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Metabonomic phenotype and identification of “heart blood stasis obstruction pattern” and “qi and yin deficiency pattern” of myocardial ischemia rat models

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Science China(Life sciences) 2009年第11期52卷 1081-1090页

作者： YAN Bei1, A JiYe1, HAO HaiPing1, WANG GuangJi1, ZHU XuanXuan2. 3, ZHA WeiBin1, LIU LinSheng1, GUAN EnZe3, ZHANG Ying1, GU ShengHua1, HUANG Qing1 & ZHENG YuanTing1 1Key Laboratory of Drug Metabolism and Pharmacokinetics, China pharmaceutical university, Nanjing 2.0009, China 2.harmacological Laboratory of Clinical Research Institute, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing 2.002., China {2. of Pharmacy, Nanjing university of Traditional Chinese Medicine, Nanjing 2.002., China 1. Key Laboratory of Drug Metabolism and Pharmacokinetics China Pharmaceutical University Nanjing 210009 China 2. Pharmacological Laboratory of Clinical Research Institute Jiangsu Provincial Hospital of Traditional Chinese Medicine Nanjing 210029 China 3. college of Pharmacy Nanjing University of Traditional Chinese Medicine Nanjing 210029 China

The traditional Chinese medicine concepts of "Xinxueyuzuzheng (heart blood stasis obstruction pattern)" and "Qiyinliangxuzheng (qi and yin deficiency pattern)" for myocardial ischemia rat models were constructed in the present study. Endogenous metabolites in rat plasma were analyzed using the GC/TOF-MS-based metabonomic method. Significant metabolic differences were observed between the control and two model groups, and the three groups were distinguished clearly by pattern recognition. Compared with those of the control, the levels of hydroxyproline, threonic acid, glutamine and citric acid were strikingly up or down-regulated in model rats. The metabolites contributing most to the classification between the two "pattern" rats were identified, such as valine, serine, threonine, ornithine, hydroxyproline, lysine, 2.hydroxybutanoic acid, 3-hydroxybutanoic acid, galactofuranose and inositol. These compounds were indicated as the potential biomarkers. The results suggested that the two "patterns" are involved in dysfunction in oxidative stress, energy metabolism and amino acid metabolism. These findings also provided the substantial foundation for exploring the scientific connotation of these two "Zhengxing (pattern types)" of myocardial ischemia, and "Bianzheng (pattern identification)".

关键词： Metabonomics GC/TOF-MS heart blood stasis obstruction pattern qi and yin deficiency pattern myocardial ischemia rat model

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Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats

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Acta Pharmacologica Sinica 2006年第11期27卷 1423-1430页

作者： Shi-ping MA~2.Lei-ming REN~(2.4)Ding ZHAO~2.Zhong-ning ZHU~2.Miao WANG~2.Hai-gang LU~3 Li-hua DUAN~3 2.Hebei Medical university School of Pharmacy,Shijiazhuang 050017,China 3 Hebei Professional college in Chemical &{2. sciences,Shijiazhuang 050031,China HebeiMedicaluniversitySchoolofPharmacy Shijiazhuang050017China HebeiProfessionalcollegeinChemical&pharmaceutical{2. Shijiazhuang050031China

Aim:To study chiral selective effects of doxazosin enantiomers on blood pres-sure and urinary bladder pressure in anesthetized ***:In anesthetizedrats,the carotid blood pressure,left ventricular pressure of the heart and theurinary bladder pressure were ***:Administration of S-doxazosinat 0.2.,2.5,2.,and 2.0 nmol/kg iv produced a dose-dependent decrease in bloodpressure,but its depressor effect was significantly weaker than that induced byR-doxazosin and racemic-doxazosin（rac-doxazosin）,and the ED30values（producinga 30% decrease in mean arterial pressure）of R-doxazosin,rac-doxazosin and S-doxazosin were 15.64,45.93,and 12..81,***-doxazosin and its enan-tiomers administered cumulatively in anesthetized rats induced a dose-dependentdecrease in the left ventricular systolic pressure and ±dp/dtmax,and the potencyorder of the 3 agents was R-doxazosin>rac-doxazosin>***-doxazosinand its enantiomers decreased the vesical micturition pressure dose-dependentlyat 2.5,2.,and 2.0 nmol/kg,and the inhibitory potency among the 3 agents was notsignificantly ***:S-doxazosin decreases the carotid blood pres-sure and left ventricular pressure of the heart less than R-doxazosin and rac-doxazosin,but its effect on the vesical micturition pressure is similar to R-doxazosinand rac-doxazosin,indicating that S-doxazosin has chiral selectivity between car-diovascular system and urinary system in anesthetized rats.

