简介:Thequestforneuroprotectivedrugstoslowtheprogressionofneurodegenerativediseases(NDDs),includingAlzheimer'sdisease(AD),Parkinson'sdisease(PD),andHuntington'sdisease(HD),hasbeenlargelyunrewarding.Preclinicalevidencesuggeststhatrepurposingquetiapine,lithium,valproate,fluoxetine,donepezil,andmemantineforearlyandpre-symptomaticdisease-modificationinNDDsmaybepromisingandcanspareregulatorybarriers.Theliteratureofthesepsychotropicsinearlystageandpre-symptomaticAD,PD,andHDisreviewedandpropitiousfindingsfollow.Mildcognitiveimpairment(MCI)phaseofAD:salutaryhumanrandomizedcontrolledtrialfindingsforlow-doselithiumand,inselectedpatients,donepezilawaitreplication.Pre-symptomaticAD:humanepidemiologicaldataindicatethatlithiumreducesADrisk.Animalmodelstudies(AMS)revealencouragingresultsforquetiapine,lithium,donepezil,andmemantine.EarlyPD:valproateAMSfindingsshowpromise.Pre-symptomaticPD:lithiumandvalproateAMSfindingsareencouraging.EarlyHD:uncontrolledclinicaldataindicatenon-progressionwithlithium,fluoxetine,donepezil,andmemantine.Pre-symptomaticHD:lithiumandvalproateareauspiciousinAMS.Manyotherpromisingfindingsawaitingreplication(valproateinMCI;lithium,valproate,fluoxetineinpre-symptomaticAD;lithiuminearlyPD;lithium,valproate,fluoxetineinpre-symptomaticPD;donepezilinearlyHD;lithium,fluoxetine,memantineinpre-symptomaticHD)arereviewed.Dose-andstage-dependenteffectsareconsidered.Suggestionsforsignal-enhancementinhumantrialsareprovidedforeachNDDstage.
简介:Neurotrophicfactorscompriseessentialsecretedproteinsthathaveseveralfunctionsinneuralandnon-neuraltissues,mediatingthedevelopment,survivalandmaintenanceofperipheralandcentralnervoussystem.Therefore,neurotrophicfactorissuehasbeenextensivelyinvestigatedintothecontextofneurodegenerativediseases.Alzheimer'sdiseaseandParkinson'sdiseaseshowchangesintheregulationofspecificneurotrophicfactorsandtheirreceptors,whichappeartobecriticalforneuronaldegeneration.Indeed,neurotrophicfactorspreventcelldeathindegenerativeprocessesandcanenhancethegrowthandfunctionofaffectedneuronsinthesedisorders.Basedonrecentreports,thisreviewdiscussesthemainfindingsrelatedtotheneurotrophicfactorsupport–mainlybrain-derivedneurotrophicfactorandglialcellline-derivedneurotrophicfactor–inthesurvival,proliferationandmaturationofaffectedneuronsinAlzheimer'sdiseaseandParkinson'sdiseaseaswellastheirputativeapplicationasnewtherapeuticapproachforthesediseasesmanagement.
