitro.MEDHODS:16 cases of bronchiolitis with RSV infection and 13 controls were studied.Serum vitamin A level of acute bronchiolitis patients and control infants were measured.The cytokines in supernatant of bronchiolitis, PBMC, IL-12 and IFN-γ, were measured by ELISA after treatment with vitamin A.RESULTS: Serum vitamin A level of patients was lower than control group.Pretreatment with lower level of vitamin A (1×10_-10mol/L) in vitro lead to higher level of IL-12 in supernatant, and significantly promoted IFN-γ secretion. Vitamin A at 1×10^-7 mol/L in vitro inhibited IL-12 secretion.CONCLUSION: The study suggested that serum concentration of vitamin A decreases at acute stage of bronchiolitis, Vitamin A associate with the level of IL-12 negatively in vitro.When vitamin A was at 1×10_-10 mol/L, it reverse the function of TH2 of bronchiolitis infants in vitro.