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Signal

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SignalSignal

    Signal

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    ;ActaPharmacolSin2003Apr;23(4):342?381

    ;SUNRenShan,CHENGTian-Min,HAOFei

    ;DepartmentofDermatology,SouthwestHospital,ThirdMilitary ;MedicalUniversity,Chongqing400038,China ;A?:Todesignsomecompoundswhichpossessthe ;capacitytoinhibitmastcelldegranulation.MTHoDS:

    ;Asetofisoquinolinecompoundsofanti..mastcellde.. ;granulationwasinvestigatedby3D-QSAR.Their ;pharmacophoremodelwasidentifiedbyDISCO ;program.Accordingtothepharmacophoremode1.3D

    ;QSARmodelsfortheactivityandtoxicitywerebuiltby ;Co】?FA.RESU[‘s:ThecrossvalidatedRcv2andnon-

    ;crossvalidatedR2(correlationcoefficient)forthestruc. ;ture.activityandstructure.toxicitymodelswere0.654 ;and0.662,0.990and0.983,respectively.Tlleconfi. ;dencelevelsofallthesemodelswereallover99%by ;referringstatisticsFtable.Thesemodelsshowedre1. ;evantandhighpredictability.CONCLUSIoN:New ;bioactiveleadcompoundsweredesignedonthebasis ;ofthesemodels.Theirpredictedactivitiesarehigher ;andpredictedtoxicityislowerthantheknown ;compounds.ThesynthesisofthesellOwcompounds ;lsinprogress.

    ;P?39SignaltransductionofTNF-alphainduced ;cardioprotectioninhypoxic/reoxygenation ;FUChen,XIAQiang,CAOChurl-Mei,JIANGHui-Di ;DepartmentofPhysiology,ZhejiangUniversitySchoolofMe~cine,

    ;Hangzl,wu310031,China

    ;AIM:Tumornecrosisfactor-a(TNF.01couldreduce

    ;myocardialischemia/reperfusioninjurybyactivating ;manganesesuperoxidedismutase(MnSOD).However, ;themechanismoftheMnSODactivationbyTNF-0is

    ;poodyunderstood.Sointhepresentstudywetriedto ;determinetheroleofreactiveoxygenspeciesandmito. ;chondrialATP-sensitivepotassium(K)channelsin ;mediatingthiseffectinculturedcardiomyocytesdur.

    ;ingsimulatedhypoxia/reoxygenation(H/R). ;HoDS:Neonatalratventricularmyocyteswere ;pretreatedwitll1NF-0ordiazoxideforl2handthen

    ;subjectedtocontinuoushypoxiafor12h,foilowedby ;reoxygenationfor6h.Inanotherseriesofexperiments, ;beforeH,R,themyocyteswerefirstpretreatedwith ;mitoehondrialantioxidaatN-acetylcysteinerNAC),mi. ;tochondrialelectrontransportinhibitorsantimycinA, ;specificnitricoxidesynthaseinhibitor-nitro-L-argi- ;ninemethylester(L-NAM1ormitochondrialselective

    ;KA11Pchannelinhibitor5-hydroxydecanoic(5-IID)for3 ;h,fbUowedby12hof1NF-0(100kU)pretreatment.

    ;TheMnSODactivityofthecellwasmeasuredafter ;hypoxia/reoxygenation.Ceumjurywasassessedinterms ;oflacticdehydrogenase(LDH)release.RESIJIS: ;TNF-0(10,50,100,or500kU/L)significantlyin- ;creasedtheMnSODactivityandreducedLDHrelease ;ofneonatalratventricularmyocytes.Diazoxide(50 ;~tmol/L),aselectiveopenerofthemitochondrialK

    ;channe1.decreasedtheLDHreleasebutdidnotelevate ;MnSODactivityofthemyocytes.Pretreatmentwith ;NAC(50~tmol/L),anfimycinA(50pmol/L),N

    ;(100~tmol/L),or5?D(100)tmol/L)attenuatedthein-

    ;creaseofMnSODactivityandreductionofLDHlevel ;inducedby1IF.0.CoNCLUSIoN:NF-0induces

    ;cardioprotectionviaoxygenradicalsignalsandactiva- ;tionofmitochondrialKATPchannels.Throughthisin. ;tracellularsignalingpathway.T0inducesMnSOD

    ;activityandattenuatesLDHreleaseincultured ;cardiomyocytes.

    ;P-40EffectsofhuperzineAandE2020onlearning ;andmemoryrelatedgeneexpressioninhippocam- ;pusofsenescence-acceleratedmice

    ;ZHOUWen-Xia,ZHANGYong-Xiang

    ;BeifingInstituteofPharmacologyandToxicology,BeOmg100850, ;China

    ;AM:T0studytheeffectsofhuperzineAandE2020. ;twocholinesteraseinhibitors,whicharebeingusedin ;thetreatmentofAlzheimer’sdisease(AD),onlearning

    ;andmemoryrelatedgeneexpressioninhippocampus ;ofsenescence-acceleratedmicerSAM).E’I田【oDS:

    ;HippocampiweredissectedandthetotalRNAwasiso- ;latedfromthetissue.Theexpressionofthegenesin. ;cludingmineralocorticoidreceptor(MR),presenilinl

    ;and2(PS-landPS.2),tau,amyloidprecursorprotein ;(APP),apoproteinE(apoE)andbcl-2inthehippocam- ;pusofSAMweredeterminedbyreversetranscription ;polymerasechainreaction(RT.PCR).Theeffectof ;huperzineAandE2O2Oonhippocampalgeneexpres- ;sionswerethenstudied.RESU1S:Theexpression ;levelsofhippocampalgenesincludingMR,tau,PS-2, ;andAPPin5.month-oldSAM.prone/8(SAMP8),ase- ;

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