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ONO-1078 reduces NMDA-induced brain injury and vascular cell adhesion molecule-1 expression in rats

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Acta Pharmacologica Sinica 2005年第4期26卷 435-440页

作者： Li-hui ZHANG~(2,3) Er-qing WEI~(2,4) 2 Department of Pharmacology,school of Medicine,Zhejiang university,hangzhou 310031 3 medical school,hangzhou Normal university,hangzhou 310018,china Department of Pharmacology School of Medicine Zhejiang University Hangzhou China medical school Hangzhou Normal University Hangzhou China

Aim:To determine whether ONO-1078 （pranlukast）,a potent cysteinyl leukotrienereceptor 1 （CysLTI） antagonist,has an effect on N-methyl-D-aspartate （NMDA）-induced brain injury and vascular cell adhesion molecule-1 （VCAM-1） expres-sion in ***:Brain injury was induced by direct microinjection of NMDA（0.3 μmol in 1 μL of sterile 0.1 mol/L PBS,pH 7.4） into the cerebral *** volume （area）,brain edema and neuron density were assessed by an imageanalyzer and the expression of VCAM-1 in the cortex was detected by Westernblot 24 h after NMDA ***-1078 （0.03,0.1,or 0.3 mg/kg） andedaravone （MCI-186,10 mg/kg）,a neuroprotective agent,were ip injected 30rain before and after NMDA ***:NMDA microinjection producedwell-defined focal lesions （Figure 1） dose- and ***-1078（0.1,0.3 mg/kg） and edaravone （10 mg/kg） decreased the total lesion volume,lesion area and brain edema induced by ***,ONO-1078 （0.1,0.3mg/kg） significantly inhibited the enhanced expression of VCAM-1 in the injuredcortices,but edaravone did not have this ***:CysLT1receptorantagonist ONO-1078 at tenufftes NMDA-induced brain damage in rats,and thismight relate to the attenuation of NMDA receptor-dependent neurotoxicity andthe inhibition of the upregulation of VCAM-1 expression.

关键词： leukotriene antagonists pranlukast N-methylaspartate vascular cell adhesion molecule-1 neurotoxicity brain injuries

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灵光独耀:沈宗灵与中国法理学

中国法律评论 2024年第4期 149-154页

作者： Peking university Law school 北京大学法学院

在其诸多弟子的追忆中,沈宗灵先生一生专心治学、淡泊名利,由此常常对世事保持一种有意的疏离。“灵光独耀,迥脱根尘”,或许便是这位法理学大家的灵魂写照。壹“经国济民”:沈宗灵的早年岁月1923年2月24日,沈宗灵出生于浙江杭州的一个... 详细信息

在其诸多弟子的追忆中,沈宗灵先生一生专心治学、淡泊名利,由此常常对世事保持一种有意的疏离。“灵光独耀,迥脱根尘”,或许便是这位法理学大家的灵魂写照。壹“经国济民”:沈宗灵的早年岁月1923年2月24日,沈宗灵出生于浙江杭州的一个商人家庭,后随家人迁居上海。

关键词：沈宗灵淡泊名利法理学浙江杭州灵光

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Inhibitory effects of cryptoporus polysaccharide on airway constriction, eosinophil release,and chemotaxis in guinea pigs

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Acta Pharmacologica Sinica 2004年第4期25卷 105-109页

作者： Xiao-yan ZHAO, Qiang-min XIE2, Ji-qiang CHEN, Chuan-kui KE3 Zhejiang Respiratory Drugs Research Laboratory of State Drugs Administration of china, medical school ofzhejiang university, hangzhou 310031 3TSBIO Science& Technology Co,Ltd, hangzhou 310006, china 浙江大学国家食品药品监督管理局呼吸药物研究实验室 Hangzhou 310031 TSBIO Science & Technology Co Ltd Hangzhou 310006

