简介：Highlevelsofarsenicarefoundinmanypartsoftheworldandmorethan100millionpeoplemayhavebeenexposedtoit.Thereisgrowingevidencetoindicatethatarsenichasadeleteriouseffectontheauditorysystem.Thispaperprovidesthegeneralinformationofarsenicanditsototoxiceffects.

简介：Styreneisextensivelyusedinindustry,butitsototoxicity,inparticularinthepregnantfemaleandtheoffspring,isstillnotwellunderstood.Inthecurrentstudy,youngadultmaleratsandpregnantfemaleratswereexposedtostyrenebygavageatdifferentdoses.Theyoungadultmaleratsreceivedatotalof12g/kgstyrenewithindifferentperiods(800mg/kg/dayfor5days/weekfor3weeks,400mg/kg/dayfor5days/weekfor6weeks,200mg/kg/dayfor5days/weekfor12weeks,and100mg/kg/dayfor5days/weekfor24weeks)andthepregnantfemaleratsreceivedstyreneatadoseof400mg/kg/dayfor5days/weekfor6weeksstartingfromthegestationday-4.Hearinglossandhaircelllosswereassessed5daysafterthestyrenetreatmentintheyoungadultmaleratsandinthemotherrats.Thecochlearimpairmentsintheratpupswereexamined2monthsaftertheirbirth.Thestyreneexposurecausedhearinglossandhaircelllossstartingfromthemid-frequencyregioninthethirdrowofouterhaircells(OHCs)andtheimpairmentsappearedtoberelatedtothedosinglevelineachsingleday.Significantly,thestyreneexposuretothepregnantratsinterferedwithauditoryfunctionaldevelopmentoftheirfetus,leadingtoadeficitofcochlearamplification,althoughtheOHCsappearedtodevelopwell.Theresultsindicatethatashort-termhigh-levelstyreneexposuremaybemoreototoxicthanalong-termlow-levelexposureforasimilartotalstyrenedoseandthestyreneinthepregnantwoman'sbodymayinterferewithauditorydevelopmentoftheirfetus.

简介：Objective:Theototoxicityofpovidone-iodinehasbeendocumentedinanimalstudies.However,thereislimitedevidenceoftheseototoxiceffectsinhumans.Thisisthefirstreporttoshowtheototoxiceffectsofpovidoneiodineinahumansubject.Patient:A36-year-oldwomancametoourhospitalcomplainingofleftunilateralpersistenthearingloss.Onemonthbeforepresentation,herchildhadaccidentallystruckheronherleftear.Sheappliedapproximatelythreedropsofpovidone-iodine(10%weight/volume)intoherleftauditorycanal.Immediatelyafterapplication,shefeltseverepainandvertigo.Anaudiogramrevealedsevereleftunilateralsensorineuralhearingloss.Magneticresonanceimagingshowedmildenhancementoftheleftvestibuleandbasalturnoftheleftcochlea.Conclusions:Evenasingleapplicationofpovidone-iodinecouldcausesignificanthearinglossanddisequilibrium.Itshould,therefore,beusedwithcaution.

简介：Themitochondrial12SrRNAhasbeenshowntobethehotspotformutationsassociatedwithbothaminoglycoside-inducedandnon-syndromichearingloss.Ofallthemutations,thehomoplasmicA1555GandC1494Tmutationsatahighlyconserveddecodingregioninthe12SrRNAhavebeenassociatedwithaminoglycoside-inducedandnon-syndromichearinglossinmanyfamiliesworldwide.TheA1555GorC1494Tmutationisexpectedtoformnovel1494C-G1555or1494U-A1555base-pairatthehighlyconservedA-siteof12SrRNA.ThesetransitionsmakethesecondarystructureofthisRNAmorecloselyresemblethecorrespondingregionofbacterial16SrRNA.Thus,thenewU-AorG-Cpairin12SrRNAcreatedbytheC1494TorA1555Gtransitionfacilitatesthebindingofaminoglycosides,therebyaccountingforthefactthattheexposuretoaminoglycosidescaninduceorworsenhearinglossinindividualscarryingthesemutations.Furthermore,thegrowthdefectandimpairmentofmitochondrialtranslationwereobservedincelllinescarryingtheA1555GorC1494Tmutationinthepresenceofhighconcentrationofaminoglycosides.Inaddition,nuclearmodifiergenesandmitochondrialhaplotypesmodulatethephenotypicmanifestationoftheA1555GandC1494Tmutations.TheseobservationsprovidethedirectgeneticandbiochemicalevidencesthattheA1555GorC1494TmutationisapathogenicmtDNAmutationassociatedwithaminoglycoside-inducedandnonsyndromichearingloss.Therefore,thesedatahavebeenprovidingvaluableinformationandtechnologytopredictwhichindividualsareatriskforototoxicity,toimprovethesafetyofaminoglycosideantibiotictherapy,andeventuallytodecreasetheincidenceofdeafness.

