WorldWideScience

Sample records for aspirin

  1. Aspirin overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002542.htm Aspirin overdose To use the sharing features on this page, please enable JavaScript. An overdose of aspirin means you have too much aspirin in your ...

  2. Aspirin Desensitization

    Science.gov (United States)

    ... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Aspirin Desensitization Kevin C. Welch, MD Zara Patel, MD Introduction The term "aspirin-sensitive asthma" (also known as "aspirin triad" or " ...

  3. Aspirin revealed

    Science.gov (United States)

    Lacey, D.; Hu, X. K.; Loboda, A. V.; Mosey, N. J.; Lipson, R. H.

    2007-03-01

    Experiments are described where the experimental conditions have been optimized to detect aspirin by MALDI mass spectrometry. Although protonated aspirin was not observed by MALDI, sodium and potassium aspirin adducts could be found. Significantly better signals could be obtained by using Rb and Cs salts as cationization sources. Quantum calculations were carried out to determine the structure and energetics of the Li, K, Rb, and Cs alkali--aspirin adducts.

  4. Aspirin and Omeprazole

    Science.gov (United States)

    The combination of aspirin and omeprazole is used to reduce the risk of stroke or heart attack in patients who have had or ... risk of developing a stomach ulcer when taking aspirin. Aspirin is in a class of medications called ...

  5. Aspirin Resistance

    OpenAIRE

    Khaled Mansour; Ali T. Taher; Khaled M. Musallam; Samir Alam

    2009-01-01

    The development of adverse cardiovascular events despite aspirin use has established an interest in a possible resistance to the drug. Several definitions have been set and various laboratory testing modalities are available. This has led to a wide range of prevalence reports in different clinical entities. The etiologic mechanism has been related to clinical, genetic, and other miscellaneous factors. The clinical implications of this phenomenon are significant and warrant concern. Management...

  6. Effect of aspirin in "aspirin sensitive" patients.

    OpenAIRE

    Asad, S I; Kemeny, D M; Youlten, L J; Frankland, A W; Lessof, M H

    1984-01-01

    Eighteen patients with a history of urticaria or asthma, or both, induced by aspirin were studied before and after provocation of symptoms with aspirin. The plasma prostaglandin F2 alpha concentration, which was characteristically raised before challenge, fell significantly at the time of adverse reactions. Repeated administration of aspirin up to a dose of 650 mg daily induced tolerance in most of the patients, and several developed bronchodilator responses to aspirin. Although median total ...

  7. Aspirin Resistance

    Directory of Open Access Journals (Sweden)

    Khaled Mansour

    2009-01-01

    Full Text Available The development of adverse cardiovascular events despite aspirin use has established an interest in a possible resistance to the drug. Several definitions have been set and various laboratory testing modalities are available. This has led to a wide range of prevalence reports in different clinical entities. The etiologic mechanism has been related to clinical, genetic, and other miscellaneous factors. The clinical implications of this phenomenon are significant and warrant concern. Management strategies are currently limited to dosing alteration and introduction of other anitplatelet agents. However, these measures have not met the expected efficacy or safety.

  8. Aspirin, Butalbital, and Caffeine

    Science.gov (United States)

    The combination of aspirin, butalbital, and caffeine comes as a capsule and tablet to take by mouth. It usually is taken every 4 ... explain any part you do not understand. Take aspirin, butalbital, and caffeine exactly as directed. Do not ...

  9. Aspirin in Neurology

    OpenAIRE

    Yolanda Aburto-Murrieta; Dulce Bonifacio-Delgadillo; Juan Marquez

    2011-01-01

    Aspirin is widely used for the prevention of recurrent stroke in patients with transient ischaemic attack (TIA) of arterial origin, because it is effective and inexpensive. Clopidogrel and the combination of aspirin and extended-release dipyridamole are more effective than aspirin, but are also much more expensive. No other antithrombotic regimens provide significant advantages over aspirin, although cilostazol and the novel platelet protease-activated receptor-1 antagonist, SCH 530348, are c...

  10. Experiments with Aspirin.

    Science.gov (United States)

    Borer, Londa L.; Barry, Edward

    2000-01-01

    Presents a series of experiments that can be used to demonstrate how aspirin can be synthesized and characterized, how the hydrolysis of aspirin can be used as an introduction to kinetics, and how coordination chemistry (chelation) can be introduced by preparing and characterizing the copper complexes of aspirin and salicylic acid. (Contains over…

  11. Paradoxical Effect of Aspirin

    Directory of Open Access Journals (Sweden)

    Christian Doutremepuich

    2012-01-01

    Full Text Available Low-dose aspirin is an important therapeutic option in the secondary prevention of myocardial infarction (MI and ischemic stroke, basedon its unique cost-effectiveness and widespread availability. In addition, based on the results of a number of large studies, aspirin is also widely used in the primary prevention of MI. This paper provides an update of the available data to offer greater clarity regarding the risks of aspirin with respect to hemorrhagic stroke. In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage. When considering whether aspirin is appropriate, the absolute therapeutic cardiovascular benefits of aspirin must be balanced with the possible risks associated with its use, being hemorrhagic stroke. Regarding these clinical facts, normal, COX 1 −/−, and COX 2 −/− mice were treated with a wide range of doses of aspirin and studied by induced hemorrhagic time. The results outlined three major conclusions: high doses of aspirin induce hemorrhage, while low doses of aspirin do not. In the absence of COX 1, ultra low doses of aspirin produce an antihemorrhagic effect not observed with intermediate doses. The absence of COX 2 induced a hemorrhagic effect that needs further research, probably originated in compensatory phenomena.

  12. Aspirin-Exacerbated Asthma

    OpenAIRE

    Varghese, Mathew; Lockey, Richard F

    2008-01-01

    This review focuses on aspirin-exacerbated asthma (AEA). The review includes historical perspective of aspirin, prevalence, pathogenesis, clinical features and treatment of AEA. The pathogenesis of AEA involves the cyclooxygenase and lipooxygenase pathway. Aspirin affects both of these pathways by inhibiting the enzyme cycooxygenase-1 (COX-1). Inhibition of COX-1 leads to a decrease in prostaglandin E2 (PGE2). The decrease in PGE2 results in an increase in cysteinyl leukotrienes by the lipoo...

  13. Aspirin for Primary Prevention.

    Science.gov (United States)

    Richman, Ilana B; Owens, Douglas K

    2017-07-01

    Aspirin reduces the risk of nonfatal myocardial infarction and stroke, and the risk of colorectal cancer. Aspirin increases the risk of gastrointestinal and intracranial bleeding. The best available evidence supports initiating aspirin in select populations. In 2016, the US Preventive Services Task Force recommended initiating aspirin for the primary prevention of both cardiovascular disease and colorectal cancer among adults ages 50 to 59 who are at increased risk for cardiovascular disease. Adults 60 to 69 who are at increased cardiovascular disease risk may also benefit. There remains considerable uncertainty about whether younger and older patients may benefit. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. [Aspirin and colorectal cancer].

    Science.gov (United States)

    Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

    2018-02-01

    Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  15. Aspirin and heart disease

    Science.gov (United States)

    ... attack . Your provider may recommend to take daily aspirin if: You do not have a history of heart disease or stroke, but you are at high risk for a heart attack or stroke. You have been diagnosed ... already. Aspirin helps get more blood flowing to your legs. ...

  16. Medications Containing Aspirin (Acetylsalicylate) and Aspirin-Like Products

    Science.gov (United States)

    updated 3/10/08 Medications Containing Aspirin (Acetylsalicylate) and Aspirin-Like Products © National Reye's Syndrome Foundation Inc. 2008 Epidemiologic research has shown an association between the development of Reye's ...

  17. Aspirin: yesterday, today, and tomorrow

    Directory of Open Access Journals (Sweden)

    Marina Nikołajewna Dołżenko

    2014-06-01

    Full Text Available Clinical utility of aspirin (acetylsalicylic acid, ASA is one of the more important issues in the primary and secondary prevention of cardiovascular disease. The present paper provides analysis of aspirin history, mechanisms of its antiplatelet activity, and expediency of the use of low- and high-dose aspirin in the groups including patients after myocardial revascularization, and requiring secondary prevention of stroke. Also gender-specific aspirin properties were mentioned, highlighting the especially important role of aspirin in women at the age of >65 years, and its utility in all women, irrespectively of age, and those who are at high risk of cardiovascular disease, including atherosclerosis-related cardiovascular disease. Moreover, the mechanisms of aspirin resistance, characterized by inability of aspirin to prevent thromboembolic complications or inadequate platelet inhibition showed in laboratory results, were mentioned. Prevalence of resistance in aspirin-treated patients is estimated to be between 1 and 68%. Stress was also put on the aspirin safety, associated with prophylaxis of peptic ulcer disease, which can be achieved i.e. by the use of the enteric-coated aspirin. This form of aspirin is associated with lower risk of gastrointestinal mucosae damage and bleeding from the gastrointestinal tract. At the end of the article, the importance of the adherence to therapeutic guidelines of aspirin use, including assessment of variation in aspirin bioavailability associated with improper dosing and altered absorption in the gastrointestinal tract, was stressed.

  18. Low dose aspirin and pregnancy: how important is aspirin resistance?

    OpenAIRE

    Navaratnam, K; Alfirevic, A; Alfirevic, Z

    2016-01-01

    Antiplatelet agents are pivotal for prevention of coronary artery disease and cerebrovascular disease worldwide. Individual patient data meta?analysis indicates that low?dose aspirin causes a 10% risk reduction in pre?eclampsia for women at high individual risk. However, in the last 15 years it has emerged that a significant proportion of aspirin?treated individuals exhibit suboptimal platelet response, determined biochemically and clinically, termed ?aspirin non?responsiveness?, ?aspirin res...

  19. Aspirin: yesterday, today, and tomorrow

    OpenAIRE

    Marina Nikołajewna Dołżenko

    2014-01-01

    Clinical utility of aspirin (acetylsalicylic acid, ASA) is one of the more important issues in the primary and secondary prevention of cardiovascular disease. The present paper provides analysis of aspirin history, mechanisms of its antiplatelet activity, and expediency of the use of low- and high-dose aspirin in the groups including patients after myocardial revascularization, and requiring secondary prevention of stroke. Also gender-specific aspirin properties were mentioned, hi...

  20. Aspirin-Exacerbated Asthma

    Directory of Open Access Journals (Sweden)

    Varghese Mathew

    2008-06-01

    Full Text Available This review focuses on aspirin-exacerbated asthma (AEA. The review includes historical perspective of aspirin, prevalence, pathogenesis, clinical features and treatment of AEA. The pathogenesis of AEA involves the cyclooxygenase and lipooxygenase pathway. Aspirin affects both of these pathways by inhibiting the enzyme cycooxygenase-1 (COX-1. Inhibition of COX-1 leads to a decrease in prostaglandin E2 (PGE2. The decrease in PGE2 results in an increase in cysteinyl leukotrienes by the lipooxygenase pathway involving the enzyme 5-lipooxygenase (5-LO. Leukotriene C4 (LTC4 synthase is the enzyme responsible for the production of leukotriene C4, the chief cysteinyl leukotriene responsible for AEA. There have been familial occurences of AEA. An allele of the LTC4 synthase gene in AEA is known as allele C. Allele C has a higher frequency in AEA. Clinical presentation includes a history of asthma after ingestion of aspirin, nasal congestion, watery rhinorrhea and nasal polyposis. Treatment includes leukotriene receptor antagonists, leukotriene inhibitors, aspirin desinsitaztion and surgery. AEA is the most well-defined phenotype of asthma. Although AEA affects adults and children with physician-diagnosed asthma, in some cases there is no history of asthma and AEA often goes unrecognized and underdiagnosed.

  1. Aspirin and Cancer.

    Science.gov (United States)

    Patrignani, Paola; Patrono, Carlo

    2016-08-30

    The place of aspirin in primary prevention remains controversial, with North American and European organizations issuing contradictory treatment guidelines. More recently, the U.S. Preventive Services Task Force recommended "initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years." This recommendation reflects increasing evidence for a chemopreventive effect of low-dose aspirin against colorectal (and other) cancer. The intent of this paper is to review the evidence supporting a chemopreventive effect of aspirin, discuss its potential mechanism(s) of action, and provide a conceptual framework for assessing current guidelines in the light of ongoing studies. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  2. Twisted aspirin crystals.

    Science.gov (United States)

    Cui, Xiaoyan; Rohl, Andrew L; Shtukenberg, Alexander; Kahr, Bart

    2013-03-06

    Banded spherulites of aspirin have been crystallized from the melt in the presence of salicylic acid either generated from aspirin decomposition or added deliberately (2.6-35.9 mol %). Scanning electron microscopy, X-ray diffraction analysis, and optical polarimetry show that the spherulites are composed of helicoidal crystallites twisted along the growth directions. Mueller matrix imaging reveals radial oscillations in not only linear birefringence, but also circular birefringence, whose origin is explained through slight (∼1.3°) but systematic splaying of individual lamellae in the film. Strain associated with the replacement of aspirin molecules by salicylic acid molecules in the crystal structure is computed to be large enough to work as the driving force for the twisting of crystallites.

  3. Aspirin desensitization for cardiovascular disease.

    Science.gov (United States)

    Woessner, Katharine M

    2015-08-01

    The use of aspirin in coronary artery disease and address the unmet need of aspirin therapy in patients with history of hypersensitivity reactions to aspirin (acetylsalicylic acid; ASA) or other nonsteroidal inflammatory drugs (NSAIDs). Aspirin hypersensitivity is reported in 1.5% of patients with cardiovascular disease. However, many of those labeled as allergic to aspirin had experienced side-effects and could be safely treated with aspirin. Those with true hypersensitivity reactions were often not placed on appropriate antiplatelet therapy. A number of protocols of varying complexity exist in the literature for aspirin desensitization. The focus of this review is to identify the types of aspirin reactions that can occur and provide a rational approach to oral aspirin challenge and desensitization. In summary, with rare exceptions, patients with a history of 'aspirin/NSAID allergy' who need ASA for cardiovascular issues will be able to safely take aspirin either after a graded challenge or desensitization providing a central role of the allergist in the management of these patients.

  4. Reye Syndrome and Aspirin

    OpenAIRE

    J Gordon Millichap

    1987-01-01

    Twenty-six cases of Reye syndrome occurring between 1973 and 1982 have been reviewed in relation to aspirin ingestion at the Children’s Hospital, Camperdown, Australia (formerly the Royal Alexandra Hospital for Children in Sydney), where Reye first described his syndrome of encephalopathy and fatty degeneration of the viscera in 1963.

  5. Aspirin, 110 years later.

    Science.gov (United States)

    Patrono, C; Rocca, B

    2009-07-01

    Although conceived at the end of the 19th century as a synthetic analgesic agent with improved gastric tolerability vs. naturally occurring salicylates, acetylsalicylic acid (marketed as aspirin in 1899) turned out to be an ideal antiplatelet agent about 90 years later, following the understanding of its mechanism of action, the development of a mechanism-based biomarker for dose-finding studies, and the initiation of a series of appropriately sized, randomized clinical trials to test its efficacy and safety at low doses given once daily. At the turn of its 110th anniversary, aspirin continues to attract heated debates on a number of issues including (i) the optimal dose to maximize efficacy and minimize toxicity; (ii) the possibility that some patients may be 'resistant' to its antiplatelet effects; and (iii) the balance of benefits and risks in primary vs. secondary prevention.

  6. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events

    NARCIS (Netherlands)

    Squizzato, Alessandro; Bellesini, Marta; Takeda, Andrea; Middeldorp, Saskia; Donadini, Marco Paolo

    2017-01-01

    Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease. This is an update to a previously published review

  7. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease

    NARCIS (Netherlands)

    Squizzato, Alessandro; Keller, Tymen; Romualdi, Erica; Middeldorp, Saskia

    2011-01-01

    Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for those at high risk and those with established cardiovascular disease. To quantify the benefit and harm of adding clopidogrel

  8. Greener Methods for Aspirin Synthesis

    OpenAIRE

    Barilone, Jessica

    2013-01-01

    In this semester long study, I used microwave irradiation to synthesize aspirin. I compared this method to a traditional method that utilizes a strong acid. I compared the percent yield and the purity of the methods to pure aspirin

  9. MACULAR DEGENERATION AND ASPIRIN USE.

    Science.gov (United States)

    Small, Kent W; Garabetian, Christine A; Shaya, Fadi S

    2017-09-01

    To review current literature of the benefits that aspirin provides for patients' cardiovascular health compared with the risk of AMD worsening. We performed a review and critically analyzed six cardiovascular and four ophthalmological trials regarding risks and benefits of aspirin use. The prospective randomized cardiovascular trials had a cumulative 167,580 while the 3 smaller ophthalmological data sets had a cumulative 12,015 subjects. The reviewed meta-analysis literature demonstrated a statistically significant 32% reduction in the risk of nonfatal stroke with regular aspirin users. The study also documented that aspirin users decreased the risk of fatal vascular deaths by 15%. Of the three ophthalmological studies highlighting the adverse affects of aspirin association with AMD, all suggested an exacerbation of AMD without statistical significance and broad confidence bands. Overall, the number, size, and quality of the cardiovascular studies recommending aspirin use are far superior to the fewer, smaller and conflicting studies suggesting a possible adverse effect of aspirin use in relation to AMD. The benefits of aspirin usage include preserving the duration and quality of life by decreasing stroke and heart attack risk. These benefits seem to far outweigh the theoretical risks of possibly exacerbating wet AMD, which can be reasonably controlled with anti-VEGF therapy.

  10. Comparative bioequivalence assessment of aspirin tablets marketed ...

    African Journals Online (AJOL)

    Purpose: In the last few years, aspirin has become a life saver against cardiovascular accidents. This investigation was carried out to determine possible bioequivalence between regular aspirin and soluble aspirin tablets marketed in Nigeria. Methods: The in vivo bioavailability profiles of three commercial brands of aspirin ...

  11. Taking Aspirin to Protect Your Heart

    Science.gov (United States)

    Toolkit No. 23 Taking Aspirin to Protect Your Heart What can taking aspirin do for me? If you are at high risk for or if you have heart disease, taking a low dose aspirin every day may help. Aspirin can also help ...

  12. Aspirin-Induced Acute Liver Injury

    OpenAIRE

    Laster, Janese; Satoskar, Rohit

    2014-01-01

    Aspirin is thought to be a relatively safe drug in adults. The association of aspirin and Reye syndrome in children is well documented. We report a 41-year-old female with pericarditis who was treated with high-dose aspirin and developed subsequent acute liver injury. After discontinuation of aspirin, liver enzyme elevation and right upper quadrant pain both resolved. We conclude that high-dose aspirin should be considered as a potentially hepatotoxic agent.

  13. Platelets, aspirin, and cardiovascular disease.

    Science.gov (United States)

    Elwood, P C; Hughes, C; O'Brien, J R

    1998-10-01

    Aspirin was first synthesised 100 years ago and its preparation and marketing is generally reckoned to have been the foundation of the pharmaceutical industry. For most of the time since then it has been used for the relief of pain and fever. The modern phase of aspirin use commenced with the reporting in 1974 of a randomised controlled trial in the secondary prevention of death by low-dose aspirin given to patients who had suffered a myocardial infarct. Reports of other trials followed and an overview of the first six trials was presented to the inaugural meeting of the Society for Clinical Trials in Philadelphia in 1980. There have been two further major overviews and the most recent, based on 145 trials, established that low-dose aspirin reduces vascular events by around one third. It has been estimated that, used appropriately, aspirin could prevent 100,000 premature deaths each year worldwide, at a cost of about 250 Pounds ($400) per life saved, and about 80 Pounds ($130) per cardiovascular event prevented. The evidence indicates that it is seriously underused at present. The aspirin story continues and trials are in progress to test other possible uses of aspirin, in vascular dementia, colorectal cancer, and cataract.

  14. Gastrointestinal symptoms in low-dose aspirin users: a comparison between plain and buffered aspirin

    NARCIS (Netherlands)

    Jaspers Focks, J.; Tielemans, M.M.; Rossum, L.G.M. van; Eikendal, T.; Brouwer, M.A.; Jansen, J.B.M.J.; Laheij, R.J.F.; Verheugt, F.W.A.; Oijen, M.G.H. van

    2014-01-01

    BACKGROUND: Aspirin is associated with gastrointestinal side effects such as gastric ulcers, gastric bleeding and dyspepsia. High-dose effervescent calcium carbasalate (ECC), a buffered formulation of aspirin, is associated with reduced gastric toxicity compared with plain aspirin in healthy

  15. Platelets, aspirin, and cardiovascular disease.

    OpenAIRE

    Elwood, P. C.; Hughes, C.; O'Brien, J. R.

    1998-01-01

    Aspirin was first synthesised 100 years ago and its preparation and marketing is generally reckoned to have been the foundation of the pharmaceutical industry. For most of the time since then it has been used for the relief of pain and fever. The modern phase of aspirin use commenced with the reporting in 1974 of a randomised controlled trial in the secondary prevention of death by low-dose aspirin given to patients who had suffered a myocardial infarct. Reports of other trials followed and a...

  16. Increased platelet expression of glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects

    Science.gov (United States)

    Floyd, Christopher N; Goodman, Timothy; Becker, Silke; Chen, Nan; Mustafa, Agnesa; Schofield, Emma; Campbell, James; Ward, Malcolm; Sharma, Pankaj; Ferro, Albert

    2014-01-01

    Aims Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects. Methods Ninety-three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11-dehydrothromboxane B2, and blood was taken to measure arachidonic acid (AA)-induced aggregation of platelet-rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. Results In two of the 93 subjects, neither AA-induced aggregation nor urinary 11-dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet glycoprotein IIIa expression in the aspirin-resistant but not aspirin-sensitive subjects. An increase in platelet glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. Conclusions In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin-resistant subjects using a novel biomarker. PMID:25099258

  17. Daily Aspirin Therapy: Understand the Benefits and Risks

    Science.gov (United States)

    Daily aspirin therapy: Understand the benefits and risks Daily aspirin therapy can be a lifesaving option, but it's not ... everyone. Get the facts before considering a daily aspirin. By Mayo Clinic Staff Daily aspirin therapy may ...

  18. Aspirin and aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Gross, Bradley A; Rosalind Lai, Pui Man; Frerichs, Kai U; Du, Rose

    2014-12-01

    Recent evidence has suggested a potential beneficial effect of aspirin on the risk of aneurysm rupture. This benefit must be weighed against its potential adverse effects as an antiplatelet agent in the setting of acute aneurysmal subarachnoid hemorrhage (SAH). A total of 747 consecutive patients with cerebral aneurysms were reviewed, comparing demographics, aneurysm features, presenting clinical and radiographic grades, vasospasm, and outcome at 1 year between patients with aneurysmal SAH taking aspirin on presentation and those who were not. The rate of hemorrhagic presentation was significantly greater in patients not taking aspirin (40% vs. 28%; P = 0.016). Among 274 patients presenting with aneurysmal SAH, there was no significant difference in presenting clinical (Hunt and Hess) and radiographic (Fisher) grade between patients taking aspirin and those who were not. There was also no significant difference in the rate of subsequent angiographic and delayed cerebral ischemia. Multivariate analysis of outcome at 1 year found only increasing age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04-1.12), Hunt and Hess grade (OR 3.01, 95% CI 1.81-5.03), and associated hypertension (OR 3.30, 95% CI 1.39-7.81) to be statistically significant risk factors for poor outcome (death or dependence), whereas aspirin use was not associated with poor outcome (OR 1.19, 95% CI 0.35-4.09; P = 0.78). In the present study, patients taking aspirin had a lower rate of hemorrhagic presentation. In addition, taking aspirin did not adversely impact presenting clinical grade or radiographic grade, vasospasm, and outcome in the setting of aneurysmal SAH. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Novel Proresolving Aspirin-Triggered DHA Pathway

    National Research Council Canada - National Science Library

    Serhan, Charles N; Fredman, Gabrielle; Yang, Rong; Karamnov, Sergey; Belayev, Ludmila S; Bazan, Nicolas G; Zhu, Min; Winkler, Jeremy W; Petasis, Nicos A

    2011-01-01

    .... We report an aspirin-triggered DHA metabolome that biosynthesizes a potent product in inflammatory exudates and human leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 [AT-(NPD1/PD1...

  20. Aspirin to Zoloft: Ways Medicines Work

    Science.gov (United States)

    ... View All Articles | Inside Life Science Home Page Aspirin to Zoloft: Ways Medicines Work By Emily Carlson ... biology of how cancer cells grow. Antihistamines, Antidepressants, Aspirin Adrenergic receptor with carazolol, a beta-blocker. View ...

  1. Aspirin during Pregnancy: Is It Safe?

    Science.gov (United States)

    Healthy Lifestyle Pregnancy week by week Is it safe to take aspirin during pregnancy? Answers from Yvonne Butler Tobah, M. ... 2015 Original article: http://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/expert-answers/aspirin-during-pregnancy/ ...

  2. Aspirin resistant patients with recent ischemic stroke.

    Science.gov (United States)

    Castilla-Guerra, L; Navas-Alcántara, M S; Fernández-Moreno, M C

    2014-04-01

    Some patients with a recent ischemic stroke who are being treated with aspirin as an antiaggregant suffer a new ischemic stroke. These patients (15-25%) have been called unresponsive to aspirin or aspirin resistant. The aspirin-resistant patients have a four-time greater risk of suffering a stroke. Furthermore, these strokes are generally more severe, with increased infarct volume and greater risk of recurrence. There is currently no ideal laboratory test to detect the resistance to the antiaggregant effect of aspirin. The study of resistance to aspirin would only be indicated in selected cases. In these patients, one should first rule out any "pseudo-resistance" to aspirin (lack of compliance, concomitant treatments that interfere with the action of the aspirin). Copyright © 2013 Elsevier España, S.L. All rights reserved.

  3. Aspirin: past, present and future.

    Science.gov (United States)

    Elwood, P C

    2001-01-01

    Many folk remedies used since pre-historic times have depended upon salicylates for their effect. One hundred years ago aspirin was formulated from salicylic and acetic acids. It was the first drug to be synthesised and its formulation is regarded as the foundation of the modern pharmaceutical industry. The benefit of low-dose aspirin as a prophylactic after a thrombotic event was first reported 25 years ago. Its use after coronary or cerebral thrombosis is virtually mandatory, unless there are signs of intolerance. A 'loading dose' of soluble aspirin should be given on first contact with a patient who may be suffering from myocardial infarction. Patients considered to be at increased risk of a vascular event should also be advised to carry their own aspirin and, if they experience sudden severe chest pain, to chew and swallow a 300 mg tablet or a soluble preparation immediately. The current phase of the aspirin story is, however, not over, and its possible value in a variety of conditions, including dementia and certain cancers, seems likely to ensure that it will long continue to play a remarkable part in clinical practice.

  4. The role of aspirin in women's health

    NARCIS (Netherlands)

    Verheugt, F.W.A.; Bolte, A.C.

    2011-01-01

    BACKGROUND: The aim of this review is to discuss the role of aspirin for various conditions in women. METHODS: A nonsystematic review of articles published on PubMed((R)) that examines the role of aspirin in women. RESULTS: Aspirin is associated with a significant reduction of stroke risk in women,

  5. Aspirin: Pharmacology and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Enma V. Paez Espinosa

    2012-01-01

    Full Text Available Antiplatelet therapy has been documented to reduce risks of cardiovascular disease after acute myocardial infarction, coronary artery bypass graft, and in chronic atrial fibrillation patients, amongst other risk factors. Conventional management of thrombosis-based disorders includes the use of heparin, oral anticoagulants, and the preferred antiplatelet agent aspirin. Interestingly, aspirin was not intended to be used as an antiplatelet agent; rather, after being repurposed, it has become one of the most widely prescribed antithrombotic drugs. To this end, there have been several milestones in the development of antiplatelet agents in the last few decades, such as adenosine diphosphate receptor inhibitors, phosphodiesterase inhibitors, and GPIIb/IIIa inhibitors. However, given some of the limitations of these therapies, aspirin continues to play a major role in the management of thrombotic and cardiovascular disorders and is expected to do so for years to come.

  6. Technetium-aspirin molecule complexes

    Energy Technology Data Exchange (ETDEWEB)

    El-Shahawy, A.S.; Mahfouz, R.M.; Aly, A.A.M.; El-Zohry, M. (Assiut Univ. (Egypt))

    1993-01-01

    Technetium-aspirin and technetium-aspirin-like molecule complexes were prepared. The structure of N-acetylanthranilic acid (NAA) has been decided through CNDO calculations. The ionization potential and electron affinity of the NAA molecule as well as the charge densities were calculated. The electronic absorption spectra of Tc(V)-Asp and Tc(V)-ATS complexes have two characteristic absorption bands at 450 and 600 nm, but the Tc(V)-NAA spectrum has one characteristic band at 450 nm. As a comparative study, Mo-ATS complex was prepared and its electronic absorption spectrum is comparable with the Tc-ATS complex spectrum. (author).

  7. TRUE RESISTANCE AND PSEUDORESISTANCE TO ASPIRIN

    Directory of Open Access Journals (Sweden)

    A. I. Martynov

    2013-01-01

    Full Text Available Low dose aspirin reduces the secondary incidence of myocardial infarction and stroke. Drug resistance to aspirin might result in treatment failure. Despite this concern, no clear definition of aspirin resistance has emerged, and estimates of its incidence have varied remarkably. Researchers from university of Pennsylvania (Philadelphia, the USA, led by Dr. Tilo Grosser, aimed to determine the specific phenotype of true pharmacological resistance to aspirin — such as might be explained by genetic causes. However the study failed to identify a single case of true drug resistance. Pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration.

  8. Compound list: aspirin [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available aspirin ASA 00014 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/aspirin....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/aspirin....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/aspirin....Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/aspirin.Rat.in_vivo.Liver.Repeat.zip ...

  9. Aspirin in patients undergoing noncardiac surgery

    DEFF Research Database (Denmark)

    Devereaux, P J; Mrkobrada, Marko; Sessler, Daniel I

    2014-01-01

    BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10......,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before...... the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum...

  10. Rapid Aspirin Challenge in Patients with Aspirin Allergy and Acute Coronary Syndromes.

    Science.gov (United States)

    Cook, Kevin A; White, Andrew A

    2016-02-01

    Aspirin allergy in a patient with acute coronary syndrome represents one of the more urgent challenges an allergist may face. Adverse reactions to aspirin are reported in 1.5% of patients with coronary artery disease. A history of adverse reaction to aspirin often leads to unnecessary withholding of this medication or use of alternative antiplatelet therapy which may be inferior or more costly. Aspirin therapy has been shown to reduce morbidity and mortality in patients with coronary artery disease. Rapid aspirin challenge/desensitization in the aspirin allergic patient has been consistently shown to be both safe and successful in patients with acute coronary syndromes.

  11. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events.

    Science.gov (United States)

    Squizzato, Alessandro; Bellesini, Marta; Takeda, Andrea; Middeldorp, Saskia; Donadini, Marco Paolo

    2017-12-14

    Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease. This is an update to a previously published review from 2011. To review the benefit and harm of adding clopidogrel to aspirin therapy for preventing cardiovascular events in people who have coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or were at high risk of atherothrombotic disease, but did not have a coronary stent. We updated the searches of CENTRAL (2017, Issue 6), MEDLINE (Ovid, 1946 to 4 July 2017) and Embase (Ovid, 1947 to 3 July 2017) on 4 July 2017. We also searched ClinicalTrials.gov and the WHO ICTRP portal, and handsearched reference lists. We applied no language restrictions. We included all randomised controlled trials comparing over 30 days use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in people with coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or at high risk of atherothrombotic disease. We excluded studies including only people with coronary drug-eluting stent (DES) or non-DES, or both. We collected data on mortality from cardiovascular causes, all-cause mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal ischaemic stroke, major and minor bleeding. The overall treatment effect was estimated by the pooled risk ratio (RR) with 95% confidence interval (CI), using a fixed-effect model (Mantel-Haenszel); we used a random-effects model in cases of moderate or severe heterogeneity (I 2 ≥ 30%). We assessed the quality of the evidence using the GRADE approach. We used GRADE profiler (GRADE Pro) to import data from Review Manager to create a 'Summary of findings' table. The search identified 13 studies in addition to the two studies in the previous version of our systematic review. Overall

  12. The role of aspirin in cancer prevention.

    Science.gov (United States)

    Thun, Michael J; Jacobs, Eric J; Patrono, Carlo

    2012-04-03

    Clinical guidelines for prophylactic aspirin use currently only consider the cardiovascular benefits of aspirin, weighed against the potential harm from aspirin-induced bleeding. Daily aspirin use has been convincingly shown to reduce the risk of colorectal cancer and recurrence of adenomatous polyps, but in average-risk populations, these benefits alone do not outweigh harms from aspirin-induced bleeding. Recently published secondary analyses of cardiovascular trials provide the first randomized evidence that daily aspirin use may also reduce the incidence of all cancers combined, even at low doses (75-100 mg daily). This Review considers the general mechanism of action that defines aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) as a class, the specific advantages of aspirin over other NSAIDs for prophylactic use, the current evidence concerning the main health outcomes affected by aspirin use, and the hypothesis that inhibition of platelet activation may mediate both the cardioprotective and cancer-preventive effects of low-dose aspirin. It also considers how even a 10% reduction in overall cancer incidence beginning during the first 10 years of treatment could tip the balance of benefits and risks favourably in average-risk populations.

  13. Aspirin resistance following pediatric cardiac surgery.

    Science.gov (United States)

    Cholette, Jill M; Mamikonian, Lara; Alfieris, George M; Blumberg, Neil; Lerner, Norma B

    2010-09-01

    Aspirin is often used to prevent thrombosis in pediatric cardiac surgery. The primary study aim was to assess aspirin resistance in this context. Secondary aims were to evaluate (1) the relationship between elevated inflammatory markers and thrombosis and (2) aspirin's effect on these levels. This was a prospective observational study of children undergoing cardiac surgery managed with and without aspirin. Aspirin response was assessed using the VerifyNow system and urinary 11-dehydrothromboxane B2 (uTxB2) measurements. Laboratory studies of inflammation were also obtained. 101 subjects were studied; 50 received aspirin. Six subjects (5.9%), 5 aspirin-treated, experienced symptomatic thrombosis. When measured by VerifyNow resistance was 43% after aspirin suppositories and 14% after additional days of oral aspirin. There was no correlation with thrombosis. Upper quartile post-operative day (POD) #5 uTxB2 was correlated with thrombosis in aspirin treated subjects (paspirin-treated subjects who experienced thrombosis had higher POD#5 uTxB2. This finding did not reach statistical significance (p=0.07). Elevated pre-operative C-reactive protein (CRP) was independently associated with thrombosis (paspirin. Aspirin inhibited ex-vivo platelet function with a low incidence of resistance. Elevated POD#5 uTxB2 and pre-operative CRP were correlated with thrombosis in aspirin treated subjects. Further studies are needed to determine whether children with high levels of uTxB2 despite aspirin therapy and/or those with elevated preoperative CRP are at increased risk for thrombosis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  14. [Pathogenesis and prevention tactics of aspirin resistance].

    Science.gov (United States)

    Zhang, Ren-gang; Zhang, Jun-ping

    2007-05-01

    Aspirin (acetylsalicylic acid) is a nonsteroidal anti-inflammatory drug. Despite its wide uses for more than 100 years, knowledge about mechanism of action and therapeutic issues of aspirin are still under discussion. The use of aspirin has been changed from an analgesic, anti-pyretic and anti-inflammatory agent to an anti-thrombotic agent, especially in secondary prevention of cardiovascular events. Aspirin has reduced the risk of cardiovascular events by 25%. However, the phenomenon of "aspirin resistance" has been described that in 5%-60% of patients aspirin may not achieve adequate efficacy of suppressing platelet activity. The convinced causes of this phenomenon are still unknown. It is probably due to drugs interaction, inadequate dosage and so on. By far the existing studies of aspirin are insufficient to explain all phenomena of aspirin resistance. And the results are not always uniform about the same research. Therefore, the characteristics in different population with aspirin resistance may account for the complexity. It is unrealistic to elucidate all aspirin resistance by only one pathway. More studies are required to investigate the mechanisms in different population respectively. According to the theory of traditional Chinese medicine and the trait of cardiovascular disease, which often relapses and has a long history, aspirin resistance should be considered as collaterals disease. It can be treated with aspirin and traditional Chinese drugs which have the power to strengthen body resistance, reduce phlegm, remove blood stasis and toxic materials from meridians. The problem of aspirin resistance might be solved by this way, because the traditional Chinese medicine has the superiority of selecting appropriate therapeutic methods based on syndrome differentiation for different population and regulating the whole body's function. Subsequently, cardiovascular disease might be effectively prevented.

  15. Talk with Your Doctor about Taking Aspirin Every Day

    Science.gov (United States)

    ... En español Talk with Your Doctor about Taking Aspirin to Prevent Disease Browse Sections The Basics Overview ... and Risks What are the benefits of taking aspirin regularly? Low-dose aspirin can reduce your risk ...

  16. Aspirin to Prevent a First Heart Attack or Stroke

    Science.gov (United States)

    ... NHLBI on Twitter. Aspirin to Prevent a First Heart Attack or Stroke Also known as aspirin primary prevention. ... if I’m taking aspirin to prevent another heart attack or stroke? The information discussed in Who may ...

  17. Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions

    OpenAIRE

    Undas, Anetta; Brummel-Ziedins, Kathleen E.; Mann, Kenneth G.

    2007-01-01

    Aspirin is effective in the prevention of cardiovascular events in high-risk patients. The primary established effect of aspirin on hemostasis is to impair platelet aggregation via inhibition of platelet thromboxane A2 synthesis, thus reducing thrombus formation on the surface of the damaged arterial wall. Growing evidence also indicates that aspirin exerts additional antithrombotic effects, which appear to some extent unrelated to platelet thromboxane A2 production. Aspirin can reduce thromb...

  18. Effects of Aspirin on Rheological Properties of Erythrocytes In Vitro

    OpenAIRE

    Elblbesy, Mohamed A.; Hereba, Abdel Rahman M.; Shawki, Mamdouh M.

    2012-01-01

    Aspirin is of proven value as an antithrombotic drug. In unstable angina it reduces the risk of death and myocardial infarction by half. Most studies on the mechanism of action of aspirin have concentrated on the effect of aspirin on platelets. In the present study we have tried to prove that there is another biophysical mechanism of aspirin, and that is through the effect of aspirin on erythrocytes. In this study ten blood samples were incubated with aspirin at different concentrations. The ...

  19. Genetic Markers for Differentiating Aspirin-Hypersensitivity

    OpenAIRE

    Kim, Seung-Hyun; Park, Hae-Sim

    2006-01-01

    Aspirin-induced asthma (AIA) and aspirin-induced urticaria/angioedema (AIU) are two major aspirin-related allergies. We summarize recent findings related to their molecular genetic mechanisms in order to identify genetic susceptibility markers for differentiating AIU and AIA. The overproduction of cysteinyl leukotriene has been suggested as a mechanism in both AIU and AIA. Increased expression of CYSLTR1 with CYLSTR1 and CYSLTR2 polymorphisms are new findings in AIA, while the ALOX5 promoter ...

  20. [From the willow to aspirin].

    Science.gov (United States)

    Lafont, Olivier

    2007-07-01

    At the beginning was the willow bark, which was considered as a medicine by Hippocrates, Dioscorides and Plinus. During the XVIIIth century, the Reverend Edward Stone re-discovered the willow for the cure of agues. In 1829, the french pharmacist Pierre Joseph Leroux isolated salicin. Raffaelle Piria was the first to synthesize salicylic acid from salicin (salicoside). Hermann Kolbe prepared salicylic acid from sodium phenate and carbon dioxide. And then acetylsalicylic acid was first prepared by Charles Gerhardt in 1853, but he did not succeed in identifying its structure. Felix Hoffmann, Arthur Eichengrun and Heinrich Dresen from Bayer Laboratories were at the origin of the use of Aspirin as a medicine. In 1971, John Vane showed that aspirin-like drugs inhibited prostaglandine synthesis.

  1. Immunological mechanisms in aspirin hypersensitivity. Studies on the immunogenicity of free aspirin.

    Science.gov (United States)

    Cîrstea, M; Suhaciu, G; Cîrje, M; Ciontescu, L

    1976-10-01

    Anti-aspiryl antibodies were produced in rabbits and guinea pigs by inoculation of aspirin incorporated in complete or incomplete Freund's adjuvant. These antibodies were readily detected by passive haemagglutination using rabbit erythrocytes incubated with aspirin at alkaline pH. Aspiryl conjugates with ovalbumin, human gamma-globulin, bovine gamma-globulin and rabbit serum were also prepared by incubating the proteins with aspirin at alkaline pH. Aspiryl conjugates prepared by this technique behaved, immunologically, identically with the conjugates prepared from aspirin chloride. By contrast, the molar absorbance at 305 nm of the conjugates prepared from aspirin was about 25 times lower than the molar absorbance of the conjugates prepared from aspirin chloride. Since the absorbance of salicylic acid is about eight times greater than that of aspirin, the conclusion is drawn that the aspiryl/salicylyl ratio is significantly higher in the conjugates prepared by incubating proteins with aspirin at alkaline pH than in the conjugates prepared from aspirin chloride. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with aspirin- or salicylic acid-treated red cells. Sera giving positive passive haemagglutination with aspirin-treated erythrocytes did not react with erythrocytes treated with salicylic acid or acetic anhydride.

  2. Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer

    DEFF Research Database (Denmark)

    Verdoodt, F.; Kjaer, S. K.; Friis, S.

    2017-01-01

    Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin....... Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.......g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian...

  3. EFFECT OF ACETYLSALICYCLIC ACID (ASPIRIN ) AND ...

    African Journals Online (AJOL)

    LIVINGSTON

    Aspirin as such, irreversibly blocks the enzyme cyclo-oxygenase (prostaglandin synthase) which catalyzes the conversion of. Archidonic acid to endoperoxide compounds. In addition to reducing the synthesis of eicosanoid mediators, ASA also interferes with the chemical mediators of the kalikrein system. As a result, aspirin ...

  4. Pharmacogenetics of the antiplatelet effect of aspirin.

    Science.gov (United States)

    Würtz, Morten; Kristensen, Steen Dalby; Hvas, Anne-Mette; Grove, Erik Lerkevang

    2012-01-01

    The concept of "pharmacogenetics" addresses genetically determined variation in how individuals respond to drugs. Accordingly, specific genetic variants have been suggested as contributors to a reduced response to various antiplatelet drugs. Aspirin is a cornerstone in secondary cardiovascular prevention and has been thoroughly investigated. The efficacy of aspirin is well documented, although with considerable interindividual variation. According to meta-analyses, a reduced antiplatelet effect of aspirin confers an increased risk of cardiovascular events. The platelet response to aspirin is assessed by in vitro evaluation of thromboxane-dependent platelet function. A reduced antiplatelet effect of aspirin can be explained by several mechanisms, which are largely determined by clinical, pharmacodynamic, biological and genetic factors. During the past decade, numerous studies have identified genetic polymorphisms significantly associated with cardiovascular events and modulating the antiplatelet effect of aspirin. However, results have been contradictory allowing only few firm conclusions to be drawn. Polymorphisms in genes encoding glycoproteins (IIb/IIIa, Ia/IIa, VI and Ibα), cyclooxygenases (1 and 2), adenosine diphosphate receptors (P2Y1 and P2Y12) and proteins of importance for haemostasis (thromboxane A2 receptor, coagulation factor XIII, etc.) have been investigated. In particular, a polymorphism in the gene encoding glycoprotein IIb/IIIa has been associated with a reduced antiplatelet effect of aspirin. The additive value of an individual's genetic makeup in predicting the antiplatelet effect of aspirin and the risk of cardiovascular events remains controversial. The present review outlines the pharmacology of aspirin and provides an overview of specific genetic variations considered to influence the antiplatelet effect of aspirin.

  5. Effect of aspirin on nasal resistance to airflow.

    OpenAIRE

    Jones, A S; Lancer, J M; Moir, A A; Stevens, J C

    1985-01-01

    The effect of aspirin on nasal resistance to airflow was investigated by rhinomanometry in 25 healthy subjects before and after ingestion of aspirin or vitamin C in a double blind crossover trial. Aspirin caused a significant increase in nasal resistance compared with vitamin C. The effect of aspirin may be due to its inhibition of the synthesis of prostaglandins.

  6. The Aspirin Foundation Scientific Conference: the history, the present state and the future of aspirin prophylaxis

    OpenAIRE

    Smith, Tom; Elwood, Peter; Keating, Conrad; Rothwell, Peter; Detering, Elmar; Freedman, Andrew; Langley, Ruth; Logan, Richard; Phillips, Ceri; DeCensi, Andrea

    2014-01-01

    The 2013 Aspirin Foundation Conference covered a range of topics from clinical and medical history, epidemiology, health economics, and the current uses of aspirin in general practice and in the treatment and prevention of cancer. The use of aspirin as primary prevention in people at risk of atherosclerotic events is now well known, but its use as a preventative agent in some cancer types is still under discussion, and data on colorectal and lung cancer were presented at this meeting. The pot...

  7. Aspirin

    Science.gov (United States)

    ... Circulation My alerts Sign In Join Sign out Facebook Twitter Home About this Journal Editorial Board General Statistics Circulation Doodle Information for Advertisers Author Reprints Commercial Reprints Customer Service and Ordering ...

  8. Aspirin

    Science.gov (United States)

    ... not make sense fear or nervousness dizziness double vision uncontrollable shaking of a part of the body confusion abnormally excited mood hallucination (seeing things or hearing voices that are not ...

  9. Mechanisms of aggregation inhibition by aspirin and nitrate-aspirin prodrugs in human platelets.

    Science.gov (United States)

    Harmon, Shona; Inkielewicz-Stepniak, Iwona; Jones, Michael; Ledwidge, Mark; Santos-Martinez, Maria Jose; Medina, Carlos; Radomski, Marek W; Gilmer, John F

    2012-01-01

    Aspirin is the mainstay of anti-platelet therapy in the secondary prevention of cardiovascular disease. However, problems with aspirin safety and resistance demand clinical strategies based on multiple pharmacological approaches. Prodrugs of aspirin may offer beneficial effects in terms of gastro-intestinal safety and multiple pharmacological approaches. However, the pharmacological profile of aspirin prodrugs in human platelets has not been completed yet. We aimed to compare the effects of aspirin and prodrugs of aspirin (1-5) on human platelet aggregation stimulated by ADP and collagen and associated receptor expression (GPIIb/IIIa and P-selectin) in platelet-rich plasma (PRP) and washed platelets (WP). As aspirin is released from prodrugs following esterase hydrolysis we studied the expression and activity of butyrylcholineterase (BuChE) and carboxyesterase (CE) in plasma and platelets. The mechanism of prodrug-induced platelet aggregation inhibition was explored by studying the effects of plasma and purified human BuChE on aggregation. Finally, the relative contribution of nitric oxide (NO) bioactivity to nitrate-containing prodrugs of aspirin-induced inhibition of aggregation was determined using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ,) a selective inhibitor of the soluble guanylyl cyclase. ST0702, 2, a nicotinic acid-aspirin codrug was equipotent with aspirin with respect to inhibition of collagen-induced platelet aggregation. Compound 4, a NO releasing aspirin was the most potent inhibitor of ADP-induced platelet aggregation, an effect partially reversed by ODQ. The platelet inhibitory effects of aspirin prodrugs were time-dependent as the maximal inhibitory effects against collagen-induced aggregation were achieved by aspirin at 2 min, 1 at 5 min and ST0702 at 15 min. The aspirin prodrugs were significantly less potent in WP than in PRP and the reverse was true of aspirin. In the presence of complete BuChE inhibition in PRP, there was almost

  10. [Aspirin: Indications and use during pregnancy].

    Science.gov (United States)

    Belhomme, N; Doudnikoff, C; Polard, E; Henriot, B; Isly, H; Jego, P

    2017-12-01

    Aspirin (acetylsalicylic acid) has been used ever since the Antiquity for its painkilling and anti-inflammatory effects. Its antiplatelet properties have then extended its indications to the field of coronaropathy and vascular cerebral disease, and finally to vascular placental disease. Aspirin has been widely prescribed since the 1980's to prevent pre-eclampsia, intra-uterine growth retardation and fetal death of vascular origin. It has also been proposed to prevent unexplained recurrent miscarriages. Its use during pregnancy is considered as safe, provided the daily doses do not exceed 100mg. Aspirin has been proven efficient to prevent pre-eclampsia and fetal growth restriction in high-risk patients. The benefits of prescribing aspirin have been demonstrated neither for vascular placental disease prevention in low risk patients, nor in cases of unexplained recurrent miscarriages. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  11. Inhibitory Effect of Aspirin on Cholangiocarcinoma Cells

    Science.gov (United States)

    Boueroy, Parichart; Aukkanimart, Ratchadawan; Boonmars, Thidarut; Sriraj, Pranee; Ratanasuwan, Panaratana; Juasook, Amornrat; Wonkchalee, Nadchanan; Vaeteewoottacharn, Kulthida; Wongkham, Sopit

    2017-11-26

    Aspirin and other non-steroidal anti-inflammatory drugs reduce the risk of cancer due to their anti-proliferative and apoptotic effects, which are the important mechanisms for their anti-tumor activity. Here, the effect of aspirin on human cholangiocarcinoma cells (KKU-214) and the underlying mechanisms of its action were explored. Cell proliferation was measured by sulforhodamine B (SRB) assay, while cell cycle distribution and apoptosis were determined by flow cytometry. Western blotting was used to explore protein expression underlying molecular mechanisms of anti-cancer treatment of aspirin. Aspirin reduced cell proliferation in a dose- and time-dependent manner, and altered the cell cycle phase distribution of KKU-214 cells by increasing the proportion of cells in the G0/G1 phase and reducing the proportion in the S and G2/M phases. Consistent with its effect on the cell cycle, aspirin also reduced the expression of cyclin D1 and cyclin‑dependent kinase 4 (Cdk-4), which are important for G0/G1 cell cycle progression. Treatment with aspirin led to increased induction of apoptosis in a dose-dependent manner. Further analysis of the mechanism underlying the effect of this drug showed that aspirin induced the expression of the tumor-suppressor protein p53 while inhibiting the anti-apoptotic protein B‑cell lymphoma-2 (Bcl-2). Correspondingly, the activation of caspase-9 and -3 was also increased. These findings suggest that aspirin causes cell cycle arrest and apoptosis, both of which could contribute to its anti-proliferative effect. Creative Commons Attribution License

  12. Exhaled Eicosanoids following Bronchial Aspirin Challenge in Asthma Patients with and without Aspirin Hypersensitivity: The Pilot Study

    Science.gov (United States)

    Mastalerz, L.; Sanak, M.; Kumik, J.; Gawlewicz-Mroczka, A.; Celejewska-Wójcik, N.; Ćmiel, A.; Szczeklik, A.

    2012-01-01

    Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC) levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS) and high-performance liquid chromatography/mass spectrometry (HPLC-MS2) or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs). At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE) which were higher in aspirin-induced asthma (AIA) than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs) remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinyl-leukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity. PMID:22291720

  13. Exhaled Eicosanoids following Bronchial Aspirin Challenge in Asthma Patients with and without Aspirin Hypersensitivity: The Pilot Study

    Directory of Open Access Journals (Sweden)

    L. Mastalerz

    2012-01-01

    Full Text Available Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS and high-performance liquid chromatography/mass spectrometry (HPLC-MS2 or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs. At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE which were higher in aspirin-induced asthma (AIA than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinyl-leukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity.

  14. High dose aspirin and left ventricular remodeling after myocardial infarction: aspirin and myocardial infarction.

    Science.gov (United States)

    Adamek, Anna; Hu, Kai; Bayer, Barbara; Wagner, Helga; Ertl, Georg; Bauersachs, Johann; Frantz, Stefan

    2007-07-01

    Proinflammatory proteins like inflammatory cytokines are implicated in myocardial depression and left ventricular remodeling after myocardial infarction. High-dose aspirin inhibits cytokine activation. Therefore, we tested the influence of high-dose aspirin treatment on left ventricular remodeling in mice after myocardial infarction. Mice were treated for 4 weeks with placebo or aspirin (120 mg/kg per day) by Alzet mini-osmotic pumps after ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography was performed at days 1, 7, and 28. Over the 4 weeks, mortality was not different between the groups (placebo 30.8%, aspirin 30.8%). On echocardiography, animals after myocardial infarction exhibited left ventricular dilatation (week 4, end-systolic area, placebo sham 8.9 +/- 1.7 vs. placebo MI 15.9 +/- 2.5 mm(2)), which was not changed by aspirin treatment (week 4, end-systolic area, aspirin MI 14.5 +/- 1.3 mm(2), p= ns vs. placebo MI). The expression of the proinflammatory cytokines TNF and IL-1beta were markedly upregulated in mice with myocardial infarction on placebo. Cytokine expression was significantly reduced by aspirin treatment while collagen deposition was not influenced. Continuous aspirin treatment (120 mg/kg/d) reduces the expression of proinflammatory cytokines after myocardial infarction, but does not affect post-infarct cardiac remodeling and cardiac function.

  15. Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study

    Science.gov (United States)

    Lee, Meng; Wu, Yi-Ling; Saver, Jeffrey L; Lee, Hsuei-Chen; Lee, Jiann-Der; Chang, Ku-Chou; Wu, Chih-Ying; Lee, Tsong-Hai; Wang, Hui-Hsuan; Rao, Neal M; Ovbiagele, Bruce

    2014-01-01

    Objective There is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke. Design Retrospective. Setting We conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database. Participants Among 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010. Primary and secondary outcome measures The primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke. Results Compared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, paspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation. PMID:25468508

  16. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.

    Science.gov (United States)

    Halkes, P H A; van Gijn, J; Kappelle, L J; Koudstaal, P J; Algra, A

    2006-05-20

    Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty. We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070). Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache. The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin.

  17. Relation of aspirin failure to clinical outcome and to platelet response to aspirin in patients with acute myocardial infarction.

    Science.gov (United States)

    Beigel, Roy; Hod, Hanoch; Fefer, Paul; Asher, Elad; Novikov, Ilia; Shenkman, Boris; Savion, Naphtaly; Varon, David; Matetzky, Shlomi

    2011-02-01

    Aspirin failure, defined as occurrence of an acute coronary syndrome despite aspirin use, has been associated with a higher cardiovascular risk profile and worse prognosis. Whether this phenomenon is a manifestation of patient characteristics or failure of adequate platelet inhibition by aspirin has never been studied. We evaluated 174 consecutive patients with acute myocardial infarction. Of them, 118 (68%) were aspirin naive and 56 (32%) were regarded as having aspirin failure. Platelet function was analyzed after ≥72 hours of aspirin therapy in all patients. Platelet reactivity was studied by light-transmitted aggregometry and under flow conditions. Six-month incidence of major adverse coronary events (death, recurrent acute coronary syndrome, and/or stroke) was determined. Those with aspirin failure were older (p = 0.002), more hypertensive (p aspirin-failure group (14.3% vs 2.5% p aspirin failure had lower arachidonic acid-induced platelet aggregation (32 ± 24 vs 45 ± 30, p = 0.003) after aspirin therapy compared to their aspirin-naive counterparts. However, this was not significant after adjusting for differences in baseline characteristics (p = 0.82). Similarly, there were no significant differences in adenosine diphosphate-induced platelet aggregation and platelet deposition under flow conditions. In conclusion, our results suggest that aspirin failure is merely a marker of higher-risk patient profiles and not a manifestation of inadequate platelet response to aspirin therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Comparative effect of clopidogrel plus aspirin and aspirin monotherapy on hematological parameters using propensity score matching

    Directory of Open Access Journals (Sweden)

    Hayasaka M

    2013-02-01

    Full Text Available Masatoshi Hayasaka,1 Yasuo Takahashi,2 Yayoi Nishida,2 Yoshikazu Yoshida,1 Shinji Hidaka,3 Satoshi Asai41Department of Pharmacy, Nihon University Itabashi Hospital, Tokyo, 2Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, 3Laboratory of Pharmaceutical Regulatory Science, Department of Pharmacy, School of Pharmacy, Nihon University, Chiba, 4Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, JapanBackground: Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Dual antiplatelet therapy with clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in real-world clinical settings. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters.Methods: We used data from the Nihon University School of Medicine Clinical Data Warehouse obtained between November 2004 and May 2011 to identify cohorts of new users (n = 130 of clopidogrel (75 mg/day plus aspirin (100 mg/day and a propensity score matched sample of new users (n = 130 of aspirin alone (100 mg/day. We used a multivariate regression model to compare serum levels of creatinine, aspartate aminotransferase, and alanine aminotransferase, as well as hematological parameters including hemoglobin level, hematocrit, and white blood cell, red blood cell, and platelet counts up to 2 months after the start of administration of the study drugs.Results: There were no significant differences for any characteristics and baseline laboratory parameters between users of clopidogrel plus aspirin and users of aspirin alone. Reductions in white blood cell and red blood cell counts, hemoglobin levels, and

  19. Aspirin and Reye's syndrome — do parents know?

    OpenAIRE

    Hall, R. W.

    1987-01-01

    Amid growing concern over the association between aspirin and Reye's syndrome, the Aspirin Foundation has recently mounted a publicity campaign advising against the use of aspirin in children. Of 50 parents questioned at a children's ward of a district general hospital, 46 (92%) had heard of the publicity, 38 via the television. The number of parents who would give aspirin to their child had dropped significantly from 45 before the campaign to five after it (P

  20. Aspirin and Reye's syndrome — do parents know?

    Science.gov (United States)

    Hall, R.W.

    1987-01-01

    Amid growing concern over the association between aspirin and Reye's syndrome, the Aspirin Foundation has recently mounted a publicity campaign advising against the use of aspirin in children. Of 50 parents questioned at a children's ward of a district general hospital, 46 (92%) had heard of the publicity, 38 via the television. The number of parents who would give aspirin to their child had dropped significantly from 45 before the campaign to five after it (PReye's syndrome as the reason. PMID:3505289

  1. The mechanism of action of aspirin.

    Science.gov (United States)

    Vane, J R; Botting, R M

    2003-06-15

    The therapy of rheumatism began thousands of years ago with the use of decoctions or extracts of herbs or plants such as willow bark or leaves, most of which turned out to contain salicylates. Following the advent of synthetic salicylate, Felix Hoffman, working at the Bayer company in Germany, made the acetylated form of salicylic acid in 1897. This drug was named "Aspirin" and became the most widely used medicine of all time. In 1971, Vane discovered the mechanism by which aspirin exerts its anti-inflammatory, analgesic and antipyretic actions. He proved that aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) inhibit the activity of the enzyme now called cyclooxygenase (COX) which leads to the formation of prostaglandins (PGs) that cause inflammation, swelling, pain and fever. However, by inhibiting this key enzyme in PG synthesis, the aspirin-like drugs also prevented the production of physiologically important PGs which protect the stomach mucosa from damage by hydrochloric acid, maintain kidney function and aggregate platelets when required. This conclusion provided a unifying explanation for the therapeutic actions and shared side effects of the aspirin-like drugs. Twenty years later, with the discovery of a second COX gene, it became clear that there are two isoforms of the COX enzyme. The constitutive isoform, COX-1, supports the beneficial homeostatic functions, whereas the inducible isoform, COX-2, becomes upregulated by inflammatory mediators and its products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis.

  2. Molecular targets of aspirin and cancer prevention

    Science.gov (United States)

    Alfonso, L; Ai, G; Spitale, R C; Bhat, G J

    2014-01-01

    Salicylates from plant sources have been used for centuries by different cultures to treat a variety of ailments such as inflammation, fever and pain. A chemical derivative of salicylic acid, aspirin, was synthesised and mass produced by the end of the 19th century and is one of the most widely used drugs in the world. Its cardioprotective properties are well established; however, recent evidence shows that it can also act as a chemopreventive agent. Its antithrombotic and anti-inflammatory actions occur through the inhibition of cyclooxygenases. The precise mechanisms leading to its anticancer effects are not clearly established, although multiple mechanisms affecting enzyme activity, transcription factors, cellular signalling and mitochondrial functions have been proposed. This review presents a brief account of the major COX-dependent and independent pathways described in connection with aspirin's anticancer effects. Aspirin's unique ability to acetylate biomolecules besides COX has not been thoroughly investigated nor have all the targets of its primary metabolite, salicylic acid been identified. Recent reports on the ability of aspirin to acetylate multiple cellular proteins warrant a comprehensive study to investigate the role of this posttranslational modification in its anticancer effects. In this review, we also raise the intriguing possibility that aspirin may interact and acetylate cellular molecules such as RNA, and metabolites such as CoA, leading to a change in their function. Research in this area will provide a greater understanding of the mechanisms of action of this drug. PMID:24874482

  3. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

  4. A critical appraisal of the phenomenon of aspirin resistance

    DEFF Research Database (Denmark)

    Svenstrup Poulsen, Tina; Risom Kristensen, Søren; Atar, Dan

    2005-01-01

    Aspirin is the mainstay antiplatelet treatment in patients with high risk of cardiovascular atherothrombotic events, and its beneficial effect is documented in several clinical trials. Nevertheless, the effectiveness of aspirin has been questioned by the emergence of the concept of 'aspirin...

  5. PIXE analysis of trace metals in aspirin-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Van Rinsvelt, H.A.; Sater, R.; Hurd, R.W.; Andres, J.M.

    1985-01-01

    Aspirin is known to complex metals, yet its effect on trace metals of the body remains poorly characterized. Chronic aspirin treatment of rats for one week produced significant alterations of serum iron, zinc, and selenium, and liver selenium and copper. Implications of metal complexation on the mechanism of action of aspirin and the association with Reye's Syndrome are discussed.

  6. PIXE analysis of trace metals in aspirin-treated rats

    Science.gov (United States)

    Van Rinsvelt, H. A.; Sater, R.; Hurd, R. W.; Andres, J. M.

    1985-05-01

    Aspirin is known to complex metals, yet its effect on trace metals of the body remains poorly characterized. Chronic aspirin treatment of rats for one week produced significant alterations of serum iron, zinc, and selenium, and liver selenium and copper. Implications of metal complexation on the mechanism of action of aspirin and the association with Reye's Syndrome are discussed.

  7. Outcomes after complete endoscopic sinus surgery and aspirin desensitization in aspirin-exacerbated respiratory disease.

