Novel Insights into Disseminated Candidiasis Pathogenesis Research and Clinical Experience Converge 英文参考文献.docVIP

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Novel Insights into Disseminated Candidiasis Pathogenesis Research and Clinical Experience Converge 英文参考文献.doc

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Novel Insights into Disseminated Candidiasis Pathogenesis Research and Clinical Experience Converge 英文参考文献

Opinion NovelInsightsintoDisseminatedCandidiasis: PathogenesisResearchandClinical ExperienceConverge Brad Spellberg C andidaspp.havebecomeleadingcausesoflethal bloodstreaminfectionsincountrieswithadvanced medicaltechnology[1].Itisgenerallyandcorrectly understoodthatdisseminatedcandidiasisis‘‘an theinvestigatorssequentiallydisruptedspeci?chostdefense elementstodeterminewhichprotectedagainstdisseminated candidiasisfromagastrointestinalsource.Consistentwith clinicalexperienceandpriormurinestudies[10,11],the investigatorsfoundthatdepletionoflymphocytesdidnot predisposetocandidaldissemination.Furthermore,even profounddepletionofgranulocytes(primarilyneutrophils) ortissuemacrophageswasinsuf?cienttoenabletrans- mucosaldisseminationtooccurinmostanimals.These depletionexperimentswereperformedbyadministering RB6-8C5antibody(forgranulocytes)orliposomalcladronate (formacrophages),andhencesparedtheentericmucosa fromthedamagethatnormallyoccursduringmyeloablation bychemotherapy.Disruptionofentericmucosalintegrity withdextransulfatewasalso,byitself,notsuf?cienttoinduce disseminatedcandidiasis.However,whenanactual chemotherapyagent(cyclophosphamide)thatbothablated neutrophilsandalsocausedgutbarrierdisruptionwas administered,lethaldisseminatedcandidiasisdeveloped. Combinationsofagents(methotrexateordextransulfatet RB6-8C5)thatbothcausedentericmucosaldisruptionand depletedgranulocytesalsoledtolethaldisseminated candidiasis. Itissurprisingthattheliverwastheprimarytargetorgan ofinfectioninthenewmodelbecauseclinicalhepatic candidiasisisrareandistypicallyseenonlyinthemost profoundlyimmunocompromisedpatients.Furthermore,in thetailveinmodelofmurinedisseminatedcandidiaisis,the primarytargetorganofinfectionisthekidney,hepatic infectionoccursatmarkedlylowerlevels,andtheliverclears infectionovertime,evenatrapidlylethalinocula[4,12].In anothergastrointestinalcolonizationmodelinwhich candidaldisseminationwasinducedbyadministrationofthe chemotherapyagent5-?uorouracil,liverswerealsomore frequentl