Disease relevance of ACETYLSALICYLIC ACID

• Pulmonary embolism in a homocystinuric patient during treatment with dipyridamole and acetylsalicylic acid [1].
• The efficacy of high-dose salicylates in reducing the coronary artery involvement of Kawasaki disease was compared in 36 children who received acetylsalicylic acid, 80 to 180 mg/kg/day, and in 18 who did not receive high-dose salicylates during the febrile phase of the disease and whose fever was controlled mainly with acetaminophen [2].
• BACKGROUND: A variety of studies have supported the finding that regular intake of aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory agents can affect colorectal cancer carcinogenesis [3].
• Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke [4].
• The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension [4].

Psychiatry related information on ACETYLSALICYLIC ACID

• BACKGROUND AND PURPOSE: The purpose of this study was to assess individual differences in the pharmacological effects of acetylsalicylic acid (ASA) on bleeding time as measured by in vitro platelet aggregation and to examine the consistency of responses over time [5].
• Intravenous injection of acetylsalicylic acid increased only the RIII,Cu threshold and relative pain threshold [6].
• It was concluded that the ASA dosage of 1500 mg daily was too high, and produced severe side-effects, probably leading to insufficient patient compliance to therapy [7].
• Risk factors for gout and intradermal tophi included renal failure in all 6, hypertension and chronic diuretic therapy in 4, and one patient each with alcohol abuse, chronic low dose acetylsalicylic acid, myeloma, and a positive family history [8].
• MPTP-induced decrease of locomotor activity was significantly attenuated by acetylsalicylic acid and meloxicam [9].

High impact information on ACETYLSALICYLIC ACID

• Effects of acetylsalicylic-acid ingestion on maternal and neonatal hemostasis [10].
• Acetylsalicylic acid (aspirin) inhibits prostanoid synthesis by irreversible acetylation of fatty acid cyclooxygenase (EC 1.14.99.1) [11].
• Cyclooxygenase (COX) II is emerging as an important component in wound healing and proliferation in intestinal epithelia and when acetylated by acetylsalicylic acid (aspirin) initiates the biosynthesis of a LXA4 receptor ligand [12].
• INTERPRETATION: The risk of stroke, myocardial infarction, and death within 30 days and 3 months of endarterectomy is lower for patients taking 81 mg or 325 mg acetylsalicylic acid daily than for those taking 650 mg or 1300 mg [13].
• METHODS: A case-control study of current users (n = 132) of NSAIDs (including acetylsalicylic acid), admitted because of bleeding peptic ulcer, was performed [14].

Chemical compound and disease context of ACETYLSALICYLIC ACID

• Effect of cimetidine on net ion fluxes across the rat gastric mucosa during mucosal damage after gastric ischemia and after intravenous acetylsalicylic acid [15].
• All patients had suffered at least three relapses despite treatment with acetylsalicylic acid, indomethacin, prednisone, or a combination [16].
• The German-Austrian aspirin trial: a comparison of acetylsalicylic acid, placebo and phenprocoumon in secondary prevention of myocardial infarction. On behalf of the German-Austrian Study Group [17].
• In contrast, the antiinflammatory agent acetylsalicylic acid failed to inhibit the activity of purified GST and caused no potentiation of chlorambucil toxicity, suggesting that the potentiation by indomethacin is not due to the effects of this drug on prostaglandin synthesis [18].
• A major factor contributing to the lower relaparotomy rate in era 2 was a significant decrease in the incidence of graft thrombosis; the authors believe this lower incidence is due to the routine use of postoperative low-dose intravenous heparin and acetylsalicylic acid [19].

Biological context of ACETYLSALICYLIC ACID

• We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension [4].
• Second-phase platelet aggregation was reversed with acetylsalicylic acid, intravenous tolbutamide, and oral glucose administration [20].
• Previous studies indicated that aspirin (acetylsalicylic acid [ASA]) can have profound immunomodulatory effects by regulating cytokine gene expression in several types of cells [21].
• The inhibitory effect of ASA on IL-4 transcription was not mediated by decreased nuclear expression of the known salicylate target nuclear factor (NF)-kappaB and was accompanied by reduced binding of an inducible factor to an IL-4 promoter region upstream of, but not overlapping, the NF of activated T cells- and NF-kappaB-binding P1 element [21].
• No significant increase in mortality occurred in mice given 67 mg/kg ASA twice daily for 7 days and one LD50 dose of virus on day 4 [22].