简介：Aminoglycosides(AmAn)arewidelyusedfortheirgreatefficiencyagainstgram-negativebacterialinfections.However,theycanalsoinduceototoxichearingloss,whichhasaffectedmillionsofpeoplearoundtheworld.Aspreviouslyreported,individualsbearingmitochondrialDNAmutationsinthe12SrRNAgene,suchasm.1555A>Gandm.1494C>T,aremorepronetoAmAn-inducedototoxicity.Thesemutationscausehumanmitochondrialribosomestomorecloselyresemblebacterialribosomesandenableastrongeraminoglycosideinteraction.Consequently,exposuretoAmAncaninduceorworsenhearinglossintheseindividuals.Furthermore,awiderangeofseverityandpenetranceofhearinglosswasobservedamongfamiliescarryingthesemutations.StudieshaverevealedthatthesemitochondriamutationsaretheprimarymolecularmechanismofgeneticsusceptibilitytoAmAnototoxicity,thoughnuclearmodifiergenesandmitochondrialhaplotypesareknowntomodulatethephenotypicmanifestation.

简介：Cisplatindamagescochlearhaircellsandspiralganglionneuronsthroughcelldeathsignalingpathwaysthatarenotfullyunderstood.Weusedfocusedapoptosisgenemicroarraystostudyearlychangesingeneexpres-sionincochlearculturesfromP3neonatalratstreatedwithcisplatin(0.2mM).After12hoursofcisplatintreat-ment,morethan50%ofthe96genesonthearrayshowedasignificantdecreaseinexpression,consistentwithwidespreadcelldeath.However,after3hoursofcisplatintreatment,10genesshowedsignificantincreaseinex-pressionintotalcochleartissue.Inexperimentswithsubsetsofcochleartissues,at3h,cisplatininducedincreasedexpressionof12genesinthecochlearsensoryepithelium(basilarmembrane)and11genesinthespiralganglion(tissueofRosenthal'scanal,containingthespiralganglion).Theseincludedpro-andanti-apoptoticgenesin-volvedinthep53signalingpathway,TNFreceptorfamily,NF-kappaBpathway,deathdomainfamily,deatheffec-tordomainfamily,Bcl-2family,CARDfamily,TRAFfamily,andGTPsignaltransduction.Althoughthechangesingeneexpressionshowedanoverlapbetweenbasilarmembraneandspiralganglion,otherchanges,whichmayreflecttheuniqueresponseofeachtissue,werealsoobserved.Pifithrin-αblockedcisplatin-inducedup-regulationofgenesinthep53signalingpathwaywhenassayedbybothsuperarrayandrealtimePCR.Thedataaddtoourunderstandingoftheinvolvementofp53incisplatin-inducedototoxicityandotoprotection,conferredbythep53inhibitorPifithrin-α.

简介：ObjectiveToinvestigatetheearlychangeofcochlearribbonsynapsesoninnerhaircellsinresponsetoaminoglycosideototoxicity.MethodsC57BL/6Jmicereceivedintraperitonealinjectionofgentamicin(100mg/kg/day),andtheapicalcoilorganofCortiwasexaminedonthe4th,7thand10thday(n=10).Litter-mateswithoutgentamicintreatmentservedascontrols(n=10).RIBEYEonthepresynapticmembraneandAMPAreceptorsonthepostsynapticmembranewerelabeledwithCtBP2orGluR2/3respectively.Threedi-mensionreconstructionwasconductedusingthe3DSMAX8.0software.ResultsTherewerenodisruptionsofouterorinnerhaircellsinallgroups.However,thenumberofribbonsynapsesoncochlearinnerhaircellsincreasedsignificantlywithin7daysaftergentamicinexposure(P<0.01),followedbyasignificantde-creaseafter7days.ConclusionDuringtheearlystageofaminoglycosideototoxicity,increasedpopulationofcochlearribbonsynapsesmayindicateasignificantdown-regulationofsynapticfunction.