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PubMed2003

Evidence that 5-lipoxygenase and acetylated cyclooxygenase 2-derived eicosanoids regulate leukocyte-endothelial adherence in response to aspirin.

(1) Unlike other nonsteroidal anti-inflammatory drugs that inhibit formation of cyclooxygenase (COX)-dependent eicosanoids, acetylation of COX-2 by aspirin switches eicosanoid biosynthesis from prostaglandin E(2) (PGE(2)) to 15-epi-lipoxin A(4) (15-epi-LXA(4) or aspirin-triggered lipoxin, ATL). ATL formation by activated leukocytes (PMN) requires the intervention of 5-lipoxygenase (5-LOX), an enzyme that is involved in leukotriene B(4) (LTB(4)) formation. (2) In the present study, we have examined the role of acetylated COX-2 and 5-LOX in modulating antiadhesive effects of aspirin on adhesion of PMN to endotoxin (LPS)-primed human umbilical endothelial cells (HUVEC). (3) Treating PMN/HUVEC cocultures with aspirin resulted in a concentration-dependent inhibition of cell-to-cell adhesion induced by LPS. Treating HUVEC with selective COX-2 inhibitors, celecoxib and rofecoxib, caused an approximately 70% reversion of antiadhesive effect of aspirin. In contrast, inhibition of neutrophil's 5-LOX pathway with 1 micro M ZD2138, a selective 5-LOX inhibitor, 1 micro M BAY-X-1005, a FLAP inhibitor, or 100 micro M licofelone, a dual COX/5-LOX inhibitor, did not affect antiadhesive properties of aspirin. (4) Exposure to celecoxib (100 micro M) or rofecoxib (10 micro M) completely suppressed ATL formation caused by aspirin without affecting LTB(4) levels. ZD2138, licofelone and BAY-X-1005 inhibited ATL formation as well as LTB(4) generation. (5) Treatment with LXA(4) reduced PMN adhesion to HUVEC and counteracted the proadhesive effect of celecoxib. In contrast, exposure to Boc-1, an LXA(4) antagonist, counteracts the antiadhesive activities of aspirin. Exposure to U75302, an LTB(4) receptor antagonist, enhances the antiadesive effect of aspirin. (6) Reversal of antiadhesive activities of aspirin by celecoxib was associated with increased expression of LFA-1 on PMN and E-selectin on HUVEC. Addition of LXA(4), ZD2138 and U75302 inhibited these changes. (7) The present results support the notion that inhibition of ATL formation is mechanistically linked to the reversal of the antiadhesive activity of aspirin caused by selective COX-1 inhibitors and suggests that the LTB(4)/ATL balance modulates pro- and antiadhesive activity of nonsteroidal anti-inflammatory drugs at the leukocyte-endothelial cell interface.

Acetates↗
PubMed1991

Separation of the impairment of haemostasis by aspirin from mucosal injury in the human stomach.

1. An increasing body of data suggests that the antihaemostatic as well as the ulcerogenic actions of aspirin and other non-steroidal anti-inflammatory drugs may be operative when patients present with haematemesis and melaena. 2. We therefore developed methods to allow separate evaluation of the erosive and anti-haemostatic actions of aspirin in the human gastric mucosa. Volunteer subjects took 300 mg of aspirin daily in the morning or 600 mg of aspirin four times a day for 5 days under blinded randomized conditions. Changes in spontaneous gastric microbleeding, endoscopic signs of injury, spontaneous bleeding per gastric erosion, biopsy-induced bleeding and eicosanoids were studied. 3. Both doses of aspirin significantly inhibited gastric mucosal synthesis of prostaglandin E2 and reduced the serum thromboxane concentration. Erosions developed and regressed rapidly; compared with baseline 300 mg of aspirin daily in the morning caused substantial numbers of gastric erosions to develop (mean 5.3, 95% confidence limits 2.7-10.2) but this was significantly less than that caused by 600 mg of aspirin four times a day (10.9, 7.2-16.5, P less than 0.05). The presence of erosions was associated with enhanced spontaneous bleeding, but only during aspirin administration. 4. Aspirin significantly increased bleeding induced by mucosal biopsy and was associated with significant enhancements in the rate of bleeding per gastric erosion. Bleeding rate per erosion but not biopsy-induced bleeding showed a significant dose-related increase with 600 mg of aspirin four times a day. Enteric coating reduced endoscopic signs of injury, but did not affect the impaired haemostasis caused by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

Pioglitazone, a specific PPAR-gamma ligand, inhibits aspirin-induced gastric mucosal injury in rats.

