FATTY ACID-DERIVED MEDIATORS OF INFLAMMATION
FATTY ACID-DERIVED MEDIATORS OF INFLAMMATION
批准号:
3140952
负责人:
SIMON J GASKELL
金额:
$13.01万
依托单位国家:
美国
项目类别:
财政年份:
1988
资助国家:
美国
项目状态:
已结题
起止时间:
1988-07-01 至 1991-06-30
关键词:
bile blood chemistry blood lipid body fluids cellular pathology diagnosis design /evaluation eicosanoid metabolism gas chromatography mass spectrometry high performance liquid chromatography human subject immunochemistry immunoconjugates inflammation laboratory rat leukotrienes lipoxygenase molecular pathology tritium urinalysis
中文摘要
提高对5-脂氧合酶(5-LO)作用的认识
英文摘要
Improved understanding of the role of 5-lipoxygenase (5-LO)
products as mediators or products of cell injury and/or
inflammation requires techniques for their accurate and precise
quantification. The requirement for analyses of high sensitivity
and selectivity, together with difficulties of data interpretation
associated with ex vivo production, indicate that it is important
to establish reference analytical methods for the the assay of
those 5-LO metabolites that most reliably reflect in vivo
production. Accordingly, we propose to develop analytical
procedures based on mass spectrometry and to evaluate these
methods with the assay of physiological fluids derived from an
animal model and from normal human volunteers. we believe it is
premature to propose expensive studies of patient populations at
this stage but we anticipate subsequent application of our
procedures to the investigation of human disease states by
separate funding. The method for the analysis of leukotriene B4
(LTB4) and related compounds will incorporate solid phase
extraction (including the use of coupled anti-LTB4 serum), HPLC
purification and detection of the pentafluorobenzyl ester,
trimethylsilyl ether derivatives by gas chromatography (GC)-
electron capture negative ion mass spectrometry (MS) with
selective reaction monitoring. The peptido-leukotrienes will be
extracted from biological fluids using C18-silica cartridges,
purified by reverse-phase HPLC and determined by continuous-
flow fast atom bombardment/tandem MS, with selected reaction
monitoring. The alternative approach will also be followed of
hydrogenation and reductive cleavage to yield 5-
hydroxyeicosanoic acid, which will be determined by GC-electron
capture negative in MS. The analytical procedures will be
assessed by analysis of biological fluids from a well understood
animal model, namely the rat subjected to endotoxin shock.
Studies in normal human volunteers will involve the determination
of 5-HETE, LTB4 and a stable metabolite (20-hydroxy LTB4) in
blood plasma and other fluids. Sampling conditions will be adopted
which minimize ex vivo production. The influence of ex vivo
stimulation on the concentration of 20-hydroxy LTB, will also be
assessed. As a further means of monitoring 5-LO activity without
the interference of ex vivo production, we will determine LTE4 in
urine. Finally, if marked inter-individual differences are apparent
in urinary LTE4 levels of normal volunteers, direct assessments of
LT production rates will be made following infusion of tritiated
analogues of the leukotrienes.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
HYBRID TANDEM MASS SPECTROMETRY OF PEPTIDE CONJUGATES
-
批准号:3305420
-
项目类别:
-
资助金额:$20.08万
-
财政年份:1992
-
负责人:SIMON J GASKELL
-
依托单位:
GAS PHASE ANALYTICAL CHEMISTRY OF PEPTIDE IONS
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批准号:3307762
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项目类别:
-
资助金额:$13.15万
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财政年份:1992
-
负责人:SIMON J GASKELL
-
依托单位:
TRIPLE QUADRUPOLE ELECTROSPRAY MASS SPECTROMETER
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批准号:3520937
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项目类别:
-
资助金额:$32.9万
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财政年份:1991
-
负责人:SIMON J GASKELL
-
依托单位:
FATTY ACID-DERIVED MEDIATORS OF INFLAMMATION
-
批准号:3140954
-
项目类别:
-
资助金额:$13.42万
-
财政年份:1988
-
负责人:SIMON J GASKELL
-
依托单位:
FATTY ACID-DERIVED MEDIATORS OF INFLAMMATION
-
批准号:3140953
-
项目类别:
-
资助金额:$13.16万
-
财政年份:1988
-
负责人:SIMON J GASKELL
-
依托单位:
TOXICOKINETICS AND DRUG TOXICITY
-
批准号:3096223
-
项目类别:
-
资助金额:$50.04万
-
财政年份:1984
-
负责人:SIMON J GASKELL
-
依托单位:
STUDIES OF ALKYLATING METABOLITE BY MASS SPECTROMETRY
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批准号:3919065
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:SIMON J GASKELL
-
依托单位:
STUDIES OF ALKYLATING METABOLITE BY MASS SPECTROMETRY
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批准号:3898331
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项目类别:
-
资助金额:$0.0万
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财政年份:--
-
负责人:SIMON J GASKELL
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依托单位:
海外基金