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Effects of combination therapy with atenolol and amlodipine on blood pressure control and stroke prevention in stroke-prone spontaneously hypertensive rats

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Acta Pharmacologica Sinica 2007年第11期28卷 1755-1760页

作者： Gang LING,Ai-jun LIU,Fu-ming SHEN,Guo-jun CAI,Jian-guo LIU,Ding-feng SU~2department of Pharmacology,School of Pharmacy second military medical university,shanghai 200433,china department of Pharmacology School of Pharmacy Second Military Medical University Shanghai China

Aim:To test the effects of atenolol and amlodipine,either alone or in combination,on blood pressure,blood pressure variability (BPV),baroreflex sensitivity (BRS),and the prevalence of stroke in stroke-prone spontaneously hypertensive rats(SHR-SP).Methods:In the first set of the study,24 8-month-old,female SHR-SPrats were randomly divided into 3 *** pressure,heart period,and BRSwere determined before and after the intragastric administration of atenolol (10mg/kg) and amlodipine (1.0 mg/kg),either alone or in *** the secondset of the study,40 male and 40 female rats were randomly assigned to 1 of thefollowing 4 groups:control,atenolol (10 mg·kg-1·d-1),amlodipine (1.0 mg·kg-1·d-1),and both (10 male and 10 female in each group).The stroke incident and survivaltime were ***:Atenolol and amlodipine,either alone or incombination,significantly decreased blood pressure,with the exception of theamlodipine-induced effect on diastolic blood ***,only the com-bination treatment significantly decreased the BPV levels for the same *** q-values calculated by the probability sum analysis were 1.17 and 2.67 forsystolic and diastolic blood pressure,respectively,and were 2.48 and 2.10 forsystolic and diastolic BPV,respectively,following *** drugexhibited any significant effect on *** and amlodipine,either alone orin combination,significantly increased the lifespan of SHR-SP,with the best ef-fect elicited by the combination ***:A significant synergismexists between atenolol and amlodipine in lowering and stabilizing blood pressurein *** therapy may be an optimal strategy for the prevention ofstroke in hypertension.

关键词： stroke hypertension stroke-prone spontaneouslyhypertensive rats atenolol amlodipine blood pressure blood pressure variability

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Interaction of Plasminogen Activator Inhibitor-2 and Proteasome Subunit, Beta Type 1

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Acta Biochimica et Biophysica Sinica 2004年第1期36卷 42-46页

作者： Jing FAN, Yu-Qing ZHANG, Ping LI, Min HOU, Li TAN, Xia WANG, and Yun-Song ZHU( department of Molecular Genetics, shanghai medical School of Fudan university, Key laboratory of Molecular medicine, Ministry of Education, shanghai 200032, china ) department of Molecular Genetics Shanghai Medical School of Fudan University Key Laboratory of Molecular Medicine Ministry of Education Shanghai 200032 China

The apoptosis protection by plasminogen activator inhibitor-2(PAI-2) is dependent on a 33 amino acid fragment between helix C and D of PAI-2 which is probably due to the interaction of PAI-2 with unknown intracellular proteins. In this study, we used the fragment between helix C and D of PAI-2 as bait to screen a HeLa cell cDNA library constructed during apoptosis in a yeast two-hybrid system and retrieved a clone encoding 241 amino acids of proteasome (prosome, macropain) subunit, beta type l(PSMβ1) which plays important roles in NF-jjjjjjjjB activation. GST-pulldown experiments confirmed the interaction between PAI-2 and PSMβ1 in vitro. These data suggest that the antiapoptosis activity of PAI-2 is probably related to its interation with PSMβ1.

关键词： plasminogen activator inhibitor type-2 proteasome (prosome, macropain) subunit, beta type 1 (PSMβ1) yeast two-hybrid system ubiquitin

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Anti-inflammatory effects of a novel peptide designed to bind with NF-κB p50 subunit

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Acta Pharmacologica Sinica 2006年第11期27卷 1474-1478页

作者： Zhen-ping WANG~2 Shao-xi CAI~(2,4)Dong-bo LIU~3 Xiang XU~3 Hua-ping LIANG~3 2 Bioengineering College,Chongqing university,Chongqing 400044,china 3 State Key laboratory of Trauma,Burns and Combined Injury,department 1,Research Institute of Surgery,Daping hospital,Third military medical university,Chongqing 400042,china Bioengineering College Chongqing University Chongqing China department 1 State Key Laboratory of Trauma Burns and Combined Injury Research Institute of Surgery Daping Hospital Third Military Medical University Chongqing China