AIM: To study effects of cryptoporus polysaccharide (CP) on antigen-induced bronchoconstriction, eosinophil peroxidase (EPO) release in vivo, and on platelet activating factor (PAF)-induced eosinophil chemotaxis in vitro in guinea pig. METHODS: The asthma model of guinea pig was formed with ovalbumin (OVA). The changes of lung resistance (RL) and dynamic lung compliance (Cdyn), EPO level in bronchoalveolar lavage fluids (BALF) and eosino- phil migration were determined. RESULTS: Pretreatment of CP at doses of 3, 9, and 27 mg/kg by intragastric gavage (ig), qd for 10 d, inhibited early asthma response in a dose-dependent manner. Inhibitory rates of mean increase value from 1 to 30 min of RL were 34.8 %, 74.4 % (P<0.05), and 79.6 % (P<0.05), respectively. Inhibi- tory rate of mean reduction value of Cdyn were 22.9 %, 40.5 % (P<0.01), and 66.5 % (P<0.01), respectively. Pretreatment of CP at doses of 3, 9, and 27 mg/kg also inhibited late asthma response, and the reduction of EPO level in BALF were 3.1 %, 16.9 % (P<0.01), and 20.1 % (P<0.01), respectively. The inhibitory rates of CP at concentrations of 0.13, 1.3, 13, 130 nmol/L to eosinophil migration induced by PAF were 6.8 %, 17.2 % (P<0.05), 29.6 % (P<0.01), and 35.9 % (P<0.01). CONCLUSION: CP protects lung against increase of RL and reduction of Cdyn, decreases EPO level in the asthma model, and inhibits eosinophil chemotaxis induced by PAF. The results suggest that CP may be a novel antiinflammatory agent for the treatment of asthma and allergic diseases.

关键词： polysaccharide ovalbumin bronchoconstriction respiratory function tests eosinophil peroxidase platelet activating factor chemotaxis asthma guinea pig

Inhibitory effect of acetamide-45 on airway inflammation and phosphodiesterase 4 in allergic rats

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Acta Pharmacologica Sinica 2005年第12期26卷 1492-1496页

作者： Kai WANG~2 Hua-hao SHEN~(2,4) Jun-chun CHEN~2 Zhong CHEN~3 2 Respiratory Department,the Second Affiliated Hospital,medical school of Zhejiang university,hangzhou 310009 3 Department of Pharmacology,medical school of Zhejiang university,hangzhou 310031,china Respiratory Department the Second Affiliated Hospital Medical School of Zhejiang University Hangzhou China Department of Pharmacology Medical School of Zhejiang University Hangzhou China

Aim:To determine the effects of acetamide-45 on respiratory function,airwayinflammation,and the activity of phosphodiesterase 4（PDE4）in allergic ***:Rats were sensitized by a single intramuscular injection with ovalbumin（OVA）and were challenged with ovalbumin applied by using an aerosol repeat-edly for 7 d after 2 ***-45 at concentrations of 5,10,or 30 mg/kg wasthen administered by intraperitoneal *** in dynamic lung compli-ance and lung resistance,the accumulation of inflammatory cells in bronchoalveolarlavage,PDE4 activity,and the concentration of interleukin-4 in rat lung tissuewere ***:Seven days of treatment with acetamide-45 preventedeosinophil accumulation in allergic *** doses of 5,10,and 30 mg/kg,aceta-mide-45 decreased lung resistance to 0.20±0.04,0.25±0.07,and 0.22±0.05cmH2O·s-1·mL-1,respectively（P<0.05 vs OVA）,and it also increased dynamic lungcompliance to 0.41±0.07,0.39±0.06,and 0.42±0.09 mL/cmH20（P<0.05 vs OVA）.After being treated with different doses of acetamide-45,the PDE4 activities inlung tissue were 281±55,273±57,and 238±36 nmol·g-1·min-1（P<0.05 vs OVA）,andthe concentrations of interleukin-4 in lung tissue were 6.22±1.13,5.95±1.20,and 5.68±2.20 μtg/g protein（P<0.05 vs OVA）.Conclusions:Acetamide-45 wasfound to improve respiratory function and inhibit airway inflammation in thisanimal model,and the PDE4 activity of lung tissue was obviously ***-45 was an effective anti-inflammatory agent in respiratory inflammation,and the mechanism of its action might depend on inhibition of PDE4.

关键词： acetamide-45 3’,5’-cyclic nucleotide phosphodiesterase respiratory function tests eosinophils asthma

Identification of differentially expressed genes in normal mucosa,adenoma and adenocarcinoma of colon by SSH

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World Journal of Gastroenterology 2001年第5期7卷 726-731页

作者： Min-Jie Luo Mao-De Lai Department of Pathology,school of Medicine,Zhejiang university,hangzhou 310031,P.R.china Department of Pathology School of Medicine Zhejiang University Hangzhou 310031 China.