    Science.gov (United States)

    Adappa, Nithin D; Ranasinghe, Viran J; Trope, Michal; Brooks, Steven G; Glicksman, Jordan T; Parasher, Arjun K; Palmer, James N; Bosso, John V

    2018-01-01

    In this study we assessed patient outcomes after complete endoscopic sinus surgery (ESS) and aspirin desensitization for patients with aspirin-exacerbated respiratory disease (AERD). A retrospective chart review was conducted for patients with aspirin challenge-proven AERD who underwent complete ESS followed by aspirin desensitization. Outcomes assessed included need for revision surgery and quality-of-life measures using the 22-item Sino-Nasal Outcomes Test (SNOT-22). Data were collected preoperatively, postoperatively prior to desensitization, and then at intervals post-desensitization through 30 months after aspirin desensitization. A longitudinal linear mixed-effects model was used for data analysis. Thirty-four patients met the inclusion criteria for this study. Thirty-two patients successfully completed aspirin desensitization and were subsequently followed for 30 months after desensitization. Two patients were unable to complete desensitization. Five patients discontinued aspirin maintenance therapy due to gastrointestinal and respiratory side effects. Within the follow-up period, there were only 3 (9.4%) revision sinus surgeries. Notably, 1 of these revision cases occurred in a patient who had discontinued aspirin maintenance therapy. After surgical treatment and prior to desensitization patients had significant reductions in SNOT-22 scores. Our results demonstrate that total SNOT-22 scores remained statistically unchanged from immediate post-desensitization throughout the 30-month follow-up period. Complete sinus surgery followed by timely aspirin desensitization and maintenance therapy is an effective combination in the long-term management of sinus disease in patients with AERD. © 2017 ARS-AAOA, LLC.

  8. Mechanisms of aspirin-sensitive asthma

    Directory of Open Access Journals (Sweden)

    Sun Ying

    2004-01-01

    Full Text Available It is now widely accepted that aspirin, along with other non-steroidal anti-inflammatory drugs (NSAIDs, may precipitate asthma attacks in a minority of susceptible individuals. The syndrome is part of a mucosal inflammatory disease that typically affects the nasal, as well as the bronchial, mucosa and sometimes the gut and skin also. Although the mucosal cellular infiltrate in aspirin-sensitive asthma and rhinitis resembles that of asthma and rhinitis in general, there is evidence of increased expression of asthma-relevant cytokines, such as interleukin-5 and granulocyte–macrophage colony stimulating factor, and a more intense infiltrate of mast cells and eosinophils. One key feature of aspirin-sensitive asthma is thought to be the overproduction of cysteinyl leukotrienes, principally by these local mast cells and eosinophils, but whether this represents a fundamental abnormality or is simply a consequence of greater numbers and activation of inflammatory cells is unclear. Genetic polymorphisms of the leukotriene C4 synthase gene, which result in elevated expression of this enzyme, may also play a role. In addition, overexpression of cysteinyl leukotriene receptors, particularly CysLT1, may contribute to an enhanced response of local inflammatory and structural cells to cysteinyl leukotrienes. Aspirin challenge in these patients is accompanied by acute further elevation of the already elevated baseline cysteinyl leukotriene synthesis, a phenomenon that is most closely related to the ability of aspirin and related NSAIDs to inhibit the cyclooxygenase enzyme COX-1. The reason for this is unknown, although it has been suggested that the COX-1 product prostaglandin E2 (PGE2 serves as a ‘brake’ to leukotriene synthesis and that somehow this mechanism is deficient in aspirin-sensitive asthmatics. A better understanding of the pathogenesis of aspirin-sensitive asthma will undoubtedly lead to better approaches to treatment. Aside from the use of

  9. Aspirin and colorectal cancer: the promise of precision chemoprevention.

    Science.gov (United States)

    Drew, David A; Cao, Yin; Chan, Andrew T

    2016-03-01

    Aspirin (acetylsalicylic acid) has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis. Several decades of research have provided considerable evidence demonstrating its potential for the prevention of cancer, particularly colorectal cancer. Broader clinical recommendations for aspirin-based chemoprevention strategies have recently been established; however, given the known hazards of long-term aspirin use, larger-scale adoption of an aspirin chemoprevention strategy is likely to require improved identification of individuals for whom the protective benefits outweigh the harms. Such a precision medicine approach may emerge through further clarification of aspirin's mechanism of action.

  10. The role of aspirin-triggered lipoxins in the mechanism of action of aspirin.

    Science.gov (United States)

    Gilroy, Derek W

    2005-01-01

    Few drugs have treated so many diseases, provided us with so much understanding of their pathogenesis, and tested our scientific creativity over the last 100 years as much as aspirin. Originally, the beneficial effects of aspirin were shown to stem from its inhibition of cyclooxygenase (COX 2)-derived prostanoids, fatty acid metabolites that modulate host defense and regulate the cardiovascular system. However, the inhibition of COX 2 enzyme activity and prostaglandin synthesis has never fully explained aspirin's repertoire of anti-inflammatory effects, leaving many questions pertaining to its true mechanism of action unanswered. Here, data from a series of comparatively recent experiments exploring aspirin's unique ability to acetylate the active site of inducible COX 2 and generate a family of lipid mediators called the epi-Lipoxins will be discussed in light of their ability to exert profound modulatory effects on the innate and adaptive immune systems.

  11. Oral aspirin for treating venous leg ulcers.

    Science.gov (United States)

    de Oliveira Carvalho, Paulo Eduardo; Magolbo, Natiara G; De Aquino, Rebeca F; Weller, Carolina D

    2016-02-18

    Venous leg ulcers (VLUs) or varicose ulcers are the final stage of chronic venous insufficiency (CVI), and are the most common type of leg ulcer. The development of VLUs on ankles and lower legs can occur spontaneously or after minor trauma. The ulcers are often painful and exudative, healing is often protracted and recurrence is common. This cycle of healing and recurrence has a considerable impact on the health and quality of life of individuals, and healthcare and socioeconomic costs. VLUs are a common and costly problem worldwide; prevalence is estimated to be between 1.65% to 1.74% in the western world and is more common in adults aged 65 years and older. The main treatment for a VLU is a firm compression bandage. Compression assists by reducing venous hypertension, enhancing venous return and reducing peripheral oedema. However, studies show that it only has moderate effects on healing, with up to 50% of VLUs unhealed after two years of compression. Non-adherence may be the principal cause of these poor results, but presence of inflammation in people with CVI may be another factor, so a treatment that suppresses inflammation (healing ulcers more quickly) and reduces the frequency of ulcer recurrence (thereby prolonging time between recurrent episodes) would be an invaluable intervention to complement compression treatments. Oral aspirin may have a significant impact on VLU clinical practice worldwide. Evidence for the effectiveness of aspirin on ulcer healing and recurrence in high quality RCTs is currently lacking. To assess the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. In May 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. Additional searches were made in trial registers and reference lists of relevant publications for

  12. A General Chemistry Laboratory Theme: Spectroscopic Analysis of Aspirin

    Science.gov (United States)

    Byrd, Houston; O'Donnell, Stephen E.

    2003-02-01

    In this paper, we describe the introduction of spectroscopy into the general chemistry laboratory using a series of experiments based on a common substance, aspirin. In the first lab the students synthesize and recrystallize aspirin and take melting points of their product, an aspirin standard, and salicylic acid. The students perform the remaining experiments on a rotating basis where the following four labs run simultaneously: structural characterization of the synthesized aspirin by IR and NMR; analysis of synthesized aspirin and commercial products by UV vis spectroscopy; analysis of synthesized aspirin and commercial products by HPLC; and analysis of calcium in commercial buffered aspirin tablets by AAS. In each of the analysis experiments, students collect, graph, and analyze their data using a spreadsheet. We have found that this series of labs has been very beneficial to our students. From the course evaluations, students indicate that they are beginning to understand how chemistry is applied outside of the classroom.

  13. Rivaroxaban with or without aspirin in stable cardiovascular disease

    DEFF Research Database (Denmark)

    Eikelboom, John W; Connolly, Stuart J; Bosch, Jackie

    2017-01-01

    BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive...... rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after...... a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P

  14. Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study.

    Science.gov (United States)

    Lee, Meng; Wu, Yi-Ling; Saver, Jeffrey L; Lee, Hsuei-Chen; Lee, Jiann-Der; Chang, Ku-Chou; Wu, Chih-Ying; Lee, Tsong-Hai; Wang, Hui-Hsuan; Rao, Neal M; Ovbiagele, Bruce

    2014-12-02

    There is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke. Retrospective. We conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database. Among 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis. Patients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010. The primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke. Compared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, paspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Reverse effect of aspirin: is the prothrombotic effect after aspirin discontinuation mediated by cyclooxygenase 2 inhibition?

    Science.gov (United States)

    Doutremepuich, Christian; Aguejouf, Omar; Eizayaga, Francisco X; Desplat, Vanessa

    2007-01-01

    While aspirin is the drug most often used to prevent cardiovascular complications, its discontinuation induces an increased risk of acute coronary syndrome and ischemic stroke in some patients. We hypothesized that infinitesimal concentrations of aspirin could persist in plasma after its discontinuation, thereby inducing a prothrombotic effect that could be due to a modification in the mechanism of action of aspirin via the cyclooxygenase 1 (COX-1) and COX-2 pathways. We studied the effects of ultra-low-dose aspirin (ULDA) as well as those of sc-560 and ns-398, specific COX-1 and COX-2 inhibitors, on induced hemorrhagic time and in a model of laser-induced thrombosis in rats. In the laser-induced thrombosis model, ULDA treatment increased the number of emboli and the duration of embolization, thereby confirming its prothrombotic effect described in previous publications. This effect was also observed in rats pretreated with sc-560 but not in those pretreated with ns-398. We demonstrated that ULDA induced a prothrombotic effect in the rats studied. This strongly suggests that a very small amount of aspirin could remain in the patient's blood after aspirin therapy, leading to cardiovascular complications. This effect may be mediated by the COX-2 pathway. Copyright 2008 S. Karger AG, Basel.

  16. Inappropriate combination of warfarin and aspirin.

    Science.gov (United States)

    Turan, Burak; Demir, Hakan; Mutlu, Ayhan; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

    2016-03-01

    A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (paspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (paspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV.

  17. [Cyclooxigenase-1 gene polymorphism and aspirin resistance].

    Science.gov (United States)

    Bondar', T N; Kravchenko, N A

    2012-01-01

    The literature data concerning structure of cyclo-oxigenase-1--the key enzyme in prostaglandin biosynthesis and the main target of anti-platelet therapy with the use of acetylsalicilic acid are presented in the review. The data on cyclooxigenase-1 gene polymorphism, distribution of the revealed variants in various populations and their possible correlation with biochemical and functional aspirin resistance are presented.

  18. Aspirin augments hyaluronidase induced adhesion inhibition ...

    African Journals Online (AJOL)

    Postoperative adhesions occur after virtually all abdomino-pelvic surgery and are the leading cause of intestinal obstruction and other gynaecologic problems. We used an animal model to test the efficacy of combined administration of aspirin and hyaluronidase on adhesion formation. Adhesions were induced using ...

  19. Van der Waals Interactions in Aspirin

    Science.gov (United States)

    Reilly, Anthony; Tkatchenko, Alexandre

    2015-03-01

    The ability of molecules to yield multiple solid forms, or polymorphs, has significance for diverse applications ranging from drug design and food chemistry to nonlinear optics and hydrogen storage. In particular, aspirin has been used and studied for over a century, but has only recently been shown to have an additional polymorphic form, known as form II. Since the two observed solid forms of aspirin are degenerate in terms of lattice energy, kinetic effects have been suggested to determine the metastability of the less abundant form II. Here, first-principles calculations provide an alternative explanation based on free-energy differences at room temperature. The explicit consideration of many-body van der Waals interactions in the free energy demonstrates that the stability of the most abundant form of aspirin is due to a subtle coupling between collective electronic fluctuations and quantized lattice vibrations. In addition, a systematic analysis of the elastic properties of the two forms of aspirin rules out mechanical instability of form II as making it metastable.

  20. Aspirin treatment reduces platelet resistance to deformation.

    Science.gov (United States)

    Burris, S M; Smith, C M; Rao, G H; White, J G

    1987-01-01

    The present investigation has evaluated the influence of aspirin, its constituents, and other nonsteroidal anti-inflammatory agents on the resistance of human platelets to aspiration into micropipettes. Aspirin increased the length of platelet extensions into the micropipette over the entire negative tension range of 0.04 to 0.40 dynes/cm after exposure to the drug in vitro or after ingestion of the agent. Other cyclooxygenase inhibitors, ibuprofen and indomethacin, did not increase platelet deformability. The influence of aspirin was mimicked to some degree by high concentrations of salicylic acid, but acetylation of platelets with acetic anhydride had little influence on platelet deformability. Incubation of platelets with both salicylic acid and acetic anhydride had no more effect than salicylic acid alone. Benzoic acid, chemically similar to salicylic acid, had a minimal effect. The studies demonstrate that aspirin makes platelets more deformable, while components of the drug or other nonsteroidal antiinflammatory agents and cyclooxygenase inhibitors do not have the same influence on resistance to deformation.

  1. Aspirin in pregnancy : clinical and biochemical studies

    NARCIS (Netherlands)

    H.A. Bremer (Henk)

    1994-01-01

    textabstractAspirin, acetylsalicylic acid, is the most frequently consumed drug in pregnancy,47 mostly taken without a prescription because of headache or a minor ailment. 226,277 Numerous preparations containing acetylsalicylic acid are freely available over the counter under a variety of

  2. Platelet hyperfunction is decreased by additional aspirin loading in patients presenting with myocardial infarction on daily aspirin therapy.

    Science.gov (United States)

    Fuchs, Ingrid; Spiel, Alexander O; Frossard, Martin; Derhaschnig, Ulla; Riedmüller, Eva; Jilma, Bernd

    2010-06-01

    Currently 162-325 mg aspirin is recommended for the treatment of acute coronary syndrome. We tested the effect of an additional loading dose of 250 mg aspirin at the onset of acute coronary syndrome in patients who were already on chronic therapy with 100 mg aspirin. This was a prospective trial in patients presenting with symptoms suggestive of acute coronary syndrome that included a randomized, double-blind, placebo-controlled trial subgroup. An emergency department in a tertiary care center. Consecutive patients with symptoms suggestive of acute coronary syndrome were enrolled, including a cohort already on chronic aspirin therapy. Patients received an intravenous infusion of 250 mg aspirin. Platelet function was measured with a platelet function analyzer in 234 patients before and after aspirin infusion. Aspirin infusion prolonged collagen epinephrine closure times in almost all patients. Aspirin infusion further lowered thromboxane B(2) levels in patients with acute coronary syndrome who were on chronic aspirin therapy before admission. Concomitantly, collagen epinephrine closure times increased by 22% from 223 secs (95% confidence interval, 192-255 secs) before to 273 secs (95% confidence interval, 252-294 secs) after aspirin infusion (p myocardial infarction on daily aspirin therapy (53%) displayed platelet hyperfunction (collagen epinephrine closure times aspirin infusion further decreased platelet function in these patients with ST-elevation myocardial infarction (30% prolongation of collagen epinephrine closure times; p myocardial infarction still displayed platelet hyperfunction (p = .02). Aspirin loading in the emergency room further reduced thromboxane B(2) levels and further inhibited platelet function in many patients with acute coronary syndrome already on 100 mg aspirin.

  3. A Review on the Relationship between Aspirin and Bone Health

    Directory of Open Access Journals (Sweden)

    Kok-Yong Chin

    2017-01-01

    Full Text Available Aspirin is a cyclooxygenase inhibitor commonly used in primary prevention of cardiovascular diseases and cancers. Its users are elderly population susceptible to osteoporosis. It also inhibits the synthesis of prostaglandin E2 essential in bone remodeling. This prompts the question whether it can influence bone health among users. This review aimed to summarize the current literature on the use of aspirin on bone health. A literature search on experimental and clinical evidence on the effects of aspirin on bone health was performed using major scientific databases. In vitro studies showed that aspirin could enhance the survival of bone marrow mesenchymal stem cells, the progenitors of osteoblasts, and stimulate the differentiation of preosteoblasts. Aspirin also inhibited the nuclear factor kappa-B (NFκB pathway and decreased the expression of receptor activator of NFκB ligand, thus suppressing the formation of osteoclast. Aspirin could prevent bone loss in animal models of osteoporosis. Despite a positive effect on bone mineral density, the limited human epidemiological studies revealed that aspirin could not reduce fracture risk. A study even suggested that the use of aspirin increased fracture risk. As a conclusion, aspirin may increase bone mineral density but its effect on fracture prevention is inconclusive. More data are needed to determine the effects of aspirin and bone health in human.

  4. Duration of increased bleeding tendency after cessation of aspirin therapy.

    LENUS (Irish Health Repository)

    Cahill, Ronan A

    2012-02-03

    BACKGROUND: Aspirin has a significant effect on hemostasis, so it is often recommended that patients taking aspirin discontinue treatment before elective surgery. While off aspirin, these patients may be at risk of thrombosis. The optimum period of time that aspirin should be withheld is controversial. The aim of this study was to establish the duration of the antihemostatic effect of prolonged aspirin therapy. STUDY DESIGN: In a prospective study, 51 healthy volunteers were randomly assigned into 3 groups, each receiving an identical tablet for 14 days. One group received a placebo tablet; individuals in the other two groups received either 75 mg or 300 mg of aspirin once a day. Template bleeding times and specific platelet function testing (using the PFA-100; Dade Behring) were carried out on subjects before therapy and again after its completion until they returned to baseline. RESULTS: Thirty-eight volunteers complied sufficiently with the protocol to provide useful results. All bleeding times normalized within 96 hours and all platelet function tests within 144 hours after stopping aspirin. There was no demonstrable hemostatic defect in any volunteer persisting by or beyond the sixth day after treatment cessation. There was no apparent difference in duration of effect between those taking either 75 mg or 300 mg of aspirin. CONCLUSIONS: This study uses sensitive measures of platelet function to demonstrate the duration of increased bleeding tendency after withdrawal of aspirin therapy. It supports discontinuation of aspirin therapy 5 days before elective surgery (with the operation being performed on the sixth day).

  5. The role of aspirin in childhood tuberculous meningitis.

    Science.gov (United States)

    Schoeman, Johan F; Janse van Rensburg, Anita; Laubscher, Jacoba A; Springer, Priscilla

    2011-08-01

    Arterial stroke is the main cause of poor outcome in childhood tuberculous meningitis. Aspirin has an antithrombotic action at low dose and anti-ischemic and anti-inflammatory properties, which are dose-related. The aim of the study was to explore the possible benefits of aspirin in children with tuberculous meningitis. A total of 146 consecutive children with a diagnosis of probable tuberculous meningitis were studied. Patients were randomized into 3 groups: (1) placebo group, (2) low-dose aspirin group, and (3) high-dose aspirin group. Twenty-nine additional patients who received aspirin before admission were excluded from the randomized study, but continued on low-dose aspirin. Aspirin, irrespective of dose, did not show any significant benefit regarding morbidity (hemiparesis and developmental outcome) and mortality. Aspirin was well tolerated, but 1 death was probably related to aspirin. The fact that the outcome of the high-dose aspirin group compared favorably with the other treatment groups despite younger age and more severe neurological involvement at baseline needs further investigation.

  6. An alkyne-aspirin chemical reporter for the detection of aspirin-dependent protein modification in living cells.

    Science.gov (United States)

    Bateman, Leslie A; Zaro, Balyn W; Miller, Stephanie M; Pratt, Matthew R

    2013-10-02

    Aspirin (acetylsalicylic acid) is widely used for the acute treatment of inflammation and the management of cardiovascular disease. More recently, it has also been shown to reduce the risk of a variety of cancers. The anti-inflammatory properties of aspirin in pain-relief, cardio-protection, and chemoprevention are well-known to result from the covalent inhibition of cyclooxygenase enzymes through nonenzymatic acetylation of key serine residues. However, any additional molecular mechanisms that may contribute to the beneficial effects of aspirin remain poorly defined. Interestingly, studies over the past 50 years using radiolabeled aspirin demonstrated that other proteins are acetylated by aspirin and enrichment with antiacetyl-lysine antibodies identified 33 potential targets of aspirin-dependent acetylation. Herein we describe the development of an alkyne-modified aspirin analogue (AspAlk) as a chemical reporters of aspirin-dependent acetylation in living cells. When combined with the Cu(I)-catalyzed [3 + 2] azide-alkyne cycloaddition, this chemical reporter allowed for the robust in-gel fluorescent detection of acetylation and the subsequent enrichment and identification of 120 proteins, 112 of which have not been previously reported to be acetylated by aspirin in cellular or in vivo contexts. Finally, AspAlk was shown to modify the core histone proteins, implicating aspirin as a potential chemical-regulator of transcription.

  7. Aspirin overutilization for the primary prevention of cardiovascular disease

    Directory of Open Access Journals (Sweden)

    VanWormer JJ

    2014-12-01

    Full Text Available Jeffrey J VanWormer,1 Aaron W Miller,2 Shereif H Rezkalla3 1Center for Clinical Epidemiology and Population Health, 2Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI, USA; 3Department of Cardiology, Marshfield Clinic, Marshfield, WI, USA Background: Aspirin is commonly used for the primary prevention of cardiovascular disease (CVD in the US. Previous research has observed significant levels of inappropriate aspirin use for primary CVD prevention in some European populations, but the degree to which aspirin is overutilized in the US remains unknown. This study examined the association between regular aspirin use and demographic/clinical factors in a population-based sample of adults without a clinical indication for aspirin for primary prevention.Methods: A cross-sectional analysis was performed using 2010–2012 data from individuals aged 30–79 years in the Marshfield Epidemiologic Study Area (WI, USA. Regular aspirin users included those who took aspirin at least every other day.Results: There were 16,922 individuals who were not clinically indicated for aspirin therapy for primary CVD prevention. Of these, 19% were regular aspirin users. In the final adjusted model, participants who were older, male, lived in northern Wisconsin, had more frequent medical visits, and had greater body mass index had significantly higher odds of regular aspirin use (P<0.001 for all. Race/ethnicity, health insurance, smoking, blood pressure, and lipid levels had negligible influence on aspirin use. A sensitivity analysis found a significant interaction between age and number of medical visits, indicating progressively more aspirin use in older age groups who visited their provider frequently.Conclusion: There was evidence of aspirin overutilization in this US population without CVD. Older age and more frequent provider visits were the strongest predictors of inappropriate aspirin use. Obesity was the only significant

  8. State of the Art: Medical treatment of aspirin exacerbated respiratory disease (AERD).

    Science.gov (United States)

    Ta, Von; Simon, Ronald

    2015-01-01

    Aspirin exacerbated respiratory disease (AERD) is characterized as adult onset asthma, nasal polyps, chronic rhinosinusitis, and hypersensitivity to a cyclooxygenase-1 (COX-1) inhibitor, viz aspirin or nonsteroidal antiinflammatory drugs (NSAIDs). The method for diagnosing AERD is with aspirin challenge, and treatment includes aspirin desensitization followed by continued daily aspirin. Although oral challenge has been the mainstay in the United States, lysyl-aspirin has been validated as a diagnostic tool for aspirin-sensitive asthma and will be discussed further in this article. The challenges with aspirin therapy surrounding endoscopy and perioperative aspirin therapy will be discussed. Additionally, daily aspirin therapy is not for everyone. Aspirin is relatively contraindicated in those with a history of gastrointestinal bleed and an absolute contraindication in pregnancy. Aspirin desensitization and subsequent treatment has been shown to be highly effective for AERD.

  9. Comparison of increased aspirin dose versus combined aspirin plus clopidogrel therapy in patients with diabetes mellitus and coronary heart disease and impaired antiplatelet response to low-dose aspirin.

    Science.gov (United States)

    Duzenli, Mehmet Akif; Ozdemir, Kurtulus; Aygul, Nazif; Soylu, Ahmet; Tokac, Mehmet

    2008-08-15

    The effects of therapy with aspirin 300 mg/day and with combined aspirin 100 mg/day plus clopidogrel 75 mg/day on platelet function were compared in patients with diabetes mellitus and coronary artery disease and impaired antiplatelet responses to aspirin 100 mg/day. The study population consisted of 151 outpatients with type II diabetes mellitus and coronary artery disease who were taking aspirin 100 mg/day. Of the 151 patients, a subgroup of subjects with impaired aspirin response were selected on the basis of the results of platelet aggregometry. Nonresponsiveness to aspirin was defined as mean aggregation > or =69% with 3 micromol/L adenosine diphosphate and mean aggregation > or =70% with 2 micromol/L collagen. Aspirin semiresponders were defined as meeting 1 but not both of these criteria. Nonresponders and semiresponders were randomized equally to aspirin 300 mg/day and aspirin 100 mg/day plus clopidogrel 75 mg/day, and aggregation tests were repeated after 2 weeks. Sixty of the 151 patients with diabetes (40%) were found to respond to aspirin inadequately. Platelet aggregation induced by adenosine diphosphate and collagen decreased significantly after aspirin 300 mg/day or combined therapy. Combined treatment was found to have a stronger inhibitory effect on platelet aggregation induced by adenosine diphosphate than aspirin 300 mg/day (p = 0.002). Impaired aspirin response was resolved by increasing the aspirin dose or adding clopidogrel to aspirin (p <0.0001 for each). However, desired platelet inhibition was achieved in significantly more patients by combined treatment than by aspirin 300 mg/day (p <0.05). In conclusion, aspirin 100 mg/day does not inhibit platelet function adequately in a significant number of patients with diabetes mellitus and coronary artery disease. Increasing the aspirin dose to 300 mg/day or adding clopidogrel to aspirin can provide adequate platelet inhibition in a significant number of those patients with impaired responses to

  10. The role of aspirin in the prevention of cardiovascular disease.

    Science.gov (United States)

    Ittaman, Sunitha V; VanWormer, Jeffrey J; Rezkalla, Shereif H

    2014-12-01

    Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary prevention. In this review, we describe the seminal trials of aspirin use in the context of current guidelines, discuss factors that may influence the effectiveness of aspirin therapy for cardiovascular disease prevention, and briefly examine patterns of use. The body of evidence supports a role for aspirin in both secondary and primary prevention of cardiovascular events in selected population groups, but practice patterns may be suboptimal. As a simple and inexpensive prophylactic measure for cardiovascular disease, aspirin use should be carefully considered in all at-risk adult patients, and further measures, including patient education, are necessary to ensure its proper use. © 2013 Marshfield Clinic.

  11. The Role of Aspirin in the Prevention of Cardiovascular Disease

    Science.gov (United States)

    Ittaman, Sunitha V.; VanWormer, Jeffrey J.; Rezkalla, Shereif H.

    2014-01-01

    Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary prevention. In this review, we describe the seminal trials of aspirin use in the context of current guidelines, discuss factors that may influence the effectiveness of aspirin therapy for cardiovascular disease prevention, and briefly examine patterns of use. The body of evidence supports a role for aspirin in both secondary and primary prevention of cardiovascular events in selected population groups, but practice patterns may be suboptimal. As a simple and inexpensive prophylactic measure for cardiovascular disease, aspirin use should be carefully considered in all at-risk adult patients, and further measures, including patient education, are necessary to ensure its proper use. PMID:24573704

  12. Aspirin resistance: Prevalence and clinical outcome in Egypt

    OpenAIRE

    Ahmed Salah; Mohammed El-Desuky; Amal Rizk; Amr El-Hadidy

    2015-01-01

    Introduction: The antiplatelet drug aspirin is considered as a cornerstone in medical treatment of patients with CV or cerebrovascular diseases. Despite its use, a significant number of patients had recurrent adverse ischemic events. Inter-individual variability of platelet aggregation in response to aspirin may be an explanation for some of these events. Multiple trials have linked aspirin resistance to these adverse events. Objectives: The aim of this study was to estimate the prevalence...

  13. Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain; numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. |

  14. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.

    Science.gov (United States)

    Eikelboom, John W; Connolly, Stuart J; Bosch, Jackie; Dagenais, Gilles R; Hart, Robert G; Shestakovska, Olga; Diaz, Rafael; Alings, Marco; Lonn, Eva M; Anand, Sonia S; Widimsky, Petr; Hori, Masatsugu; Avezum, Alvaro; Piegas, Leopoldo S; Branch, Kelley R H; Probstfield, Jeffrey; Bhatt, Deepak L; Zhu, Jun; Liang, Yan; Maggioni, Aldo P; Lopez-Jaramillo, Patricio; O'Donnell, Martin; Kakkar, Ajay K; Fox, Keith A A; Parkhomenko, Alexander N; Ertl, Georg; Störk, Stefan; Keltai, Matyas; Ryden, Lars; Pogosova, Nana; Dans, Antonio L; Lanas, Fernando; Commerford, Patrick J; Torp-Pedersen, Christian; Guzik, Tomek J; Verhamme, Peter B; Vinereanu, Dragos; Kim, Jae-Hyung; Tonkin, Andrew M; Lewis, Basil S; Felix, Camilo; Yusoff, Khalid; Steg, P Gabriel; Metsarinne, Kaj P; Cook Bruns, Nancy; Misselwitz, Frank; Chen, Edmond; Leong, Darryl; Yusuf, Salim

    2017-10-05

    We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; Paspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; Paspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

  15. Improving the Gastrointestinal Tolerability of Aspirin in Older People

    OpenAIRE

    Newton, Julia L.

    2006-01-01

    Interventions to reduce mortality and disability in older people are vital. Aspirin is cheap and effective and known to prevent cardiovascular and cerebrovascular disease, many cancers, and Alzheimer dementia. The widespread use of aspirin in older people is limited by its gastrointestinal side effects. Understanding age-related changes in gastrointestinal physiology that could put older people at risk of the side effects of aspirin may direct strategies to improve tolerance and hence lead to...

  16. Aspirin and Other COX-1 inhibitors.

    Science.gov (United States)

    Patrono, Carlo; Rocca, Bianca

    2012-01-01

    Currently available antiplatelet drugs interfere with the process of platelet activation and aggregation by selectively blocking key enzymes involved in the synthesis of platelet agonists, or membrane receptors mediating activation signals. Pharmacological interference with critical molecular pathways of platelet activation and aggregation may reduce the risk of atherothrombotic complications through mechanisms that are also responsible for an increased risk of bleeding. Acetylsalicylic acid (aspirin) represents a prototypic antiplatelet agent. The aim of this chapter is to integrate our current understanding of the molecular mechanism of action of aspirin with the results of clinical trials and epidemiological studies assessing its efficacy and safety. Moreover, the antiplatelet properties of reversible inhibitors of the same drug target will also be reviewed.

  17. Aspirin: a history, a love story.

    Science.gov (United States)

    Wick, Jeannette Y

    2012-05-01

    Most pharmacists know that aspirin's origins lie with willow bark, but they may be unaware of its role in the development of the pharmaceutical industry. Evolving from salacin (the active ingredient in many plant remedies) to salicylic acid (an analgesic in its own right) to the more effective, less toxic acetylsalicylic acid, this pain reliever cornered the nonsteroidal anti-inflammatory market for more than 70 years. It helped the dye industry branch into pharmaceuticals, and is now used in multiple indications.

  18. Aspirin for primary prevention of cardiovascular disease in diabetes mellitus

    Science.gov (United States)

    Pignone, Michael; Williams, Craig D.

    2011-01-01

    Aspirin is effective for the prevention of cardiovascular events in patients with a history of vascular disease, as so-called secondary prevention. In general populations with no history of previous myocardial infarction or stroke, aspirin also seems useful for primary prevention of cardiovascular events, although the absolute benefits are smaller than those seen in patients with previous cardiovascular disease. Patients with diabetes mellitus are at an increased risk of cardiovascular events, but new trials have raised questions about the benefit of aspirin for primary prevention in patients with this disorder. This Review comprehensively examines the basic pharmacology of aspirin and provides an overview of the randomized, controlled trials of aspirin therapy that have included patients with diabetes mellitus. On the basis of currently available evidence from primary prevention trials, aspirin is estimated to reduce the relative risk of myocardial infarction and stroke by about 10% in patients with diabetes mellitus; however, aspirin also increases the risk of gastrointestinal bleeding. As such, low-dose aspirin therapy (75–162 mg) is reasonable for patients with diabetes mellitus and a 10-year risk of cardiovascular events >10%. Results from upcoming large trials will help clarify the effects of aspirin with greater precision, including whether the benefits differ between men and women. PMID:20856266

  19. Aspirin and metformin exhibit antitumor activity in murine breast cancer.

    Science.gov (United States)

    Zhao, Maoyuan; Wang, Yuyi; Du, Chi; Liu, Yanyang; Zhang, Nan; Luo, Feng

    2018-03-01

    Studies have shown that aspirin and metformin play important roles in chemoprevention and repression of breast cancers, even though the exact mechanism remains unclear. Aspirin is capable of stimulating apoptosis through prostaglandin-dependent or prostaglandin-independent pathways. Metformin inhibits cell growth by enhancing the tumor suppressive function of transforming growth factor (TGF-β). In the present study, we report a new link between aspirin, metformin, TGF-β1 and murine breast cancer inhibition. Specifically, we showed that aspirin and metformin enhanced 4T1 cell apoptosis by inducing secretion of TGF-β1, whereas estradiol weakened the effect.

  20. NO-aspirin: mechanism of action and gastrointestinal safety.

    Science.gov (United States)

    Fiorucci, S; Del Soldato, P

    2003-05-01

    Nitric oxide-releasing aspirins are new chemical entities obtained by adding a nitric oxide-releasing moiety to aspirin. NCX-4016 is the prototype of this family of molecules. NCX-4016 consists of the parent molecule (aspirin) linked to a 'spacer' via an ester linkage, which is in turn connected to a nitric oxide-releasing moiety. Both aspirin and nitric oxide moieties of NCX-4016 contribute to its effectiveness, the latter occurring via both cyclic guanosyl monophosphate-dependent and -independent mechanisms. In vitro studies have shown that NCX-4016 inhibits platelet aggregation induced by aspirin-sensitive (arachidonic acid) and aspirin-insensitive (thrombin) agonist. In contrast to aspirin, NCX-4016 exerts a multilevel regulation of inflammatory target, including caspase-1 and NF-kappaB. This broad spectrum of activities translates to an increased potency of this drug in modulating cardiovascular inflammation. Human studies have shown, that while nitric oxide-aspirin maintains its anti-thrombotic activity, it spares the gastrointestinal tract. Indeed, a 7-day course of NCX-4016 results in 90% reduction of gastric damage caused by equimolar doses of aspirin. Further studies are ongoing to define whether this superior anti-inflammatory and anti-thrombotic profile translates in clinical benefits in patients with cardiovascular diseases.

  1. Protocatechualdehyde synergizes with aspirin at the platelet cyclooxygenase-1 level.

    Science.gov (United States)

    Sun, Shiqing; Hao, Haiping; Gong, Ping; Tang, Zhiyuan; Li, Feiyan; Chen, Xiaohu; Shi, Haibo; Wang, Guangji

    2011-11-01

    Polyphenol-aspirin interactions were recently identified; however, the interaction mode and underlying mechanisms remained elusive. Here, we quantitatively assessed the potential interactions among two important polyphenolic compounds, caffeic acid (CA) and protocatechualdehyde (Pro), and aspirin in the AA-induced platelet aggregation model by applying the isobologram and universal response surface approach (URSA) methods. A molecular docking approach and an originally developed platelet-associated aspirin clearance approach (PAACA) were then applied to explore the potential interaction mechanisms. Although Pro and CA themselves exhibited weak inhibitory effect on arachidonic acid (AA)-induced platelet aggregation and the production of thromboxane B₂ (TXB₂), both Pro and CA potentiated aspirin action in a synergistic manner. The most prominent synergism was found between Pro and aspirin. Pro formed a stable complex into the cyclooxygenase-1 (COX-1) channel by in silico docking and significantly promoted the platelet-associated aspirin clearance, suggesting that the Pro interaction with COX-1 was favorable to the binding of aspirin with COX-1. Taken together, our findings suggest that the capacity of Pro and potentially other structurally similar polyphenolic compounds on promoting the binding of aspirin on platelet COX-1 might be the main mechanism of their synergism with aspirin. © Georg Thieme Verlag KG Stuttgart · New York.

  2. ESPRIT: is aspirin plus dipyridamole superior to aspirin alone in TIA or minor stroke patients?

    Science.gov (United States)

    Rouhl, R P W; Lodder, J

    2008-11-01

    Transient ischemic attack (TIA) or a (minor) ischemic stroke increases the risk of a recurrent stroke or death. Antiplatelet therapy with aspirin or clopidogrel is, in the absence of a potential cardiac embolic source, common practice to lower this risk. Until recently, adjuvant dipyridamole or low intensity oral anticoagulation were not generally prescribed in secondary prevention. In this article, we will summarize and discuss the published results of the European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT). In this trial, treatments with anticoagulants, aspirin alone and the combination of aspirin plus dipyridamole were compared, in a multicenter, three-armed, randomized, open-label study in patients with TIA or minor stroke.

  3. [Rapid aspirin desensitization in patients with a history of aspirin hypersensitivity requiring coronary angioplasty. Report of four cases].

    Science.gov (United States)

    Veas P, Nicolás; Martínez, Gonzalo; Jalil M, Jorge; Martínez S, Alejandro; Castro G, Pablo

    2013-02-01

    Aspirin use is necessary after a coronary angioplasty. It should not be used in patients with a history of hypersensitivity. However, rapid desensitization protocols have been reported to allow its use in such patients. One of these protocols consists in the administration of progressive doses of aspirin, from 1 to 100 mg in a period of 5.5 hours, in a controlled environment. We report four male patients aged 45,49, 59 and 73 years with a history of aspirin hypersensitivity, who were subjected to a coronary angioplasty. In all, the rapid aspirin desensitization protocol was successfully applied, allowing the use of the drug after the intervention without problems.

  4. Aspirin content determination with control systems by image processing technology. Gazo shori gijutsu wo katsuyoshita jozai aspirin kensa sochi

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, K. (Lion Corp., Tokyo (Japan))

    1990-08-05

    An inspection apparatus for aspirin tablets utilizing image processing technology was developed. One side of a tablet consists of aspirin layer and another side consists of alkiline layer. The alkaline layer is opaque at all but the aspirin layer is translucent. Image of overall configuration of the tablet is taken in CCD camera by illumination from all surrounding sides. The area is measured by using these images. Then, when switching off the surrounding illumination and illuminating the aspirin side, only aspirin side layer shines. The area is determined by taking the image in CCD. Aspirin content is calculated by the ratio of overall images to aspirin image and the predetermined tablet weight. Tablets of different aspirin content were prepared, and the content determined by this method and the chemically determined contents were compared. High correlation was found between both contents, indicating the validity of the image processing method. When the aspirin content is out of 330 {plus minus} 10mg, the controlling mechanism works, by which unmanned operation will be possible. 8 figs.

  5. Aspirin decreases vascular endothelial growth factor release during myocardial ischemia.

    Science.gov (United States)

    Gerrah, Rabin; Fogel, Mina; Gilon, Dan

    2004-03-01

    Vascular Endothelial Growth Factor (VEGF) is an important angiogenesis factor involved in pathophysiology of cardiovascular diseases. Controlling this factor's level in the serum might have significant prognostic outcomes. Twenty-four patients undergoing coronary artery bypass grafting were prospectively categorized into two groups according to aspirin administration before surgery. Vascular Endothelial Growth Factor levels were compared and correlated and adjusted with platelets count between two groups in the serum, before and after the surgery. Serum creatine kinase (CK) levels were determined before and after the operation in parallel to other clinical data. Vascular Endothelial Growth Factor levels were significantly lower in patients of the aspirin group compared to those of the non-aspirin group; 94+/-61 vs. 241+/-118 pg/ml, p=0.0003, respectively, this-despite an absence of difference in the platelet count between the groups. These titers decreased postoperatively in both groups, 94+/-61 to 10+/-9 pg/ml, p=0.001 in aspirin group and from 241+/-118 to 84+/-54 pg/ml, p=0.001 in control group. Serum creatine kinase levels were higher in the non-aspirin group, 214+/-83 u/l compared to 70+/-32 u/l in the aspirin group. Creatine kinase levels increased significantly postoperatively in both groups; however, the aspirin group had a significantly lower creatine kinase levels compared to non-aspirin group, 107+/-51 vs. 401+/-127 u/l, respectively, p=<0.0001. A significant correlation was seen between VEGF levels and platelets count in both groups, r=0.5. Aspirin treated patients have lower Vascular Endothelial Growth Factor titer levels in the perioperative course. This difference between the aspirin and the non-aspirin group is not accounted for by the platelets count.

  6. Aspirin use and endometrial cancer risk and survival.

    Science.gov (United States)

    Takiuchi, Tsuyoshi; Blake, Erin A; Matsuo, Koji; Sood, Anil K; Brasky, Theodore M

    2018-01-01

    The role of acetylsalicylic acid (aspirin) as a chemo-preventive and adjuvant therapeutic agent for cancers is generating attention. Mounting evidence indicates that aspirin reduces the incidence and mortality of certain obesity-related cancers, particularly colorectal cancer. In endometrial cancer, previous studies examining the effect of aspirin remain inconsistent as to the reduction in the risk of endometrial cancer. While some evidence indicates protective effects in obese women, other studies have showed a potential deleterious effect of these medications on endometrial cancer outcomes. However, exposure measurement across studies has been inconsistent in recording dose, duration, and frequency of use; thus making comparisons difficult. In this article, we review the evidence for the association between endometrial cancer and obesity, the pharmacological differences between regular- and low-dose aspirin, as well as the potential anti-tumor mechanism of aspirin, supporting a possible therapeutic effect on endometrial cancer. A proposed mechanism behind decreased cancer mortality in endometrial cancer may be a result of inhibition of metastasis via platelet inactivation and possible prostaglandin E 2 suppression by aspirin. Additionally, aspirin use in particular may have a secondary benefit for obesity-related comorbidities including cardiovascular disease in women with endometrial cancer. Although aspirin-related bleeding needs to be considered as a possible adverse effect, the benefits of aspirin therapy may exceed the potential risk in women with endometrial cancer. The current evidence reviewed herein has resulted in conflicting findings regarding the potential effect on endometrial cancer outcomes, thus indicating that future studies in this area are needed to resolve the effects of aspirin on endometrial cancer survival, particularly to identify specific populations that might benefit from aspirin use. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Aspirin dose and ticagrelor benefit in PLATO: fact or fiction?

    Science.gov (United States)

    Serebruany, Victor L

    2010-01-01

    To summarize the available evidence regarding whether or not a higher aspirin maintenance dose inversely affects the ticagrelor benefit observed in the US cohort of the PLATO trial. In the recent PLATO trial, the daily aspirin dosages in the USA were split between 81 and 325 mg while the vast majority of dosing outside of the USA was 75 or 100 mg. The FDA conducted exhaustive analyses of the aspirin dosage in a framework of primary clinical efficacy. Considering the post hoc, not prespecified nature of such analyses as well as multiple confounding problems with biologic plausibility, sensitivity to reclassification of small numbers of cases regarding loading versus maintenance aspirin dosing, and the distribution of events in high-dose aspirin observed outside of the USA, the FDA documents clearly suggest that aspirin dosing does not explain the disparate outcome results. In addition, the Advisory Committee members found no evidence to establish a reasonable link, and they uniformly rejected the hypothesis that aspirin dose affects the heterogeneity of outcomes in PLATO. Additional evidence driven from the FDA review on aspirin dose and PLATO outcomes is reassessed. The wide distribution of outcomes differing from country to country, and inconsistency in European data despite identical aspirin doses, preclude the acceptance of the hypothesis that aspirin affects PLATO outcomes in general or adversely impacts the benefit of ticagrelor in the US cohort in particular. Differences in primary site monitoring by the study sponsor in most countries versus a third-party CRO in the USA represent an alternative explanation and deserve further attention. There is no solid evidence that aspirin dose affects outcomes after ticagrelor. Reevaluation of the overall endpoint differences, especially focusing on mortality, driven from sponsor-monitored sites versus outcomes observed by independent CROs is neccessary. The practice of self-monitoring in pivotal indication

  8. The thrombolytic effect of aspirin in animal model.

    Science.gov (United States)

    Karmohapatra, Soumendra K; Kahn, Nighat N; Sinha, Asru K

    2007-10-01

    The aspirin induced platelet aggregation has been reported to be mediated through the inhibition of platelet prostaglandin synthesis. This compound has also been recently reported to stimulate nitric oxide synthesis in platelets. Since nitric oxide has been reported to produce fibrinogen/fibrinolytic effect, investigation was carried out to determine fibrinolytic effect of in vivo exposure of platelets to aspirin in normal volunteers on the fibrinolysis of the clotted platelet-rich plasma in vitro. The thrombolytic effect of aspirin in situ was also carried out by injecting aspirin solution in the mice with ADP induced formed thrombi in the coronary artery. It was found that the clotted platelet-rich plasma prepared from the volunteers (n = 10, F = 5, M = 5) who ingested 150 mg aspirin, began to undergo spontaneous and progressive fibrinolysis for 200 min at 37 degrees C with the generation of fibrin degradation products in the lysate. No such fibrinolysis could be seen in control experiments. When platelet thrombi were produced in the coronary artery of mice by injecting ADP, and these animals subsequently received intravenous injection of aspirin (4 muM final), they not only survived (P < 0.0001, n = 10) the thrombogenic assault but the lysis of the platelet thrombi was also noted in the post mortem examination. The thrombolytic effect of aspirin was found to be comparable to that of streptokinase in these animals. Aspirin, through the stimulation of NO synthesis, may produce thrombolysis in vivo.

  9. Aspirin and lipid mediators in the cardiovascular system.

    Science.gov (United States)

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

    Aspirin is an unique compound because it bears two active moieties within one and the same molecule: a reactive acetyl group and the salicylate metabolite. Salicylate has some effects similar to aspirin, however only at higher concentrations, usually in the millimolar range, which are not obtained at conventional antiplatelet aspirin doses of 100-300 mg/day. Pharmacological actions of aspirin in the cardiovascular system at these doses are largely if not entirely due to target structure acetylation. Several classes of lipid mediators become affected: Best known is the cyclooxygenase-1 (COX-1) in platelets with subsequent inhibition of thromboxane and, possibly, thrombin formation. By this action, aspirin also inhibits paracrine thromboxane functions on other lipid mediators, such as the platelet storage product sphingosine-1-phosphate (S1P), an inflammatory mediator. Acetylation of COX-2 allows for generation of 15-(R)HETE and subsequent formation of "aspirin-triggered lipoxin" (ATL) by interaction with white cell lipoxygenases. In the cardiovascular system, aspirin also acetylates eNOS with subsequent upregulation of NO formation and enhanced expression of the antioxidans heme-oxygenase-1. This action is possibly also COX-2/ATL mediated. Many more acetylation targets have been identified in live cells by quantitative acid-cleavable activity-based protein profiling and might result in discovery of even more aspirin targets in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Synthesis of peptide derivatives of aspirin and their antibiogram ...

    African Journals Online (AJOL)

    Peptide derivatives of Aspirin (1 to 8) were synthesized by using Ac2O/AcOH reaction with Salicyclic acid. Aspirin was coupled with amino acid amide and dipeptide amide and tripeptide amide using its p-nitro phenyl (NP) ester. The ester (Aspirin–ONP) was prepared using p-nitro phenol and DCC in EtOAc and was ...

  11. Aspirin Risks in Perspective: A Comparison against Marathon Running

    Science.gov (United States)

    Morgan, Gareth

    2014-01-01

    Aspirin has public health potential to reduce the risk of ischaemic vascular events and sporadic cancer. One objection to the wider use of aspirin for primary prevention, however, is the undesirable effects of the medicine, which include increasing risk of bleeding and haemorrhagic stroke. Marathons also carry risks of serious events such as…

  12. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease

    NARCIS (Netherlands)

