简介：Despitetheadvancesincombinatorialorsyntheticchemistryandbioinformatics,recentliteraturehasdemonstratedtherelevanceofnatureandbiomassasasourceofnewmoleculestotreatdifferentpathologies,i.e.,bioactivecompoundsobtainedfromEcteinascidiaturbinatetotreatsometypesofcancerorrapamycinfromStreptomyceshygroscopicustopreventorganrejectionaftertransplant.Thistrend

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：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.

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简介：Microtubulesplayimportantrolesinneuronalmorphogenesis,includingcellularpolarization,neuritegrowth,andbranching.Amicrotubuleisapolymerofα-andβ-tubulinheterodimersthatareformedbyamultistepprocessassistedbyatleastfivetubulin-foldingcofactors(TBCA–E)(Lopez-Fanarragaetal.,2001).Newlysynthesizedα-andβ-tubulinsassociatewiththecytosolicchaperonincomplex(CCT),andthenthequasi-nativetubulinsinteractwith

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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.

简介：BACKGROUND:ResearchesindicatethatpatientswithWilsondisease(WD)haveabnormalskeletalmetabolism,whichisinducedbyvariousfactors.OBJECTIVE:ToprobeintothechangingcharacteristicsofabnormalskeletalmetabolisminWDpatientsandobservetheeffectofdecoppertherapy.DESIGN:Case-contrastandself-controlstudy.SETTING:DepartmentofNeurology,AffiliatedHospitalofNeurologicalInstitute,AnhuiCollegeofTraditionalChineseMedicine.PARTICIPANTS:Atotalof35patientswithWDincluding21malesand14femalesagedfrom10to42yearswiththemeanageof(20±8)yearswereselectedfromDepartmentofNeurology,AffiliatedHospitalofNeurologicalInstitute,AnhuiCollegeofTraditionalChineseMedicinefromSeptember2000toFebruary2001.Allthepatientswereincompliancewiththediagnosticcriteria:historyoffamilyheredity;conesymptomsinvitro,physicalsignorliversymptoms;positiveKayser-Fleischerring;serumcopperprotein＜200mg/LorAcopperoxidase＜0.2;urinecopper＞1.6μmol/24hours;livercopper＞250μg/g(dryweight).Thecontrolgroupwasselectedfrom25casesofhealthindividualsincluding13malesand12femalesagedfrom16to35yearswiththemeanageof(22±6)years.Allpatientswhoparticipatedinthestudywereinformedfirstandconsented.METHODS:Patientsintreatmentgroupweretreatedwithvenousinjectionof1.0gsodiumdimercaptosulfonate,onceadayfortotally6successivedays.Andthen,patientsrestedfor2days.Thisprocedurementionedabovewasregardedasacourse,andthetreatmentlastedfor4-8courses.Beforeandafterinjectionofsodiumdimercaptosulfonate,serumcalcitonin(CT),osteocalcin(BGP),parathyroidhormone(PTH)and1,25-(OH)2VitD3weremeasuredwithradio-immunitymethod:blood,urinecalcium,phosphorumandurinecreatinineweremeasuredwithbiochemicalanalyzer;urinedihydropyrimidinedehydrogenase(DPD)wasdetectedwithenzyme-immunitymethod;bonemineraldensity(BMD)wascheckedattheonethirdfromdistalendofulnaandradiuswithsingle

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简介：Overthepastdecade,nineseparategenetherapyclinicaltrialsforadvancedParkinson’sdisease(PD)havebeenlaunchedandcompleted,involvingthedosingofnearly12-dozenPDvolunteerswhoincurredsignificantriskstohopefullyreducesymptomsand

简介：Alzheimer’sdisease(AD)isoneofthemostdevastatingdiseasesaffectingthelifeandhealthofagingpopulation.TwohallmarksofADaresenileplaquesandneurofibrillarytangles,andADiswellknownforthemassivelossofneuronsandimpairedcognitivefunctionsespeciallymemoryloss.Despiteextensivesearchforeffectivetreatment,available