关键词： R-doxazosin S-doxazosin blood pressure ventricular pressure urinary bladder pressure rat

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Synthesis and Characterization of Mg_3(PO_4)_2.coated Li_(1.05)Ni_(1/3)Mn_(1/3)Co_(1/3)O_2.Cathode Material for Li-ion Battery

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Journal of Wuhan university of Technology(Materials Science) 2009年第3期24卷 347-353页

作者：陈玉红 Department of Chemical and Environmental Engineering Hebei Chemical & Pharmaceutical Vocational Technology Colege

Mg3（PO4）2.coated Li1.05Ni1/3Mn1/33Co1/3O2.cathode materials were synthesized via co-precipitation method. The morphology, structure, electrochemical performance and thermal stability were characterized by scanning electron microscopy （SEM）, X-ray diffraction （XRD）, cyclic voltammetry（CV）, electrochemical impedance spectroscopy（EIS）, charge/discharge cycling and differential scanning calorimeter （DSC）. SEM analysis shows that Mg3（PO4）2.coating changes the morphologies of their particles and increases the grains size. XRD and CV results show that Mg3（PO4）2.coating powder is homogeneous and has better layered structure than the bare one. Mg3（PO4）2.coating improved high rate discharge capacity and cycle-life performance. The reason why the cycling performance of Mg3（PO4）2.coated sample at 55 ℃ was better than that of room temperature was the increasing of lithium-ion diffusion rate and charge transfer rate with temperature rising. Mg3（PO4）2.coating improved the cathode thermal stability, and the result was consistent with thermal abuse tests using Li-ion cells： the Mg3（PO4）2.coated Li1.05Ni1/3Mn1/3Co1/3O2.cathode did not exhibit thermal runaway with smoke and explosion, in contrast to the cells containing the bare Li1.05Ni1/3Mn1/3Co1/3O2.

关键词： lithium-ion batteries cathode materials Li1.05Ni1/3Mn1/3Co1/3O2 co-precipitation

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Comparison of the Content,Uniformity of Dosage Units and Dissolution Rate of Triphasic Oral Contraceptives from Two pharmaceutical Factories

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Journal of Reproduction and Contraception 2009年第2期20卷 123-129页

作者： Huan LIU Ying LI Jian-Ping LIU China pharmaceutical university Nanjing 210009 China Institute of Planned Parenthood Research of Jiangsu Province Nanjing 210036 China

Objective To compare the content, uniformity of dosage units and dissolution rate of triphasic oral contraceptives from two pharmaceutical factories A and B. Methods A High Performance Liquid Chromatography （HPLC） method for the simultaneous determination of levonorgestrel and ethinylestradiol was used. The content of levonorgestrel （LNG） was monitored by an UV detector at 2.7 nm, while ethinylestradiol （EE） was monitored by fluorescence detector with the excitation of 2.5 nm and emission wavelengths of 310 nm. The dissolution test was performed using the paddle method. Results The content of levonorgestrel （LNG） and ethinylestradiol （EE） in product A was within 100.5%-12..4% while product B within 12..6%-140.9%. The uniformity value of dosage units of tablets from two factories was more than 15. The dissolution rate of tables from two factories was more than 60% within 60 min. Conclusion Only the content of product A was in the ±2.% range of label claim. The uniformity of two products was not up to standard. The dissolution rate of the tablets from two products met the requirement of ChP2.05.