    Eikelboom, John W.; Connolly, Stuart J.; Bosch, Jackie; Dagenais, Gilles R.; Hart, Robert G.; Shestakovska, Olga; Diaz, Rafael; Alings, Marco; Lonn, Eva M.; Anand, Sonia S.; Widimsky, Petr; Hori, Masatsugu; Avezum, Alvaro; Piegas, Leopoldo S.; Branch, Kelley R. H.; Probstfield, Jeffrey; Bhatt, Deepak L.; Zhu, Jun; Liang, Yan; Maggioni, Aldo P.; Lopez-Jaramillo, Patricio; O'Donnell, Martin; Kakkar, Ajay K.; Fox, Keith A. A.; Parkhomenko, Alexander N.; Ertl, Georg; Störk, Stefan; Keltai, Matyas; Ryden, Lars; Pogosova, Nana; Dans, Antonio L.; Lanas, Fernando; Commerford, Patrick J.; Torp-Pedersen, Christian; Guzik, Tomek J.; Verhamme, Peter B.; Vinereanu, Dragos; Kim, Jae-Hyung; Tonkin, Andrew M.; Lewis, Basil S.; Felix, Camilo; Yusoff, Khalid; Steg, P. Gabriel; Metsarinne, Kaj P.; Cook Bruns, Nancy; Misselwitz, Frank; Chen, Edmond; Leong, Darryl; Yusuf, Salim; Aboyans, V.; Ha, J.; Keltai, K.; Lamy, A.; Liu, L.; Moayyedi, P.; Sharma, M.; Stoerk, S.; Varigos, J.; Bhagirath, V.; Bogaty, P.; Botto, F.; Catanese, L.; Donato Magno, J.; Fabbri, G.; Gabizon, I.; Gosselin, G.; Halon, D.; Heldmann, M.; Lamelas, P.; Lauw, M.; Leong, Y.; Liang, D.; Lutay, Y.; Maly, M.; Mikulik, R.; Nayar, S.; Ng, K.; Perera, K.; Pirvu, O.; Ronner, E.; Sato, S.; Smyth, A.; Sokolova, E.; Wiendl, M.; Winkelmann, B.; Yang, X.; Yufereva, Y.; Cairns, J.; Sleight, P.; deMets, D.; Momomura, S. I.; Prins, M. [=Martin H.; Ramsay, T.; Goto, S.; Rouleau, J. L.; Schumi, J.; Thabane, L.; Casanova, A.; Bangdiwala, S.; Deng, E.; Dyal, L.; Khatun, R.; Marsden, T.; Pogue, J.; Tang, C.; Wong, G.; Yuan, F.; Aman, S.; Ariz, A.; Ashton, H.; Belanger, J.; Belanger, M.; Brettell, K.; Chandra, J.; Choppick, C.; Cisternino, D.; Cuncins-Hearn, A.; Di Marino, M.; Diao, L.; Dwomoh, S.; Dykstra, A.; Galatsis, E.; Gasic, T.; Gutierrez, J.; Hamilton, L.; Irwin, L.; Lapensee, C.; Li, A.; Lu, X.; MacRae, L.; Malik, S.; Malvestiti, A.; Mastrangelo, J.; Maystrenko, A.; O'Donnell, L.; Reeh, K.; Szymkow, P.; Thomas, S.; Thrasher, D.; Tyrwhitt, J.; White, L.; Bastone, R.; Berkowitz, S.; Dias, A.; Ho, K.; Keller, L.; Lanius, V.; Lister, K.; Merten, C.; Muehlhofer, E.; Schmidt, K.; Tasto, C.; Tsihlias, E.; Woroniecka-Osio, A.; Orlandini, A.; Niemann, G.; Pascual, A.; Toscanelli, S.; Cabezón, M.; Debaveye, B.; Meeusen, K.; Luys, C.; Broos, K.; Vandenberghe, K.; Luyten, A.; Oliveira, G. B. F.; Vila Nova, D. C.; Konishi, M. Y. N.; Lonn, A.; Turbide, G.; Cayer, M.; Rovito, C.; Standen, D.; Li, J.; Lopez Pico, M.; Dusek, R.; Buzalka, V.; Larsen, J.; Paucar, M. J.; Saarinen, M.; Simon, T.; Bezault, M.; Le Lay, M.; Epstein, L.; Fajardo-Moser, M.; Röser, C.; Putz-Todd, G.; Scheidemantel, F.; Poehler, D.; Renner, J.; Hargitai, A.; Doherty, A. O.; Duffy, N.; Roarty, C.; Nolan, A.; Power, A.; Yuval, R.; Ben Ari, M.; Greenblatt, S.; Marmor, Y.; Lucci, D.; Ceseri, M.; Baldini, E.; Cipressa, L.; Miccoli, M.; Goto, M.; Yamasowa, H.; Kajiwara, M.; Takase, D.; Ikeguchi, K.; Matsumoto, M.; Ishii, M.; Asai, J.; Nozaki, D.; Akatsuka, T.; Yoshida, T.; Shahadan, S.; Md Nasir, N.; Schut, Astrid; Vinck, Leonie; van Leeuwen, Marjelle; Sanchez, J.; Aquino, M. R.; Mararac, T.; Benedyk, K.; Iordache, A.; Ciobanu, A.; Rimbas, R.; Dragoi Galrinho, R.; Magda, S.; Mihaila, S.; Mincu, R.; Suran, B.; Cotoban, A.; Matei, L.; Kursakov, A.; Rusnak, P.; Zakharova, A.; Demidova, E.; Commerford, A.; Lee, S.; Ju, I.; Gunolf, M.; Lorimer, A.; Parkhomenko, L.; Johnson, J.; Anderson, J.; Norby-Slycord., C.; Sala, J.; Sicer, M.; Rasmussen, M.; Luciani, C.; Cartasegna, L.; Beltrano, C.; Medek, G.; Vico, M.; Lanchiotti, P.; Martella, C.; Hominal, M.; Castoldi, M.; Casali, W.; Raimondi, S.; Hasbani, E.; Prado, A.; Paterlini, G.; Waisman, F.; Leonard, M.; Caccavo, A.; Alarcon, V.; Zaidman, C.; Guerlloy, F.; Vogel, D.; Imposti, H.; Dominguez, A.; Hrabar, A.; Fernandez, A.; Schygiel, P.; Sokn, F.; Cuneo, C.; Gutierrez Carrillo, N.; Martinez, G.; Luquez, H.; Costantino, M.; Ruiz, M.; Beccetti, N.; Mackinnon, I.; Cluigt, N.; Ahuad Guerrero, R.; Fanuele, M.; Campisi, V.; Costabel, J.; Romanelli, M.; Bartolacci, I.; Echeverria, M.; Pedrotti, M.; Montaña, O.; Camino, A.; Crespo, C.; Barbieri, M.; Lopez Santi, R.; Tonin, H.; Heffes, R.; Gomez Vilamajo, O.; Vanesio, F.; Allegrini, E.; Garcia Duran, R.; Garcia, C.; Garcia Duran, L.; Schiavi, L.; Mana, M.; Bordonava, A.; Rodriguez, M.; Gutierrez, M.; Garrido, M.; Rodriguez, C.; Ingaramo, A.; Costamagna, O.; Almagro, S.; Gerbaudo, C.; Pelagagge, M.; Bustamante Labarta, M.; Novaretto, L.; Maldini, A.; Lopez, L.; Albisu Di Gennero, J.; Ibanez Saggia, L.; Garcia Vilkas, A.; Alvarez, M.; Stoermann, W.; Vita, N.; Vottero, E.; Macin, S.; Cocco, M.; Onocko, M.; Dran, R.; Gimenez, C.; Cardona, M.; Guzman, L.; Guzman, P.; Martinez, D.; Sarjanovich, R.; Huerta, C.; Scaro, G.; Cuadrado, J.; Rodriguez, G.; Nani, S.; Guardiani, F.; Litvak Bruno, M.; Ceconi, G.; Chacon, C.; Casado, M.; Fernandez Moutin, M.; Maffei, L.; Sassone, S.; Yantorno, M.; Grinfeld, D.; Vensentini, N.; Rolandi, F.; Fallabrino, L.; Majul, C.; Paez, O.; Visser, M.; Luciardi, H.; Mansilla, V.; Gonzalez Colaso, P.; Ferre Pacora, F.; Jure, H.; Parody, M.; Espeche, E.; Whelan, A.; Boyle, A.; Collins, N.; Roberts-Thomson, P.; Rogers, J.; Caroll, P.; Colquhoun, D.; Williams, L.; Shaw, J.; Blombery, P.; Amerena, J.; Lee, C.; Hii, C.; Royse, A.; Royse, C.; Singh, B.; Selvanayagam, J.; Jansen, S.; Thompson, P.; Lo, W.; Hammett, C.; Poulter, R.; Graves, S.; Narasimhan, S.; van den Heuvel, P.; Wollaert, B.; Sinnaeve, P.; Fourneau, I.; Meuris, B.; Vanassche, T.; Ector, B.; Janssens, L.; Debonnaire, P.; Vandekerckhove, Y.; van de Borne, P.; Wautrecht, J.; Motte, S.; Leroy, J.; Schroë, H.; Vrolix, M.; Ferdinande, B.; Vranckx, P.; Benit, E.; Elegeert, I.; Lerut, P.; Wallaert, P.; Hoffer, E.; Borgoens, P.; Dujardin, K.; Brasil, C. 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O.; de Carvalho Cantarelli, M. J.; Tytus, R.; Pasyk, E.; Pandey, A. S.; Rowe, A.; Cha, J.; Vizel, S.; Babapulle, M.; Semelhago, L.; Saunders, K.; Haligowski, D.; Berlingieri, J.; Nisker, W.; Kiaii, B.; Romsa, J.; Chu, M.; Nagpal, D.; Guo, R.; Mckenzie, N.; Quantz, M.; Bhargava, R.; Bhargava, M.; Mehta, P.; Hill, L.; Heslop, W.; Fell, D.; Hess, A.; Zadra, R.; Zeman, P.; Srivamadevan, M.; Lam, A.; Tai, S.; Al-Qoofi, F.; Spence, F.; Anderson, T.; Kieser, T.; Kidd, W.; Fedak, P.; Smith, E.; Har, B.; Brown, C.; Forgie, R.; Hassan, A.; Pelletier, M.; Searles, G.; Marr, D.; Bessoudo, R.; Douglas, G.; Legare, J.; Petrella, R.; Pavlosky, W.; Ricci, J.; Galiwango, P.; Janmohamed, A.; Kassam, S.; Mukherjee, A.; Vijayaraghavan, R.; Burstein, J.; D'Mello, N.; Glanz, A.; Noiseux, N.; Stevens, L. M.; Basile, F.; Prieto, I.; Normandin, L.; Helou, J.; Do, Q. B.; Bainey, K.; Tymchak, W.; Welsh, R.; Merali, F.; Pandith, V.; Heffernan, M.; Orfi, J.; Mcconachie, D.; Jedrzkiewicz, S.; Della Siega, A.; Robinson, S.; Nadra, I.; Poirier, P.; Dagenais, F.; Voisine, P.; Mohammadi, S.; Doyle, D.; Baillot, R.; Charbonneau, E.; Dumont, E.; Kalavrouziotis, D.; Perron, J.; Jacques, F.; Laflamme, M.; Brulotte, S.; Crete, M.; Degrâce, M.; Delage, F.; Grondin, F.; Lemieux, A.; Michaud, N.; Saulnier, D.; Ross, M. K.; Nguyen, M.; Harvey, R.; Daneault, B.; Hartleib, M.; Guzman, R.; Nguyen, T.; Singal, R.; Bourgeois, R.; Landry, D.; Kamel, S.; Rupka, D.; Kuritzky, R.; Khaykin, Y.; Phaneuf, D. C.; Desjardins, V.; Coll, X.; Huynh, T.; Pilon, C.; Mansour, S.; Lemire, F.; Kokis, A.; Potvin, J.; Campeau, J.; Audet, M.; Boulianne, M.; Dupuis, R.; Lauzon, C.; Pruneau, G.; Senay, B.; Pichette, F.; Cieza, T.; Breton, R.; Belisle, P.; Barabas, M.; Diaz, A.; Costa, R.; Absi, F.; Garand, M.; Rheault, A.; Lemay, C.; Gisbert, A.; Raymond, A.; Barrero, M.; Gagne, C. E.; Rheault, P.; Pepin-Dubois, Y.; Johnston, J.; Mundi, A.; Cohen, G.; Shukle, P.; Baskett, R.; Hirsch, G.; Ali, I.; Stewart, K.; Fenton, J.; Pudupakkam, S.; Willoughby, R.; Czarnecki, W.; Roy, A.; Montigny, M.; Descarries, L.; Mayrand, H.; Comtois, H.; Essiambre, R.; Ringuette, G.; Boutros, G.; Gendreau, R.; Pham, L.; Nguyen, V.; Nguyen-Thanh, H. K.; Ben-Yedder, N.; Nawaz, S.; Fremes, S.; Moussa, F.; Shukla, D.; Labonte., R.; Jano, G.; Bobadilla, B.; Saavedra, J.; Bahamondes, J.; Cobos, J.; Grunberg, E.; Corbalan, R.; Verdejo, H.; Medina, M.; Vega, M.; Nahuelpan, L.; Castañia, F.; Raffo, C.; Vargas, A.; Reyes, T.; Vargas, D.; Perez, L.; Arriagada, G.; Potthoff, S.; Godoy, J.; Stockins, B.; Larenas, G.; Quiñinao, F.; Sepulveda, P.; Trucco, V.; Pincetti, C.; Saavedra, S.; Silva, P.; Vejar, M.; Rodríguez, T.; Rodriguez, J.; Tian, H.; Zhang, J.; Meng, Y.; Wu, X.; Wu, Q.; Wang, Q.; Mu, Y.; Yang, J.; Wang, F.; Zhang, W.; Ke, Y.; Jiang, H.; Yin, P.; Jia, K.; Chen, C.; Wang, Z.; Qi, B.; Yu, L.; Feng, G.; Li, L.; Jiang, L.; Wu, S.; Yu, H.; Wu, Z.; Ding, R.; Liu, S.; Xu, H.; Cao, H.; Bai, X.; Zheng, Y.; Liu, Z.; Sun, H.; Yang, P.; Li, B.; Feng, Z.; Yang, Y.; Xu, Z.; Wu, W.; Meng, Q.; Ge, J.; Dai, Y.; Yang, H.; Chen, X.; Tian, X.; Shi, Y.; Hu, T.; Zhang, R.; Zhao, Q.; Quan, W.; Zhu, Y.; Zheng, Z.; Zhang, S.; Zhao, Y.; Zhao, C.; Wang, R.; Tao, L.; Hu, D.; Wang, Y.; Fan, F.; Huang, W.; Xia, X.; Fu, G.; Jiang, D.; Wang, M.; Li, C.; Xu, K.; Dong, Y.; Chen, Y.; Wu, D.; Wang, C.; Sun, X.; Lu, S.; Zhou, X.; Kong, Y.; Zhang, B.; Sotomayor, A.; Suarez, M.; Ripoll, D.; Herrera, O.; Accini Mendoza, J.; Saad Cure, C.; Reyes, M.; Vidal, T.; Donado Beltran, P.; Hernandez Jaimes, E.; Castillo, H.; Rocha, C.; Forero, L.; Zarate Bernal, D.; Vanstrrahle Gonzalez, L.; Urina Triana, M.; Quintero, A.; Ramirez, N.; Balaguera Mendoza, J.; Aroca Martinez, G.; Cotes, C.; Mercado, A.; Lastra Percy, X.; Perez Mayorga, M.; Rodriguez, N.; Molina de Salazar, D.; Perez Agudelo, J.; Lopez Villegas, L.; Agudelo Ramos, L.; Melo Polo, M.; Esparza Albornoz, A.; Forero Gomez, J.; Sanchez Vallejo, G.; Aristizabal, J.; Gallego, A.; Contreras, C.; Yepez, J.; Angel Escobar, J.; Manzur J, F.; Cohen, L.; Boneu, D.; Garcia Lozada, H.; Barrios, L.; Celemin, C.; Diego, M.; Garcia Ortiz, L.; Montoya, C.; Ramirez, E.; Arcos Palma, E.; Ceron, J.; Acosta, G.; Gomez Mesa, J.; 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Yuba, K.; Miyajima, H.; Tobetto, Y.; Yoneda, K.; Ogura, R.; Kobayashi, H.; Takamura, T.; Enkou, K.; Ochi, Y.; Yamada, D.; Kuramochi, T.; Misumi, K.; Iiduka, D.; Hirose, M.; Tone, K.; Taniguchi, Y.; Ebihara, T.; Makino, M.; Yokota, M.; Nitta, M.; Udo, A.; Shimizu, S.; Fujii, K.; Iwakura, K.; Okamura, A.; Inoue, K.; Nagai, H.; Hirao, Y.; Tanaka, K.; Tanaka, N.; Yamasaki, T.; Oka, T.; Iwamoto, M.; Tanaka, T.; Nakamaru, R.; Okada, M.; Takayasu, K.; Sumiyoshi, A.; Inoue, H.; Kitagaki, R.; Ninomiya, Y.; Mizutomi, K.; Koizumi, I.; Funada, A.; Tagawa, S.; Kamide, S.; Saku, K.; Ideishi, M.; Ogawa, M.; Uehara, Y.; Iwata, A.; Nishikawa, H.; Ike, A.; Sugihara, M.; Imaizumi, S.; Fujimi, K.; Kawamura, A.; Sako, H.; Morito, N.; Morii, J.; Fukuda, Y.; Yahiro, E.; Matsunaga, A.; Matsumoto, N.; Noda, K.; Shiga, Y.; Nagata, Y.; Kimura, K.; Ebina, T.; Hibi, K.; Iwahashi, N.; Maejima, N.; Konishi, M.; Matsushita, K.; Minamimoto, Y.; Kawashima, C.; Nakahashi, H.; Kimura, Y.; Takahashi, H.; Matsuzawa, Y.; Kirigaya, J.; Sato, R.; Kikuchi, S.; Ogino, Y.; Kirigaya, H.; Kashiwase, K.; Hirata, A.; Takeda, Y.; Amiya, R.; Higuchi, Y.; Sakaguchi, T.; Nakano, T.; Matsusaki, N.; Suzuki, S.; Hayashi, T.; Nakatani, S.; Koide, M.; Kobayashi, T.; Hamanaka, Y.; Makino, N.; Sotomi, Y.; Abe, M.; Fujieda, H.; Hashimoto, K.; Teratani, Y.; Abe, Y.; Yokoyama, Y.; Higashino, H.; Okuda, H.; Yamazato, M.; Noda, T.; Arai, M.; Ono, K.; Hirose, T.; Iwama, M.; Warita, S.; Goto, Y.; Abe, S.; Kojima, T.; Yoshizane, T.; Tanihata, S.; Fujii, T.; Yagasaki, H.; Miwa, H.; Ishiguro, M.; Kato, T.; Watanabe, R.; Horio, S.; Mita, T.; Hirayama, A.; Watanabe, I.; Hiro, T.; Nakai, T.; Takayama, T.; Yoda, S.; Yajima, Y.; Okubo, K.; Okumura, Y.; Kato, M.; Fukamachi, D.; Aizawa, Y.; Sonoda, K.; Iida, K.; Sasaki, N.; Iso, K.; Takahashi, K.; Kougo, T.; Haruta, H.; Kurokawa, S.; Mano, H.; Nagashima, K.; Onaka, H.; Doi, H.; Hirano, N.; Okamoto, F.; Mori, K.; Ri, G.; Zushi, R.; Otsuka, K.; Inoko, M.; Haruna, T.; Nakane, E.; Miyamoto, S.; Izumi, T.; Honjo, S.; Ikeda, H.; Wada, Y.; Funasako, M.; Hayashi, H.; Hamasaki, A.; Sasaki, K.; Seko, Y.; Nakasone, K.; Hanyu, M.; Iwasaki, Y.; Iwasaki, K.; Ayano, S.; Hirokami, M.; Omoto, Y.; Sasaki, H.; Sato, H.; Yuda, S.; Okubo, M.; Matsuo, H.; Tsuchiya, K.; Kawase, Y.; Miyake, T.; Kondo, H.; Hattori, A.; Kikuchi, J.; Okamoto, S.; Hirata, T.; Kawamura, I.; Ota, H.; Omori, H.; Tanigaki, T.; Kamiya, H.; Sobue, Y.; Komoda, T.; Akatsuka, Y.; Yamamoto, M.; Isegawa, K.; Takanezawa, M.; Kataoka, C.; Imamaki, M.; Shibata, Y.; Yasuda, K.; Shimano, M.; Ozaki, R.; Morishita, Y.; Okabe, K.; Kondo, K.; Miura, A.; Manita, M.; Tabata, K.; Asahi, T.; Mashidori, T.; Higa, N.; Nakata, M.; Himi, T.; Matsudo, Y.; Sekine, T.; Hou, K.; Tonoike, N.; Hama, Y.; Tanaka, S.; Ge, B.; Takahara, M.; Ishimura, M.; Shikada, T.; Ueno, H.; Amemiya, H.; Hisamatsu, Y.; Sada, K.; Sato, T.; Harada, K.; Nakamura, T.; Ako, J.; Tojo, T.; Shimohama, T.; Kishihara, J.; Ishii, S.; Fukaya, H.; Meguro, K.; Nishino, Y.; Inoue, M.; Matsui, Y.; Omura, Y.; Kawakami, H.; Matsuoka, H.; Oshita, A.; Seike, F.; Kondo, N.; Miyoshi, T.; Yamada, Y.; Uchiya, T.; Kikuchi, Y.; Koretsune, Y.; Abe, H.; Shinouchi, K.; Nishida, H.; Yasumura, K.; Date, M.; Ueda, Y.; Iida, Y.; Idemoto, A.; Toriyama, C.; Yokoi, K.; Mishima, T.; Yamada, T.; Fukunami, M.; Morita, T.; Furukawa, Y.; Kawasaki, M.; Kikuchi, A.; Tamaki, S.; Seo, M.; Shirakawa, Y.; Ikeda, I.; Fukuhara, E.; Kawai, T.; Kayama, K.; Kawahira, M.; Tanabe, K.; Nakamura, J.; Shimomura, H.; Kudo, T.; Morisaki, S.; Ogura, Y.; Chazono, N.; Onoue, Y.; Matsumuro, Y.; Shirakawa, T.; Nishi, M.; Kinoshita, N.; Nakamura, R.; Miyai, N.; Ohta, K.; Sawanishi, T.; Takahashi, A.; Hada, T.; Nakajima, S.; Taniguchi, N.; Mizuguchi, Y.; Takahashi, Y.; Hashimoto, S.; Machida, M.; Hirabayashi, K.; Morimoto, S.; Higashino, Y.; Otsuji, S.; Takiuchi, S.; Yabuki, M.; Hasegawa, K.; Shishikura, D.; Ibuki, M.; Ishibuchi, K.; Nagayama, S.; Ishii, R.; Tamaru, H.; Yamamoto, W.; Utsu, N.; Miyakoshi, K.; Nakashima, D.; Tsukuda, K.; Ueda, K.; Nakano, A.; Fukuda, T.; Ikeda, S.; Tsuchiya, H.; Toshima, S.; Tateno, R.; Ishikubo, T.; Suguta, M.; Nakamura, S.; Funatsu, A.; Mizobuchi, M.; Tanaka, M.; Nagai, T.; Hirano, S.; Hashimoto, T.; Doi, T.; Shirasaka, A.; Takeda, S.; Sasaki, Y.; Ohya, H.; Hosokawa, A.; Nishina, N.; Koki, B.; Ando, K.; Hiramori, S.; Soga, Y.; Tomoi, Y.; Tohoku, S.; Shirai, S.; Hyodo, M.; Isotani, A.; Domei, T.; Kuramitsu, S.; Morinaga, T.; Hayashi, M.; Hiromasa, T.; Nagae, A.; Yamaji, Y.; Nakao, K.; Sakamoto, T.; Taguchi, E.; Tsurugi, T.; Tanaka, Y.; Suzuyama, H.; Koyama, J.; Nagano, M.; Okamatsu, H.; Kodama, K.; Nakamura, M.; Horibata, Y.; Sone, M.; Tsunemori, M.; Bando, M.; Nakayama, T.; Tanigaito, Y.; Nomoto, M.; Sawamura, T.; Unoki, T.; Lim, C. W.; Zainal Rashid, R.; Najme Khir, R.; Ibrahim, K. S.; Wan Azman, W. A.; Sridhar, G. S.; Watson, T.; Abu Kassim, Z.; Mahmood Zuhdi, A. S.; Abdul Hafidz, M. I.; Abu Hassan, M. R.; Wan Rahimi Shah, W. F.; Karthikesan, D.; Mohd Suan, M. A.; Md Ali, S. M.; Kasim, S.; Mohd Arshad, M. K.; Ismail, J. R.; Ibrahim, Z. O.; Chua, N. Y. L.; Abdul Rahim, A. A.; Rusani, B. I.; Yap, L. B.; Zamrin, D. M.; Amir, M. A.; Ismail, N. I.; Mohammad Razi, A. A.; Prins, F.; Bendermacher, P.; Burg, M.; Lok, D.; van der Sluis, A.; Martens, F.; Badings, E.; Milhous, J.; van Rossum, P.; Viergever, E.; van Hessen, M.; Willems, F.; Tjon Joe Gin, R.; Swart, H.; Oomen, A.; Kromhout, S.; Lauwerijssen, I.; Daalmans, M.; Breedveld, R.; de Vries, K.; Feenema Aardema, M.; Hofma, S.; van der Borgh, R.; van Nes, E.; Göbel, E.; Oei, F.; Dorman, H.; Bos, R.; Zoet-Nugteren, S.; Emans, M.; Kragten, H.; Lenderink, T.; Feld, R.; Herrman, J.; van Bergen, P.; Gosselink, M.; Elvan, A.; Hoekstra, E.; The, S.; de Vries, R.; Zegers, E.; Oude Ophuis, T.; Remmen, J.; Bech, J.; Kooistra, J.; den Hartog, F.; Oosterhof, T.; Bartels, G.; Posma, J.; Nierop, P.; Liem, A.; van der Zwaan, C.; Asselman, M.; van Eck, J.; Gevers, R.; van Gorselen, E.; van Hal, J.; Terpstra, W.; Groenemeijer, B.; Jerzewski, A.; Hoogslag, P.; Geertman, J.; de Groot, M.; Dijkstra, B.; Loyola, A.; Sulit, D.; Mercado, M. J.; Rey, N.; Evangelista, L.; Abola, M.; Padua, L.; Morales, D.; Palomares, E.; Abat, M.; Santos, R.; Rogelio, G.; Chua, P.; Baello, R.; del Pilar, J.; Alianza, M.; Alcaraz, J.; Alcaraz, L.; Ebo, G.; Guido-Saliot, I.; Tirador, L.; Estoce, E.; Ygpuara, M.; Cruz, J.; Anonuevo, J.; Pitargue, A.; Janion, M.; Drewniak, Z.; Guzik, B.; Nowak, M.; Nosal, M.; Niewiara, Ł; Gajos, G.; Bury, K.; Czubek, U.; Misztal, M.; Grzybczak, R.; Zalewski, J.; Kruszelnicka-Kwiatkowska, O.; Żabówka, M.; Rynkiewicz, A.; Grzybowski, A.; Szałkowski, P.; Broncel, M.; Gorzelak, P.; Możdżan, M.; Olszewska Banaszczyk, M.; Szuba, A.; Tabin, M.; Chachaj, A.; Czarnecka, D.; Terlecki, M.; Klocek, M.; Maga, P.; Coman, I.; Tarlea, M.; Ghionea, M.; Gavrila, C.; Dimulescu, D.; Popescu, A.; Stoicescu, C.; Vintila, V.; Florescu, M.; Baghilovici Cretu, D.; Suran, M.; Mihalcea, D.; Lungeanu Juravle, L.; Cinteza, M.; Calin, I.; Bicescu, G.; Vasile Toma, N.; Udroiu, C.; Gherghinescu, C.; Darabont, R.; Patrascu, N.; Constantinescu, C.; Popescu, I.; Sinescu, C.; Andrei, C.; Axente, L.; Arsenescu, C.; Statescu, C.; Ardeleanu, I.; Anghel, L.; Benedek, I.; Benedek, T.; Kinga, P.; Banga, D. K.; Bobescu, E.; Doka, B.; Dobreanu, D.; Sirbu, V.; Rudzik, R.; Kantor, K.; Sus, I.; Gaita, D.; Maximov, D.; Brie, D.; Mosteoru, S.; Olariu, I.; Iancu, A.; Marc, M.; Hagiu, R.; Manole, V.; Molnar, A.; Dregoesc, I.; Iliesiu, A.; Armean, P.; Parvu, I.; Deleanu, A.; Lighezan, D.; Buzas, R.; Petrescu, L.; Nicola, R.; Dan, R.; Crisan, S.; Trasca, L.; Teodorescu, I.; Zara, O.; Tiron, T.; Tesloianu, D.; Spiridon, M.; Vintila, M.; Baluta, M.; Chioncel, O.; Stoica, E.; Kulcsar, I.; Antohi, L.; Strazhesko, I.; Tkacheva, O.; Sharashkina, N.; Pykhtina, V.; Vasyuk, Y.; Shkolnik, E.; Khadzegova, A.; Sadulaeva, I.; Ivanova, S.; Nesterova, E.; Nesvetov, V.; Shupenina, E.; Shcherbak, M.; Sizova, Z.; Beloborodova, A.; Pozdnyakov, Y.; Tarasov, A.; Shvedov, I.; Zabashta, S.; Ryzhikova, I.; Barbarash, O.; Pecherina, T.; Vatutin, M.; Inozemceva, A.; Kazachek, Y.; Mineeva, E.; Kupriyanova, T.; Voevoda, M.; Gafarov, V.; Gromova, E.; Panov, D.; Voevoda, E.; Kovalkova, N.; Ragino, Y.; Poponina, T.; Poponina, Y.; Garganeeva, N.; Repin, A.; Vershinina, E.; Borodina, E.; Kalashnikova, T.; Safyanova, O.; Osipova, I.; Antropova, O.; Pyrikova, N.; Polyakova, I.; Efremushkina, A.; Guryanova, N.; Kiseleva, E.; Lomteva, E.; Shtyrova, T.; Novikova, N.; Parfenov, D.; Volovchenko, A.; Averkov, O.; Pavlikova, E.; Vaulina, L.; Pletnikova, I.; Mishchenko, L.; Saranin, S.; Tsupko, I.; Kuznetsova, N.; Zateyshchikov, D.; Dankovtseva, E.; Vlazneva, Y.; Tolokonnikova, N.; Zhurina, M.; Zubova, E.; Aseycheva, O.; Sigalovich, E.; Vertkin, A.; Rodiukova, I.; Komissarov, S.; Sokolova, R.; Ausheva, A.; Salbieva, A.; Yusubova, A.; Isakova, S.; Hranai, M.; Obona, P.; Cisar, P.; Semetko, J.; Vanova, P.; Ferencikova, Z.; Vykoukalova, T.; Gaspar, L.; Caprnda, M.; Bendzala, M.; Pella, D.; Fedacko, J.; Hatalova, K.; Drozdakova, E.; Peter, O.; Ntsekhe, M.; de Andrade, M.; Seedat, S.; Gani, M.; van Zyl, L.; Naude, M.; Cronje, T.; van Zyl, F.; Engelbrecht, J.; Jansen, J.; Roos, J.; Makotoko, E.; Pretorius, C.; Mirna, S.; Nell, H.; Pretorius, M.; Basson, M.; Njovane, X.; Mohamed, Z.; Pillay, T.; Dawood, S.; Horak, A.; Lloyd, E.; Hitzeroth, J.; Mabin, T.; Abelson, M.; Klug, E.; Gebka, M.; Hellig, F.; Alison, M.; Bae, J.; Kim, C.; Kim, D.; Joo, S.; Park, C.; Kim, Y.; Jarnert, C.; Rydén, L.; Mooe, T.; Binsell-Gerdin, E.; Dellborg, M.; Torstensson, I.; Albertsson, P.; Hiller, M.; Perers, E.; Johansson, L.; Jansson, J. H.; Al-Khalili, F.; Almroth, H.; Andersson, T.; Eriksson Östman, M.; Pantev, E.; Utter, F.; Tengmark, B. O.; Olsson, Å; Liu, B.; Rasmanis, G.; Wahlgren, C. M.; Thott, O.; Moccetti, T.; Rossi, M. G.; Crljenica, C.; Dovgan, N.; Skarzhevskyi, O.; Kozhukhov, S.; Tseluyko, V.; Mishchuk, N.; Kuznetsov, I.; Semenikhin, S.; Matviichuk, N.; Matuzok, O.; Yakovleva, L.; Volkov, V.; Zaprovalna, O.; Serik, S.; Riabukha, V.; Koval, O.; Kaplan, P.; Ivanov, A.; Romanenko, S.; Skoromna, A.; Kononenko, L.; Saprychova, L.; Lazareva, S.; Prokhorov, O.; Vdovychenko, V.; Bychkov, M.; Demydova, A.; Kapustynska, O.; Bazylevych, A.; Dutka, R.; Vlasyuk, Z.; Shabat, M.; Rudenko, L.; Beregova, O.; Fedtchouk, L.; Gusak, I.; Vizir, V.; Sadomov, A.; Shkolovoy, V.; Nasonenko, O.; Demidenko, O.; Karpenko, O.; Ponomarenko, K.; Oryshych, G.; Nevolina, I.; Mitskevych, L.; Bezuglova, S.; Kizim, S.; Todoriuk, L.; Brodi, N.; Karpenko, L.; Malynovsky, Y.; Fedotov, S.; Malynovska, O.; Goydenko, O.; Miroshnykov, S.; Rabota, I.; Koval, V.; Ohirko, O.; Khaba, U.; Storozhuk, B.; Danylchuk, I.; Danylchuk, A.; Gutsuliak, R.; Cotton, J.; Luckraz, H.; Wrigley, B.; Venkataraman, A.; Maher, A.; Moriarty, A.; McEneaney, D.; Connolly, D.; Davis, R.; Banerjee, P.; Davey, P.; Elmahi, E.; Senior, R.; Ahmed, A.; Birdi, I.; Gedela, S.; Singh, A.; Calvert, J.; Butler, M.; Donnelly, P.; Jasinka, A.; Orr, C.; Trevelyan, J.; Routledge, H.; Carter, J.; Oxenham, H.; Peace, A.; McNeill, A.; Austin, D.; Jackson, M.; Kukreja, N.; Kotwinski, P.; Hilton, T.; Bilizarian, S.; Srivastava, S.; Walsh, R.; Fields, R.; Portnay, E.; Gogia, H.; Deits, R.; Salacata, A.; Hunter, J.; Bacharach, J.; Shammas, N.; Suresh, D.; Gurbel, P.; Banerjee, S.; Grena, P.; Bedwell, N.; Sloan, S.; Lupovitch, S.; Soni, A.; Gibson, K.; Pepper, D.; Sangrigoli, R.; Mehta, R.; Patel, J.; I-Hsuan Tsai, P.; Gillespie, E.; Harrison, A.; Dempsey, S.; Phillips, R.; Hamroff, G.; Hametz, C.; Black, R.; Lader, E.; Kostis, J.; Bittner, V.; Mcguinn, W.; Cheng, R.; Pal, J.; Malhotra, V.; Michaelson, S.; Vacante, M.; Mccormick, M.; Arimie, R.; Dukkipati, R.; Camp, A.; Dagher, G.; Kosh y, N.; Culp, J.; Thew, S.; Ferraro, A.; Costello, F.; Heiman, M.; Chilton, R.; Moran, M.; Adler, F.; Balingit, P.; Comerota, A.; Seiwert, A.; French, W.; Vardi, G.; Singh, T.; Serota, H.; Qayyum, U.; Das, S.; Harrison, R.; Vora, A.; Bakeen, F.; Omer, S.; Chandra, L.; Casaccia, G.; Tinto, J.; Sighel, C.; Giozzi, E.; Morell, Y.; Bianchini, M.; Yossen, M.; Hoyos, M.; Venturini, C.; Merkusa, C.; Carrique, A.; Carrique, P.; Fracaro, V.; Torres, M.; Crunger, P.; Espinosa, M.; Passarello, A.; Zaidman, M.; Ledesma, M.; Troncoso, C.; Aviles, A.; Rodera Vigil, S.; Vogel, M.; Takla, M.; Funosas, C.; Ferreiro, M.; Bruno, T.; Buzzetti, C.; Lozano, J.; Alvarez Dámelio, A.; Bocanera, M.; Vicente, D.; Cenci, A.; Deluca, C.; Santana, R.; Ahuad Calvelo, A.; Alvarez D'Amelio, A.; Ahuad Calvelo, J.; Herrero, S.; Robertson, M.; Tapia, D.; Escalante, M.; Cañas, M.; Cendali, G.; Esposito, L.; Muñiz, M.; Montaña, J.; Di Vruno, M.; Strevezza, M.; Lopez Santi, M.; Massei, N.; Garate, V.; Perlo, D.; Campora, F.; Jakubowski, I.; Gonzalez Moisello, M.; Actis, M.; Schiavi, S.; Aguirre, M.; Ceirano, C.; Zillo, M.; Yunis, M.; Berdini, A.; Gerbaudo, R.; Berdini, J.; Palma, F.; Pinero, S.; Virulio, S.; Vitale, A.; Sosa Flores, G.; Ibanez Saggia, C.; Ibanez Saggia, D.; Roses, A.; Martinelli, C.; Vargas, L.; Galarza Salazan, M.; Dran, P.; Tinnirello, V.; Pelayes, S.; Bordoni, P.; Navarro, A.; Barilati, P.; Serra, R.; Nigro, A.; Cleiman, S.; Bianchi, M.; Vallejo, M.; Ingratta, M.; Tonelli, L.; Levantini, M.; Bonifacio, M.; Hansen, V.; Chaieb, A.; Majul, S.; Medina, F.; Gallinotti, P.; Madariaga, T.; Andrea, G.; Blumberg, C.; Volpe, M.; Gandur, H.; Benincasa, V.; Barreto, M.; Jure, D.; Tulloch, G.; Greenwell, D.; Forrest, N.; Nyman, E.; Mcintosh, C.; O'May, V.; Grabek, T.; Conway, B.; O’Donoghue, M.; Brady, L.; Duroux, M.; Ratcliffe, M.; Shone, S.; Connelly, A.; Ferreira-Jardim, A.; Vandernet, R.; Downes, R.; Davids, F.; Teal, L.; Knight, S.; Soraghan, D.; Spence, C.; Smith, K.; Tivendale, L.; Williams, Z.; O'Connor, M.; Walker, I.; Ferguson, L.; Holiday, J.; Griffin, R.; Palethorpe, L.; Hindom, L.; Lilwall, L.; Wadham, S.; Narasimhan, K.; van Extergem, P.; Joris, I.; Oreglia, M.; Jacobs, C.; Leus, W.; Robesyn, V.; Vanheule, K.; van den Bossche, K.; Albertijn, S.; Vissers, C.; Badts, G.; Vangenechten, K.; Derycker, K.; Dejaegher, K.; de Grande, T.; de Clippel, M.; Gayet, F.; Jorion, M.; Jourdan, A.; Tartaglia, K.; Zwinnen, W.; Roijakkers, I.; van Genechten, G.; Schoonis, A.; Bollen, J.; Janssen, A.; de Coninck, M.; Ruell, S.; Grimonprez, A.; Bouckaert, N.; van Eeckhoutte, H.; Malmendier, D.; Massoz, M.; Jacquet, S.; Vanhalst, E.; Casier, T.; Barroso, S. L.; Tamashiro, N.; Correa, C. P.; Sehnem, E. A. B.; Precoma, C. B.; Pinheiro, L.; Ruschel, K. B.; dos Reis, A. L.; Santos, M. S.; de Oliveira, L. O. S. P.; de Carvalho, L. M. G.; dos Santos, M. E. S.; Reis, L. L. F.; da Cunha, G. T.; França, F. F.; Bessa, S. K.; Vicente, C.; Ormundo, C.; Trama, L.; Pires, N. F.; Esteves, D.; Sila, O. L.; Góes, N. C.; Amorin, R. C.; Faria, M. O.; Bucalon, E. C.; Marin, L. P.; Herek, L.; Araujo, V. L.; Silva, A. F.; Lima, F.; Gomes, C. G.; Pagnan, L. G.; Novelli, C. M.; Carvalho, J. K. C.; Teodoro, A. R.; Zimmermann, E. M. B.; Beiersdorf, J. R.; Machado, B. G.; Pedroso, F. B. V.; de Vargas, T.; Peres, C. S.; dos Santos, T. F.; de Souza, S. F.; Luiz, R. O.; Ferreira, P.; Souza, D. F.; Cunha, S. M. C.; de Resende, I. M.; Furtado, C. C. F.; Soprane, A. A.; Brum, A. B.; Zorzo, J. A. T.; dos Santos, J. C.; Queiroz, L. B.; Barros, F. E.; Vianna, C. O.; Zanateli, A.; Vieira, A. P. Z.; Melo, G.; Zambonin, G. E. C.; Paiva, P.; Viana, R. M. M.; Yagihara, M. M.; Takiuti, M. M.; Miyamoto, P. B.; da Silva, M. F.; Borin, L. A.; Chiazzini, S. M. L.; Fleck, N.; Batista, R. F.; Cardoso, D. T.; MCamasmie, P.; Assompção, R. P.; Marques, L. L.; Leung, S.; Lewis, C.; Tytus, A.; Clarus, S.; Juranics, S.; Pandey, M.; Frenette, L.; Magi, A.; Nowacki, B.; Otis, J.; Fox, B.; Corke, R.; Miller, B.; Rizzo, A.; Trombetta, L.; Power, P.; Richert, L.; Haligowski, R.; Macrae, C.; Kooistra, L.; Urso, C.; Fox, S.; Felbel, S.; Stafford, C.; Stata, C.; Barnabe, B.; Mehta, K.; Faul, J.; Gohel, J.; Bhakta, S.; Harwood, A.; McPherson, C.; Marucci, J.; Manasterski, L.; Veenhuyzen, J.; Ramadan, D.; Madden, B.; Jetha, A.; Pajevic, M.; Dube, C.; Rolfe, B.; O’Blenis, G.; Roy, L.; Dihel, C.; Butler, J.; Simmavong, K.; Bartol, C.; Bozek, B.; Hart, B.; Shier, M.; Coughlin, M.; Lamantia, C.; Lamantia, D.; Vilag, C.; Fecteau, J.; Dionne, J.; Péloquin, G.; Hogg, N.; Welsh, S.; Weerasingam, S.; Lantz, M.; Lounsbury, N.; Martin, E.; Mitchell, L.; Morgen, G.; Nelson, S.; Pelzer, E.; Sorensen, S.; Leblanc, A.; Bourlaud, A. S.; Prémont, A.; Léger, P.; Larivière, M. M.; Tremblay, H.; Bergeron, A.; Dumont, J.; Keilani, S.; Landry, P.; Deneufbourg, I.; Breton, C.; Bilodeau, N.; Côté, M.; Dumont, F.; Dufort, L.; Marcoux, D.; David, M.; Otis, R.; Parks, J.; Cepidoza, C.; Janz, W.; Weighell, W.; Yaworski, S.; Boyd, K.; Lambert, J.; Shea-Landry, G.; Reid, K.; Thiessen, S.; Nemtean, D.; Futers, S.; Drouin, K.; Masson, C.; Arseneault, M. C.; Lachance, N.; Bergeron, C.; Boudreault, C.; Perkins, L.; Barnett, A.; Fortin, J.; Duclos, R.; Vallières, C.; Bouchard-Pilote, C.; Ouimet, F.; Roberge, B.; Couture, M. L.; Deshaies, D.; Bastien, A.; Chartrand, M. J.; Gagné, N. L.; Desbiens, K.; Alarie, P.; Cassan, J.; Ducharme, Y.; Roy D Tapps, I.; Bolduc, H.; Laliberté, J.; Hickey, L.; Spero, M.; Bernstein, M.; Clement, J.; Pawluch, A.; Ricci-Bonzey, M.; Richer, J.; Vaillancourt, J.; Ward, B.; Mostafai Rad, P.; Oleski, L.; Karkhanis, R.; Hartleib, V.; Poirier, R.; Hidalgo, J.; Hernandez, C.; Obreque, C.; Quilapi, D.; Villa, F.; Iturriaga, C.; Ferrada, M.; Navarrete, S.; Becerra, E.; Vargas, C.; Roque, C.; Alarcon, J.; Diaz, D.; Sepulveda, M.; Villan, C.; Garcia, N.; Lara, C.; Lezana, B.; Basso, N.; Torres, G.; Pasmino, C.; Gonzalez, S.; Medina, D.; Rodriguez, T.; Guo, T.; Chen, S.; Han, W.; Shi, D.; Zhang, Q.; Li, W.; Cui, L.; Huang, Z.; Gong, X.; Liu, D.; Tan, S.; Caicedo, L.; Rodriguez, A.; Mejia, I.; Escalante Ruiz, J.; Camera Ochoa, C.; Conrrado Ortega, Y.; Accini Diaz, A.; Rodriguez, B.; Lopez-Lopez, J.; Di Stefano, K.; Florez, L.; Manco, T.; Rodriguez, D.; Urina, A.; de La Hoz, L.; Almendrales, L.; Bello, O.; Urrea Valencia, H.; Correa Rivera, P.; Perdomo, I.; Alzate, J.; Rivera, E.; Jimenez, N. N.; DMoreno, N.; Guzman, A.; Betancourt, S.; Mendoza Marin, H.; Leyva, M.; Ortiz, M.; Marin, E.; Angie Lorena, A.; Alvarez, Y.; Cervantes Hurtado, A.; Accini Mendoza, A.; Trujillo Accini, M.; Eguis, B.; del Portillo, C.; Ortega, M.; Delgado, P.; Arciniegas, J.; Rodriguez, L.; Melo Sanchez, S.; Chavera, I.; Pastrana Mendoza, M.; Negrette Quintero, A.; Zidek, M.; Hajkova, D.; Rozskowska, P.; Opavska, I.; Souckova, E.; Matuskova, E.; Kratochvilova, T.; Pavelec, P.; Zelenkova, V.; Dolezalova, Z.; Márquez, M.; Moreira, D.; Zuleta, M.; Santana, G.; Coello, A.; Andrade, G.; Salazar, J.; Rivadeneira, J.; Vaerma, J.; Lappalainen, S.; Silvennoinen, S.; Haaraoja, A.; Valimaki, S.; Roine, E.; Abergel, H.; Msakni, W.; Fuentes, A.; Briday, G.; David, A.; Soltani, S.; Decorps, A.; Chettouh, M.; Douillet, M.; Zamiti-Smondel, A.; Cuccu, L.; Salhi, N.; Helene, M.; Martin, S.; Merah, A.; Daher, P.; Laurie, S.; Roussel, L.; Leperchois, C.; Delelo, E.; Thalamy, A.; Chazot, E.; Tahirovic, E.; Watson, S.; Brettschneider, B.; Maas, M.; Euler, K.; Rahn, G.; Beissner, S.; Anuschek, V.; Tu, E.; Buerger, M.; Schemann, J.; Klinger, C.; Kurzidim, T.; Sahbani, S.; Laszig, S.; Beilfuss, M.; Foerster, A.; Eichinger, G.; Rupprecht, M.; Kuehnert, J.; Wendler-Huelse, I.; Buelow-Johansen, B.; Baierlein, A.; Iselt, M.; Sievert, B.; Frommhold, R.; Wolf, T.; Hahn, M.; Schoen, B.; Acimic, C.; Ludwig, M.; Funkat, A.; Wagner, I.; Schink, M.; Calvo-Sanchez, D.; Felfoldine Feil, J.; Patakine Sumegi, T.; Miko-Pauer, R.; Courcy, M.; Kelly, C.; Farrell, D.; Kirrane, C.; Hall, M.; Gilroy, E.; Kelsey, M.; Andrew, G.; Joyce, M.; Conway, S.; Duane, L.; Omer, T.; Zuker, S.; Platner, N.; Saranga, H.; Kaufman, E.; Livshitz, L.; Genin, I.; Klainman, M.; Uziel Iunger, K.; Abitbul, A.; Fishman, B.; Greenshtein, I.; Tubul, O.; Lasri, E.; Zvi, R.; Yablonski, A.; Helmer Levin, L.; Lunetto, M. L.; Savoldi, D.; Fiorini, M.; Ramani, F.; Mariottoni, B.; Rizzotti, D.; Di Matteo, C.; Musio, S.; Pieroni Minciaroli, S.; Serani, S.; Aloisi, A.; Attanasio, C.; Tricoli, M.; Giordano, V.; Andrioli, V.; Biundo, V.; Tullio, L.; Schiff, D.; Trovarelli, P.; Chiodi, R.; Sampaolesi, S.; Cina, M. T.; Abatello, M.; de Tora, M.; Pietrucci, F.; Pezzetta, S.; Chiminelli, E.; Dall’Asta, A.; Bennati, M.; Elia, A.; Bizzoco, M.; Iaquaniello, A.; Spigarelli, R.; Cremonesi, C.; Gagliardi, M.; Torricelli, L.; Ijichi, N.; Shiraiwa, K.; Murakami, M.; Takeshita, K.; Sato, M.; Shiratori, A.; Kinjo, K.; Tomita, K.; Mizuno, M.; Kurihara, F.; Tachibana, M.; Nitta, Y.; Unno, K.; Hiramatsu, H.; Sano, A.; Nanatsumura, M.; Tanikawa, I.; Uesugi, K.; Banno, S.; Miyata, T.; Kujuji, A.; Kawai, K.; Maegawa, A.; Koseki, T.; Watanabe, Y.; Aoki, S.; Maesawa, M.; Suzuki, A.; Itose, Y.; Konishi, K.; Fujieda, K.; Nakade, S.; Minami, M.; Yoneda, J.; Akiyama, R.; Sakai, S.; Nakatani, K.; Yamazaki, A.; Funama, M.; Kaneko, E.; Morii, S.; Onishi, M.; Sone, A.; Sagawa, N.; Iwai, F.; Kawahara, A.; Hasimoto, C.; Ueki, M.; Kamiji, M.; Ando, M.; Yokoo, M.; Okada, Y.; Yamada, H.; Matsushige, N.; Nagato, A.; Matsumoto, R.; Nishikawa, M.; Oka, I.; Kitou, S.; Tachiuchi, M.; Nakagawa, M.; Yoneda, S.; Iwasa, K.; Matsuda, J.; Oda, A.; Tokudome, S.; Kaneyuki, Y.; Higaki, M.; Yoneda, H.; Kajita, C.; Suwa, K.; Sato, E.; Nagata, T.; Kubo, Y.; Umesu, A.; Ohashi, K.; Takeuchi, M.; Tanaka, I.; Nobehara, T.; Yamano, R.; Yumiba, A.; Hamada, M.; Nishihata, T.; Ohashi, Y.; Morita, M.; Endo, M.; Matsugi, M.; Tateishi, H.; Nakamori, R.; Yamashita, Y.; Okabe, M.; Matsuo, M.; Ono, T.; Shigeyama, Y.; Ichiyanagi, M.; Sugimori, K.; Ohmura, C.; Igarashi, M.; Aotsuka, S.; Komoda, N.; Watanabe, M.; Enomoto, Y.; Suzuki, Y.; Kawaguchi, A.; Kasahara, A.; Koide, A.; Sakatani, T.; Kurihara, T.; Yokota, S.; Futagi, R.; Amemiya, Y.; Ono, E.; Maeda, A.; Kadono, K.; Ishiguchi, Y.; Kikuchi, R.; Kuramatsu, M.; Nakamura, E.; Chiba, S.; Higa, A.; Kitahashi, M.; Tanaka, H.; Ito, T.; Oba, M.; Tsubouchi, M.; Toshima, M.; Morishita, M.; Miyano, A.; Kondo, M.; Watanabe, K.; Shibata, R.; Tosaki, Y.; Ito, Y.; Saoda, M.; Yamasaki, E.; Kadosaki, S.; Motooka, S.; Akiyoshi, H.; Morio, S.; Nemoto, H.; Yoshizawa, S.; Okabe, N.; Semba, K.; Yoshida, A.; Lee, Y.; Yoshida, M.; Iwashita, Y.; Takeda, A.; Maezato, M.; Kawahira, K.; Yoshikawa, M.; Okamoto, N.; Nishimura, M.; Matsuura, K.; Fukunaga, M.; Fukai, K.; Osakabe, Y.; Yamamura, K.; Koike, M.; Shibuya, S.; Shiramata, M.; Ono, Y.; Tsujimoto, Y.; Tadokoro, T.; Morishita, N.; Matsuo, Y.; Yumoto, I.; Sakazaki, S.; Atarashi, A.; Nabata, Y.; Okuda, N.; Fujita, A.; Matsuo, A.; Ishizawa, Y.; Shibata, H.; Ootsuka, M.; Taimatsu, R.; Takeuchi, A.; Sumi, Y.; Yamamoto, F.; Araki, Y.; Tanaka, A.; Kuroda, S.; Sakata, R.; Okada, N.; Sawada, Y.; Miyata, M.; Asayama, H.; Koga, N.; Miki, T.; Yamaguchi, N.; Hashimoto, A.; Fukuike, C.; Kubo, A.; Yamasaki, M.; Mori, Y.; Nakayama, S.; Kobayashi, Y.; Takenaka, S.; Mashima, M.; Katsuta, H.; Matsumura, T.; Yanagida, S.; Watanabe, N.; Kodama, S.; Kusano, M.; Yamamoto, N.; Kamada, R.; Suzuki, K.; Itami, K.; Hasebe, Y.; Fujita, N.; Kubota, S.; Usuki, A.; Okamoto, M.; Uno, S.; Chikuma, A.; Kishikawa, H.; Yano K Nakano, C.; Otaguro, M.; Kayashima, Y.; Shinoda, M.; Jaafar, S. M.; Baharuddin, S.; Gembor, J.; Ahmad, H.; Syed Mansor, S. M.; Abdullah, W. M.; Shafie, Z.; Muhamad Yunus, S.; Alwi, S. M.; Hussin, N.; Basri, N. A.; Ling Ling, L.; Naem, N. S.; Rutten, R.; Rademaker, H.; van Buijsen, M.; Scholten, M.; Stuij, S.; van Zeijst, M.; van Houwelingen, K.; Engelen, W.; Kramer, H.; Maassen, E.; Verhoeven, P.; Awater, J.; Terwisscha van Scheltinga, C.; Meijlis, P.; Blom, L.; Bos, M.; van der Wal, M.; van Laerhoven, G.; Jacobs, T.; Tan-Urgert, B.; van de Gaag, J.; den Boer, P.; Verlek, E.; Lardinois, R.; Coenjaerds, C.; Hendrick, R.; Schoep, J.; Froma, E.; van Nes, C.; Beuving, D.; Krikken, J.; Drent, I.; Geerlings, F.; Buvelot, S.; Wissenburg, A.; Dijkshoorn, A.; van Setten van der Meer, L.; Singerling, M.; van Wijk, D.; Bor, A.; Aukema-Wouda, Z.; Hendriks-van Woerden, M.; Kort, I.; Danse, I.; van der Knaap, M.; de Jong, C.; Temminck, M.; Schaefer, T.; van der Ven, N.; Drost, I.; Mulder, R.; de Vos, A.; de Hoop, M.; Post, G.; Wielandt, D.; Edorot, N.; de Castro, K.; Flotildes, M.; Mulingtapang, T.; Vasquez, S.; Facundo, S.; Peralta, M.; Jose, M.; Bandiez, J.; Sulit, P.; Joaquin, F.; Arbis, M. G.; Silva, C.; Delgado, D.; de Leon, R.; Maglasang, P.; Sian, A.; Alagban, C.; Alcorano, J.; Marcelo, M. J.; Dela Pena, C.; Hyra, I.; Malkiewicz, B.; Mosakowska, K.; Cana, I.; Dobrin, I.; Lautaru, A.; Manescu, G.; Samoila, N.; Lacatus, M.; Apostoie, A.; Prunoiu, M.; Tilinca, M.; Budeanu, A.; Nedelcu, C.; Dumitrache, N.; Boeru, L.; Zhuravleva, E.; Gundova, M.; Hoffmannova, J.; Svitkova, M.; Pekarova, T.; Ujacka, K.; Zsoriova, T.; Kubincova, K.; Jankovicova, Z.; Talliard, C.; Tyumbu, N.; Mngoma, N.; Kannemeyer, M.; Mostert, J.; Page, A.; Krahenbuhl, C.; Tredoux, C.; Hendricks, L.; Oliver, S.; Le Grange, M.; Naidoo, V.; Bae, Y.; Kim, H.; Lee, J.; Yu, N.; An, S.; Kim, E.; Yang, K.; Woo, J.; Kim, S.; Rasck, J.; Smetana, S.; Ajax, K.; Bylander, L.; Lindberg, A.; Dellborg, H.; Hultsberg-Olsson, G.; Harsmar, K.; Knutsson, A.; Håkansson, L.; Kåveryd-Holmström, M.; Lundmark, L. M.; Norrfors, B.; Löf, P.; Skoglund, K.; Torgersruud, M.; Johansson, K.; Mattsson, A.; Quist, M.; Haglund, P.; Lundell, L.; Gunvasdotter, S.; Rangman, B.; Liu, R.; Shi, J.; Förstedt, G.; Nylund, L.; Welin-Berger, B.; Nilsson, O.; Garcia-Värlid, A.; Forlenza, R.; Kaminska, K.; Nagorna, T.; Cottam, V.; Harper, R.; Gilchrist, M.; Musanhu, R.; Mackin, A.; Turner, A.; Willetts, S.; Cadd, A.; Evans, J.; Young, G.; Sevillano, A.; Brodie, K.; Eccles, A.; Kelly, S.; Doughty, A.; Gray, J.; Gibson, M.; Finlayson, M.; Domingo, D.; Brazee, L.; Renaud, K.; Doman, A.; Meyer, R.; Beatty, J.; Morgan, T.; Rodas, E.; Campbell, D.; Mcquarrie, M.; Battistelli, E.; Eisenbraun, P.; Farley, R.; Park, H.; Dwyer, J.; Adams, K.; Schneider, W.; Barbour, C.; Whyne, E.; Budzinski, S.; Craig, M.; Gilley Elmore, J.; Scott, D.; Bellini, S.; Pepper, M.; Gunderson, K.; Stipek, I.; Schwarz, L.; Watkins, K.; Moore, V.; Palao, A.; Keane-Richmond, P.; Franklin, L.; Ward, L.; Kostedt, G.; Bailey, S.; Hollenweger, L.; Solomon, A.; Johnson, D.; Gloer, K.; Meyer, M.; Boleyn, M.; Nieters, D.; Humphrey, K.; Bohn, A.; Mueller, G.; Mckenzie, H.; Edwards, T.; Velky, J.; Cole, C.; Diederick, M.; Burg, S.; Coulson, T.; Karunaratne, K.; Gunasekera, R.; Cook, S.; Fisher, S.; Garrison, K.; Passey, L.; Kuykendall, K.; Luck, K.; Ramia, L.; Joan, H.; Reynoso, F.; Farley, M.; Shuman, S.; Santana-Fernandes, E.; Ventimiglia, A.; Steele, V.; Gers, L.; Brown, P.; Wilson, J.; Freebersyser, J.; Reno, M.; Buettner, N.; McGovern, M.; Hubbard, T.; Elmore, H.; Payne, D.; Mccann, M.; Decker, S.; Sharp, A.; Forgey, E.; Broussard, E.; Juett, U.; Siddiqui, A.

    2017-01-01

    We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg

  13. The role of aspirin in women’s health

    Directory of Open Access Journals (Sweden)

    Verheugt FWA

    2011-06-01

    Full Text Available Freek WA Verheugt1, Antoinette C Bolte21Department of Cardiology, Onze Lieve Vrouwe Gasthuis (OLVG, Amsterdam, The Netherlands; 2VU University Medical Center, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Amsterdam, The NetherlandsBackground: The aim of this review is to discuss the role of aspirin for various conditions in women.Methods: A nonsystematic review of articles published on PubMed® that examines the role of aspirin in women.Results: Aspirin is associated with a significant reduction of stroke risk in women, which may be linked to age. However, despite this evidence, underutilization of aspirin in eligible women is reported. In women of reproductive age, it may also have a role to play in reducing early-onset preeclampsia and intrauterine growth restriction, and in the prevention of recurrent miscarriage in women with antiphospholipid antibodies; it may also reduce cardiovascular risk in associated systemic conditions such as lupus. Aspirin may reduce colorectal cancer risk in women, but its role in breast cancer warrants further data from controlled trials.Conclusions: The risk–benefit threshold for aspirin use in women has been established for several conditions. Reasons why women are less likely to be prescribed aspirin have not been established, but the overall underuse of aspirin in women needs to be addressed.Keywords: CVD, cancer, menopause, preeclampsia

  14. Synthesis, characterization and antibacterial activity of aspirin and ...

    African Journals Online (AJOL)

    Dr J. T. Ekanem

    Novel complexes of Co (11), Ni (11) and Fe (111) with aspirin and paracetamol have synthesized and characterized using infrared, electronic and Hnmr spectral, melting point and conductivity measurements. The two ligands have been found to act as bidentate chelating agents. Aspirin complexes coordinate through the ...

  15. Aspirin plus Heparin or Aspirin Alone in Women with Recurrent Miscarriage

    NARCIS (Netherlands)

    Kaandorp, Stef P.; Goddijn, Mariette; van der Post, Joris A. M.; Hutten, Barbara A.; Verhoeve, Harold R.; Hamulyak, Karly; Mol, Ben Willem; Folkeringa, Nienke; Nahuis, Marleen; Papatsonis, Dimitri N. M.; Buller, Harry R.; van der Veen, Fulco; Middeldorp, Saskia

    2010-01-01

    BACKGROUND Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. METHODS In this randomized

  16. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage

    NARCIS (Netherlands)

    Kaandorp, Stef P.; Goddijn, Mariëtte; van der Post, Joris A. M.; Hutten, Barbara A.; Verhoeve, Harold R.; Hamulyák, Karly; Mol, Ben Willem; Folkeringa, Nienke; Nahuis, Marleen; Papatsonis, Dimitri N. M.; Büller, Harry R.; van der Veen, Fulco; Middeldorp, Saskia

    2010-01-01

    Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. In this randomized trial, we enrolled 364

  17. The role of aspirin desensitization in patients with aspirin-exacerbated respiratory disease (AERD).

    Science.gov (United States)

    Spies, Jonas Willian; Valera, Fabiana Cardoso Pereira; Cordeiro, Daniel Loiola; de Mendonça, Taís Nociti; Leite, Marcelo Gonçalves Junqueira; Tamashiro, Edwin; Arruda, Luiza Karla; Anselmo-Lima, Wilma Terezinha

    2016-01-01

    Aspirin-exacerbated respiratory disease (AERD) consists of a classic tetrad: moderate/severe asthma, chronic rhinosinusitis, nasal polyps, and intolerance to aspirin or other nonsteroidal anti-inflammatory drugs. Clinical control with drugs, surgery, and desensitization are treatment options. To evaluate the efficacy and tolerability of aspirin desensitization in patients with AERD. Periodic symptom assessment and endoscopy in patients with AERD undergoing surgery who were desensitized. Seventeen patients were desensitized. Eight patients completed the desensitization and were followed for a minimum of a one-year period (mean 3.1 years). These patients showed improvement in all symptoms. Moreover, surgical reassessment was not indicated in any of these patients and there was a decrease in costs with medication and procedures. Eight patients did not complete desensitization, mainly due to procedure intolerance and uncontrolled asthma, whereas another patient was lost to follow-up. Aspirin desensitization, when tolerated, was effective in patients with AERD and with poor clinical/surgical response. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  18. Aspirin as a Chemopreventive Agent for Cancer: a New Hope?

    Directory of Open Access Journals (Sweden)

    Isnatin Miladiyah

    2016-01-01

    Full Text Available Introduction: inflammation has been shown to play a major role in the pathogenesis of cancer. Inflammatory process activates the immune system through pro-inflammatory mediators and subsequent triggers transformation into malignant cells. Some tumors or cancers has been associated with chronic infections, such as hepatitis B and C viruses (hepatocellular carcinoma, human papilloma virus (cervical cancer, Helicobacter pylori (gastric cancer and lymphoma, and prostatitis (prostate cancer. A considerable study have investigated the benefits of aspirin for the prevention and treatment of cancer or tumors. Objectives: This paper aims to describe the relationship between inflammation and cancer incidence, so that use of aspirin as an anti-inflammatory agent is a rational choice in the treatment and prevention of cancer. Conclusion: Aspirin potential for chemoprevention of various types of cancer. Considering the high risk of side effects of aspirin, aspirin is not intended as a routine therapy to prevent the occurrence of cancer.

  19. Monitoring aspirin therapy with the Platelet Function Analyzer-100

    DEFF Research Database (Denmark)

    Mortensen, Jette; Poulsen, Tina Svenstrup; Grove, Erik Lerkevang

    2008-01-01

    . The Platelet Function Analyzer-100 (PFA-100) is a commonly used platelet function test. We aimed to assess the reproducibility of the PFA-100 and the agreement with optical platelet aggregometry (OPA) in healthy volunteers and in patients with coronary artery disease (CAD) treated with low-dose aspirin....... MATERIAL AND METHODS: Twenty-one healthy volunteers and 43 patients with CAD took part in the study. During treatment with aspirin 75 mg daily, all participants had platelet function assessed in duplicate with the PFA-100 and OPA on 4 consecutive days. Additionally, platelet function was assessed before...... aspirin treatment in healthy subjects. Serum-thromboxane B(2) (S-TxB(2)) was measured to assess compliance. RESULTS: In healthy volunteers not receiving aspirin, duplicate measurements resulted in coefficients of variation (CV) of 7.9 % for the PFA-100 and 5.2 % for OPA. During aspirin treatment, CVs were...

  20. Aspirin decreases platelet uptake on Dacron vascular grafts in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Mackey, W.C.; Connolly, R.J.; Callow, A.D.; Keough, E.M.; Ramberg-Laskaris, K.; McCullough, J.L.; O' Donnell, T.F. Jr.; Melaragno, A.; Valeri, C.R.; Weiblen, B.

    1984-07-01

    The influence of a single dose of aspirin (5.4-7.4 mg/kg) on platelet uptake on 4-mm Dacron interposition grafts was studied in a baboon model using gamma camera scanning for 111-Indium labeled platelets. In vitro assessment of platelet function after aspirin administration revealed that in the baboon, as in the human, aspirin abolished arachidonic acid-induced platelet aggregation, prolonged the lag time between exposure to collagen and aggregation, and decreased plasma thromboxane B2 levels. Aspirin also prolonged the template bleeding time. Scans for 111-Indium labeled platelets revealed that pretreatment with a single dose of aspirin decreased platelet uptake on 4-mm Dacron carotid interposition grafts. This decrease in platelet uptake was associated with a significant improvement in 2-hour graft patency and with a trend toward improved 2-week patency.

  1. Is aspirin a cause of Reye's syndrome? A case against.

    Science.gov (United States)

    Orlowski, James P; Hanhan, Usama A; Fiallos, Mariano R

    2002-01-01

    Reye's syndrome was a rare disease which appeared suddenly in the early 1950s and disappeared just as suddenly in the late 1980s. An association between Reye's syndrome and the ingestion of aspirin (acetylsalicylic acid) was claimed, although no proof of causation was ever established. The presence of salicylates in the blood or urine of Reye's syndrome patients has not been demonstrated, and no animal model of Reye's syndrome has been developed where aspirin causes the disease. It is clear from epidemiological data that the incidence of Reye's syndrome was decreasing well before warning labels were placed on aspirin products. Reye's syndrome disappeared from countries where aspirin was not used in children as well as from countries which continued to use aspirin in children. Reye's syndrome was probably either a viral mutation which spontaneously disappeared, or a conglomeration of metabolic disorders that had not been recognized or described at that time.

  2. Willow species and aspirin: different mechanism of actions.

    Science.gov (United States)

    Vlachojannis, J; Magora, F; Chrubasik, S

    2011-07-01

    Many believe that willow is the natural source of aspirin. However, willow species contain only a low quantity of the prodrug salicin which is metabolized during absorption into various salicylate derivatives. If calculated as salicylic acid, the daily salicin dose is insufficient to produce analgesia. Salicylic acid concentrations following an analgesic dose of aspirin are an order of magnitude higher. Flavonoids and polyphenols contribute to the potent willow bark analgesic and anti-inflammatory effect. The multi-component active principle of willow bark provides a broader mechanism of action than aspirin and is devoid of serious adverse events. In contrast to synthetic aspirin, willow bark does not damage the gastrointestinal mucosa. An extract dose with 240 mg salicin had no major impact on blood clotting. In patients with known aspirin allergy willow bark products are contraindicated. Copyright © 2011 John Wiley & Sons, Ltd.

  3. Aspirin inhibits formation of cholesterol rafts in fluid lipid membranes.

    Science.gov (United States)

    Alsop, Richard J; Toppozini, Laura; Marquardt, Drew; Kučerka, Norbert; Harroun, Thad A; Rheinstädter, Maikel C

    2015-03-01

    Aspirin and other non-steroidal anti-inflammatory drugs have a high affinity for phospholipid membranes, altering their structure and biophysical properties. Aspirin has been shown to partition into the lipid head groups, thereby increasing membrane fluidity. Cholesterol is another well known mediator of membrane fluidity, in turn increasing membrane stiffness. As well, cholesterol is believed to distribute unevenly within lipid membranes leading to the formation of lipid rafts or plaques. In many studies, aspirin has increased positive outcomes for patients with high cholesterol. We are interested if these effects may be, at least partially, the result of a non-specific interaction between aspirin and cholesterol in lipid membranes. We have studied the effect of aspirin on the organization of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) membranes containing cholesterol. Through Langmuir-Blodgett experiments we show that aspirin increases the area per lipid and decreases compressibility at 32.5 mol% cholesterol, leading to a significant increase of fluidity of the membranes. Differential scanning calorimetry provides evidence for the formation of meta-stable structures in the presence of aspirin. The molecular organization of lipids, cholesterol and aspirin was studied using neutron diffraction. While the formation of rafts has been reported in binary DPPC/cholesterol membranes, aspirin was found to locally disrupt membrane organization and lead to the frustration of raft formation. Our results suggest that aspirin is able to directly oppose the formation of cholesterol structures through non-specific interactions with lipid membranes. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

    Science.gov (United States)

    Chan, Andrew T.; Arber, Nadir; Burn, John; Chia, John Whay-Kuang; Elwood, Peter; Hull, Mark A.; Logan, Richard F.; Rothwell, Peter M.; Schrör, Karsten; Baron, John A.

    2011-01-01

    Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term post-trial follow-up of nearly 14,000 patients from 4 randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about 5 years was associated with a 34% reduction in 20-year CRC mortality. A separate meta-analysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in 4 randomized adenoma prevention trials demonstrated that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least 2 years, there was a ≥ 50% reduction in the risk of CRC commencing 5 years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin’s anticancer effect require further investigation. PMID:22084361

  5. Prevention of dipyrone (metamizole) induced inhibition of aspirin antiplatelet effects.

    Science.gov (United States)

    Polzin, Amin; Richter, Stefan; Schrör, Karsten; Rassaf, Tienush; Merx, Marc W; Kelm, Malte; Hohlfeld, Thomas; Zeus, Tobias

    2015-07-01

    We have recently shown that dipyrone (metamizole), a non-opioid analgesic, can nullify aspirin (acetylsalicylic acid; ASA) antiplatelet effects in patients with coronary artery disease (CAD). In this study, we analysed the aspirin and dipyrone drug-drug interaction in order to identify strategies to prevent the dipyrone induced inhibition of asprin antiplatelet effects. Platelet function was measured by arachidonic acid-induced light-transmission aggregometry, thromboxane (TX) B2- formation by immunoassay. Dipyrone metabolite plasma levels were determined by high-performance-liquid-chromatography (HPLC). In seven healthy individuals, in vitro ASA (30 µM/ 100 µM/ 300 µM/ 1,000 µM) and dipyrone (10 µM) coincubation revealed, that the aspirin and dipyrone interaction can be overcome by increasing doses of aspirin. In 36 aspirin and dipyrone comedicated CAD patients, addition of ASA (30 µM/ 100 µM) in vitro inhibited, but did not completely overcome the dipyrone induced reduction of aspirin antiplatelet effects. Notably, the inhibition of thromboxane formation in aspirin and dipyrone comedicated CAD patients coincided with dipyrone plasma levels. In a cross-over designed study in four healthy individuals, we were able to prove that inhibition of aspirin (100 mg/ day) effects by dipyrone (750 mg/ day) was reversible. Furthermore, aspirin (100 mg/ day) medication prior to dipyrone (750 mg/ day) intake prevented the inhibition of antiplatelet effects by dipyrone in 12 healthy individuals. In conclusion, aspirin medication prior to dipyrone intake preserves antiplatelet effects, circumventing the pharmacodynamic drug-drug interaction at the level of cyclooxygenase-1.

  6. Aspirin: History and Applications; Cross-Curricular Instructional Strategies, Ideas, and Applications for Teaching about Aspirin in the Science Classroom

    Science.gov (United States)

    Hademenos, George

    2005-01-01

    Of the thousands of drugs and medicines available for the prevention, treatment, and control of human disease and discomfort, the most widely used is aspirin. The primary reason for aspirin's popularity is its capabilities as a pain reliever, fever reducer, and anti-inflammatory agent. This article explores the historical development of aspirin…

  7. Controlled delivery of aspirin: effect of aspirin on polymer degradation and in vitro release from PLGA based phase sensitive systems.

    Science.gov (United States)

    Tang, Yu; Singh, Jagdish

    2008-06-05

    The objective of this study was to develop poly (d,l-lactide-co-glycolide) (PLGA) based injectable phase sensitive in situ gel forming delivery system for controlled delivery of aspirin, and to characterize the effect of drug/polymer interaction on the in vitro release of aspirin and polymer degradation. Aspirin was dissolved into PLGA solution in 1-methyl-2-pyrrolidone. Poly(ethylene glycol)400 was used as plasticizer to reduce initial burst release. The solution formulation was injected into aqueous release medium to form a gel depot. Released samples were withdrawn periodically and assayed for aspirin content by high performance liquid chromatography. The effect of aspirin on the degradation of PLGA matrix was evaluated using Proton Nuclear Magnetic Resonance and Gel Permeation Chromatography. PLGA based in situ gel forming formulations controlled the in vitro release of aspirin for 7 days only. Analysis of PLGA matrix residuals revealed that PLGA in aspirin loaded formulations exhibited a significantly (pdegradation compared to blank formulations. These findings suggest that aspirin causes an unusually faster degradation of PLGA. Such faster degradation of PLGA has not been noticed for any other drugs reported in the literature.

  8. Comparative effect of clopidogrel and aspirin versus aspirin alone on laboratory parameters: a retrospective, observational, cohort study

    Science.gov (United States)

    2013-01-01

    Background Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Combination therapy of clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in patients in routine clinical practice. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters using a clinical database. Methods We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between November 2004 and April 2011, to identify cohorts of new users (n = 159) of clopidogrel (75 mg/day) plus aspirin (100 mg/day) and new users (n = 834) of aspirin alone (100 mg/day). We used a multivariable regression model and regression adjustment with the propensity score to adjust for differences in baseline covariates between settings, and compare the mean changes in serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase and hematological parameters, including hemoglobin level, hematocrit, and white blood cell (WBC), red blood cell and platelet counts up to two months after the start of study drug administration. Results After adjustment, the reduction of WBC count in clopidogrel plus aspirin users was significantly greater than that in aspirin alone users. All other tests showed no statistically significant difference in the mean change from baseline to during the exposure period between clopidogrel plus aspirin users and aspirin alone users. The combination of clopidogrel and aspirin increased the risk of gastrointestinal bleeding compared with aspirin alone, with a relative risk ranging from 2.06 (95% CI, 1.02 to 4.13; p = 0.043) for the multivariate model and 2.61 (95% CI, 1.18 to 5.80; p = 0.0184) for propensity adjustment. Conclusion Our findings suggested that

  9. Genetics of hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Kim, Seung-Hyun; Sanak, Marek; Park, Hae-Sim

    2013-05-01

    Various hypersensitivity reactions have been reported with aspirin and nonsteroidal anti-inflammatory drugs. Hypersensitivity can occur regardless of a chemical drug structure or its therapeutic potency. Allergic conditions include aspirin-exacerbated respiratory disease (AERD or aspirin-induced asthma), aspirin-induced urticaria/angioedema (AIU), and anaphylaxis. Several genetic studies on aspirin hypersensitivity have been performed to discover the genetic predisposition to aspirin hypersensitivity and to gain insight into the phenotypic diversity. This article updates data on the genetic mechanisms that govern AERD and AIU and summarizes recent findings on the molecular genetic mechanism of aspirin hypersensitivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Effect of aspirin desensitization on T-cell cytokines and plasma lipoxins in aspirin-exacerbated respiratory disease.