简介:BACKGROUND:Conventionalmethods(suchasocclusiontherapy,finemanipulation,complementary,andalternativemedicine)takeeffectsslowly,aretimeandlaborconsuming,andhaveuncertaincurativeeffectsinthetreatmentofamblyopia.Perceptuallearning,anewmethodfortreatingamblyopia,improvestheabilitytoprocesssignalsfromthecerebralopticnervesystembyspecificvisualstimulationandvisuallearning,aswellasactivationofthevisualsignalpathwayutilizingbrainnervoussystemplasticity.OBJECTIVE:Thisstudyinvestigatedandevaluatedthecurativeeffectsofperceptuallearning,whichcandirectionallyincreasebrainplasticity,onthetreatmentofamblyopiainchildren.Therelationshipbetweencurativeeffectandtimewasalsoanalyzed.DESIGN:Aself-controlexperiment.SETTING:VisualScienceandOptometryCenter,People'sHospitalofGuangxiZhuangAutonomousRegion.PARTICIPANTS:Atotalof125amblyopicchildren(250amblyopiceyes),73males,52females,averaging(6±2)yearsofage,receivedtreatmentattheVisualScienceandOptometryCenter,People'sHospitalofGuangxiZhuangAutonomousRegionbetweenSeptember2006andFebruary2007andwererecruitedforthisstudy.Allchildrenpresentedwithnostructuraldiseaseoftheeyeballs.Writteninformedconsentfortherapeuticregimentswasobtainedfromeachchild'sparent.TheprotocolreceivedapprovalfromtheHospital'sEthicsCommittee.METHODS:Visualfunctionwastestedwithaperceptuallearningsystem(ResearchCenterforHumanHealthandDevelopmentofSunYat-senUniversity,NationalEngineeringTechniqueResearchCenterforMedicalCareImplement)forvisualnoise,positionnoise,contourdiscrimination,contrastsensitivity,gratingstereogram,andrandom-dotfusion.Thesetestshelpedtoevaluatetheefficiencyofvisualinformationprocessingofthesechildren,andtodeterminethedegreeofdefectsoftheopticnervecellsandtheconnectionsofvisualcorticalneurons.Accordingtoresultsofvisualfunct
简介:BACKGROUND:Traditionalsubhibernationtherapymayeasilycausecomplications,suchasrespiratorydepressionandhyportensionbecauseofapplicationofchlorpromazinehydrochlorideandpromethazineinalargedosage.OBJECTIVE:Toobservetherapeuticeffectofmodifiedsubhibernationtherapy(alterativeapplicationoffiveanticonvulsantsaccordingtothehalflife)onstatusepilepticusinchildrenwithsevereviralencephalitis(VE).DESIGN:Contrastobservation.SETTING:DepartmentofPediatrics,theFirstHospitalofJilinUniversity.PARTICIPANTS:Theparticipantsinpresentstudywere96patientswithsevereviralencephalitisincluding52boysand44girlswhoreceivedtreatmentintheDepartmentofPediatrics,theFirstHospitalofJilinUniversityfromFebruary2000toMarch2006.AllchildrenmetthediagnosticcriteriaofZhufutongPracticePediatrics(theseventhedition).Twoweeksago,theyevergotupperrespiratoryinfectionorenteronitisandsoonbeforetheonset,spiritabnormal,behaviordisorder,limbsactdisorder,vomit,headache,convulsion,nervoussystemmasculinesignssuchaslimbsactdisord,autonomicnervedamagemanifestation,brainnervepalsy,dysreflexia,meningealirritationsign,cerebrospinalfluidandelectroencephalography(EEG)abnormity.Allparentsprovidedtheconfirmedconsent.Thepatientswererandomlydividedintocontrolgroup(n=40)andexperimentalgroup(n=56).METHODS:Patientsinthecontrolgroupreceivedanticonvulsion,icecompressandroutinetreatment.Theconvulsionwastreatedwithfivedrugs:0.5mg/kgwinterminandphenergan,respectively,100g/Lchlorpromazinehydrochloride(0.5mL/kg),5mg/kgluminal,0.3mg/kgansiolin.Whenconvulsionattacked,thosefivedrugsweregivenalternatively;however,thosewerenotgiveniftheconvulsiondidnotattack.Childrenintheexperimentalgroupweretreatedwithimprovedsubhibernationtherapybasedonroutinetreatment.Thedosagesofanticonvulsantswereasthesameasthoseinthecontrolgroup.Bas