Anatomical context of ACETYLSALICYLIC ACID

• Parameters of barrier disruption were then determined before and after exposure of the gastric mucosa to 40mM acetylsalicylic acid [23].
• Acetylsalicylic acid-induced gastric hemorrhage preceded an increase in net H+ flux from serosa to mucosa, although net Na+ and K+ fluxes were unaffected [15].
• Acetylsalicylic acid initially increased cell membrane resistances and Ra/Rb, whereafter a rapid decrease of Ra/Rb and Rt occurred [24].
• Here, ASA triggered transcellular biosynthesis of a previously unrecognized class of eicosanoids during coincubations of human umbilical vein endothelial cells (HUVEC) and neutrophils [polymorphonuclear leukocytes (PMN)] [25].
• To examine this, cultured acetylsalicylic acid (ASA)-treated endothelial cells (EC) from bovine aorta (BAEC) or from human umbilical vein (HUVEC) were incubated with washed, ASA-treated human platelets [26].

Associations of ACETYLSALICYLIC ACID with other chemical compounds

• The effects of luminal aspirin [acetylsalicylic acid (ASA)] at luminal pH 4.5 and pH 3.0 on Ussing chambered amphibian gastric fundic and antral mucosae were investigated using different concentrations of HCO3- ([HCO3-]) in the nutrient solution in histamine-stimulated or metiamide-treated tissues [27].
• The effect of the intra-articular injection of acetylsalicylic acid in patients with rheumatoid arthritis was compared with that of hydrocortisone acetate and with that of saline in blind, controlled, clinical trials [28].
• The simultaneous oral administration of acetylsalicylic acid (64 mg per kg) and taurocholic acid (2.5 mM) to rats induced gastric hemorrhagic mucosal bleeding in 82.4% of animals compared with 29.7% of animals given acetylsalicylic acid alone [29].
• The effects of acetylsalicylic acid on gastric mucosal ATP and phosphocreatine and mucosal O2 consumption were studied using in vitro bullfrog gastric mucosa [30].
• The endothelium-dependent constrictions to serotonin or arachidonate were also blocked by pretreatment of the mouse with cyclooxygenase inhibitors, acetylsalicylic acid (100 mg/kg i.p.) or indomethacin (5 mg/kg) [31].

Gene context of ACETYLSALICYLIC ACID

• In contrast, ASA did not affect IL-13, interferon-gamma, and IL-2 expression [21].
• In this study, we analyzed the effects of aspirin (acetylsalicylic acid) on serine phosphorylation of insulin receptor substrate 1 (IRS-1) in cells treated with tumor necrosis factor (TNF)-alpha [32].
• CONCLUSIONS: The discovery of a functional single-nucleotide polymorphism in the cyclooxygenase 1 locus may ultimately improve the safe and effective use of acetylsalicylic acid by better tailoring of dosage with an individual's genetic variation [33].
• In addition, a nonselective (acetylsalicylic acid) or selective cyclooxygenase (COX) 1 inhibitor (SC-560) completely abrogated the 8-iso-PGF(2alpha) and PGF(2alpha) formation in kidneys subjected to ischemia [34].
• Therefore, the transcription factor NF-kappaB plays a vital role in PDGF-B chain transformation of mouse fibroblast cells, and the NF-kappaB activity is sensitive to treatment with ASA [35].

Analytical, diagnostic and therapeutic context of ACETYLSALICYLIC ACID

• In a case-control study, we evaluated the effects of maternal ingestion of acetylsalicylic acid (aspirin) within 10 days of delivery on maternal and neonatal hemostasis [10].
• Antral ulcers were produced in unanesthetized rats in 3 hr by simultaneous intravenous administration of acetylsalicylic acid (ASA) and gastric perfusion with 0.15 M HCl [36].
• Low-dose versus high-dose acetylsalicylic acid in carotid endarterectomy [37].
• METHODS: In a randomised, double-blind, controlled trial, 2849 patients scheduled for endarterectomy were randomly assigned 81 mg (n=709), 325 mg (n=708), 650 mg (n=715), or 1300 mg (n=717) acetylsalicylic acid daily, started before surgery and continued for 3 months [13].
• Complete patency of the stent was noted in 10 of 15 patients in the acetylsalicylic acid group and in 14 of 19 patients in the control group [38].

References