A5028764377- Asthma and respiratory diseases
- Eicosanoids and Hypertension Pharmacology
- Antioxidant Activity and Oxidative Stress
- Carbohydrate Chemistry and Synthesis
- Organic Chemistry Cycloaddition Reactions
- Fluorine in Organic Chemistry
- Free Radicals and Antioxidants
- Inflammatory mediators and NSAID effects
- Synthesis and Reactions of Organic Compounds
- Synthesis and Biological Evaluation
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- Mast cells and histamine
- Asymmetric Synthesis and Catalysis
- Chemical Synthesis and Reactions
- Nitric Oxide and Endothelin Effects
- Oxidative Organic Chemistry Reactions
- Synthesis of Organic Compounds
- Genomics, phytochemicals, and oxidative stress
- Analytical Chemistry and Chromatography
- Porphyrin and Phthalocyanine Chemistry
- Click Chemistry and Applications
- Synthesis of heterocyclic compounds
- Eosinophilic Disorders and Syndromes
- Synthesis and biological activity
Florida Institute of Technology
2014-2023
McGill University
1995-2009
Christie (Canada)
2009
University of Pennsylvania
1998-2006
Rafael Advanced Defense Systems (Israel)
2005
Heinrich Heine University Düsseldorf
2004
Düsseldorf University Hospital
2004
University of Perugia
2004
Hôpital Lyon Sud
2004
University of California, San Diego
2001
Alzheimer's disease (AD) includes a group of dementing neurodegenerative disorders that have diverse etiologies but the same hallmark brain lesions. Since oxidative stress may play role in pathogenesis AD and isoprostanes are chemically stable peroxidation products arachidonic acid, we measured both iPF2α-III iPF2α -VI using gas chromatography-mass spectrometry control brains. The levels isoprostanes, not 6-keto PGF1α, an index prostaglandin production, were markedly elevated frontal...
L-663,536 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid) is a potent inhibitor of leukotriene (LT) biosynthesis in intact human polymorphonuclear leukocytes (PMN) (IC 50 , 2.5 nM). Similarly, inhibited A23187-induced LTB 4 formation by rat peripheral blood and elicited PMN. At concentrations where inhibition occurred whole (1.1 μM), no effect was seen on cyclooxygenase or 12-lipoxygenase, an also observed washed platelets. The compound had porcine...
The isoprostane 8,12-iso-iPF2alpha-VI is a sensitive and specific marker of in vivo lipid peroxidation. We found elevated levels the urine, blood, cerebrospinal fluid patients with Alzheimer's disease (AD) that correlated measures cognitive functional impairment, established biomarkers AD pathology (cerebrospinal tau amyloid) number apolipoprotein E epsilon4 alleles. These results suggest useful biomarker oxidative damage AD.
F2-Isoprostanes are prostaglandin (PG) isomers formed in situ cell membranes by peroxidation of arachidonic acid. 8-epi PGF2alpha and IPF2alpha-I F2-isoprostanes produced humans which circulate plasma excreted urine. Measurement may offer a sensitive, specific, noninvasive method for measuring oxidant stress clinical settings where reactive oxygen species putatively involved. We determined whether isoprostanes were present human atherosclerotic lesions, lipid is thought to occur vivo. ranged...
Background —F 2 isoprostanes are stable, free radical–catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. Methods and Results —Specific assays were developed by use mass spectrometry for the F iPF 2α -III -VI (AA). Urinary excretion was significantly increased hypercholesterolemic patients, whereas substrate AA urine did not differ between groups. (pmol/mmol creatinine) elevated ( P <0.0005) homozygous familial (HFH) patients (85±5.5; n=38) compared with age-...
L-660,711 (3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl) ((3-dimethyl amino-3-oxo propyl)thio)methyl)thio)propanoic acid is a potent and selective competitive inhibitor of [ 3 H]leukotriene D 4 binding in guinea pig (K i value, 0.22 nM) human 2.1 lung membranes but essentially inactive versus C (IC 50 value lung, 23 μM). Functionally it competitively antagonized contractions trachea ileum induced by leukotriene (LT) (respective pA 2 values, 9.4 10.5) LTE 9.1 10.4) LTD (pA 8.5). (5.8 × 10 −8...