BACKGROUND: Neutrophils activation and tumour necrosis factor-alpha (TNF-alpha) induction play a critical role in aspirin-induced gastric mucosal injury. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, has recently been implicated as a regulator of inflammatory responses. The aim of the present study was to determine whether pioglitazone, a specific PPAR-gamma ligand, can ameliorate aspirin-induced gastric mucosal injury in rats, and whether the agent can inhibit the increase in neutrophil accumulation associated with TNF-alpha expression. METHODS: Aspirin-induced injury was produced by the intragastric administration of aspirin (200 mg/kg) and HCl (0.15 N, 8.0 mL/kg). Pioglitazone was given to the rats by gastric intubation 1 h before the aspirin administration. Thiobarbituric acid-reactive substances and tissue-associated myeloperoxidase activity were measured in gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. The gastric concentration of TNF-alpha and the expression of TNF-alpha mRNA was determined by ELISA and reverse transcriptase-polymerase chain reaction. RESULTS: The intragastric administration of acidified aspirin induced hyperemia and haemorrhagic erosions in rat stomachs. The increase in the total gastric erosive area after aspirin administration was significantly inhibited by treatment with pioglitazone in a dose-dependent manner. The increases in thiobarbituric acid-reactive substances and myeloperoxidase activity after aspirin administration were both significantly inhibited by pre-treatment with pioglitazone (10 mg/kg). The gastric content of TNF-alpha increased and the expression of TNF-alpha mRNA was up-regulated after aspirin treatment. However, the peak TNF-alpha mRNA expression 1 h after aspirin administration was inhibited by pioglitazone. CONCLUSION: Based on these data, the beneficial effects of pioglitazone on aspirin-induced gastric mucosal injury may be attributed to its anti-inflammatory properties.

Animals↗
PubMed1982

Aspirin treatment of migraine attacks: plasma drug level data.

Plasma aspirin and salicylate levels were measured at intervals over a two hour period during migraine attacks in 10 subjects given 900 mg oral aspirin alone, in 10 subjects given 900 mg oral aspirin plus 10 mg oral metoclopramide, and in 10 subjects given 900 mg oral aspirin plus an intramuscular injection of 10 mg metoclopramide. Higher peak aspirin and salicylate levels occurred in patients given aspirin with metoclopramide. Aspirin tended to appear in plasma earlier in patients given aspirin with oral metoclopramide than in patients given aspirin alone, or aspirin with intramuscular metoclopramide. Patients given aspirin with oral metoclopramide tended to obtain better early pain relief than the other two treatment groups, though by one hour from dosage use of injected metoclopramide was also associated with better pain relief.

Adolescent↗
PubMed1984

Dose-related kinetics of aspirin. Presystemic acetylation of platelet cyclooxygenase.

When aspirin is administered by mouth in low doses, poor systemic bioavailability may contribute to its apparent dose-related "selective inhibition" of thromboxane A2 formation. Systemic bioavailability of orally administered aspirin is necessary to inhibit prostacyclin synthesis by systemic vascular endothelium, whereas cumulative inhibition of thromboxane A2 formation by platelets may occur in the presystemic (portal) circulation. We simultaneously administered unlabeled aspirin orally and deuterium-labeled aspirin intravenously in five healthy volunteers. This permitted an estimation of the bioavailability of an oral dose from the ratio of plasma drug concentration-time curves for the labeled and the unlabeled species. Systemic bioavailability ranged from 46 to 51 per cent of single oral doses of 20, 40, 325, and 1300 mg of aspirin. Bioavailability was similar after single-dose and long-term oral administration of 325 mg. Thromboxane B2 formation in serum ex vivo after oral administration of 20 mg of unlabeled aspirin was reduced 39 per cent before aspirin was detected in the systemic circulation. Furthermore, incubation of simulated peak plasma aspirin concentrations in whole blood in vitro underestimated the inhibition of thromboxane B2 ex vivo after oral administration of 20 or 40 mg of unlabeled aspirin. These data are consistent with presystemic inhibition of platelets by aspirin and suggest that biochemical "selectivity" might be enhanced by slow administration of very low doses of aspirin, thereby optimizing conditions for cumulative, presystemic acetylation of platelet cyclooxygenase and inhibition of thromboxane formation.