Aim:To explore the anti-inflammatory effects of a novel peptide designed to bindwith the NF-κB p50 ***:The affinity of the peptide binding withp50 was measured with a *** of tumor necrosis factor-α(TNF-α)and interleukin 6(IL-6)from a human acute monocytic leukemia cell line(THP-1)treated with lipopolysaccharide(LPS)were measured using the ELISA method,Invivo anti-inflammatory effects of the peptide were tested with phorbol myristateacetate(PMA)-induced ear edema and zymosan A-induced peritonitis in ***:The peptide has the ability to interact with the NF-κB p50 subunit andcan effectively inhibit TNF-α and IL-6 production in the THP-1 cell line,PMA-induced ear edema and zymosan A-induced peritonitis in ***:Thepeptide may have therapeutic potential for the treatment of local acute inflammation.

关键词： NF-kB anti-inflammatory agents cytokines

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儿童注意缺陷、多动障碍的药物治疗

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中国新药与临床杂志 2004年第4期23卷 259-262页

作者：徐通周翊中国人民解放军第二军医大学附属长征医院儿科中国人民解放军第二军医大学附属长征医院儿科上海200003

注意缺陷、多动障碍 (ADHD)是儿童期最为常见的一种心理行为疾病 ,药物治疗是ADHD主要的治疗方法之一。中枢兴奋药是治疗ADHD最常用的药物 ,作用快、疗效好 ,且不良反应较少。可乐定和抗抑郁剂也有较好的治疗效果 ,可乐定主要适用于伴... 详细信息

注意缺陷、多动障碍 (ADHD)是儿童期最为常见的一种心理行为疾病 ,药物治疗是ADHD主要的治疗方法之一。中枢兴奋药是治疗ADHD最常用的药物 ,作用快、疗效好 ,且不良反应较少。可乐定和抗抑郁剂也有较好的治疗效果 ,可乐定主要适用于伴抽动或情绪异常的ADHD病儿 ,而抗抑郁剂多用于伴抑郁或焦虑的ADHD病儿 ,但不良反应较明显。本文还介绍了近年来出现的一些治疗AD HD的新药

关键词：注意力缺陷障碍伴多动中枢神经系统刺激剂可乐定抗抑郁药儿童

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A Novel Gene Delivery System Targeting Urokinase Receptor

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Acta Biochimica et Biophysica Sinica 2004年第7期36卷 485-491页

作者： Xing-Hui SUN, Li TAN, Chun-Yang LI, Chang TONG, Jin FAN, Ping LI, and Yun-Song ZHU*department of Molecular Genetics, Key laboratory of Molecular medicine of Ministry Education,shanghai medical College of Fudan university, shanghai 200032, china department of Molecular Genetics Key Laboratory of Molecular Medicine of Ministry Education Shanghai Medical College of Fudan UniversityShanghai 200032 China

Recombinant proteins that combine different functions required for cell targeting and intra- cellular delivery of DNA present an attractive approach for the development of nonviral gene delivery vectors. Here, we described a novel protein termed ATF-lys10 which facilitated cell-specific gene transfer via receptor-mediated endocytosis. ATF-lys10 was composed of the amino-terminal fragment of urokinase and ten lysines at the carboxyl terminus. Bacterially expressed ATF-lys10 protein existed in soluble form, and had antigenicity of human urokinase. Purified ATF-lys10 specifically bound to uPAR-expressing cells and formed protein-DNA complexes with plasmid pGL3-control. After neutralization of excess negative charge with poly-L-lysine, these complexes served as a specific gene delivery vector for uPAR-expressing cells. Lyso- somotropic compounds, such as chloroquine, drastically increased the ATF-lys10 mediated gene delivery efficiency. Our results suggest that the recombinant protein ATF-lys10 with the properties of DNA binding and tumor cell targeting represents a promising method for gene transfer and expression in tumor cells.