To address the hypothesis that elevated blood alcohol increases systemic oxidant stress, we measured urinary excretion of isoprostanes (iPs), free radical–catalyzed products arachidonic acid. Ten healthy volunteers received acute doses (Everclear-R) or placebo under randomized, controlled, double-blind conditions. Urinary iPF2a-III increased in a time- and dosage-dependent manner after dosing with alcohol, peak correlating rise alcohol. determine whether stress was associated alcohol-induced...
Arachidonic acid metabolism has been explored in preparations of purified human lung mast cells prelabeled with arachidonic (AA). Cells were 83 to greater than 96% purity, and each experiment was performed four six different cells. After overnight culture the presence 3H-AA, followed by extensive washing buffer, cell uptake labeled AA 61.4 +/- 14.8 pmol/10(6) 21 2.4% label phospholipids, 73 2.1% neutral lipids, 3.6 0.8% as free AA. Analysis distribution radioactivity phospholipid classes...
Background —The enzyme 12/15-lipoxygenase (12/15-LO) has been implicated in the oxidative modification of LDL. In a murine model, we tested hypothesis that deletion 12/15-LO decreases atherogenesis by reducing oxidant stress, as measured 2 indices lipid peroxidation: isoprostane generation and autoantibody formation to malondialdehyde (MDA)-LDL, an epitope LDL formed result modification. Methods Results —12/15-LO–deficient (12/15-LO −/− ) mice were crossed with apolipoprotein E–deficient...
Isoprostanes are prostaglandin isomers produced from arachidonic acid by a free radical-catalyzed mechanism. Urinary excretion of 8- iso -prostaglandin F 2α , an isomer the PGG/H synthase (cyclooxygenase or COX) enzyme product, (PGF ), has exhibited promise as index oxidant stress in vivo. We have developed quantitative method to measure isoprostane -I, (IPF -I) class I (8- -PGF is IV), using gas chromatography/mass spectrometry. IPF -I severalfold abundant human urine iso- PGF with mean...
Background The role of oxidant stress in cardiac ischemia/reperfusion injury humans remains controversial. This is due, part, to the limitations available indices vivo. Isoprostanes are stable, free radical–catalyzed products arachidonic acid. We assessed their formation patients undergoing coronary reperfusion via percutaneous transluminal angioplasty (PTCA). Methods and Results developed specific, mass spectrometry assays for two structurally distinct F 2 isoprostanes, 8-epi-PGF 2α IPF -I....
Rabbits were immunized with leukotriene C4 (LTC4) coupled to thiolated keyhole limpet hemocyanin (KLH) by using 6-N-maleimidohexanoic acid as a spacer molecule. Immune serum was obtained 7.9 nmol of LTC4-specific immunoglobulin per milliliter and mean association constant 2.1 X 10(9) M-1. A radioimmunoassay developed that detected 0.1 pmol LTC4 1-ml sample. LTD4 LTE4, three isomers LTC4, the sulfones LTD4, one isomer reacted varying degrees in assay. number other structurally related...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRegioselective synthesis of acylpyrrolesMasatoshi Kakushima, Pierre Hamel, Richard Frenette, and Joshua RokachCite this: J. Org. Chem. 1983, 48, 19, 3214–3219Publication Date (Print):September 1, 1983Publication History Published online1 May 2002Published inissue 1 September 1983https://pubs.acs.org/doi/10.1021/jo00167a014https://doi.org/10.1021/jo00167a014research-articleACS PublicationsRequest reuse permissionsArticle...
Isoprostanes (iPs) are free radical catalyzed prostaglandin isomers. Analysis of individual isomers PGF(2alpha)-F(2)-iPs-in urine has reflected lipid peroxidation in humans. However, up to 64 F(2)-iPs may be formed, and it is unknown whether coordinate generation, disposition, excretion occurs To address this issue, we developed methods measure members the four structural classes F(2)-iPs, using liquid chromatography/tandem mass spectrometry (LC/MS/MS), which sample preparation minimized....
We have proposed a nomenclature system for the isoprostanes, new class of natural products formed in vivo by free-radical peroxidation polyunsaturated fatty acids. Our is based on assignment four 1, 9, 17, and 25, as representatives classes isoprostanes derived from arachidonic acid (AA). attempted much possible to retain elements familiar prostaglandin nomenclature. In this proposal, we used abbreviation iP isoprostane. classified isoprostane or types ω-carbon being starting reference....