Acetylation↗
PubMed1995

Aspirin and the risk of colorectal cancer in women.

BACKGROUND: Most data suggest that the regular use of aspirin reduces the risk of colorectal cancer, but some apparently conflicting evidence exists. The effects of the dose and the duration of aspirin consumption on the risk of colorectal cancer are not well understood. METHODS: We determined rates of colorectal cancer according to the number of consecutive years of regular aspirin use (defined as two or more tablets per week) among women in the Nurses' Health Study who reported regular aspirin use on three consecutive questionnaires (1980, 1982, and 1984) and compared the rates in this group with the rates among women who said they did not use aspirin. Cases of cancer occurring from 1984 through 1992 (the eight years after the 1984 questionnaire) were included. RESULTS: From 1984 through 1992, we documented 331 new cases of colorectal cancer during 551,651 person-years of follow-up. Women who consistently took two or more aspirin tablets per week had no appreciable reduction in the risk of colorectal cancer as compared with nonusers after four years (relative risk, 1.06; 95 percent confidence interval, 0.78 to 1.45) or after five to nine years (relative risk, 0.84; 95 percent confidence interval, 0.55 to 1.28). There was a slight reduction in risk among women who took aspirin for 10 to 19 years, but it was not statistically significant (relative risk, 0.70; 95 percent confidence interval, 0.41 to 1.20). However, there was a statistically significant reduction after 20 years of consistent use of aspirin (relative risk, 0.56; 95 percent confidence interval, 0.36 to 0.90; P for trend = 0.008). The maximal reduction in risk was observed among women who took four to six tablets per week; higher doses had a similar apparent benefit. Controlling for risk factors for colorectal cancer, including diet, did not change the results, and the earlier diagnosis and removal of colorectal adenomas among aspirin users did not account for the results. CONCLUSIONS: Regular aspirin use, at doses similar to those recommended for the prevention of cardiovascular disease, substantially reduces the risk of colorectal cancer. However, this benefit may not be evident until after at least a decade of regular aspirin consumption.

Adult↗
PubMed2005

Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding.

BACKGROUND: Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin. We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients. METHODS: We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months. The end point was recurrent ulcer bleeding. RESULTS: We enrolled 320 patients (161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole). Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent (95 percent confidence interval, 4.1 to 13.1 percent) among patients who received clopidogrel and 0.7 percent (95 percent confidence interval, 0 to 2.0 percent) among those who received aspirin plus esomeprazole (difference, 7.9 percentage points; 95 percent confidence interval for the difference, 3.4 to 12.4; P=0.001). CONCLUSIONS: Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment, aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding. Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel.

Aged↗
PubMed2002

Topically applied aspirin decreases histamine-induced wheal and flare reactions in normal and SLS-inflamed skin, but does not decrease itch. A randomized, double-blind and placebo-controlled human study.

Topically applied aspirin has recently been reported to decrease histamine-induced itch in human volunteers. Our aim is to confirm this and to study the antipruritic ability of topical aspirin in inflamed skin. In 24 non-atopic volunteers, an inflammatory skin reaction was induced in forearm skin at 5 different sites by sodium lauryl sulphate contained in Finn Chambers. Aspirin 10%, aspirin 1%, mepyramine 5% and vehicle were applied to the inflamed and corresponding non-inflamed areas 20 min before itch induction with intradermal histamine injection. Itch and pain were scored on a visual analogue scale at regular intervals. Wheal and flare areas were measured. No difference in itch intensities was found after application of aspirin, mepyramine and vehicle, but more itch was induced in aspirin and mepyramine pretreated sites in inflamed skin compared to normal skin (p<0.05). In normal skin, flare areas were smaller after pretreatment with aspirin 10% (p<0.05) and mepyramine (p<0.001), as were wheal areas after mepyramine (p<0.01), compared to vehicle pretreatments. In inflamed skin, flare areas were smaller after pretreatment with aspirin 10% (p<0.01) and mepyramine (p<0.001), as were wheal areas after aspirin 10% (p<0.01), aspirin 1% (p<0.05) and mepyramine (p<0.001). We conclude that despite a significant skin penetration as measured by the influence on wheal and flare reactions, topically applied aspirin did not decrease histamine-induced itch in the model used.