    Science.gov (United States)

    Aksu, Kurtuluş; Kurt, Emel; Alatas, Özkan; Gülbas, Zafer

    2014-01-01

    The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is thought to be based on, mainly, overproduction of eicosanoid lipid mediators and on defective anti-inflammatory regulators. Aspirin desensitization treatment, the mainstay of controlling asthma and rhinitis in AERD patients, however, is the least understood aspect of the disease. The study was designed to determine the effect of aspirin desensitization on T-lymphocyte cytokine expression and on plasma lipoxin levels in AERD. Spirometry, skin-prick test and asthma control test were documented and intracellular cytokine expression in T lymphocytes and plasma lipoxin levels were measured in 23 AERD patients, 17 aspirin-tolerant asthmatic (ATA) patients, and 16 healthy controls. In the AERD group nasal symptom and smell scores were assessed. Of the 23 AERD patients 15 accepted to undergo aspirin desensitization protocol and 14 of them were desensitized successfully. In the desensitized AERD group, cytokine and lipoxin measurements were repeated after 1-month aspirin treatment. CD4(+) IL-10 levels were higher in AERD patients than in healthy controls and CD4(+) interferon (IFN) gamma levels were higher in AERD and ATA patients than in controls. Plasma lipoxin-A4 and 15-epi-lipoxin-A4 levels were similar among the three study groups. In the AERD group, subjects underwent aspirin desensitization followed by a 1-month aspirin treatment. Clinical parameters improved and CD4(+) IFN-gamma levels decreased significantly. No significant change in lipoxin levels was recorded. CD4(+) IFN-gamma and CD4(+) IL-10 levels in AERD patients after 1-month aspirin desensitization treatment were similar to the healthy controls. The study confirms aspirin desensitization is effective clinically in AERD patients and suggests that IFN gamma and IL-10 expression in CD4(+) T lymphocytes may be related to the mechanism of action.

  11. [Aspirin hypersensitivity: characteristics and diagnostic approach].

    Science.gov (United States)

    Baudrand, H; Zaouche, S; Dubost, R; Carsin, A; Chatte, G; Freymond, N; Piperno, D; Dubreuil, C; Froehlich, P; Pacheco, Y; Devouassoux, G

    2015-03-01

    In routine medical practice, the diagnosis of aspirin hypersensitivity (AH) remains difficult. No clinical feature or biomarker is available to reliably confirm this diagnosis and oral provocation tests (OPT) are rarely performed. To compare asthmatics with and without AH. The clinical characteristics of 21 asthmatics with and 24 without AH respectively were determined. AH was defined by a positive OPT. A full blood count was done before and 24 hours after the OPT. The medical history was associated with a weak sensitivity (52%) and a good specificity (96%) for assessing the diagnosis of AH. There was a higher prevalence of AH in women, and a higher frequency of allergic rhinitis in AH, but no characteristic was useful to facilitate the diagnosis of AH in asthmatic patients. Our results demonstrate higher values of platelets in AH patients. Following OPT, in AH patients only, a decrease in blood eosinophils and an increase in neutrophils was observed. These results confirm that the diagnosis of AH is challenging, with the history having only weak sensitivity. The observation that fluctuations in eosinophils and neutrophils occur following OPT in AH patients only warrants further investigations and suggests a rapid pro-inflammatory role for aspirin. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  12. Lipoxin and Aspirin-Triggered Lipoxins

    Directory of Open Access Journals (Sweden)

    Mario Romano

    2010-01-01

    Full Text Available Lipoxins and their 15 epimers, aspirin triggered lipoxins (ATL, are eicosanoids derived from sequential lipoxygenase (LO metabolism of arachidonic acid. The main routes of lipoxin biosynthesis involve cooperation between 15- and 5-LO, and between 12- and 5-LO. ATL are generated by interactions between 5-LO and aspirin-acetylated cyclooxygenase-2. Cellular models recapitulating these interactions involve leukocytes, platelets, vascular endothelium, and epithelium. To circumvent rapid lipoxin and ATL metabolism and inactivation, stable analogs, bearing potent and long-lasting biological activity, have been synthesized. Some of these analogs displayed therapeutic potential by showing strong anti-inflammatory activity in a number of animal models of disease, including reperfusion injury; arthritis; gastrointestinal, renal, respiratory, and vascular inflammatory disorders; eye damage; periodontitis; and selected infectious diseases. Counter-regulatory signaling by lipoxin A4 and 15-epi-lipoxin A4 is triggered by the activation of a seven-transmembrane domain receptor, termed FPR2/ALX, which is highly expressed in myeloid cells and has been recognized as a main anti-inflammatory receptor.

  13. Beclin 1 acetylation impairs the anticancer effect of aspirin in colorectal cancer cells

    OpenAIRE

    Sun, Ting; Ming, Liang; Yan, Yunmeng; Zhang, Yan; Xue, Haikuo

    2017-01-01

    Regular use of aspirin can reduce cancer incidence, recurrence, metastasis and cancer-related mortality. Aspirin suppresses proliferation and induces apoptosis and autophagy in colorectal cancer cells, but the precise mechanism is not clear. In this study, we demonstrated that aspirin induced autophagosome formation in colorectal cancer cells, but autophagic degradation was blocked through aspirin-mediated Beclin 1 acetylation. Blocked autophagic degradation weakened aspirin-induced cell deat...

  14. Mechanistic insights into a classic wonder drug--aspirin.

    Science.gov (United States)

    Lei, Jinping; Zhou, Yanzi; Xie, Daiqian; Zhang, Yingkai

    2015-01-14

    Aspirin, one of the oldest and most common anti-inflammatory agents, has recently been shown to reduce cancer risks. The principal pharmacological effects of aspirin are known to arise from its covalent modification of cyclooxygenase-2 (COX-2) through acetylation of Ser530, but the detailed mechanism of its biochemical action and specificity remains to be elucidated. In this work, we have filled this gap by employing a state-of-the-art computational approach, Born-Oppenheimer molecular dynamics simulations with ab initio quantum mechanical/molecular mechanical potential and umbrella sampling. Our studies have characterized a substrate-assisted inhibition mechanism for aspirin acetylating COX: it proceeds in two successive stages with a metastable tetrahedral intermediate, in which the carboxyl group of aspirin serves as the general base. The computational results confirmed that aspirin would be 10-100 times more potent against COX-1 than against COX-2, and revealed that this inhibition specificity between the two COX isoforms can be attributed mainly to the difference in kinetics rate of the covalent inhibition reaction, not the aspirin-binding step. The structural origin of this differential inhibition of the COX enzymes by aspirin has also been elucidated.

  15. Mode of action of aspirin as a chemopreventive agent.

    Science.gov (United States)

    Dovizio, Melania; Bruno, Annalisa; Tacconelli, Stefania; Patrignani, Paola

    2013-01-01

    Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer. The finding of aspirin benefit at low-doses given once daily, used for cardioprevention, locates the antiplatelet effect of aspirin at the center of its antitumor efficacy. In fact, at low-doses, aspirin acts mainly by an irreversible inactivation of platelet cyclooxygenase (COX)-1 in the presystemic circulation, which translates into a long-lasting inhibition of platelet function. Given the short half-life of aspirin in the human circulation(approximately 20 min) and the capacity of nucleated cells to resynthesize the acetylated COX-isozyme(s), it seems unlikely that a nucleated cell could be the target of aspirin chemoprevention. These findings convincingly suggest that colorectal cancer and atherothrombosis may share a common mechanism of disease, i.e. platelet activation in response to epithelial(in tumorigenesis) and endothelial(in tumorigenesis and atherothrombosis) injury. Activated platelets may also enhance the metastatic potential of cancer cells (through a direct interaction and/or the release of soluble mediators or exosomes) at least in part by inducing the overexpression of COX-2. COX-independent mechanisms of aspirin, such as the inhibition of NF-kB signaling and Wnt/β-catenin signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemopreventive effects. However, their relevance remains to be demonstrated in vivo at clinical doses.

  16. Aspirin and clonidine in non-cardiac surgery

    DEFF Research Database (Denmark)

    Garg, Amit; Kurz, Andrea; Sessler, Daniel I

    2014-01-01

    INTRODUCTION: Perioperative Ischaemic Evaluation-2 (POISE-2) is an international 2×2 factorial randomised controlled trial of low-dose aspirin versus placebo and low-dose clonidine versus placebo in patients who undergo non-cardiac surgery. Perioperative aspirin (and possibly clonidine) may reduce...... and preoperative chronic aspirin use. At the time of randomisation, a subpopulation agreed to a single measurement of serum creatinine between 3 and 12 months after surgery, and the authors will examine intervention effects on this outcome. ETHICS AND DISSEMINATION: The authors were competitively awarded a grant...

  17. Comparative effects of aspirin and enteric-coated aspirin on loss of chromium 51-labeled erythrocytes from the gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Robbins, D.C.; Schwartz, R.S.; Kutny, K.; Vallejo, G.; Horton, E.S.; Cotter, J.M.

    1984-01-01

    Sodium chromate Cr 51 was used to label red blood cells of 19 healthy male volunteers, whose stools were collected for four days before and four days during oral administration of either uncoated (N . 9) or enteric-coated (N . 10) aspirin. Each subject received 2.925 gm/day of aspirin, in three equal doses separated by eight-hour intervals, for a total of seven days. During drug use, stools were collected on days 4 through 7. Fecal blood content, estimated by measuring radioactivity in the stools, was significantly higher (P less than 0.001) during use of either type of aspirin than at baseline, but losses measured during use of the coated aspirin (mean, 1.54 ml/day) were significantly lower (P less than 0.001) than those measured during use of the uncoated aspirin (mean, 4.33 ml/day). The two types of aspirin produced equivalent serum concentrations of salicylates. We conclude that enteric-coated aspirin reduces gastrointestinal blood loss.

  18. Safety and outcomes of aspirin desensitization for aspirin-exacerbated respiratory disease: A single-center study.

    Science.gov (United States)

    Waldram, Jeremy; Walters, Kristen; Simon, Ronald; Woessner, Katherine; Waalen, Jill; White, Andrew

    2018-01-01

    Aspirin desensitization is an effective treatment option for aspirin-exacerbated respiratory disease. Aspirin desensitization protocol modifications have improved the safety and efficiency of this procedure, yet some providers remain reluctant to perform it. The primary objective of this study was to evaluate the safety and outcomes of outpatient aspirin desensitization procedures. A secondary objective was to assess clinical characteristics that might predict reaction severity during aspirin desensitization. Two hundred seventy-five patients underwent aspirin desensitization at Scripps Clinic between January 2009 and August 2015. Baseline patient characteristics and reaction results were analyzed in the 167 patients who reacted during desensitization. All of the 167 reactors, including 23 who were classified as severe reactors, were successfully desensitized in the outpatient setting. The average desensitization duration among reactors was 1.67 days, and the average duration for gastrointestinal reactors was 2.29 days. The mean baseline Sino-Nasal Outcome Test score was higher in severe reactors compared with nonsevere reactors (P = .05). Overall, patients receiving omalizumab had a similar reaction profile to those not receiving omalizumab. Most patients undergoing aspirin desensitization will have symptoms. It remains difficult to predict the severity of these symptoms. However, desensitization can be done safely and efficiently in an appropriately equipped outpatient setting. This treatment option should be made available to all patients with aspirin-exacerbated respiratory disease. The Sino-Nasal Outcome Test score might be able to predict more severe reactions and merits further study. Eight of the 9 patients receiving omalizumab reacted during desensitization, suggesting that it does not block reactions during aspirin desensitization. Published by Elsevier Inc.

  19. Aspirin as a chemoprevention agent for colorectal cancer.

    LENUS (Irish Health Repository)

    Lee, Chun Seng

    2012-11-01

    Colorectal cancer (CRC) is one of the leading causes of mortality in the western world. It is widely accepted that neoplasms such as colonic polyps are precursors to CRC formation; with the polyp-adenoma-carcinoma sequences well described in medical literature [1, 2]. It has been shown that Aspirin and other non-steroid anti-inflammatory drugs (NSAID) have a negative effect on polyp and cancer formation. This review aims to describe some of the mechanism behind the chemoprotective properties of aspirin; COX 2 inhibition, regulation of proliferation and apoptosis and effects on the immune system and also the current evidence that supports its use as a chemoprevention agent against CRC. We will also aim to explore the side effects with the use of aspirin and the pitfalls of using aspirin routinely for primary prophylaxis against CRC.

  20. The Role of Platelet and its Interaction with Aspirin

    Directory of Open Access Journals (Sweden)

    Luisa Fernanda Zúñiga Cerón

    2016-04-01

    Conclusion. It is recognized the role of platelet in different physiopathological processes and thus its interaction with aspirin, preventing its aggregation and thrombus formation in the spleen and other organs, this way contributing to the prevention of future cardiovascular events.

  1. Perioperative aspirin and clonidine and risk of acute kidney injury

    DEFF Research Database (Denmark)

    Garg, Amit X; Kurz, Andrea; Sessler, Daniel I

    2014-01-01

    IMPORTANCE: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain...... and each intervention has the potential for harm. OBJECTIVE: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: A 2 × 2 factorial randomized, blinded, clinical trial of 6905...... patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. INTERVENTIONS: Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days...

  2. Using the Platelet Function Analyzer-100 for monitoring aspirin therapy

    DEFF Research Database (Denmark)

    Poulsen, Tina Svenstrup; Mickley, Hans; Korsholm, Lars

    2007-01-01

    INTRODUCTION: The aim of the study was to evaluate the test characteristics of the Platelet Function Analyzer-100 (PFA-100) in patients treated with aspirin. METHODS AND RESULTS: The study consisted of two sub-studies. In study 1, 10 patients with ischemic heart disease (IHD) and 10 controls had...... platelet function assessed by optical platelet aggregation and the PFA-100 method in two 5-week periods. Patients with IHD were treated with aspirin 150 mg/day (first 5-week period), and 300 mg/day (second 5-week period), whereas the controls only received aspirin (150 mg/day) during the second 5-week...... period. From the results of study 1, we found that a cut-off value for the PFA-100 collagen/epinephrine cartridge aspirin (sensitivity 0.91, specificity 1.00). A good agreement between the PFA-100 method and optical platelet aggregation was found. Within...

  3. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

    DEFF Research Database (Denmark)

    Weitz, Jeffrey I; Lensing, Anthonie W A; Prins, Martin H

    2017-01-01

    BACKGROUND: Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin. METHODS: In this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous...... thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months...... in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio...

  4. Can an Aspirin a Day Keep a Pregnancy Complication Away?

    Science.gov (United States)

    ... html Can an Aspirin a Day Keep a Pregnancy Complication Away? Odds of preeclampsia dropped 62 percent for ... suggests. "Preeclampsia is one of the most serious complications of pregnancy, with a high risk of death for the ...

  5. Aspirin Prophylaxis for the Prevention of Thrombosis: Expectations and Limitations

    Directory of Open Access Journals (Sweden)

    Gundu H. R. Rao

    2012-01-01

    Full Text Available Platelets play a very important role in the pathogenesis of acute vascular events leading to thrombosis of the coronary and cerebral arteries. Blockage of these arteries leading to regional ischemia of heart and brain tissues precipitate heart attacks and stroke. Acetyl salicylic acid (Aspirin has been the drug of choice for over half a century for the primary and secondary prophylaxis of thrombotic events. In spite of its extensive use as an antiplatelet drug for the prevention of vascular thrombosis, there is considerable concern about the degree of protection it offers, to patients under aspirin therapy. In this paper, we explain the phenomenon of aspirin resistance, discuss the limitations of aspirin therapy, and suggest methods to monitor “at-risk” individuals. Ability to monitor and determine at risk patients will provide opportunities for the clinicians to customize antiplatelet therapies.

  6. Aspirin resistance: Prevalence and clinical outcome in Egypt

    Directory of Open Access Journals (Sweden)

    Ahmed Salah

    2015-04-01

    Results: Prevalence of aspirin resistance was 48% in our study group. Aspirin resistance was significantly higher in patients with family history of CAD (p = 0.044, smoking (p = 0.011, history of MI (p = 0.024, history of percutaneous coronary intervention (PCI (p = 0.001, and concomitant NSAIDs intake (p = 0.047. Moreover, aspirin resistance was more common among patients with multi-vessel CAD (p = 0.024. Aspirin-resistant patients had a significantly higher rate of UA (p = 0.001 and all major adverse cardiac events (MACE (p < 0.001.

  7. [Study of aspirin and its interaction with DNA by Raman and UV spectroscopies].

    Science.gov (United States)

    Kang, Qian-qian; Zhou, Guang-ming

    2012-03-01

    Normal Raman spectroscopy and surface-enhanced Raman spectroscopy of aspirin and aspirin tablet were reported, and the vibrational and enhanced peaks were assigned; the interaction of aspirin with DNA was investigated by SERS and UV. The results showed that NRS and SERS of aspirin and aspirin tablet were consistent basically, which indicated that excipient hardly affected the detection of aspirin; in SERS, aspirin was absorbed perpendicularly on silver colloid through the carboxyl group and the benzene ring; The interaction was mainly caused by the inserting-action mode between aspirin and DNA, and the benzene ring and C=O of aspirin were inserted between the base pair of the double helix structure of DNA, which provided important information and useful reference for understanding deeply the mechanism of action of this kind of drug.

  8. Novel Resveratrol-Based Aspirin Prodrugs: Synthesis, Metabolism, and Anticancer Activity.

    Science.gov (United States)

    Zhu, Yingdong; Fu, Junsheng; Shurlknight, Kelly L; Soroka, Dominique N; Hu, Yuhui; Chen, Xiaoxin; Sang, Shengmin

    2015-08-27

    Regular aspirin use has been convincingly shown to reduce the risk of colorectal cancer. However, long-term use of aspirin leads to gastrotoxicity. Herein, we designed and synthesized a novel class of resveratrol-based aspirin prodrugs to simultaneously release aspirin and resveratrol to attenuate the side effects caused by aspirin. Prodrug RAH exerted enhanced anticancer activities which are better than a physical mixture of aspirin and resveratrol as well as each individually. Metabolism of RAH in mice showed that the majority of RAH is decomposed to release resveratrol and aspirin or salicylic acid either in the intestine or after absorption. Mechanistic studies demonstrate RAH inhibits cell cycle arrest through downregulation of cyclins and induces apoptosis by activation of caspase-3 in cancer cells. These findings highlighted the improved anticancer properties of resveratrol-based aspirin prodrugs. RAH may represent novel and safe alternatives of aspirin for the purpose of daily use in the future.

  9. Antiplatelet effects of aspirin in chronic kidney disease patients.

    Science.gov (United States)

    Polzin, A; Dannenberg, L; Sansone, R; Levkau, B; Kelm, M; Hohlfeld, T; Zeus, T

    2016-02-01

    ESSENTIALS: Chronic kidney disease (CKD) patients have a high risk of cardiovascular events. A pharmacodynamic evaluation of the effects of aspirin in 116 patients was carried out. The antiplatelet effects of aspirin are associated with impaired renal function. The optimal antithrombotic regimen in CKD patients must be investigated on a larger scale. The pharmacodynamic response to aspirin varies significantly between individuals. Insufficient antiplatelet effects of aspirin are associated with increased risk of ischemic events. Chronic kidney disease (CKD) is suggested to affect the pharmacodynamic response to antiplatelet medication. High on-treatment platelet reactivity (HTPR) to clopidogrel has been reported to partially account for the enhanced risk of death and cardiovascular events in CKD patients. Objective To investigate the antiplatelet effects of aspirin in patients with CKD. We conducted a cross-sectional study in 116 patients on permanent aspirin medication. The pharmacodynamic response to aspirin was determined by arachidonic acid-induced thromboxane formation. HTPR to aspirin was more frequent in patients with impaired renal function (47% vs. 22%; odds ratio, 3.16; 95% confidence interval [CI], 1.34-7.41; P = 0.008). The pharmacodynamic response to aspirin was impaired in patients with moderate/severe CKD (92; interquartile range [IQR], 282 ng mL(-1) ) as compared to patients with normal/mildly reduced renal function (36; IQR, 100 ng mL(-1) ; difference in medians, 57; CI, 5-110 ng mL(-1) ; P = 0.013). Bivariate Pearson analysis showed residual thromboxane formation to be correlated with glomerular filtration rate (R = -0.303; R(2) = 0.092; P = 0.001). Patients with CKD were older and more frequently female. Multivariate linear regression analysis revealed that the correlation was independent of age (R = -0.314; R(2) = 0.082; P = 0.002) and gender (R = -0.305; R(2) = 0.077; P = 0.006). Renal function is correlated with pharmacodynamic response to

  10. Drug Resistance and Pseudoresistance: An Unintended Consequence of Enteric Coating Aspirin

    Science.gov (United States)

    Grosser, Tilo; Fries, Susanne; Lawson, John A.; Kapoor, Shiv C.; Grant, Gregory R.; FitzGerald, Garret A.

    2013-01-01

    Background Low dose aspirin reduces the secondary incidence of myocardial infarction and stroke. Drug resistance to aspirin might result in treatment failure. Despite this concern, no clear definition of “aspirin resistance” has emerged and estimates of its incidence have varied remarkably. We aimed to determine the commonality of a mechanistically consistent, stable and specific phenotype of true pharmacological resistance to aspirin – such as might be explained by genetic causes. Methods and Results Healthy volunteers (n=400) were screened for their response to a single oral dose of 325 mg immediate release or enteric coated aspirin. Response parameters reflected the activity of aspirin's molecular target, cyclooxygenase-1. Individuals who appeared “aspirin resistant” on one occasion underwent repeat testing and if still “resistant” were exposed to low dose enteric coated aspirin (81 mg) and clopidogrel (75 mg) for one week each. Variable absorption caused a high frequency of apparent resistance to a single dose of 325 mg enteric coated aspirin (up to 49%) but not to immediate release aspirin (0%). All individuals responded to aspirin upon repeated exposure, extension of the post dosing interval or addition of aspirin to their platelets ex vivo. Conclusions Pharmacological resistance to aspirin is rare; this study failed to identify a single case of true drug resistance. Pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration. Clinical Trial Registration Information clinicaltrials.gov. Identifier: NCT00948987. PMID:23212718

  11. 'Aspirin resistance' or treatment non-compliance: Which is to blame for cardiovascular complications?

    Directory of Open Access Journals (Sweden)

    Shantsila Eduard

    2008-08-01

    Full Text Available Abstract Aspirin is one of the 'cornerstone' drugs in our current management of cardiovascular disorders. However, despite the prescription of aspirin recurrent vascular events still occur in 10–20% of patients. These, data together with the observations of diminished antiaggregatory response to aspirin in some subjects have provided the basis of the current debate on the existence of so-called "aspirin resistance". Unfortunately, many of the tests employed to define 'aspirin resistance' lack sufficient sensitivity, specificity, and reproducibility. The prevalence of 'aspirin resistance' as defined by each test varies widely, and furthermore, the value of a single point estimate measure of aspirin resistance is questionable. The rate of 'aspirin resistance' is law if patients observed to ingest aspirin, with large proportion of patients to be pseudo-'aspirin resistant', due to non-compliance. What are the implications for clinical practice? Possible non-adherence to aspirin prescription should also be carefully considered before changing to higher aspirin doses, other antiplatelet drugs (e.g. clopidogrel or even combination antiplatelet drug therapy. Given the multifactorial nature of atherothrombotic disease, it is not surprising that only about 25% of all cardiovascular complications can usually be prevented by any single medication. We would advocate against routine testing of platelet sensitivity to aspirin (as an attempt to look for 'aspirin resistance' but rather, to highlight the importance of clinicians and public attention to the problem of treatment non-compliance.

  12. Aspirin for primary prevention of cardiovascular disease in diabetes mellitus

    OpenAIRE

    Pignone, Michael; Williams, Craig D.

    2010-01-01

    Aspirin is effective for the prevention of cardiovascular events in patients with a history of vascular disease, as so-called secondary prevention. In general populations with no history of previous myocardial infarction or stroke, aspirin also seems useful for primary prevention of cardiovascular events, although the absolute benefits are smaller than those seen in patients with previous cardiovascular disease. Patients with diabetes mellitus are at an increased risk of cardiovascular events...

  13. An Efficient Microscale Procedure for the Synthesis of Aspirin

    Science.gov (United States)

    Pandita, Sangeeta; Goyal, Samta

    1998-06-01

    The synthesis of aspirin is a part of many undergraduate organic synthesis labs and is frequently used in qualitative organic analysis laboratory for the identification of salicylic acid. We have found that aspirin can be synthesized on microscale by a simple and efficient procedure that eliminates the heating step employed in literature procedures and gives a pure, ferric-negative product (no purple color with alcoholic ferric chloride solution).

  14. A Review on the Relationship between Aspirin and Bone Health

    OpenAIRE

    Chin, Kok-Yong

    2017-01-01

    Aspirin is a cyclooxygenase inhibitor commonly used in primary prevention of cardiovascular diseases and cancers. Its users are elderly population susceptible to osteoporosis. It also inhibits the synthesis of prostaglandin E2 essential in bone remodeling. This prompts the question whether it can influence bone health among users. This review aimed to summarize the current literature on the use of aspirin on bone health. A literature search on experimental and clinical evidence on the effects...

  15. Aspirin Use and Mortality in Two Contemporary US Cohorts.

    Science.gov (United States)

    Huang, Wen-Yi; Daugherty, Sarah E; Shiels, Meredith S; Purdue, Mark P; Freedman, Neal D; Abnet, Christian C; Hollenbeck, Albert R; Hayes, Richard B; Silverman, Debra T; Berndt, Sonja I

    2018-01-01

    Daily aspirin use has been recommended for secondary prevention of cardiovascular disease, but its use for primary prevention remains controversial. We followed 440,277 men and women from the NIH-AARP Diet and Health Study (ages 50-71) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (ages 55-74) for mortality for 13 years on average. Frequency of aspirin use was ascertained through self-report, and cause of death by death certificates. We calculated multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality using Cox proportional hazards models for each cohort and combined by meta-analysis. We found a consistent U-shaped relationship between aspirin use and mortality in both studies, with differential risk patterns for cardiovascular mortality by disease history. Among individuals with a history of cardiovascular disease, daily aspirin use was associated with reduced cardiovascular mortality [HR = 0.78 (95% CI, 0.74, 0.82)]. However, among those without a previous history, we observed no protection for daily aspirin users [HR = 1.06 (1.02, 1.11)], and elevated risk of cardiovascular mortality for those taking aspirin twice daily or more [HR = 1.29 (1.19, 1.39)]. Elevated risk persisted even among participants who lived beyond 5 years of follow-up and used aspirin without other nonsteroidal antiinflammatory drugs [HR = 1.31 (1.17, 1.47)]. Results from these 2 large population-based US cohorts confirm the utility of daily aspirin use for secondary prevention of cardiovascular mortality; however, our data suggest that caution should be exercised in more frequent use, particularly among individuals without a history of cardiovascular disease.

  16. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

    OpenAIRE

    Shrestha Palikhe, Nami; Kim, Seung-Hyun; Jin, Hyun Jung; Hwang, Eui-Kyung; Nam, Young Hee; Park, Hae-Sim

    2012-01-01

    Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the resp...

  17. Effect of Aspirin on Fractalkine in Rats with Pulmonary Embolism ...

    African Journals Online (AJOL)

    Results: The serum levels of FKN, IL-8, TNF-α and IL-1β were significantly decreased by treatment with aspirin compared with the PE group (p < 0.05). Furthermore, mRNA expressions of lung FKN, TNF- α and IL-1β in PE group were markedly decreased by treatment with aspirin compared with that in PE group. PE-induced ...

  18. Mechanistic Insights into a Classic Wonder Drug?Aspirin

    OpenAIRE

    Lei, Jinping; Zhou, Yanzi; Xie, Daiqian; Zhang, Yingkai

    2014-01-01

    Aspirin, one of the oldest and most common anti-inflammatory agents, has recently been shown to reduce cancer risks. The principal pharmacological effects of aspirin are known to arise from its covalent modification of cyclooxygenase-2 (COX-2) through acetylation of Ser530, but the detailed mechanism of its biochemical action and specificity remains to be elucidated. In this work, we have filled this gap by employing a state-of-the-art computational approach, Born?Oppenheimer molecular dynami...

  19. Management options for patients with aspirin and nonsteroidal antiinflammatory drug sensitivity.

    Science.gov (United States)

    Knowles, Sandra R; Drucker, Aaron M; Weber, Elizabeth A; Shear, Neil H

    2007-07-01

    To evaluate and provide management strategies for patients with aspirin or nonselective nonsteroidal antiinflammatory drug (NSAID) sensitivity. Literature retrieval was accessed through MEDLINE (1966-March 2007) using the terms acetaminophen, aspirin, antiinflammatory agents nonsteroidal, urticaria, angioedema, asthma, leukotriene antagonists, desensitization, and tacrolimus. Article references retrieved were hand-searched for other relevant articles. All studies published in English were evaluated. Studies, review articles, and commentaries on aspirin-induced asthma and aspirin- or NSAID-induced urticaria/angioedema were included in the review. Aspirin sensitivity is most often manifested as respiratory reactions (eg, bronchospasm, profuse rhinorrhea, conjunctival injection) or urticaria/angioedema. The primary mechanism is believed to be inhibition of the cyclooxygenase 1 (COX-1) enzyme; as such, patients with aspirin sensitivity often display cross-reactions to nonselective NSAIDs that inhibit the COX-1 enzyme. Management strategies include avoidance of aspirin and cross-reacting nonselective NSAIDs. However, desensitization to aspirin is a viable option for patients with aspirin-induced respiratory reactions, especially for those who require aspirin for thromboembolic prophylaxis. Aspirin desensitization is maintained indefinitely with a daily aspirin dose. There is limited evidence of the use of leukotriene modifiers in preventing aspirin-induced asthma. COX-2 selective NSAIDs, especially in patients with aspirin-induced asthma, have not been found to cross-react. However, approximately 4% of patients with a history of aspirin-induced skin reactions may experience a cutaneous reaction following a challenge to a COX-2 selective NSAID. Since acetaminophen is a weak inhibitor of the COX-1 enzyme, patients with aspirin-induced asthma should not take more than 1000 mg of acetaminophen in a single dose. Management of patients with aspirin/NSAID sensitivity includes

  20. Interaction of aspirin and vitamin C with bovine serum albumin.

    Science.gov (United States)

    Nafisi, Shohreh; Bagheri Sadeghi, Golshan; PanahYab, Ataollah

    2011-12-02

    Vitamin C (L-ascorbic acid) has a major biological role as a natural antioxidant. Aspirin belongs to the nonsteroidal anti-inflammatory drugs and functions as an antioxidant via its ability to scavenge-OH radicals. Bovine serum albumin (BSA) is the major soluble protein constituent of the circulatory system and has many physiological functions including transport of a variety of compounds. In this report, the competitive binding of vitamin C and aspirin to bovine serum albumin has been studied using constant protein concentration and various drug concentrations at pH 7.2. FTIR and UV-Vis spectroscopic methods were used to analyze vitamin C and aspirin binding modes, the binding constants and the effects of drug complexation on BSA stability and conformation. Spectroscopic evidence showed that vitamin C and aspirin bind BSA via hydrophilic interactions (polypeptide and amine polar groups) with overall binding constants of K(vitamin C-BSA)=1.57×10(4)M(-1) and K(aspirin-BSA)=1.15×10(4)M(-1); assuming that there is one drug molecule per protein. The BSA secondary structure was altered with major decrease of α-helix from 64% (free protein) to 57% (BSA-vitamin C) and 54% (BSA-aspirin) and β-sheet from 15% (free protein) to 6-7% upon drug complexation, inducing a partial protein destabilization. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Aspirin resistance as cardiovascular risk after kidney transplantation

    Science.gov (United States)

    Sandor, Barbara; Varga, Adam; Rabai, Miklos; Toth, Andras; Papp, Judit; Toth, Kalman; Szakaly, Peter

    2014-05-01

    International surveys have shown that the leading cause of death after kidney transplantation has cardiovascular origin with a prevalence of 35-40%. As a preventive strategy these patients receive aspirin (ASA) therapy, even though their rate of aspirin resistance is still unknown. In our study, platelet aggregation measurements were performed between 2009 and 2012 investigating the laboratory effect of low-dose aspirin (100 mg) treatment using a CARAT TX4 optical aggregometer. ASA therapy was considered clinically effective in case of low ( i.e., below 40%) epinephrine-induced (10 μM) platelet aggregation index. Rate of aspirin resistance, morbidity and mortality data of kidney transplanted patients (n = 255, mean age: 49 ± 12 years) were compared to a patient population with cardio- and cerebrovascular diseases (n = 346, mean age: 52.6 ± 11 years). Rate of aspirin resistance was significantly higher in the renal transplantation group (RT) compared to the positive control group (PC) (35.9% vs. 25.6%, p aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

  2. European guidelines on perioperative venous thromboembolism prophylaxis: Aspirin.

    Science.gov (United States)

    Jenny, Jean-Yves; Pabinger, Ingrid; Samama, Charles Marc

    2018-02-01

    : There is a good rationale for the use of aspirin in venous thromboembolism prophylaxis in some orthopaedic procedures, as already proposed by the 9th American College of Chest Physicians' guidelines (Grade 1C). We recommend using aspirin, considering that it may be less effective than or as effective as low molecular weight heparin for prevention of deep vein thrombosis and pulmonary embolism after total hip arthroplasty, total knee arthroplasty and hip fracture surgery (Grade 1C). Aspirin may be less effective than or as effective as low molecular weight heparins for prevention of deep vein thrombosis and pulmonary embolism after other orthopaedic procedures (Grade 2C). Aspirin may be associated with a low rate of bleeding after total hip arthroplasty, total knee arthroplasty and hip fracture surgery (Grade 1B). Aspirin may be associated with less bleeding after total hip arthroplasty, total knee arthroplasty and hip fracture surgery than other pharmacological agents (Grade 1B). No data are available for other orthopaedic procedures. We do not recommend aspirin as thromboprophylaxis in general surgery (Grade 1C). However, this type of prophylaxis could be interesting especially in low-income countries (Grade 2C) and adequate large-scale trials with proper study designs should be carried out (Grade 1C).

  3. TRIAL OF ASPIRIN AND CALCIUM ON PREVENTION OF PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    ALI AKBA TAHERIAN

    2002-06-01

    Full Text Available ntroduction. Preelampsia is a common and serious complication of pregnancy that affects both mother and newborn. This study designed to determine whether low-dose aspirin or calcium supplements taken throughout pregnancy reduce the incidence of preeclampsia. Methods. The present study was a randomized controlled clinical trial. 990 healthy nulliparous women, who were pregnant for 13 to 20 weeks were chosen to receive daily treatment with low dose of aspirin 75 mg (330 patients, aspirin group, calcium D 500 mg (330 Patients, calcium group and no medication (330 patients, control group for remainder of theirs pregnancies. Data included demographic, obstetric, prenatal care, hospital records and final diagnosis were collected. Statistical analysis was performed using Chi-Squre, ANOVA and Duncan test at significance level of 0.05. Results. Preeclampsia occurred in 15 of 330 women in the aspirin group (4.6%, 13 of 330 women in the calcium group (4% and in 33 of 330 women in control group (10.1%. There were significant differences between aspirin and control groups (4.6% vs. 10.1% P < 0.05 also between calcium and control group (4% vs. 10.1% P < 0.05. Discussion. These results suggest that low dose of aspirin or calcium D during pregnancy in healthy nulliparous women is effective to reduce the prevalence of preeclampsia.

  4. Mechanistic and Pharmacological Issues of Aspirin as an Anticancer Agent

    Directory of Open Access Journals (Sweden)

    Paola Patrignani

    2012-12-01

    Full Text Available Recent findings have shown that aspirin, taken for several years, reduces the long-term risk of some cancers, particularly colorectal cancer. The result that aspirin benefit is detectable at daily low-doses (at least 75mg, the same used for the prevention of cardiovascular disease, positions the antiplatelet action of aspirin at the center of its antitumor efficacy. At low-doses given every 24 h, aspirin is acting by a complete and persistent inhibition of cyclooxygenase (COX-1 in platelets (in the pre-systemic circulation while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (approximately 20 min; nucleated cells have the ability to resynthesize the acetylated COX-isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin, such as the inhibition of Wnt/ b-catenin and NF-kB signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemo-preventive effects, but their relevance remains to be demonstrated in vivo at clinical doses. In conclusion, the results of clinical pharmacology and the analysis of randomized and epidemiological studies suggest that colorectal cancer and atherothrombosis share a common mechanism of disease, i.e. enhanced platelet activation in response to injury at distinct sites.

  5. Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis.

    OpenAIRE

    Hawthorne, A B; Mahida, Y R; Cole, A T; Hawkey, C J

    1991-01-01

    1. Gastric damage induced by low-dose aspirin and the protective effect of enteric-coating was assessed in healthy volunteers in a double-blind placebo-controlled cross-over trial using Latin square design. Each was administered placebo, plain aspirin 300 mg daily, plain aspirin 600 mg four times daily, enteric-coated aspirin 300 mg daily, or enteric-coated aspirin 600 mg four times daily for 5 days. Gastric damage was assessed endoscopically, and gastric mucosal bleeding measured. 2. Aspirin...

  6. Aspirin and omeprazole for secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers.

    Science.gov (United States)

    García-Rayado, Guillermo; Sostres, Carlos; Lanas, Angel

    2017-08-01

    Cardiovascular disease is the most important cause of morbidity and mortality in the world and low-dose aspirin is considered the cornerstone of the cardiovascular disease prevention. However, low-dose aspirin use is associated with gastrointestinal adverse effects in the whole gastrointestinal tract. In this setting, co-therapy with a proton pump inhibitor is the most accepted strategy to reduce aspirin related upper gastrointestinal damage. In addition, some adverse effects have been described with proton pump inhibitors long term use. Areas covered: Low-dose aspirin related beneficial and adverse effects in cardiovascular system and gastrointestinal tract are reviewed. In addition, this manuscript summarizes current data on upper gastrointestinal damage prevention and adverse events with proton pump inhibition. Finally, we discuss the benefit/risk ratio of proton pump inhibitor use in patients at risk of gastrointestinal damage taking low-dose aspirin. Expert commentary: Nowadays, with the current available evidence, the combination of low-dose aspirin with proton pump inhibitor is the most effective therapy for cardiovascular prevention in patients at high gastrointestinal risk. However, further studies are needed to discover new effective strategies with less related adverse events.

  7. Evaluation of aspirin use in patients with diabetes receiving care in community health.

    Science.gov (United States)

    Fosmire Rundgren, Elaine W; Anderson, Sarah L; Marrs, Joel C

    2015-02-01

    The American Diabetes Association (ADA) recommends low-dose aspirin therapy as a primary prevention strategy in patients with type 1 or type 2 diabetes mellitus (DM) at increased cardiovascular risk. However, not all patients who are indicated are taking aspirin therapy, and it is not routinely documented in the electronic health record (EHR). To determine frequencies of appropriate aspirin use and documentation in the EHR in adult patients with DM. Adult patients with DM were randomized and contacted for participation in a telephonic survey between January and October 2013. Patients who consented were administered a standardized oral telephone survey regarding aspirin use. Patient demographics, current medications, allergies, past medical history, and pertinent laboratory values were collected. Patients were then stratified by the ADA-defined indication for aspirin. The primary outcomes were rates of appropriate aspirin use and documentation of aspirin therapy in the EHR. Investigators contacted 276 patients for inclusion. Of the 81 patients surveyed, 74% were indicated for aspirin therapy. Nearly all (92.3%) patients reporting aspirin use were indicated for aspirin therapy compared with only 57.1% of patients who did not report aspirin but were indicated (P = 0.0003). Alternatively, 96.7% of patients with aspirin use documented in their EHR were indicated for aspirin therapy compared with only 60.8% of patients who did not have aspirin use documented in the EHR but had an indication (P = 0.0002). Approximately 20% of the patients indicated for and reporting aspirin use did not have aspirin documented in their EHR. Aspirin use in patients with DM who are indicated for therapy is significantly underutilized and underdocumented. © The Author(s) 2014.

  8. Clopidogrel and Aspirin versus Aspirin Alone for Stroke Prevention: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Shuai Tan

    Full Text Available Antiplatelet therapy is widely used for the primary or secondary prevention of stroke. Drugs like clopidogrel have emerged as alternatives for traditional antiplatelet therapy, and dual therapy with clopidogrel and aspirin is of particular interest. We conducted this meta-analysis to systematically review studies about dual therapy comparing monotherapy with aspirin alone.Randomized controlled trials were searched in PubMed (1966-May, 2015, EMBASE (1947-May, 2015, the Cochrane Central Register of Controlled Trials (CENTRAL (1948-May, 2015, WHO International Clinical Trial (ICTRP (2004-May, 2015, China Biology Medicine disc (CBM disc (1978-May, 2015 and were included into the final analysis according to the definite inclusion criteria mentioned in the study selection section. Risk ratio (RR was pooled with 95% confidence interval (CI for dichotomous data. The heterogeneity was considered significant if the χ2 test was significant (P value 50.00%. Subgroup analyses were carried out on the long and short time periods, the race and region.We included 5 studies involving 24,084 patients. A pooled analysis showed that dual therapy with clopidogrel and aspirin had a lower stroke incidence than monotherapy in both the short term and long term (RR = 0.69, 95% CI: 0.59-0.82, P <0.05; RR = 0.84, 95% CI: 0.72-0.98, P = 0.03, respectively. With regard to safety, dual therapy had a higher risk of bleeding than monotherapy for both periods (RR = 1.51, 95% CI: 1.03-2.23, P = 0.04; RR = 1.54, 95% CI: 1.32-1.79, P<0.05, respectively.Dual therapy with clopidogrel and aspirin could be a preferable choice to prevent stroke in patients who have had a previous stroke or transient ischemic attack, as well as those who are at high risk for stroke. And the effect of dual therapy seems to be more obvious for short-term. However, it is associated with a higher risk of bleeding.

  9. Stability studies of aspirin-magaldrate double layer tablets.

    Science.gov (United States)

    al-Gohary, O M; al-Kassas, R S

    2000-04-01

    Accelerated stability testing was performed on aspirin-magaldrate double layer tablets as well as aspirin-maalox marketed double layer tablets (Ascriptin) in order to evaluate the effect of the presence of the alkaline moieties of the antacid (magaldrate and maalox) on the chemical stability of aspirin. The results were compared simultaneously with that obtained from the marketed Aspro plain tablets. The results revealed that the presence of the alkaline moieties in the tested tablets has increased the rate of aspirin decomposition and reduced its shelf-life. This effect was more pronounced for aspirin tablets containing magaldrate antacid. Determination of shelf-lives at 25 degrees C for the prepared and the marketed tablets was carried out using Arrhenius plots and the results showed that they were 35, 34.5 and 13.5 months for Aspro, Ascriptin and aspirin-magaldrate double layer tablets, respectively. The effect of storage for 50 days and at different temperatures, on the crushing strength and the disintegration time of the prepared and the marked tablets showed a slight decrease in the disintegration time and the crushing strength of the tablets as the storage temperature increased. Aspro tablets did not produce the same results. The in vitro release data of the prepared aspirin-magaldrate double layer tablets and the marketed Ascriptin tablets stored for 50 days and at different storage temperatures as well as Aspro tablets stored at 70 degrees C were best fitted to the first-order kinetics model. The release data of Aspro tablets stored at 50 and 60 degrees C for 50 days were best fitted to Higuchi's model.

  10. Low prevalence and assay discordance of "aspirin resistance" in children.

    Science.gov (United States)

    Yee, D L; Dinu, B R; Sun, C W; Edwards, R M; Justino, H; Teruya, J; Bray, P F; Bomgaars, L

    2008-07-01

    Although "aspirin resistance" (AR-inadequate platelet inhibition as suggested by in vitro testing of aspirin-treated patients) has been widely studied in adults and linked to increased risk of adverse outcomes, its prevalence and clinical significance are largely unknown in children. To determine AR prevalence in children and its relationship to assay methodology, we undertook a cross-sectional study of 44 children (1-17 years, 24 male) on aspirin for various indications and considered three published definitions of AR in adults: platelet aggregation >/=70% to 10 microM adenosine diphosphate and >/=20% to 0.5 mg/ml arachidonic acid (AA), normal PFA-100(R) closure time and elevated urinary 11-dehydro thromboxane B(2) (11dhTxB(2)) concentration. Six subjects exhibited AR according to at least one of the criteria (5 by PFA-100(R), 1 by aggregometry and 11dhTxB(2) criteria); nearly all subjects had low levels of 11dhTxB(2) compared with controls. Subjects studied prior to therapy showed pronounced changes in AR parameters after aspirin dosing (e.g., mean aggregation to AA decreased from 82% to 6%, P aspirin effect. Subjects with AR did not differ from aspirin responsive subjects in terms of age, race, platelet count, or aspirin dose, indication or therapy duration. There was minimal correlation between assays. In this initial prevalence study of a clinically diverse group of pediatric patients, frequencies of AR were assay-dependent; however, the prevalence of true AR is likely low in children (2.3%; 95% CI 0.1-10.7%), in agreement with adult studies. To better define the clinical relevance of AR in children, multicenter, prospective cohort studies are imperative. (c) 2008 Wiley-Liss, Inc.

  11. Aspirin for Reducing Your Risk of Heart Attack and Stroke: Know the Facts

    Science.gov (United States)

    ... the-Counter Medicines Safe Daily Use of Aspirin Aspirin for Reducing Your Risk of Heart Attack and ... State & Local Officials Consumers Health Professionals Science & Research Industry Scroll back to top Popular Content Home Latest ...

  12. Aspirin, but not clopidogrel, reduces collateral conductance in a rabbit model of femoral artery occlusion

    NARCIS (Netherlands)

    Hoefer, Imo E.; Grundmann, Sebastian; Schirmer, Stephan; van Royen, Niels; Meder, Benjamin; Bode, Christoph; Piek, Jan J.; Buschmann, Ivo R.

    2005-01-01

    OBJECTIVES The objective of this study was to test the potential of aspirin and clopidogrel to influence collateral artery growth (arteriogenesis). BACKGROUND Aspirin and clopidogrel are antiplatelet agents commonly used in the treatment of ischemic cardiovascular disease. Both inhibit platelet

  13. Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery

    DEFF Research Database (Denmark)

    Graham, Michelle M; Sessler, Daniel I; Parlow, Joel L

    2017-01-01

    Background: Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. Objective: To evaluate benefits and harms of perioperative aspirin in patients with prior PCI. Design: Nonprespecified subgroup analysis of a mul...

  14. Purine Pathway Implicated in Mechanism of Resistance to Aspirin Therapy: Pharmacometabolomics-Informed-Pharmacogenomics

    Science.gov (United States)

    Yerges-Armstrong, Laura M.; Ellero-Simatos, Sandrine; Georgiades, Anastasia; Zhu, Hongjie; Lewis, Joshua; Horenstein, Richard B.; Beitelshees, Amber L.; Dane, Adrie; Reijmers, Theo; Hankemeier, Thomas; Fiehn, Oliver; Shuldiner, Alan R.; Kaddurah-Daouk, Rima

    2014-01-01

    Though aspirin is a well-established antiplatelet agent, the mechanisms of aspirin resistance remain poorly understood. Metabolomics allows for measurement of hundreds of small molecules in biological samples enabling detailed mapping of pathways involved in drug response. We defined the metabolic signature of aspirin exposure in subjects from the Heredity and Phenotype Intervention (HAPI) Heart Study. Many metabolites, including known aspirin catabolites, changed upon exposure to aspirin and pathway enrichment analysis identified purine metabolism as significantly affected by drug exposure. Further, purines were associated with aspirin response and poor responders had higher post-aspirin adenosine and inosine than good responders (N=76;paspirin response. Combining metabolomics and genomics allowed for more comprehensive interrogation of mechanisms of variation in aspirin response - an important step toward personalized treatment approaches for cardiovascular disease. PMID:23839601

  15. Aspirin provocation increases 8-iso-PGE2 in exhaled breath condensate of aspirin-hypersensitive asthmatics.

    Science.gov (United States)

    Mastalerz, Lucyna; Januszek, Rafał; Kaszuba, Marek; Wójcik, Krzysztof; Celejewska-Wójcik, Natalia; Gielicz, Anna; Plutecka, Hanna; Oleś, Krzysztof; Stręk, Paweł; Sanak, Marek

    2015-09-01

    Isoprostanes are bioactive compounds formed by non-enzymatic oxidation of polyunsaturated fatty acids, mostly arachidonic, and markers of free radical generation during inflammation. In aspirin exacerbated respiratory disease (AERD), asthmatic symptoms are precipitated by ingestion of non-steroid anti-inflammatory drugs capable for pharmacologic inhibition of cyclooxygenase-1 isoenzyme. We investigated whether aspirin-provoked bronchoconstriction is accompanied by changes of isoprostanes in exhaled breath condensate (EBC). EBC was collected from 28 AERD subjects and 25 aspirin-tolerant asthmatics before and after inhalatory aspirin challenge. Concentrations of 8-iso-PGF2α, 8-iso-PGE2, and prostaglandin E2 were measured using gas chromatography/mass spectrometry. Leukotriene E4 was measured by immunoassay in urine samples collected before and after the challenge. Before the challenge, exhaled 8-iso-PGF2α, 8-iso-PGE2, and PGE2 levels did not differ between the study groups. 8-iso-PGE2 level increased in AERD group only (p=0.014) as a result of the aspirin challenge. Urinary LTE4 was elevated in AERD, both in baseline and post-challenge samples. Post-challenge airways 8-iso-PGE2 correlated positively with urinary LTE4 level (p=0.046), whereas it correlated negatively with the provocative dose of aspirin (p=0.027). A significant increase of exhaled 8-iso-PGE2 after inhalatory challenge with aspirin was selective and not present for the other isoprostane measured. This is a novel finding in AERD, suggesting that inhibition of cyclooxygenase may elicit 8-iso-PGE2 production in a specific mechanism, contributing to bronchoconstriction and systemic overproduction of cysteinyl leukotrienes. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Impact of aspirin on the transcriptome of Streptococcus pneumoniae D39

    OpenAIRE

    Afzal, Muhammad; Shafeeq, Sulman

    2017-01-01

    Aspirin or acetylsalicylic acid (ASA) is a medicine used to treat pain, fever, and inflammation. Here, we for the very first time reported the genome-wide transcriptional profiling of aspirin-regulated genes in Streptococcus pneumoniae in the presence of 5?mM aspirin in chemically-defined medium (CDM) using microarray analysis. Our results showed that expression of several genes was differentially expressed in the presence of aspirin. These genes were further grouped into COG (Clusters of Ort...

  17. The Effects of Cyclosporine and Aspirin on Platelet Function in Normal Dogs.

    Science.gov (United States)

    Thomason, J; Archer, T; Wills, R; Press, S; Mackin, A

    2016-07-01

    Cyclosporine increases thromboxane synthesis in dogs, potentially increasing the thrombogenic properties of platelets. Our hypothesis was that the concurrent administration of low-dose aspirin and cyclosporine would inhibit cyclosporine-associated thromboxane synthesis without altering the antiplatelet effects of aspirin. The objective was to determine the effects of cyclosporine and aspirin on primary hemostasis. Seven healthy dogs. A randomized, crossover study utilized turbidimetric aggregometry and a platelet function analyzer to evaluate platelet function during the administration of low-dose aspirin (1 mg/kg PO q24h), high-dose aspirin (10 mg/kg PO q12h), cyclosporine (10 mg/kg PO q12h), and combined low-dose aspirin and cyclosporine. The urine 11-dehydro-thromboxane-B2 (11-dTXB2 )-to-creatinine ratio also was determined. On days 3 and 7 of administration, there was no difference in the aggregometry amplitude or the platelet function analyzer closure time between the low-dose aspirin group and the combined low-dose aspirin and cyclosporine group. On day 7, there was a significant difference in amplitude and closure time between the cyclosporine group and the combined low-dose aspirin and cyclosporine group. High-dose aspirin consistently inhibited platelet function. On both days, there was a significant difference in the urinary 11-dTXB2 -to-creatinine ratio between the cyclosporine group and the combined low-dose aspirin and cyclosporine group. There was no difference in the urinary 11-dTXB2 -to-creatinine ratio among the low-dose aspirin, high-dose aspirin, and combined low-dose aspirin and cyclosporine groups. Low-dose aspirin inhibits cyclosporine-induced thromboxane synthesis, and concurrent use of these medications does not alter the antiplatelet effects of aspirin. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  18. Platelet testing to guide aspirin dose adjustment in pediatric patients after cardiac surgery.

    Science.gov (United States)

    Emani, Sirisha; Zurakowski, David; Mulone, Michelle; DiNardo, James A; Trenor, Cameron C; Emani, Sitaram M

    2017-11-01

    Thrombosis is associated with increased morbidity and mortality in pediatric patients undergoing cardiac surgery. Although aspirin commonly is used for thromboprophylaxis, the utility of laboratory-based tests that assess aspirin efficacy have not been evaluated. We sought to determine the relationship between platelet aggregation testing and aspirin dose adjustment on thrombosis rates in this population. Pediatric patients undergoing cardiac surgery who received aspirin and underwent platelet testing were studied retrospectively. Patients were excluded if they were treated with multiple agents or experienced thrombosis before the initiation of aspirin. Thrombosis events within 30 days after initiation of aspirin were recorded. Associations between aspirin responsiveness and thrombosis rate and aspirin dose adjustment and thrombosis rate were assessed with the use of multivariable logistic regression analysis. Suboptimal platelet response to aspirin was detected in 64 of 430 patients (15%) and thrombosis was detected in 11 patients (2.6%). Lack of aspirin responsiveness on initial testing was a significant risk factor for thrombosis (P aspirin dose. Dose escalation based on aspirin testing was performed in 40 of 64 patients, and significantly lower rate of thrombosis was observed in patients who underwent dose escalation compared with those without dose escalation (0/40 vs 9/24, P aspirin dose after initial unresponsiveness (P aspirin dosing may lead to subtherapeutic platelet inhibition in some children. Aspirin unresponsiveness is associated with increased risk of thrombosis after specific pediatric cardiac surgical procedures. Aspirin dose increase in unresponsive patients is associated with reduced risk of thrombosis. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  19. Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters

    Directory of Open Access Journals (Sweden)

    Kunal Kanani

    2015-08-01

    Full Text Available Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer’s clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA is rapidly converted into its main active metabolite, salicylic acid (SA. Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters.

  20. Aspirin Prevents Colorectal Cancer by Normalizing EGFR Expression.

    Science.gov (United States)

    Li, Haitao; Zhu, Feng; Boardman, Lisa A; Wang, Lei; Oi, Naomi; Liu, Kangdong; Li, Xiang; Fu, Yang; Limburg, Paul J; Bode, Ann M; Dong, Zigang

    2015-05-01

    Aspirin intake reduces the risk of colorectal cancer (CRC), but the molecular underpinnings remain elusive. Epidermal growth factor receptor (EGFR), which is overexpressed in about 80% of CRC cases, is implicated in the etiology of CRC. Here, we investigated whether aspirin can prevent CRC by normalizing EGFR expression. Immunohistochemistry staining was performed on paraffin-embedded tissue sections from normal colon mucosa, adenomatous polyps from FAP patients who were classified as regular aspirin users or nonusers. The interplay between cyclooxygenase-2 (COX-2) and EGFR was studied in primary intestinal epithelial cells isolated from Apc(Min) mice, immortalized normal human colon epithelial cells (HCEC) as well as murine embryonic fibroblasts (MEFs). Immunohistochemistry staining results established that EGFR overexpression is an early event in colorectal tumorigenesis, which can be greatly attenuated by regular use of aspirin. Importantly, EGFR and COX-2 were co-overexpressed and co-localized with each other in FAP patients. Further mechanistic studies revealed that COX-2 overexpression triggers the activation of the c-Jun-dependent transcription factor, activator protein-1 (AP-1), which binds to the Egfr promoter. Binding facilitates the cellular accumulation of EGFR and lowers the threshold required for pre-neoplastic cells to undergo transformation. Aspirin might exert its chemopreventive activity against CRC, at least partially, by normalizing EGFR expression in gastrointestinal precancerous lesions.

  1. Aspirin: promise and resistance in the new millennium.

    Science.gov (United States)

    Patrono, Carlo; Rocca, Bianca

    2008-03-01

    Although conceived at the end of the 19th century, aspirin remains the gold standard of antiplatelet therapy. Approximately 100 randomized clinical trials have established its efficacy and safety in the prevention of myocardial infarction, ischemic stroke, and vascular death among high-risk patients treated for a few weeks, at one end of the spectrum, and in low-risk subjects treated up to 10 years at the other. Despite this wealth of data, several issues continue to be debated concerning the use of aspirin as an antiplatelet agent, and novel opportunities appear on the horizon for this 110-year-old drug. These issues include: (1) the optimal dose for cardiovascular prophylaxis; (2) the uncertain threshold of cardiovascular risk for its use in primary prevention; (3) the apparent gender-related difference in its cardioprotective effects; (4) the increasingly popular theme of aspirin "resistance"; (5) the opportunities of chemoprevention in colorectal cancer; and (6) the renewed interest in aspirin as an analgesic agent in osteoarthritic patients at high cardiovascular risk. The aim of this review is to address these issues by integrating our current understanding of the molecular mechanism of action of the drug with the results of clinical trials and epidemiological studies of aspirin as an antiplatelet drug.

  2. Use and Safety of Non-Steroidal Inflammatory Drugs and Aspirin

    NARCIS (Netherlands)

    V.E. Valkhoff (Vera)

    2012-01-01

    textabstractThe use of acetylsalicylic acid, better known as aspirin, dates back to the Egyptians in 1534 BC. Aspirin-like compounds are naturally derived from willow tree bark and myr-tle. At the end of the 19th century aspirin was patented by Bayer as the world’s first syn-thetic drug. The

  3. Aspirin resistance in children with heart disease at risk for thromboembolism: prevalence and possible mechanisms.

    Science.gov (United States)

    Heistein, Lisa C; Scott, William A; Zellers, Thomas M; Fixler, David E; Ramaciotti, Claudio; Journeycake, Janna M; Lemler, Matthew S

    2008-03-01

    Aspirin is used to prevent thromboembolism in children with heart disease without evidence supporting its efficacy. Studies in adults report a 5%-51% prevalence of aspirin resistance, yet the mechanisms involved are poorly understood. Our aims were to determine its prevalence in these children and to explore its possible mechanisms. One hundred twenty-three cardiac patients routinely receiving aspirin were prospectively enrolled. Platelet function was measured by Platelet Function Analyzer (PFA)-100 using epinephrine and adenosine diphosphate (ADP) agonists. Aspirin resistance was defined as failure to prolong the epinephrine closure time following aspirin administration. Urine levels of 11-dehydro-thromboxane B(2) (11-dTXB(2)) were measured to determine inhibition of the cyclo-oxygenase pathway. The prevalence of aspirin resistance was 26%. Median ADP closure time was shorter for aspirin-resistant (79.60-115 s) than for aspirin-sensitive (100.60-240 s) patients (p aspirin resistance. Aspirin-resistant patients had higher 11-dTXB(2) levels before (7297 vs. 4160 pg/mg creatinine; p aspirin, with a similar percentage decrease in thromboxane (70.5% vs. 66.1%; p = 0.43). Our findings suggest that resistance is not entirely due to lack of inhibition of platelet thromboxane production. Alternative sources of thromboxane and thromboxane-independent mechanisms, such as ADP-induced platelet activation, may contribute to aspirin resistance.

  4. Histone deacetylase inhibitors and aspirin interact synergistically to induce cell death in ovarian cancer cells.

    Science.gov (United States)

    Sonnemann, Jürgen; Hüls, Isabel; Sigler, Michael; Palani, Chithra D; Hong, Le Thi Thu; Völker, Uwe; Kroemer, Heyo K; Beck, James F

    2008-07-01

    Histone deacetylase inhibitors (HDIs) as well as non-steroidal anti-inflammatory drugs including aspirin show promise as antineoplastic agents. The treatment with both HDIs and aspirin can result in hyperacetylation of proteins. In this study, we investigated whether HDIs and aspirin interacted in inducing anticancer activity and histone acetylation. We found that the HDIs, suberoylanilide hydroxamic acid and sodium butyrate, and aspirin cooperated to induce cell death in the ovarian cancer cell line, A2780. The effect was synergistic, as evidenced by CI-isobologram analysis. However, aspirin had no effect on histone acetylation, neither in the absence nor presence of HDIs. To gain insight into the mechanism underlying the synergistic action of HDIs and aspirin, we employed the deacetylated metabolite of aspirin, salicylic acid, and the cyclooxygenase-1- and -2-selective inhibitors, SC-560 and NS-398, respectively. We found that HDIs and salicylic acid interacted synergistically, albeit less efficiently than HDIs and aspirin, to induce cancer cell death, suggesting that the acetyl and the salicyl moiety contributed to the cooperative interaction of aspirin with HDIs. SC-560 and NS-398 had little effect both when applied alone or in conjunction with HDIs, indicating that the combinatorial effect of HDIs and aspirin was not the result of cyclo-oxygenase inhibition. In conclusion, our study demonstrates that HDIs and aspirin synergize to induce cancer cell death and, thus, provides a rationale for a more in-depth exploration into the potential of combining HDIs and aspirin as a strategy for anticancer therapy.

  5. Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU).

