Prostaglandins & Oxidative Damage in ADAPT Participants
Prostaglandins & Oxidative Damage in ADAPT Participants
批准号:
7273520
负责人:
John C S Breitner
金额:
$29.43万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2003
资助国家:
美国
项目状态:
已结题
起止时间:
2003-09-30 至 2009-08-31
关键词:
AftercareAge-associated memory impairmentAlzheimer disease preventionAlzheimer&aposs DiseaseAnti-Inflammatory AgentsAnti-inflammatoryAspirinBiological AssayBiological MarkersClinicalClinical ResearchClinical TreatmentClinical TrialsCultured CellsDataDementiaDoseDrug usageDrug userEicosanoid ProductionEnd PointEnrollmentEnzymesEpidemiologic StudiesFoundationsFundingGoalsHumanIbuprofenImpaired cognitionIncidenceIndividualLaboratoriesLipid PeroxidationMeasuresNeuraxisOutcomeParticipantPathogenesisPathologic ProcessesPatientsPeptidesPharmaceutical PreparationsPhasePreventionProceduresProcessProductionProstaglandin ProductionProstaglandin-Endoperoxide SynthaseProstaglandinsRateResearch PersonnelResourcesSpecimenStagingTestingTransgenic MiceTreatment Efficacycyclooxygenase 1cyclooxygenase 2insightpre-clinicalpreventprogesterone 11-hemisuccinate-(2-iodohistamine)protective effect
中文摘要
几项大型流行病学研究表明,阿尔茨海默氏症的发病率显著降低
服用非类固醇抗炎药(NSAIDs)时间超过
2年。然而,在已确诊的AD患者中进行的非类固醇抗炎药的临床试验并未显示出疗效。这有
导致假设非类固醇抗炎药抑制对AD的启动至关重要的病理过程,并且这些
这一过程可能与抑制环氧合酶和随后的前列腺素(PG)有关。
制作。我们建议通过量化受试者内源性二十烷类化合物的产生来检验这一假说。
参加由NIA赞助的阿尔茨海默病抗炎预防试验(Adapt)
非甾体抗炎药在预防阿尔茨海默病中的作用。具体地说,我们将1)确定选择性和非选择性的疗效
选择性非甾体类抗炎药抑制1种定量标记物的系统和临床应用
适应受试者的中枢神经系统;2)确定非类固醇抗炎药抑制
系统性氧化损伤和适应性中枢神经系统氧化损伤的定量生物标志物
参与者;以及3)PG产生的生物标志物水平的变化与氧化损伤的相关性
认知功能减退的速度在适应中确定。我们已经开发出高度精确和精确的
对前列腺素、前列腺素代谢产物和脂质过氧化产物进行定量的质谱分析是常规的
在我们的实验室进行这些检测。这些研究将为了解这些机制提供重要的见解。
非甾体类抗炎药通过它来预防AD。
英文摘要
Several large epidemiological studies have associated a profound reduction in the incidence of Alzheimer's
Disease (AD) in older individuals who took non-steroidal anti-inflammatory drugs (NSAIDs) for longer than
2 years. However, clinical trials of NSAIDs in patients with established AD failed to show efficacy. This has
led to the hypothesis that NSAIDs suppress pathologic processes critical to the initiation of AD and that these
processes may be related to inhibition of the cyclooxygenase enzymes and subsequent prostaglandin (PG)
production. We propose to test this hypothesis by quantifying endogenous eicosanoid production in subjects
enrolled in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT), an NIA-sponsored study
of NSAIDs in the prevention of AD. Specifically, we will 1) determine the efficacy of selective and non-
selective NSAIDs t o suppress 1 evels o f quantitative b iomarkers o f P G p reduction systemically and in t he
central nervous system of ADAPT participants; 2) determine the efficacy of NSAIDs to suppress levels of
quantitative biomarkers of oxidative damage systemically and in the central nervous system of ADAPT
participants; and 3) correlate changes in the levels of biomarkers of PG production and oxidative damage
with rates of cognitive decline as determined in ADAPT. We have developed highly accurate and precise
mass spectrometric assays to quantify PGs, PG metabolites, and lipid peroxidation products and are routinely
performing these assays in our laboratory. These studies will provide important insights into the mechanisms
by which NSAIDs prevent AD.