Administration, Topical↗
PubMed2003

Low frequency of upper gastrointestinal complications in a cohort of high-risk patients taking low-dose aspirin or NSAIDS and omeprazole.

BACKGROUND: There is very little information available on the incidence of complications and on the best prevention therapy in high-risk patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and/or aspirin. Randomized-controlled trials in such patients are rare for ethical reasons. We studied the incidence of gastrointestinal complications in high-risk patients taking long-term low-dose aspirin or non-aspirin-NSAIDs combined with omeprazole in a real-life clinical setting. METHODS: This was a multicentre, prospective and observational study including 247 consecutive high-risk patients who had a clinical indication for long-term treatment with either low-dose aspirin or non-aspirin NSAIDs and omeprazole therapy. The occurrence of gastrointestinal complications was measured. RESULTS: In addition to a recent history of peptic ulcer bleeding, all patients had at least 1 other risk factor and 112 (45.3%) had 3 or more risk factors; 78.9% were taking low-dose aspirin and the remainder non-aspirin NSAIDs. Mean follow-up was 14.6 +/- 10.38 months. Three patients taking low-dose aspirin developed upper gastrointestinal bleeding (1.2%; 95% CI 0.3-3.5; 1.0 event/100 patients/year). This was similar to the rate observed in studies involving non-high-risk patients taking low-dose aspirin and higher than that observed in patients not taking low-dose aspirin. Two additional patients developed a lower gastrointestinal bleeding event (0.81% (0.04%-3.12%); 0.67 events/100 patients/year), which was within the range expected in NSAID users. CONCLUSIONS: The use of omeprazole in the high-risk patient taking low-dose aspirin or NSAIDs seems to be a safe therapeutic approach in this population and is associated with a low frequency of upper gastrointestinal complications.

Adult↗
PubMed2002

Towards a definition of aspirin resistance: a typological approach.

'Aspirin resistance' is a poorly defined term to describe the inability of aspirin to protect individuals from thrombotic complications and there are conflicting reports on incidence rates and clinical relevance of this phenomenon. Using collagen (1 microg/ml)-induced platelet aggregation and thromboxane formation (measured as thromboxane B(2)) in citrated platelet-rich plasma, this study demonstrates that aspirin resistance can be classified into three distinct types. In aspirin responders, both, collagen-induced platelet aggregation and thromboxane formation was completely (>95%) inhibited by oral aspirin treatment (100 mg/day). In type I resistance (pharmacokinetic type), oral treatment with aspirin was ineffective but addition of aspirin (100 microM) in vitro resulted in a complete inhibition of collagen-induced platelet aggregation and thromboxane formation. In type II resistance (pharmacodynamic type), neither oral treatment with aspirin nor addition of aspirin in vitro inhibited collagen-induced platelet aggregation and thromboxane formation. In type III resistance (pseudo-resistance), platelet aggregation was induced by a low concentration of collagen (1 microg/ml) despite of a complete inhibition of thromboxane formation by oral aspirin treatment. This typology of aspirin resistance should help to clarify the mechanisms, the actual rate, and the possible clinical consequences of this phenomenon.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

A prospective study of aspirin use and the risk of pancreatic cancer in women.