    Science.gov (United States)

    Jull, Andrew; Wadham, Angela; Bullen, Chris; Parag, Varsha; Kerse, Ngaire; Waters, Jill

    2017-11-24

    Objective  To determine the effect of low dose aspirin on ulcer healing in patients with venous leg ulcers. Design  Pragmatic, community based, parallel group, double blind, randomised controlled trial. Setting  Five community nursing centres in New Zealand. Participants  251 adults with venous leg ulcers who could safely be treated with aspirin or placebo: 125 were randomised to aspirin and 126 to placebo. Interventions  150 mg oral aspirin daily or matching placebo for up to 24 weeks treatment, with compression therapy as standard background treatment. Main outcome measures  The primary outcome was time to complete healing of the reference ulcer (largest ulcer if more than one ulcer was present). Secondary outcomes included proportion of participants healed, change in ulcer area, change in health related quality of life, and adverse events. Analysis was by intention to treat. Results  The median number of days to healing of the reference ulcer was 77 in the aspirin group and 69 in the placebo group (hazard ratio 0.85, 95% confidence interval 0.64 to 1.13, P=0.25). The number of participants healed at the endpoint was 88 (70%) in the aspirin group and 101 (80%) in the placebo group (risk difference -9.8%, 95% confidence interval -20.4% to 0.9%, P=0.07). Estimated change in ulcer area was 4.1 cm 2 in the aspirin group and 4.8 cm 2 in the placebo group (mean difference -0.7 cm 2 , 95% confidence interval -1.9 to 0.5 cm 2 , P=0.25). 40 adverse events occurred among 29 participants in the aspirin group and 37 adverse events among 27 participants in the placebo group (incidence rate ratio 1.1, 95% confidence interval 0.7 to 1.7, P=0.71). Conclusion  Our findings do not support the use of low dose aspirin as adjuvant treatment for venous leg ulcers. Trial registration  ClinicalTrials.gov NCT02158806. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Antiplatelet effect of aspirin in patients with coronary artery disease.

    Science.gov (United States)

    Grove, Erik Lerkevang

    2012-09-01

    Cardiovascular disease is the number one cause of death globally, and atherothrombosis is the underlying cause of most cardiovascular events. Several studies have shown that antiplatelet therapy, including aspirin (acetylsalicylic acid), reduces the risk of cardiovascular events and death. However, it is well-known that many patients experience cardiovascular events despite treatment with aspirin, often termed "aspirin low-responsiveness". This fact has caused considerable debate: does biochemical aspirin low-responsiveness have prognostic value? Can low-responders be reliably identified? And if so, should antithrombotic treatment be changed? Is the whole discussion of antiplatelet drug response merely a result of low compliance? Compliance should be carefully optimised, before evaluating the pharmacological effect of a drug. It is well-known that cardiovascular disease is multifactorial, and, therefore, total risk reduction is not feasible. Aetiological factors to the variable platelet inhibition by aspirin seem to include genetic factors, pharmacological interactions, smoking, diabetes mellitus, and increased platelet turnover. It is a captivating thought that antiplatelet therapy may be improved by individually tailored therapy based on platelet function testing. Ongoing studies are challenging the current one-size-fits-all dosing strategy, but the preceding evaluation of platelet function assays has not been adequate. The overall objective of this thesis was to evaluate the reproducibility of and aggreement between a number of widely used platelet function tests and to explore the importance of platelet turnover for the antiplatelet effect of aspirin in patients with coronary artery disease. In the intervention studies (studies 1, 3, and 4), optimal compliance was confirmed by measurements of serum thromboxane, which is the most sensitive assay to confirm compliance with aspirin. In study 1, platelet function tests widely used to measure the antiplatelet effect

  7. Use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs and risk of glioma

    DEFF Research Database (Denmark)

    Gaist, David; García-Rodríguez, L A; Sørensen, H T

    2013-01-01

    Background:Few studies have examined the association between use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and risk of glioma and the results have been equivocal. We therefore investigated the influence of NSAID use on glioma risk in a nationwide setting.Methods:We used...... exposure to low-dose aspirin or non-aspirin (NA) NSAIDs into ever use or long-term use, defined as continuous use for 5 years. Conditional logistic regression was used to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with NSAID use, adjusted for potential...... confounders.Results:A total of 2688 glioma cases and 18 848 population controls were included in the study. Ever use of low-dose aspirin (OR=0.90; 95% CI: 0.77-1.04) or NA-NSAIDs (OR=1.05; 95% CI: 0.96-1.14) was not associated with glioma risk. Compared with never use, long-term use of low-dose aspirin...

  8. Current Knowledge and Management of Hypersensitivity to Aspirin and NSAIDs.

    Science.gov (United States)

    Laidlaw, Tanya M; Cahill, Katherine N

    Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most common culprits of drug-induced hypersensitivity reactions, and can lead to a wide array of adverse effects. The accurate and timely diagnosis of aspirin and NSAID-induced hypersensitivity reactions is important for both patient safety and for the initiation of appropriate disease-specific management and treatment. Because there are no reliably validated in vitro tests available, aspirin and NSAID challenges are considered to be the criterion standard for the diagnosis of these hypersensitivity reactions, though in some patients the diagnosis can be made on the basis of a clear clinical history. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. High-pressure polymorphism of acetylsalicylic acid (aspirin): Raman spectroscopy

    Science.gov (United States)

    Crowell, Ethan L.; Dreger, Zbigniew A.; Gupta, Yogendra M.

    2015-02-01

    Micro-Raman spectroscopy was used to elucidate the high-pressure polymorphic behavior of acetylsalicylic acid (ASA), an important pharmaceutical compound known as aspirin. Using a diamond anvil cell (DAC), single crystals of the two polymorphic phases of aspirin existing at ambient conditions (ASA-I and ASA-II) were compressed to 10 GPa. We found that ASA-I does not transform to ASA-II, but instead transforms to a new phase (ASA-III) above ∼2 GPa. It is demonstrated that this transformation primarily introduces structural changes in the bonding and arrangement of the acetyl groups and is reversible upon the release of pressure. In contrast, a less dense ASA-II shows no transition in the pressure range studied, though it appears to exhibit a disordered structure above 7 GPa. Our results suggest that ASA-III is the most stable polymorph of aspirin at high pressures.

  10. Functionalized bimodal mesoporous silicas as carriers for controlled aspirin delivery

    Science.gov (United States)

    Gao, Lin; Sun, Jihong; Li, Yuzhen

    2011-08-01

    The bimodal mesoporous silica modified with 3-aminopropyltriethoxysilane was performed as the aspirin carrier. The samples' structure, drug loading and release profiles were characterized with X-ray diffraction, scanning electron microscopy, N 2 adsorption and desorption, Fourier transform infrared spectroscopy, TG analysis, elemental analysis and UV-spectrophotometer. For further exploring the effects of the bimodal mesopores on the drug delivery behavior, the unimodal mesoporous material MCM-41 was also modified as the aspirin carrier. Meantime, Korsmeyer-Peppas equation ft= ktn was employed to analyze the dissolution data in details. It is indicated that the bimodal mesopores are beneficial for unrestricted drug molecules diffusing and therefore lead to a higher loading and faster releasing than that of MCM-41. The results show that the aspirin delivery properties are influenced considerably by the mesoporous matrix, whereas the large pore of bimodal mesoporous silica is the key point for the improved controlled-release properties.

  11. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    Science.gov (United States)

    Alsop, Richard; Barrett, Matthew; Zheng, Sonbo; Dies, Hannah; Rheinstadter, Maikel

    2014-03-01

    Aspirin (ASA) is often prescribed for patients with high levels of cholesterol for the secondary prevention of myocardial events, a regimen known as the Low-Dose Aspirin Therapy. We have recently shown that Aspirin partitions in lipid bilayers. However, a direct interplay between ASA and cholesterol has not been investigated. Cholesterol is known to insert itself into the membrane in a dispersed state at moderate concentrations (under ~37.5%) and decrease fluidity of membranes. We prepared model lipid membranes containing varying amounts of both ASA and cholesterol molecules. The structure of the bilayers as a function of ASA and cholesterol concentration was determined using high-resolution X-ray diffraction. At cholesterol levels of more than 40mol%, immiscible cholesterol plaques formed. Adding ASA to the membranes was found to dissolve the cholesterol plaques, leading to a fluid lipid bilayer structure. We present first direct evidence for an interaction between ASA and cholesterol on the level of the cell membrane.

  12. Epidural Hematoma Following Interlaminar Epidural Injection in Patient Taking Aspirin.

    Science.gov (United States)

    Sanders, Rebecca A; Bendel, Markus A; Moeschler, Susan M; Mauck, William D

    2018-01-09

    We present a case report of a patient who developed an epidural hematoma following an interlaminar epidural steroid injection with no risk factors aside from old age and aspirin use for secondary prevention. A 79-year-old man developed an epidural hematoma requiring surgical treatment following an uncomplicated interlaminar epidural steroid injection performed for neurogenic claudication. In the periprocedural period, he continued aspirin for secondary prophylaxis following a myocardial infarction. For patients taking aspirin for primary or secondary prophylaxis, the American Society of Regional Anesthesia and Pain Medicine antiplatelet and anticoagulation guidelines for spine and pain procedures recommend a shared assessment and risk stratification when deciding to hold the medication for intermediate-risk neuraxial procedures. Cases such as this serve to highlight the importance of giving careful consideration to medical optimization of a patient even when a low- or intermediate-risk procedure is planned.

  13. Regular use of aspirin and pancreatic cancer risk

    Directory of Open Access Journals (Sweden)

    Mahoney Martin C

    2002-09-01

    Full Text Available Abstract Background Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs has been consistently associated with reduced risk of colorectal cancer and adenoma, and there is some evidence for a protective effect for other types of cancer. As experimental studies reveal a possible role for NSAIDs is reducing the risk of pancreatic cancer, epidemiological studies examining similar associations in human populations become more important. Methods In this hospital-based case-control study, 194 patients with pancreatic cancer were compared to 582 age and sex-matched patients with non-neoplastic conditions to examine the association between aspirin use and risk of pancreatic cancer. All participants received medical services at the Roswell Park Cancer Institute in Buffalo, NY and completed a comprehensive epidemiologic questionnaire that included information on demographics, lifestyle factors and medical history as well as frequency and duration of aspirin use. Patients using at least one tablet per week for at least six months were classified as regular aspirin users. Unconditional logistic regression was used to compute crude and adjusted odds ratios (ORs with 95% confidence intervals (CIs. Results Pancreatic cancer risk in aspirin users was not changed relative to non-users (adjusted OR = 1.00; 95% CI 0.72–1.39. No significant change in risk was found in relation to greater frequency or prolonged duration of use, in the total sample or in either gender. Conclusions These data suggest that regular aspirin use may not be associated with lower risk of pancreatic cancer.

  14. The effectiveness of aspirin for migraine prophylaxis: a systematic review.

    Science.gov (United States)

    Baena, Cristina Pellegrino; D'Amico, Raíssa Campos; Slongo, Helena; Brunoni, André Russowsky; Goulart, Alessandra Carvalho; Benseñor, Isabela

    2017-01-01

    Many researchers have suggested that aspirin prevents migraines. However, the evidence is unclear. The aim of this study was to analyze the available evidence on the effect of aspirin as a migraine prophylactic. Systematic review, conducted at the Pontifícia Universidade Católica do Paraná, Brazil, and at the University of São Paulo, Brazil. We performed electronic searches in the databases of MEDLINE/PubMed, Embase, WEB OF SCIENCE, the World Health Organization, CENTRAL and OpenGrey, and we also searched manually for interventional studies published before April 2016 that compared the effects of aspirin with a control, in adults. Two authors independently extracted data on the publication, population recruited, intervention (aspirin dosage, follow-up and combined treatment) and main outcomes (frequency, severity and duration of migraine). We evaluated the quality of the studies using the Cochrane risk-of-bias tool. Our search retrieved 1,098 references, of which 8 met the selection criteria for this systematic review. The total population was 28,326 participants (18-64 years old); most (96%) were men. The dosage varied from 50 to 650 mg/day across the studies. The risk of bias was generally low or unclear. The only outcome for which most of the studies included (6/8) reported a significant reduction was frequency of migraine, which was reduced at an aspirin dosage of at least 325 mg/day. Aspirin can reduce the frequency of migraines. However, the optimal dosage is unclear.

  15. The effectiveness of aspirin for migraine prophylaxis: a systematic review

    Directory of Open Access Journals (Sweden)

    Cristina Pellegrino Baena

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: Many researchers have suggested that aspirin prevents migraines. However, the evidence is unclear. The aim of this study was to analyze the available evidence on the effect of aspirin as a migraine prophylactic. DESIGN AND SETTING: Systematic review, conducted at the Pontifícia Universidade Católica do Paraná, Brazil, and at the University of São Paulo, Brazil. METHODS: We performed electronic searches in the databases of MEDLINE/PubMed, Embase, WEB OF SCIENCE, the World Health Organization, CENTRAL and OpenGrey, and we also searched manually for interventional studies published before April 2016 that compared the effects of aspirin with a control, in adults. Two authors independently extracted data on the publication, population recruited, intervention (aspirin dosage, follow-up and combined treatment and main outcomes (frequency, severity and duration of migraine. We evaluated the quality of the studies using the Cochrane risk-of-bias tool. RESULTS: Our search retrieved 1,098 references, of which 8 met the selection criteria for this systematic review. The total population was 28,326 participants (18-64 years old; most (96% were men. The dosage varied from 50 to 650 mg/day across the studies. The risk of bias was generally low or unclear. The only outcome for which most of the studies included (6/8 reported a significant reduction was frequency of migraine, which was reduced at an aspirin dosage of at least 325 mg/day. CONCLUSION: Aspirin can reduce the frequency of migraines. However, the optimal dosage is unclear.

  16. [Aspirin in primary and secondary prevention of colorectal carcinomas].

    Science.gov (United States)

    Schrör, Karsten; Rauch, Bernhard

    2013-11-01

    Observational but also some randomized trials suggest that regular long-term use of aspirin (acetylsalicylic acid) might reduce the risk of colorectal carcinomas by 15-40%. The efficacy appears to be increased with longer duration of treatment, i.e. beyond 5-10 years, but not with increasing doses. Aspirin at 75-100 mg daily appears to be sufficient in both primary as well as secondary prevention of recurrent tumors in sensitive persons, including prevention of distant metastases. The pharmacological mode of aspirin action is unclear as is the question whether only one or more sites of action exist. In any case, the mechanism(s) in charge should work at aspirin plasma levels of 10 microM or less which is the maximum concentration to be expected after antiplatelet doses. Inhibition of COX-1 and/or COX-2 is most likely involved. Follow-up reactions, such as inhibition of platelet-dependent thromboxane formation and action, release of storage products such as VEGF or sphingosine-1-phosphate and acetylation of COX-2 with subsequent generation of antioncogenic lipid mediators, such as lipoxins, are also possible. There is not much likelihood for "direct" actions of aspirin, shown in vitro at concentrations of 5 mM and more, which uncouple oxidative phosphorylation and paralyse the cell energy metabolism. benefit/risk profile, specifically regarding severe or fatal bleedings (GI-tract, cerebral). Accordingly, the actual German guideline "colorectal carcinoma" does not recommend aspirin use for prophylactic purposes. What is strongly needed are definitions of risk patients in terms of biomarkers or genetic profiling as well as data from long-term prospective randomized trials--both are underway.

  17. Aspirin use among adults in the U.S.: results of a national survey.

    Science.gov (United States)

    Williams, Craig D; Chan, Andrew T; Elman, Miriam R; Kristensen, Alyson H; Miser, W Fred; Pignone, Michael P; Stafford, Randall S; McGregor, Jessina C

    2015-05-01

    The use of aspirin in patients without cardiovascular disease remains controversial. Patients' understanding of the risks and benefits of aspirin likely contribute to the decision of whether or not to use aspirin regularly. The purpose of this study is to assess patients' knowledge of aspirin and identify factors contributing to regular use. A survey of U.S. adults aged 45-75 years was performed to ascertain aspirin use and factors that may be associated with use. Multivariate logistic regression was used to identify predictors of current use of aspirin among those with a primary prevention indication. The survey was completed in 2012 with data analysis performed in 2013. Among 2,509 respondents, 52% reported current aspirin use. Among 2,039 respondents without a history of cardiovascular disease, current use of aspirin was 47%. Regular use of aspirin for primary prevention was associated with the presence of major cardiovascular disease risk factors (OR=3.0, 95% CI=2.4, 3.7), high self-assessed knowledge of aspirin (OR=9.1, 95% CI=5.2, 15.7), and having discussed aspirin therapy with a provider (OR=25.9, 95% CI=19.7, 34.1). Several markers of healthy lifestyle choices were also associated with regular use. After multivariate analysis, the strongest independent predictor of regular aspirin use was having discussed aspirin therapy with a provider (OR=23.79, 95% CI=17.8, 31.5). Approximately half of the nationwide survey of U.S. adults reported regular aspirin use. Among those with a primary prevention indication, having discussed aspirin with a provider was the strongest predictor of regular use. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Platelet-rich fibrin/aspirin complex promotes alveolar bone regeneration in periodontal defect in rats.

    Science.gov (United States)

    Du, J; Mei, S; Guo, L; Su, Y; Wang, H; Liu, Y; Zhao, Z; Wang, S; Liu, Y

    2018-02-01

    The efficacy and outcomes of aspirin in local defects and the use of platelet-rich fibrin (PRF) in periodontal defects were investigated. Whether the PRF/aspirin complex is a suitable scaffold and delivery system to carry sustained-release aspirin/salicylic acid to promote periodontal bone regeneration was determined. PRF and PRF/aspirin complex were prepared. The concentrations of aspirin/salicylic acid released from the PRF/aspirin complex were calculated at 37°C. Periodontal ligament mesenchymal cells were cultured on six-well plates with PRF or PRF/aspirin complex gel to analyze proliferation and migration. The alveolar bone between the inferior buccal mesial root and anterior buccal distal root of the first maxillary molar was removed in 15 rats randomly divided into three groups: no treatment, PRF or PRF/aspirin complex. Twelve weeks post-transplantation, 2D/3D micro-computed tomography and histomorphometric technique were used for quantitative analyses. The PRF/aspirin complex provided a sustained-release aspirin/salicylic acid. Peak concentrations occurred 4 hours after transplantation and were sustained to 48 hours at 37°C; the total concentration of released aspirin/salicylic acid was 83.5 mg/mL, respectively. The sustained-release promoted the proliferation and migration of periodontal ligament mesenchymal cells. Micro-computed tomography and histological data showed that both the PRF and PRF/aspirin complex enhanced periodontal bone formation (P<.05). Moreover, the new bone formation was two times greater in the PRF/aspirin complex group than the PRF group. Aspirin/salicylic acid could be sustained-released from PRF/aspirin complex, which could inhibit inflammation and improve the function of mesenchymal cells. The data might provide a new safe and easy clinical therapeutic strategy to promote periodontal bone reparation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. The aspirin story - from willow to wonder drug.

    Science.gov (United States)

    Desborough, Michael J R; Keeling, David M

    2017-06-01

    The story of the discovery of aspirin stretches back more than 3500 years to when bark from the willow tree was used as a pain reliever and antipyretic. It involves an Oxfordshire clergyman, scientists at a German dye manufacturer, a Nobel Prize-winning discovery and a series of pivotal clinical trials. Aspirin is now the most commonly used drug in the world. Its role in preventing cardiovascular and cerebrovascular disease has been revolutionary and one of the biggest pharmaceutical success stories of the last century. © 2017 John Wiley & Sons Ltd.

  20. Aspirin for Prophylaxis Against Venous Thromboembolism After Orthopaedic Oncologic Surgery.

    Science.gov (United States)

    Mendez, Gregory M; Patel, Yash M; Ricketti, Daniel A; Gaughan, John P; Lackman, Richard D; Kim, Tae Won B

    2017-12-06

    Patients who undergo orthopaedic oncologic surgical procedures are at increased risk of developing a venous thromboembolism (VTE). Guidelines from surgical societies are shifting to include aspirin as a postoperative VTE prophylactic agent. The purpose of this study was to review our experience using aspirin as postoperative VTE prophylaxis for orthopaedic oncologic surgical procedures. This study was a retrospective review of patients diagnosed with a primary malignant soft-tissue or bone tumor or metastatic carcinoma. Demographic information, histopathologic diagnosis, VTE history, surgical procedure, and VTE prophylaxis were analyzed. VTE rates in the overall and prophylactic-specific cohorts were recorded and compared. A total of 142 distinct surgical procedures in 130 patients were included. VTE prophylaxis with aspirin was used after 103 procedures, and non-aspirin prophylaxis was used after 39. In 33 cases, imaging was used to investigate for VTE because of clinical signs and symptoms. VTE developed after 7 (4.9%) of the 142 procedures. There were 6 deep venous thromboses (DVTs) and 1 pulmonary embolism, and 2 of the VTEs presented in patients with a VTE history. VTE developed in 2.9% (3) of the 103 aspirin cases and 10.3% (4) of the 39 non-aspirin cases. No patient in the aspirin group who had been diagnosed with metastatic carcinoma, malignant soft-tissue sarcoma, lymphoma, or multiple myeloma developed a VTE. Risk factors for VTE development included diabetes mellitus (odds ratio [OR] = 10.40, 95% confidence interval [CI] = 1.61 to 67.30), a history of VTE (OR = 7.26, 95% CI = 1.19 to 44.25), postoperative transfusion (OR = 34.50, 95% CI = 3.94 to 302.01), and estimated blood losses of 250 mL (OR = 1.50, 95% CI = 1.11 to 2.03), 500 mL (OR = 2.26, 95% CI = 1.23 to 4.13), and 1,000 mL (OR = 5.10, 95% CI = 1.52 to 17.04). Aspirin may be a suitable and effective option for VTE chemoprophylaxis in patients treated with orthopaedic oncologic surgery, especially

  1. Aspirin Versus Aspirin Plus Clopidogrel as Antithrombotic Treatment Following Transcatheter Aortic Valve Replacement With a Balloon-Expandable Valve: The ARTE (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation) Randomized Clinical Trial.

    Science.gov (United States)

    Rodés-Cabau, Josep; Masson, Jean-Bernard; Welsh, Robert C; Garcia Del Blanco, Bruno; Pelletier, Marc; Webb, John G; Al-Qoofi, Faisal; Généreux, Philippe; Maluenda, Gabriel; Thoenes, Martin; Paradis, Jean-Michel; Chamandi, Chekrallah; Serra, Vicenç; Dumont, Eric; Côté, Mélanie

    2017-07-10

    The aim of this study was to compare aspirin plus clopidogrel with aspirin alone as antithrombotic treatment following transcatheter aortic valve replacement (TAVR) for the prevention of ischemic events, bleeding events, and death. Few data exist on the optimal antithrombotic therapy following TAVR. This was a randomized controlled trial comparing aspirin (80 to 100 mg/day) plus clopidogrel (75 mg/day) (dual antiplatelet therapy [DAPT]) versus aspirin alone (single-antiplatelet therapy [SAPT]) in patients undergoing TAVR with a balloon-expandable valve. The primary endpoint was the occurrence of death, myocardial infarction (MI), stroke or transient ischemic attack, or major or life-threatening bleeding (according to Valve Academic Research Consortium 2 definitions) within the 3 months following the procedure. The trial was prematurely stopped after the inclusion of 74% of the planned study population. A total of 222 patients were included, 111 allocated to DAPT and 111 to SAPT. The composite of death, MI, stroke or transient ischemic attack, or major or life-threatening bleeding tended to occur more frequently in the DAPT group (15.3% vs. 7.2%, p = 0.065). There were no differences between groups in the occurrence of death (DAPT, 6.3%; SAPT, 3.6%; p = 0.37), MI (DAPT, 3.6%; SAT, 0.9%; p = 0.18), or stroke or transient ischemic attack (DAPT, 2.7%; SAPT, 0.9%; p = 0.31) at 3 months. DAPT was associated with a higher rate of major or life-threatening bleeding events (10.8% vs. 3.6% in the SAPT group, p = 0.038). There were no differences between groups in valve hemodynamic status post-TAVR. This small trial showed that SAPT (vs. DAPT) tended to reduce the occurrence of major adverse events following TAVR. SAPT reduced the risk for major or life-threatening events while not increasing the risk for MI or stroke. Larger studies are needed to confirm these results. (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation: The ARTE

  2. Hemorrhagic Cholecystitis in an Elderly Patient Taking Aspirin and Cilostazol

    Directory of Open Access Journals (Sweden)

    David S. Morris

    2008-06-01

    Full Text Available Hemorrhage is a rare complication of acute cholecystitis. Patients who develop this complication often are receiving anticoagulation therapy or have a pathologic coagulopathy. We present a case of an elderly patient who developed hemorrhagic cholecystitis while taking aspirin and cilostazol, a phosphodiesterase inhibitor. The patient underwent an emergent abdominal exploration. A large, blood-filled gallbladder was found along with a large hematoma between the liver and gallbladder. We also briefly review the literature regarding hemorrhagic cholecystitis, hemorrhage into the biliary tree, and hemorrhage as a complication of aspirin and phosphodiesterase inhibitor therapy.

  3. Optimizing the use of aspirin for cardiovascular prevention.

    Science.gov (United States)

    Casado-Arroyo, Rubén; Sostres, Carlos; Lanas, Angel

    2013-06-01

    This article describes the mechanism of action, pharmacokinetics, and pharmacodynamics of aspirin at doses used for cardiovascular prevention and provides specific management recommendations for optimal use in clinical practice. The paper highlights practical aspects related to antiplatelet therapy, including the optimal dose of aspirin, concomitant treatment with other NSAIDs, and strategies for the prevention of gastrointestinal toxicity. Specifically, we revise the benefits and hazards in different clinical settings to help the clinician in the decision-making process for individuals who have different risks for cardiovascular and gastrointestinal bleeding events.

  4. Determination of aspirin by pre-column transacetylation reaction of 3-aminophenol and reversed-phase high-performance liquid chromatography: simultaneous determination of aspirin, acetaminophen, and caffeine.

    Science.gov (United States)

    Verma, K K; Sanghi, S K; Jain, A; Gupta, D

    1987-07-01

    The accuracy of the measurement of aspirin by high-performance liquid chromatography (HPLC) is reduced by its hydrolysis into salicylic and acetic acids during sample preparation. The ready and quantitative transacetylation of 3-aminophenol by aspirin, giving 3-hydroxyacetanilide (which is stable), has been utilized as a pre-column reaction for the determination of aspirin either alone or in the presence of acetaminophen and caffeine by reversed-phase HPLC.

  5. Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line

    Directory of Open Access Journals (Sweden)

    Isabella Massimi

    2015-01-01

    Full Text Available Overexpression of efflux transporters, in human cells, is a mechanism of resistance to drug and also to chemotherapy. We found that multidrug resistance protein-4 (MRP4 overexpression has a role in reducing aspirin action in patients after bypass surgery and, very recently, we found that aspirin enhances platelet MRP4 levels through peroxisome proliferator activated receptor-α (PPARα. In the present paper, we verified whether exposure of human embryonic kidney-293 cells (Hek-293 to aspirin modifies MRP4 gene expression and its correlation with drug elimination and cell toxicity. We first investigated the effect of high-dose aspirin in Hek-293 and we showed that aspirin is able to increase cell toxicity dose-dependently. Furthermore, aspirin effects, induced at low dose, already enhance MRP4 gene expression. Based on these findings, we compared cell viability in Hek-293, after high-dose aspirin treatment, in MRP4 overexpressing cells, either after aspirin pretreatment or in MRP4 transfected cells; in both cases, a decrease of selective aspirin cell growth inhibition was observed, in comparison with the control cultures. Altogether, these data suggest that exposing cells to low nontoxic aspirin dosages can induce gene expression alterations that may lead to the efflux transporter protein overexpression, thus increasing cellular detoxification of aspirin.

  6. Up-regulation of Ciliary Neurotrophic Factor in Astrocytes by Aspirin

    Science.gov (United States)

    Modi, Khushbu K.; Sendtner, Michael; Pahan, Kalipada

    2013-01-01

    Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor, and the mechanisms by which CNTF expression could be increased in the brain are poorly understood. Acetylsalicylic acid (aspirin) is one of the most widely used analgesics. Interestingly, aspirin increased mRNA and protein expression of CNTF in primary mouse and human astrocytes in a dose- and time-dependent manner. Aspirin induced the activation of protein kinase A (PKA) but not protein kinase C (PKC). H-89, an inhibitor of PKA, abrogated aspirin-induced expression of CNTF. The activation of cAMP-response element-binding protein (CREB), but not NF-κB, by aspirin, the abrogation of aspirin-induced expression of CNTF by siRNA knockdown of CREB, the presence of a consensus cAMP-response element in the promoter of CNTF, and the recruitment of CREB and CREB-binding protein to the CNTF promoter by aspirin suggest that aspirin increases the expression of the Cntf gene via the activation of CREB. Furthermore, we demonstrate that aspirin-induced astroglial CNTF was also functionally active and that supernatants of aspirin-treated astrocytes of wild type, but not Cntf null, mice increased myelin-associated proteins in oligodendrocytes and protected oligodendrocytes from TNF-α insult. These results highlight a new and novel myelinogenic property of aspirin, which may be of benefit for multiple sclerosis and other demyelinating disorders. PMID:23653362

  7. Aspirin Inhibits Colon Cancer Cell and Tumor Growth and Downregulates Specificity Protein (Sp) Transcription Factors

    Science.gov (United States)

    Pathi, Satya; Jutooru, Indira; Chadalapaka, Gayathri; Nair, Vijayalekshmi; Lee, Syng-Ook; Safe, Stephen

    2012-01-01

    Acetylsalicylic acid (aspirin) is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NFκB). Moreover, we also showed by RNA interference that β-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite. PMID:23110215

  8. Preparation and analysis of deuterium-labeled aspirin: application to pharmacokinetic studies

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, A.K.; FitzGerald, G.A.

    1985-02-01

    Inhibition of endogenous prostacyclin and thromboxane biosynthesis by aspirin is critically dose-dependent in humans. Gastrointestinal and hepatic hydrolysis may limit systemic availability of aspirin, especially in low doses, perhaps contributing to the biochemical selectivity of aspirin. Existing analytical methods do not permit determination of systemic bioavailability when low (less than 100 mg) doses of aspirin are administered. Deuterium-labeled aspirin (2-acetoxy(3,4,5,6-/sup 2/H4)benzoic acid) was synthesized from salicylic acid by catalytic exchange and subsequent acetylation. Analysis of the compounds as benzyl esters by GC-MS followed extractive alkylation from plasma. Heptadeuterated compounds were used as internal standards. Simultaneous administration of tetradeuterated aspirin intravenously with native aspirin orally to anesthetized dogs permitted kinetic studies of both aspirin and salicylic acid. The sensitivity of the method is superior to published methods using HPLC and, thus, more applicable to studies of low dose aspirin. Pulse administration of stable isotope-labeled aspirin permits detailed and repeated studies of dose-related aspirin pharmacokinetics in humans.

  9. Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs

    Science.gov (United States)

    Li, Xuanwen; Fries, Susanne; Li, Ruizhi; Lawson, John A.; Propert, Kathleen J.; Diamond, Scott L.; Blair, Ian A.; FitzGerald, Garret A.; Grosser, Tilo

    2014-01-01

    The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be influenced by interactions with antiplatelet doses of aspirin. We sought to quantitate precisely the propensity of commonly consumed NSAIDs—ibuprofen, naproxen, and celecoxib—to cause a drug–drug interaction with aspirin in vivo by measuring the target engagement of aspirin directly by MS. We developed a novel assay of cyclooxygenase-1 (COX-1) acetylation in platelets isolated from volunteers who were administered aspirin and used conventional and microfluidic assays to evaluate platelet function. Although ibuprofen, naproxen, and celecoxib all had the potential to compete with the access of aspirin to the substrate binding channel of COX-1 in vitro, exposure of volunteers to a single therapeutic dose of each NSAID followed by 325 mg aspirin revealed a potent drug–drug interaction between ibuprofen and aspirin and between naproxen and aspirin but not between celecoxib and aspirin. The imprecision of estimates of aspirin consumption and the differential impact on the ability of aspirin to inactivate platelet COX-1 will confound head-to-head comparisons of distinct NSAIDs in ongoing clinical studies designed to measure their cardiovascular risk. PMID:25385584

  10. Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line.

    Science.gov (United States)

    Massimi, Isabella; Ciuffetta, Ambra; Temperilli, Flavia; Ferrandino, Francesca; Zicari, Alessandra; Pulcinelli, Fabio M; Felli, Maria Pia

    2015-01-01

    Overexpression of efflux transporters, in human cells, is a mechanism of resistance to drug and also to chemotherapy. We found that multidrug resistance protein-4 (MRP4) overexpression has a role in reducing aspirin action in patients after bypass surgery and, very recently, we found that aspirin enhances platelet MRP4 levels through peroxisome proliferator activated receptor-α (PPARα). In the present paper, we verified whether exposure of human embryonic kidney-293 cells (Hek-293) to aspirin modifies MRP4 gene expression and its correlation with drug elimination and cell toxicity. We first investigated the effect of high-dose aspirin in Hek-293 and we showed that aspirin is able to increase cell toxicity dose-dependently. Furthermore, aspirin effects, induced at low dose, already enhance MRP4 gene expression. Based on these findings, we compared cell viability in Hek-293, after high-dose aspirin treatment, in MRP4 overexpressing cells, either after aspirin pretreatment or in MRP4 transfected cells; in both cases, a decrease of selective aspirin cell growth inhibition was observed, in comparison with the control cultures. Altogether, these data suggest that exposing cells to low nontoxic aspirin dosages can induce gene expression alterations that may lead to the efflux transporter protein overexpression, thus increasing cellular detoxification of aspirin.

  11. Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp) transcription factors.

    Science.gov (United States)

    Pathi, Satya; Jutooru, Indira; Chadalapaka, Gayathri; Nair, Vijayalekshmi; Lee, Syng-Ook; Safe, Stephen

    2012-01-01

    Acetylsalicylic acid (aspirin) is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NFκB). Moreover, we also showed by RNA interference that β-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite.

  12. Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp transcription factors.

    Directory of Open Access Journals (Sweden)

    Satya Pathi

    Full Text Available Acetylsalicylic acid (aspirin is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NFκB. Moreover, we also showed by RNA interference that β-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite.

  13. Glucose-aspirin: Synthesis and in vitro anti-cancer activity studies.

    Science.gov (United States)

    Jacob, James N; Tazawa, Makio J

    2012-05-01

    Glucose-aspirin (GA) was synthesized by conjugating aspirin (ASA) to glucose. The water solubility and biological activity of GA was studied in comparison to aspirin. The human serum protease activity on the ester showed a slower hydrolysis rate, compared to ASA. Glucose-aspirin was sevenfold more water soluble than aspirin and it was about 8- to 9-fold more active in inhibiting cell growth than aspirin in their anti-cancer cell culture activity on breast (SKBR3), pancreatic (PANC-1), and prostate (PC3) cell lines, whereas the activity was similar on a benign non-cancerous cell line (WI 38). In conclusion, GA is a highly water soluble derivative of aspirin. Although the serum hydrolysis for GA was slower, there was significant anti-cancer activity at the doses studied under the experimental conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Once- versus twice-daily aspirin treatment in patients with essential thrombocytosis

    DEFF Research Database (Denmark)

    Larsen, Mads Lamm; Pedersen, Oliver Heidmann; Hvas, Anne-Mette

    2018-01-01

    Insufficient platelet inhibition has been reported in up to 40% of aspirin-treated patients, including patients with essential thrombocytosis. To maintain sufficient platelet inhibition, a shorter dosing interval with aspirin has been suggested. We aimed to investigate the antiplatelet effect...... of low-dose aspirin given twice-daily compared to standard once-daily dosing in patients with essential thrombocytosis. We included 22 patients, who were treated for 7 days with standard once-daily aspirin (75 mg once-daily) followed by 7 days treatment of twice-daily aspirin (37.5 mg twice......-daily). The two regimens were separated by 14 days aspirin washout. Blood samples were obtained 1h and 24h/12h after the last pill intake in each regimen. The effect of aspirin was evaluated by: (1) platelet aggregation measured by whole blood impedance aggregometry (Multiplate® Analyser) using arachidonic acid...

  15. The administration of a loading dose of aspirin to patients presenting with acute myocardial infarction while receiving chronic aspirin treatment reduces thromboxane A2-dependent platelet reactivity.

    Science.gov (United States)

    Santos, Maria Teresa; Madrid, Isabel; Moscardo, Antonio; Latorre, Ana M; Bonastre, Juan; Ruano, Miguel; Valles, Juana

    2014-01-01

    Abstract The optimal dose of aspirin for patients presenting with acute myocardial infarction (AMI) while receiving chronic aspirin therapy has not been clearly established. We evaluated whether continued treatment with 100 mg of aspirin or a loading dose (200-500 mg) influences thromboxane A2 (TX) suppression or platelet reactivity. Sixty-four consecutive patients with AMI and 98 healthy subjects (82 aspirin-free and 16 receiving 100 mg daily for a week) were evaluated. Treatment was at the discretion of the attending physician. Collagen (1 µg/ml)-induced TX synthesis, (14)C-serotonin-release, platelet aggregation, and the PFA-100 assay were evaluated. The platelet TX synthesis of patients receiving a loading dose of aspirin was sixfold lower than that of patients receiving 100 mg of aspirin (psynthesis (aspirin-free subjects) revealed that 8% of the patients treated with loading doses had a poor response (aspirin to patients with AMI during existing chronic aspirin treatment induced greater reductions in platelet TX synthesis and TX-dependent platelet reactivity than the continued treatment alone.

  16. 15-epi-lipoxin A4-mediated induction of nitric oxide explains how aspirin inhibits acute inflammation.

    OpenAIRE

    Paul-Clark, M. J.; Van Cao, T.; Moradi-Bidhendi, N.; Cooper, D.; Gilroy, D. W.

    2004-01-01

    The established model for the mechanism of action of aspirin is the inhibition of prostaglandin synthesis. However, this has never fully explained aspirin's repertoire of antiinflammatory properties. We found in acute pleuritis that aspirin, but not salicylate, indomethacin, or piroxicam, increased plasma nitric oxide (NO), which correlated with a reduction in inflammation. Inhibiting aspirin-elicited NO pharmacologically in this model nullified the antiinflammatory effects of aspirin. Moreov...

  17. Intracellular Erythrocyte Platelet-activating Factor Acetylhydrolase I Inactivates Aspirin in Blood*

    Science.gov (United States)

    Zhou, Gang; Marathe, Gopal K.; Willard, Belinda; McIntyre, Thomas M.

    2011-01-01

    Aspirin (acetylsalicylic acid) prophylaxis suppresses major adverse cardiovascular events, but its rapid turnover limits inhibition of platelet cyclooxygenase activity and thrombosis. Despite its importance, the identity of the enzyme(s) that hydrolyzes the acetyl residue of circulating aspirin, which must be an existing enzyme, remains unknown. We find that circulating aspirin was extensively hydrolyzed within erythrocytes, and chromatography indicated these cells contained a single hydrolytic activity. Purification by over 1400-fold and sequencing identified the PAFAH1B2 and PAFAH1B3 subunits of type I platelet-activating factor (PAF) acetylhydrolase, a phospholipase A2 with selectivity for acetyl residues of PAF, as a candidate for aspirin acetylhydrolase. Western blotting showed that catalytic PAFAH1B2 and PAFAH1B3 subunits of the type I enzyme co-migrated with purified erythrocyte aspirin hydrolytic activity. Recombinant PAFAH1B2, but not its family member plasma PAF acetylhydrolase, hydrolyzed aspirin, and PAF competitively inhibited aspirin hydrolysis by purified or recombinant erythrocyte enzymes. Aspirin was hydrolyzed by HEK cells transfected with PAFAH1B2 or PAFAH1B3, and the competitive type I PAF acetylhydrolase inhibitor NaF reduced erythrocyte hydrolysis of aspirin. Exposing aspirin to erythrocytes blocked its ability to inhibit thromboxane A2 synthesis and platelet aggregation. Not all individuals or populations are equally protected by aspirin prophylaxis, the phenomenon of aspirin resistance, and erythrocyte hydrolysis of aspirin varied 3-fold among individuals, which correlated with PAFAH1B2 and not PAFAH1B3. We conclude that intracellular type I PAF acetylhydrolase is the major aspirin hydrolase of human blood. PMID:21844189

  18. Influence of non-steroidal anti-inflammatory drugs on antiplatelet effect of aspirin.

    Science.gov (United States)

    Yokoyama, H; Ito, N; Soeda, S; Ozaki, M; Suzuki, Y; Watanabe, M; Kashiwakura, E; Kawada, T; Ikeda, N; Tokuoka, K; Kitagawa, Y; Yamada, Y

    2013-02-01

    It has been reported that ibuprofen interferes with the antiplatelet effect of low-dose aspirin. This interaction is ascribed to steric hindrance at the active site of cyclooxygenase-1 by ibuprofen, when aspirin is administered after ibuprofen. However, whether other non-steroidal anti-inflammatory drugs (NSAIDs) interact with aspirin similarly is not well defined. The aim of this study was to assess the influence of nine NSAIDs on the antiplatelet effect of aspirin. We investigated the antiplatelet effect of NSAIDs using steady-state plasma concentration reported after usual doses. We studied the in vitro antiplatelet effect of NSAID alone, aspirin alone, aspirin before NSAID addition and aspirin after NSAID addition to platelet-rich plasma. The rates of platelet aggregation induced by collagen were determined. The final concentration of aspirin used was the 50% effective concentration (EC(50)) previously estimated in vitro. Ibuprofen and mefenamic acid interfere with the antiplatelet effect of aspirin when added before the latter. The rate of platelet aggregation was reduced by 48·1% and 22·7%, respectively. The other NSAIDs tested did not significantly affect the aspirin antiplatelet effect when exposure was prior to aspirin. None of the nine NSAIDs altered the aspirin effect if administration followed that of aspirin. Naproxen and flurbiprofen have significant antiplatelet effects at plasma concentrations seen with usual doses. Our in vitro model suggests that the antiplatelet effect of aspirin is significantly diminished when taken after, but not before, ibuprofen or mefenamic acid. None of the other NSAIDs tested had any effect irrespective of the timing of dosing. © 2012 Blackwell Publishing Ltd.

  19. USE AND MISUSE OF ASPIRIN IN RURAL ETHIOPIA P. DUNCAN ...

    African Journals Online (AJOL)

    hi-tech

    2006-01-01

    Jan 1, 2006 ... sex, age, urban or rural residence and highest educational level attained (by father if the respondent was aged .... availability of aspirin after adjustment for age, sex and literacy (OR for rural vs urban availability ... advertising, and possibly a difference in prevalence of malaria fever, may explain the different ...

  20. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

    NARCIS (Netherlands)

    Weitz, Jeffrey I.; Lensing, Anthonie W. A.; Prins, Martin H.; Bauersachs, Rupert; Beyer-Westendorf, Jan; Bounameaux, Henri; Brighton, Timothy A.; Cohen, Alexander T.; Davidson, Bruce L.; Decousus, Hervé; Freitas, Maria C. S.; Holberg, Gerlind; Kakkar, Ajay K.; Haskell, Lloyd; van Bellen, Bonno; Pap, Akos F.; Berkowitz, Scott D.; Verhamme, Peter; Wells, Philip S.; Prandoni, Paolo; Bianchi, Alessandra; Brighton, Tim; Carroll, Patrick; Chong, Beng; Chunilal, Sanjeev; Coughlin, Paul; Curnow, Jennifer; Jackson, David; Tran, Huyen; Ward, Chris; Brodmann, Marianne; Kyrle, Paul; Marschang, Peter; Petkov, Ventzislav; Hainaut, Philippe; Jordens, Paul; Vandekerkhof, Jos; Wautrecht, Jean-Claude; Annichino-Bizzacchi, Joyce; Correa, Joao; Cukier, Alberto; Freire, Antonio; Pereira, Adamastor; Porto, Carmen; Sacilotto, Roberto; Vasconcelos Costa, Agenor; Della Siega, Anthony; Dolan, Sean; Le Gal, Gré goire; Gross, Peter; Kahn, Susan; Kassis, Jeannine; Kovacs, Michael; Pesant, Yves; Ritchie, Bruce; Schulman, Sam; Shivakumar, Sudeep; Solymoss, Susan; Chang, Shu; Chen, Rongchang; Chen, Zhong; Chen, Hong; Dai, Xiangchen; Fang, Baoming; Fu, Weiguo; Gao, Xinglin; Huang, Jinhua; Lai, Yanping; Li, Li; Li, Xiaoqiang; Li, Yiqing; Liu, Jinming; Liu, Shuang; Ma, Wenjiang; Ni, Songshi; Qin, Zhiqiang; Shi, Guochao; Tian, Hongyan; Wang, Shenming; Wang, Lie; Xiao, Wei; Ying, Kejing; Yu, Guanfeng; Yuan, Yadong; Zhang, Jie; Zhang, Jin; Zhang, Xinri; Zhang, Liyan; Zhu, Lei; Chlumský , Jaromir; Chochola, Jiri; Dunaj, Milna; Kovarova, Katerina; Lang, Pavel; Matoš ka, Petr; Podpera, Ivo; Spacek, Rudolf; Stehlikova, Olga; Brø nnum-Schou, Jens; Egstrup, Kenneth; Gislason, Gunnar; Jeppesen, Jorgen; May, Ole; Nielsen, Henrik; Wiggers, Henrik; Achkar, Antoine; Aquilanti, Sandro; Benhamou, Ygal; Brisot, Dominique; Bura-Riviere, Alessandra; Castella, Nadine; Elias, Antoine; Falvo, Nicolas; Ferrari, Emile; Lacroix, Philippe; Mahe, Isabelle; Meneveau, Nicolas; Messas, Emmanuel; Mismetti, Patrick; Montaclair, Karine; Mottier, Dominique; Moumneh, Thomas; Paleiron, Nicolas; Parent, Florence; Pernod, Gilles; Sanchez, Olivier; Schmidt, Jeannot; Simoneau, Guy; Stephan, Dominique; Amann, Berthold; Blessing, Erwin; Czihal, Michael; Espinola-Klein, Christine; Kahrmann, Gerd; Licka, Manuela; Neumeister, Axel; Schellong, Sebastian; Boda, Zoltan; Farkas, Katalin; Gurzo, Mihaly; Katona, Andras; Riba, Maria; Sipos, Gyula; Tó th, Kalman; Braester, Andrei; Elias, Mazen; Gafter-Gvili, Anat; Gavish, Dov; Hussein, Osamah; Lishner, Michael; Schiff, Elad; Spectre, Galia; Tzoran-Rozenthal, Inna; Zimlichman, Reuven; Ageno, Walter; Agnelli, Giancarlo; Bova, Carlo; Garbelotto, Raffaella; Ghirarduzzi, Angelo; Imberti, Davide; Pesavento, Raffaele; Porreca, Ettore; Visonà , Adriana; Flota Cervera, Luis; Llamas Esperó n, Guillermo; Rodriguez-Gonzalez, Daniel; Solis Morales, Lucas; Boersma, Willem; ten Cate, Hugo; Erdkamp, Franciscus; Grifioen-Keijzer, Anita; Marwijk Kooy, Marinus; Meijer, Karina; Middeldorp, Saskia; Swart-Heikens, Janneke; ten Wolde, Marije; Westerweel, Peter; Braithwaite, Irene; Harper, Paul; Merriman, Eileen; Ockelford, Paul; Royle, Gordon; Smith, Mark; Ghanima, Waleed; Sandset, Per Morten; Abola, Maria; Chę ciń ski, Pawel; Grzelakowski, Pawel; Lewczuk, Jerzy; Sobkowicz, Bozena; Tomkowski, Witold; Abramov, Igor; Chechulov, Pavel; Karpenko, Andrey; Katelnitskiy, Ivan; Kazakov, Andrey; Makarova, Olga; Panchenko, Elizaveta; Sergeeva, Elena; Subbotin, Yuriy; Suchkov, Igor; Zeltser, Mikhail; Adler, David; Breedt, Johannes; Fourie, Nyda; Isaacs, Rashid; Jacobson, Barry; Siebert, Heidi; van Zyl, Louis; Choi, Jung-Hyun; Kang, Seok-Min; Kim, Kye-Hun; Kim, Hyo-Soo; Kim, Dong-Ik; Min, Seung-Kee; Park, Ki Hyuk; Garcí a-Bragado Dalmau, Fernando; Gó mez Cerezo, Jorge; Mirete, Jose Carlos Ferrer; Riera, Antonio; del Toro, Jorge; Eriksson, Henry; Torstensson, Ingemar; Banyai, Martin; Baumgartner, Iris; Mazzolai, Lucia; Periard, Daniel; Righini, Marc; Staub, Daniel; Chiang, Chern-En; Chiu, Kuan-Ming; Pai, Pei-Ying; Angchaisuksiri, Pantep; Chansung, Kanchana; Ö ngen, Gul; Tuncay, Esin; Alikhan, Raza; Chetter, Ian; Kesteven, Patrick; Nokes, Tim; Bauer, Kenneth; Comerota, Anthony; Elias, Darlene; Garcia, David; Gibson, Kathleen; Ginsberg, Daniel; Jenkins, Jeffrey; Kingsley, Edwin; Lambert, Richard; Lyons, Roger; Pullman, John; Shah, Vinay; Smith, S. Wayne; Stein, Robert; Tapson, Victor; Walsh, John; Wang, Tzu-Fei; Do Loi, Doan; Do Quang, Huan; Pham, Nguyen

    2017-01-01

    BACKGROUND Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin. METHODS In this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous

  1. USE AND MISUSE OF ASPIRIN IN RURAL ETHIOPIA P. DUNCAN ...

    African Journals Online (AJOL)

    hi-tech

    2006-01-01

    Jan 1, 2006 ... East African Medical Journal Vol. 83 No. 1 January 2006. USE AND MISUSE OF ASPIRIN IN RURAL ETHIOPIA. P. Duncan, BSc, G. Aref-Adib, BSc, A. Venn, PhD, J. Britton, MD, Division of Epidemiology and Public Health, University of Nottingham, City Hospital,. Hucknall Road, Nottingham NG5 1PB and ...

  2. The kinetics of hydrolysis of acetylsalicylic acid (Aspirin) in different ...

    African Journals Online (AJOL)

    The kinetics of hydrolysis of Acetylsalicylic acid (Aspirin) to salicylic acid was followed by the direct spectrophotometric measurement of the amount of salicylic acid produced with time. Salicylic acid was complexed with ferric ion giving a characteristic purple colour (λlm 523nm). The kinetics of hydrolysis was found to follow ...

  3. In vitro effects of aspirin and paracetamol on human erythrocyte ...

    African Journals Online (AJOL)

    The activity of glutathione-S-transferase of human erythrocytes was monitored spectrophotometically in the presence and absence of two analgesics (aspirin and paracetamol). Five different concentrations (1.0, 3.0, 5.0, 7.0, 9.0 and 10.0 mg/ml) of each analgesic were used which covers the reported therapeutic and toxic ...

  4. Modelling of drug release from ensembles of aspirin microcapsules ...

    African Journals Online (AJOL)

    Purpose: In order to determine the drug release profile of an ensemble of aspirin crystals or microcapsules from its particle distribution a mathematical model that considered the individual release characteristics of the component single particles was developed. The model assumed that under sink conditions the release ...

  5. Heparin and Aspirin in Pregnant Sudanese women with Recurrent ...

    African Journals Online (AJOL)

    This was a prospective clinical trial conducted at Khartoum Fertility Center, during the period June 2002 to February 2005 to investigate the efficacy of unfractionated heparin and low-dose aspirin as prophylaxis against pregnancy loss in 58 pregnant Sudanese women with recurrent (>3) miscarriages associated with ...

  6. Low-dose aspirin and risk of intracranial bleeds

    DEFF Research Database (Denmark)

    Cea Soriano, Lucía; Gaist, David; Soriano-Gabarró, Montse

    2017-01-01

    OBJECTIVE: To quantify the risk of intracranial bleeds (ICBs) associated with new use of prophylactic low-dose aspirin using a population-based primary care database in the United Kingdom. METHODS: A cohort of new users of low-dose aspirin (75-300 mg; n = 199,079) aged 40-84 years and a 1:1 matched...... cohort of nonusers of low-dose aspirin at baseline were followed (maximum 14 years, median 5.4 years) to identify incident cases of ICB, with validation by manual review of patient records or linkage to hospitalization data. Using 10,000 frequency-matched controls, adjusted rate ratios (RRs) with 95......% confidence intervals (CIs) were calculated for current low-dose aspirin use (0-7 days before the index date [ICB date for cases, random date for controls]); reference group was never used. RESULTS: There were 1,611 cases of ICB (n = 743 for intracerebral hemorrhage [ICH], n = 483 for subdural hematoma [SDH...

  7. Transfer of Low Dose Aspirin Into Human Milk.

    Science.gov (United States)

    Datta, Palika; Rewers-Felkins, Kathleen; Kallem, Raja Reddy; Baker, Teresa; Hale, Thomas W

    2017-05-01

    Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography-tandem mass spectrometry. Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.

  8. Acetaminophen, aspirin and progression of advanced chronic kidney disease

    NARCIS (Netherlands)

    Evans, Marie; Fored, Carl Michael; Bellocco, Rino; Fitzmaurice, Garrett; Fryzek, Jon P.; McLaughlin, Joseph K.; Nyren, Olof; Elinder, Carl-Gustaf

    Background. Although many studies have investigated the possible association between analgesic use (acetaminophen and aspirin) and the development of chronic kidney disease (CKD), the effect of analgesics on the progression of established CKD of any cause has not yet been investigated. Methods. In

  9. Integrative medicine on optimizing clopidogrel and aspirin therapy.

    Science.gov (United States)

    Chen, Hui

    2018-01-15

    This article reviews the available published data on optimizing clopidogrel and aspirin therapy using translational and integrative medicine. Translational and evidence-based medical studies show that the CYP2C19 gene mutation (CYP2C19*2 and CYP2C19*3) could affect > 50% of the Chinese population, and that this mutation is closely associated with clopidogrel resistance and an increased risk of major adverse cardiovascular events, particularly stent thrombosis in patients following percutaneous coronary intervention (PCI). Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation (AF), and warfarin is substantially more efficacious than aspirin. However, a poor compliance is a big problem in warfarin use especially in China. The genetic variants of vitamin K expoxide reductase might account for the universally lower warfarin dosage used in Chinese population. The available evidence indicates that the integrating mainstream treatments (e.g., clopidogrel, CYP2C19 genotyping) and non-mainstream medicines [e.g., Chinese medicines, Naoxintong Capsule (, NXT)] to treat CYP2C19 gene mutation patients following PCI can be effective. Aspirin combined NXT and the adjusted-dose warfarin was equally effective in elderly patients with non-valvular AF in prevention of ischemic stroke.

  10. Reye's syndrome: the case for a causal link with aspirin.

    Science.gov (United States)

    Glasgow, John F T

    2006-01-01

    Reye's syndrome is a serious, acute encephalopathy that has been linked with aspirin (acetylsalicylic acid) use in children and teenagers Reye's syndrome and ingestion of aspirin during the febrile prodrome. The drug appears to act as a co-factor in susceptible individuals. Although some of the epidemiological data indicate an association between the two, the burden of evidence suggests actual causality and is both consistent and specific as well as strong and time related. Some of the evidence points to illness severity being dose related although it seems that in the presence of a viral infection, no dose of aspirin can be considered safe. No published work, using methodology that can be critically evaluated, has shown evidence to contradict these conclusions and they have been widely accepted. Since government health warnings were appended to aspirin-containing formulations, the decline in case numbers on both sides of the Atlantic has been nothing short of remarkable. Recent in vitro findings have pinpointed the site of action of the drug on the long chain hydroxyacyl-CoA dehydrogenase enzyme (a component of the mitochondrial trifunctional enzyme) and, even at therapeutic concentrations, oxidation is impaired in cultured fibroblasts from patients who have recovered from the disorder. This is quite unlike that seen in cells from normal controls. Even when major influenza outbreaks occur in the future, Reye's syndrome is preventable provided government health warnings are heeded and the cogent evidence set forth here is acted upon by the parents of feverish children and self-medicating teenagers.

  11. Synthesis, characterization and antibacterial activity of aspirin and ...

    African Journals Online (AJOL)

    Aspirin complexes coordinate through the carbonyl oxygen of the carboxyl and the ester groups, while paracetamol complexes coordinate through the oxygen of the hydroxyl and the amide groups. Antibacterial screening of the complexes against Bacillus substilis, Serratia species and Escherichia coli, was also ...

  12. Effect of Aspirin on Fractalkine in Rats with Pulmonary Embolism

    African Journals Online (AJOL)

    Cai B, Sun C, Wang LC, and Qian H: Curcumin improves the outcomes of acute pulmonary embolism in rats. Zhejiang Med J 2011; 33: 457-459. 8. Widmer BJ, Bassora R, Warrender WJ, Abboud JA: Thromboembolic events are uncommon after open treatment of proximal humerus fractures using aspirin and compression ...

  13. Aspirin for Prevention of Preeclampsia in Lupus Pregnancy

    Directory of Open Access Journals (Sweden)

    Amelie M. Schramm

    2014-01-01

    Full Text Available Preeclampsia, the onset of hypertension and proteinuria during pregnancy, is a common medical disorder with high maternal and fetal mortality and morbidity. The underlying pathology remains poorly understood and includes inflammation, endothelial dysfunction, and an unbalanced thromboxane A2/prostacyclin ratio. For women with systemic lupus erythematosus (SLE, particularly those with preexisting renal disease or with active lupus, the risk of developing preeclampsia is up to 14% higher than it is among healthy individuals. The mechanism is still unknown and the data for preventing preeclampsia in lupus pregnancies are rare. Modulating the impaired thromboxane A2/prostacyclin ratio by administration of low-dose aspirin appears to be the current best option for the prevention of preeclampsia. After providing an overview of the pathogenesis of preeclampsia, preeclampsia in lupus pregnancies, and previous trials for prevention of preeclampsia with aspirin treatment, we recommend low-dose aspirin administration for all lupus patients starting prior to 16 weeks of gestation. Patients with SLE and antiphospholipid syndrome should receive treatment with heparin and low-dose aspirin during pregnancy.

  14. Aspirin in the 21st century-common mechanisms of disease and their modulation by aspirin: a report from the 2015 scientific conference of the international aspirin foundation, 28 August, London, UK.

    Science.gov (United States)

    Smith, Tom; Hutchison, Pippa; Schrör, Karsten; Clària, Joan; Lanas, Angel; Patrignani, Paola; Chan, Andrew T; Din, Farhat; Langley, Ruth; Elwood, Peter; Freedman, Andrew; Eccles, Ron

    2015-01-01

    Professor Peter Rothwell of Oxford University chaired the annual Scientific Conference of the International Aspirin Foundation in London on 28 August 2015. It took the form of four sessions. Aspirin has more than one action in its effects on disease. Its acetylation of cyclooxygenase 2 (COX-2) in platelets leads to the blockade of pro-inflammatory chemicals and generation of anti-inflammatory mediators and increase in nitrous oxide (NO) production, which helps to preserve arterial endothelium. But platelets are not its only target. There is now evidence that aspirin has a direct antitumour effect on intestinal mucosal cells that block their potential transformation into cancer cells. Randomised placebo-controlled trials (RCTs) in people with histories of colorectal neoplasia have shown that aspirin reduces the risk of recurrent adenomas and reduces long-term cancer incidence in patients with Lynch syndrome. Among women given aspirin for cardiovascular disease, there were fewer cancers than in those given placebo. Epidemiological evidence has suggested that aspirin treatment after cancer is diagnosed reduces the incidence of metastases and prolongs survival, and long-term studies of anticancer treatment with aspirin are under way to confirm this. Apart from cancer studies, aspirin use is now firmly established as treatment for antiphospholipid syndrome (Hughes syndrome) and is being used to prevent and treat the heightened risk of cardiovascular disease in diabetes mellitus and in patients with HIV.

  15. Aspirin in the 21st century—common mechanisms of disease and their modulation by aspirin: a report from the 2015 scientific conference of the international aspirin foundation, 28 August, London, UK

    Science.gov (United States)

    Smith, Tom; Hutchison, Pippa; Schrör, Karsten; Clària, Joan; Lanas, Angel; Patrignani, Paola; Chan, Andrew T; Din, Farhat; Langley, Ruth; Elwood, Peter; Freedman, Andrew; Eccles, Ron

    2015-01-01

    Professor Peter Rothwell of Oxford University chaired the annual Scientific Conference of the International Aspirin Foundation in London on 28 August 2015. It took the form of four sessions. Aspirin has more than one action in its effects on disease. Its acetylation of cyclooxygenase 2 (COX-2) in platelets leads to the blockade of pro-inflammatory chemicals and generation of anti-inflammatory mediators and increase in nitrous oxide (NO) production, which helps to preserve arterial endothelium. But platelets are not its only target. There is now evidence that aspirin has a direct antitumour effect on intestinal mucosal cells that block their potential transformation into cancer cells. Randomised placebo-controlled trials (RCTs) in people with histories of colorectal neoplasia have shown that aspirin reduces the risk of recurrent adenomas and reduces long-term cancer incidence in patients with Lynch syndrome. Among women given aspirin for cardiovascular disease, there were fewer cancers than in those given placebo. Epidemiological evidence has suggested that aspirin treatment after cancer is diagnosed reduces the incidence of metastases and prolongs survival, and long-term studies of anticancer treatment with aspirin are under way to confirm this. Apart from cancer studies, aspirin use is now firmly established as treatment for antiphospholipid syndrome (Hughes syndrome) and is being used to prevent and treat the heightened risk of cardiovascular disease in diabetes mellitus and in patients with HIV. PMID:26557879

  16. Population Trends in Aspirin Use for Cardiovascular Disease Prevention 1980-2009: The Minnesota Heart Survey.

    Science.gov (United States)

    Luepker, Russell V; Steffen, Lyn M; Duval, Sue; Zantek, Nicole D; Zhou, Xia; Hirsch, Alan T

    2015-12-23

    Daily low-dose aspirin is recommended for primary prevention of myocardial infarction and stroke in higher-risk patients. Population trends in aspirin use for cardiovascular disease (CVD) prevention in an urban population (Minneapolis/St. Paul, 2010 population 2.85 million) from 1980 to 2009 were evaluated. Surveys of randomly selected adults aged 25 to 74 years were collected at 5-year intervals. Self-reports of regular aspirin use for CVD prevention and history of CVD were obtained. Six cross-sectional surveys included 12 281 men and 14 258 women. Age-adjusted aspirin use for primary prevention increased during this period from 1% to 21% among men and 1% to 12% among women. Aspirin use was highest in those aged 65 to 74 years. For secondary prevention, age-adjusted aspirin use increased from 19% to 74% among men and 11% to 64% among women. While data are based on self-report, a substudy using a biochemical indicator of aspirin use (serum thromboxane B2) supports the validity of self-report. Aspirin for CVD prevention is commonly used by a large and growing portion of the general population. It is not known if this is based on professional advice or self-prescribed use. It is also likely that many who would benefit do not use aspirin and others use aspirin inappropriately. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  17. Increased platelet aggregation and serum thromboxane levels in aspirin-treated patients with prior myocardial infarction.

