-
簡介:BIOLOGICALACTIVITIESOFCURCUMINANDITSANALOGUESCONGENERSMADEBYMANANDMOTHERNATUREPREETHAANANDA,SHERINGTHOMASB,AJAIKUMARBKUNNUMAKKARAA,CHITRASUNDARAMA,KUZHUVELILBHARIKUMARA,BOKYUNGSUNGA,SHEEJATTHARAKANA,KRISHNAMISRAC,INDIRAKPRIYADARSINID,KALLIKATNRAJASEKHARANB,BHARATBAGGARWALA,ACYTOKINERESEARCHLABORATORY,DEPARTMENTOFEXPERIMENTALTHERAPEUTICS,UNIT143,THEUNIVERSITYOFTEXASMDANDERSONCANCERCENTER,1515HOLCOMBEBOULEVARD,HOUSTON,TX77030,USABDEPARTMENTOFCHEMISTRY,UNIVERSITYOFKERALA,THIRUVANANTHAPURAM,INDIACBIOINFORMATICSDIVISION,INDIANINSTITUTEOFINFORMATIONTECHNOLOGY,ALLAHABAD,INDIADRADIATIONANDPHOTOCHEMISTRYDIVISION,BHABHAATOMICRESEARCHCENTRE,MUMBAI400085,INDIA1INTRODUCTIONCURCUMIN,COMMONLYCALLEDDIFERULOYLMETHANE,ISAHYDROPHOBICPOLYPHENOLDERIVEDFROMTHERHIZOMETURMERICOFTHEHERBCURCUMALONGATURMERICHASBEENUSEDTRADITIONALLYFORMANYAILMENTSBECAUSEOFITSWIDESPECTRUMOFPHARMACOLOGICALACTIVITIESCURCUMINHASBEENIDENTIFIEDASTHEACTIVEPRINCIPLEOFTURMERICCHEMICALLY,ITISABISA,BUNSATURATEDBDIKETONETHATEXHIBITSKETOENOLTAUTOMERISMCURCUMINHASBEENSHOWNTOEXHIBITANTIOXIDANT,ANTIINFLAMMATORY,ANTIMICROBIAL,ANDANTICARCINOGENICACTIVITIESITALSOHASHEPATOPROTECTIVEANDNEPHROPROTECTIVEACTIVITIES,SUPPRESSESTHROMBOSIS,PROTECTSAGAINSTMYOCARDIALINFARCTION,ANDHASHYPOGLYCEMICANDANTIRHEUMATICPROPERTIESMOREOVER,CURCUMINHASBEENSHOWNINVARIOUSANIMALMODELSANDHUMANSTUDIESTOBEEXTREMELYSAFEEVENATVERYHIGHDOSES1–12INBIOCHEMICALPHARMACOLOGY7620081590–1611ARTICLEINFOARTICLEHISTORYRECEIVED27JUNE2008ACCEPTED7AUGUST2008KEYWORDSCURCUMINSYNTHETICANALOGUESBIOAVAILABILITYLIPOSOMESNANOPARTICLESABSTRACTCURCUMIN,AYELLOWPIGMENTPRESENTINTHEINDIANSPICETURMERICASSOCIATEDWITHCURRYPOWDER,HASBEENLINKEDWITHSUPPRESSIONOFINFLAMMATIONANGIOGENESISTUMORIGENESISDIABETESDISEASESOFTHECARDIOVASCULAR,PULMONARY,ANDNEUROLOGICALSYSTEMS,OFSKIN,ANDOFLIVERLOSSOFBONEANDMUSCLEDEPRESSIONCHRONICFATIGUEANDNEUROPATHICPAINTHEUTILITYOFCURCUMINISLIMITEDBYITSCOLOR,LACKOFWATERSOLUBILITY,ANDRELATIVELYLOWINVIVOBIOAVAILABILITYBECAUSEOFTHEMULTIPLETHERAPEUTICACTIVITIESATTRIBUTEDTOCURCUMIN,HOWEVER,THEREISANINTENSESEARCHFORA‘‘SUPERCURCUMIN’’WITHOUTTHESEPROBLEMSMULTIPLEAPPROACHESAREBEINGSOUGHTTOOVERCOMETHESELIMITATIONSTHESEINCLUDEDISCOVERYOFNATURALCURCUMINANALOGUESFROMTURMERICDISCOVERYOFNATURALCURCUMINANALOGUESMADEBYMOTHERNATURESYNTHESISOF‘‘MANMADE’’CURCUMINANALOGUESREFORMULATIONOFCURCUMINWITHVARIOUSOILSANDWITHINHIBITORSOFMETABOLISMEG,PIPERINEDEVELOPMENTOFLIPOSOMALANDNANOPARTICLEFORMULATIONSOFCURCUMINCONJUGATIONOFCURCUMINPRODRUGSANDLINKINGCURCUMINWITHPOLYETHYLENEGLYCOLCURCUMINISAHOMODIMEROFFERULOYLMETHANECONTAININGAMETHOXYGROUPANDAHYDROXYLGROUP,AHEPTADIENEWITHTWOMICHAELACCEPTORS,ANDANA,BDIKETONESTRUCTURALHOMOLOGUESINVOLVINGMODIFICATIONOFALLTHESEGROUPSAREBEINGCONSIDEREDTHISREVIEWFOCUSESONTHESTATUSOFALLTHESEAPPROACHESINGENERATINGA‘‘SUPERCURCUMIN’’2008ELSEVIERINCALLRIGHTSRESERVEDCORRESPONDINGAUTHORTEL17137921817FAX17137456339EMAILADDRESSAGGARWALMDANDERSONORGBBAGGARWALAVAILABLEATWWWSCIENCEDIRECTCOMJOURNALHOMEPAGEWWWELSEVIERCOM/LOCATE/BIOCHEMPHARM00062952/–SEEFRONTMATTER2008ELSEVIERINCALLRIGHTSRESERVEDDOI101016/JBCP200808008DIKETONELINKINTHISMOLECULE,THEA,BUNSATURATEDBDIKETONEMOIETYOFCURCUMINISREPLACEDBYANA,BUNSATURATEDDIHYDROPYRANONEMOIETYTODATE,NOTMANYBIOLOGICALSTUDIESONCYCLOCURCUMINHAVEBEENREPORTEDINONESTUDY,SIMONETAL14REPORTEDTHATTHISANALOGUEWASINEFFECTIVEININHIBITINGMCF7TUMORCELLPROLIFERATIONANDARRESTOFCELLCYCLEPROGRESSIONINTHELASTFEWDECADES,EFFORTSHAVEBEENMADETOISOLATECURCUMINOIDSFROMDIFFERENTSOURCES,INCLUDINGCURCUMALONGA,CURCUMAZEDOARIA,ANDCURCUMAAROMATICASEVERALRESEARCHGROUPSHAVEINVESTIGATEDANDCOMPAREDTHEIRANTIOXIDANT,CARDIOPROTECTIVE,NEUROPROTECTIVE,ANTIDIABETIC,ANTITUMOR,ANDCHEMOPREVENTIVEACTIVITIES,EMPLOYINGTHEMEITHERINDIVIDUALLYORASMIXTURESTHECURCUMINOIDSHAVEBEENSHOWNTOBESCAVENGERSOFFREERADICALSANDREACTIVEOXYGENSPECIESROS,SUCHASHYDROXYLRADICALS,SUPEROXIDERADICALS,SINGLETOXYGEN,PEROXYLRADICALS,ANDPEROXYNITRITE,WHOSEPRODUCTIONISIMPLICATEDINTHEINDUCTIONOFOXIDATIVESTRESSTABLE1–ACTIVITIESOFCURCUMINANALOGUESDERIVEDFROMTURMERICANDOFCURCUMINMETABOLITES?BDMCISMOREACTIVETHANDMCORCURCUMINFORCYTOTOXICITYAGAINSTOVARIANCANCERCELLS32?BDMCISLESSACTIVETHANCURCUMINORDMCASANANTIOXIDANTANDASANOXIDATIVEDNACLEAVINGAGENT15?BDMCISLESSACTIVETHANCURCUMINORDMCASANINHIBITOROFPEROXYNITRITESCAVENGER16?BDMCWASMOSTACTIVEWHENCOMPAREDWITHDMCORCURCUMINFORANTIMUTAGENICANDANTICARCINOGENICACTIVITY31?BDMCISMOREACTIVETHANCURCUMINORDMCFORANTITUMORANDANTIOXIDANTACTIVITY24?BDMCISMOREACTIVETHANCURCUMINORDMCFORSUPPRESSIONOFCARCINOGENESIS31?BDMCWASMOREACTIVETHANCURCUMINFORREDUCINGNICOTINEINDUCEDOXIDATIVESTRESS121?BDMCIMPROVEDINNATEIMMUNITYANDTRANSCRIPTIONOFMGATIIIANDTOLLLIKERECEPTORSINADPTS29?BDMCISMOREACTIVETHANCURCUMINFORMODULATIONOFMDR1GENE58?BDMCISLESSACTIVETHANCURCUMINORDMCININHIBITINGSINGLETOXYGENINDUCEDDNADAMAGE18?BDMCISLESSACTIVETHANCURCUMINORDMCINBINDINGANDINHIBITINGPGPANDSENSITIZINGCELLSTOVINBLASTIN35?BDMCISLESSACTIVETHANCURCUMINORDMCINBINDINGANDINHIBITINGMRP1ANDSENSITIZINGCELLSTOETOPOSIDE37?BDMCWASMOREACTIVETHANCURCUMINORDMCINPROTECTINGNERVEANDENDOTHELIALCELLSFROMBETAAMYLOIDINDUCEDOXIDATIVESTRESS27?BDMCPREVENTSDMHINDUCEDCOLONCARCINOGENESIS67?BDMCISASACTIVEASCURCUMININPREVENTINGDMHINDUCEDCOLONCARCINOGENESIS36?BDMCISMOREACTIVETHANCURCUMININPREVENTINGALCOHOLANDPUFAINDUCEDOXIDATIVESTRESS99?BDMCISMOREACTIVETHANCURCUMININPREVENTINGCCL4INDUCEDHEPATOTOXICITYINRATS122?BDMCISMOREACTIVETHANCURCUMININPREVENTINGALCOHOLANDPUFAINDUCEDCHOLESTEROL,TGS,PLSANDFFA104?BDMC,CURCUMIN,ANDDMCEXHIBITEQUIVALENTACTIVITYINSUPPRESSIONOFBLOODGLUCOSELEVELSINDIABETICMICETHROUGHBINDINGTOPPARG25?BDMCISLESSACTIVETHANCURCUMINANDDMCINPROTECTINGRATSFROMLEADINDUCEDNEUROTOXICITY28?BDMCISLESSACTIVETHANCURCUMINANDDMCINSUPPRESSINGNFKBACTIVATION30?BDMCISMOREACTIVETHANDMCORCURCUMINININDUCINGNRF2MEDIATEDINDUCTIONOFHEMEOXYGENASE136?BDMCISLEASTACTIVETHANDMCORCURCUMINININDUCINGP38MAPKMEDIATEDINDUCTIONOFHEMEOXYGENASE123?BDMCISLEASTACTIVETHANDMCORCURCUMINININHIBITINGH2O2INDUCEDLIPIDPEROXIDATIONANDHEMOLYSISOFEYTHROCYTES21?BDMCISLEASTACTIVETHANDMCORCURCUMINININHIBITINGTHEPROLIFERATIONOFVSMCINDUCEDBYOXLDLANDINDUCTIONOFLDLR21?BDMCISLEASTACTIVETHANDMCORCURCUMINININHIBITINGTHELIPOSOMALPEROXIDATIONANDOFCOX1ANDCOX2ACTIVITY20?DMCISMOREPOTENTTHANCURCUMIN,BDMCANDCYCLOCURCUMINININHIBITINGPROLIFERATIONOFBREASTCANCERCELLS14?DMCISMOREPOTENTTHANCURCUMINANDBDMCININDUCINGNEMATOCIDALACTIVITY13?THCISLESSPOTENTTHANCURCUMINININHIBITINGTHEACTIVITYOF5LOXBUTMOREPOTENTTHANCURCUMINININHIBITINGCOXDEPENDENTARACHIDONICACIDMETABOLISM60?THCISMOREACTIVETHANCURCUMININPREVENTINGDMHINDUCEDACFFORMATIONINMICE61?THCDOESNOTINDUCESROSPRODUCTIONANDMEMBRANEMOBILITYCOEFFICIENTBUTCURCUMINDOES185?THCISLESSACTIVETHANCURCUMININPREVENTINGPMAINDUCEDSKINTUMORPROMOTIONINMICE33?THCISMOREACTIVETHANCURCUMINASANANTIOXIDANT39THCISLESSACTIVETHANCURCUMINASANANTIOXIDANT186?THCISLESSACTIVEUNDERAERATEDCONDITIONTHANCURCUMINBUTUNDERN2OPURGEDCONDITIONS,THCISMOREACTIVETHANCURCUMININSUPPRESSINGRADIATIONINDUCEDLIPIDPEROXIDATION41?THCWASLESSACTIVETHANCURCUMIN,DMCORBDMCINSUPPRESSINGNFKBACTIVATION30?THC,HHC,OHCARELESSACTIVETHANCURCUMININSUPPRESSINGNFKBACTIVATION59?THCISMOREACTIVETHANCURCUMININSUPPRESSINGNITRILOTRIACETATEINDUCEDOXIDATIVERENALDAMAGE43?THCISMOREACTIVETHANCURCUMININPROTECTINGFROMCHLOROQUINEINDUCEDHEPATOTOXICITYINRATS45?THCISMOREACTIVETHANCURCUMININPREVENTINGBRAINLIPIDPEROXIDATIONINDIABETICRATS51?THCISMOREPOTENTTHANCURCUMINFORANTIOXIDANTANDANTIDIABETICEFFECTSINRATS48?THCISMOREPOTENTTHANCURCUMINFORMODULATIONOFRENALANDHEPATICFUNCTIONALMARKERSINDIABETICRATS56?THCISMOREPOTENTTHANCURCUMINFORMODULATIONOFBLOODGLUCOSE,PLASMAINSULINANDERYTHROCYTETBARSINDIABETICRATS55?THCISMOREPOTENTTHANCURCUMININDECREASINGBLOODGLUCOSEANDINCREASINGPLASMAINSULININDIABETICRATS50?THCISLESSPOTENTTHANCURCUMININMODULATIONOFABCDRUGTRANSPORTERS58?THC’SEFFECTWASCOMPARABLEWITHCURCUMINONREDUCTIONOFACCUMMULATIONANDCROSSLINKINGOFCOLLAGENINDIABETICRATS53?THCEXHIBITSSTRONGERANTIOXIDANTACTIVITYTHANHHCOHCCURCUMINDMCBDMC17?THCWASMOREPOTENTTHANCURCUMININSUPPRESSINGLDLOXIDATION42?THCISMOREACTIVETHANCURCUMININSUPPRESSINGLIPIDPEROXIDATIONOFERYTHROCYTEMEMBRANEGHOSTS40?CYCLOCUREXHIBITSWEEKANTICANCERACTIVITY14NOTEBDMC,BISDEMETHOXYCURCUMINCOX,CYCLOOXYGENASEDMC,DEMETHOXYCURCUMINHHC,HEXAHYDROCURCUMINLDL,LOWDENSITYLIPOPROTEINSNFKB,NUCLEARFACTORKAPPABOHC,OCTAHYDROCURCUMINROS,REACTIVEOXYGENSPECIESTHC,TETRAHYDROCURCUMINBIOCHEMICALPHARMACOLOGY7620081590–16111592
下載積分: 10 賞幣
上傳時間:2024-03-13
頁數(shù): 22
大?。?1.23(MB)
子文件數(shù):
-
簡介:NATUREBIOTECHNOLOGYVOL18NOVEMBER2000HTTP//BIOTECHNATURECOM1151BIOPHARMACEUTICALSHAVETRADITIONALLYBEENPRODUCEDUSINGAVARIETYOFTRANSGENICSYSTEMS,INCLUDINGCULTUREDMAMMALIANCELLS,BACTERIA,ANDFUNGI1–3INTHEFUTURE,DEMANDFOREXISTINGBIOPHARMACEUTICALSEG,ERYTHROPOIETINTOTREATANEMIAANDINSULINTOTREATDIABETES,ASWELLASNEWTHERAPEUTICPROTEINSDISCOVEREDTHROUGHGENOMICSEFFORTS,ISEXPECTEDTORISECONSIDERABLY2ITISPRUDENT,THEREFORE,TOEVALUATEALTERNATIVETRANSGENICPRODUCTIONSYSTEMSANDDETERMINEHOWTHEFUTUREAVAILABILITYOFSAFERECOMBINANTBIOPHARMACEUTICALSCANBEENSUREDINACOSTEFFECTIVEMANNERPRODUCINGTHERAPEUTICPROTEINSINPLANTSHASMANYECONOMICANDQUALITATIVEBENEFITS,INCLUDINGREDUCEDHEALTHRISKSFROMPATHOGENCONTAMINATION,COMPARATIVELYHIGHYIELDS,ANDPRODUCTIONINSEEDSOROTHERSTORAGEORGANS2THECULTIVATION,HARVESTING,STORAGE,ANDPROCESSINGOFTRANSGENICCROPSWOULDALSOUSEANEXISTINGINFRASTRUCTUREANDREQUIRERELATIVELYLITTLECAPITALINVESTMENT2–4,MAKINGTHECOMMERCIALPRODUCTIONOFBIOPHARMACEUTICALSANEXCITINGPROSPECTPLANTSAREPOTENTIALLYACHEAPSOURCEOFRECOMBINANTPRODUCTS4–6KUSNADIETAL7HAVEESTIMATEDTHATTHECOSTOFPRODUCINGRECOMBINANTPROTEINSINPLANTSCOULDBE10TO50FOLDLOWERTHANPRODUCINGTHESAMEPROTEINBYESCHERICHIACOLIFERMENTATION,DEPENDINGONTHECROPMANYRECOMBINANTTHERAPEUTICPROTEINSAREPRODUCEDUSINGMAMMALIANEXPRESSIONSYSTEMSABIGADVANTAGEOFTHESE,ANDOFINSECTTISSUECULTURESYSTEMS,ISTHATTHEYCORRECTLYSYNTHESIZEANDPROCESSMAMMALIANPRODUCTSHOWEVER,PRODUCTYIELDSAREGENERALLYLOW,ANDTHEREQUIREMENTFORFETALBOVINESERUMINTHEGROWTHMEDIUMMAKESPRODUCTIONEXPENSIVE2INADDITION,CULTUREDMAMMALIANCELLSARESENSITIVETOSHEARFORCESTHATOCCURDURINGINDUSTRIALSCALECULTURE,ANDTOVARIATIONSINTEMPERATURE,PH,DISSOLVEDOXYGEN,ANDCERTAINMETABOLITESTHISMAKESITNECESSARYTOCONTROLCULTURECONDITIONSCAREFULLY,BECAUSEVARIATIONINCELLGROWTHCANAFFECTFERMENTATIONANDPRODUCTPURITYALTHOUGHBACTERIALANDFUNGALSYSTEMSAREMOREROBUST,THEYARENOTIDEALFORSYNTHESIZINGMANYMAMMALIANPROTEINSBECAUSEOFDIFFERENCESINMETABOLICPATHWAYS,PROTEINPROCESSING,CODONUSAGE,ANDTHEFORMATIONOFINCLUSIONBODIES3ALTHOUGHSOMEDIFFERENCESEXISTINPOSTTRANSLATIONPROCESSINGANDINCODONUSAGEBETWEENPLANTSANDMAMMALS,THESEAREFEWCOMPAREDWITHDIFFERENCESBETWEENMAMMALSANDMICROORGANISMS2,8,9WHEREDIFFERENCESINPROCESSINGDOREPRESENTAPROBLEM,ITMAYBEPOSSIBLETOENGINEERPLANTSWITHALTEREDPROTEINMATURATIONPATHWAYS3,10BIOPHARMACEUTICALSPRODUCEDINCELLCULTURESYSTEMSHAVETOBEPURIFIEDFROMTHECULTURESUPERNATANT,ANEXPENSIVEPROCESSPLANTSCANBEMADETOSTOREPROTEINSINSEEDENDOSPERM,FROMWHERETHEYCANBEEASILYEXTRACTED2,11NEVERTHELESS,PURIFICATIONISPOTENTIALLYANEXPENSIVESTEP,ANDVARIOUSMETHODSAREBEINGDEVELOPEDTOOVERCOMETHISPROBLEM,INCLUDINGTHEEXPRESSIONOFPROTEINSASFUSIONSWITHOLEOSINSEEDISCUSSIONBELOWFORHIRUDIN4–6ANALTERNATIVEAPPROACHISTOCOVERTHECOSTSOFPURIFICATIONWITHTHEINCOMEFROMTHEEXTRACTIONOFCONVENTIONALPRODUCTS,SUCHASMEAL,OIL,ORSTARCHTHECOSTSOFISOLATINGHUMANSERUMALBUMINFROMSTARCHPOTATOES,FOREXAMPLE,COULDBELARGELYCOVEREDBYCONCOMITANTSTARCHPRODUCTION4,5,12INADDITION,PURIFICATIONMAYNOTALWAYSBENECESSARY,FOREXAMPLE,INTHECASEOFEDIBLEVACCINESPLANTDERIVEDPRODUCTS,WHETHERPURIFIEDORNOT,ARELESSLIKELYTOBECONTAMINATEDWITHHUMANPATHOGENICMICROORGANISMSTHANTHOSEDERIVEDFROMANIMALCELLS,BECAUSEPLANTSDON’TACTASHOSTSFORHUMANINFECTIOUSAGENTS13INTHISSHORTREVIEW,WEOUTLINETHEMAINTYPESOFPLANTEXPRESSIONSYSTEMSEMPLOYEDFORTHEAGRICULTURALPRODUCTIONOFBIOPHARMACEUTICALSANDPROVIDEANOVERVIEWOFTHETYPESOFVACCINE,ANTIBODY,ANDTHERAPEUTICPROTEINPRODUCTSCURRENTLYUNDERDEVELOPMENTFORAREVIEWONFOREIGNPROTEINPRODUCTIONINPLANTTISSUECULTURE,SEEREF14AGRICULTURALPRODUCTIONSYSTEMSTWOTRANSFORMATIONAPPROACHESARECOMMONLYUSEDTOPRODUCERECOMBINANTPHARMACEUTICALSINPLANTS8,10,15–17INTHEFIRST,STABLYTRANSGENICPLANTSASFACTORIESFORBIOPHARMACEUTICALSGLYNISGIDDINGS,GORDONALLISON,DOUGLASBROOKS,ANDADRIANCARTERINSTITUTEOFBIOLOGICALSCIENCES,UNIVERSITYOFWALES,ABERYSTWYTH,CLEDWYNBUILDING,ABERYSTWYTHCEREDIGIONSY233DD,UKCORRESPONDINGAUTHORGDGABERACUKRECEIVED12NOVEMBER1999ACCEPTED11AUGUST2000PLANTSHAVECONSIDERABLEPOTENTIALFORTHEPRODUCTIONOFBIOPHARMACEUTICALPROTEINSANDPEPTIDESBECAUSETHEYAREEASILYTRANSFORMEDANDPROVIDEACHEAPSOURCEOFPROTEINSEVERALBIOTECHNOLOGYCOMPANIESARENOWACTIVELYDEVELOPING,FIELDTESTING,ANDPATENTINGPLANTEXPRESSIONSYSTEMS,WHILECLINICALTRIALSAREPROCEEDINGONTHEFIRSTBIOPHARMACEUTICALSDERIVEDFROMTHEMONETRANSGENICPLANTDERIVEDBIOPHARMACEUTICAL,HIRUDIN,ISNOWBEINGCOMMERCIALLYPRODUCEDINCANADAFORTHEFIRSTTIMEPRODUCTPURIFICATIONISPOTENTIALLYANEXPENSIVEPROCESS,ANDVARIOUSMETHODSARECURRENTLYBEINGDEVELOPEDTOOVERCOMETHISPROBLEM,INCLUDINGOLEOSINFUSIONTECHNOLOGY,WHICHALLOWSEXTRACTIONWITHOILBODIESINSOMECASES,DELIVERYOFABIOPHARMACEUTICALPRODUCTBYDIRECTINGESTIONOFTHEMODIFIEDPLANTPOTENTIALLYREMOVESTHENEEDFORPURIFICATIONSUCHBIOPHARMACEUTICALSANDEDIBLEVACCINESCANBESTOREDANDDISTRIBUTEDASSEEDS,TUBERS,ORFRUITS,MAKINGIMMUNIZATIONPROGRAMSINDEVELOPINGCOUNTRIESCHEAPERANDPOTENTIALLYEASIERTOADMINISTERSOMEOFTHEMOSTEXPENSIVEBIOPHARMACEUTICALSOFRESTRICTEDAVAILABILITY,SUCHASGLUCOCEREBROSIDASE,COULDBECOMEMUCHCHEAPERANDMOREPLENTIFULTHROUGHPRODUCTIONINTRANSGENICPLANTSKEYWORDSBIOPHARMACEUTICALS,GMCROPS,EDIBLEVACCINE,ANTIBODIES,PRODUCTIONSYSTEMSREVIEW?2000NATUREAMERICAINCHTTP//BIOTECHNATURECOM?2000NATUREAMERICAINCHTTP//BIOTECHNATURECOMNATUREBIOTECHNOLOGYVOL18NOVEMBER2000HTTP//BIOTECHNATURECOM1153ONEIMPORTANTTARGETFORCURRENTVACCINEEFFORTSISHEPATITISB,AVIRUSRESPONSIBLEFORTHEMAJORITYOFPERSISTENTVIREMIAINHUMANSTHATCANCAUSECHRONICLIVERDISEASETHEFIRSTCOMMERCIALLYAVAILABLERECOMBINANTVACCINEWASDEVELOPEDINYEASTAFTERCONCERNSABOUTTHESAFETYOFSERUMDERIVEDANTIGENSINMANYPLACES,EXPENSE,TOGETHERWITHALACKOFFACILITIESEG,REFRIGERATIONINSTALLATIONSHASPROHIBITEDTHEUSEOFRECOMBINANTVACCINESIN1992,THEWORLDHEALTHORGANIZATIONGENEVAANDACONSORTIUMOFOTHERPHILANTHROPICORGANIZATIONSBEGANTHECHILDREN’SVACCINEINITIATIVEASPARTOFTHISEFFORT,THANAVALAETAL43INITIALLYDEVELOPEDTRANSGENICTOBACCO,ANDTHENPOTATOES,THATEXPRESSHEPATITISBSURFACEANTIGENHBSAG43,45BYMAXIMIZINGTHEIMMUNOGENICITYOFUNTREATEDEDIBLEPLANTTISSUES,THEGROUPHOPESTOPRODUCEVACCINESFORDEVELOPINGCOUNTRIESTHEYHAVERECENTLYSHOWNTHATHBSAGTRANSGENICPOTATOESADMINISTEREDORALLYTOMICECANELICITHUMORALIMMUNERESPONSES45ULTIMATELY,ATTENTIONWILLFOCUSONTHEMODIFICATIONOFBANANAS,WHICHAREGROWNEXTENSIVELYTHROUGHOUTTHEDEVELOPINGWORLDAND,INCONTRASTTOPOTATOES,CANBEEATENRAW23BANANAVACCINES,DELIVEREDASAPURéE,WOULDCOSTJUSTASMALLFRACTIONOFTHEPRICEOFTRADITIONALVACCINESINTHEFUTURE,BANANAVACCINESCOULDBEPRODUCEDAGAINSTARANGEOFDISEASES,INCLUDINGMEASLES,POLIO,DIPHTHERIA,YELLOWFEVER,ANDCERTAINTYPESOFVIRALDIARRHEAANTIBODIESTHEALTERNATIVETOINDUCINGTHEIMMUNESYSTEMTOPRODUCEANTIBODIESISTODELIVERTHEMDIRECTLYALTHOUGHTHETHERAPEUTICPOTENTIALOFANTIBODIESHASLONGBEENRECOGNIZEDEG,FORINDIVIDUALSNEEDINGSHORTTERMPROTECTIONAGAINSTINFECTIOUSAGENTS,DIFFICULTIESASSOCIATEDWITHTHEIRPRODUCTIONHAVELIMITEDCLINICALUSE8,40IN1989,HIATTETAL17FIRSTDEMONSTRATEDTHATFUNCTIONALANTIBODIESCOULDBEPRODUCEDINTRANSGENICPLANTSSINCETHEN,ACONSIDERABLEAMOUNTOFEFFORTHASBEENINVESTEDINDEVELOPINGPLANTSFORANTIBODYOR“PLANTIBODY”PRODUCTION8,9,11,17,31,33,40,42RECOMBINANTANTIBODIESCANBETARGETEDTOSEEDSANDTUBERS9,11,31,33,ANDEVENTUALLYITSHOULDBEPOSSIBLETOSTORE,TRANSPORT,ANDADMINISTERANTIBODIESINSUCHPLANTTISSUES,WHICHWOULDBEADVANTAGEOUSFORIMMUNIZATIONPROGRAMSINDEVELOPINGCOUNTRIES9,33,47MANYOFTHEANTIBODIESPRODUCEDINTRANSGENICPLANTSHAVEAPPLICATIONSFORHUMANANDANIMALHEALTHCARE8,33,40,48TABLE2,ANDTHEYMAYALSOPROVEUSEFULFOROTHERAPPLICATIONSSUCHASBIOREMEDIATION9RECOMBINANTANTIBODIESINCLUDEFULLYASSEMBLEDWHOLEIMMUNOGLOBULINS17,48,ANTIGENBINDINGFRAGMENTSOFIMMUNOGLOBULINS,ANDSYNTHETICSINGLECHAINVARIABLEFRAGMENTGENEFUSIONSSCFV9,31SINGLECHAINFVANTIBODIESAREENCODEDBYANARTIFICIALGENEMADEBYJOININGTOGETHERLIGHTANDHEAVYCHAINVARIABLESEQUENCES9,11,31,33PLANTIBODIESCOULDBEOFPARTICULARBENEFITFORTOPICALIMMUNOTHERAPY8,16,40PASSIVEIMMUNIZATIONOFTHEMUCOSALSITESCOULDBEEFFECTIVEAGAINSTBACTERIA,FUNGI,ANDVIRUSES8PLANTIBODIESAGAINSTCELLSURFACEANTIGENSOFSTREPTOCOCCUSMUTANSHAVEBEENSHOWNTOREDUCETOOTHDECAYINANIMALMODELSANDHUMANS44,45REPEATEDLARGEDOSESOFANTIBODYAREREQUIREDFORTOPICALPASSIVEIMMUNOTHERAPY,ANDTRANSGENICPLANTSCOULDBEUSEFULFORPRODUCINGSUCHLARGEQUANTITIES40FURTHERMORE,ITHASBEENSHOWNTHATTRANSGENICPLANTSCANBEGENERATEDTHATWILLEFFICIENTLYASSEMBLECOMPLEXSECRETORYANTIBODIES,SOMETHINGPREVIOUSLYTHOUGHTDIFFICULTTOACHIEVEINPLANTS8,40THISWASACCOMPLISHEDBYCONSTRUCTINGTOBACCOPLANTSEXPRESSINGFOURTRANSGENESTHROUGHCROSSINGOFPLANTSTRANSFORMEDWITHSINGLETRANSGENESGENESTACKING17THERESULTINGQUADRUPLETRANSGENICSEFFICIENTLYASSEMBLESECRETORYIMMUNOGLOBULINASIGA,THEPREDOMINANTIMMUNOGLOBULINTHATPROTECTSAGAINSTMICROBIALINFECTIONATMUCOSALSITES8,40SECRETORYIGAISBOTHMOREEFFICIENTATBINDINGANTIGENSANDMORESTABLETHANTHEPLANTIBODIESINITIALLYPRODUCED,BEINGMORERESISTANTTOPROTEOLYSISBECAUSEOFTHISINCREASEDSTABILITY,TREATMENTOFALLMUCOSALSITESMAYBEPOSSIBLE,INCLUDINGTHEGASTROINTESTINALTRACT8THEUSEOFEDIBLEPLANTSFORTHISISOBVIOUSLYANATTRACTIVEPOSSIBILITY40THEABILITYTOASSEMBLEIMMUNOGLOBULINSISAMAJORADVANTAGETHATPLANTSHAVEOVERBACTERIALEXPRESSIONSYSTEMSBIOPHARMACEUTICALSTRANSGENICPLANTSHAVEBEENCONSTRUCTEDTHATEXPRESSPROTEINSSUCHASENKEPHALINS26,ΑINTERFERON2,24,HUMANSERUMALBUMIN12,ANDTWOOFTHEMOSTEXPENSIVEDRUGSGLUCOCEREBROSIDASE13,41ANDGRANULOCYTE–MACROPHAGECOLONYSTIMULATINGFACTOR2,13,41TABLE3APPLIEDPHYTOLOGICSAPISACRAMENTO,CAHASMODIFIEDRICEPLANTSTOPRODUCEHUMANΑ1ANTITRYPSIN,APROTEINOFTHERAPEUTICPOTENTIALINCYSTICFIBROSIS,LIVERDISEASE,ANDHEMORRHAGESTRIALSOFΑ1ANTITRYPSINTRANSGENICRICECOMMENCEDIN1998,WITHPROTEINEXTRACTEDFROMMALTEDGRAINAPIHOPESTOHAVEREGULATORYAPPROVALFORTRANSGENICPLANTMEDICALPRODUCTSBY2004GAUCHER’SDISEASEISARECESSIVELYINHERITEDLYSOSOMALSTORAGEDISORDERRESULTINGFROMDEFICIENCIESOFLYSOSOMALHYDROLASEGLUCOCEREBROSIDASEENZYME13ADRUGDEVELOPEDFROMENZYMEPURIFIEDFROMHUMANPLACENTASISHIGHLYEFFECTIVEATREDUCINGCLINICALSYMPTOMSHOWEVER,10–12TONS/YEAROFPLACENTASAREREQUIREDTOPRODUCEENOUGHGLUCOCEREBROSIDASEFORTHEAVERAGETYPEIGAUCHER’SPATIENT,MAKINGITONEOFTHEWORLD’SMOSTEXPENSIVEDRUGS41ARECENTSWITCHTOPRODUCTIONINMAMMALIANCELLCULTURESYSTEMSHASREDUCEDTHISCOST,BUTDIDN’TREMOVETHEDRUGFROMTHE“MOSTEXPENSIVE”LEAGUEGLUCOCEREBROSIDASEPRODUCTIONINTRANSGENICTOBACCO13,41WASPATENTEDBYCRAM
下載積分: 10 賞幣
上傳時間:2024-03-13
頁數(shù): 5
大小: 0.12(MB)
子文件數(shù):
-
簡介:NEUROLOGICALREVIEWPREVENTIVEANTIBIOTICSFORINFECTIONSINACUTESTROKEASYSTEMATICREVIEWANDMETAANALYSISDIEDERIKVANDEBEEK,MD,PHDEELCOFMWIJDICKS,MD,PHDFREDERIQUEHVERMEIJ,MDROBJDEHAAN,PHDJANMPRINS,MD,PHDLODEWIJKSPANJAARD,MD,PHDDIEDERIKWJDIPPEL,MD,PHDPAULJNEDERKOORN,MD,PHDOBJECTIVETOPROVIDEASYSTEMATICOVERVIEWANDMETAANALYSISOFRANDOMIZEDCLINICALTRIALSEVALUATINGPREVENTIVEANTIBIOTICSINPATIENTSWITHACUTESTROKEDATASOURCESTHEMEDLINE1966FEBRUARY2009ANDCOCHRANEDATABASESANDREFERENCELISTSOFRETRIEVEDARTICLESSTUDYSELECTIONRANDOMIZEDCONTROLLEDTRIALSONPREVENTIVEANTIBIOTICTREATMENTINSTROKEFORINCLUSION,ATLEASTCASEFATALITYORINFECTIONRATEHADTOBERECORDEDDATAEXTRACTIONEACHSTUDYWASSCOREDFORMETHODOLOGICALKEYISSUESANDAPPRAISEDBYTHEJADADSCALEWEEXTRACTEDTHEDATAUSINGAPREDETERMINEDPROTOCOLANDINCLUDEDALLPATIENTSWHOWERERANDOMIZEDORWHOSTARTEDTHERAPYINANINTENTTOTREATANALYSISDATASYNTHESISWEIDENTIFIED4RANDOMIZEDCLINICALTRIALSINCLUDING426PATIENTS94HADISCHEMICSTROKESTUDYINTERVENTIONSWEREFLUOROQUINOLONESIN2ANDTETRACYCLINEORACOMBINATIONOF?LACTAMANTIBIOTICWITH?LACTAMASEINHIBITORIN1THERAPYWASSTARTEDWITHIN24HOURSOFSTROKEONSETDURATIONOFTHERAPYVARIEDBETWEEN3AND5DAYSTHEMETHODOLOGICALQUALITYRANGEDFROM2TO5ONTHEJADADSCALE,ANDSTUDIESWERESUBJECTTOPOTENTIALBIASTHEPROPORTIONOFPATIENTSWITHINFECTIONWASSIGNIFICANTLYSMALLERINTHEANTIBIOTICGROUPTHANINTHEPLACEBO/CONTROLGROUP32OF136235VS53OF139381PATIENTSTHEPOOLEDODDSRATIOFORINFECTIONWAS04495CONFIDENCEINTERVAL,023086TENOF210PATIENTS48INTHEANTIBIOTICGROUPDIED,COMPAREDWITH13OF21660INTHEPLACEBO/CONTROLGROUPTHEPOOLEDODDSRATIOFORMORTALITYWAS06395CONFIDENCEINTERVAL,022178NOMAJORHARMORTOXICITYWASREPORTEDCONCLUSIONSINADULTSWITHACUTESTROKE,PREVENTIVEANTIBIOTICSREDUCEDTHERISKOFINFECTION,BUTDIDNOTREDUCEMORTALITYTHEOBSERVEDEFFECTWARRANTSEVALUATIONOFPREVENTIVEANTIBIOTICSINLARGESTROKETRIALSARCHNEUROL200966910761081INFECTIONISACOMMONCOMPLICATIONINTHEACUTEPHASEAFTERSTROKEANDHASBEENDESCRIBEDINUPTO40OFPATIENTS1THEMOSTCOMMONINFECTIONAFTERACUTESTROKEISPNEUMONIA,WITHREPORTEDRATESUPTO30PNEUMONIAISANEARLYINFECTIONABOUTHALFOFTHECASESOCCURWITHINTHEFIRST48HOURSAFTERSTROKEONSETANDALMOSTALLWITHINTHEFIRSTWEEK1THEMORTALITYANDMORBIDITYASSOCIATEDWITHPNEUMONIAISHIGHINACOMMUNITYBASEDSTUDYINCLUDING14293PATIENTSWITHSTROKE,2PNEUMONIAWASASSOCIATEDWITHARELATIVERISKOF30FORMORTALITY95CONFIDENCEINTERVALCI,2437WHENADJUSTEDFORADMISSIONSEVERITYANDPROPENSITYFORPNEUMONIAINTHEUNITEDSTATES,THEANNUALCOSTOFPNEUMONIAASACOMPLICATIONAFTERACUTESTROKEHASBEENESTIMATEDTOBE459MILLION3OVERTHELAST3YEARS,SEVERALSTUDIESHAVEEVALUATEDPREVENTIVEUSEOFANTIBIOTICSINPATIENTSWITHACUTESTROKE,WITHCONFLICTINGRESULTS1CURRENTGUIDELINESONACUTESTROKEMANAGEMENTSTATETHATPREVENTIVEADMINISTRATIONOFANTIBIOTICSISNOTINDICATEDBECAUSETHISTREATMENTHASNOTBEENPROVENEFFECTIVE4HEREINWEPROVIDEASYSTEMATICOVERVIEWOFALLRANDOMIZEDCLINICALTRIALSEVALUATINGPREVENTIVEANTIBIOTICSINPATIENTSWITHACUTESTROKEMETHODSWESELECTEDSTUDIESONPREVENTIVEANTIBIOTICTREATMENTINACUTESTROKEELIGIBLEPATIENTSWEREADULTSPREDEFINEDASAGED16YEARSOROLDERWITHACUTESTROKE,RANDOMIZEDFORORALORINTRAVENOUSANTIBIOTICSOFANYTYPEORAPLACEBOORCONTROLGROUPEACHSTUDYWASSCOREDFORMETHODOLOGICALKEYISSUES,SUCHASINCLUSIONANDEXCLUSIONCRITERIA,TREATMENTINTERVENAUTHORAFFILIATIONSDEPARTMENTSOFNEUROLOGYDRSVANDEBEEKANDNEDERKOOM,CLINICALEPIDEMIOLOGYANDBIOSTATISTICSDRDEHAAN,INFECTIOUSDISEASESDRPRINS,ANDMEDICALMICROBIOLOGYDRSPANJAARD,CENTEROFINFECTIONANDIMMUNITYAMSTERDAMCINIMA,ACADEMICMEDICALCENTER,AMSTERDAM,THENETHERLANDSDEPARTMENTOFNEUROLOGY,DIVISIONOFCRITICALCARENEUROLOGY,MAYOCLINIC,ROCHESTER,MINNESOTADRWIJDICKSANDTHEDEPARTMENTOFNEUROLOGYDRSVERMEIJANDDIPPEL,ERASMUSUNIVERSITYMEDICALCENTER,ROTTERDAM,THENETHERLANDSREPRINTEDARCHNEUROL/VOL66NO9,SEP2009WWWARCHNEUROLCOM1076?2009AMERICANMEDICALASSOCIATIONALLRIGHTSRESERVEDDOWNLOADEDFROMHTTP//ARCHNEURJAMANETWORKCOM/BYAUNIVERSITYOFAMSTERDAMUSERON08/16/2013CRITERIAORINABILITYTOCOMPLETETHETREATMENTPROTOCOLPATIENTSWHOMETELIGIBILITYCRITERIABUTWEREEXCLUDEDAFTERTHERANDOMIZATIONPROCESSWEREINCLUDEDINTHECURRENTANALYSISONESTUDYDIDNOTDESCRIBEWITHDRAWALS10INTHISTRIAL,PATIENTSWITHALIFEEXPECTANCYOFFEWERTHAN90DAYSWEREEXCLUDED,WHICHRESULTEDINANOVERALLMORTALITYRATEOF010ONESTUDYDIDNOTHAVEABLINDEDOUTCOMEASSESSMENT8THISWASALSOTHESTUDYTHATUSEDQUASIRANDOMIZATION8THEPRIMARYOUTCOMEMEASURESWERETHEINFECTIONRATEINTHE2STUDIESANDTHEPROPORTIONOFPATIENTSWITHFEVERDURINGADMISSIONIN1STUDYTHEDEFINITIONSUSEDFORINFECTIONDIFFEREDSUBSTANTIALLYBETWEENSTUDIESTHECRITERIAFORINFECTIONAREPRESENTEDINTABLE2ONESTUDYADHEREDTOTHEOFFICIALCRITERIAOFTHEUSCENTERSFORDISEASECONTROLANDPREVENTION,BUTUSEDHEAVILYMODIFIEDCRITERIA11INFECTIONRATESWERENOTEVALUATEDINALLSTUDIESONESTUDYFOCUSEDONTHENEUROPROTECTIVEEFFECTSOFMINOCYCLINEANDDIDNOTEVALUATEINFECTIONRATES8THEPRIMARYOUTCOMEINTHISTRIALWASTHEDIFFERENCEBETWEENTHENIHSSSCORESOFINDIVIDUALPATIENTSATTHEBASELINEANDONDAY90OVERALL,SECONDARYOUTCOMESWERESCORESONTHEMODIFIEDRANKIN,6,10NIHSS,6,8ANDBARTELINDEX6,9THESESECONDARYOUTCOMESWEREASSESSED90DAYSAFTERRANDOMIZATIONCASEFATALITYRATESWEREREPORTEDINALLSTUDIESSAMPLESIZECALCULATIONSWEREPERFORMEDIN2STUDIES6,9ONESTUDYWASPOWEREDTODETECTSIGNIFICANTEFFECTONTHERATEOFINFECTIONBASEDONTHEASSUMPTIONOFAREDUCTIONFROM30TO15OR,041,REQUIRING480PATIENTS6THISSTUDYWASTERMINATEDAFTERINCLUSIONOF130PATIENTSBECAUSENOEFFECTWASTOBEEXPECTEDWITHINCLUSIONOFALL480PATIENTSATTHEMOMENTOFTERMINATIONOFENROLLMENT,THEPROPORTIONOFPATIENTSWITHINFECTIONWAS17INPLACEBOGROUPAND18INTHELEVOFLOXACINGROUP6EFFICACYOFANTIBIOTICPROPHYLAXISRESULTSOFTHESTUDIESARENOTEDINTABLE3THESTUDYPOPULATIONSMAINLYINCLUDEDPATIENTSWITHISCHEMICSTROKE410OF436INCLUDEDPATIENTS94ONESTUDYALSOINCLUDEDPATIENTSWITHHEMORRHAGEDEEPHEMATOMA,17LOBARHEMATOMA,96THEOVERALLNUMBEROFPARTICIPANTSWITHINFECTIONWASSIGNIFICANTLYSMALLERINTHEANTIBIOTICGROUPTHANINTHEPLACEBOORCONTROLGROUP32OF136235VS53OF139381PATIENTSTABLE3THENUMBERNEEDEDTOTREATTOPREVENTINFECTIONWAS7THEPOOLEDORFORINFECTIONWAS04495CI,023086FIGUREINFECTIONSWEREPNEUMONIAN61,URINARYTRACTINFECTIONSN21,BRONCHITISN5,ANDOTHERSN5THEINFECTIONSTHATWEREPREVENTEDBYANTIBIOTICTHERAPYWERETHOSETHATOCCURREDMOSTFREQUENTLY,PNEUMONIAANDURINARYTRACTINFECTIONSTENOF21048PATIENTSWHOWERETREATEDWITHANTIBIOTICSDIED,COMPAREDWITH13OF21660RECEIVINGPLACEBOORNOTREATMENTTABLE3THENUMBERNEEDEDTOTREATTOPREVENTDEATHWAS83THEPOOLEDORFORMORTALITYWAS06395CI,022178FIGURECASEFATALITYRATESVARIEDBETWEENSTUDIESFROM0TO7TWOSTUDIESHADPOSITIVERESULTSONTHEIRPRIMARYOUTCOME1ONIMPROVEMENTOFBASELINENIHSSSCOREMEANSD,1619VS6538P?001AND1ONOCCURRENCEOFFEVERP?058,10IN1STUDY,THERESULTOFPRIMARYANALYSISWASPOSITIVEFORTHEPERPROTOCOLANALYSISONLYOCCURRENCEOFINFECTIONS,6OF3517VS13OF3142PATIENTSP039IN1STUDY,THEPROPORTIONOFPATIENTSWITHFAVORABLENEUROLOGICALOUTCOMEWASSTATISTICALLYSIGNIFICANTLYREDUCEDANDNOEFFECTWASOBSERVEDONMORTALITY8THERATEOFINFECTIONWASNOTEVALUATEDINTHISSTUDYSAFETYOFANTIBIOTICPROPHYLAXISADVERSEEVENTSWEREDESCRIBEDIN3ARTICLESANTIBIOTICTREATMENTWASNOTASSOCIATEDWITHANYSIDEEFFECTSIN2STUDIESTHESTUDYEVALUATINGMEZLOCILLINPLUSSULBACTAMDESCRIBEDEXANTHEMAANDELEVATEDLIVERENZYMESEACHIN1PATIENT10ANTIBIOTICSUSCEPTIBILITYTESTINGOFESCHERICHIACOLIISOLATESWASPERFORMEDIN1STUDY9NODIFFERENCEWASFOUNDINANTIBIOTICRESISTANCEPATTERNSBETWEENBACTERIALISOLATESFROMPATIENTSINTHEMOXIFLOXACINANDPLACEBOGROUPSTABLE2DEFINITIONSUSEDFORINFECTIONSOURCEDEFINITIONCHAMORROETAL6TEMPERATURE?375°CIN2DETERMINATIONS?378°CINASINGLEDETERMINATIONINPATIENTSWITHSUGGESTIVESYMPTOMSWHITEBLOODCELLCOUNT?11000/MLOR?4000/MLPULMONARYINFILTRATEONCHESTXRAYSORCULTURESPOSITIVEFORAPATHOGENLAMPLETAL8NOTEVALUATEDHARMSETAL9APNEUMONIA,?1OFABNORMALRESPIRATORYEXAMINATIONORPULMONARYINFILTRATESINCHESTXRAYS,ORPRODUCTIVECOUGHWITHPURULENTSPUTUM,MICROBIOLOGICALCULTURESFROMLOWERRESPIRATORYTRACTORBLOODCULTURES,LEUKOCYTOSIS,ELEVATIONOFCRPUTI,?1OFTHEFOLLOWINGFEVERTEMPERATURE?380°C,URINESAMPLEPOSITIVEFORNITRITE,LEUKOCYTURIA,SIGNIFICANTBACTERIURIASCHWARZETAL10BPNEUMONIA,NEWINFILTRATEONCHESTXRAYCOMPATIBLEWITHTHEDIAGNOSISOFINFECTIONPLUSATLEAST1OFTHEFOLLOWINGFEVERTEMPERATURE?380°C,LEUKOCYTOSIS?12000/ΜLORLEUKOPENIA?3000/ΜL,PURULENTTRACHEALSECRETIONSTRACHEOBRONCHITIS,PURULENTTRACHEALSECRETIONSORSPUTUMPLUSATLEAST1OFTHEFOLLOWINGFEVERTEMPERATURE?380°C,LEUKOCYTOSIS?12000/ΜLORLEUKOPENIA?3000/ΜLUTI,?25LEUKOCYTES/ΜLINTHEURINEIFNOTEXPLAINEDBYOTHERFINDINGSBACTEREMIA,BACTERIAINBLOODCULTURESSEPSIS,CLINICALEVIDENCEOFANINFECTIONWITHATLEAST2OFTHEFOLLOWINGTEMPERATURE?38°COR?35°C,TACHYCARDIA?90/MIN,TACHYPNEA?20/MIN,LEUKOCYTOSIS?12000/ΜLORLEUKOPENIA?3000/ΜLINFECTIONOFUNCLEARORIGINOROTHERINFECTIONS,CLINICALEVIDENCEOFANINFECTIONOFUNKNOWNORIGINORANYOTHERSYSTEMICINFECTIONABBREVIATIONSCRP,CREACTIVEPROTEINUTI,URINARYTRACTINFECTIONACRITERIAMODIFIEDFROMUSCENTERSFORDISEASECONTROLANDPREVENTIONCRITERIABCRITERIAFROMPAULEHRLICHSOCIETYFORCHEMOTHERAPYREPRINTEDARCHNEUROL/VOL66NO9,SEP2009WWWARCHNEUROLCOM1078?2009AMERICANMEDICALASSOCIATIONALLRIGHTSRESERVEDDOWNLOADEDFROMHTTP//ARCHNEURJAMANETWORKCOM/BYAUNIVERSITYOFAMSTERDAMUSERON08/16/2013
下載積分: 10 賞幣
上傳時間:2024-03-13
頁數(shù): 6
大?。?0.1(MB)
子文件數(shù):
-
簡介:THEREARE18MAMMALIANFIBROBLASTGROWTHFACTORSFGF1–FGF10ANDFGF16–FGF23WHICHAREGROUPEDINTO6SUBFAMILIESBASEDONDIFFERENCESINSEQUENCEHOMOLOGYANDPHYLOGENYFGF1ANDFGF2FGF3,FGF7,FGF10,FGF22FGF4,FGF5ANDFGF6FGF8,FGF17ANDFGF18FGF9,FGF16ANDFGF20ANDFGF19,FGF21ANDFGF23REF1THENUMBERED‘FGFS’THATAREUNASSIGNEDTOSUBFAMILIESTHEFGFHOMOLOGOUSFACTORSPREVIOUSLYKNOWNASFGF11–FGF14HAVEHIGHSEQUENCEIDENTITYWITHTHEFGFFAMILYBUTDONOTACTIVATEFGFRECEPTORSFGFRSANDARETHEREFORENOTGENERALLYCONSIDEREDMEMBERSOFTHEFGFFAMILY2BOX1FGF15ISTHEMOUSEORTHOLOGUEOFHUMANFGF19FGFSARECLASSICALLYCONSIDEREDTOBEPARACRINEFACTORSANDAREKNOWNFORTHEIRROLESINTISSUEPATTERNINGANDORGANOGENESISDURINGEMBRYOGENESISTHEFIRSTFIVESUBFAMILIESFALLINTOTHISCATEGORYBYCONTRAST,THEFGF19,FGF21ANDFGF23SUBFAMILYHASRECENTLYBEENSHOWNTOFUNCTIONINANENDOCRINEMANNER,DEPENDENTONTHEPRESENCEOFKLOTHOPROTEINSINTHEIRTARGETTISSUES,TOREGULATEBILEACID,CHOLESTEROL,GLUCOSE,VITAMINDANDPHOSPHATEHOMEOSTASIS3–6THEINVOLVEMENTOFFGFSIGNALLINGINHUMANDISEASEISWELLDOCUMENTEDDEREGULATEDFGFSIGNALLINGCANCONTRIBUTETOPATHOLOGICALCONDITIONSEITHERTHROUGHGAINORLOSSOFFUNCTIONMUTATIONSINTHELIGANDSTHEMSELVESFOREXAMPLE,FGF23GAINOFFUNCTIONINAUTOSOMALDOMINANTHYPOPHOSPHATAEMICRICKETS7,FGF10LOSSOFFUNCTIONINLACRIMOAURICULODENTODIGITALSYNDROMELADDSYNDROME8,FGF3LOSSOFFUNCTIONINDEAFNESS9ANDFGF8LOSSOFFUNCTIONINKALLMANNSYNDROME10ORTHROUGHGAINORLOSSOFFUNCTIONMUTATIONSINFGFRS,WHICHCONTRIBUTETOMANYSKELETALSYNDROMES41,KALLMANNSYNDROME36,LADDSYNDROME54ANDCANCERTHERAPEUTICAPPROACHESUSINGEXOGENOUSFGFS,ANTIBODIESORSMALLMOLECULESARESTILLRELATIVELYNEW,ANDMANYAVENUESOFINVESTIGATIONREMAINOPENRECOMBINANTFGF7ISALREADYINUSEFORTHETREATMENTOFCHEMORADIATIONINDUCEDORALMUCOSITISFUTUREAPPLICATIONOFTHEFGFSINRENALDISEASE,GLUCOSEANDPHOSPHATEHOMEOSTASIS,STEMCELLRESEARCH,TISSUEREPAIRANDBIOENGINEERING,ANDANGIOGENESISISEXPECTEDCONTINUEDEFFORTSTOUNDERSTANDTHESTRUCTURALBIOLOGYOFFGF–FGFRINTERACTIONSWILLPLAYAKEYPARTINDRIVINGTHEDISCOVERYOFNEWTHERAPIESINTHISARTICLE,WEBRIEFLYREVIEWCURRENTKNOWLEDGEREGARDINGFGF–FGFRSIGNALLINGANDTHENFOCUSONTHEBIOLOGY,PATHOLOGYANDRECENTDEVELOPMENTSREGARDINGTHEPHARMACOLOGICALAPPLICATIONSOFEACHLIGANDTHEFGF–FGFRSIGNALLINGSYSTEMFGFSALLFGFS,EXCEPTTHOSEINSUBFAMILIESFGF1ANDFGF2,ANDFGF9,FGF16ANDFGF20,HAVESIGNALPEPTIDESTHEFGF9,FGF16ANDFGF20SUBFAMILYISNONETHELESSSECRETEDTHROUGHTHETRADITIONALENDOPLASMICRETICULUMER–GOLGISECRETORYPATHWAY11,WHEREASTHEFGF1ANDFGF2SUBFAMILYISSECRETEDINDEPENDENTLY12FGFSHAVEAHOMOLOGOUSCOREREGIONTHATCONSISTSOF120–130AMINOACIDSORDEREDINTO12ANTIPARALLELΒSTRANDSΒ1–Β12FLANKEDBYDIVERGENTAMINOANDCARBOXYLTERMINIFIG1AINGENERAL,PRIMARYSEQUENCEVARIATIONOFTHENANDCTERMINALTAILSOFFGFSACCOUNTSFORTHEDIFFERENTBIOLOGYOFTHELIGANDS13FIG1BTHEHEPARANSULPHATEGLYCOSAMINOGLYCANHSGAGBINDINGSITEHBSWITHINTHEFGFCOREISCOMPOSEDOFTHEΒ1–Β2LOOPANDPARTSOFTHEREGIONSPANNINGΒ10ANDΒ12FORPARACRINEFGFS,DEPARTMENTOFPHARMACOLOGY,NEWYORKUNIVERSITYSCHOOLOFMEDICINE,NEWYORK,NEWYORK10016,USAEMAILSANDREWBEENKENMEDNYUEDUMOOSAMOHAMMADINYUMCORGDOI101038/NRD2792AUTOSOMALDOMINANTHYPOPHOSPHATAEMICRICKETSAHEREDITARYDISORDEROFPHOSPHATEWASTINGCHARACTERIZEDBYRICKETS,LOWEREXTREMITYDEFORMITIESANDOSTEOMALACIALACRIMOAURICULODENTODIGITALSYNDROMELADDASYNDROMECHARACTERIZEDBYABNORMALITIESOFTHEDIGITSANDTEETH,LOWSETEARSANDAPLASIAOFTHELACRIMALANDSALIVARYGLANDSMUTATIONSINFGFR2ANDFGF10AREKNOWNTOCAUSELADDKALLMANNSYNDROMETHISSYNDROMERESULTSFROMADEFICIENCYOFGONADOTROPINRELEASINGHORMONE,WHICHLEADSTOHYPOGONADISMMUTATIONSINFGFR1CANDFGF8AREKNOWNTOCAUSEKALLMANNSYNDROMETHEFGFFAMILYBIOLOGY,PATHOPHYSIOLOGYANDTHERAPYANDREWBEENKENANDMOOSAMOHAMMADIABSTRACT|THEFAMILYOFFIBROBLASTGROWTHFACTORSFGFSREGULATESAPLETHORAOFDEVELOPMENTALPROCESSES,INCLUDINGBRAINPATTERNING,BRANCHINGMORPHOGENESISANDLIMBDEVELOPMENTSEVERALMITOGENIC,CYTOPROTECTIVEANDANGIOGENICTHERAPEUTICAPPLICATIONSOFFGFSAREALREADYBEINGEXPLORED,ANDTHERECENTDISCOVERYOFTHECRUCIALROLESOFTHEENDOCRINEACTINGFGF19SUBFAMILYINBILEACID,GLUCOSEANDPHOSPHATEHOMEOSTASISHASSPARKEDRENEWEDINTERESTINTHEPHARMACOLOGICALPOTENTIALOFTHISFAMILYTHISREVIEWDISCUSSESTRADITIONALAPPLICATIONSOFRECOMBINANTFGFSANDSMALLMOLECULEFGFRECEPTORKINASEINHIBITORSINTHETREATMENTOFCANCERANDCARDIOVASCULARDISEASEANDTHEIREMERGINGPOTENTIALINTHETREATMENTOFMETABOLICSYNDROMEANDHYPOPHOSPHATAEMICDISEASESREVIEWSNATUREREVIEWS|DRUGDISCOVERYVOLUME8|MARCH2009|235?2009MACMILLANPUBLISHERSLIMITEDALLRIGHTSRESERVEDCANATUREREVIEWS|DRUGDISCOVERYFGF1FGF2FGF3FGF7FGF10FGF22FGF4FGF5FGF6FGF8FGF17FGF18FGF9FGF16FGF20FGF19FGF21FGF23EKFNLPPGNYKKPKLLYCGSGAFPPGHFKDPKRLYCGGVYEHLGGAPRRRKLYCRSYDYMEGGDIRVRRLFCVRSYNHLQGDVRWRKLFSPRSYPHLEGDVRWRRLFSSGAGDYLLGIKRLRRLYCQSSFQWSPSGRRTGSLYCNWESGYLVGIKRQRRLYCLVTDQLSRRLIRTYQLYSAMTDQLSRRQIREYQLYSRARDDVSRKQLRLYQLYSVTDLDHLKGILRRRQLYCPTDFAHLKGILRRRQLYCAAQLAHLHGILRRRQLYCPHVHYGWGDPIRLRHLYTSSPLLQFGGQVRQRYLYTNASPLLGSSWGGLIHLYT143734556831726774424343494852333527313451728548898491596060666569505244BΒ1CTERMINUSNTERMINUSΒ9Β8Β6Β4Β7Β5Β3Β2Β10Β11Β1Β12FGFR1ATLEASTTHREEGENETICDISORDERSCANBEATTRIBUTEDTOMUTATIONSINFGFR1KALLMAN’SSYNDROME36,OSTEOGLOPHONICDYPLASIAANDPFEIFFER’SSYNDROME37PATHOLOGICALFGFR1SIGNALLINGALSOOCCURSINVARIOUSMALIGNANCIESGLIOBLASTOMABRAINTUMOURSEXHIBITFGFR1KINASEDOMAINGAINOFFUNCTIONMUTATIONS38,ANDFGFR1ISABNORMALLYACTIVATEDCRANIOSYNOSTOSISTHISCONDITIONRESULTSFROMTHEPREMATURECLOSUREOFSUTURESOFADEVELOPINGSKULLBEFORETHECOMPLETIONOFBRAINGROWTHTHEBRAINCONTINUESTOGROWINAREASOFTHESKULLWHERESUTURESHAVENOTCLOSED,LEADINGTOAMALFORMEDCRANIUMAPERT’SSYNDROMEONEOFTHEMOSTCOMMONCRANIOSYNOSTOSISSYNDROMESTHATEXHIBITSSEVERESYNDACTYLYDIGITFUSIONOFTHEHANDSANDFEETAPERT’SSYNDROMEISOFTENASSOCIATEDWITHVISCERALABNORMALITIESOFTHECARDIOVASCULAR,RESPIRATORYANDUROGENITALSYSTEMSOSTEOGLOPHONICDYSPLASIAABONEDISORDERPRESENTINGWITHDWARFISM,VERTEBRALFRAGILITY,CRANIOSYNOSTOSISANDFAILURETOTHRIVETHETERMOSTEOGLOPHONICREFERSTOTHE‘HOLLOWEDOUT’APPEARANCEOFTHEMETAPHYSESINXRAYS,WHICHARETHEGROWTHZONESOFLONGBONESPFEIFFER’SSYNDROMEACRANIOSYNOSTOSISDISORDERTHATCANALSOPRESENTWITHPOLYDACTYLYGLIOBLASTOMAANAGGRESSIVETUMOURDERIVEDFROMGLIALCELLSTHATEXHIBITSHIGHLEVELSOFNEOVASCULARIZATIONMODULATORSOFFGFSIGNALLINGFGFBINDINGPROTEINFGFBPISACARRIERPROTEIN27THATACTIVATESFGFSBYRELEASINGTHEMFROMTHEEXTRACELLULARMATRIX,WHERETHEYAREBOUNDBYHSGAGS28FGFBPHASBEENSHOWNTOINCREASEFGF2DEPENDENTPROLIFERATIONOFFIBROBLASTCELLS29ANDMAYHAVEANIMPORTANTROLEINTHEDEVELOPMENTOFSOMECANCERS30OTHERACTIVATORSOFFGFSIGNALLINGINCLUDEFIBRONECTINLEUCINERICHTRANSMEMBRANEPROTEIN3FLRT3,WHICHFACILITATESFGF8ACTIVITYTHROUGHTHEMAPKPATHWAY31THESPROUTYFAMILYOFPROTEINSPLAYANIMPORTANTPARTININHIBITINGRECEPTORTYROSINEKINASERTKSIGNALLINGANDWEREFIRSTDISCOVEREDASINHIBITORSOFFGFSINDROSOPHILAMELANOGASTER32FGFSIGNALLINGACTIVATESSPROUTYPROTEINS,WHICHCANTHENINTURNINHIBITFGFSTIMULATIONOFTHEMAPKPATHWAYBYINTERACTINGWITHGRB2GROWTHFACTORRECEPTORBOUNDPROTEIN2,SOS1ORRAF1REF33MKP3MAPKPHOSPHATASE3ISANOTHERGENERALINHIBITOROFRTKSIGNALLINGTHATALSOIMPINGESONFGFACTIVITYBYDEPHOSPHORYLATINGEXTRACELLULARSIGNALREGULATEDKINASEERK34SEFISASPECIFICINHIBITOROFFGFSTHATCANFUNCTIONATMULTIPLEPOINTSALONGTHESIGNALLINGPATHWAYTOATTENUATESIGNALLING34FGFRPATHOPHYSIOLOGYANDTHERAPYGERMLINEGAINOFFUNCTIONMUTATIONSINFGFRSARERESPONSIBLEFORVARIOUSDISEASES,SUCHASCRANIOSYNOSTOSIS,DWARFINGSYNDROMESANDCANCERMOSTOFTHEFGFRMUTATIONSARELIGANDINDEPENDENT,BUTAFEWSUCHASSER252TRPANDPRO253ARGINTHEECTODOMAINOFFGFR2MANIFESTONLYDURINGLIGANDBINDINGTHESEMUTATIONSCAUSEAPERT’SSYNDROMEBYENHANCINGLIGANDBINDINGAFFINITYANDPROMOTINGTHEBINDINGOFINAPPROPRIATELIGANDS35,278–280REMARKABLY,MANYOFTHEGERMLINEMUTATIONSTHATCAUSESKELETALSYNDROMESALSOCONTRIBUTE,THROUGHSOMATICMUTATIONS,TOTHEDEVELOPMENTOFCANCERFURTHERMORE,MUTATIONSINFGFR1–FGFR3OFTENOCCURINHOMOLOGOUSRESIDUESANDACCOUNTFORMULTIPLEPATHOLOGIESFIGURE1|STRUCTURALFEATURESOFFIBROBLASTGROWTHFACTORSFGFSA|FGF1,SHOWINGITS12ANTIPARALLELΒSHEETSANDAMINOANDCARBOXYLTERMINIB|THE18FGFS,GROUPEDACCORDINGTOSUBFAMILYTHESEQUENCEALIGNMENTINTHEREGIONOFTHEDIVERGENTNTERMINUSPROXIMALTOTHEΒTREFOILCOREISGIVENTHEΒ1STRANDOFFGF1ISPROVIDEDTOINDICATETHELIMITOFTHENTERMINUSC|FGF19SUPERIMPOSEDONTOFGF2FROMTHEFGF2–FGFRECEPTOR1–HEPARINTERNARYSTRUCTUREPROTEINDATABANKFGF2ANDFGF19ARERENDEREDASRIBBONSANDHEPARINISSHOWNASSTICKSOXYGENRED,NITROGENBLUE,CARBONBEIGE,ANDSULPHURGREENATOMSARESHOWNTHECOREREGIONSOFBOTHLIGANDSARECOLOUREDGREY,ANDTHEHEPARINBINDINGREGIONSOFFGF2ANDFGF19ARECOLOUREDCYANANDORANGE,RESPECTIVELYHEPARINFROM1FQ9CLASHESWITHTHERIDGESINTHEHEPARINBINDINGREGIONOFFGF19TOELIMINATETHESECLASHES,HEPARINMUSTTRANSLOCATEAWAYFROMFGF19BUT,INDOINGSO,CRUCIALCONTACTSBETWEENHEPARINANDTHEFGF19BACKBONECANNOTBEMADETHEWEAKENEDHEPARINBINDINGOBSERVEDINTHEFGF19SUBFAMILYMEMBERSISRESPONSIBLEFORTHEIRENDOCRINEBEHAVIOURREVIEWSNATUREREVIEWS|DRUGDISCOVERYVOLUME8|MARCH2009|237?2009MACMILLANPUBLISHERSLIMITEDALLRIGHTSRESERVED
下載積分: 10 賞幣
上傳時間:2024-03-13
頁數(shù): 19
大?。?0.81(MB)
子文件數(shù):
-
簡介:JSERBCHEMSOC717733–7442006UDC54728854291361528JSCS–3467ORIGINALSCIENTIFICPAPERSYNTHESISANDANTIBACTERIALACTIVITYOFSOMESCHIFFBASECOMPLEXESRNAIR1,ASHAH2,SBALUJA2ANDSCHANDA11DEPARTMENTOFBIOSCIENCESAND2DEPARTMENTOFCHEMISTRY,SAURASHTRAUNIVERSITY,RAJKOT360005,GUJARAT,INDIAEMAILSUMITRACHANDAYAHOOCOMRECEIVED6JULY,REVISED9NOVEMBER2005ABSTRACTTWOSCHIFFBASESWERESYNTHESIZEDFROMRACEACETOPHENONE1ADS14ETHYL6{E13NITROPHENYLIMINOETHYL}BENZENE1,3DIOLAND2ADS34ETHYL6{E12NITROPHENYLIMINOETHYL}BENZENE1,3DIOLTHENTHEIRMETALCOMPLEXESWEREFORMEDTHEMETALSSELECTEDFORTHEPREPARATIONOFCOMPLEXESWERECOPPER,NICKEL,IRONANDZINCHENCE,INTOTAL8METALCOMPLEXESWERESYNTHESIZEDANDSCREENEDFORANTIBACTERIALACTIVITYAGAINSTSOMECLINICALLYIMPORTANTBACTERIA,SUCHASPSEUDOMONASAERUGINOSA,PROTEUSVULGARIS,PROTEUSMIRABILIS,KLEBSIELLAPNEUMONIAEANDSTAPHYLOCOCCUSAUREUSTHEINVITROANTIBACTERIALACTIVITYWASDETERMINEDBYTHEAGARDITCHTECHNIQUEUSINGDMFPOLARAND1,4DIOXANENONPOLARASSOLVENTSTHESCHIFFBASESSHOWEDGREATERACTIVITYTHANTHEIRMETALCOMPLEXESTHEMETALCOMPLEXESSHOWEDDIFFERENTIALEFFECTSONTHEBACTERIALSTRAINSINVESTIGATEDANDTHESOLVENTUSED,SUGGESTINGTHATTHEANTIBACTERIALACTIVITYISDEPENDENTONTHEMOLECULARSTRUCTUREOFTHECOMPOUND,THESOLVENTUSEDANDTHEBACTERIALSTRAINUNDERCONSIDERATIONTHESCHIFFBASEADS3INTHEPOLARSOLVENTDMFSHOWEDBETTERANTIBACTERIALACTIVITYTOWARDSTHEINVESTIGATEDBACTERIALSTRAINSAMONGSTTHEFOURMETALS,ZNSHOWEDTHEBESTANTIBACTERIALACTIVITYFOLLOWEDBYFEIN1,4DIOXANEWHILENIFOLLOWEDBYZNANDFESHOWEDTHEBESTANTIBACTERIALACTIVITYINDMFPVULGARISWASTHEMOSTRESISTANTBACTERIAKEYWORDSSCHIFFBASECOMPLEXES,ANTIBACTERIALACTIVITY,DMF,1,4DIOXANEINTRODUCTIONTOOVERCOMETHEALARMINGPROBLEMOFMICROBIALRESISTANCETOANTIBIOTICS,THEDISCOVERYOFNOVELACTIVECOMPOUNDSAGAINSTNEWTARGETSISAMATTEROFURGENCYMANYOFTHECRUDEDRUGS,WHICHARESOURCESOFMEDICINALPREPARATIONS,STILLORIGINATEFROMWILDGROWINGMATERIALHOWEVER,PLANTBASEDDRUGSHAVESHORTENEDTHELIFESPANOFTHESOURCEOFMATERIALTHEREISACONTINUOUSSEARCHFORMOREPOTENTANDCHEAPERRAWMATERIALSTOFEEDTHEINDUSTRYCOMPOUNDS,WHICHONDISSOLUTIONDONOTGIVEIONSOFWHICHTHEYAREMADEBUTINSTEADGIVECOMPLEXIONSARECALLEDCOORDINATIONCOMPOUNDSCOORDINATIONCOMPO733DOI102298/JSC0607733NAUTHORFORCORRESPONDENCENOLIC–OHGROUPTHEMETALSSELECTEDFORTHEPREPARATIONOFTHECOMPLEXESWERECOPPER,NICKEL,IRONANDZINCTHESYNTHESISOFMETALCOMPLEXESWASSTUDIEDATDIFFERENTPHVALUESFORDIFFERENTMETALS,THEMAXIMUMYIELDWASOBSERVEDATDIFFERENTPHVALUESTHEPHOFMAXIMUMYIELDWASSELECTEDFORTHESYNTHESISOFEACHCOMPLEXFOREACHMETALCOMPLEX,DIFFERENTMETALSALTSOLUTIONSWEREPREPAREDTHESOLUTIONSUSEDFORTHESYNTHESISOFTHECOPPER,NICKEL,IRONANDZINCCOMPLEXESWERECUPRICCHLORIDE,NICKELCHLORIDE,FERROUSAMMONIUMSULPHATEANDZINCCHLORIDE,RESPECTIVELYSYNTHESISOFCOPPERCOMPLEXES01MSOLUTIONOFLIGANDANDCUPRICCHLORIDEWEREPREPAREDIN1,4DIOXANEANDDISTILLEDWATER,RESPECTIVELYACETICACIDANDSODIUMACETATEWEREADDEDTOTHECUPRICCHLORIDESOLUTIONTOMAINTAINTHEPH65–70THELIGANDSOLUTIONWASADDEDDROPWISETOTHEMETALIONSOLUTIONADARKBROWNPRECIPITATEWASOBTAINEDTHEPHOFSOLUTIONWASMAINTAINEDBYTHEBUFFERSOLUTIONANDTHESOLUTIONWASREFLUXEDFOR4–5HINAWATERBATHTHEPRECIPITATEWASFILTEREDANDWASHED,FIRSTWITH1,4DIOXANEANDTHENWITHHOTWATERTOREMOVEEXCESSLIGANDANDMETALIONS,RESPECTIVELYTHEPRECIPITATEWASTHENDRIEDSYNTHESISOFNICKELCOMPLEXES01MSOLUTIONOFLIGANDANDNICKELCHLORIDEAREPREPAREDIN1,4DIOXANEANDDISTILLEDWATER,RESPECTIVELYTHELIGANDSOLUTIONWASADDEDDROPWISETOTHEMETALIONSOLUTIONTHEPHWASMAINTAINEDBETWEEN10–105BYADDINGAMMONIUMHYDROXIDEAYELLOWISHORANGEPRECIPITATEWASOBTAINEDONREFLUXINGTHESOLUTIONONAWATERBATHFOR4–5HTHEPRECIPITATEWASFILTEREDANDWASHEDWITHHOTWATERAND1,4DIOXANETOREMOVEEXCESSLIGANDANDMETALIONS,RESPECTIVELYTHEPRECIPITATEWASTHENDRIEDSYNTHESISOFIRONCOMPLEXES01MLIGANDSOLUTIONIN1,4DIOXANEWASADDEDDROPWISETOA01MFERROUSAMMONIUMSULPHATESOLUTIONINTHEPRESENCEOFABUFFERSOLUTIONAMMONIUMHYDROXIDEACETICACIDTOMAINTAINTHEPHBETWEEN7–75THESOLUTIONWASREFLUXEDFOR5–6HTHEFORMEDYELLOWISHBROWNPRECIPITATEWASFILTERED,WASHEDWITHHOTWATERAND1,4DIOXANETOREMOVEEXCESSLIGANDANDMETALIONS,RESPECTIVELYTHEPRECIPITATEWASTHENDRIEDSYNTHESISOFZINCCOMPLEXES01MLIGANDSOLUTIONIN1,4DIOXANEWASADDEDDROPWISETOA01MZINCCHLORIDESOLUTIONINPRESENCEOFBUFFERSOLUTIONANDAMMONIUMHYDROXIDETOMAINTAINTHEPHBETWEEN10–11THESOLUTIONWASREFLUXEDFOR4–5HINAWATERBATHTHEFORMEDBROWNPRECIPITATEWASFILTERED,WASHEDWITHHOTWATERAND1,4DIOXANETOREMOVEEXCESSLIGANDANDMETALIONS,RESPECTIVELYTHEPRECIPITATEWASTHENDRIEDANTIBACTERIALACTIVITYANTIBACTERIALACTIVITYWASDETERMINEDBYTHEAGARDITCHMETHOD15THEINVESTIGATEDMICROORGANISMSWEREPSEUDOMONASAERUGINOSA,PROTEUSVULGARIS,PROTEUSMIRABILIS,KLEBSIELLAPNEUMONIAEANDSTAPHYLOCOCCUSAUREUSTHECOMPOUNDSWEREDISSOLVEDINONEOFTHETWOSOLVENTS1,4DIOXANEORDMFTOOBTAINAFINALCONCENTRATION1MG/01MLALOOPFULLOFTHEGIVENTESTSTRAINWASINOCULATEDIN25MLOFNBROTHNUTRIENTBROTHANDINCUBATEDFOR24HINANINCUBATORAT37oCINORDERTOACTIVATETHEBACTERIALSTRAIN28–30MLOFTHENUTRIENTAGARMEDIAWASADDEDINTOA100MMDIAMETERPETRIPLATEINOCULATIONWASDONEBYTHEPOURPLATETECHNIQUE02MLOFTHEACTIVATEDSTRAINWASINOCULATEDINTOTHEMEDIAWHENITREACHEDATEMPERATUREOF40–45oCTHECOMPLETEPROCEDUREOFTHEPLATEPREPARATIONWASDONEINALAMINARAIRFLOWTOMAINTAINSTRICTSTERILEANDASEPTICCONDITIONTHEMEDIUMWASALLOWEDTOSOLIDIFYAFTERSOLIDIFICATIONOFTHEMEDIA,AWELLWASMADEINTHEPLATESWITHTHEHELPOFACUPBORER085CM,WHICHWASTHENFILLEDWITHONEOFTHETESTSAMPLESOLUTIONSCONTROLSWERERUNFOREACHBACTERIALSTRAINANDEACHSOLVENT,WHEREPURESOLVENTWASINOCULATEDINTOTHEWELLTHEPLATESWEREINCUBATEDFOR24HAT37oCTHEINHIBITIONZONEFORMEDBYTHESECOMPOUNDSSCHIFFBASECOMPLEXES735
下載積分: 10 賞幣
上傳時間:2024-03-14
頁數(shù): 12
大?。?0.32(MB)
子文件數(shù):
-
下載積分: 14 賞幣
上傳時間:2024-01-07
頁數(shù): 0
大?。?2.81(MB)
子文件數(shù):
-
下載積分: 15 賞幣
上傳時間:2024-01-07
頁數(shù): 0
大?。?5.72(MB)
子文件數(shù):
-
下載積分: 14 賞幣
上傳時間:2024-01-07
頁數(shù): 0
大小: 2.36(MB)
子文件數(shù):
-
下載積分: 14 賞幣
上傳時間:2024-01-07
頁數(shù): 0
大?。?2.32(MB)
子文件數(shù):
-
下載積分: 14 賞幣
上傳時間:2024-01-07
頁數(shù): 0
大小: 1.01(MB)
子文件數(shù):
-
下載積分: 15 賞幣
上傳時間:2024-01-07
頁數(shù): 0
大?。?7.57(MB)
子文件數(shù):
-
下載積分: 14 賞幣
上傳時間:2024-01-07
頁數(shù): 0
大小: 2.29(MB)
子文件數(shù):
-
下載積分: 14 賞幣
上傳時間:2024-01-07
頁數(shù): 0
大?。?3.05(MB)
子文件數(shù):
-
下載積分: 14 賞幣
上傳時間:2024-01-07
頁數(shù): 0
大?。?3.26(MB)
子文件數(shù):
-
下載積分: 14 賞幣
上傳時間:2024-01-07
頁數(shù): 0
大?。?1.07(MB)
子文件數(shù):