简介:Inthepresentstudy,aseriesofnovelnitricoxide-hydrogensulfidereleasingderivativesof(S)-3-n-butylphthalide((S)-NBP)weredesigned,synthesized,andevaluatedaspotentialantiplateletagents.CompoundNOSH-NBP-5displayedthestrongestactivityininhibitingthearachidonicacid(AA)-andadenosinediphosphate(ADP)-inducedplateletaggregationinvitro,with3.8-and7.0-foldmoreeffectivenessthan(S)-NBP,respectively.Furthermore,NOSH-NBP-5couldreleasemoderatelevelsofNOandH2S,whichwouldbebeneficialinimprovingcardiovascularandcerebralcirculation.Moreover,NOSH-NBP-5couldrelease(S)-NBPwhenincubatedwithratbrainhomogenate.Inconclusion,thesefindingsmayprovidenewinsightsintothedevelopmentofnovelantiplateletagentsforthetreatmentofthrombosis-relatedischemicstroke.
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: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:摘要目的对ICU护理风险与各变量之间的关系进行分析,为针对性预防ICU护理风险提供依据。方法采用自行设计的《ICU护理风险影响因素调查表》,抽样调查365名贵州省三级医院ICU护理人员,运用结构方程模型对数据进行拟合与评估,构建护理风险影响因素的结构方程模型。结果构建的结构方程模型各项拟合指标均符合要求,组织管理、制度建设、支持系统、患者因素四项外在因素对护理风险有直接和间接影响,影响总效果分别为-0.749、-0.247、-0.206、-0.182。护士基本素质、知识技能、服务态度、协作能力四项内在因素是影响护理风险的中介环节,影响总效果分别为-0.342、-0.178、-0.052、-0.046。结论护理风险的发生受内外因的共同影响,管理者需要加强外因建设,通过外因影响内因,提高护士风险防范能力,从而减少ICU护理风险的发生。
简介:摘要目的探索S拉钩在阴道试产失败中转剖宫产病例中的临床效果。方法选取2013年1月至2016年8月期间我院收治的30例阴道试产失败中转剖宫产产妇,将产妇动态随机化分为两组,两组产妇各有15例,对照组和观察组分别采用传统剖宫术和s拉钩辅助剖宫术。结果观察组产妇的术中出血量(164.35±10.84)ml、手术时间(35.69±3.95)min、子宫切口延伸发生率(6.67%)、新生儿窒息发生率(0.00%)、子宫切口裂伤发生率(6.67%)、产后24小时疼痛评分(3.05±1.65)分、产后48小时疼痛评分(1.05±0.98)分、产后72小时疼痛评分(0.56±0.36)分均优于对照组产妇(P<0.05)。结论S拉钩在阴道试产失败中转剖宫产病例中效果显著。