BACKGROUND: In vitro experiments and limited animal studies suggest that aspirin and nonsteroidal anti-inflammatory drugs may inhibit pancreatic carcinogenesis. Because few studies have examined the association between aspirin use and pancreatic cancer in humans and the results have been inconsistent, we examined the relationship between aspirin use and the development of pancreatic cancer in the Nurses' Health Study. METHODS: Among 88 378 women without cancer at baseline, we documented 161 cases of pancreatic cancer during 18 years of follow-up. Aspirin use was first assessed at baseline in 1980 and updated biennially thereafter. All statistical tests were two-sided. RESULTS: Participants were classified according to history of aspirin use. In a multivariable analysis, the risk of pancreatic cancer was not associated with current regular aspirin use (defined as two or more standard tablets per week; relative risk [RR] = 1.20, 95% confidence interval [CI] = 0.87 to 1.65), compared with use of fewer than two tablets per week. Increasing duration of regular aspirin use, compared with non-use, was associated with a statistically significant increase in risk: Women who reported more than 20 years of regular aspirin use had an increased risk of pancreatic cancer (RR = 1.58, 95% CI = 1.03 to 2.43; P(trend) =.01). Among women who reported aspirin use on at least two of three consecutive biennial questionnaires compared with consistent non-users of aspirin, the risk increased with dose (one to three tablets per week: RR = 1.11, 95% CI = 0.70 to 1.76; four to six tablets per week: RR = 1.29, 95% CI = 0.70 to 2.40; seven to 13 tablets per week: RR = 1.41, 95% CI = 0.76 to 2.61; and > or = 14 tablets per week: RR = 1.86, 95% CI = 1.03 to 3.35) (P(trend) =.02). CONCLUSION: Extended periods of regular aspirin use appear to be associated with a statistically significantly increased risk of pancreatic cancer among women.

Adult↗
PubMed2002

Heat shock protein and high-dose aspirin: effects on random skin flap survival in a rat model.

The heat shock response is known to have a protective effect against flap ischemia. It has been shown that heat shock protein (hsp) expression can be augmented in vivo with the administration of high-dose aspirin before heat treatment. The authors hypothesized that administration of aspirin before hsp induction through heat stress would enhance further the protective effects of the heat shock response against skin flap ischemia. They used a random dorsal skin flap model in 32 rats divided into four groups (N = 8 each): control, heat shock, aspirin plus heat shock, and aspirin. Before surgery, rats in the two heat shock groups were placed in a 45 degrees C water bath until core body temperature measured 42 degrees C, and they were maintained at 42 degrees C for 15 minutes. Rats in the two aspirin groups received a single oral dose of aspirin (100 mg per kilogram) 1 hour before heat bath or surgery. Immunohistochemistry confirmed hsp expression in the two heat groups. Skin flap survival was improved significantly (p < 0.05) in the heat shock (55%), aspirin plus heat shock (58%), and aspirin (60%) groups when compared with controls (45%). Contrary to their hypothesis, aspirin combined with hsp induction did not offer greater protection from ischemia than hsp induction alone (p > 0.05). However, high-dose aspirin administration alone did improve skin flap survival when compared with controls. Future studies are needed to investigate further the role of pharmacological therapy combined with hsp induction in improving skin flap survival and to delineate the dose-response relationship between aspirin and hsp.

Animals↗
PubMed2006

Genetic mechanism of aspirin-induced urticaria/angioedema.

PURPOSE OF REVIEW: Aspirin-induced urticaria/angioedema is a major aspirin-related hypersensitivity often associated with aspirin-intolerant asthma. Genetic studies on aspirin-intolerant asthma have shown chronic overproduction of cysteinyl leukotrienes. The genetic analysis of aspirin-induced urticaria/angioedema is limited, however. RECENT FINDINGS: A recent study on HLA genotypes has suggested that the HLA alleles DRB11302 and DQB10609 may be genetic markers for aspirin-induced urticaria/angioedema. A polymorphism study that examined nine single-nucleotide polymorphisms of five leukotriene-related genes [ALOX5 (encoding 5-lipoxygenase), ALOX5AP (5-lipoxygenase-activating protein), PTGS2 (cyclooxygenase 2), LTC4S (leukotriene C4 synthase), and CYSLTR1 (cysteinyl leukotriene receptor 1)] found that promoter polymorphisms of ALOX5 (-1708A>G) and CYSLTR1 (-634C>T) were significantly different between aspirin-intolerant asthma and aspirin-induced urticaria/angioedema, suggesting different contributions to the lipoxygenase pathway. A second polymorphism study, conducted on histamine-related genes, did not find any significant associations with aspirin-induced urticaria/angioedema for the genes HNMT (encoding histamine N-methyltransferase), HRH1 or HRH2 (encoding histamine receptor types 1 and 2 respectively), or the gene encoding high-affinity IgE receptor Ibeta (FcepsilonRIbeta); however, the FcepsilonRIalpha gene promoter polymorphism was significantly associated with aspirin-induced urticaria/angioedema. This finding has been supported by in vitro functional studies. SUMMARY: The HLA alleles DRB11302 and DQB10609, and the ALOX5 and FcepsilonRIalpha promoter polymorphisms, may contribute to the pathogenesis of aspirin-induced urticaria/angioedema. Further investigation to identify candidate genetic markers would help to elucidate the pathogenic mechanism of this condition.