简介：BACKGROUND:GenetherapyforParkinson'sdiseaseisbeingexploredasaneffectivestrategytorestoreandprotectthefunctionofneuronalcellsinthesubstantianigra.Regulationofgeneexpressionisnecessaryforgenetherapytoavoidadverseeffectsduetoexcessivesynthesisoftransgeneproducts.OBJECTIVE:Herewedevelopedrecombinantadeno-associatedvirus(AAV)asaviralvector-mediatedgeneregulationsystembasedonCrerecombinasefusedtothemutatedligand-bindingdomainoftheestrogenreceptor(CreERT2)+inducingagenttamoxifen.InducibleCrerecombinasewasusedtoreducetyrosinehydroxylasegeneexpressionandtopreventtheexcessiveincreaseindopamine.DESIGN,TIMEANDSETTING:Ageneticengineeringinvitrocomparativestudyandrandomizedcontrolledanimalexperiment.ThisstudywasconductedattheGeneTherapyCenter,JichiMedicalSchool,JapanfromJune2002toJune2004.METHODS:ToconstructarecombinantAAVvectorcarryingadopaminesynthasegene.ThetyrosinehydroxylasegenewasinsertedusingaloxPfragmentthatcouldberegulatedbyCrerecombinase.TherecombinantAAVvectorcarryingtheCreERT2genewasco-transducedwithHEK293cellsandthecorpusstriatuminaratmodelofParkinson'sdisease,withinducingagenttamoxifentoregulategeneexpression.MAINOUTCOMEMEASURES:ThelevelsofdopamineandaromaticL-aminoaciddecarboxylase(AADC)activityweredetectedinHEK293cellmediumandinthecorpusstriatuminaratmodelofParkinson'sdiseaseusinghigh-performanceliquidchromatography.ImmunofluorescencedoublestainingwasusedtoobservetyrosinehydroxylaseandCreorAADCco-expressioninHEK293cellmedium.ImmunohistochemicalstainingwasemployedtoobservetyrosinehydroxylaseandAADCexpressionandbehavioralchangesweremeasuredinParkinson'srats.RESULTS:TransfectedAAV-CreERT2andAAVexpressingdopaminesynthesisenzymescouldincreasethesynthesisofdopamineinHEK293mediumandParkinson'sratstriatum(P<0.01)andimprovetherotationalbehaviorofParkin

简介：Alzheimer’sdisease(AD)isthemostcommontypeofdementiainelderlypopulation.WithagrowingagingpopulationnotonlyintheUnitedStatesbutalsointheworldwide,ADconstitutesanemergentpublichealthproblem.Overdecades,theprevailinghypothesiswasthatneurodegenerationmightresultfromoneortwoofthespecificlesions

简介：Thisstudyadaptedastatisticalprobabilisticanatomicalmapofthebrainforsinglephotonemissioncomputedtomographyimagesofdepressiveend-stagerenaldiseasepatients.Thisresearchaimedtoinvestigatetherelationshipbetweensymptomclusters,diseaseseverity,andcerebralbloodflow.Twenty-sevenpatients(16males,11females)withstages4and5end-stagerenaldiseasewereenrolled,alongwith25healthycontrols.Allpatientsunderwentdepressivemoodassessmentandbrainsinglephotonemissioncomputedtomography.Thestatisticalprobabilisticanatomicalmapimageswereusedtocalculatethebrainsinglephotonemissioncomputedtomographycounts.AsymmetricindexwasacquiredandPearsoncorrelationanalysiswasperformedtoanalyzethecorrelationbetweensymptomfactors,severity,andregionalcerebralbloodflow.ThedepressionfactorsoftheHamiltonDepressionRatingScaleshowedanegativecorrelationwithcerebralbloodflowintheleftamygdale.Theinsomniafactorshowednegativecorrelationswithcerebralbloodflowintheleftamygdala,rightsuperiorfrontalgyrus,rightmiddlefrontalgyrus,andleftmiddlefrontalgyrus.Theanxietyfactorshowedapositivecorrelationwithcerebralglucosemetabolisminthecerebellarvermisandanegativecorrelationwithcerebralglucosemetabolismintheleftglobuspallidus,rightinferiorfrontalgyrus,bothtemporalpoles,andleftparahippocampus.Theoveralldepressionseverity(totalscoresofHamiltonDepressionRatingScale)wasnegativelycorrelatedwiththestatisticalprobabilisticanatomicalmapresultsintheleftamygdalaandrightinferiorfrontalgyrus.Inconclusion,ourresultsdemonstratedthatthediseaseseverityandextentofcerebralbloodflowquantifiedbyaprobabilisticbrainatlaswasrelatedtovariousbrainareasintermsoftheoverallseverityandsymptomfactorsinend-stagerenaldiseasepatients.

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