简介:BACKGROUND:Itisdifficulttoattractinterestinnon-compulsory,preventive,medicalcare,andpersonsdiagnosedwithcertaindiseasesoftenignoretheexistenceofthesediseases.However,Huntington'sdisease(HD)isanexception.OBJECTIVE:ToqualitativelyanalyzefactorsmotivatingHDpatientstoparticipateinastudy,namelytheEuropeanHuntington'sDiseaseNetwork(EHDN)REGISTRY.DESIGN,TIMEANDSETTING:AnobservationalsurveywasconductedintheEHDNStudySiteinPoznan,Polandbetween2007and2008.PARTICIPANTS:Thestudyinvolved22personsaffectedwithHDand3pre-symptomaticindividuals,totaling9malesand16females.The24participantsinthisstudyhad24differentcaregivers.Atotalof25symptomaticorpre-symptomaticsubjectsparticipatedintheinitialREGISTRYvisit,aswellas6inthesecond,and1inthethird.Allsubjectsdidnotknoweachotherpriortothevisit.METHODS:AmutationintheIT15genewasconfirmedineachpatientorpre-symptomaticmutationcarrier.Anin-depthinterviewproduceddetailedinformationontheHDpatients,aswellasthecaregivers,fortheREGISTRYstudy.MAINOUTCOMEMEASURES:AqualitativeanalysisofthefactorsmotivatingHDpatientsandthepre-symptomaticmutationcarrierstoparticipateintheREGISTRYlongitudinal,observational,researchprojectwasperformed.RESULTS:TheprimarymotivatingfactorforinvolvementofHDpatientsandthecaregiversintheREGISTRYstudywasthehopethataneffectiveHDtherapywouldsoonbediscovered.InHDpatientsandthepre-symptomaticgroup,theresponsetoparticipateintheREGISTRYprojectreached100%,despitethefactthattheyknewtheprojectwasonlyanobservationalstudy.CONCLUSION:Patienthopeisthoughttobeafactorforengaginginpreventive,therapeuticactivities.However,thisisrarelymentionedinmedicalpapersandclinicaltextbooks,andisusuallyoverlookedinmedicalteaching.Clearly,effortsshouldbemadetoincludethisinclinicalpractice.
简介:BACKGROUND:Theuseofacupuncturehasreceivedrecognitiontoeffectivelytreatcerebralpalsy.Moreover,musictherapycanbeusedtomodifytreatmentofcerebralpalsy.OBJECTIVE:Tostudytheeffectsofcombinedtreatmentusingacupunctureandmusictherapyongrossmotorfunctionmeasure(GMFM)ofchildrenwithcerebralpalsy,comparedwithacupuncturetreatmentalone.DESIGN,TIMEANDSETTING:Randomized,controlled,clinicalstudy.TheexperimentwasconductedinShenzhenHospitalofTraditionalChineseMedicinebetweenJanuary2007andSeptember2007.PARTICIPANTS:AllchildrenwithcerebralpalsyinthetrialwerefromtheoutpatientdepartmentofShenzhenHospitalofTraditionalChineseMedicine.Thechildrenwererandomlydividedintotwogroups:30childreninGroupBreceivedacupunctureandmusictherapy,while30childreninGroupAreceivedonlyacupuncturetherapy.METHODS:SubjectsinGroupsAandBreceivedacupuncturebasedonsyndromedifferentiation.Themainacupointswerenecessaryforallparticipants.Atfirst,flashneedlingwasappliedtotheacupoints.Fortheremainingacupoints,thetechniqueoftransverseneedlingwasappliedtotheheadacupoints,andperpendicularneedlingwasusedfortheotherpoints.Theinsertedneedlesweretwirledandthenmaintainedfor30minutes.Theneedlewastwirledforonesecondeveryother10minutes,withoutreinforcing-reducingtechniques.Thetherapywasperformedeveryotherday.Thetrialconsistedofthreeperiodseach,andlastedfor84days.SubjectsinGroupBreceivedmusictherapy.Theylistenedtomusicthattheypreferredwhileacupuncturewasbeingperformed.Followingacupuncture,theywereallowedtoperformmusicalactivities,suchaspercussion,singing,anddancing.Themusictherapywasscheduledforonehour,includinglisteningtomusicfor30minutesandmusicactivitiesfor30minutes.MAINOUTCOMEMEASURES:ThecomprehensivefunctionalevaluationscaleofcerebralpalsyandtheGMFMwereappliedtotestsymptomsbeforeand