    Science.gov (United States)

    Larsen, Sanne Bøjet; Neergaard-Petersen, Søs; Grove, Erik Lerkevang; Kristensen, Steen Dalby; Hvas, Anne-Mette

    2012-07-01

    The antiplatelet effect of aspirin displays considerable inter-individual variability. We investigated the antiplatelet effect of aspirin in patients with coronary artery disease on aspirin mono-therapy with and without prior myocardial infarction (MI). Further, we investigated whether the effect of aspirin differed between patients with and without aspirin use at the time of MI onset. We performed a study on 231 patients, including 171 with prior MI. Among patients with only one prior MI (116 patients), 59 patients were on aspirin at the time of MI onset. All patients received 75 mg aspirin as mono-therapy. Platelet aggregation was assessed by multiple electrode aggregometry (Multiplate) and VerifyNow, and platelet activation was evaluated by soluble P-selectin. Furthermore, we measured serum thromboxane B2. MI patients had higher median platelet aggregation levels than patients without prior MI when evaluated by Multiplate (parachidonic acidaspirin before MI onset had significantly higher median aggregation levels compared with MI patients not on aspirin when evaluated by Multiplate (pcollagen=0.02) and VerifyNow (paspirin dose and optimal compliance. Serum thromboxane B2 levels were higher in MI patients than in patients without prior MI. Finally, patients on aspirin before MI onset had higher aggregation levels compared with patients not on aspirin.

  18. Effect of Aspirin and Indomethacin on Prostaglandin E2 Synthesis in C6 Glioma Cells

    Directory of Open Access Journals (Sweden)

    Shiuh-Lin Hwang

    2004-01-01

    Full Text Available Prostaglandin E2 (PGE2 plays an important role in immunosuppression and tumor growth. PGE2 inhibitors such as aspirin and indomethacin suppress experimental tumor growth. Little is known of the relationship between PGE2 synthesis in brain tumors and the dose of aspirin or indomethacin. The present study was undertaken to evaluate the effect of different doses of aspirin and indomethacin on PGE2 synthesis in C6 glioma cells. C6 glioma cells were incubated with different concentrations (2, 4, and 8 μM of aspirin and indomethacin for 1, 2, 4, 6, 8, 12, and 24 hours. Intracellular PGE2 concentration was measured by enzyme immunoassay. Each concentration of aspirin and indomethacin effectively inhibited PGE2 synthesis. Concentrations of 2, 4, and 8 μM of aspirin significantly inhibited PGE2 production at 6, 4, and 1 hours, respectively, and the inhibition persisted for more than 24 hours (p 0.05. Indomethacin 8 μM was effective at 1 hour and the inhibition persisted beyond 24 hours (p < 0.05. Our study demonstrates that aspirin and indomethacin inhibit PGE2 synthesis in C6 glioma cells and that low-dose aspirin is as effective as high-dose aspirin. This study may encourage future clinical use of low-dose aspirin in the prevention or treatment of brain tumors.

  19. Should This Patient Receive Aspirin?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

    Science.gov (United States)

    Burns, Risa B; Graham, Kelly; Sawhney, Mandeep S; Reynolds, Eileen E

    2017-12-05

    Aspirin exerts antiplatelet effects through irreversible inhibition of cyclooxygenase-1, whereas its anticancer effects may be due to inhibition of cyclooxygenase-2 and other pathways. In 2009, the U.S. Preventive Services Task Force endorsed aspirin for primary prevention of cardiovascular disease. However, aspirin's role in cancer prevention is still emerging, and no groups currently recommend its use for this purpose. To help physicians balance the benefits and harms of aspirin in primary disease prevention, the Task Force issued a guideline titled, "Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer" in 2016. In the evidence review conducted for the guideline, cardiovascular disease mortality and colorectal cancer mortality were significantly reduced among persons taking aspirin. However, there was no difference in nonfatal stroke, cardiovascular disease mortality, or all-cause mortality, nor in total cancer mortality, among those taking aspirin. Aspirin users were found to be at increased risk for major gastrointestinal bleeding. In this Beyond the Guidelines, the guideline is reviewed and 2 experts discuss how they would apply it to a 57-year-old man considering starting aspirin for primary prevention. Our experts review the data on which the guideline is based, discuss how they would balance the benefits and harms of aspirin therapy, and explain how they would incorporate shared decision making into clinical practice.

  20. Aspirin resistance in children and young adults with splenectomized thalassemia diseases.

    Science.gov (United States)

    Sirachainan, Nongnuch; Wijarn, Piyathida; Chuansumrit, Ampaiwan; Kadegasem, Praguywan; Wongwerawattanakoon, Pakawan; Soisamrong, Anucha

    2015-05-01

    Aspirin is now recommended for splenectomized thalassemia patients with high platelet counts. However, aspirin resistance defined by arachinodic acid (ACA) induced platelet aggregation ≥20%, has never been reported in this group of patients. In this study, twenty-four splenectomized thalassemia patients (15.7±4.1years), with platelet counts ≥800x10(9)/L, and 21 non-splenectomized severe thalassemia patients (14.3±3.2years), were enrolled. After taking aspirin (2mg/kg/day), seven patients (29.2%) displayed aspirin resistance. Serum thromboxane B2 (TXB2) levels in the aspirin responsive group decreased significantly [52.6(8.8-174.6) vs 4.0(1.6-7.3) mcg/mL, paspirin resistant group. Having increased aspirin to 4mg/kg/day, three of the seven aspirin resistant patients responded, while one developed upper GI bleeding from esophageal varices and was withdrawn from the study. For the three remaining patients, their doses were increased to the maximum of 300mg/day, and two of the three responded. Thrombin antithrombin complex and D-dimer levels were significantly decreased after taking aspirin (2mg/kg/day), although D-dimer level was still significantly higher than that in non-splenectomized group. Therefore, aspirin dosage can be adjusted individually to reach maximum effect of platelet inhibition. In addition, aspirin can reduce the levels of coagulation markers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Aspirin and blood pressure: Effects when used alone or in combination with antihypertensive drugs.

    Science.gov (United States)

    Costa, Ana Catarina; Reina-Couto, Marta; Albino-Teixeira, António; Sousa, Teresa

    Arterial hypertension is a major risk factor for cardiovascular and renal events. Lowering blood pressure is thus an important strategy for reducing morbidity and mortality. Since low-dose aspirin is a cornerstone in the prevention of adverse cardiovascular outcomes, combined treatment with aspirin and antihypertensive drugs is very common. However, the impact of aspirin therapy on blood pressure control remains a subject of intense debate. Recent data suggest that the cardioprotective action of aspirin extends beyond its well-known antithrombotic effect. Aspirin has been shown to trigger the synthesis of specialized pro-resolving lipid mediators from arachidonic acid and omega-3 fatty acids. These novel anti-inflammatory and pro-resolving mediators actively stimulate the resolution of inflammation and tissue regeneration. Additionally, they may contribute to other protective effects on redox status and vascular reactivity that have also been attributed to aspirin. Of note, aspirin has been shown to improve vasodilation through cyclooxygenase-independent mechanisms. On the other hand, higher aspirin doses have been reported to exert a negative impact on blood pressure due to inhibition of cyclooxygenase-2 activity, which reduces renal blood flow, glomerular filtration rate and sodium and water excretion. This review aims to provide an overview of the effects of aspirin on blood pressure and the underlying mechanisms, focusing on the interaction between aspirin and antihypertensive drugs. Studies in both experimental and human hypertension are presented. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

    Science.gov (United States)

    Zwolinska-Wcislo, Malgorzata; Brzozowski, Tomasz; Ptak-Belowska, Agata; Targosz, Aneta; Urbanczyk, Katarzyna; Kwiecien, Slawomir; Sliwowski, Zbigniew

    2011-01-01

    AIM: To determine the effect of non-selective cyclooxygenase (COX) inhibitors, selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis. METHODS: Rats with 2,4,6 trinitrobenzenesulfon-ic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle, aspirin (ASA) (a non-selective COX inhibitor), celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days. The area of colonic lesions, colonic blood flow (CBF), myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2, inducible form of nitric oxide synthase (iNOS), IL-1β and tumor necrosis factor (TNF)-α were assessed. The effects of glyceryl trinitrate (GTN), a NO donor, and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-​tetramethyl-1H-imidazolyl-1-oxy-3-oxide, onopotassium salt (carboxy-PTIO), a NO scavenger, administered without and with ASA or NO-ASA, and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined. RESULTS: Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF, a significant rise in colonic weight, MPO activity and plasma IL-1β and TNF-α levels. These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560), but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E2 (PGE2) analog. Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NOx content and CBF, suppression of MPO and downregulation of COX-2, iNOS, IL-1β and TNF-α mRNAs. Treatment with GTN, the NO donor, significantly inhibited the ASA-induced colonic lesions and increased CBF, while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASA-induced improvement of colonic healing and the accompanying increase in the CBF. These effects were restored by co

  3. Risk Factors for Upper GI Damage in Low-Dose Aspirin Users and the Interaction Between H. pylori Infection and Low-Dose Aspirin Use.

    Science.gov (United States)

    Iijima, Katsunori; Shimosegawa, Tooru

    2015-01-01

    Nowadays, low-dose aspirin is widely administered at low dose as an antithrombotic drug for the prevention of cerebrovascular and cardiovascular diseases. However, aspirin, even at a low dose, can induce varying degrees of gastroduodenal mucosal injury (erosion, ulcer, ulcer bleeding). Hence, co-prescription of proton pump inhibitors with low-dose aspirin is recommended for those at high risk for adverse gastroduodenal events. At present, a history of peptic ulcer, especially that of complicated ulcer, is the most important risk factor for low-dose aspirin-associated gastroduodenal adverse events. Additionally, concomitant use of non-steroidal anti-inflammatory drugs including COX-2 selective inhibitors, anti-platelet agents, anti-coagulants, and oral corticosteroid is recognized to increase the risk for adverse gastroduodenal events in low-dose aspirin users. H. pylori infection could also be associated with the increased risk for adverse gastroduodenal events in low-dose aspirin users, especially in patients with histories of peptic ulcers. Therefore, eradication therapy for such patients can prevent ulcer recurrence. However, the efficacy of eradication therapy on low-dose aspirin-related gastroduodenal lesions in unselected H. pylori-positive lowdose aspirin users without histories of peptic ulcers remains to be clarified.

  4. Monitoring the hydrolyzation of aspirin during the dissolution testing for aspirin delayed-release tablets with a fiber-optic dissolution system

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2012-10-01

    Full Text Available The purpose of this study was to investigate the hydrolyzation of aspirin during the process of dissolution testing for aspirin delayed-release tablets. Hydrolysis product of salicylic acid can result in adverse effects and affect the determination of dissolution rate assaying. In this study, the technique of differential spectra was employed, which made it possible to monitor the dissolution testing in situ. The results showed that the hydrolyzation of aspirin made the percentage of salicylic acid exceed the limit of free salicylic acid (4.0, and the hydrolyzation may affect the quality detection of aspirin delayed-release tablets. Keywords: Aspirin delayed-release tablets, Drug dissolution test, Fiber-optic dissolution system, UV–vis spectrum

  5. A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Burn, John; Bishop, D Timothy; Chapman, Pamela D

    2011-01-01

    Evidence supporting aspirin and resistant starch (RS) for colorectal cancer prevention comes from epidemiologic and laboratory studies (aspirin and RS) and randomized controlled clinical trials (aspirin). Familial adenomatous polyposis (FAP) strikes young people and, untreated, confers virtually...

  6. Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention.

    Science.gov (United States)

    Ornelas, Argentina; Zacharias-Millward, Niki; Menter, David G; Davis, Jennifer S; Lichtenberger, Lenard; Hawke, David; Hawk, Ernest; Vilar, Eduardo; Bhattacharya, Pratip; Millward, Steven

    2017-07-31

    After more than a century, aspirin remains one of the most commonly used drugs in western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and analgesic properties, a multitude of clinical studies have provided convincing evidence that regular, low-dose aspirin use dramatically lowers the risk of cancer. These observations coincide with recent studies showing a functional relationship between platelets and tumors, suggesting that aspirin's chemopreventive properties may result, in part, from direct modulation of platelet biology and biochemistry. Here, we present a review of the biochemistry and pharmacology of aspirin with particular emphasis on its cyclooxygenase-dependent and cyclooxygenase-independent effects in platelets. We also correlate the results of proteomic-based studies of aspirin acetylation in eukaryotic cells with recent developments in platelet proteomics to identify non-cyclooxygenase targets of aspirin-mediated acetylation in platelets that may play a role in its chemopreventive mechanism.

  7. Aspirin prevents diabetic oxidative changes in rat lacrimal gland structure and function.

    Science.gov (United States)

    Jorge, Angélica Gobbi; Módulo, Carolina Maria; Dias, Ana Carolina; Braz, Alexandre Martins; Filho, Rubens Bertazolli; Jordão, Alceu A; de Paula, Jayter Silva; Rocha, Eduardo Melani

    2009-04-01

    The aim of this study is to evaluate whether aspirin reduces Diabetis Mellitus (DM) oxidative damage in the lacrimal gland (LG), and ocular surface (OS). Ten weeks after streptozotocin induced DM and aspirin treatment, LG and OS of rats were compared for tear secretion, hidtology, peroxidase activity, and expression of uncoupling proteins (UCPs). DM reduction of tear secretion was prevented by aspirin (P aspirin-treated diabetic rats. Peroxidase activity levels were higher and UCP-2 was reduced in DM LG but not in aspirin treated (P = 0.0025 and P aspirin indicate a direct inhibitory effect on oxidative pathways in LG and their inflammatory consequences, preserving the LG structure and function against hyperglycemia and/or insulin deficiency damage.

  8. 24-hour antiplatelet effect of aspirin in patients with previous definite stent thrombosis

    DEFF Research Database (Denmark)

    Würtz, Morten; Hvas, Anne-Mette; Jensen, Lisette O

    2014-01-01

    OBJECTIVE: Once-daily aspirin is standard treatment, but recent studies point towards increased platelet function at the end of the dosing interval. Stent thrombosis (ST) has been linked with reduced antiplatelet effect of aspirin, so we investigated if platelet inhibition by aspirin declines...... with 100 patients with stable coronary artery disease and 50 healthy volunteers. All participants were on aspirin 75 mg/day mono antiplatelet therapy. Platelet aggregation was measured 1 and 24 h after aspirin intake using platelet aggregometry (Multiplate® Analyzer). Cyclooxygenase-1 activity, platelet...... activation, immature platelets, and thrombopoietin were measured. RESULTS: Platelet aggregation increased by 109±150 (arachidonic acid) and 47±155 (collagen) aggregation units per minute from 1 to 24 h after aspirin intake (p-values

  9. Prevention and treatment of cancer with aspirin: where do we stand?

    Science.gov (United States)

    Pasche, Boris; Wang, Minghui; Pennison, Michael; Jimenez, Hugo

    2014-06-01

    Aspirin is arguably the synthesized drug that has been used most commonly in human history. Aspirin was originally developed and marketed for the treatment of inflammatory disorders at the end of the 19th century, but its mechanism of action remained unknown until the second half of the 20th century. Since the latter part of the 20th century aspirin also has been used for the primary and secondary prevention of cardiovascular diseases given its anti-thrombotic properties. An association between intake of aspirin and decreased cancer risk was identified in the past decades. Whether aspirin can be used as an anticancer agent in patients with a diagnosis of cancer was unknown until recently. Recent studies suggest that aspirin might provide therapeutic benefit in the adjuvant treatment of certain forms of cancer. This review provides a critical update on this topic, which has potential implications for oncologists and their patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Perbandingan Efektivitas antara Aspirin dengan Madu dan Propolis Sebagai Antiplatelet Berdasarkan Waktu Perdarahan pada Ekor Mencit

    OpenAIRE

    Ramar, Logaselvi A/P

    2016-01-01

    The prevalence of cardiovascular disease (CVD) and its mortality continues to increase. Various studies have shown that aspirin can reduce CVD mortality but it has adverse side effects. Research to examine the comparative effectiveness of aspirin with honey and propolis has not been done even though both have antiplatelet effects. This study aimed to prove the antiplatelet effects on honey and propolis and to compare the antiplatelet effects of aspirin with honey and propolis based on the ...

  11. Effect of Aspirin and Indomethacin on Prostaglandin E2 Synthesis in C6 Glioma Cells

    OpenAIRE

    Hwang, Shiuh-Lin; Lee, Kung-Shing; Lin, Chih-Lung; Lieu, Ann-Shung; Cheng, Chi-Yun; Loh, Joon-Khim; Hwang, Yan-Fen; Su, Yu-Feng; Howng, Shen-Long

    2004-01-01

    Prostaglandin E2 (PGE2) plays an important role in immunosuppression and tumor growth. PGE2 inhibitors such as aspirin and indomethacin suppress experimental tumor growth. Little is known of the relationship between PGE2 synthesis in brain tumors and the dose of aspirin or indomethacin. The present study was undertaken to evaluate the effect of different doses of aspirin and indomethacin on PGE2 synthesis in C6 glioma cells. C6 glioma cells were incubated with different concentrations (2, 4, ...

  12. The Effects of Cyclosporine and Aspirin on Platelet Function in Normal Dogs

    OpenAIRE

    Thomason, J.; Archer, T.; Wills, R.; Press, S.; Mackin, A.

    2016-01-01

    Background Cyclosporine increases thromboxane synthesis in dogs, potentially increasing the thrombogenic properties of platelets. Hypothesis/Objectives Our hypothesis was that the concurrent administration of low?dose aspirin and cyclosporine would inhibit cyclosporine?associated thromboxane synthesis without altering the antiplatelet effects of aspirin. The objective was to determine the effects of cyclosporine and aspirin on primary hemostasis. Animals Seven healthy dogs. Methods A randomiz...

  13. The use of preoperative aspirin in cardiac surgery: A systematic review and meta-analysis.

    Science.gov (United States)

    Aboul-Hassan, Sleiman Sebastian; Stankowski, Tomasz; Marczak, Jakub; Peksa, Maciej; Nawotka, Marcin; Stanislawski, Ryszard; Kryszkowski, Bartosz; Cichon, Romuald

    2017-12-01

    Despite the fact that aspirin is of benefit to patients following coronary artery bypass grafting (CABG), continuation or administration of preoperative aspirin before CABG or any cardiac surgical procedure remains controversial. Therefore, we performed a systematic review and meta-analysis to assess the influence of preoperative aspirin administration on patients undergoing cardiac surgery. Medline database was searched using OVID SP interface. Similar searches were performed separately in EMBASE, PubMed, and Cochrane Central Registry of Controlled Trials. Twelve randomized controlled trials and 28 observational studies met our inclusion criteria and were included in the meta-analysis. The use of preoperative aspirin in patients undergoing CABG at any dose is associated with reduced early mortality as well as a reduced incidence of postoperative acute kidney injury (AKI). Low-dose aspirin (≤160 mg/d) is associated with a decreased incidence of perioperative myocardial infarction (MI). Administration of preoperative aspirin at any dose in patients undergoing cardiac surgery increases postoperative bleeding. Despite this effect of preoperative aspirin, it did not increase the rates of surgical re-exploration due to excessive postoperative bleeding nor did it increase the rates of packed red blood cell transfusions (PRBC) when preoperative low-dose aspirin (≤160 mg/d) was administered. Preoperative aspirin increases the risk for postoperative bleeding. However, this did not result in an increased need for chest re-exploration and did not increase the rates of PRBC transfusion when preoperative low-dose (≤160 mg/d) aspirin was administered. Aspirin at any dose is associated with decreased mortality and AKI and low-dose aspirin (≤160 mg/d) decreases the incidence of perioperative MI. © 2017 Wiley Periodicals, Inc.

  14. Aspirin versus warfarin in atrial fibrillation: decision analysis may help patients' choice.

    LENUS (Irish Health Repository)

    Romero-Ortuno, Roman

    2012-03-01

    the primary prevention of ischaemic stroke in chronic non-valvular atrial fibrillation (AF) typically involves consideration of aspirin or warfarin. CHA(2)DS(2)-VASc estimates annual stroke rates for untreated AF patients, which are reduced by 60% with warfarin and by 20% with aspirin. HAS-BLED estimates annual rates of major bleeding on warfarin. The latter risk with aspirin is 0.5-1.2% per year.

  15. Aspirin induces nitric oxide release from vascular endothelium: a novel mechanism of action

    OpenAIRE

    Taubert, D; Berkels, R; Grosser, N; Schröder, H; Gründemann, D; Schömig, E

    2004-01-01

    The study was designed to test the hypothesis that aspirin may stimulate nitric oxide (NO) release from vascular endothelium, a pivotal factor for maintenance of vascular homeostasis.Clinical evidence suggests that low-dose aspirin may improve vascular endothelial function. Since other cyclooxygenase (COX) inhibitors showed no beneficial vascular effects, aspirin may exhibit a vasculoprotective, COX-independent mechanism.Luminal NO release was monitored in real time on dissected porcine coron...

  16. Trends in the incidence of Reye's syndrome and the use of aspirin.

    OpenAIRE

    Porter, J. D.; Robinson, P.H.; Glasgow, J F; Banks, J H; Hall, S. M.

    1990-01-01

    In 1986 there was a public warning in the United Kingdom about a link between the consumption of aspirin and Reye's syndrome. To find out if the use of aspirin and paracetamol in children had altered, and whether the incidence of Reye's syndrome had changed since a previous study, parents were interviewed in Belfast and London, and the British Reye's Syndrome Surveillance System data were reviewed. Children with febrile illnesses were 17 times more likely to have received aspirin before admis...

  17. Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line

    OpenAIRE

    Isabella Massimi; Ambra Ciuffetta; Flavia Temperilli; Francesca Ferrandino; Alessandra Zicari; Pulcinelli, Fabio M.; Maria Pia Felli

    2015-01-01

    Overexpression of efflux transporters, in human cells, is a mechanism of resistance to drug and also to chemotherapy. We found that multidrug resistance protein-4 (MRP4) overexpression has a role in reducing aspirin action in patients after bypass surgery and, very recently, we found that aspirin enhances platelet MRP4 levels through peroxisome proliferator activated receptor-α (PPARα). In the present paper, we verified whether exposure of human embryonic kidney-293 cells (Hek-293) to aspirin...

  18. Aspirin: The Mechanism of Action Revisited in the Context of Pregnancy Complications

    OpenAIRE

    Cadavid, Angela P.

    2017-01-01

    Aspirin is one of the most frequently used and cheapest drugs in medicine. It belongs to the non-steroidal anti-inflammatory drugs with a wide range of pharmacological activities, including analgesic, antipyretic, and antiplatelet properties. Currently, it is accepted to prescribe a low dose of aspirin to pregnant women who are at high risk of preeclampsia (PE) because it reduces the onset of this complication. Another pregnancy alteration in which a low dose of aspirin is recommended is the ...

  19. Aspirin vs Heparin for the Prevention of Preeclampsia.

    Science.gov (United States)

    Katsi, Vasiliki; Kanellopoulou, Theoni; Makris, Thomas; Nihoyannopoulos, Petros; Nomikou, Efrosyni; Tousoulis, Dimitrios

    2016-07-01

    Preeclampsia is a hypertensive disorder of pregnancy that remains a significant cause of maternal morbidity and mortality worldwide. Preeclampsia can be resolved by delivery, and most of the proposed preventive treatment approaches are based on processes involved in placental development in early pregnancy. Yet, none of these has been established in clinical practice. Low-dose aspirin is the most promising candidate, nevertheless; while some individual randomized controlled trials showed minimal or no statistically significant benefit, recent metanalyses showed that early initiation before 16 weeks of gestation is associated with prevention of early-onset preeclampsia and reduction in prevalence of perinatal death or morbidity of pregnant women. Heparin could be an alternative antithrombotic and anti-inflammatory median to prevent preeclampsia either alone or in combination with aspirin; however, results are conflicting concerning efficacy.

  20. A Disease Marker for Aspirin-Induced Chronic Urticaria

    Science.gov (United States)

    Hsieh, Chia-Wei; Lee, Jeen-Wei; Liao, En-Chih; Tsai, Jaw-Ji

    2014-01-01

    There are currently no diagnostic methods in vitro for aspirin-induced chronic urticaria (AICU) except for the provocation test in vivo. To identify disease markers for AICU, we investigated the single nucleotide polymorphism (SNP) of the promoter loci of high-affinity IgE receptor (FcεRIα) and CD203c expression level in Chinese patients with AICU. We studied two genotypic and allelic frequencies of rs2427827 (–344C/T) and rs2251746 (–66T/C) gene polymorphisms of FcεRIα in 20 patients with AICU, 52 subjects with airway hypersensitivity without aspirin intolerance, and 50 controls in a Chinese population. The results showed that the frequencies of two SNPs (–344C>T, –66C>T) were similar to the normal controls. The allele frequency of –344CC was significantly higher in the patients with AICU compared to those with airway sensitivity (p = 0.019). We also studied both histamine release and CD203c expression on KU812 cells to assess aspirin-induced basophil activation. We found that the activity of basophil activation of AICU was significantly higher in the patients with AICU compared to those with airway hypersensitivity without aspirin intolerance. The mean fluorescence intensity of the CD203c expression were 122.5 ± 5.2 vs. 103.3 ± 3.3 respectively, (p T) is less likely to develop AICU and the basophil activation activity in the sera by measuring CD203c expression can be applicable to confirm the diagnosis of AICU. PMID:25029546

  1. Enhancement of anti-inflammatory property of aspirin in mice by a nano-emulsion preparation.

    Science.gov (United States)

    Subramanian, Balajikarthick; Kuo, Fonghsu; Ada, Earl; Kotyla, Tim; Wilson, Thomas; Yoganathan, Subbiah; Nicolosi, Robert

    2008-11-01

    Aspirin, a non-steroidal anti-inflammatory drug, widely used for its anti-inflammatory properties is associated with several systemic side effects including gastro-intestinal discomfort. Inflammation can be mediated by pro-inflammatory cytokines and, along with various other host factors eventually give rise to edema at the inflamed site. Because of the adverse side effects oftentimes associated with systemic exposure to aspirin, the aim of the present study was to investigate whether the anti-inflammatory property of aspirin would enhance if delivered as nano-emulsion preparation. Nano-emulsion preparations of aspirin prepared with a Microfluidizer Processor were evaluated in the croton-oil-induced ear edema CD-1 mouse model using ear lobe thickness and the accumulation of specific in situ cytokines as biomarkers of inflammation. The results showed that particle size (90 nm) populations of nano-emulsion preparations of aspirin compared to an aspirin suspension (363 nm), significantly decreased (pemulsion further reduced the auricular levels of IL-1alpha (-37%) and TNFalpha (-69%) compared to the aspirin suspension preparation (pemulsion preparation of aspirin significantly improved the anti-inflammatory properties of an aspirin suspension in a CD-1 mouse model of induced inflammation.

  2. Role of aspirin for prevention and treatment of perioperative cardiovascular events.

    Science.gov (United States)

    Duceppe, E; Mrkobrada, M; Thomas, S; Devereaux, P J

    2015-06-01

    Among adults undergoing non-cardiac surgery who are at risk of a myocardial infarction, a long-standing question has been whether these patients should receive aspirin throughout the perioperative period. A large (n = 10,010 patients) international trial (POISE-2) demonstrated that perioperative aspirin did not prevent myocardial infarction, and the result was consistent both for patients who had been taking aspirin before the trial (continuation stratum, 4382 patients) and for patients who had not been taking aspirin before the trial (initiation stratum, 5628 patients). Aspirin did, however, increase the risk of major bleeding. Therefore, the best evidence does not support the use of aspirin for the prevention of myocardial infarction in patients undergoing non-cardiac surgery. In patients who have an indication for long-term aspirin usage and have their aspirin held during the perioperative period, it is important to ensure aspirin is restarted after the high-risk period for bleeding has passed (i.e., 8-10 days after surgery). © 2015 International Society on Thrombosis and Haemostasis.

  3. Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers

    OpenAIRE

    Teng, Renli; Maya, Juan; Butler, Kathleen

    2012-01-01

    The results of two independent, randomized, two-period crossover, single-center studies, conducted to assess the pharmacokinetics of ticagrelor???aspirin, inhibition of platelet aggregation (IPA) with ticagrelor/aspirin vs. clopidogrel/aspirin, and safety, tolerability, and bleeding times are reported here. In Study A (open-label), 16 volunteers received ticagrelor (50?mg bid Days 1?5; 200?mg bid Days 6?9; one 200?mg dose on Day 10)???300?mg qd aspirin (Days 1?10). In Study B (double-blind, d...

  4. Fabrication, characterization, thermal stability and nanoassemblies of novel pullulan-aspirin conjugates

    Directory of Open Access Journals (Sweden)

    Muhammad A. Hussain

    2017-05-01

    Full Text Available Present study deals with homogeneous and one-pot synthesis of novel macromolecular prodrugs (MPDs of aspirin onto naturally occurring hydrophilic biopolymer pullulan. Pullulan-aspirin conjugates were synthesized by using green carboxylic acid activating reagent 1,1′-carbonyldiimidazole (CDI. The aspirin was first reacted with CDI to prepare aspirin-imidazolide at RT for 24 h which in situ reacted with pre-dissolved pullulan and the reaction preceded further for 24 h at 80 °C under nitrogen. Degree of substitution (DS 0.32–0.40 of aspirin onto pullulan was calculated from 1H NMR spectroscopy. Spectroscopic techniques confirmed the high covalent drug loading and purity. Thermal analysis has revealed that new MPDs of aspirin are thermally more stable than pure aspirin. The activation energy, order and frequency factor of the degradation reactions were calculated using Broido, Friedman and Chang models. The amphiphilic pullulan-aspirin conjugates self-assembled in nanoparticles without further structural modifications at solvent interface in the range of 500–680 nm as examined by transmission electron microscopy. These novel pullulan-aspirin conjugates with masked COOH functional group could be potentially safe prodrugs for the stomach.

  5. Aspirin and Risk of Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Phan, Kevin; Moore, Justin M; Griessenauer, Christoph J; Ogilvy, Christopher S; Thomas, Ajith J

    2017-05-01

    Recent studies have suggested that the use of low-dose aspirin may reduce the risk of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to evaluate any association between aspirin use and risk of aSAH based on the literature, and whether this is influenced by duration or frequency of aspirin use. A search of electronic databases was done from inception to September 2016. For each study, data on risk of aSAH in aspirin versus nonaspirin users were used to generate odds ratios and 95% confidence intervals, and combined using inverse variance-weighted averages of logarithmic odds ratios in a random-effects models. From 7 included studies, no significant difference was noted between aspirin use of any duration or frequency and nonaspirin users (odds ratio, 1.00; 95% confidence interval, 0.81-1.24; P =0.99). We found a significant association between short-term use of aspirin (3 years of durations of use. No significant association was found between infrequent aspirin use (≤2× per week) or frequent use (≥3× per week) with risk of aSAH. Current evidence suggests that short-term (aspirin is associated with increased risk of aSAH. Limitations include substantial heterogenity of the included studies. The role of long-term aspirin in reducing risk of aSAH remains unclear and ideally should be addressed by an appropriately designed randomized controlled trial. © 2017 American Heart Association, Inc.

  6. Synergistically killing activity of aspirin and histone deacetylase inhibitor valproic acid (VPA) on hepatocellular cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaofei; Zhu, Yanshuang [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); He, Huabin [Department of Orthopedics, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Lou, Lianqing; Ye, Weiwei; Chen, Yongxin [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Wang, Jinghe, E-mail: Xiaofeili2000@163.com [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China)

    2013-06-28

    Highlights: •Novel combination therapy using aspirin and valproic acid (VPA). •Combination of aspirin and VPA elicits synergistic cytotoxic effects. •Combination of aspirin and VPA significantly reduces the drug dosage required alone. •Combination of aspirin and VPA significantly inhibit tumor growth. •Lower dose of aspirin in combination therapy will minimize side effects of aspirin. -- Abstract: Aspirin and valproic acid (VPA) have been extensively studied for inducing various malignancies growth inhibition respectively, despite their severe side effects. Here, we developed a novel combination by aspirin and VPA on hepatocellular cancer cells (HCCs). The viability of HCC lines were analyzed by MTT assay, apoptotic analysis of HepG2 and SMMC-7721 cell was performed. Real time-PCR and Western blotting were performed to determine the expression of apoptosis related genes and proteins such as Survivin, Bcl-2/Bax, Cyclin D1 and p15. Moreover, orthotopic xenograft tumors were challenged in nude mice to establish murine model, and then therapeutic effect was analyzed after drug combination therapy. The viability of HCC lines’ significantly decreased after drug combination treatment, and cancer cell apoptosis in combination group increasingly induced compared with single drug use. Therapeutic effect was significantly enhanced by combination therapy in tumor volume and tumor weight decrease. From the data shown here, aspirin and VPA combination have a synergistic killing effect on hepatocellular cancers cells proliferation and apoptosis.

  7. Prostaglandin D₂: a dominant mediator of aspirin-exacerbated respiratory disease.

    Science.gov (United States)

    Cahill, Katherine N; Bensko, Jillian C; Boyce, Joshua A; Laidlaw, Tanya M

    2015-01-01

    Aspirin desensitization followed by high-dose aspirin therapy is routinely performed for patients with aspirin-exacerbated respiratory disease (AERD). Little is known about the contributions of mediators other than cysteinyl leukotrienes to aspirin reactions and to the therapeutic benefit of high-dose aspirin therapy. We investigated differences in urinary eicosanoid metabolite levels and blood eosinophil counts in patients with AERD who tolerate and those who fail aspirin desensitization and also in patients with AERD who were successfully treated with high-dose aspirin therapy. Twenty-nine patients with AERD were stratified into those who tolerated aspirin desensitization (group I) and those who did not (group II). Urine was analyzed for eicosanoid metabolites at baseline, during aspirin reactions, and during high-dose aspirin therapy. Blood was analyzed for cell differentials at baseline and during aspirin therapy. Basal prostaglandin D2 metabolite (PGD-M; 13.6 ± 2.7 vs 7.0 ± 0.8 pmol/mg creatinine [Cr], P < .05) and thromboxane metabolite (TX-M; 1.4 ± 0.3 vs 0.9 ± 0.1 pmol/mg Cr, P < .01) levels were higher in group II than in group I. During aspirin reactions, PGD-M levels remained unchanged, whereas TX-M levels (0.7 ± 0.1 pmol/mg Cr, P = .07) tended to decrease in group I. In contrast, PGD-M levels increased dramatically in group II (61.3 ± 19.9 pmol/mg Cr, P < .05), whereas TX-M levels did not change. The decrease in FEV1 inversely correlated with basal urinary levels of both leukotriene E4 and PGD-M. Blood eosinophil and basophil levels increased and urinary PGD-M levels (2.2 ± 0.8 pmol/mg Cr, P < .001) decreased on 2 months of high-dose aspirin therapy in group I. Failure to tolerate aspirin desensitization in a subset of patients with AERD is associated with prostaglandin D2 overproduction. The increase in blood eosinophil and basophil counts during high-dose aspirin therapy might reflect the functional consequences of decreased prostaglandin D2

  8. Fabrication, characterization, thermal stability and nanoassemblies of novel pullulan-aspirin conjugates

    OpenAIRE

    Muhammad A. Hussain; Khawar Abbas; Bilal A. Lodhi; Muhammad Sher; Muhammad Ali; Muhammad N. Tahir; Wolfgang Tremel; Saima Iqbal

    2017-01-01

    Present study deals with homogeneous and one-pot synthesis of novel macromolecular prodrugs (MPDs) of aspirin onto naturally occurring hydrophilic biopolymer pullulan. Pullulan-aspirin conjugates were synthesized by using green carboxylic acid activating reagent 1,1′-carbonyldiimidazole (CDI). The aspirin was first reacted with CDI to prepare aspirin-imidazolide at RT for 24 h which in situ reacted with pre-dissolved pullulan and the reaction preceded further for 24 h at 80 °C under nitrogen....

  9. Aspirin inhibition of platelet deposition at angioplasty sites: demonstration by platelet scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Cuningham, D.A.; Kumar, B.; Siegel, B.A.; Gilula, L.A.; Totty, W.G.; Welch, M.J.

    1984-05-01

    In-111 platelet scintigraphy was used to evaluate the effects of prior aspirin administration on the accumulation of In-111-labeled autologous platelets at sites of arterial injury resulting from iliac, femoral, or popliteal transluminal angioplasty in a nonrandomized study of 17 men. The degree of platelet localization at angioplasty sites was significantly less in nine men who had received aspirin in varying doses within the 4 days before angioplasty than in eight men who had not received aspirin for at least two weeks. The results suggest that aspirin treatment before angioplasty limits the early platelet deposition at the angioplasty site in men.

  10. Effect of genetic polymorphism of ALOX15 on aspirin-exacerbated respiratory disease

    National Research Council Canada - National Science Library

    Song, Young-Sin; Yang, Eun-Mi; Kim, Seung-Hyun; Jin, Hyun Jung; Park, Hae-Sim

    2012-01-01

    Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome associated with chronic inflammation in the airways coincident with chronic rhinitis, sinusitis, recurrent polyposis and asthma...

  11. [A short history of anti-rheumatic therapy. II. Aspirin].

    Science.gov (United States)

    Pasero, G; Marson, P

    2010-01-01

    The discovery of aspirin, an antipyretic, anti-inflammatory and analgesic drug, undoubtedly represents a milestone in the history of medical therapy. Since ancient times the derivatives of willow (Salix alba) were used to treat a variety of fevers and pain syndromes, although the first report dates back to 1763 when the English Reverend Edward Stone described the effect of an extract of the bark willow in treating malaria. In the XIX century many apothecaries and chemists, including the Italian Raffaele Piria and Cesare Bertagnini, developed the biological processes of extraction and chemical synthesis of salicylates, and then analyzed their therapeutic properties and pharmacokinetic and pharmacodynamic characteristics. In 1899 the Bayer Company, where Felix Hoffmann, Heinrich Dreser and Arthur Eichengrün worked, recorded acetyl-salicylic acid under the name "Aspirin". In the XX century, besides the definition of the correct applications of aspirin in the anti-rheumatic therapy being defined, Lawrence L. Crawen identified the property of this drug as an anti-platelet agent, thus opening the way for more widespread uses in cardiovascular diseases.

  12. Low dose aspirin therapy and renal function in elderly patients

    Directory of Open Access Journals (Sweden)

    Akinwusi PO

    2013-01-01

    Full Text Available Patience Olayinka Akinwusi,1,2 Rotimi Oluyombo,2 Paul Sunday Ogunro,3 Adetunji Oladeni Adeniji,4 Oluyomi Olusola Okunola,5 Olugbenga Edward Ayodele21Department of Medicine, Osun State University, Osogbo, Osun State, Nigeria; 2Department of Medicine, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 3Department of Chemical Pathology, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 4Department of Obstetrics and Gynecology, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 5Department of Medicine, Obafemi Awolowo University, Ile-Ife, Osun State, NigeriaPurpose: To determine whether low dose aspirin has any deleterious effects on renal function in elderly patients.Methods: We conducted a prospective pilot study of 30 Nigerians older than 60 years with various chronic ailments necessitating the use of low dose aspirin. Patients gave their consent, and institutional ethical clearance was obtained. Each patient's baseline samples at enrolment (before commencing aspirin use served as a control, and subsequent weekly samples were compared. The weekly mean of each parameter was calculated, and the differences of means from baseline were determined, and values were compared for statistical differences with the Statistical Package for the Social Sciences, version 16.Results: We found that a majority of patients (86.67% had basal renal functions at chronic kidney disease stages 1 and 2. When compared with the corresponding baseline parameters, the mean weekly serum and urinary electrolytes, urea, creatinine, and uric acid parameters did not change, and the P-value did not show any statistical significance. However, there was positive statistical significance for the creatinine clearance (P = 0.025. Also, unlike in previous studies, anemia and hypoalbuminemia did not affect the renal function parameters.Conclusion: This study did not show any deleterious effects with short-term, low dose (75 mg daily aspirin use on kidney functions in

  13. Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer: Summary of epidemiologic evidence of cancer risk and prognosis.

    Science.gov (United States)

    Verdoodt, F; Kjaer, S K; Friis, S

    2017-06-01

    Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence and prognosis of ovarian and endometrial cancer. The evidence of a preventive effect of NSAID use on risk of ovarian or endometrial cancer is based primarily on results from observational studies and, consequently, is only suggestive. Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian or endometrial cancer risk and prognosis are warranted. In the present review, we discuss the importance of comprehensive exposure definitions (i.e., duration, timing, consistency and intensity/dose) and evaluation of potential effect modification according to user characteristics, with the aim of identifying women who may experience the largest benefit of aspirin or non-aspirin NSAID use on risk or prognosis of ovarian and endometrial cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Before Using Aspirin to Lower Your Risk of Heart Attack or Stroke, Here Is What You Should Know

    Science.gov (United States)

    ... Medicines Safe Daily Use of Aspirin Before Using Aspirin to Lower Your Risk of Heart Attack or ... State & Local Officials Consumers Health Professionals Science & Research Industry Scroll back to top Popular Content Home Latest ...

  15. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Trabert, Britton; Ness, Roberta B; Lo-Ciganic, Wei-Hsuan

    2014-01-01

    BACKGROUND: Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. METHODS: We analyzed pooled data from 12 ...

  16. High platelet reactivity on aspirin in patients with acute ST elevation myocardial infarction.

    Science.gov (United States)

    Dillinger, Jean-Guillaume; Saeed, Alaa; Spagnoli, Vincent; Sollier, Claire Bal Dit; Sideris, Georgios; Silberman, Stephane Manzo; Voicu, Sebastian; Drouet, Ludovic; Henry, Patrick

    2016-08-01

    Despite dual antiplatelet treatment, major ischemic events are common following ST elevation myocardial infarction (STEMI). We aimed to assess high platelet reactivity on aspirin (HPR-aspirin) and its association with P2Y12i (HPR-P2Y12i) during the acute phase of STEMI. We included all consecutive patients admitted for STEMI treated by primary angioplasty in our center for 1year. All patients received a loading dose followed by a maintenance dose of aspirin (75mg/day) and prasugrel (ticagrelor or clopidogrel if contraindicated). Platelet reactivity was assessed 4±1days and 75±15days after admission using light transmission aggregometry with arachidonic acid (LTA-AA-HPR-aspirin) and VASP (HPR-P2Y12i) to define HPR as well as serum Thromboxane-B2 and LTA-ADP. Major cardiac and cerebrovascular events were recorded for 1year. We included 106 patients - mean age was 61y.o., 76% were male and 20% had diabetes. STEMI was anterior in 52% and LV ejection fraction at discharge was 51±9%. 50% of patients were treated with prasugrel and 34% with ticagrelor. At day 4 after STEMI, HPR-aspirin was found in 26% patients and HPR-P2Y12i in 7%. HPR- both aspirin and P2Y12i was found in 4%. Diabetes and age were predictors of HPR-aspirin. HPR-aspirin was persistent 75days later in 36% patients. At 1year, 7.9% patients had experienced major adverse cardiovascular and cerebrovascular events (MACCE). HPR-aspirin and HPR on both aspirin and P2Y12i were significantly associated with MACCE. HPR-aspirin is frequent just after STEMI and associated with MACCE especially when associated with HPR-P2Y12i. Copyright © 2016. Published by Elsevier Ltd.

  17. Aspirin Resistance Predicts Adverse Cardiovascular Events in Patients with Symptomatic Peripheral Artery Disease.

    Science.gov (United States)

    Pasala, Tilak; Hoo, Jennifer Soo; Lockhart, Mary Kate; Waheed, Rehan; Sengodan, Prasanna; Alexander, Jeffrey; Gandhi, Sanjay

    2016-12-01

    Antiplatelet therapy reduces the risk of myocardial infarction, stroke, and vascular death in patients who have symptomatic peripheral artery disease. However, a subset of patients who take aspirin continues to have recurrent cardiovascular events. There are few data on cardiovascular outcomes in patients with peripheral artery disease who manifest aspirin resistance. Patients with peripheral artery disease on long-term aspirin therapy (≥4 wk) were tested for aspirin responsiveness by means of the VerifyNow Aspirin Assay. The mean follow-up duration was 22.6 ± 8.3 months. The primary endpoint was a composite of death, myocardial infarction, or ischemic stroke. Secondary endpoints were the incidence of vascular interventions (surgical or percutaneous), or of amputation or gangrene caused by vascular disease. Of the 120 patients enrolled in the study, 31 (25.8%) were aspirin-resistant and 89 (74.2%) were aspirin-responsive. The primary endpoint occurred in 10 (32.3%) patients in the aspirin-resistant group and in 13 (14.6%) patients in the aspirin-responsive group (hazard ratio=2.48; 95% confidence interval, 1.08-5.66; P=0.03). There was no significant difference in the secondary outcome of revascularization or tissue loss. By multivariate analysis, aspirin resistance and history of chronic kidney disease were the only independent predictors of long-term adverse cardiovascular events. Aspirin resistance is highly prevalent in patients with symptomatic peripheral artery disease and is an independent predictor of adverse cardiovascular risk. Whether intervening in these patients with additional antiplatelet therapies would improve outcomes needs to be explored.

  18. Deposition and aggregation of aspirin molecules on a phospholipid bilayer pattern.

    Science.gov (United States)

    Mao, Guangzhao; Chen, Dongzhong; Handa, Hitesh; Dong, Wenfei; Kurth, Dirk G; Möhwald, Helmuth

    2005-01-18

    Aspirin and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) are deposited from their alcoholic mixed solution onto highly oriented pyrolytic graphite (HOPG) by spin coating. The film structure and morphology are characterized by atomic force microscopy (AFM). The barely soluble DMPE forms a highly oriented stripe phase as a result of its one-dimensional epitaxy with the HOPG lattice. The bilayer stripe pattern exposes the cross section of the lipid bilayer lamellae and enables the direct visualization of the molecular interactions of drug or biological molecules with either the hydrophobic or the hydrophilic part of the phospholipid bilayer. The bilayer pattern affects the aspirin molecular deposition and aggregation. AFM shows that the aspirin molecules prefer to deposit and aggregate along the aliphatic interior part of the bilayer pattern, giving rise to parallel dimer rods in registry with the underlying pattern. The nonpolar interactions between aspirin and the phospholipid bilayer are consistent with the lipophilic nature of aspirin. The bilayer pattern not only stabilizes the rodlike aggregate structure of aspirin at low aspirin concentration but also inhibits crystallization of aspirin at high aspirin concentration. Molecular models show that the width of the DMPE aliphatic chain interior can accommodate no more than two aspirin dimers. The bilayer confinement may prevent aspirin from reaching its critical nucleus size. This study illustrates a general method to induce a metastable or amorphous form of an active pharmaceutical ingredient (API) by chemical confinement under high undercooling conditions. Metastable and amorphous solids often display better solubility and bioavailability than the stable crystalline form of the API.

  19. Safety of continuing aspirin therapy during spinal surgery: A systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Chenggui; Wang, Guodong; Liu, Xiaoyang; Li, Yang; Sun, Jianmin

    2017-11-01

    Questions whether to continue or discontinue aspirin administration in the perioperative period of spinal surgery has not been systematically evaluated. The present systematic review is carried out to assess the impact of continuing aspirin administration on the bleeding and cardiovascular events in perispinal surgery period. Studies were retrieved through MEDLINE, EMBASE, and Springer Link Databases (search terms, aspirin, continue or discontinue, and spinal fusion), bibliographies of the articles retrieved, and the authors' reference files. We included studies that enrolled patients who underwent spinal surgery who were anticoagulated with aspirin alone and that reported bleeding or cardiovascular events as an outcome. Study quality was assessed using a validated form. 95% confidence interval (95% CI) was pooled to give summary estimates of bleeding and cardiovascular risk. We identified 4 studies assessing bleeding risk associated with aspirin continuation or cardiovascular risk with aspirin discontinuation during spinal surgery. The continuation of aspirin will not increase the risk of blood loss during the spinal surgery (95% CI, -111.72 to -0.59; P = .05). Also, there was no observed increase in the operative time (95% CI, -33.29 to -3.89; P = .01) and postoperative blood transfusion (95% CI, 0.00-0.27; P = .05). But as for the cardiovascular risk without aspirin continuation and mean hospital length of stay with aspirin continuation, we did not get enough samples to make an accurate decision about their relations with aspirin. Patients undergoing spinal surgery with continued aspirin administration do not have an increased risk for bleeding. In addition, there is no observed increase in the operation time and postoperative blood transfusion.

  20. Aspirin and incident depressive symptoms: A longitudinal cohort study over 8 years.

    Science.gov (United States)

    Veronese, Nicola; Koyanagi, Ai; Stubbs, Brendon; Solmi, Marco; Fornaro, Michele; Fernandes, Brisa S; Muller, Christoph; Thompson, Trevor; Carvalho, André F; Maggi, Stefania

    2018-02-01

    Aspirin exhibits anti-atherosclerotic and anti-inflammatory properties-two potential risk factors for depression. The relationship between aspirin use and depression, however, remains unclear. We investigated whether the aspirin use is associated with a decreased incidence of depressive symptoms in a large North American cohort. Data from the Osteoarthritis Initiative dataset, a multicenter, longitudinal study on community-dwelling adults was analyzed. Aspirin use was defined through self-report in the past 30 days and confirmed by a trained interviewer. Incident depressive symptoms were defined as a score of ≥16 in the 20-item Center for Epidemiologic Studies-Depression scale. A total of 137 participants (mean age 65 y, 55.5% female) were using aspirin at baseline. Compared with 4003 participants not taking aspirin, no differences in Center for Epidemiologic Studies-Depression at baseline were evident (P = .65). After a median follow-up time of 8 years, the incidence of depressive symptoms was similar in those taking aspirin at baseline (43; 95% CI, 3-60) and in aspirin nonusers (38; 95% CI, 36-41) per 1000 y; log-rank test = 0.63). Based on Cox's regression analysis adjusted for 11 potential confounders, aspirin use was not significantly associated with the development of depressive symptoms (hazard ratio = 1.12; 95% CI, 0.78-1.62; P = .54). Adjustment for propensity scores or the use of propensity score matching did not alter the results. Our study found that prescription of aspirin offered no significant protection against incident depressive symptoms. Whether aspirin is beneficial in a subgroup of depression with high levels of inflammation remains to be investigated in future studies. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Aspirin inhibits ErbB2 to induce apoptosis in cervical cancer cells.

    Science.gov (United States)

    Xiang, Shuanglin; Sun, Zhenhua; He, Qiongzhi; Yan, Feng; Wang, Yijun; Zhang, Jian

    2010-06-01

    The use of aspirin is associated with a lower risk of many cancer types. However, there are few reports about cervical cancer. The proto-oncogene ErbB2 is overexpressed in cervical cancer, and considered as a therapeutic target. In the present study, we investigated whether aspirin had therapeutic value in cervical cancer and examined the effects of aspirin on the amplification and expression of ErbB2. To investigate the effects of aspirin on apoptosis and proliferation, we tested apoptosis by Hoechst 33258 staining and Annexin V-FITC/PI method; MTT assay and colony formation assay were used to detect proliferation. Induction of apoptosis and inhibition of proliferation were observed in HeLa cells incubated with aspirin. Western blot and immunocytochemical staining showed that aspirin induced a dose- and time-dependent reduction of ErbB2 expression that was due to proteosome-mediated degradation of this protein. To further investigate the underlying mechanism by which aspirin exerts its apoptosis effects, we studied the ErbB2 downstream cell survival signaling pathways and the expression of anti-apoptosis gene Bcl-2. We found that aspirin inhibited the activation of extracellular signal-regulated kinase (ERK) and AKT. The inhibition of Bcl-2 expression was also observed. These data reveal that aspirin significantly induces apoptosis and inhibits proliferation, which maybe via inhibiting ErbB2 downstream cell survival signaling pathways. Taken together, our article describes a novel mechanism of action for anti-tumor activity of aspirin and implicates aspirin as a novel agent for cervical cancer.

  2. Fourteen-Year Follow-Up From CABADAS : Vitamin K Antagonists or Dipyridamole Not Superior to Aspirin

    NARCIS (Netherlands)

    Veeger, Nic J. G. M.; Zijlstra, Felix; Hillege, Hans L.; van der Meer, Jan

    2010-01-01

    Background. Secondary prophylaxis using aspirin is standard of care after coronary artery bypass graft surgery. Limited data are available for long-term results. We evaluated the effect of aspirin, aspirin with dipyridamole, and vitamin K antagonists (VKA) on 14-year clinical outcome of patients

  3. Aspirin and Reye's syndrome: the change in prescribing habits of health professionals.

    Science.gov (United States)

    Rahwan, G L; Rahwan, R G

    1986-02-01

    Epidemiological studies demonstrate the possible increased risk of Reye's syndrome after aspirin ingestion in children suffering from viral influenza or chicken pox. This study was conducted to determine whether the possible association between aspirin and Reye's syndrome in viral influenza and chicken pox deterred pediatricians and pharmacists in a large American city (Columbus, Ohio) from prescribing or recommending aspirin to their pediatric patients suffering from other causes of fever or pain. The results indicate that 90.6 percent of pediatricians and 97.8 percent of pharmacists no longer recommend aspirin to their pediatric patients, and an almost identical percentage recommend acetaminophen instead of aspirin. This change in prescribing habits of health professionals is reflected in a drop in sales of pediatric aspirin products with a simultaneous rise in sales of pediatric acetaminophen products reported by 93.3 percent of pharmacies. However, only 69.8 percent of pediatricians and 86.7 percent of pharmacists noted that their abstention from prescribing or recommending aspirin to children was rooted in a belief in a possible association between aspirin and Reye's syndrome.

  4. Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study) : a randomised controlled trial

    NARCIS (Netherlands)

    van Es, RF; Jonker, JJC; Verheugt, FWA; Deckers, JW; Grobbee, DE

    2002-01-01

    Background Antiplatelet treatment with aspirin and oral anticoagulants reduces reocurrence of ischaemic events after myocardial infarction. We aimed to investigate which of these drugs is more effective in the long term after acute coronary events, and whether the combination of aspirin and oral

  5. Effects of aspirin on clot structure and fibrinolysis using a novel in vitro cellular system.

    Science.gov (United States)

    Ajjan, R A; Standeven, K F; Khanbhai, M; Phoenix, F; Gersh, K C; Weisel, J W; Kearney, M T; Ariëns, R A S; Grant, P J

    2009-05-01

    The purpose of this study was to investigate the direct effects of aspirin on fibrin structure/function. Chinese Hamster Ovary cell lines stably transfected with fibrinogen were grown in the absence (0) and presence of increasing concentrations of aspirin. Fibrinogen was purified from the media using affinity chromatography, and clots were made from recombinant protein. Mean final turbidity [OD(+/-SEM)] was 0.083(+/-0.03), 0.093(+/-0.002), 0.101(+/-0.005), and 0.125(+/-0.003) in clots made from 0, 1, 10, and 100 mg/L aspirin-treated fibrinogen, respectively (Paspirin respectively (Pstructure and increased fiber thickness of clots made from aspirin-treated fibrinogen, whereas rheometer studies showed a significant 30% reduction in clot rigidity. Fibrinolysis was quicker in clots made from aspirin-treated fibrinogen. Ex vivo studies in 3 normal volunteers given 150 mg aspirin daily for 1 week demonstrated similar changes in clot structure/function. Aspirin directly altered clot structure resulting in the formation of clots with thicker fibers and bigger pores, which are easier to lyse. This study clearly demonstrates an alternative mode of action for aspirin, which should be considered in studies evaluating the biochemical efficacy of this agent.

  6. Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer

    DEFF Research Database (Denmark)

    Movahedi, Mohammad; Bishop, D Timothy; Macrae, Finlay

    2015-01-01

    in patients with Lynch syndrome (LS). PATIENTS AND METHODS: Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2 × 2 factorial design). Mean intervention period...

  7. Two cases of wheat-dependent anaphylaxis induced by aspirin administration but not by exercise.

    Science.gov (United States)

    Matsukura, S; Aihara, M; Sugawara, M; Kunimi, Y; Matsuki, M; Inoue, Y; Kambara, T; Ikezawa, Z

    2010-04-01

    Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to enhance the symptoms of wheat-dependent exercise-induced anaphylaxis (WDEIA). In contrast to many reports on WDEIA, there have been only a few reports of wheat-dependent aspirin-induced anaphylaxis not induced by the combination of wheat and exercise. Two patients with wheat-dependent anaphylaxis underwent provocation tests to clarify the cause of their symptoms. Skin-prick testing (SPT) was also performed with and without administration of aspirin. Specific IgE antibody to wheat, gluten, and omega-5 gliadin were examined. In the provocation tests, anaphylactic reactions were not induced by wheat or aspirin alone or by the combination of wheat and exercise, but were induced by the combination of wheat and aspirin. An increase in the blood histamine level was detected after provocation in both patients. Pretreatment with aspirin enhanced the SPT reactions to wheat and gluten in both patients. Specific IgE antibodies to wheat and gluten were expressed in the serum of both patients, and specific omega-5 gliadin IgE antibody was detected in the serum of one patient. We present two cases of specific wheat-dependent anaphylaxis induced by aspirin but not by exercise. We suggest that pretreatment with aspirin under controlled conditions is useful to confirm the diagnosis of food allergy when a challenge test with food alone or with food and exercise fails to induce positive reactions.

  8. of aspirin The use of renal enzymes indication of renal toxicity dose ...

    African Journals Online (AJOL)

    1983-04-30

    Apr 30, 1983 ... Ten volunteers participated in a study comparing the effects on renal enzymes of multiple oral doses of aspirin relative to no treatment. The total urinary output was collected daily for 21 days from all sub- jects. The first 7 days were treatment-free. During the second 7-day period the subjects received aspirin ...

  9. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial

    NARCIS (Netherlands)

    Alexander, J.H.; Lopes, R.D.; Thomas, L.; Alings, M.; Atar, D.; Aylward, P.; Goto, S.; Hanna, M.; Huber, K.; Husted, S.; Lewis, B.S.; McMurray, J.J.; Pais, P.; Pouleur, H.; Steg, P.G.; Verheugt, F.W.A.; Wojdyla, D.M.; Granger, C.B.; Wallentin, L.

    2014-01-01

    AIMS: We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). METHODS AND RESULTS: In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was

  10. Use and misuse of aspirin in rural Ethiopia | Duncan | East African ...

    African Journals Online (AJOL)

    Objectives: To investigate ability to distinguish simple analgesics, to document misconceptions about aspirin use, and to identify strategies to diminish potentially harmful aspirin use in Ethiopia. Design: Qualitative study (eight focus group discussions) used to inform cross-sectional survey. Setting: Butajira, a small town in ...

  11. Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers | Division of Cancer Prevention

    Science.gov (United States)

    This randomized phase II trial studies the effects of aspirin and zileuton on genes related to tobacco use in current smokers. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers. |

  12. UP-REGULATION OF ANTITHROMBOTIC ECTONUCLEOTIDASES BY ASPIRIN IN HUMAN ENDOTHELIAL-CELLS IN-VITRO

    NARCIS (Netherlands)

    CHEUNG, PK; VISSER, J; BAKKER, WW

    1994-01-01

    Ecto ATP-diphosphohydrolase (apyrase) activity of human endothelial cells following aspirin treatment has been studied in-vitro. It was shown by HPLC analysis of supernatant samples that pre-incubation of the cultures with aspirin resulted in a significantly increased turnover of supplemented ATP

  13. The mortality reducing effect of aspirin in colorectal cancer patients: Interpreting the evidence.

    Science.gov (United States)

    Frouws, Martine A; van Herk-Sukel, Myrthe P P; Maas, Huub A; Van de Velde, Cornelis J H; Portielje, Johanneke E A; Liefers, Gerrit-Jan; Bastiaannet, Esther

    2017-04-01

    In 1971 the first study appeared that suggested a relationship between aspirin and cancer. Currently publications on the subject of aspirin and cancer are numerous, with both a beneficial effect of aspirin on cancer incidence and a beneficial effect on cancer survival. This review focusses on the relation between the use of aspirin and improved survival in colorectal cancer patients. Various study designs have been used, with the main part being observational studies and post hoc meta-analyses of cancer outcomes in cardiovascular prevention trials. The results of these studies are unambiguously pointing towards an effect of aspirin on colorectal cancer survival, and several randomised controlled trials are currently ongoing. Some clinicians feel that the current evidence is conclusive and that the time has come for aspirin to be prescribed as adjuvant therapy. However, until this review, not much attention has been paid to the specific types of bias associated with these studies. One of these biases is confounding by indication, because aspirin is indicated for patients as secondary prevention for cardiovascular disease. This review aims to provide perspective on these biases and provide tools for the interpretation of the current evidence. Albeit promising, the current evidence is not sufficient to already prescribe aspirin as adjuvant therapy for colorectal cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Aspirin and its related non-steroidal anti-inflammatory drugs

    African Journals Online (AJOL)

    Aspirin and its related non-steroidal anti-inflammatory drugs. Aspirin or acetylsalicylic acid has been utilised by physicians for hundreds of years as an analgesic, anti-inflammatory and antipyretic (1). Derived from plant sources, such as the willow tree, it has the ability to induce apoptosis in cancer cells and stimulate.

  15. An Audit Of Aspirin Use For Prevention Of Vascular Complications In ...

    African Journals Online (AJOL)

    Background: Cardiovascular events represent the major cause of death in individuals with diabetes mellitus. The American Diabetes Association has recommended that diabetic adults with addition risk factor for cardiovascular disease be treated with aspirin. We aimed to assess the use of aspirin in diabetic patients.