AIM: To construct subtracted cDNA libraries and further identify differentially expressed genes that are related to the development of colorectal carcinoma(CRC). METHODS: Suppression subtractive hybridization(SSH) was done on cDNAs of normal mucosa, adenoma and adenocarcinoma tissues from the same patient. Three subtracted cDNA libraries were constructed and then hybridized with forward and backward subtracted probes for differential screening. Positive clones from each subtracted cDNA library were selected for sequencing and BLAST analysis. Finally, virtual Northern Blot confirmed such differential expression. RESULTS: By this way, there were about 3-4 X 10(2) clones identified in each subtracted cDNA library, in which about 85% positive clones were differentially screened. Sequencing and BLAST homology search revealed some clones containing sequences of known gene fragments and several possibly novel genes showing few or no sequence homologies with any known sequences in the database. CONCLUSION: All results confirmed the effectiveness and sensitivity of SSH. The differentially expressed genes during the development of CRC can be used to shed light on the pathogenesis of CRC and be useful genetic markers for early diagnosis and therapy.

关键词： Gene Expression Regulation, Neoplastic Adenocarcinoma Adenoma Blotting, Northern Colorectal Neoplasms Gene Library Genetic Markers Humans Intestinal Mucosa Polymerase Chain Reaction RNA, Messenger Research Support, Non-U.S. Gov't

Cloning of cytochrome P-450 2C9 cDNA from human liver and its expression in CHL cells

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World Journal of Gastroenterology 2002年第2期8卷 318-322页

作者： Ge-Jian Zhu Ying-Nian Yu,Department of Pathophysiology and Laboratory of medical Molecular Biology,Zhejiang university school of Medicine,hangzhou 310031,Zhejiang Province,china Xin Li,Department of pharmaceutical analysis & drug metabolism,College of Pharmacology Science,Zhejiang university,hangzhou 310031,Zhejiang Province,china Yu-Li Qian, Present address:Center of laboratory,Women’s hospital,school of Medicine,Zhejiang university,hangzhou 310031,Zhejiang Province,china Department of Pathophysiology and Laboratory of medical Molecular Biology Zhejiang University School of Medicine Hangzhou 310031 Zhejiang Province China.

AIM: Using bacterial, yeast, or mammalian cell expressing a human drug metabolism enzyme would seem good way to study drug metabolism-related problems. Human cytochrome P-450 2C9(CYP2C9) is a polymorphic enzyme responsible for the metabolism of a large number of clinically important drugs. It ranks among the most important drug metabolizing enzymes in humans. In order to provide a sufficient amount of the enzyme for drug metabolic research, the CYP2C9 cDNA was cloned and expressed stably in CHL cells. METHODS: After extraction of total RNA from human liver tissue, the human CYP2C9 cDNA was amplified with reverse transcription-polymerase chain reaction (RT-PCR), and cloned into cloning vector pGEM-T. The cDNA fragment was identified by DNA sequencing and subcloned into a mammalian expression vector pREP9. A transgenic cell line was established by transfecting the recombinant vector of pREP9-CYP2C9 into CHL cells. The enzyme activity of CYP2C9 catalyzing oxidation of tolbutamide to hydroxy tolbutamide in S9 fraction of the cell was determined by high performance liquid chromatography(HPLC). RESULTS: The amino acid sequence predicted from the cDNA segment was identical to that of CYP2C9*1, the wild type CYP2C9. However, there were two base differences, i.e. 21T>C, 1146C>T, but the encoding amino acid sequence was the same, L7, P382. The S9 fraction of the established cell line metabolizes tolbutamide to hydroxy tolbutamide; tolbutamide hydroxylase activity was found to be 0.465 +/- 0.109 ***(-1).g(-1) S9 protein or 8.62 +/- ***(-1).mol(-1) CYP, but was undetectable in parental CHL cell. CONCLUSION: The cDNA of human CYP2C9 was successfully cloned and a cell line of CHL- CYP2C9, efficiently expressing the protein of CYP2C9, was established.

关键词： Cloning, Molecular Animals Aryl Hydrocarbon Hydroxylases Cell Fractionation Cell Line china Gene Expression Humans Hypoglycemic Agents Liver Protein Isoforms Recombinant Proteins Research Support, Non-U.S. Gov't Tolbutamide

FUNCTIONAL MODULUS OF CONTINUITY FOR BROWNIAN MOTION IN HLDER NORM

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Chinese Annals of Mathematics,Series B 2001年第2期22卷 223-232页

作者： WEI QICAI school of Economics, Zhejiang university, hangzhou 310028, china. school of Economics Zhejiang University Hangzhou 310028 China

The author establishes a large deviation for k-dimensional Brownian motion B in stronger topology, by which the functional modulus of continuity for B in Holder norm can be obtained.

关键词： Large deviations Functional modulus of continuity k-dimensional Brownian motion Holder norm

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Chiral metabolism of propafenone in rat hepatic microsomes treated with two inducers

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World Journal of Gastroenterology 2001年第6期7卷 830-835页

作者： Quan Zhou~(1,2) Tong-Wei Yao~1 Su Zeng~1 1 College of Pharmaceutical Sciences2 Second Hospital of medical school,Zhejiang university,hangzhou 310031,Zhejiang Province,china College of Pharmaceutical Sciences Zhejiang University Hangzhou Zhejiang Province China.

AIM: To study the influence of inducers of drug metabolism enzyme, beta-naphthoflavone (BNF) and dexamethasone (DEX), on the stereoselective metabolism of propafenone in the rat hepatic microsomes. METHODS: Phase I metabolism of propafenone was studied using the microsomes induced by BNF and DEX and the non-induced microsome was used as the control. The enzymatic kinetics parameters of propafenone enantiomers were calculated by regress analysis of Eadie-Hofstee Plots. Propafenone enantiomer concentrations were assayed by a chiral HPLC. RESULTS: The metabolite of propafenone, N-desalkylpropafenone, was found after incubation of propafenone with the rat hepatic microsomes induced by BNF and DEX. In these two groups, the stereoselectivity favoring R(-) isomer was observed in metabolism at low substrate concentrations of racemic propafenone, but lost the stereoselectivity at high substrate concentrations. However, in control group, no stereoselectivity was observed. The enzyme kinetic parameters were: (1) K(m). Control group: R(-) 83+/-6, S(+) 94+/-7; BNF group: R(-) 105+/-6, S(+)128+/-14; DEX group: R(-) 86+/-11, S(+) 118+/-16; (2)V(max). Control group: R(-) 0.75+/-0.16, S(+) 0.72+/-0.07; BNF group: R(-) 1.04+/-0.15, S(+)1.07+/-14; DEX group: R(-) 0.93+/-0.06, S(+) 1.04+/-0.09; (3)Cl(int). Control group: R(-) 8.9+/-1.1, S(+) 7.6+/-0.7; BNF group: R(-) 9.9+/-0.9, S(+)8.3+/-0.7; DEX group: R(-) 10.9+/-0.8, S(+) 8.9+/-0.9. The enantiomeric differences in K(m) and Cl(int) were both significant, but not in V(max), in BNF and DEX group. Whereas enantiomeric differences in three parameters were all insignificant in control group. Furthermore, K(m) and V(max) were both significantly less than those in BNF or DEX group. In the rat liver microsome induced by DEX, nimodipine (NDP) decreased the stereoselectivity in propafenone metabolism at low substrate concentration. The inhibition of NDP on the metabolism of propafenone was stereoselective with R(-)-isomer being impaired more

关键词： Animals Anti-Arrhythmia Agents Dexamethasone Male Microsomes, Liver Propafenone Rats Rats, Sprague-Dawley Research Support, Non-U.S. Gov't Stereoisomerism beta-Naphthoflavone

Asymptotics of discounted aggregate claims for renewal risk model with risky investment

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Applied Mathematics(A Journal of Chinese Universities) 2010年第2期25卷 209-216页

作者： JIANG Tao school of Finance, Zhejiang Gongshang university, hangzhou 310018, china school of Finance Zhejiang Gongshang University Hangzhou China

Under the assumption that the claim size is subexponentially distributed and the insurance surplus is totally invested in risky asset, a simple asymptotic relation of tail probability of discounted aggregate claims for renewal risk model within finite horizon is obtained. The result extends the corresponding conclusions of related references.

关键词： Discounted aggregate claims ruin probability within finite horizon renewal risk model risky investment subexponential class.

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