Angioedema↗
PubMed1975

The effect of metoclopramide on the absorption of effervescent aspirin in migraine.

1 The absorption of effervescent aspirin was studied in two groups of patients during attacks of migraine. The first group received effervescent aspirin alone whilst the second group received intramuscular metoclopramide before effervescent aspirin. 2 After effervescent aspirin alone there was significant impairment in the rate of aspirin absorption during migraine attacks compared with the rate of aspirin absorption in normal volunteers and in the same patients when headache-free. 3 When metoclopramide was given before effervescent aspirin the rate of aspirin absorption during migraine attacks was not significantly different from that obtained in normal volunteers given effervescent aspirin alone or from that obtained in the patients themselves when given both metoclopramide and effervescent aspirin when headache-free. 4 It is concluded that the impairment of absorption of effervescent aspirin during migraine attacks is related to impaired gastro-intestinal motility with delayed gastric emptying and that this impaired motility can be overcome by parenteral metoclopramide.

Adult↗
PubMed2005

Aspirin is efficacious for the treatment of acute migraine.

BACKGROUND: More than 50% of migraine sufferers rely on over-the-counter medications for the treatment of migraine. Along with other over-the-counter products, aspirin is considered by the US Headache Consortium to be an option for first-line migraine treatment. This study assessed the efficacy and tolerability of aspirin versus placebo for the acute treatment of a single acute attack of migraine. METHODS: This prospective, randomized, double-blind, parallel-group, placebo-controlled study evaluated the efficacy of a single, 1000-mg dose of aspirin for the treatment of acute moderate to severe migraine, with or without aura. Subjects recorded all study evaluations in a diary at baseline and at .5, 1, 2, 3, 4, 5, 6, and 24 hours after treatment. Pain was rated on a 4-point ordinal scale from no pain to severe pain. The primary efficacy end point was headache response at 2 hours. Secondary efficacy parameters included reduction of nausea, photophobia and phonophobia, pain intensity difference, and headache recurrence at 24 hours. RESULTS: Of 485 subjects enrolled, 409 took study medication and 401 treated a confirmed migraine attack (201 with aspirin and 200 with placebo). Baseline demographic and migraine characteristics were not significantly different between groups. The 2-hour headache response rate was 52% with aspirin versus 34% with placebo (P<.001). Aspirin was significantly more effective than placebo for pain reduction beginning 1 hour after dosing (P<.001) and continuing throughout the 6-hour evaluation period. Significantly (P<.05), more subjects were pain free from the 1-hour evaluation through the 6-hour evaluation. Of the aspirin-treated subjects, 20% were pain free at 2 hours versus only 6% of placebo-treated subjects. At 24 hours, the headache recurrence rate was 21.8% for aspirin (23 of 105 subjects) and 27.7% for placebo (19 of 68 subjects). Only 34% of aspirin-treated subjects needed rescue medication at 24 hours compared with 52% of placebo-treated subjects (P<.001). Aspirin was well tolerated, and adverse events were not significantly different between groups. CONCLUSIONS: This study demonstrates that aspirin is safe and effective for treatment of acute migraine in appropriately selected patients.

Acute Disease↗
PubMed1998

Prevalence of aspirin use among patients calling 9-1-1 for chest pain.