  16. Effect of clopidogrel added to aspirin in patients with atrial fibrillation

    NARCIS (Netherlands)

    Connolly, Stuart J.; Pogue, Janice; Hart, Robert G.; Hohnloser, Stefan H.; Pfeffer, Marc; Chrolavicius, Susan; Yusuf, Salim; Connolly, S. J.; Yusuf, S.; Camm, J.; Chrolavicius, S.; Commerford, P.; Flather, M.; Hart, R. G.; Hohnloser, S. H.; Joyner, C.; Pfeffer, M.; Gaudin, C.; Blumenthal, M.; Marchese, C.; Pogue, J.; Hart, R.; Hohnloser, S.; Anand, I.; Arthur, H.; Avezum, A.; Budaj, A.; Ceremuzynski, L.; de Caterina, R.; Diaz, R.; Dorian, P.; Flaker, G.; Fox, K. A. A.; Franzosi, M. G.; Goldhaber, S.; Golitsyn, S.; Granger, C.; Halon, D.; Hermosillo, A.; Hunt, D.; Jansky, P.; Karatzas, N.; Keltai, M.; Kozan, O.; Lanas, F.; Lau, C. P.; Le Heuzey, J. Y.; Lewis, B. S.; Morais, J.; Morillo, C.; Paolasso, E.; Peters, R. J.; Pfisterer, M.; Piegas, L.; Pipilis, A.; Sitkei, E.; Swedberg, K.; Talajic, M.; Valentin, V.; van Mieghem, W.; Varigos, J.; Ameriso, S.; Atra, M.; Berwanger, O.; Bonilla, C.; Bornstein, N.; Chamiec, T.; Chan, Y. K.; Cottin, Y.; Csiba, L.; Cybulski, J.; Czepiel, A.; de Raedt, H.; Dvorakova, H.; Eikelboom, J.; Ergene, O.; Fodor, G.; Galli, M.; Gardinale, E.; Gross, B.; Goodfield, P.; Happola, O.; Healey, J.; Himbert, D.; Jacobsson, F.; Kalvach, P.; Kies, B.; Laine, M.; Lam, A.; Lewis, S.; Leys, D.; Maggioni, A. P.; Massaro, A.; Mayosi, B. M.; Norrving, B.; Okay, T.; Olah, L.; Osende, J. O.; Oto, A.; Peeters, A.; Penicka, M.; Perakis, A.; Pizzolato, G.; Rafti, F.; Renkin, J.; Siva, A.; Steg, P. G.; Stockins, B.; Strozynska, E.; Turazza, F.; Vanderhoven, L.; Vizel, S.; Widimsky, P.; Zaborski, J.; Albers, G.; Hankey, G.; Shuaib, A.; Silva, J.; Wyse, D. G.; Cairns, J. A.; Gent, M.; Hirsh, J.; Marler, J.; Pritchett, E.; Wittes, J.; Beresh, H.; Floyd, L.; Gasic, Z.; Holadyk-Gris, I.; Lawrence, M.; Moro, I.; Perry, S.; Roberts, J.; Rodrigues, T.; Robinson, L.; Stevens, C.; Worthy, L.; Yuan, F.; Ahuad Guerrero, R. A.; Allall, O.; Amuchastegui, L. M.; Boskis, M.; Bustamante Labarta, M. H.; Castellanos, C. R.; Chiale, P.; Cuneo, C. A.; Czcczuo, A.; Gabito, A. J.; Garrido, M.; Guzmán, L. A.; Hasban, E. G.; Hershson, A. R.; Hominal, M. A.; Krauss, J. G.; Luciardi, H. L.; Marzetti, E. M.; Montaña, O. R.; Rabinovich, R. F.; Ramos, H. R.; Sanchez, A. S.; Schygiel, P. O.; Sumay, G. M.; Vogel, D. R.; Zaidman, C. J.; Aroney, G. M.; Ashby, D. T.; Barlow, M. A.; Cooke, P.; Cross, D. B.; Fitzpatrick, M. A.; Garrahy, P.; Karrasch, J.; Nelson, G. I.; Rees, D.; Roger, S. D.; Rogers, J.; Singh, B. B.; Stickland, J. F.; Waites, J. H.; Walsh, W. F.; Eichinger, J.; Huber, K.; Leisch, F.; Boland, J.; Conraads, V. M.; Cools, F. J. C.; de Roy, L.; El Allaf, D.; Mairesse, G. H.; Vankelecom, B.; Abrantes, J.; Armaganijan, D.; Atié, J.; Blacher, C.; Bodanese, L. C.; Braga, J. C. F.; Braile, M. V.; Chaves, H.; Coelho, O. R.; Cunha, C. L. P.; de Lima, G. G.; de Paola, A. A. V.; Esteves, J. P.; Francischetti, A.; Francischetti, A. E.; Lorga-Filho, A. M.; Maia, L. N.; Marcussi, D. M.; Marin-Neto, J. A.; Meneghelo, Z. M.; Rocha, R. Mourilhe; Nogueira, P. R.; Oigman, W.; Paiva, M.; Précoma, D. B.; Rabelo, W.; Rabelo, A.; Rassi, S.; Rassi, A.; Reis, G.; Rossi, P. R.; Rossi Neto, J. M.; Saraiva, J. K.; Sobral-Filho, D. C.; Zimmermann, S. L.; Ashton, T. A.; Bhargava, R.; Carroll, S.; Chehayeb, R.; Connors, S. P.; Constance, C.; Costi, P.; Coutu, B.; Crystal, E.; Douketis, J. D.; Fortin, C.; Fox, B. A.; Gupta, M. K.; Krahn, A. D.; Kuritzky, R.; Kwok, K.; Leader, R.; Ma, P.; Mangat, I.; Maranda, C. R.; Matangi, M. F.; Moddel, G.; Mukherjee, A.; Nawaz, S.; Palaic, M.; Pandey, A. S.; Rebane, T. M.; Ruel, M.; Sapp, J. L.; Senaratne, M. P.; St-Hilaire, R.; Talbot, P.; To, T. B.; Vakani, M.; Weigel, M. A.; Wulffhart, Z.; Yao, L.; Zaniol, D.; Conejeros, C. R.; Corbalán, R.; Dussaillant, G. R.; Escobar, E.; Hassi, M. E.; Parra, C. A.; Stockins, B. A.; Varleta, P. E.; Berka, L.; Dedek, V.; Florian, J.; Hejhal, O.; Herold, M.; Klimsa, Z.; Kotik, I.; Simon, J.; Smetana, K.; Spinar, J.; Spinarová, L.; Tousek, F.; Husted, S.; Nielsen, T.; Pehrson, S.; Tuxen, C.; Harjola, V. P.; Huikuri, H. V.; Kettunen, R. V. J.; Melin, J. H.; Peuhkurinen, K.; Carlioz, R.; Coisne, D.; Decoulx, E.; Defaye, P.; Demarcq, J. M.; Gacem, K.; Galley, D. L.; Lardoux, H. M.; Mabo, P.; Mansour, M.; Olive, T. G.; Poulard, J. E.; Pruvot, C. F.; Rey, J. L.; Bauer, W. R.; Baumann, G.; Berghöfer, G.; Boehm, G.; Borggrefe, M. M.; Brücker, G.; Darius, H.; Duray, G. Z.; Felix, S. B.; Fink, P.; Fritz, H.; Haberl, R.; Hoffmann, S.; Horacek, T.; Kalusche, D. W.; Kasper, W.; Katus, H. A.; Klepzig, H. H.; Loos, U.; Merher, R.; Munzel, T.; Neuzner, J.; Ochs, H. R.; Pieske, B.; Pollock, B. W.; Schmidt, A.; Schumacher, M.; Seidl, K.; Speier, U.; Spitzer, S. G.; Stenzel, G.; Volkmann, H.; Wunderlich, J.; Zacharzowsky, U.; Antonakoudis, H.; Georgakopoulos, N.; Goudevenos, J. A.; Iliopoulos, T. A.; Kallikazaros, I.; Pyrgakis, V. N.; Skoufas, P.; Chan, W. K.; Chan, H. W.; Fung, J. W. H.; Li, S. K.; Wong, K. S.; Forster, T.; Kárpáti, P.; Keltai, K.; Kovacs, A.; Kurta, G.; Laszlo, Z.; Rapi, J.; Regos, L.; Rostas, L.; Szakál, I.; Tomcsanyi, J.; Toth, C.; Bloch, L.; Khader, N.; Klainman, E.; Koukoui, D.; Lotan, C.; Marmor, A.; Omary, M. Z.; Reisin, L. H.; Vered, Z.; Zeltser, D.; Zimlichman, R.; Bianconi, L.; Bicego, D.; Cosmi, D.; Filigheddu, F.; Garini, A.; Lunati, M.; Moretti, L.; Mos, L.; Pontiroli, A. E.; Renda, G.; Ricci, S.; Rossi, P.; Santonastaso, M.; Scioli, G. A.; Stramba-Badiale, M.; Terrosu, P.; Omar, R.; Ong, T. K.; Ahmad, W. A. Wan; Alvarado, R.; Calvo, C.; Cordero-Cabra, J. A.; Hernández, I.; Jerjes-Sanchez, C.; Lara, S.; Lopez Rosas, E.; Molina, L.; Morales, E.; Petersen-Aranguren, F.; Picos Bovio, E. M.; Pozas, G.; Robles Torres, F. J.; Holwerda, K.; Lok, D. J. A.; Nierop, R.; Pieterse, M. G. C.; van der Heijden, R.; van Kempen, L.; Oie, B. K.; Omland, T. M.; Otterstad, J.; von Brandis, C.; Bronisz, M.; Chizynski, K.; Czerski, T.; Dluzniewski, M.; Gessek, J.; Gieroba, A.; Gniot, J. R.; Gorny, J.; Halaczuiewicz, H.; Janik, K.; Janion, M.; Jerzykowska, O.; Kawka-Urbanek, T.; Kincel, K.; Kocon, S.; Kopaczewski, J.; Krasowski, W.; Makuch, M.; Malinowski, S.; Miastkowski, Z.; Mickiewicz-Pawlowska, M.; Miekus, P.; Obrebska-Tabaczka, E.; Ogorek, M.; Piasecka-Krysiak, E.; Piepiorka, A. W.; Piotrowski, W.; Pluta, W.; Puzio, E.; Rekosz, J.; Sinkiewicz, W.; Stopinski, M.; Szelemej, R.; Tendera, M.; Trusz-Gluza, M.; Wilkoszynski, M.; Zalska, B.; Antunes, E.; Carrageta, M. O.; de Sousa, J.; Martins, L.; Mendonca, M. I.; Silvestre, I.; Akatova, E. V.; Aleksandrov, V.; Antuch, E. A.; Arutyunov, G.; Bart, B.; Belousov, Y. B.; Chernichka, I. I.; Dovgalevsky, P.; Gratsiansky, N.; Ivleva, A. Y.; Kislyak, O. A.; Mareyev, V. Y.; Maykov, E. B.; Milyagin, V.; Novikova, T. N.; Panchenko, E. P.; Reshetko, O.; Semernin, E.; Sidorenko, B. A.; Sinopalnikov, A.; Skvortsova, V.; Solomatin, A.; Sukhinina, T. S.; Suslina, Z. A.; Titkov, Y.; Tsyrline, V.; Chan, B.; Foo, D.; Omar, A. R.; teo, W. S.; Brown, B. G.; Ebrahim, I. O.; Gibson, G. J.; Klug, E.; Marx, J. D.; Mntla, P. S.; Okreglicki, A.; Pretorius, M.; Roos, J. S.; Snyders, F.; van Zyl, L. J.; Cano, L.; Garcia-Puig, J.; Hernandez-Madrid, A.; Mostaza, J. M.; Orriach, M. D.; Sabate, X.; Viñolas, X.; Blomström, P.; Johansson, L.; Klintberg, L.; Lycksell, M.; Nilsson, O.; Rasmanis, G.; Nilehn, K. E. Saldeen; Ulvenstam, G.; Baumgartner, R. W.; François, M.; Gallino, A.; Moccetti, T.; Tettenborn, B. E.; Chou, H.-T.; Kuo, J.-Y.; Lai, W.-T.; Lin, J. L.; Lin, L.-J.; Ueng, K. C.; Yeih, D.-F.; Bakar, M.; Ilerigelen, B.; Kumral, E.; Nisanci, Y.; Savas, Z. I.; Adgey, Y.; Brack, M. J.; Cleland, J.; Davey, P. P.; Davies, J.; Glen, S. K.; Jennings, K.; Levy, T.; Lip, G. Y. H.; Moriarty, A. J.; Pearson, C.; Purvis, J. A.; Pye, M. P.; Savelieva, I.; Senior, R.; Trouton, T. G.; Ahmed, I. S.; Amin, M.; Anderson, J. L.; Bauernfeind, R. A.; Belew, K.; Bilazarian, S. D.; Black, R. A.; Burton, M. E.; Cebe, J. E.; Chandrashekhar, Y. S.; Chen, C.; Das, D.; Denny, D. M.; Desai, V.; Fahmy, R. N.; Fishbein, G. J.; Gelernt, M. D.; Gerber, J.; Goldberg, M. C.; Grena, P. G.; Honan, M. B.; Hunter, J. J.; Jacobson, J.; Jarmukli, N. F.; Klancke, K.; Kobayashi, J. F.; Lewis, S. J.; Little, T.; Mallis, I.; Marani, A. M.; Marshall, J. J.; Meltzer, P.; Menapace, F. J.; O'Neill, P. G.; Pearce, D. J.; Quick, A.; Ravipudi, S.; Rivera, E.; Sackett, M.; Salerno, D. M.; Schussheim, A.; Sheikh, K.; Shettigar, U. R.; Treasure, C. B.; Vidaillet, H.; Vijay, N.; Wagner, D.; Walker, J. L.; Winters, S. L.; Young, D. R.; Zoble, R. G.

    2009-01-01

    BACKGROUND: Vitamin K antagonists reduce the risk of stroke in patients with atrial fibrillation but are considered unsuitable in many patients, who usually receive aspirin instead. We investigated the hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in

  17. Aspirin for primary prevention of cardiovascular disease and cancer. A benefit and harm analysis

    NARCIS (Netherlands)

    Stegeman, Inge; Bossuyt, Patrick M.; Yu, Tsung; Boyd, Cynthia; Puhan, Milo A.

    2015-01-01

    Background Aspirin is widely used for prevention of cardiovascular disease. In recent years randomized trials also suggested a preventive effect for various types of cancer. We aimed to assess, in a quantitative way, benefits and harms of aspirin for primary prevention of both cardiovascular disease

  18. Variability in the Responsiveness to Low-Dose Aspirin: Pharmacological and Disease-Related Mechanisms

    Directory of Open Access Journals (Sweden)

    Bianca Rocca

    2012-01-01

    Full Text Available The main pharmacological aspects of pharmacodynamics (PD and pharmacokinetics (PK of aspirin as antiplatelet agent were unravelled between the late sixties and the eighties, and low-dose aspirin given once daily has been shown to be a mainstay in the current treatment and prevention of cardiovascular disorders. Nevertheless, several PD and PK aspects of aspirin in selected clinical conditions have recently emerged and deserve future clinical attention. In 1994, the term “aspirin resistance” was used for the first time, but, until now, no consensus exists on definition, standardized assay, underlying mechanisms, clinical impact, and possible efficacy of alternative therapeutic interventions. At variance with an undefined aspirin-resistant status, in the last 5 years, the concept of variability in response to aspirin due to specific pathophysiological mechanisms and based on PK and/or PD of the drug has emerged. This growing evidence highlights the existence and possible clinical relevance of an interindividual variability of pharmacological aspirin response and calls for new, large studies to test new low-dose aspirin-based regimens which may ameliorate platelet acetylation, reduce variability in drug responsiveness, and improve clinical efficacy on selected populations.

  19. Effect of chronic aspirin ingestion on epithelial proliferation in rat fundus, antrum, and duodenum

    Energy Technology Data Exchange (ETDEWEB)

    Eastwood, G.L.; Quimby, G.F.

    1972-05-01

    We studied the effect of chronic aspirin ingestion on gastroduodenal epithelial proliferation by feeding rats aspirin in the drinking water. A control group of rats received plain water. At the end of 4 wk, (3H)-thymidine was given intravenously to label proliferating cells, and the rats were killed 1 h later. Sections of fundus, antrum, and proximal duodenum were processed for light autoradiography. We found that chronic aspirin ingestion stimulated epithelial proliferation in fundic mucosa but had no effect in the antrum. In the duodenum, aspirin increased proliferation in the lowest four crypt-cell positions, which most likely indicates an increase in stem-cell production. None of the tissues contained evidence of inflammation or ulceration. The proliferative effects of aspirin may help explain the previously observed phenomenon of mucosal adaptation in the rat after repeated exposure to aspirin. Further, if human gastroduodenal epithelium responds in a similar manner to chronic aspirin exposure, the effects on proliferation may explain in part the distribution of aspirin-associated ulcers.

  20. Aspirin induces Beclin-1-dependent autophagy of human hepatocellular carcinoma cell.

    Science.gov (United States)

    Huang, Zhenjun; Fang, Weilun; Liu, Weihua; Wang, Li; Liu, Bin; Liu, Shiming; Liu, Shaojun

    2018-01-31

    Aspirin not only reduces the incidence of hepatocellular carcinoma (HCC) but also plays a synergistic role with chemotherapy for HCC treatment. However, the underlying mechanisms remain incompletely elucidated. Given that autophagy triggers cancer cell death, the present study examined the autophagic effect of aspirin on HCC cells. Results showed that aspirin increased LC3II/LC3I ratio, decreased p62 expression, and enhanced autophagic flux (autophagosome and autolysosome puncta) in Hep3B, HepG2, or SMMC-7721 cells, reflecting the autophagy of HCC cells. The autophagic effects of aspirin depended on Beclin-1 expression. Aspirin disrupted the interaction between Bcl-2 and Beclin-1. In addition to activating the AMP-activated protein kinase, c-Jun N-terminal kinase, and Glycogen synthase kinase-3 pathways, aspirin inhibited the mammalian-target-of rapamycin-S6K1/4E-BP1 signaling. Aspirin induced autophagy of HCC cell. This study contributes to understanding the chemoprotective and inhibitory effects of aspirin on HCC development. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Influence of renal function and platelet turnover on the antiplatelet effect of aspirin.

    Science.gov (United States)

    Würtz, Morten; Wulff, Lise N; Grove, Erik L; Kristensen, Steen D; Hvas, Anne-Mette

    2012-04-01

    Kidney disease predisposes to cardiovascular events. This study investigated the influence of renal function and platelet turnover on the antiplatelet effect of aspirin in patients with coronary artery disease. We included 124 aspirin-treated patients with coronary artery disease and normal to moderately reduced renal function. All tests were performed one hour after aspirin ingestion. Renal function was assessed using creatinine, estimated glomerular filtration rate (eGFR), and cystatin C. The antiplatelet effect of aspirin was evaluated using the VerifyNow Aspirin assay and multiple electrode aggregometry (MEA, Multiplate) induced by collagen (1.0 μg/mL) and arachidonic acid (1.0 mmol/L). Von Willebrand factor was measured as a marker of endothelial dysfunction. Platelet turnover was evaluated by measurements of immature, reticulated platelets. Renal function did not influence the antiplatelet effect of aspirin evaluated by MEA (r=-0.2-0.09, p=0.03-0.77) or the VerifyNow (r=-0.12-0.11, all p-values>0.1). In contrast, renal function correlated inversely with von Willebrand factor levels (r(creatinine)=0.48, pantiplatelet effect of aspirin may be explained by an increased number of immature platelets. Moderately impaired renal function was associated with high levels of von Willebrand factor, but not with a reduced antiplatelet effect of aspirin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Monitoring aspirin therapy in children after interventional cardiac catheterization: laboratory measures, dose response, and clinical outcomes.

    Science.gov (United States)

    Schmugge, Markus; Speer, Oliver; Kroiss, Sabine; Knirsch, Walter; Kretschmar, Oliver; Rand, Margaret L; Albisetti, Manuela

    2015-07-01

    Very few studies have investigated dose response of aspirin and agreement of different platelet function assays in children. One hundred five children were studied at baseline and after interventional cardiac catheterization during aspirin treatment and, in cases of aspirin resistance (AR), after dose increase. Results from arachidonate-induced aggregation (AA) were compared with aggregation induced by ADP, PFA-100 closure times (CTs), urinary 11-dehydro-thromboxane B2 (urinary 11-dhTxB2) levels, and Impact-R % surface coverage. Aspirin at 2-5 mg/kg/day inhibited platelet function in a large majority. While 19 % showed bruising and mild epistaxis, no thrombotic complications were recorded. AR was detected by AA in seven children (6.7 %). After dose increase, the majority showed inhibition by aspirin. Infants had higher urinary 11-dhTxB2 baseline levels; this assay showed some correlation with AA. Both assays manifested high sensitivity and specificity for aspirin while inferior results were found for the other assays. With the PFA-100, 15.2 % of patients were found to have AR, but this corresponded to AR by AA in only one of seven children. While there was poor agreement among assays, AA and urinary 11-dhTxB2 show good specificity for the monitoring of aspirin therapy in children. Aspirin at 2-5 mg/kg inhibits platelet function; AR in children is rare and can be overcome by dose increase.

  3. Prevalence of aspirin resistance in patients with an evolving acute myocardial infarction

    DEFF Research Database (Denmark)

    Poulsen, Tina Svenstrup; Jørgensen, Bo; Korsholm, Lars

    2007-01-01

    OBJECTIVE: To study the prevalence and importance of aspirin resistance in patients with an evolving acute myocardial infarction (AMI) by use of the Platelet Function Analyzer-100. INTRODUCTION: Previous studies have demonstrated the existence of aspirin resistance, but the clinical relevance...

  4. Aspirin increases metabolism through germline signalling to extend the lifespan of Caenorhabditis elegans.

    Science.gov (United States)

    Huang, Xiao-Bing; Mu, Xiao-Hui; Wan, Qin-Li; He, Xiao-Ming; Wu, Gui-Sheng; Luo, Huai-Rong

    2017-01-01

    Aspirin is a prototypic cyclooxygenase inhibitor with a variety of beneficial effects on human health. It prevents age-related diseases and delays the aging process. Previous research has shown that aspirin might act through a dietary restriction-like mechanism to extend lifespan. To explore the mechanism of action of aspirin on aging, we determined the whole-genome expression profile of Caenorhabditis elegans treated with aspirin. Transcriptome analysis revealed the RNA levels of genes involved in metabolism were primarily increased. Reproduction has been reported to be associated with metabolism. We found that aspirin did not extend the lifespan or improve the heat stress resistance of germline mutants of glp-1. Furthermore, Oil Red O staining showed that aspirin treatment decreased lipid deposition and increased expression of lipid hydrolysis and fatty acid β-oxidation-related genes. The effect of germline ablation on lifespan was mainly mediated by DAF-12 and DAF-16. Next, we performed genetic analysis with a series of worm mutants and found that aspirin did not further extend the lifespans of daf-12 and daf-16 single mutants, glp-1;daf-12 and glp-1;daf-16 double mutants, or glp-1;daf-12;daf-16 triple mutants. The results suggest that aspirin increase metabolism and regulate germline signalling to activate downstream DAF-12 and DAF-16 to extend lifespan.

  5. Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS)

    DEFF Research Database (Denmark)

    Bath, Philip M; Woodhouse, Lisa J; Appleton, Jason P

    2017-01-01

    BACKGROUND: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel...

  6. Impact of aspirin on the transcriptome ofStreptococcus pneumoniaeD39.

    Science.gov (United States)

    Afzal, Muhammad; Shafeeq, Sulman

    2017-06-01

    Aspirin or acetylsalicylic acid (ASA) is a medicine used to treat pain, fever, and inflammation. Here, we for the very first time reported the genome-wide transcriptional profiling of aspirin-regulated genes in Streptococcus pneumoniae in the presence of 5 mM aspirin in chemically-defined medium (CDM) using microarray analysis. Our results showed that expression of several genes was differentially expressed in the presence of aspirin. These genes were further grouped into COG (Clusters of Orthologous Groups) functional categories based on the putative functions of the corresponding proteins. Most of affected genes belong to COG category E (Amino acid transport and metabolism), G (Carbohydrate transport and metabolism), J (Translation, ribosomal structure and biogenesis), and I (Lipid transport and metabolism). Transcriptional profiling data of aspirin-regulated genes was deposited to Gene Expression Omnibus (GEO) database under accession number GSE94514.

  7. Impact of aspirin on the transcriptome of Streptococcus pneumoniae D39

    Directory of Open Access Journals (Sweden)

    Muhammad Afzal

    2017-06-01

    Full Text Available Aspirin or acetylsalicylic acid (ASA is a medicine used to treat pain, fever, and inflammation. Here, we for the very first time reported the genome-wide transcriptional profiling of aspirin-regulated genes in Streptococcus pneumoniae in the presence of 5 mM aspirin in chemically-defined medium (CDM using microarray analysis. Our results showed that expression of several genes was differentially expressed in the presence of aspirin. These genes were further grouped into COG (Clusters of Orthologous Groups functional categories based on the putative functions of the corresponding proteins. Most of affected genes belong to COG category E (Amino acid transport and metabolism, G (Carbohydrate transport and metabolism, J (Translation, ribosomal structure and biogenesis, and I (Lipid transport and metabolism. Transcriptional profiling data of aspirin-regulated genes was deposited to Gene Expression Omnibus (GEO database under accession number GSE94514.

  8. Low-dose aspirin or other nonsteroidal anti-inflammatory drug use and prostate cancer risk

    DEFF Research Database (Denmark)

    Skriver, Charlotte; Dehlendorff, Christian; Borre, Michael

    2016-01-01

    Purpose Increasing evidence suggests that aspirin use may protect against prostate cancer. In a nationwide case–control study, using Danish high-quality registry data, we evaluated the association between the use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs......) and the risk of prostate cancer. Methods We identified 35,600 patients (cases) with histologically verified prostate cancer during 2000–2012. Cases were matched to 177,992 population controls on age and residence by risk-set sampling. Aspirin and nonaspirin NSAID exposure was defined by type, estimated dose......, duration, and consistency of use. We used conditional logistic regression to estimate odds ratios (ORs), with 95 % confidence intervals (CIs), for prostate cancer associated with low-dose aspirin (75–150 mg) or nonaspirin NSAID use, adjusted for potential confounders. Results Use of low-dose aspirin...

  9. By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma.

    Science.gov (United States)

    Li, Sainan; Dai, Weiqi; Mo, Wenhui; Li, Jingjing; Feng, Jiao; Wu, Liwei; Liu, Tong; Yu, Qiang; Xu, Shizan; Wang, Wenwen; Lu, Xiya; Zhang, Qinghui; Chen, Kan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Fan, Xiaoming; Xu, Ling; Guo, Chuanyong

    2017-12-15

    Hepatocellular carcinoma (HCC) is one of the few cancers with a continuous increase in incidence and mortality. Drug resistance is a major problem in the treatment of HCC. In this study, two sorafenib-resistant HCC cell lines and a nude mouse subcutaneously tumor model were used to explore the possible mechanisms leading to sorafenib resistance, and to investigate whether aspirin could increase the sensitivity of hepatoma cells to sorafenib. The combination of aspirin and sorafenib resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo. High glycolysis and PFKFB3 overexpression occupied a dominant position in sorafenib resistance, and can be targeted and overcome by aspirin. Aspirin plus sorafenib induced apoptosis in tumors without inducing weight loss, hepatotoxicity or inflammation. Our results suggest that aspirin overcomes sorafenib resistance and their combination may be an effective treatment approach for HCC. © 2017 UICC.

  10. Combined effects of aspirin and vitamin D3 on two OSCC cell lines: a preliminary study.

    Science.gov (United States)

    Xiao, Ting-Ting; Li, Xian; Feng, Jia-Li; Li, Yong

    2018-01-18

    We evaluated the potential effects of aspirin combined with vitamin D3 on cell proliferation and apoptosis in oral cancer cells. Compared to the untreated control or individual drug, the combinations of aspirin and vitamin D3 significantly decreased the rates of cell proliferation by CCK-8 assay, and caused higher rates of cell apoptosis in both CAL-27 and SCC-15 cells by Annexin V-FITC apoptosis assay and flow cytometry. Remarkably, the combined treatment with aspirin and vitamin D3 significantly suppressed the expression of Bcl-2 protein and p-Erk1/2 protein, examined by western blot analysis. Our study demonstrates that aspirin and vitamin D3 have biological activity against two human OSCC cell lines and their activity is synergistic or additive when two drugs used in combination with therapeutic concentrations. The combination of aspirin and vitamin D3 may be an effective approach for inducing cell death in OSCC.

  11. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease

    DEFF Research Database (Denmark)

    Anand, Sonia S; Bosch, Jackie; Eikelboom, John W

    2018-01-01

    . The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5...... mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043). INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased......, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb...

  12. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome

    DEFF Research Database (Denmark)

    Burn, John; Bishop, D Timothy; Mecklin, Jukka-Pekka

    2008-01-01

    BACKGROUND: Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect...... on the colon. METHODS: In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome...... developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) (relative risk, 1.0; 95% confidence interval [CI], 0.7 to 1.4). There were no significant...

  13. Exonic variants associated with development of aspirin exacerbated respiratory diseases.

    Directory of Open Access Journals (Sweden)

    Seung-Woo Shin

    Full Text Available Aspirin-exacerbated respiratory disease (AERD is one phenotype of asthma, often occurring in the form of a severe and sudden attack. Due to the time-consuming nature and difficulty of oral aspirin challenge (OAC for AERD diagnosis, non-invasive biomarkers have been sought. The aim of this study was to identify AERD-associated exonic SNPs and examine the diagnostic potential of a combination of these candidate SNPs to predict AERD. DNA from 165 AERD patients, 397 subjects with aspirin-tolerant asthma (ATA, and 398 normal controls were subjected to an Exome BeadChip assay containing 240K SNPs. 1,023 models (210-1 were generated from combinations of the top 10 SNPs, selected by the p-values in association with AERD. The area under the curve (AUC of the receiver operating characteristic (ROC curves was calculated for each model. SNP Function Portal and PolyPhen-2 were used to validate the functional significance of candidate SNPs. An exonic SNP, exm537513 in HLA-DPB1, showed the lowest p-value (p = 3.40×10-8 in its association with AERD risk. From the top 10 SNPs, a combination model of 7 SNPs (exm537513, exm83523, exm1884673, exm538564, exm2264237, exm396794, and exm791954 showed the best AUC of 0.75 (asymptotic p-value of 7.94×10-21, with 34% sensitivity and 93% specificity to discriminate AERD from ATA. Amino acid changes due to exm83523 in CHIA were predicted to be "probably damaging" to the structure and function of the protein, with a high score of '1'. A combination model of seven SNPs may provide a useful, non-invasive genetic marker combination for predicting AERD.

  14. Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications

    Directory of Open Access Journals (Sweden)

    García Rodríguez Luis A

    2006-09-01

    Full Text Available Abstract Background To balance the cardiovascular benefits from low-dose aspirin against the gastrointestinal harm caused, studies have considered the coronary heart disease risk for each individual but not their gastrointestinal risk profile. We characterized the gastrointestinal risk profile of low-dose aspirin users in real clinical practice, and estimated the excess risk of upper gastrointestinal complications attributable to aspirin among patients with different gastrointestinal risk profiles. Methods To characterize aspirin users in terms of major gastrointestinal risk factors (i.e., advanced age, male sex, prior ulcer history and use of non-steroidal anti-inflammatory drugs, we used The General Practice Research Database in the United Kingdom and the Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria in Spain. To estimate the baseline risk of upper gastrointestinal complications according to major gastrointestinal risk factors and the excess risk attributable to aspirin within levels of these factors, we used previously published meta-analyses on both absolute and relative risks of upper gastrointestinal complications. Results Over 60% of aspirin users are above 60 years of age, 4 to 6% have a recent history of peptic ulcers and over 13% use other non-steroidal anti-inflammatory drugs. The estimated average excess risk of upper gastrointestinal complications attributable to aspirin is around 5 extra cases per 1,000 aspirin users per year. However, the excess risk varies in parallel to the underlying gastrointestinal risk and might be above 10 extra cases per 1,000 person-years in over 10% of aspirin users. Conclusion In addition to the cardiovascular risk, the underlying gastrointestinal risk factors have to be considered when balancing harms and benefits of aspirin use for an individual patient. The gastrointestinal harms may offset the cardiovascular benefits in certain groups of patients where the

  15. Lower Mortality Rate in Elderly Patients With Community‐Onset Pneumonia on Treatment With Aspirin

    Science.gov (United States)

    Falcone, Marco; Russo, Alessandro; Cangemi, Roberto; Farcomeni, Alessio; Calvieri, Camilla; Barillà, Francesco; Scarpellini, Maria Gabriella; Bertazzoni, Giuliano; Palange, Paolo; Taliani, Gloria; Venditti, Mario; Violi, Francesco

    2015-01-01

    Background Pneumonia is complicated by high rate of mortality and cardiovascular events (CVEs). The potential benefit of aspirin, which lowers platelet aggregation by inhibition of thromboxane A2 production, is still unclear. The aim of the study was to assess the impact of aspirin on mortality in patients with pneumonia. Methods and Results Consecutive patients admitted to the University‐Hospital Policlinico Umberto I (Rome, Italy) with community‐onset pneumonia were recruited and prospectively followed up until discharge or death. The primary end point was the occurrence of death up to 30 days after admission; the secondary end point was the intrahospital incidence of nonfatal myocardial infarction and ischemic stroke. One thousand and five patients (age, 74.7±15.1 years) were included in the study: 390 were receiving aspirin (100 mg/day) at the time of hospitalization, whereas 615 patients were aspirin free. During the follow‐up, 16.2% of patients died; among these, 19 (4.9%) were aspirin users and 144 (23.4%; Paspirin nonusers. Overall, nonfatal CVEs occurred in 7% of patients, 8.3% in nonaspirin users, and 4.9% in aspirin users (odds ratio, 1.77; 95% confidence interval, 1.03 to 3.04; P=0.040). The Cox regression analysis showed that pneumonia severity index (PSI), severe sepsis, pleural effusion, and PaO2/FiO2 ratio aspirin therapy was associated with improved survival. Compared to patients receiving aspirin, the propensity score adjusted analysis confirmed that patients not taking aspirin had a hazard ratio of 2.07 (1.08 to 3.98; P=0.029) for total mortality. Conclusions This study shows that chronic aspirin use is associated with lower mortality rate within 30 days after hospital admission in a large cohort of patients with pneumonia. PMID:25564372

  16. Estimates of benefits and harms of prophylactic use of aspirin in the general population

    Science.gov (United States)

    Cuzick, J.; Thorat, M. A.; Bosetti, C.; Brown, P. H.; Burn, J.; Cook, N. R.; Ford, L. G.; Jacobs, E. J.; Jankowski, J. A.; La Vecchia, C.; Law, M.; Meyskens, F.; Rothwell, P. M.; Senn, H. J.; Umar, A.

    2015-01-01

    Background Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. Methods The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer. Results The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50–65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. Conclusions Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit–harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening–eradication before starting aspirin prophylaxis. PMID:25096604

  17. Effect of Aspirin in Postoperative Management of Adult Ischemic Moyamoya Disease.

    Science.gov (United States)

    Zhao, Yahui; Zhang, Qian; Zhang, Dong; Zhao, Yuanli

    2017-09-01

    Aspirin has been implicated in the postoperative management of moyamoya disease (MMD) in order to avoid bypass failure and decrease the incidence of subsequent stroke. However, its effect has not been completely determined yet. In this study, we retrospectively reviewed data of 184 adult patients (197 hemispheres) presented with ischemic-onset MMD who had undergone direct or combined revascularization in our hospital, to clarify the effect of postoperative aspirin therapy in the management of moyamoya disease. Fifty-nine hemispheres that had been administered with aspirin (100 mg/day) after bypass surgery were defined as the "aspirin group," whereas 138 that hadn't been given aspirin postoperatively were defined as the "control group". Among 197 hemispheres, the mortality rate was 0. The incidence of postoperative newly developed infarction, transient ischemic attack, and hemorrhage were not significantly different between the aspirin and control groups. The patency rate of bypass graft was not significantly different between the groups, either. Notably, more patients experienced major stroke in the control group (9/138) than the aspirin group (1/59), but no statistical difference was found (P > 0.05). In the aspirin group, more patients had improved outcome than the control group (P = 0.04). Our findings showed that aspirin might not decrease the incidence of postoperative ischemic stroke or increase patency rate of bypass graft, but it does not increase the risk of hemorrhages, either. Also, postoperative aspirin therapy might improve outcome. More studies are needed to provide evidence for postoperative antiplatelet therapy in MMD management. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Aspirin use is associated with lower mammographic density in a large screening cohort.

    Science.gov (United States)

    Wood, Marie E; Sprague, Brian L; Oustimov, Andrew; Synnstvedt, Marie B; Cuke, Melissa; Conant, Emily F; Kontos, Despina

    2017-04-01

    Observational and biologic studies suggest that aspirin is a promising prevention therapy for breast cancer. However, clinical trials to date have not corroborated this evidence, potentially due to study design. We evaluated the effect of aspirin on mammographic density (MD), an established modifiable risk factor for breast cancer. Electronic medical records from the University of Pennsylvania were evaluated for women who underwent screening mammography, saw their primary care provider, and had a confirmed list of medications during 2012-2013. Logistic regression was performed to test for associations between clinically recorded MD and aspirin use, after adjusting for age, body mass index (BMI), and ethnicity. We identified 26,000 eligible women. Mean age was 57.3, mean BMI was 28.9 kg/m 2 , 41% were African American, and 19.7% reported current aspirin use. Aspirin users were significantly older and had higher BMI. There was an independent, inverse association between aspirin use and MD (P trend  aspirin users than women with scattered fibroglandular density (OR 0.73; 95% CI 0.57-0.93). This association was stronger for younger women (P = 0.0002) and for African Americans (P = 0.011). The likelihood of having dense breasts decreased with aspirin dose (P trend  = 0.007), suggesting a dose response. We demonstrate an independent association between aspirin use and lower MD in a large, diverse screening cohort. This association was stronger for younger and African American women: two groups at greater risk for ER- breast cancer. These results contribute to the importance of investigating aspirin for breast cancer prevention.

  19. Aspirin counteracts cancer stem cell features, desmoplasia and gemcitabine resistance in pancreatic cancer

    Science.gov (United States)

    Zhang, Yiyao; Liu, Li; Fan, Pei; Bauer, Nathalie; Gladkich, Jury; Ryschich, Eduard; Bazhin, Alexandr V.; Giese, Nathalia A.; Strobel, Oliver; Hackert, Thilo; Hinz, Ulf; Gross, Wolfgang; Fortunato, Franco; Herr, Ingrid

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis. An inflammatory microenvironment triggers the pronounced desmoplasia, the selection of cancer stem-like cells (CSCs) and therapy resistance. The anti-inflammatory drug aspirin is suggested to lower the risk for PDA and to improve the treatment, although available results are conflicting and the effect of aspirin to CSC characteristics and desmoplasia in PDA has not yet been investigated. We characterized the influence of aspirin on CSC features, stromal reactions and gemcitabine resistance. Four established and 3 primary PDA cell lines, non-malignant cells, 3 patient tumor-derived CSC-enriched spheroidal cultures and tissues from patients who did or did not receive aspirin before surgery were analyzed using MTT assays, flow cytometry, colony and spheroid formation assays, Western blot analysis, antibody protein arrays, electrophoretic mobility shift assays (EMSAs), immunohistochemistry and in vivo xenotransplantation. Aspirin significantly induced apoptosis and reduced the viability, self-renewal potential, and expression of proteins involved in inflammation and stem cell signaling. Aspirin also reduced the growth and invasion of tumors in vivo, and it significantly prolonged the survival of mice with orthotopic pancreatic xenografts in combination with gemcitabine. This was associated with a decreased expression of markers for progression, inflammation and desmoplasia. These findings were confirmed in tissue samples obtained from patients who had or had not taken aspirin before surgery. Importantly, aspirin sensitized cells that were resistant to gemcitabine and thereby enhanced the therapeutic efficacy. Aspirin showed no obvious toxic effects on normal cells, chick embryos or mice. These results highlight aspirin as an effective, inexpensive and well-tolerated co-treatment to target inflammation, desmoplasia and CSC features PDA. PMID:25846752

  20. Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications.

    Science.gov (United States)

    Hernández-Díaz, Sonia; García Rodríguez, Luis A

    2006-09-20

    To balance the cardiovascular benefits from low-dose aspirin against the gastrointestinal harm caused, studies have considered the coronary heart disease risk for each individual but not their gastrointestinal risk profile. We characterized the gastrointestinal risk profile of low-dose aspirin users in real clinical practice, and estimated the excess risk of upper gastrointestinal complications attributable to aspirin among patients with different gastrointestinal risk profiles. To characterize aspirin users in terms of major gastrointestinal risk factors (i.e., advanced age, male sex, prior ulcer history and use of non-steroidal anti-inflammatory drugs), we used The General Practice Research Database in the United Kingdom and the Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria in Spain. To estimate the baseline risk of upper gastrointestinal complications according to major gastrointestinal risk factors and the excess risk attributable to aspirin within levels of these factors, we used previously published meta-analyses on both absolute and relative risks of upper gastrointestinal complications. Over 60% of aspirin users are above 60 years of age, 4 to 6% have a recent history of peptic ulcers and over 13% use other non-steroidal anti-inflammatory drugs. The estimated average excess risk of upper gastrointestinal complications attributable to aspirin is around 5 extra cases per 1,000 aspirin users per year. However, the excess risk varies in parallel to the underlying gastrointestinal risk and might be above 10 extra cases per 1,000 person-years in over 10% of aspirin users. In addition to the cardiovascular risk, the underlying gastrointestinal risk factors have to be considered when balancing harms and benefits of aspirin use for an individual patient. The gastrointestinal harms may offset the cardiovascular benefits in certain groups of patients where the gastrointestinal risk is high and the cardiovascular risk is low.

  1. Ascorbic Acid may Exacerbate Aspirin-Induced Increase in Intestinal Permeability.

    Science.gov (United States)

    Sequeira, Ivana R; Kruger, Marlena C; Hurst, Roger D; Lentle, Roger G

    2015-09-01

    Ascorbic acid in combination with aspirin has been used to prevent aspirin-induced oxidative GI damage. We aimed to determine whether ascorbic acid reduces or prevents aspirin-induced changes in intestinal permeability over a 6-hr period using saccharidic probes mannitol and lactulose. The effects of administration of 600 mg aspirin alone, 500 mg ascorbic acid alone and simultaneous dosage of both agents were compared in a cross-over study in 28 healthy female volunteers. These effects were also compared with that of a placebo. The ability of ascorbic acid to mitigate the effects of aspirin when administered either half an hour before or after dosage with aspirin was also assessed in 19 healthy female volunteers. The excretion of lactulose over the 6-hr period was augmented after consumption of either aspirin or ascorbic acid compared with that after consumption of placebo. Dosage with ascorbic acid alone augmented the excretion of lactulose more than did aspirin alone. Simultaneous dosage with both agents augmented the excretion of lactulose in an additive manner. The timing of dosage with ascorbic acid in relation to that with aspirin had no significant effect on the excretion of the two sugars. These findings indicate that ascorbic acid does not prevent aspirin-induced increase in gut permeability rather that both agents augment it to a similar extent. The additive effect on simultaneous dosage with both agents in augmenting the absorption of lactulose suggests that each influences paracellular permeability by different pathways. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  2. Antiplatelet effect of aspirin during 24h in patients with type 2 diabetes without cardiovascular disease.

    Science.gov (United States)

    Vernstrøm, Liv; Funck, Kristian Løkke; Grove, Erik Lerkevang; Laugesen, Esben; Baier, Jonathan Mathias; Hvas, Anne-Mette; Poulsen, Per Løgstrup

    2018-01-01

    The antiplatelet effect of low-dose aspirin in patients with type 2 diabetes (T2DM) without cardiovascular disease (CVD) has not been thoroughly explored. We investigated if platelet aggregation increased during the standard 24-hour aspirin dosing interval in patients with T2DM compared to non-diabetic controls. Furthermore, we evaluated baseline platelet aggregation, the acute effects of aspirin on platelet aggregation and platelet turnover. We included 21 patients with T2DM and 21 age and sex-matched controls. Platelet aggregation was measured by impedance aggregometry (Multiplate® Analyzer) and markers of platelet turnover by flow cytometry (Sysmex® XE-5000). Blood samples were obtained at baseline and 1h after administration of 75mg of aspirin. Participants were then treated for 6days with once-daily aspirin, and blood sampling was repeated 1h and 24h after aspirin intake. After 6days of treatment, platelet aggregation levels increased during the 24-hour aspirin dosing interval in both patients and controls (p<0.001) with no difference between patients and controls. At baseline, patients with diabetes had increased platelet aggregation compared to controls (p=0.03). Platelet aggregation was reduced after the first dose of aspirin and significantly further reduced after six days of treatment (p<0.001). Patients with T2DM had numerically higher immature platelet count compared to controls (p=0.09), indicating an increased platelet turnover. Patients with T2DM without a history of CVD and controls had increased platelet aggregation at the end of the standard 24-hour dosing interval of aspirin. Further, aspirin-naïve T2DM patients had increased platelet aggregation compared to controls. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Pharmacological action of choline and aspirin coadministration on acute inflammatory pain.

    Science.gov (United States)

    Yong-Ping, Shi; Jin-Da, Wang; Ru-Huan, Wang; Xiang-Di, Zhao; Hai-Tao, Yu; Hai, Wang

    2011-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain but undesirable side effects limit their clinical usefulness. Choline is a α7 nicotinic receptor agonist that has antinociceptive effects in a variety of pain models. Drug combination is a strategy in the management of pain to reduce side effects. The aim of the study was to evaluate the nature of the interaction between choline and aspirin in two distinct inflammatory pain models. The analgesic mechanism of choline was also investigated. In the writhing test, intravenous administration of choline or aspirin showed dose-dependent antinociceptive activity, and isobolographic analysis revealed a synergistic nature of the interaction between choline and aspirin. More importantly, coadministration choline with aspirin could significantly shorten the antinociceptive latency of aspirin and prolong the antinociceptive duration of aspirin in the writhing test. In the carrageenan test, single administration of choline or aspirin significantly attenuated carrageenan-induced thermal hyperalgesia in a dose-dependent relationship. Coadministration of non-analgesic doses of aspirin with choline significantly suppressed the thermal hyperalgesia, with a longer duration efficacy. Furthermore, we found that α7 nicotinic, muscarinic, and opioid-receptors are involved in the antinociceptive effect of choline in the writhing test and the antinociceptive effect produced by systemically administered choline may be via a peripheral mechanism. In conclusion, coadministration of choline and aspirin holds promise for development as a safe analgesic drug combination for inflammatory pain, with a higher potency and longer duration than either aspirin or choline alone. Copyright © 2011 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  4. Aspirin induces nitric oxide release from vascular endothelium: a novel mechanism of action.

    Science.gov (United States)

    Taubert, D; Berkels, R; Grosser, N; Schröder, H; Gründemann, D; Schömig, E

    2004-09-01

    1. The study was designed to test the hypothesis that aspirin may stimulate nitric oxide (NO) release from vascular endothelium, a pivotal factor for maintenance of vascular homeostasis. 2. Clinical evidence suggests that low-dose aspirin may improve vascular endothelial function. Since other cyclooxygenase (COX) inhibitors showed no beneficial vascular effects, aspirin may exhibit a vasculoprotective, COX-independent mechanism. 3. Luminal NO release was monitored in real time on dissected porcine coronary arteries (PCA) by an amperometric, NO-selective sensor. Additionally, endothelial NO synthase (eNOS) activity was measured in EA.hy 926 cell homogenates by an l-[(3)H]citrulline/l-[(3)H]arginine conversion assay. Superoxide scavenging capacity was assessed by lucigenin-enhanced luminescence. 4. Aspirin induced an immediate concentration-dependent NO release from PCA with an EC(50) of 50 nm and potentiated the NO stimulation by the receptor-dependent agonist substance P. These effects were independent of an increase in intracellular calcium and could be mimicked by stimulation with acetylating aspirin derivatives. The aspirin metabolite salicylic acid or the reversible cyclooxygenase inhibitor indomethacin failed to modulate NO release. Incubation of soluble eNOS for 15 min with 100 microm aspirin or acetylating aspirin analogues increased the l-[(3)H]citrulline yield by 40-80%, while salicylic acid had no effect. Aspirin and salicylic acid showed a similar, but only modest, magnitude and velocity of superoxide scavenging. 5. Our findings demonstrate that therapeutically relevant concentrations of aspirin elicit NO release from vascular endothelium. This effect appears to be due to a direct acetylation of the eNOS protein, but is independent of COX inhibition or inhibition of superoxide-mediated NO degradation.

  5. The difference in association between aspirin use and other thrombocyte aggregation inhibitors and survival in patients with colorectal cancer.

    Science.gov (United States)

    Frouws, M A; Rademaker, E; Bastiaannet, E; van Herk-Sukel, M P P; Lemmens, V E; Van de Velde, C J H; Portielje, J E A; Liefers, G J

    2017-05-01

    Several studies have suggested that the association between aspirin and improved cancer survival is mediated through the mechanism of aspirin as thrombocyte aggregation inhibitors (TAI). The aim of this study was to provide epidemiological evidence for this mechanism assessing the association between overall survival and the use of aspirin and non-aspirin TAI in patients with colorectal cancer. In this observational study, data from the Netherlands Comprehensive Cancer Organisation were linked to PHARMO Database Network. Patients using aspirin or aspirin in combination with non-aspirin TAI (dual users) were selected and compared with non-users. The association between overall survival and the use of (non-)aspirin TAI was analysed using Cox regression models with the use of (non-)aspirin TAI as a time-varying covariate. In total, 9196 patients were identified with colorectal cancer and 1766 patients used TAI after diagnosis. Non-aspirin TAI were mostly clopidogrel and dipyridamole. Aspirin use was associated with a significant increased overall survival and hazard ratio (HR) 0.41 (95% confidence interval [CI] 0.37-0.47), and the use of non-aspirin TAI was not associated with survival of HR 0.92 (95% CI 0.70-1.22). Dual users did not have an improved overall survival when compared with patients using solely aspirin. Aspirin use after diagnosis of colorectal cancer was associated with significantly lower mortality rates and this effect remained significant after adjusting for potential confounders. No additional survival benefit was observed in patients using both aspirin and another TAI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Aspirin protects human coronary artery endothelial cells against atherogenic electronegative LDL via an epigenetic mechanism: a novel cytoprotective role of aspirin in acute myocardial infarction.

    Science.gov (United States)

    Chang, Po-Yuan; Chen, Yi-Jie; Chang, Fu-Hsiung; Lu, Jonathan; Huang, Wen-Huei; Yang, Tzu-Ching; Lee, Yuan-Teh; Chang, Shwu-Fen; Lu, Shao-Chun; Chen, Chu-Huang

    2013-07-01

    L5 is the most negatively charged subfraction of human low-density lipoprotein (LDL) and is the only subfraction of LDL capable of inducing apoptosis in cultured vascular endothelial cells (ECs) by inhibiting fibroblast growth factor-2 (FGF2) transcription. We examined whether plasma L5 levels are elevated in patients with ST-segment elevation myocardial infarction (STEMI) and whether aspirin provides epigenetic protection of human coronary artery ECs (HCAECs) exposed to L5. Plasma L5 levels were compared between patients with STEMI (n = 10) and control subjects with chest pain syndrome but a normal coronary arteriogram (n = 5). L5 was isolated from the plasma of STEMI patients and control subjects, and apoptosis, FGF2 expression, and FGF2 promoter methylation were examined in HCAECs treated with L5 and aspirin. Plasma L5 levels were significantly higher in STEMI patients than in control subjects (P aspirin (0.2 mM) attenuated the adverse effects of L5 on HCAEC survival, FGF2 expression, and FGF2 promoter methylation. In contrast, high concentrations of aspirin (≥1.0 mM) accentuated the effects of L5. Our results show that L5 levels are significantly increased in STEMI patients. Furthermore, L5 impairs HCAEC function through CpG methylation of the FGF2 promoter, which is suppressed in the presence of low-concentration aspirin. Our results provide evidence of a novel mechanism of aspirin in the prevention of MI.

  7. Up-regulation of ciliary neurotrophic factor in astrocytes by aspirin: implications for remyelination in multiple sclerosis.

    Science.gov (United States)

    Modi, Khushbu K; Sendtner, Michael; Pahan, Kalipada

    2013-06-21

    Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor, and the mechanisms by which CNTF expression could be increased in the brain are poorly understood. Acetylsalicylic acid (aspirin) is one of the most widely used analgesics. Interestingly, aspirin increased mRNA and protein expression of CNTF in primary mouse and human astrocytes in a dose- and time-dependent manner. Aspirin induced the activation of protein kinase A (PKA) but not protein kinase C (PKC). H-89, an inhibitor of PKA, abrogated aspirin-induced expression of CNTF. The activation of cAMP-response element-binding protein (CREB), but not NF-κB, by aspirin, the abrogation of aspirin-induced expression of CNTF by siRNA knockdown of CREB, the presence of a consensus cAMP-response element in the promoter of CNTF, and the recruitment of CREB and CREB-binding protein to the CNTF promoter by aspirin suggest that aspirin increases the expression of the Cntf gene via the activation of CREB. Furthermore, we demonstrate that aspirin-induced astroglial CNTF was also functionally active and that supernatants of aspirin-treated astrocytes of wild type, but not Cntf null, mice increased myelin-associated proteins in oligodendrocytes and protected oligodendrocytes from TNF-α insult. These results highlight a new and novel myelinogenic property of aspirin, which may be of benefit for multiple sclerosis and other demyelinating disorders.

  8. Aspirin and the Primary Prevention of Cardiovascular Diseases: An Approach Based on Individualized, Integrated Estimation of Risk.

    Science.gov (United States)

    Volpe, Massimo; Battistoni, Allegra; Gallo, Giovanna; Coluccia, Roberta; De Caterina, Raffaele

    2017-09-01

    While the use of aspirin in the secondary prevention of cardiovascular (CVD) is well established, aspirin in primary prevention is not systematically recommended because the absolute CV event reduction is similar to the absolute excess in major bleedings. Recently, emerging evidence suggests the possibility that the assumption of aspirin, may also be effective in the prevention of cancer. By adding to the CV prevention benefits the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in the primary prevention in favour of the latter and broaden the indication for treatment with in populations at average risk. While prospective and randomized study are currently investigating the effect of aspirin in prevention of both cancer and CVD, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention could be already based on a balanced evaluation of the benefit/risk ratio.

  9. Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations.

    Science.gov (United States)

    Sheth, Harsh; Northwood, Emma; Ulrich, Cornelia M; Scherer, Dominique; Elliott, Faye; Barrett, Jennifer H; Forman, David; Wolf, C Roland; Smith, Gillian; Jackson, Michael S; Santibanez-Koref, Mauro; Haile, Robert; Casey, Graham; Jenkins, Mark; Win, Aung Ko; Hopper, John L; Marchand, Loic Le; Lindor, Noralane M; Thibodeau, Stephen N; Potter, John D; Burn, John; Bishop, D Timothy

    2018-01-01

    Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05). Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001). Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively), however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that

  10. Diffuse scattering study of aspirin forms (I) and (II).

    Science.gov (United States)

    Chan, E J; Welberry, T R; Heerdegen, A P; Goossens, D J

    2010-12-01

    Full three-dimensional diffuse scattering data have been recorded for both polymorphic forms [(I) and (II)] of aspirin and these data have been analysed using Monte Carlo computer modelling. The observed scattering in form (I) is well reproduced by a simple harmonic model of thermally induced displacements. The data for form (II) show, in addition to thermal diffuse scattering (TDS) similar to that in form (I), diffuse streaks originating from stacking fault-like defects as well as other effects that can be attributed to strain induced by these defects. The present study has provided strong evidence that the aspirin form (II) structure is a true polymorph with a structure quite distinct from that of form (I). The diffuse scattering evidence presented shows that crystals of form (II) are essentially composed of large single domains of the form (II) lattice with a relatively small volume fraction of intrinsic planar defects or faults comprising misoriented bilayers of molecular dimers. There is evidence of some local aggregation of these defect bilayers to form small included regions of the form (I) structure. Evidence is also presented that shows that the strain effects arise from the mismatch of molecular packing between the defect region and the surrounding form (II) lattice. This occurs at the edges of the planar defects in the b direction only.

  11. Interaction of aspirin (acetylsalicylic acid) with lipid membranes.

    Science.gov (United States)

    Barrett, Matthew A; Zheng, Songbo; Roshankar, Golnaz; Alsop, Richard J; Belanger, Randy K R; Huynh, Chris; Kučerka, Norbert; Rheinstädter, Maikel C

    2012-01-01

    We studied the interaction of Aspirin (acetylsalicylic acid) with lipid membranes using x-ray diffraction for bilayers containing up to 50 mol% of aspirin. From 2D x-ray intensity maps that cover large areas of reciprocal space we determined the position of the ASA molecules in the phospholipid bilayers and the molecular arrangement of the molecules in the plane of the membranes. We present direct experimental evidence that ASA molecules participate in saturated lipid bilayers of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and preferably reside in the head group region of the membrane. Up to 50 mol% ASA molecules can be dissolved in this type of bilayer before the lateral membrane organization is disturbed and the membranes are found to form an ordered, 2D crystal-like structure. Furthermore, ASA and cholesterol were found to co-exist in saturated lipid bilayers, with the ASA molecules residing in the head group region and the cholesterol molecules participating in the hydrophobic membrane core.

  12. Interaction of aspirin (acetylsalicylic acid with lipid membranes.

    Directory of Open Access Journals (Sweden)

    Matthew A Barrett

    Full Text Available We studied the interaction of Aspirin (acetylsalicylic acid with lipid membranes using x-ray diffraction for bilayers containing up to 50 mol% of aspirin. From 2D x-ray intensity maps that cover large areas of reciprocal space we determined the position of the ASA molecules in the phospholipid bilayers and the molecular arrangement of the molecules in the plane of the membranes. We present direct experimental evidence that ASA molecules participate in saturated lipid bilayers of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine and preferably reside in the head group region of the membrane. Up to 50 mol% ASA molecules can be dissolved in this type of bilayer before the lateral membrane organization is disturbed and the membranes are found to form an ordered, 2D crystal-like structure. Furthermore, ASA and cholesterol were found to co-exist in saturated lipid bilayers, with the ASA molecules residing in the head group region and the cholesterol molecules participating in the hydrophobic membrane core.

  13. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

    Directory of Open Access Journals (Sweden)

    Nami Shrestha Palikhe

    2012-01-01

    Full Text Available Aspirin-exacerbated respiratory disease (AERD refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis.

  14. A short history of anti-rheumatic therapy. II. Aspirin

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

    Full Text Available The discovery of aspirin, an antipyretic, anti-inflammatory and analgesic drug, undoubtedly represents a milestone in the history of medical therapy. Since ancient times the derivatives of willow (Salix alba were used to treat a variety of fevers and pain syndromes, although the first report dates back to 1763 when the English Reverend Edward Stone described the effect of an extract of the bark willow in treating malaria. In the XIX century many apothecaries and chemists, including the Italian Raffaele Piria and Cesare Bertagnini, developed the biological processes of extraction and chemical synthesis of salicylates, and then analyzed their therapeutic properties and pharmacokinetic and pharmacodynamic characteristics. In 1899 the Bayer Company, where Felix Hoffmann, Heinrich Dreser and Arthur Eichengrün worked, recorded acetyl-salicylic acid under the name “Aspirin”. In the XX century, besides the definition of the correct applications of aspirin in the anti-rheumatic therapy being defined, Lawrence L. Crawen identified the property of this drug as an anti-platelet agent, thus opening the way for more widespread uses in cardiovascular diseases.

  15. Aspirin exacerbated respiratory disease: Current topics and trends.

    Science.gov (United States)

    Rodríguez-Jiménez, José Carlos; Moreno-Paz, Fernanda Judith; Terán, Luis Manuel; Guaní-Guerra, Eduardo

    2018-02-01

    Aspirin-exacerbated respiratory disease is a chronic and treatment-resistant disease, characterized by the presence of eosinophilic rhinosinusitis, nasal polyposis, bronchial asthma, and nonsteroidal anti-inflammatory drugs hypersensitivity. Alterations in arachidonic acid metabolism may induce an imbalance between pro-inflammatory and anti-inflammatory substances, expressed as an overproduction of cysteinyl leukotrienes and an underproduction of prostaglandin E2. Although eosinophils play a key role, recent studies have shown the importance of other cells and molecules in the development of the disease like mast cells, basophils, lymphocytes, platelets, neutrophils, macrophages, epithelial respiratory cells, IL-33 and thymic stromal lymphopoietin, making each of them promissory diagnostic and treatment targets. In this review, we summarize the most important clinical aspects of the disease, including the current topics about diagnosis and treatment, like provocation challenges and aspirin desensitization. We also discuss recent findings in the pathogenesis of the disease, as well as future trends in diagnosis and treatment, including monoclonal antibodies and a low salicylate diet as a treatment option. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Effects of aspirin on fracture healing in OPF rats.

    Science.gov (United States)

    Wei, Jin-Song; Zeng, Rong; Chen, Si-Yuan; Lin, Hao; Wu, Shao-Ke; Zheng, Jin-Chang

    2014-10-01

    To study the effect of aspirin on healing process of osteoporotic fracture (OPF) in rats. A total of 50 female Wistar rats aged 3 months were randomly divided into observation group and control group, castration method was adopted to establish the osteoporosis (OP) model. After artificial preparing fractures on the midpoint of left femur, fixing gram needle intramedullary, OPF modeling was complete. Aspirin lavage of 33 mg once a day was adopted in observation group after modeling, same amount of normal saline was used in the control as placebo. From each group, selected 5 rats at the 2nd, 4th, 8th and 12th week after modeling to measure the bone mineral density (BMD) and histological examination of the fracture callus, radiology observation was conducted at the 8th and 12th week. Left femur biomechanical measurement was taken at the 12th week. BMD values of observation group at each time point were significantly higher than that of the control group after modeling (POPF rats, increase bone density and biomechanics strength, and promote fracture healing of osteoporotic rats. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  17. Trans fat, aspirin, and ischemic stroke in postmenopausal women.

    Science.gov (United States)

    Yaemsiri, Sirin; Sen, Souvik; Tinker, Lesley; Rosamond, Wayne; Wassertheil-Smoller, Sylvia; He, Ka

    2012-11-01

    To examine the associations between dietary fat intake and ischemic stroke among postmenopausal women. We conducted a prospective cohort study of 87,025 generally healthy postmenopausal women (age, 50-79 years) enrolled in the Women's Health Initiative Observational Study. Repeated and validated dietary assessments were done using a self-administered food frequency questionnaire. We used Cox proportional hazards models to estimate hazard ratios (HRs) of ischemic stroke based on quintiles of the cumulative average of fat intake. We documented 1,049 incident cases of ischemic stroke over 663,041 person-years of follow-up. Women in the highest quintile of trans fat intake had a significantly higher incidence of ischemic stroke (HR, 1.39; 95% confidence interval [CI], 1.08-1.79; p-trend = 0.048) compared with women in the lowest quintile, while controlling for multiple covariates. The observed association was modified by aspirin use (p-interaction = 0.02). The HR was 1.66 (95% CI, 1.21-2.36; p-trend fat and ischemic stroke or any ischemic stroke subtypes. In this large cohort of postmenopausal women, higher intake of trans fat was associated with incident ischemic stroke independent of major lifestyle/dietary factors. Aspirin use may attenuate the potential adverse effect of trans fat intake on ischemic stroke. Copyright © 2012 American Neurological Association.