简介:Parkinsonsdisease(PD)isacommon,progressiveneurodegenerativediseasecharacterisedbydegenerationofnigrostriataldopaminergicneurons,aggregationofα-synucleinandmotorsymptoms.Currentdopamine-replacementstrategiesprovidesymptomaticrelief,howevertheireffectivenesswearoffovertimeandtheirprolongeduseleadstodisablingside-effectsinPDpatients.ThereisthereforeacriticalneedtodevelopnewdrugsanddrugtargetstoprotectdopaminergicneuronsandtheiraxonsfromdegenerationinPD.Overrecentyears,therehasbeenrobustevidencegeneratedshowingthatepigeneticdysregulationoccursinPDpatients,andthatepigeneticmodulationisapromisingtherapeuticapproachforPD.Thisarticlefirstdiscussesthepresentevidenceimplicatingglobal,anddopaminergicneuron-specific,alterationsinthemethylomeinPD,andthetherapeuticpotentialofpharmacologicallytargetingthemethylome.Itthenfocusesonanothermechanismofepigeneticregulation,histoneacetylation,anddescribeshowthehistoneacetyltransferase(HAT)andhistonedeacetylase(HDAC)enzymesthatmediatethisprocessareattractivetherapeutictargetsforPD.Itdiscussestheuseofactivatorsand/orinhibitorsofHDACsandHATsinmodelsofPD,andhowtheseapproachesfortheselectivemodulationofhistoneacetylationelicitneuroprotectiveeffects.Finally,itoutlinesthepotentialofemployingsmallmoleculeepigeneticmodulatorsasneuroprotectivetherapiesforPD,andthefutureresearchthatwillberequiredtodetermineandrealisethistherapeuticpotential.
简介:Propofolcaninhibittheinflammatoryresponseandreducethesecretionandharmfuleffectsofastrocyte-derivedproinflammatorycytokines.Inthisstudy,afterpropofolwasinjectedintotheinjuredsciaticnerveofmice,nuclearfactorkappaBexpressionintheL4-6segmentsofthespinalcordintheinjuredsidewasreduced,apoptosiswasdecreased,nervemyelindefectswerealleviated,andthenerveconductionblockwaslessened.Theexperimentalfindingsindicatethatpropofolinhibitstheinflammatoryandimmuneresponses,decreasestheexpressionofnuclearfactorkappaB,andreducesapoptosis.Theseeffectsofpropofolpromoteregenerationfollowingsciaticnerveinjury.
简介:BACKGROUND:ToevaluatethequalityoftheliteratureaddressingtraditionalChinesemedicinefortreatingParkinson'sdisease.DATASOURCE:Acomputer-basedonlinesearchofChinesepublicationsfromJanuary2001toJuly2008wasconductedinChineseBiologyMedicalDiscDatabaseandChinaNationalKnowledgeInfrastructure.SearchkeywordswereParkinson'sdisease,integratedtraditionalChineseandWesternmedicine,traditionalChinesemedicinetherapy,andChineseherbtherapy.DATASELECTION:Articlesdescribingrandomized,controlledtrialsandquasi-randomized,controlledtrialswereincluded.Literaturequalitywasassessedusingthecriteria-SystematicevaluationofclinicalliteraturerelatedtotreatmentofParkinson'sdiseasewithtraditionalChinesemedicine.Thisincludedmethodology,interventionsinthetreatment/controlgroup,evaluationcriterionofoutcomes,andfrequency.MAINOUTCOMEMEASURES:Evaluationcriterionofoutcomes(variousscoremethodsandevaluationscales),