OBJECTIVE: Early aspirin administration during an acute myocardial infarction (AMI) decreases morbidity and mortality. This investigation examined the extent to which patients with a complaint of chest pain, the symptom most identified with AMI by the general population, self-administer aspirin before the arrival of emergency medical services (EMS) personnel. METHODS: In this prospective, cross-sectional prevalence study, data were derived through the analysis of EMS incident reports for patients with a complaint of chest pain from June 1, 1997, to August 31, 1997. RESULTS: The study included 694 subjects. One hundred two (15%) took aspirin for their chest pain before the arrival of EMS personnel. Of the 322 subjects who reported taking aspirin on a regular basis, 82 (26%) took additional aspirin for their acute chest pain. Only 20 (5%) of the 370 patients who were not using regular aspirin therapy self-administered aspirin acutely (p<0.001). In addition, patients with lower intensity of chest pain (p = 0.03) were more likely to take aspirin for their chest pain. CONCLUSION: Only a relatively small fraction of individuals calling 9-1-1 with acute chest pain take aspirin prior to the arrival of EMS personnel. These individuals are more likely to self-administer aspirin if they are already taking it on a regular basis. It is also possible that they are less likely to take aspirin if their chest pain is more severe.

Acute Disease↗
PubMed1998

Effects of copper-aspirin complex on platelet aggregation and thrombosis in rabbits and mice.

The effects of intragastric and intraduodenal copper-aspirin complex on rabbit platelet aggregation were observed by Born's method. Myers's method was used to evaluate the antithrombotic effect of copper-aspirin complex in mice. In-vitro copper-aspirin complex selectively inhibited arachidonic acid-induced platelet aggregation with an IC50 value (concentration resulting in 50% inhibition) of 13.2 microM (95% confidence limits 9.1-16.8 microM). Copper-aspirin complex (10 mg kg(-1) given intragastrically or intraduodenally) was more potent than aspirin in inhibiting arachidonic acid-induced platelet aggregation. Copper-aspirin complex (10 mg kg(-1)) had a stronger inhibitory effect and a longer duration of action when given intragastrically than when given intraduodenally. It was shown by radioimmunoassay that copper-aspirin complex significantly reduced the level of thromboxane B2 in plasma while markedly increasing that of 6-ketoprostaglandin F1alpha (6keto-PGF1alpha). Copper-aspirin complex (10 mg kg(-1) given intragastrically for 7 days) significantly reduced mouse mortality caused by intravenous injection of arachidonic acid. The results suggest that both in-vitro and in-vivo copper-aspirin complex is more potent in selectively inhibiting arachidonic acid-induced platelet aggregation than aspirin. When given intragastrically the complex has a more potent antiplatelet effect and a longer duration of action than when given intraduodenally. The antithrombotic effect of the complex was more potent than that of aspirin.

6-Ketoprostaglandin F1 alpha↗
PubMed2005

Nitric oxide-donating aspirin inhibits colon cancer cell growth via mitogen-activated protein kinase activation.

Nitric oxide-donating aspirin (NO-aspirin), representing a new concept in the development of more efficacious nonsteroidal anti-inflammatory drugs, consists of traditional aspirin bearing -ONO(2), which releases NO. Conventional aspirin prevents human colon cancer, but its toxicity precludes its application as a chemopreventive agent. NO-aspirin seems safer and in cultured cancer cells it is >1000-fold more potent than aspirin. To determine the mechanism by which NO-aspirin inhibits cell growth, we studied its effect on mitogen-activated protein kinase (MAPK) signaling in HT-29 human colon cancer cells. NO-aspirin stimulated the phosphorylation of extracellular signal-regulated kinase 1/2 and Akt only marginally. The greatest increases in phosphorylation were seen in cJun NH(2)-terminal kinase (JNK) and p38 MAP kinases, which were observed as early as 5 min and after 1 h of treatment, averaged more than 10-fold over control. The activation of JNK and p38 was accompanied by large increases in the phosphorylation of the downstream transcription factors cJun and activating transcription factor 2 (ATF-2). We used specific MAPK inhibitors, small interfering (siRNA) gene silencing methods, and dominant-negative cJun to determine the relevance of these phosphorylation events to the ability of NO-aspirin to inhibit colon cancer cell growth. Only the dual inhibitor of p38 and JNK and the use of combined siRNA silencing of p38 and cJun abrogated the ability of NO-aspirin to block cell growth. Our data indicate that NO-aspirin is dependent on both the p38 and the JNK MAP kinase pathways for its ability to inhibit the growth of colon cancer cells.

Aspirin↗