关键词： levonorgestrel ethinylestradiol dissolution assay uniformity of dosage units

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CJZ3,a Iomerizine derivative,modulates P-glycoprotein function in rat brain microvessel endothelial cells

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Acta Pharmacologica Sinica 2006年第4期27卷 414-418页

作者： Bian-sheng JI~2.Ling HE~3 Xiao-qu LI~4 Guo-qing LIU~(3,5) ~2.nstitute of Pharmacy,Henan university,Kaifeng 475001.China ~3Department of Pharmacology,China Pharmaccutical university.Nanjing 2.0009,China:~4School of Life{2.,Beijing Normal university,Beijing 100875,China Institute of Pharmacy Henan University Kaifeng China Department of Pharmacology China Pharmaceutical University Nanjing China School of Life sciences Beijing Normal University Beijing China

Aim:To investigate the modulatory effect of CJZ3,a lomerizine derivative,onP-glycoprotein(P-gp)function in rat brain microvessel endothelial cells(RBMEC).Methods:RBMEC were isolated and cultured in Dulbecco's modified Eagle's me-dium/F12.1:1)medium,and the amount of intracellular rhodamine 12.(Rh 12.)wasdetermined using a fluorescence spectrophotometer to evaluate the modulatoryeffect of CJZ3 on P-gp ***:The accumulation of Rh 12. was poten-tiated in a concentration-dependent manner after incubation with CJZ3 for RBMEC,but not for human umbilical vein endothelial cells(HUVEC).CJZ3 caused theaccumulation of intracellular Rh12. in a time-dependent manner and significantlydecreased the effiux of Rh 12. from the *** inhibitory effect of CJZ3 on P-gpfunction was reversible and remained for 12. min after CJZ3(2.5 μmol/L)wasremoved from the ***:CJZ3 has a potent in vitro effect on theinhibition of P-gp function.

关键词： CJZ3 P-glycoprotein blood-brain barrier

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Receptor subtype involved in α-adrenergic receptor-mediated Ca2. signaling in cardiomyocytes

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Acta Pharmacologica Sinica 2007年第7期 968-974页

作者： Da-li LUO~(2.3,4),Jian GAO~2.Lin-lin FAN~2.Yu TANG~2.You-yi ZHANG~3,Qi-de HAN~3~2.Department of Pharmacology,School of Chemical Biology and pharmaceutical sciences,Capital{2. of Medical sciences,Beijing100069,China ~3 Institute of Cardiovascular Science at the Health Science Center,Peking{2.,Beijing 100083,China

Aim:The enhancement of intracellular Ca2.signaling in response to α1-adrener-gic receptor （α1-AR） stimulation is an essential signal transduction event in theregulation of cardiac functions,such as cardiac growth,cardiac contraction,andcardiac adaptation to various *** present study was intended todetermine the role（s） of the α1-AR subtype（s） in mediating this ***:We evaluated the effects of subtype-specific agonists and antagonists of the α1-AR on the intracellular Ca2.signaling of neonatal rat ventricular myocytes usinga confocal ***:After being cultured for 48 h,the myocytesexhibited spontaneous local Ca2.release,sparks,and global Ca2.*** of the α1-AR with phenylephrine,a selective agonist of the α1-AR,dose-dependently increased the frequency of Ca2.transients with an EC50valueof 2.3 μmol/*** the α1A-AR subtype with 5-methylurapidil （5-Mu） inhi-bited the stimulatory effect of phenylephrine with an IC50value of 6.7 nmol/***,blockade of the α1B-AR and α1D-AR subtypes with chloroethylclonidineand BMY 7378,respectively,did not affect the phenylephrine ***,thelocal Ca2.spark numbers were also increased by the activation of the α1-AR,andthis effect could be abolished selectively by *** importantly,A61603,anovel selective α1A-AR agonist,mimicked the effects of phenylephrine,but withmore potency (EC50value=6.9 nmol/L) in the potentiation of Ca2.transients,andblockade of the α1A-AR by 5-Mu caused abolishment of its ***:These results indicate that α1-adrenergic stimulation of intracellular Ca2.activityis mediated selectively by the α1A-AR.

关键词： α1-adrenergic receptor subtype cardiomyocyte Ca2. signaling A61603

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A model of 3D-structure of H+, K+-ATPase catalytic subunit derived by homology modeling

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Acta Pharmacologica Sinica 2004年第4期25卷 76-81页

作者： Dong YAN, Yuan-dong HU1, Song LI1, Mao-sheng CHENG2. Shenyang pharmaceutical university, Shenyang 110016 1Academy of Military Medical{2., Beijing 100850, China Shenyang pharmaceutical university cademy of Military Medical sciences

AIM: To build a model of 3D-structure of H+, K+-ATPase catalytic subunit for theoretical study and anti-ulcer drug design. METHODS: The model was built on the basis of structural data from the Ca2.-ATPase. Structurally conserved regions were defined by amino acid sequence comparisons, optimum interconnecting loops were se- lected from the protein databank, and amino (N)- and carboxyl (C)-terminal ends were generated as random coil structures. Applying molecular mechanics method then minimized the model energy. Molecular dynamics tech- nique was used to do further structural optimization. RESULTS: The model of 3D-structure of H+, K+-ATPase was derived. The model is reasonable according to several validation criteria. There were ten transmembrane helices (TM1-TM10) in the model and inhibitor-binding site was identified on the TM5-8 riched negatively charged residues. CONCLUSION: The 3D-structure model from our study is informative to guide future molecular biology study about H+, K+-ATPase and drug design based on database searching.

关键词： peptic ulcer H(+)-K(+)-exchanging ATPase protein structural homology drug design

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Determination of enantiomeric impurity of etomidate by high performance liquid chromatography

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Journal of pharmaceutical Analysis 2010年第2期22卷 102-104页

作者： Xiao-Dan Wang,Xiao-Juan Chai,Su Zeng Department of pharmaceutical Analysis and Drug Metabolism,college of pharmaceutical sciences,Zhejiang university,Hangzhou 310058,China. Department of pharmaceutical Analysis and Drug Metabolism College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China

Objective To determine enantiomeric impurity of etomidate using high performance liquid chromatography. Methods (R)-etomidate and (S)-etomidate were separated on a CHIRALPAK AD-H column. The mobile phase consisted of 2.∶80(v/v) isopropanol-n-hexane. The flow rate of the mobile phase was 0.5mL/min. The detected wavelength was 2.2.m. Results (R)-etomidate and (S)-etomidate could be separated completely under these conditions. The precision of (R)-etomidate was 1.57% (n=3). The limit of detection of (R)-etomidate was 4.2.ng/mL. The average percentage content of (S)-etomidate was 0.09% in the samples. Conclusion The method was repeatable and sufficiently sensitive to determine the enantiomeric impurity of etomidate. It allows the quantitation of the impurities at the 0.085% (w/w) level relative to etomidate at a concentration of the test solution of 5mg/mL.

关键词： etomidate enantiomeric impurity high performance liquid chromatography

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Preparation of two triflate precursors for O-(2.[^(18)F] fluoroethyl)-L-tyrosine used in positron emission tomography (PET)

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Science China Chemistry 2009年第12期52卷 2195-2199页

作者： LIU ChunYan1,2.& JIANG ShenDe1 1 School of pharmaceutical Science and Technology,Tianjin university,Tianjin 300072.China 2.Department of Pharmacy,North China Coal Medical{2.,Tangshan 063000,China 1. School of pharmaceutical Science and Technology Tianjin University Tianjin 300072 China 2. Department of Pharmacy North China Coal Medical College Tangshan 063000 China

Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography (PET) for tumor imaging,O-(2.trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2.trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine tert-butyl ester 9b,are synthesized. The triflate agent,9a or 9b,is prepared by esterification of methanol or transesterification of tert-butyl acetate with L-tyrosine,protection of the amine group with di-tert-butyl dicarbonate,alkylation with chlorohydrin,and triflation with trifluoromethanesulfonic anhydride in four steps with overall yields of 30% and 15%,respectively.

关键词： positron emission tomography triflate L-tyrosine [18F]FET precursor PET imaging

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A highly selective recognition of pyrophosphate with Zn(Ⅱ) complex of terpyridine

A highly selective recognition of pyrophosphate with Zn(Ⅱ) ...

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“2.11国际化学年在中国”——中国化学会第十届全国发光分析学术研讨会

作者： Li Jiao Liang~(a,b),Cheng Zhi Huang~(a,c*) (a Education Ministry Key Laboratory on Luminescence and Real-Time Analysis,college of Chemistry and Chemical Engineering,southwest{2. b,School of Chemistry and Environmental Engineering, chongqing Three Gorges{2. c,college of pharmaceutical sciences,southwest{2., chongqing,400715,PR China.)

Pyrophosphate ion(PO,PPi) is known to be one crucial anion not only because of its important role in a wide range of critically biological processes,but also its widespread use in various industrial ***,the highly selective recognition of PPi based on fluorescence reagents have been widely reported in recent *** this contribution,one tpy derivative,4-(methylphenyl)-2.2.:6’,2.-

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