关键词： amino-terminal fragment urokinase gene transfer endocytosis urokinase receptor

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Construction and characterization of an HCV-derived multi-epitope peptide antigen containing B-cell HVR1 mimotopes and T-cell conserved epitopes

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Science china(Life Sciences) 2006年第5期49卷 490-499页

作者： GAO Jun1,2,GONG Yuping1,ZHAO Ping1,ZHU Qing3,YANG Xiaoping1 & QI Zhongtian1 1.department of Microbiology,Stake Key laboratory of medical Immunology,second military medical university,shanghai 200433,china 2.department of Gastroenterology,Changhai hospital,second military medical university,shanghai 200433,china 3.department of Epidemiology,Naval medical Research Institute,shanghai 200433,china department of Microbiology Stake Key Laboratory of Medical Immunology Second Military Medical University Shanghai 200433 China department of Gastroenterology Changhai Hospital Second Military Medical University Shanghai 200433 China department of Microbiology Stake Key Laboratory of Medical Immunology Second Military Medical University Shanghai 200433 China department of Epidemiology Naval Medical Research Institute Shanghai 200433 China

Hepatitis C (HCV) genome is highly variable, particularly in the hypervariable region 1 (HVR1) of its E2 envelope gene. The variability of HCV genome has been a major obstacle for developing HCV vaccines. Due to B-cell HVR1 mimotopes mimicking the antigenicity of natural HVR1 epitopes; some T-cell epitopes from the consensus sequence of HCV genes conserving among the different HCV genotypes, we synthesized an minigene of HCV-derived multi-epitope peptide antigen (CMEP), which contains 9 B-cell HVR1 mimotopes in E2, 2 conserved CTL epitopes in C, 1 conserved CTL epitope in NS3; 1 conserved Th epitope in NS3. This minigene was cloned into a GST expression vector to generate a fusion protein GST-CMEP. The immunogenic properties of CEMP were characterized by HCV infected patients’ sera,; found that the reactivity frequency reached 75%. The cross reactivity of anti-CEMP antibody with different natural HVR1 variants was up to 90%. Meanwhile, we constructed an HCV DNA vaccine candidate, plasmid pVAX1.0-st-CMEP carrying the recombinant gene (st) of a secretion signal peptide; PADRE universal Th cell epitope sequence in front of the CMEP minigene. Immunization of rabbits with pVAX1.0-st-CMEP resulted in the production of antibody, which was of the same cross reactivity as the fusion protein GST-CMEP. Our findings indicate that the HCV-derived multi-epitope peptide antigen in some degree possessed the characteristics of neutralizing HCV epitopes,; would be of the value as a candidate for the development of HCV vaccines.

关键词： hepatitis C virus multi-epitope peptide HVR1 mimotopes T-cell conserved epitopes

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Corticosterone activates Erk1/2 mitogen-activated protein kinase in primary hippocampal cells through rapid nongenomic mechanism

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Progress in Natural Science:Materials International 2005年第4期 38-43页

作者： QI Aiqun 1, QIU Jian 1, XIAO Lin 2 and CHEN Yizhang 2,3 *(1. department of Physiology, second military medical university, shanghai 200433, china 2. department of Neurobiology, second military medical university, shanghai 200433, china 3. Institute of Neuroscience, second military medical university, shanghai 200433, china) department of Physiology，second military medical university，shanghai 200433，china department of Neurobiology，second military medical university，shanghai 200433，china department of Neurobiology，second military medical university，shanghai 200433，china Institute of Neuroscience，second military medical university，shanghai 200433，china

Nongenomic effects of glucocorticoids (GC) in various cell types have been well documented, but it still remains unknown whether the mechanism also works in hippocampus which is a crucial target of glucocorticoids in neural system during physiological and/or pathophysiological processes. We present here that corticosterone (B) could rapidly activate Erk1/2 mitogen activated protein kinase (MAPK) in primarily cultured hippocampal cells within minutes, with a bell shaped time dependent curve which peaked at 15min and then went down to normal level in 30 min. This activation was blocked by protein kinase C (PKC) inhibitor (G6976), G protein inhibitor (GDPs), and MEK(MAPK/extracellular signal regulated kinase kinase) inhibitor(PD98059), but not by protein kinase A (PKA) inbibitor (H89), tyrosine kinase inhibitor (genistein), and glucocorticoid receptor (GR) antagonist (RU38486). Thus, the rapid activation of Erk1/2 MAPK in primary hippocampal cells induced by B was likely mediated by a G protein coupled receptor (GPCR) pathway with involvement of PKC, which belonged to the nongenomic rather than genomic mechanism of GC's effects.

