Posted 12 August 2007 - 09:38 PM
The studies below drew my attention. A recently completed prospective 5 year clinical trial using large numbers (ca. 22,000 healthy male doctors), and a randomized placibo control approach:
Am J Respir Crit Care Med. 2007 Jan 15;175(2):120-5.: "The aspirin component was terminated after 4.9 yr due principally to the emergence of a statistically extreme 44% reduction in risk of first myocardial infarction among those randomly assigned to aspirin."
The above interested me, especially when I found evidence in the literature for a a potential interplaybetween fish oil use and aspirin (thought it does complicate dosing of these individual components, and prospective studies would need to be done, still):
J Exp Med. 2005 Mar 7;201(5):671-4: "New experimental evidence adds resolvin E1 to this group of endogenous inhibitors and provides further rationale for the beneficial effects of dietary supplementation with fish oils. It also highlights an unexpected twist in the pharmacology of aspirin."
J Biol Chem. 2007 Mar 30;282(13):9323-34: Resolvin D1 and its aspirin-triggered 17R epimer. "These results may contribute to the beneficial actions of aspirin and omega-3 fish oils in humans"
The question of proper dosage and frequency of these two items, aspirin, and fish oil, don't seem very clear at present. Something to talk about with one's clinician, and perhaps do additional research on.
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Am J Respir Crit Care Med. 2007 Jan 15;175(2):120-5. Epub 2006 Oct 26. Links
Aspirin and decreased adult-onset asthma: randomized comparisons from the physicians' health study.Barr RG, Kurth T, Stampfer MJ, Buring JE, Hennekens CH, Gaziano JM.
Division of General Medicine, Department of Medicine, Columbia University Medical Center, New York, NY, USA.
RATIONALE: In an observational cohort study, women who self-selected for frequent aspirin use developed less newly diagnosed asthma than women who did not take aspirin. OBJECTIVE: To explore whether low-dose aspirin decreased the risk of newly diagnosed asthma in a randomized, double-blind, placebo-controlled trial. METHODS: The Physicians' Health Study randomized 22,071 apparently healthy male physicians, aged 40-84 yr at baseline and tolerant of aspirin, over an 18-wk run-in period, to 325 mg aspirin or placebo on alternate days. The aspirin component was terminated after 4.9 yr due principally to the emergence of a statistically extreme 44% reduction in risk of first myocardial infarction among those randomly assigned to aspirin. MEASUREMENTS: Physicians could self-report an asthma diagnosis on questionnaires at baseline, 6 mo, and annually thereafter. Asthma was not an a priori endpoint of the trial. RESULTS: Among 22,040 physicians without reported asthma at randomization, there were 113 new asthma diagnoses in the aspirin group and 145 in the placebo group. The hazard ratio was 0.78 (95% confidence interval, 0.61-1.00; p = 0.045). This apparent 22% lower risk of newly diagnosed asthma among those assigned to aspirin was not modified by baseline characteristics including smoking, body mass index, or age. CONCLUSIONS: Aspirin reduced the risk of newly diagnosed adult-onset asthma in a large, randomized clinical trial of apparently healthy, aspirin-tolerant men. This result requires replication in randomized trials designed a priori to test this hypothesis; it does not imply that aspirin improves symptoms in patients with asthma.
PMID: 17068328 [PubMed - indexed for MEDLINE]
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J Exp Med. 2005 Mar 7;201(5):671-4. Links
Controlling inflammation: a fat chance?Flower RJ, Perretti M.
The William Harvey Research Institute, London EC1M 6BQ, UK. r.j.flower@qmul.ac.uk
The inflammatory response protects the body against infection and injury but can itself become deregulated with deleterious consequences to the host. It is now clear that several endogenous biochemical pathways activated during defense reactions can counterregulate inflammation. New experimental evidence adds resolvin E1 to this group of endogenous inhibitors and provides further rationale for the beneficial effects of dietary supplementation with fish oils. It also highlights an unexpected twist in the pharmacology of aspirin.
PMID: 15753201 [PubMed - indexed for MEDLINE]
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J Biol Chem. 2007 Mar 30;282(13):9323-34. Epub 2007 Jan 23. Links
Resolvin D1 and its aspirin-triggered 17R epimer. Stereochemical assignments, anti-inflammatory properties, and enzymatic inactivation.Sun YP, Oh SF, Uddin J, Yang R, Gotlinger K, Campbell E, Colgan SP, Petasis NA, Serhan CN.
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
We recently uncovered two new families of potent docosahexaenoic acid-derived mediators, termed D series resolvins (Rv; resolution phase interaction products) and protectins. Here, we assign the stereochemistry of the conjugated double bonds and chirality of alcohols present in resolvin D1 (RvD1) and its aspirin-triggered 17R epimer (AT-RvD1) with compounds prepared by total organic synthesis. In addition, docosahexaenoic acid was converted by a single lipoxygenase in a "one-pot" reaction to RvD1 in vitro. The synthetic compounds matched the physical and biological properties of those enzymatically generated. RvD1 proved to be 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid, AT-RvD1 matched 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid, and they both stopped transendothelial migration of human neutrophils (EC(50) approximately 30 nM). In murine peritonitis in vivo, RvD1 and AT-RvD1 proved equipotent (at nanogram dosages), limiting polymorphonuclear leukocyte infiltration in a dose-dependent fashion. RvD1 was converted by eicosanoid oxidoreductase to novel 8-oxo- and 17-oxo-RvD1 that gave dramatically reduced bioactivity, whereas enzymatic conversion of AT-RvD1 was sharply reduced. These results establish the complete stereochemistry and actions of RvD1 and AT-RvD1 as well as demonstrate the stereoselective basis for their enzymatic inactivation. RvD1 regulates human polymorphonuclear leukocyte transendothelial migration and is anti-inflammatory. When its carbon 17S alcohol is enzymatically converted to 17-oxo-RvD1, it is essentially inactive, whereas the 17R alcohol configuration in its aspirin-triggered form (AT-RvD1) resists rapid inactivation. These results may contribute to the beneficial actions of aspirin and omega-3 fish oils in humans.
PMID: 17244615 [PubMed - indexed for MEDLINE]
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