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Prostaglandins & Oxidative Damage in ADAPT Participants
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批准号:6794320
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项目类别:
-
资助金额:$28.54万
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财政年份:2003
-
负责人:John C S Breitner
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依托单位:
Prostaglandins & Oxidative Damage in ADAPT Participants
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批准号:6933146
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项目类别:
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资助金额:$31.04万
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财政年份:2003
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负责人:John C S Breitner
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依托单位:
Prostaglandins & Oxidative Damage in ADAPT Participants
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批准号:6802719
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项目类别:
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资助金额:$27.89万
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财政年份:2003
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负责人:John C S Breitner
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依托单位:
Prostaglandins & Oxidative Damage in ADAPT Participants
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批准号:7119183
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项目类别:
-
资助金额:$30.31万
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财政年份:2003
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负责人:John C S Breitner
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依托单位:
PREVENTION OF ALZHEIMER DEMENTIA & COGNITIVE DECLINE
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批准号:6725374
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项目类别:
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资助金额:$421.11万
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财政年份:2000
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负责人:John C S Breitner
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依托单位:
PREVENTION OF ALZHEIMER DEMENTIA & COGNITIVE DECLINE
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批准号:6502289
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项目类别:
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资助金额:$12.4万
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财政年份:2000
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负责人:John C S Breitner
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依托单位:
Prevention of Alzheimer Dementia and Cognitive Decline
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批准号:7916459
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项目类别:
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资助金额:$286.98万
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财政年份:2000
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负责人:John C S Breitner
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依托单位:
PREVENTION OF ALZHEIMER DEMENTIA & COGNITIVE DECLINE
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批准号:7049675
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项目类别:
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资助金额:$613.16万
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财政年份:2000
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负责人:John C S Breitner
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依托单位:
PREVENTION OF ALZHEIMER DEMENTIA & COGNITIVE DECLINE
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批准号:6754733
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项目类别:
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资助金额:$10.0万
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财政年份:2000
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负责人:John C S Breitner
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依托单位:
PREVENTION OF ALZHEIMER DEMENTIA & COGNITIVE DECLINE
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批准号:6041161
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项目类别:
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资助金额:$478.78万
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财政年份:2000
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负责人:John C S Breitner
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依托单位:
PREVENTION OF ALZHEIMER DEMENTIA & COGNITIVE DECLINE
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批准号:6362223
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项目类别:
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资助金额:$679.78万
-
财政年份:2000
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负责人:John C S Breitner
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依托单位:
PREVENTION OF ALZHEIMER DEMENTIA & COGNITIVE DECLINE
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批准号:6594396
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项目类别:
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资助金额:$12.01万
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财政年份:2000
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负责人:John C S Breitner
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依托单位:
PREVENTION OF ALZHEIMER DEMENTIA & COGNITIVE DECLINE
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批准号:6509864
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项目类别:
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资助金额:$518.82万
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财政年份:2000
-
负责人:John C S Breitner
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依托单位:
PREVENTION OF ALZHEIMER DEMENTIA & COGNITIVE DECLINE
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批准号:6682750
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项目类别:
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资助金额:$560.46万
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财政年份:2000
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负责人:John C S Breitner
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依托单位:
PREVENTION OF ALZHEIMER DEMENTIA & COGNITIVE DECLINE
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批准号:7188320
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项目类别:
-
资助金额:$539.7万
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财政年份:2000
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负责人:John C S Breitner
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依托单位:
Prevention of Alzheimer Dementia and Cognitive Decline
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批准号:7467669
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项目类别:
-
资助金额:$311.58万
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财政年份:2000
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负责人:John C S Breitner
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依托单位:
HEAD INJURY & ALZHEIMER'S DISEASE
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批准号:2294208
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项目类别:
-
资助金额:$23.37万
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财政年份:1994
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负责人:John C S Breitner
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依托单位:
HEAD INJURY & ALZHEIMER'S DISEASE
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批准号:2294206
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项目类别:
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资助金额:$118.12万
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财政年份:1994
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负责人:John C S Breitner
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依托单位:
EPIDEMIOLOGY OF ALZHEIMERS DEMENTIA IN CACHE COUNTY UT
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批准号:2052560
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项目类别:
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资助金额:$140.1万
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财政年份:1994
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负责人:John C S Breitner
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依托单位:
HEAD INJURY & ALZHEIMER'S DISEASE
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批准号:2294204
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项目类别:
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资助金额:$72.41万
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财政年份:1994
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负责人:John C S Breitner
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依托单位:
海外基金