关键词： glucocorticoid MAPK rapid effects nongenomic mechanism.

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Molecular cloning and characterization of a 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase Gene from Cephalotaxus harringtonia

Molecular cloning and characterization of a 2C-methyl-D-eryt...

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中华中医药学会第九届中药鉴定学术会议

作者： Junfeng Chen~1,Wansheng Chen~2,Lei Zhang~1 1 department of Pharmacy,changzheng hospital,second military medical university, shanghai 200003,china 2 department of Pharmacognosy,School of Pharmacy,second military medical university, shanghai 200433,china

The full-length MECPS cDNA sequence(designated as Chmecps,GenBank accession No.:DQ415658) was isolated by rapid amplification of cDNA ends(RACE) for the first time from Cephalotaxus *** full-length cDNA of Chmecps was 1146 bp containing a 753 bp open reading frame(ORF) encoding a polypeptide of 250 amino acids with a calculated mass of 26.67 kDa and an isoelectric point of *** and bioinformatics analyses revealed that ChMECPS showed extensive homology with MECPSs from other plant *** analysis indicated ChMECPS was more ancient than other plant *** hybridization analysis of the genomic DNA showed that Chmecps was a single copy *** expression pattern analysis revealed that ChMECPS expressed strongly in root and leaf,weakly in stem.

关键词： 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase(MECPS) Cephalotaxus harringtonia Non-mevalonate pathway(MEP) rapid amplification of cDNA ends(RACE)

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Detection of germline mutations of hMLH1 and hMSH2 based on cDNA sequencing in china

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World Journal of Gastroenterology 2005年第42期11卷 6620-6623页

作者： Chao-Fu Wang, Xiao-Yan Zhou, Tai-Ming Zhang, Meng-Hong Sun, Da-Ren Shi, laboratory of Molecular Pathology, Cancer hospital of Fudan university department of Oncology, shanghai medical College of Fudan university, shanghai 200032, china laboratory of Molecular Pathology Cancer Hospital of Fudan University Shanghai 20032 China.

AIM： TO detect the germline mutations Of hMLH1 and hMSH2 based on mRNA sequencing to identify hereditary non polyposis oolorectal cancer （HNPCC） families. METHODS： Total RNA was extracted from peripberal blood of 14 members from 12 different families fulfilling Amsterdam criteria II. mRNA of hMLH1 and hMSH2 was reversed with special primers and heat-resistant reverse tmnscriptase, cDNA was amplified with expand long template PCR and cDNA sequendng analysis was followed. RESULT： Seven germline mutations were found in 6 families （6/12, 50%）, in 4 hMLH1 and 3 hMSH2 mutations （4/12, 33.3%）; （3/12, 25%）. The mutation types involved 4 missense, 1 silent and 1 frame shift mutations as well as 1 mutation in the non-coding area. Four out of the seven mutations have not been reported previously. The 4 hMLH1 mutations were distributed in exons 8, 12, 16, and 19. The 3 hMSH2 mutations were distributed in exons 1 and 2. Six out of the 7 mutations were pathological, which were dislTibuted in 5 HNPCC families. CONCLUSION： Germline mutations of hMLH1 and hMSH2 can be found based on cDNA sequencing so as to identify HNPCC family, which is highly sensitive and has the advantages of cost and time saving.

关键词： hMLH1 hMSH2 Colorectal cancer Hereditarynon-polyposis Reverse transcription Germline mutation

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The Technique of Standards and Specimens in Biomedical EDX Quantitative Microanalysis

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电子显微学报 1991年第2期 209-210页

作者： Yang Yongji Zheng Zhun Xia YuanyaoThe second military medical university department of Centrallaboratory shanghai P.R.china

EDX quantitative microanalysis has been extensively appliedto the area of biomedicine. The accuracy of EDX quantitativemicroanalysis depends on suitable standards and preparation ***,it is difficult to get suitable standards andto prepare specimens for biomedical EDX quantitativemicroanalysis. We have done some works in the preparingstandards and specimens. We will introduce the preparation ofstandards and specimens from the two ways.

关键词： EDX

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