methodologicalquality,andfrequencydistributionwereallmeasured.RESULTS:Atotalof33articleswithrandomized,controlledtrialswereincluded.Ofthese,sixdescribedarandommethod,andtheremainingdidnotdescriberandomallocationmethodsorrandomsequencegenerationmethods.Noneofthestudiesestimatedsamplesize.Casedescriptionsofwithdrawalandlosstofollow-upwereunclear.BoththeUnifiedParkinson'sDiseaseRatingScaleandWebsterscalewereusedintheeligiblestudiesasevaluationcriteria.CONCLUSION:Therearenohigh-qualitystudiesthataddresstraditionalChinesemedicinetherapyandintegratedtraditionalChineseandWesternmedicinefortreatingParkinson'sdiseaseinChina.EligiblestudieswerenotperformedinaccordancewithConsolidatedStandardsofReportingTrialsstatementorStandardsforReportingInterventionsinControlledTrialsofAcupuncturecriteria,andtheliteraturequalitywaslow.ThepresentlyusedcriteriaforevaluatingtherapeuticeffectsdonotcompletelyassessoutcomesoftraditionalCh
简介:Parkinson’sdisease(PD)isanage-relatedneurodegenerativedisordercharacterizedbytypicalmotorsignsandsymptomsthatareduetodopamine(DA)depletioninthebasalganglia.ThetreatmentofPDissymptomatic,andaimsatreplacingthelostDAinputusingeitherL-DOPAorDAagonists.ThecausesofPDareunknownin
简介:SubthalamicnucleusdeepbrainstimulationhasbecomeastandardneurosurgicaltherapyforadvancedParkinson’sdisease.Subthalamicnucleusdeepbrainstimulationcandramaticallyimprovethemotorsymptomsofcarefullyselectedpatientswiththisdisease.Surprisingly,somespecificdimensionsofqualityoflife,"psychological"aspectsandsocialadjustmentdonotalwaysimprove,andtheycouldsometimesbeevenworse.Patientsandtheirfamiliesshouldfullyunderstandthatsubthalamicnucleusdeepbrainstimulationcanalterthemotorstatusandtimeisneededtoreadapttotheirnewpostoperativestateandlifestyles.Thispaperreviewstheliteraturesregardingeffectsofbilateralsubthalamicnucleusdeepbrainstimulationonsocialadjustment,qualityoflifeandcopingstrategiesinpatientswithParkinson’sdisease.ThefindingsmayhelptounderstandthepsychosocialmaladjustmentandpoorimprovementinqualityoflifeinsomeParkinson’sdiseasepatients.
简介:Genisteiniseffectiveagainstamyloid-βtoxicity,buttheunderlyingmechanismsareunclear.Wehypothesizedthatgenisteinmayprotectneuronsbyinhibitingthemitochondrialapoptoticpathway,andtherebyplayaroleinthepreventionofAlzheimer'sdisease.AratmodelofAlzheimer'sdiseasewasestablishedbyintraperitonealinjectionofD-galactoseandintracerebralinjectionofamyloid-βpeptide(25–35).Inthegenisteintreatmentgroups,a7-daypretreatmentwithgenistein(10,30,90mg/kg)wasgivenpriortoestablishingAlzheimer'sdiseasemodel,for49consecutivedays.Terminaldeoxyribonucleotidyltransferase-mediateddUTPnickendlabelingassaydemonstratedareductioninapoptosisinthehippocampusofratstreatedwithgenistein.Westernblotanalysisshowedthatexpressionlevelsofcapase-3,Baxandcytochromecweredecreasedcomparedwiththemodelgroup.Furthermore,immunohistochemicalstainingrevealedreductionsincytochromecandBaximmunoreactivityintheserats.MorriswatermazerevealedasubstantialshorteningofescapelatencybygenisteininAlzheimer'sdiseaserats.Thesefindingssuggestthatgenisteindecreasesneuronallossinthehippocampus,andimproveslearningandmemoryability.Theneuroprotectiveeffectsofgenisteinareassociatedwiththeinhibitionofthemitochondrialapoptoticpathway,asshownbyitsabilitytoreducelevelsofcaspase-3,Baxandcytochromec.