  18. An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

    Science.gov (United States)

    Chen, Justin R; Buchmiller, Brett L; Khan, David A

    2015-01-01

    Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  19. Oxylipid Profile of Low-Dose Aspirin Exposure: A Pharmacometabolomics Study.

    Science.gov (United States)

    Ellero-Simatos, Sandrine; Beitelshees, Amber L; Lewis, Joshua P; Yerges-Armstrong, Laura M; Georgiades, Anastasia; Dane, Adrie; Harms, Amy C; Strassburg, Katrin; Guled, Faisa; Hendriks, Margriet M W B; Horenstein, Richard B; Shuldiner, Alan R; Hankemeier, Thomas; Kaddurah-Daouk, Rima

    2015-10-26

    While aspirin is a well-established and generally effective anti-platelet agent, considerable inter-individual variation in drug response exists, for which mechanisms are not completely understood. Metabolomics allows for extensive measurement of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response. We used a mass-spectrometry-based metabolomics platform to investigate the changes in the serum oxylipid metabolome induced by an aspirin intervention (14 days, 81 mg/day) in healthy subjects (n=156). We observed a global decrease in serum oxylipids in response to aspirin (25 metabolites decreased out of 30 measured) regardless of sex. This decrease was concomitant with a significant decrease in serum linoleic acid levels (-19%, P=1.3×10(-5)), one of the main precursors for oxylipid synthesis. Interestingly, several linoleic acid-derived oxylipids were not significantly associated with arachidonic-induced ex vivo platelet aggregation, a widely accepted marker of aspirin response, but were significantly correlated with platelet reactivity in response to collagen. Together, these results suggest that linoleic acid-derived oxylipids may contribute to the non-COX1 mediated variability in response to aspirin. Pharmacometabolomics allowed for more comprehensive interrogation of mechanisms of action of low dose aspirin and of variation in aspirin response. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  20. Effects of aspirin on small-cell lung cancer mortality and metastatic presentation.

    Science.gov (United States)

    Maddison, Paul

    2017-04-01

    Although meta-analysis data have shown that taking regular aspirin may reduce lung cancer mortality, individual trial data results are conflicting, and the data on the effects of aspirin on different histological subtypes of lung tumours, in particular small-cell lung cancer, are sparse. We conducted a prospective observational study of 313 patients with a new diagnosis of small-cell lung cancer and recorded use of aspirin before and after tumour diagnosis. Seventy-one (23%) patients were taking regular daily aspirin for more than 2 years at the time of tumour diagnosis. We found that regular use of aspirin had no effect on survival nor metastatic presentation compared to data from small-cell lung cancer patients not taking aspirin. The lack of survival benefit in patients with small-cell lung cancer taking long-term aspirin may be due to the low expression of cyclooxygenase-2 in small-cell lung cancer tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Transrectal ultrasound-guided biopsy of the prostate: aspirin increases the incidence of minor bleeding complications

    Energy Technology Data Exchange (ETDEWEB)

    Halliwell, O.T. [Department of Radiology, Southampton General Hospital, Southampton (United Kingdom)], E-mail: hallo99@doctors.org.uk; Yadegafar, G. [Public Health Sciences and Medical Statistics Division, School of Medicine, Southampton General Hospital, Southampton University, Southampton (United Kingdom); Lane, C.; Dewbury, K.C. [Department of Radiology, Southampton General Hospital, Southampton (United Kingdom)

    2008-05-15

    Aim: To assess whether patients taking aspirin were more likely to experience bleeding complications after transrectal ultrasound (TRUS)-guided prostate biopsy. Materials and methods: Three hundred and eighty-seven patients taking aspirin who underwent prostate biopsy over a 3.5 year period and 731 patients not taking aspirin over a 2 year period returned a questionnaire assessing the incidence and severity of bleeding complications. Results: Patients taking aspirin had a significantly higher cumulative incidence of haematuria and rectal bleeding, but not of haemospermia. They also had a longer mean duration of bleeding, but no increase in bleeding severity. Severe bleeding was very uncommon in both groups and no patients required intervention for bleeding complications. Conclusion: Aspirin exacerbates minor bleeding complications in patients undergoing TRUS guided biopsy of the prostate, but in this large group of aspirin-taking patients no dangerous bleeding complications were encountered. It may be that the risks associated with aspirin cessation outweigh the risks of haemorrhagic complications.

  2. Aspirin use and ovarian cancer mortality in a Danish nationwide cohort study.

    Science.gov (United States)

    Verdoodt, Freija; Kjaer, Susanne K; Dehlendorff, Christian; Friis, Søren

    2018-01-09

    Increasing data suggest that aspirin use may improve cancer survival; however, the evidence is sparse for ovarian cancer. We examined the association between postdiagnosis use of low-dose aspirin and mortality in a nationwide cohort of women with epithelial ovarian cancer between 2000 and 2012. Information on filled prescriptions of low-dose aspirin, dates and causes of death, and potential confounding factors was obtained from nationwide Danish registries. We used Cox regression models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for ovarian cancer-specific or other-cause mortality associated with low-dose aspirin use. Among 4117 patients, postdiagnosis use of low-dose aspirin was associated with HRs of 1.02 (95% CI: 0.87-1.20) for ovarian cancer mortality and 1.06 (95% CI: 0.77-1.47) for other-cause mortality. Hazard ratios remained neutral according to patterns of low-dose aspirin use, including prediagnosis use or established mortality predictors. Low-dose aspirin use did not reduce mortality among ovarian cancer patients.British Journal of Cancer advance online publication, 9 January 2018; doi:10.1038/bjc.2017.449 www.bjcancer.com.

  3. Rivaroxaban with or without aspirin in patients with stable coronary artery disease

    DEFF Research Database (Denmark)

    Connolly, Stuart J; Eikelboom, John W; Bosch, Jackie

    2018-01-01

    with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, pbleeds were...... seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, pbleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1...... disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23...

  4. Trypanosoma cruzi: In vitro effect of aspirin with nifurtimox and benznidazole.

    Science.gov (United States)

    López-Muñoz, Rodrigo; Faúndez, Mario; Klein, Sebastián; Escanilla, Sebastián; Torres, Gloria; Lee-Liu, Dasfne; Ferreira, Jorge; Kemmerling, Ulrike; Orellana, Myriam; Morello, Antonio; Ferreira, Arturo; Maya, Juan D

    2010-02-01

    Nifurtimox and benznidazole are the only active drugs against Trypanosoma cruzi; however, they have limited efficacy and severe side effects. During primoinfection, T. cruzi infected macrophages mount an antiparasitic response, which the parasite evades through an increase of tumor growth factor beta and PGE(2) activation as well as decreased iNOS activity. Thus, prostaglandin synthesis inhibition with aspirin might increase macrophage antiparasitic activity and increase nifurtimox and benznidazole effect. Aspirin alone demonstrated a low effect upon macrophage antiparasitic activity. However, isobolographic analysis of the combined effects of aspirin, nifurtimox and benznidazole indicated a synergistic effect on T. cruzi infection of RAW cells, with combinatory indexes of 0.71 and 0.61, respectively. The observed effect of aspirin upon T. cruzi infection was not related with the PGE(2) synthesis inhibition. Nevertheless, NO() levels were restored by aspirin in T. cruzi-infected RAW cells, contributing to macrophage antiparasitic activity improvement. Thus, the synergy of aspirin with nifurtimox and benznidazole is due to the capability of aspirin to increase antiparasitic activity of macrophages. Copyright 2009 Elsevier Inc. All rights reserved.

  5. 24-hour antiplatelet effect of aspirin in patients with previous definite stent thrombosis.

    Science.gov (United States)

    Würtz, Morten; Hvas, Anne-Mette; Jensen, Lisette O; Kaltoft, Anne K; Tilsted, Hans H; Kristensen, Steen D; Grove, Erik L

    2014-08-01

    Once-daily aspirin is standard treatment, but recent studies point towards increased platelet function at the end of the dosing interval. Stent thrombosis (ST) has been linked with reduced antiplatelet effect of aspirin, so we investigated if platelet inhibition by aspirin declines through 24 h in patients with previous definite ST. Furthermore, we explored whether increased levels of immature platelets and thrombopoietin are associated with a particularly rapid recovery of platelet function. This case-control study included 50 patients with previous definite ST matched with 100 patients with stable coronary artery disease and 50 healthy volunteers. All participants were on aspirin 75 mg/day mono antiplatelet therapy. Platelet aggregation was measured 1 and 24 h after aspirin intake using platelet aggregometry (Multiplate® Analyzer). Cyclooxygenase-1 activity, platelet activation, immature platelets, and thrombopoietin were measured. Platelet aggregation increased by 109±150 (arachidonic acid) and 47±155 (collagen) aggregation units per minute from 1 to 24 h after aspirin intake (p-values aspirin-treated patients with previous definite ST or stable coronary artery disease and in healthy individuals. Increased levels of immature platelets and thrombopoietin were observed in patients with previous definite ST. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Antecedent Aspirin Use Is Associated with Less Severe Symptoms on Admission for Ischemic Stroke.

    Science.gov (United States)

    Nelson, Sarah; Cloonan, Lisa; Kanakis, Allison S; Fitzpatrick, Kaitlin M; Shideler, Kelsey I; Perilla, Adriana S; Furie, Karen L; Rost, Natalia S

    2016-10-01

    Aspirin is known to reduce stroke risk; however, its role in reducing severity of ischemic syndrome is not clear. We sought to investigate the relationship between antecedent aspirin use and stroke severity in patients presenting with acute ischemic stroke (AIS). We retrospectively analyzed a prospectively collected database of consecutive AIS patients presenting to our center. Clinical characteristics (including antecedent aspirin use), imaging findings, and laboratory data were assessed in association with presenting stroke severity, as measured by the National Institutes of Health Stroke Scale (NIHSS). Logistic regression models were used to determine univariate and multivariate predictors of baseline NIHSS. Of the 610 AIS patients with admission brain magnetic resonance imaging available for volumetric analysis of acute infarct size, 241 (39.5%) used aspirin prior to stroke onset. Antecedent aspirin use (P = .0005), history of atrial fibrillation (P stroke subtype (P stroke severity in univariate analysis. Antecedent aspirin use (P stroke severity, even after accounting for acute infarct volume. While the underlying biology of this apparent protective relationship requires further study, patients at high risk of stroke may benefit from routine aspirin use. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  7. The effect of aspirin on blood loss and transfusion requirements in patients with femoral neck fractures.

    LENUS (Irish Health Repository)

    Manning, Brian J

    2012-02-03

    Although it is widely accepted that aspirin will increase the risk of intra- and post-operative bleeding, clinical studies have not consistently supported this assumption. We aimed to assess the effect of pre-operative aspirin on blood loss and transfusion requirements in patients undergoing emergency fixation of femoral neck fractures. A prospective case-control study was undertaken in patients presenting with femoral neck fractures. Parameters recorded included intra-operative blood loss, post-operative blood loss, transfusion requirements and peri-operative reduction in haemoglobin concentration. Of 89 patients presenting with femoral neck fractures 32 were on long-term aspirin therapy. Pre-operative aspirin ingestion did not significantly affect peri-operative blood loss, or change in haemoglobin concentration or haematocrit. However those patients taking aspirin pre-operatively had a significantly lower haemoglobin concentration and haematocrit and were more likely to be anaemic at presentation than those who were not receiving aspirin. Patients taking aspirin were also more likely to receive blood transfusion post-operatively.

  8. Transcriptomic analysis of pancreatic cancer cells in response to metformin and aspirin: an implication of synergy

    Science.gov (United States)

    Yue, Wen; Wang, Tao; Zachariah, Emmanuel; Lin, Yong; Yang, Chung S.; Xu, Qing; DiPaola, Robert S.; Tan, Xiang-Lin

    2015-01-01

    Metformin and aspirin have been studied extensively as cancer preventative and therapeutic agents. However, the underlying molecular mechanisms for the inhibitory effects of pancreatic cancer development remain undefined. To gain further insight into their biological function in pancreatic cancer, we conducted a transcriptomic analysis using RNA sequencing to assess the differential gene expression induced by metformin (5 mM) and aspirin (2 mM), alone or in combination, after treatment of PANC-1 cells for 48 hours. Compared to an untreated control, metformin down-regulated 58 genes and up-regulated 91 genes, aspirin down-regulated 12 genes only, while metformin plus aspirin down-regulated 656 genes and up-regulated 449 genes (fold-change > 2, P  10, P aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated ≥ 20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated ≥ 10-fold. Ingenuity Pathway Analysis (IPA) revealed that the pathways, “cholesterol biosynthesis”, “cell cycle: G1/S checkpoint regulation”, and “axonal guidance signaling” were the most statistically significant pathways modulated by metformin plus aspirin. Although the results need further functional validation, these data provide the first evidence for the synergistic action between metformin and aspirin in modulating the transcriptional profile of pancreatic cancer cells. PMID:26294325

  9. The Effect of Combined Aspirin and Clopidogrel Treatment on Cancer Incidence.

    Science.gov (United States)

    Leader, Avi; Zelikson-Saporta, Ravit; Pereg, David; Spectre, Galia; Rozovski, Uri; Raanani, Pia; Hermoni, Doron; Lishner, Michael

    2017-07-01

    Multiple studies have shown an association between aspirin treatment and a reduction in newly diagnosed cancer. Conversely, there are conflicting clinical and laboratory data on the effect of combined clopidogrel and aspirin therapy on cancer incidence, including analyses suggesting an increased cancer risk. No large-scale cohort study has been performed to address this issue in a heterogeneous real-world scenario. We investigated the effect of clopidogrel and aspirin on cancer incidence compared with aspirin alone and no antiplatelet therapy. A population-based historical cohort study of subjects aged ≥50 years covered by Clalit Health Services, an Israeli health maintenance organization, was performed. Patients treated with the newer antiplatelet drugs, prasugrel or ticagrelor, which, like clopidogrel, inhibit adenosine diphosphate receptors, and those with prior cancer were excluded. Prescription records of antiplatelet medication were retrieved. The cohort included 183,912 subjects diagnosed with 21,974 cancer cases based upon the International Classification of Diseases, Ninth Revision. Dual aspirin and clopidogrel was prescribed in 9.6%, while 49% received aspirin alone and 41% used neither. Compared with nonusers, there was a lower risk of cancer in subjects exposed to aspirin with (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.44-0.49) or without clopidogrel (HR 0.54; 95% CI, 0.52-0.56), on long-term follow-up. Combined treatment was associated with a lower cancer risk than the aspirin-only group (HR 0.92; 95% CI, 0.86-0.97). Dual clopidogrel and aspirin treatment is safe regarding the cancer risk. This study generates the hypothesis that clopidogrel may reduce cancer incidence. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

    Directory of Open Access Journals (Sweden)

    Ning Ma

    Full Text Available OBJECTIVES: To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. METHODS: From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. RESULTS: Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5% with acute thrombosis, 5 patients (1.8% with subacute thrombosis, 17 patients (6.2% with stroke, and 2 death (0.7% in low-dose aspirin group, compared with no patient (0% with acute thrombosis, 2 patient (2.1% with subacute thrombosis, 6 patients (6.2% with stroke, and 2 death (2.1% in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. CONCLUSION: Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

  11. Aspirin does not prevent growth of vestibular schwannomas: A case-control study.

    Science.gov (United States)

    MacKeith, Samuel; Wasson, Joseph; Baker, Charlotte; Guilfoyle, Matthew; John, Deepa; Donnelly, Neil; Mannion, Richard; Jefferies, Sarah; Axon, Patrick; Tysome, James R

    2018-02-06

    To determine if aspirin intake is associated with reduced growth of vestibular schwannomas (VS). To determine the prevalence of contraindications to regular aspirin in patients with VS. Retrospective, observational case-control study. The study utilized a postal questionnaire and telephone interviews to determine aspirin exposure. Propensity score matching was used to control for age, sex, and tumor size. Cases were defined as patients with VS proven to have grown on serial magnetic resonance imaging (MRI). Controls were defined as patient with VS stable on serial MRI. Prevalence of regular aspirin use was compared in patients with growing VS versus stable VS. Absolute and relative contraindications to aspirin intake were recorded. Six hundred fifty-three patients with VS were contacted, and responses were received by 67% (220 cases and 217 controls). The mean tumor size was 11.3 mm (9.0 mm and 13.3 mm in controls and cases, respectively). Aspirin exposure was more common in stable VS than growing VS (22.1% vs. 17.3%). However, following matching to control for covariates, aspirin was not found to be associated with VS stability (P = .475). Multiple logistic regression (analysis of variance) found tumor size to be the only factor strongly associated with tumor growth (P < .0001). Ninety-two percent of patients were able to take aspirin, with the majority being at low risk of complications from regular use. This study aimed to examine the relationship between aspirin intake and VS stability. In contrast to previous reports, after controlling for covariates, the findings do not demonstrate an association. Only tumor size at diagnosis appears predictive of risk of VS growth. 3b. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Aspirin and Risk of Gastric Cancer After Helicobacter pylori Eradication: A Territory-Wide Study.

    Science.gov (United States)

    Cheung, Ka Shing; Chan, Esther W; Wong, Angel Y S; Chen, Lijia; Seto, Wai Kay; Wong, Ian C K; Leung, Wai K

    2018-01-19

    Despite successful H. pylori (HP) eradication, some individuals remain at risk of developing gastric cancer (GC). Previous studies showed that aspirin was associated with a reduced GC risk. However, whether aspirin can reduce GC risk in HP-eradicated subjects remains unknown. We aimed to determine the chemopreventive effect of aspirin in HP-eradicated subjects. We identified subjects who had received a prescription of clarithromycin-based triple therapy for HP between 2003 and 2012 from a territory-wide health care database. The observation period started from commencement of HP therapy (index date), and the follow-up was censored at the end of the study (December 2015), death, or GC diagnosis. Aspirin use was defined as use once or more often weekly. Subjects who failed HP eradication or were diagnosed with GC within 12 months of HP therapy were excluded. The hazard ratio (HR) of GC with aspirin use was calculated by Cox model with Propensity Score adjustment for age, sex, comorbidities, and concurrent medications. All statistical tests were two-sided. The median follow-up was 7.6 years (interquartile range [IQR] = 5.1-10.3 years), and 169 (0.27%) out of 63 605 patients developed GC. The incidence rate of GC was 3.5 per 10 000 person-years. Aspirin use was associated with a reduced GC risk (HR = 0.30, 95% confidence interval [CI] = 0.15 to 0.61). The risk of GC decreased with increasing frequency, duration, and dose of aspirin (all Ptrend < .001). Aspirin use was associated with a frequency-, dose-, and duration-dependent reduction in GC risk after HP eradication. The effect was most prominent in those who used aspirin daily or for five or more years.

  13. Effect of Aspirin on Spinal Cord Injury: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Hamed Reihani Kermani

    2016-05-01

    Full Text Available Aspirin is an anti-inflammatory drug, peroxyl radical scavenger, and antioxidant agent that inhibits phospholipases, nitric oxide synthetases, and cyclooxygenase enzymes. The existing literature contains no studies on the effects of various doses of aspirin on spinal cord injury (SCI. Therefore, we sought to investigate the putative effects of aspirin on experimental SCI. The weight-drop injury model was used to produce SCI in 100 albino Wistar rats. The animals were allocated to five groups: a control group, where the rats did not undergo any surgical or medical intervention except for anesthesia; a sham-treated group, where laminectomy was performed without SCI and no further therapy was administered; and three other groups, where the rats with SCI received low-dose aspirin [20 mg/kg], high-dose aspirin [80 mg/kg], and a vehicle, respectively. Half of the rats were sacrificed 24 hours later, and their spinal cords were excised for biochemical studies. The other rats were subjected to Basso, Beattie, and Bresnahan (BBB locomotor rating scale scoring once a week for 6 consecutive weeks. Aspirin decreased lipid peroxidation following SCI as the mean (± standard error catalase level was significantly higher in the high-dose aspirin group (46.10±12.01 than in the sham-treated group (16.07±2.42 and the vehicle-treated group (15.31±3.20 (P<0.05; P<0.05, respectively. Both of the groups treated with high-dose and low-dose aspirin demonstrated a higher mean BBB score than did the control group (P<0.001 and the sham-treated group (P<0.001. Our data provide evidence in support of the potential effects of aspirin in biochemical and neurobehavioral recovery after SCI.

  14. The Interplay between Stroke Severity, Antiplatelet Use, and Aspirin Resistance in Ischemic Stroke.

    Science.gov (United States)

    Agayeva, Nergiz; Topcuoglu, Mehmet Akif; Arsava, Ethem Murat

    2016-02-01

    The issue of whether prior antiplatelet use favorably affects stroke severity is currently unresolved. In this study, we evaluated the effect of antiplatelet use on clinical stroke severity and ischemic lesion volume, and assessed the confounding effect of laboratory-defined aspirin resistance on this relationship. Admission National Institutes of Health Stroke Scale (NIHSS) score, ischemic lesion volumes on diffusion-weighted imaging (DWI), and in vitro aspirin resistance, in addition to other pertinent stroke features, were determined in a series of ischemic stroke patients. Univariate and multivariate analyses were performed to compare clinical and imaging markers of stroke severity among patients with and without prior antiplatelet use, taking into consideration the presence or absence of aspirin resistance. Antiplatelet users experienced more severe strokes, per NIHSS score, in comparison to antiplatelet-naive patients (P = .007). No significant difference was observed with respect to admission DWI lesion volume. When analyses were repeated after adjustment for stroke subtype and other confounders, no association was observed between antiplatelet use and stroke severity. On the other hand, NIHSS scores were significantly higher in aspirin-unresponsive patients than in both aspirin responders (P = .049) and aspirin nonusers (P = .005). We were unable to demonstrate a substantial positive influence of prestroke antiplatelet usage on stroke severity. Although the presence of more severe strokes among patients with laboratory resistance suggests a protective influence of aspirin sensitivity on stroke severity, the hypothesis could not be validated as no difference was observed among aspirin-naive and aspirin-sensitive patients with respect to admission NIHSS score or DWI lesion volume. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.

    Directory of Open Access Journals (Sweden)

    Morten Würtz

    Full Text Available Platelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms determine platelet aggregation in aspirin-treated individuals.To identify platelet-related single nucleotide polymorphisms (SNPs influencing platelet aggregation during aspirin treatment. Furthermore, we explored to what extent changes in cyclooxygenase-1 activity and platelet activation may explain such influence.We included 985 Danish patients with stable coronary artery disease treated with aspirin 75 mg/day mono antiplatelet therapy. Patients were genotyped for 16 common SNPs in platelet-related genes using standard PCR-based methods (TaqMan. Platelet aggregation was evaluated by whole blood platelet aggregometry employing Multiplate Analyzer (agonists: arachidonic acid and collagen and VerifyNow Aspirin. Serum thromboxane B2 was measured to confirm aspirin adherence and was used as a marker of cyclooxygenase-1 activity. Soluble P-selectin was used as marker of platelet activation. Platelet aggregation, cyclooxygenase-1 activity, and platelet activation were compared across genotypes in adjusted analyses.The A-allele of the rs12041331 SNP in the platelet endothelial aggregation receptor-1 (PEAR1 gene was associated with reduced platelet aggregation and increased platelet activation, but not with cyclooxygenase-1 activity. Platelet aggregation was unaffected by the other SNPs analyzed.A common genetic variant in PEAR1 (rs12041331 reproducibly influenced platelet aggregation in aspirin-treated patients with coronary artery disease. The exact biological mechanism remains elusive, but the effect of this polymorphism may be related to changes in platelet activation. Furthermore, 14 SNPs previously suggested to influence aspirin efficacy were not associated with on-aspirin platelet aggregation.ClinicalTrials.gov NCT01383304.

  16. Synergistic interaction between choline and aspirin against acute inflammation induced by carrageenan and lipopolysaccharide.

    Science.gov (United States)

    Pan, Zhi-Yuan; Wang, Hai

    2014-05-01

    The simultaneous use of drugs with different mechanisms of anti-inflammatory action is a strategy for achieving effective control of inflammation while minimizing dose-related side effects. Choline was described to potentiate the antinociceptive action of aspirin at small doses in several inflammatory pain models. However, these findings are only limited to alleviating pain, more associated data are required to confirm the effectiveness of the combined choline and aspirin therapy against inflammatory disorders. Moreover, no report is available regarding the mechanism responsible for their synergism. Here, we first investigated the anti-inflammatory activity and pharmacological mechanisms of co-administration of choline and aspirin in 2 commonly studied inflammation models, carrageenan-induced paw edema and lipopolysaccharide (LPS)-induced sepsis in mice. Isobolographic analysis revealed that combined choline and aspirin administration exhibited a strong synergistic interaction in reducing carrageenan-mediated edema, and the estimated combination index values at 50%, 75%, and 90% effective dose (ED50, ED75, and ED90) were 0.25, 0.32, and 0.44. Drug co-administration also afforded synergistic protection against LPS-induced sepsis and mortality, since aspirin or choline alone was inadequate to improve survival. The effects of choline-aspirin co-administration were blocked by methyllycaconitine, suggesting that activation of alpha 7 nicotinic acetylcholine receptor participates in the interaction between choline and aspirin. Furthermore, co-administration of choline and aspirin was more likely to inhibit the production of pro-inflammatory mediators induced by LPS. Our results indicated that combined choline and aspirin therapy represented a significant synergistic interaction in attenuating acute inflammatory response. This preclinical relevant evidence provides a promising approach to treat inflammation-based diseases such as arthritis and sepsis. Copyright © 2014

  17. COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss.

    Science.gov (United States)

    Crabb, Simon J; Martin, Karen; Abab, Julia; Ratcliffe, Ian; Thornton, Roger; Lineton, Ben; Ellis, Mary; Moody, Ronald; Stanton, Louise; Galanopoulou, Angeliki; Maishman, Tom; Geldart, Thomas; Bayne, Mike; Davies, Joe; Lamb, Carolynn; Popat, Sanjay; Joffe, Johnathan K; Nutting, Chris; Chester, John; Hartley, Andrew; Thomas, Gareth; Ottensmeier, Christian; Huddart, Robert; King, Emma

    2017-12-01

    Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears. Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL. Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Aspirin for Evidence-Based Preeclampsia Prevention trial: influence of compliance on beneficial effect of aspirin in prevention of preterm preeclampsia.

    Science.gov (United States)

    Wright, David; Poon, Liona C; Rolnik, Daniel L; Syngelaki, Argyro; Delgado, Juan Luis; Vojtassakova, Denisa; de Alvarado, Mercedes; Kapeti, Evgenia; Rehal, Anoop; Pazos, Andrea; Carbone, Ilma Floriana; Dutemeyer, Vivien; Plasencia, Walter; Papantoniou, Nikos; Nicolaides, Kypros H

    2017-12-01

    The Aspirin for Evidence-Based Preeclampsia Prevention trial was a multicenter study in women with singleton pregnancies. Screening was carried out at 11-13 weeks' gestation with an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor). Those with an estimated risk for preterm preeclampsia of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/d) vs placebo from 11-14 until 36 weeks' gestation. Preterm preeclampsia with delivery at preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial. This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of preeclampsia at screening and the participating center. The choice of cut-off of 90% was based on an exploratory analysis of the treatment effect. Logistic regression analysis was used to investigate predictors of compliance ≥90% among maternal characteristics and medical history. Preterm preeclampsia occurred in 5/555 (0.9%) participants in the aspirin group with compliance ≥90%, in 8/243 (3.3%) of participants in the aspirin group with compliance preeclampsia was 0.24 (95% confidence interval, 0.09-0.65) for compliance ≥90% and 0.59 (95% confidence interval, 0.23-1.53) for compliance preeclampsia and negatively associated with smoking, maternal age preeclampsia in a previous pregnancy. The beneficial effect of aspirin in the prevention of preterm preeclampsia appears to depend on compliance. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Preventive Aspirin and Other Antiplatelet Medication Use Among U.S. Adults Aged ≥40 Years: Data from the National Health and Nutrition Examination Survey, 2011–2012

    Science.gov (United States)

    Dillon, Charles F.; Eberhardt, Mark S.; Wright, Jacqueline D.; Burt, Vicki L.

    2015-01-01

    Objective We estimated the prevalence of preventive aspirin and/or other antiplatelet medication use and the dosage of aspirin use in the U.S. adult population. Methods We conducted cross-sectional analyses of a representative sample (n=3,599) of U.S. adults aged ≥40 years from the National Health and Nutrition Examination Survey, 2011–2012. Results In 2011–2012, one-third of U.S. adults aged ≥40 years reported taking preventive aspirin and/or other antiplatelet medications, 97% of whom indicated preventive aspirin use. Preventive aspirin use increased with age (from 11% of those aged 40–49 years to 54% of those ≥80 years of age, paspirin than non-Hispanic Asian (20%, paspirin. Among those with cardiovascular disease, 76% reported taking preventive aspirin and/or other antiplatelet medications, of whom 91% were taking preventive aspirin. Among adults without cardiovascular disease, 28% reported taking preventive aspirin. Adherence rates to medically recommended aspirin use were 82% overall, 91% for secondary prevention, and 79% for primary prevention. Among current preventive aspirin users, 70% were taking 81 milligrams (mg) of aspirin daily and 13% were taking 325 mg of aspirin daily. Conclusion The vast majority of antiplatelet therapy is preventive aspirin use. A health-care provider's recommendation to take preventive aspirin is an important determinant of current preventive aspirin use. PMID:26556936

  20. Preventive Aspirin and Other Antiplatelet Medication Use Among U.S. Adults Aged ≥ 40 Years: Data from the National Health and Nutrition Examination Survey, 2011-2012.

    Science.gov (United States)

    Gu, Qiuping; Dillon, Charles F; Eberhardt, Mark S; Wright, Jacqueline D; Burt, Vicki L

    2015-01-01

    We estimated the prevalence of preventive aspirin and/or other antiplatelet medication use and the dosage of aspirin use in the U.S. adult population. We conducted cross-sectional analyses of a representative sample (n=3,599) of U.S. adults aged ≥ 40 years from the National Health and Nutrition Examination Survey, 2011-2012. In 2011-2012, one-third of U.S. adults aged ≥ 40 years reported taking preventive aspirin and/or other antiplatelet medications, 97% of whom indicated preventive aspirin use. Preventive aspirin use increased with age (from 11% of those aged 40-49 years to 54% of those ≥ 80 years of age, paspirin than non-Hispanic Asian (20%, paspirin. Among those with cardiovascular disease, 76% reported taking preventive aspirin and/or other antiplatelet medications, of whom 91% were taking preventive aspirin. Among adults without cardiovascular disease, 28% reported taking preventive aspirin. Adherence rates to medically recommended aspirin use were 82% overall, 91% for secondary prevention, and 79% for primary prevention. Among current preventive aspirin users, 70% were taking 81 milligrams (mg) of aspirin daily and 13% were taking 325 mg of aspirin daily. The vast majority of antiplatelet therapy is preventive aspirin use. A health-care provider's recommendation to take preventive aspirin is an important determinant of current preventive aspirin use.

  1. Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers

    Science.gov (United States)

    Teng, Renli; Maya, Juan; Butler, Kathleen

    2013-01-01

    The results of two independent, randomized, two-period crossover, single-center studies, conducted to assess the pharmacokinetics of ticagrelor ± aspirin, inhibition of platelet aggregation (IPA) with ticagrelor/aspirin vs. clopidogrel/aspirin, and safety, tolerability, and bleeding times are reported here. In Study A (open-label), 16 volunteers received ticagrelor (50 mg bid Days 1–5; 200 mg bid Days 6–9; one 200 mg dose on Day 10) ± 300 mg qd aspirin (Days 1–10). In Study B (double-blind, double-dummy), 16 volunteers received aspirin (300 mg loading dose/75 mg qd Days 2–9) with either ticagrelor (200 mg bid Days 4–8, one 200 mg dose on Day 9) or clopidogrel (300 mg loading dose Day 4, 75 mg qd Days 5–9). At steady-state ticagrelor (50 mg bid, or 200 mg bid), concomitant aspirin (300 mg qd) had no effect on mean maximum plasma concentration (C max), median time to C max (t max), or mean area under the plasma concentration-time curve for the dosing interval (AUC0– τ) for ticagrelor and its primary metabolite, AR-C124910XX. Following 200 mg bid ticagrelor, mean C max and AUC0– τ for both parent and metabolite were comparable with co-administration of aspirin at 75 mg and 300 mg qd. Aspirin (300 mg qd) had no effect on IPA (ADP-induced) by ticagrelor. However, aspirin and ticagrelor had an additive effect on IPA (collagen-induced). Ticagrelor/aspirin increased bleeding times vs. baseline. Ticagrelor/aspirin co-administration was well tolerated at all dose combinations evaluated. In summary, the findings of this study demonstrate that co-administration of aspirin (300 mg qd) with ticagrelor (50 mg bid, or 200 mg bid) had no effect on ticagrelor pharmacokinetics or IPA (ADP-induced) by ticagrelor. PMID:23249161

  2. Formulasi dan Evaluasi Pemakaian Cangkang Kapsul Alginat untuk Pembuatan Sediaan Floating dari Dispersi Padat Aspirin

    OpenAIRE

    Anggono, Jeriko

    2015-01-01

    Background: Aspirin is the group of non steroid anti-inflamatory drug besides that is used as antiplatelet drug. Aspirin is poorly soluble in water and can cause the irritation in the stomach in oral route. Therefore, it is necessary to modify solid dispersion dosage form that can remain in the stomach, as the example is floating dosage form by using alginate as capsule shell. Purpose: The aim of this study was to prepare floating dosage form of aspirin solid dispersion that can remain in ...

  3. Elastic properties of aspirin in its crystalline and glassy phases studied by micro-Brillouin scattering

    Science.gov (United States)

    Ko, Jae-Hyeon; Lee, Kwang-Sei; Ike, Yuji; Kojima, Seiji

    2008-11-01

    The acoustic waves propagating along the direction perpendicular to the (1 0 0) cleavage plane of aspirin crystal were investigated using micro-Brillouin spectroscopy from which C11, C55 and C66 were obtained. The temperature dependence of the longitudinal acoustic waves could be explained by normal anharmonic lattice models, while the transverse acoustic waves showed an abnormal increase in the hypersonic attenuation at low temperatures indicating their coupling to local remnant dynamics. The sound velocity as well as the attenuation of the longitudinal acoustic waves of glassy aspirin showed a substantial change at ˜235 K confirming a transition from glassy to supercooled liquid state in vitreous aspirin.

  4. Low-Dose Aspirin in Heart Failure Not Complicated by Atrial Fibrillation

    DEFF Research Database (Denmark)

    Madelaire, Christian; Gislason, Gunnar; Kristensen, Søren L

    2018-01-01

    OBJECTIVES: This study sought to assess safety and effectiveness of low-dose aspirin in heart failure (HF) not complicated by atrial fibrillation. BACKGROUND: Despite lack of evidence, low-dose aspirin is widely used in patients with HF and sinus rhythm with and without prior ischemic heart disease....... An increased risk of HF readmission was observed in the aspirin group (HR: 1.25; 95% CI: 1.17 to 1.33). No difference in bleeding was observed. In subgroup analyses on the basis of a history of ischemic heart disease, the results were similar to the main result. CONCLUSIONS: No association was detected between...

  5. Global Trends in Aspirin Resistance-Related Research from 1990 to 2015: A Bibliometric Analysis.

    Science.gov (United States)

    Al-Jabi, Samah W

    2017-12-01

    Aspirin resistance can be defined as the inability of the usual dose of aspirin medication to produce its antithrombotic effect. Patients with diabetes or cardiovascular disease are at higher risk of stroke, myocardial infarction or cardiovascular death due to aspirin resistance. The aim of this bibliometric study was to identify and analyse the status and trends of aspirin resistance research production at global level through publications indexed in the Scopus database; this will shed new light on future research trends and help researchers predict dynamic direction of research. Literature search using the Scopus database was conducted to assess publications related to aspirin resistance. The selected publications included the terms related to aspirin resistance in the title, abstract or keywords. The searching was accomplished on 20 March 2016 and can be considered to include all publications up to 31 December 2015. Global cumulative publication output on aspirin resistance consists of 986 papers during 1990-2015. Among the 986 documents, 19 (1.9%) were published before 2000, 567 (57.5%) were published from 2000 to 2009 and 400 (40.6%) were published from 2010 to 2015, with peak of publications on this topic in 2008. The leading country in the field of aspirin resistance was the United States, which had the greatest counts of independent articles (165) and international collaboration articles (44). Turkey was in the second rank with 78 articles, followed by Italy (68), the UK (62) and Poland (60). The total number of citations for all documents was 26,342, and the average citations per document were 26.7. The h-index for all aspirin resistance publications was 82. This study presents the results of the first bibliometric study (including quantitative and qualitative analysis) of scientific publications in the field of aspirin renitence at global level. Aspirin resistance-related researches have notably increased in the last years, especially from 2000 to 2015

  6. Aspirin non-responsiveness in pregnant women at high-risk of pre-eclampsia.

    Science.gov (United States)

    Navaratnam, Kate; Alfirevic, Ana; Jorgensen, Andrea; Alfirevic, Zarko

    2018-02-01

    Low-dose aspirin is recommended for prevention of pre-eclampsia in high-risk pregnant women. Current doses provide a conservative risk reduction and some individuals demonstrate 'aspirin non-responsiveness', with insufficient antiplatelet effects. We aimed to determine if aspirin non-responsiveness could be identified in women at high risk of pre-eclampsia and assess for potential associations with placentally-mediated adverse outcomes. Prospective cohort study. 180 women at high-risk of pre-eclampsia, by NICE criteria, prescribed 75 mg dispersible aspirin daily were recruited from antenatal clinics of Liverpool Women's Hospital between 17/01/14 and 31/03/16. Platelet function (Multiplate™ impedance aggregometry, VerifyNow™ and 11-dehydrothromboxane B2) and aspirin metabolites (nuclear magnetic resonance and liquid chromatography mass spectrometry) were assessed at 5 + 0-20 + 6 and 33 + 0-35 + 6 weeks. Pearson's chi-square test was used to assess for associations between longitudinal response to aspirin and (1) any pre-eclampsia (2) composite adverse placentally-mediated outcome (one, or combination of pre-eclampsia, placental abruption, IUGR and perinatal mortality). A Bonferroni correction was applied to correct for multiple analyses. 180 women were recruited, there were 4 withdrawals and no women were lost to follow-up. After 15 women delivered prior to the completion of follow-up, sufficient sample volumes for longitudinal platelet function and aspirin adherence testing were obtained from 156 women. There were no consistent aspirin non-responders in the cohort. 59% (n = 92) women exhibited normal response to aspirin, 34% (n = 53) variable response (switching response status between study visits) and in 7% (n = 11) response could not be determined as they exhibited lack of platelet response on a background of undetectable aspirin metabolites. There was no significant association between indeterminate or inconsistent (variable or

  7. The clinical importance of laboratory-defined aspirin resistance in patients presenting with non-ST elevation acute coronary syndromes.

    Science.gov (United States)

    Acikel, Sadik; Yildirir, Aylin; Aydinalp, Alp; Bal, Ugur; Kaynar, Gamze; Ozin, Bulent; Muderrisoglu, Haldun

    2009-09-01

    In this study, we aimed to assess the factors associated with laboratory-defined aspirin resistance and the relationship of this laboratory-defined aspirin resistance with thrombolysis in myocardial infarction risk score, markers of cardiac necrosis, and inflammatory and thrombotic risk factors in patients with unstable angina or non-ST elevation myocardial infarction. Ninety-seven patients who were under aspirin therapy and hospitalized with unstable angina/non-ST elevation myocardial infarction were included in the study. Laboratory-defined aspirin sensitive and resistant groups were determined by platelet function analyzer; aspirin resistance was defined as collagen/epinephrine closure time less than 165 s. Laboratory-defined aspirin resistance was noted in 29 patients (29.9%), and non-ST elevation myocardial infarction was observed in 46 patients (47.4%). Patients in the group with laboratory-defined aspirin resistance had significantly higher thrombolysis in myocardial infarction risk scores (P myocardial band and troponin I values were higher in laboratory-defined aspirin-resistant group. Multivariate analyses revealed that laboratory-defined aspirin resistance was an independent predictor of non-ST elevation myocardial infarction (P = 0.022). Laboratory-defined aspirin resistance is associated with non-ST elevation myocardial infarction, higher markers of cardiac necrosis and thrombolysis in myocardial infarction risk score in patients hospitalized with unstable angina/non-ST elevation myocardial infarction.

  8. Aspirin inhibits the SHH/GLI1 signaling pathway and sensitizes malignant glioma cells to temozolomide therapy.

    Science.gov (United States)

    Ming, Jianguang; Sun, Bo; Li, Ziwei; Lin, Lin; Meng, Xiangqi; Han, Bo; Wang, Ruijia; Wu, Pengfei; Li, Jianlong; Cai, Jinquan; Jiang, Chuanlu

    2017-04-01

    Aberrant activation of sonic hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) pathway plays an important role in the tumorigenicity of malignant glioma cells and resistance to temozolomide (TMZ). Here we investigated the aspirin's antineoplastic molecular route by targeting SHH/GLI1 pathway and examined the feasibility of aspirin combined with TMZ therapy. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that the activity of the SHH/GLI1 pathway was strongly inhibited by aspirin. Aspirin acted as the glioma growth-inhibitory and pro-apoptosis roles by inhibiting the SHH/GLI1 pathway and reprogramming the epithelial to mesenchymal transition (EMT). The immunofluorescence assay showed aspirin could prevent the nuclear translocation of GLI1 to inhibit its transcriptional regulation. The stable lentiviral overexpression of GLI1 reversed the DNA double strand breaks (DSBs) caused by the GANT61 and TMZ. Furthermore, aspirin combined with TMZ enhanced chemosensitivity and GLI1-induced chemoprotection was partly blocked by aspirin in vitro and in vivo . Collectively, aspirin has a therapeutic potential for SHH/GLI1 targeted therapy against glioma cells. Acquired activation of GLI1 protects glioma cells against TMZ therapy. Impairment of DNA DSBs repair activity might be involved in the route of aspirin-induced chemosensitivity. Combined aspirin with TMZ may be a promising strategy against malignant glioma.

  9. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    Science.gov (United States)

    Kan, Xianwen; Geng, Zhirong; Zhao, Yao; Wang, Zhilin; Zhu, Jun-Jie

    2009-04-01

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe3O4 nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

  10. Spectroscopic structural studies of salicylic acid, salicylamide and aspirin

    Science.gov (United States)

    El-Shahawy, Anwar S.

    The electronic absorption spectra of the salicylic acid and the salicylamide molecules have been studied using SCF—CL calculations. The singlet and the triplet electronic transition energies have been calculated. The state functions of eight excited states for these molecules have been calculated in addition to the oscillator strengths, charge densities, ionization potentials and electron affinities. Our calculations lead to the presence of salicylic acid and salicylamide in the β-forms in which the carboxylic hydroxyl group or the amino group is directed toward the enolic hydroxyl group. The salicylic acid and the salicylamide molecules have the Cs point group symmetry, but the aspirin molecule has the C1 point group symmetry, in which the acetyl group does not lie in the plane of the salicylic acid molecule.

  11. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Kan Xianwen; Geng Zhirong; Zhao Yao; Wang Zhilin; Zhu Junjie [State Key Laboratory of Coordination Chemistry, MOE Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)], E-mail: wangzl@nju.edu.cn, E-mail: jjzhu@nju.edu.cn

    2009-04-22

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe{sub 3}O{sub 4} nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

  12. Aspirin for the Prevention of Preeclampsia and Intrauterine Growth Restriction.

    Science.gov (United States)

    Roberge, Stephanie; Odibo, Anthony O; Bujold, Emmanuel

    2016-06-01

    Low-dose aspirin (LDA) has been used for several years for the prevention of preeclampsia (PE). LDA started in early pregnancy is associated with improvement of placental implantation. The best evidence suggest that LDA can prevent more than half of PE cases in high-risk women when started before 16 weeks of gestation. Moreover, LDA started in early pregnancy reduces the risk of other placenta-mediated complications such as intrauterine growth restriction (IUGR) and perinatal death. The efficacy of LDA has been demonstrated in women with abnormal first-trimester uterine artery Doppler or with prior history of chronic hypertension or preeclampsia. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Promising psyllium-based composite containing TiO2 nanoparticles as aspirin-carrier matrix

    Directory of Open Access Journals (Sweden)

    Marcela-Corina Rosu

    2014-06-01

    Full Text Available Composite nanomaterials represent a new trend in the biomedical field. Coupling inorganic/organic constituents with non-toxicity/biocompatibility properties leads to develop the new systems having special characteristics that can be used in various bio-applications. This paper describes the preparation and characterization of psyllium-based composites containing TiO2 nanoparticles in order to develop new therapeutic strategies for aspirin drug delivery. The structural characteristics of obtained materials were investigated by FTIR spectroscopy. The UV–vis spectrophotometric analysis was performed to evaluate the aspirin release behavior under different pH conditions at 37 °C. Combining psyllium (as an excellent source of fiber with TiO2 inorganic unit (as vehicle of aspirin it was found that polymeric-TiO2 networks have promising potential for controlled aspirin release as therapeutic agent.

  14. Study Shows Aspirin Reduces Colorectal Cancer in Those at High Risk

    Science.gov (United States)

    Findings from the first large clinical trial of its kind indicate that taking high doses of aspirin daily for at least 2 years substantially reduces the risk of colorectal cancer among people at increased risk of the disease.

  15. Role of Dispersion Interactions in the Polymorphism and Entropic Stabilization of the Aspirin Crystal

    Science.gov (United States)

    Reilly, Anthony M.; Tkatchenko, Alexandre

    2014-08-01

    Aspirin has been used and studied for over a century but has only recently been shown to have an additional polymorphic form, known as form II. Since the two observed solid forms of aspirin are degenerate in terms of lattice energy, kinetic effects have been suggested to determine the metastability of the less abundant form II. Here, first-principles calculations provide an alternative explanation based on free-energy differences at room temperature. The explicit consideration of many-body van der Waals interactions in the free energy demonstrates that the stability of the most abundant form of aspirin is due to a subtle coupling between collective electronic fluctuations and quantized lattice vibrations. In addition, a systematic analysis of the elastic properties of the two forms of aspirin rules out mechanical instability of form II as making it metastable.

  16. Impact of aspirin on fetal growth in diabetic pregnancies according to White classification.

    Science.gov (United States)

    Adkins, Katlynn; Allshouse, Amanda A; Metz, Torri D; Heyborne, Kent D

    2017-10-01

    Current US Preventive Services Task Force and other guidelines recommend low-dose aspirin for all pregnant women with pregestational diabetes mellitus to prevent preeclampsia and small-for-gestational-age birth. The Maternal-Fetal Medicine Units High-Risk Aspirin trial did not show a reduction in either preeclampsia or small-for-gestational-age birth in diabetic women. Our objective was to reassess the impact of aspirin on fetal growth in diabetic pregnancies overall and according to White classification. We hypothesized that aspirin improves fetal growth in pregnancies with vascular complications of diabetes at highest risk for poor fetal growth. We conducted secondary analysis of the cohort of diabetic women enrolled in the Maternal-Fetal Medicine Units High-Risk Aspirin trial. The impact of aspirin prophylaxis on birthweight was assessed in the overall cohort and in 2 groups categorized according to White classification as nonvascular (White class B, C, D) or vascular (White class R, F, RF). Birthweight was converted to Z-score normalized for gestational age at delivery and neonatal sex. Difference in birthweight Z-score between aspirin and placebo was tested with a 2-sample t test. The effect of vascular group, aspirin vs placebo randomization, and the interaction of the 2 on normalized birthweight percentile was estimated with linear regression with a multivariable model including covariates body mass index, tobacco use, race, and parity. The percentage of small and large-for-gestational-age newborns born to aspirin- vs placebo-treated women was compared between groups using Pearson exact χ 2 analysis, and an adjusted model was estimated by logistic regression. All 444 women with pregestational diabetes and complete outcome data were included (53 vascular, 391 nonvascular). Aspirin was significantly associated with a higher birthweight Z-score (0.283; 95% confidence interval, 0.023-0.544) in the overall cohort (P = .03). In the adjusted model, the

  17. Prediction of antiplatelet effects of aspirin in vivo based on in vitro results.

    Science.gov (United States)

    Yokoyama, Haruko; Ito, Naoko; Soeda, Shinji; Ozaki, Masahiro; Suzuki, Yuji; Watanabe, Masayuki; Kashiwakura, Emiko; Kawada, Tsutomu; Ikeda, Noriyuki; Tokuoka, Kentaro; Kitagawa, Yasuhisa; Yamada, Yasuhiko

    2013-01-01

    The aim of this study was to establish a method to predict the antiplatelet effects of aspirin in vivo based on in vitro results. Aspirin in 5 different concentrations was added to the platelet-rich plasma samples, and the rates of platelet aggregation induced by collagen were determined in vitro. In addition, platelet aggregation and plasma drug concentration values were determined in vivo before and after the administration of aspirin (162 mg). The 50% effective concentration (EC50) values obtained from the in vivo and in vitro experiments were shown to have relevance, because the EC50 ratio for each subject was the same (0.23 ± 0.03). The actual and predicted values for the rate of inhibition of platelet aggregation were well correlated (P antiplatelet effects of aspirin can be predicted using blood samples obtained before its administration.

  18. FPIN's Clinical Inquiries. Aspirin use in children for fever or viral syndromes.

    Science.gov (United States)

    Beutler, Anthony I; Chesnut, Gregory T; Mattingly, John C; Jamieson, Barbara

    2009-12-15

    Aspirin should not be used to treat acute febrile viral illness in children. (Strength of Recommendation [SOR]: C, based on case-control studies). Although no causal link has been proven, data from case-control and historic cohort studies demonstrate an association between aspirin use and Reye syndrome. The risk of Reye syndrome decreases with age, becoming extremely rare by the late teenage years. Other nonsteroidal anti-inflammatory drugs are effective antipyretics and are not associated with the constellation of symptoms seen in Reye syndrome, which includes nausea, vomiting, headache, excitability, delirium, combativeness, and coma. Aspirin use in children younger than 19 years should be limited to diseases in which aspirin has a proven benefit, such as Kawasaki disease and the juvenile arthritides. (SOR: C, based on expert opinion).

  19. Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Kommalage, Mahinda; Höglund, A Urban

    2004-01-01

    Aspirin and paracetamol have been shown to suppress non-inflammatory pain conditions like thermal, visceral and mechanical pain in mice and rats. The non-inflammatory antinociception appears to be mediated by central receptor mechanisms, such as the cholinergic system. In this study, we tested...... the hypothesis that the non-inflammatory antinociception of aspirin and paracetamol could be mediated by an increase of intraspinal acetylcholine release. Microdialysis probes were placed intraspinally in anesthetized rats for acetylcholine sampling. Subcutaneously administered aspirin 100 and 300 mg....../kg increased, while paracetamol 300 mg/kg decreased intraspinal acetylcholine release. Intraspinal drug administration did not affect acetylcholine release. Our results suggest that an increased intraspinal acetylcholine release could be involved in part of the non-inflammatory pain suppression by aspirin...

  20. Resistance to aspirin: prevalence, mechanisms of action and association with thromboembolic events. A narrative review

    National Research Council Canada - National Science Library

    Cañivano Petreñas, L; García Yubero, C

    2010-01-01

    The purpose of this study is to review the prevalence of aspirin resistance in patients with a high risk of cardiovascular events, and secondly, to investigate its epidemiology and mechanism of action...

  1. Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation

    Directory of Open Access Journals (Sweden)

    Hiroaki Matsuo

    2013-01-01

    Conclusions: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

  2. Preoperative aspirin administration improves oxygenation in patients undergoing coronary artery bypass grafting.

    Science.gov (United States)

    Gerrah, Rabin; Elami, Amir; Stamler, Alon; Smirnov, Asya; Stoeger, Zeev

    2005-05-01

    Release of thromboxane (Tx) A(2) by platelets may be one of multiple factors that are responsible for lung injury after cardiopulmonary bypass, leading to pulmonary vasoconstriction and impaired oxygenation. In experimental models, the inhibition of Tx receptor or its production improved lung function. The use of aspirin, which is used widely in the treatment of ischemic heart disease because of its antiplatelet activity, is usually discontinued a week before the patient undergoes the operation to restore normal platelet hemostatic function. The purpose of this study was to determine the relationship between the time of cessation of aspirin before coronary artery bypass surgery, and postoperative oxygenation and bleeding. A prospective clinical study comparing the effect of aspirin on postoperative oxygenation in patients who had been treated or had not been treated with aspirin. Tx levels in the pericardial fluid, oxygenation, and bleeding were compared between the two groups. Thirty-two patients with coronary artery disease who were undergoing coronary artery bypass grafting. Fourteen of these patients received aspirin until the day of the operation, whereas 18 patients stopped receiving aspirin at least 1 week before undergoing the operation. Mean (+/- SD) Tx levels in the pericardial fluid were significantly lower in the aspirin group (117 +/- 47 pg/mL) compared to those in the control group (1,306 +/- 2,048 pg/mL; p = 0.02). The duration of ventilation after the operation was significantly longer in the nonaspirin group (9.6 +/- 5.6 h vs 3.8 +/- 1.4 h, respectively; p = 0.0004). Po(2) reached a higher level while patients breathed 100% O(2) in the aspirin group (235 +/- 54 mm Hg vs 176 +/- 27 mm Hg, respectively; p = 0.001). The mean amount of bleeding during the first 24 h after surgery was increased in the aspirin group (710 +/- 202 mL) compared with the nonaspirin group (539 +/- 143 mL; p = 0.01), but these patients did not require more transfusions. The

  3. Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

    Science.gov (United States)

    Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

    2017-11-01

    Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the

  4. Aspirin augments the expression of Adenomatous Polyposis Coli protein by suppression of IKKβ

    Energy Technology Data Exchange (ETDEWEB)

    Ashida, Noboru, E-mail: nashida@kuhp.kyoto-u.ac.jp [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Kishihata, Masako [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Tien, Dat Nguyen [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kamei, Kaeko [Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kimura, Takeshi [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Yokode, Masayuki [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan)

    2014-04-04

    Highlights: • Clinical studies revealed aspirin inhibits cancer, but the mechanism is not known. • Adenomatous Polyposis Coli (APC) is a well-known tumor-suppressing gene. • We found aspirin up-regulates the protein of APC. • Aspirin suppressed the expression of IKKβ, an essential kinase in NFκB activation. • The deletion of IKKβ significantly increases the expression of APC protein. - Abstract: Aspirin has been widely used as analgesic, antipyretic and anti-inflammatory medicine for long. In addition to these traditional effects, clinical studies suggest that aspirin can protect against cancer, but its mechanism has not been explored. To unveil it, we identified the proteins up- or down-regulated after incubation with aspirin by using proteomics analysis with Nano-flow LC/MALDI-TOF system. Interestingly, the analysis identified the protein of Adenomatous Polyposis Coli (APC) as one of the most up-regulated protein. APC regulates cell proliferation or angiogenesis, and is widely known as a tumor-suppressing gene which can cause colorectal cancer when it is mutated. Western blots confirmed this result, and real-time PCR indicated it is transcriptionally regulated. We further tried to elucidate the molecular mechanism with focusing on IKKβ. IKKβ is the essential kinase in activation of nuclear factor-kappa B (NF-κB), major transcriptional factors that regulate genes responsible for inflammation or immune response. Previous reports indicated that aspirin specifically inhibits IKKβ activity, and constitutively active form of IKKβ accelerates APC loss. We found that aspirin suppressed the expression of IKKβ, and the deletion of IKKβ by siRNA increases the expression of APC in HEK294 cells. Finally, we observed similar effects of aspirin in human umbilical vein endothelial cells. Taken together, these results reveal that aspirin up-regulates the expression of APC via the suppression of IKKβ. This can be a mechanism how aspirin prevents cancer at

  5. Aspirin Use for the Primary Prevention of Myocardial Infarction Among Men in North Carolina, 2013.

    Science.gov (United States)

    Tchwenko, Samuel; Fleming, Eleanor; Perry, Geraldine S

    2015-11-19

    The US Preventive Services Task Force recommends aspirin use for men aged 45 to 79, when the potential benefit of preventing myocardial infarctions outweighs the potential harm of gastrointestinal hemorrhage. We determined prevalence and predictors of aspirin use for primary prevention of myocardial infarction vis-à-vis risk among men aged 45 to 79 in North Carolina. The study used data for men aged 45 to 79 without contraindications to aspirin use or a history of cardiovascular disease from the 2013 North Carolina Behavioral Risk Factor Surveillance System survey. Stratification by risk of myocardial infarction was based on history of diabetes, high cholesterol, high blood pressure, and smoking. Analyses were performed in Stata version 13.0 (StataCorp LP); survey commands were used to account for complex sampling design. Most respondents, 74.2% (95% confidence interval [CI], 71.2%-77.0%), had at least one risk factor for myocardial infarction. Prevalence of aspirin use among respondents with risk factors was 44.8% (95% CI, 41.0-48.5) and was significantly higher than the prevalence among respondents without risk factors (prevalence ratio: 1.44 [95% CI, 1.17-1.78]). No significant linear dose (number of risk factors)-response (taking aspirin) relationship was found (P for trend = .25). Older age predicted (P = .03) aspirin use among respondents with at least one myocardial infarction risk factor. Most men aged 45 to 79 in North Carolina have at least one risk factor for myocardial infarction, but less than half use aspirin. Interventions aimed at boosting aspirin use are needed among at-risk men in North Carolina.

  6. The risk of lower gastrointestinal bleeding in low-dose aspirin users.

    Science.gov (United States)

    Chen, W-C; Lin, K-H; Huang, Y-T; Tsai, T-J; Sun, W-C; Chuah, S-K; Wu, D-C; Hsu, P-I

    2017-06-01

    Aspirin increases the risk of gastrointestinal bleeding. To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users. Low-dose (75-325 mg daily) aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers. A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, PAspirin (hazard ratio [HR]: 2.75, 95% confidence interval [CI]: 2.06-3.65), NSAIDs (HR: 8.61, 95% CI: 3.28-22.58), steroids (HR: 10.50, 95% CI: 1.98-55.57), SSRIs (HR: 11.71, 95% CI: 1.40-97.94), PPIs (HR: 8.47, 95% CI: 2.26-31.71), and H2RAs (HR: 10.83, 95% CI: 2.98-39.33) were significantly associated with LGIB. The risk of LGIB was higher in low-dose aspirin users than in aspirin nonusers in this nationwide cohort. Low-dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB. © 2017 John Wiley & Sons Ltd.

  7. Enoxaparin and aspirin therapy for recurrent pregnancy loss due to anti-phospholipid syndrome (APS

    Directory of Open Access Journals (Sweden)

    Khalid Abd Aziz Mohamed

    2014-09-01

    Conclusions: Use of low dose aspirin and enoxaparin 40 mg subcutaneously daily in patients with RPL due to antiphospholipid syndrome resulted in higher live birth rates compared to low dose aspirin alone. Solid conclusions from this study are limited due to the small number of patients, non-randomization of groups and discrepancy in number between groups because the choice of the interventional drug was left to patient’s preference after counselling. A larger RCT is needed.

  8. Aspirin Is Associated with Improved Survival in Severely Thrombocytopenic Cancer Patients with Acute Myocardial Infarction.

    Science.gov (United States)

    Feher, Attila; Kampaktsis, Polydoros N; Parameswaran, Rekha; Stein, Eytan M; Steingart, Richard; Gupta, Dipti

    2017-02-01

    Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin are not known in thrombocytopenic cancer patients experiencing acute myocardial infarction (AMI). Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as a platelet count aspirin as a treatment for AMI. Compared with patients without sTP with AMI, patients with sTP with AMI were less likely to receive aspirin (83% vs. 43%; p = .0001) and thienopyridine treatment (27% vs. 3%; p = .0005). During median follow-up of 3.7 years after AMI, survival was lower in patients with sTP than in those with no sTP (23% vs. 50% at 1 year; log rank p = .003). Patients with sTP who received aspirin for AMI had improved survival compared with those who did not (92% vs. 70% at 7 days, 72% vs. 33% at 30 days, and 32% vs. 13% at 1 year; log rank p = .008). In multivariate regression models, aspirin use was associated with improved 30-day survival both in the overall patient cohort and in sTP patients. No fatal bleeding events occurred. Major bleeding was not associated with sTP or aspirin use. Treatment of AMI with aspirin in patients with hematologic malignancies and sTP is associated with improved survival without increase in major bleeding. The Oncologist 2017;22:213-221Implications for Practice: In patients with hematologic malignancies and acute myocardial infarction with severe thrombocytopenia (platelet count aspirin therapy was associated with improved survival without an increase in major bleeding in this high-risk patient cohort. © AlphaMed Press 2017.

  9. Pyrazolinone analgesics prevent the antiplatelet effect of aspirin and preserve human platelet thromboxane synthesis.

    Science.gov (United States)

    Hohlfeld, T; Zimmermann, N; Weber, A-A; Jessen, G; Weber, H; Schrör, K; Höltje, H-D; Ebel, R

    2008-01-01

    Anti-inflammatory analgesics, including ibuprofen and naproxen, are known to interfere with the antiplatelet effect of aspirin, presumably as a result of a drug-drug interaction at the level of platelet cyclooxygenase-1 (COX-1). We studied whether dipyrone, which has recently been reported to inhibit COX isoforms by a mechanism different from conventional non-steroidal anti-inflammatory drugs (NSAIDs), also interferes with the antiplatelet effect of aspirin. Arachidonic acid- and collagen-induced aggregation, as well as thromboxane formation, were measured in human platelet-rich plasma. Platelet P-selectin expression was determined by flow cytometry and cell-free COX enzyme activity was quantified by luminol-enhanced luminescence of human platelet microsomes. In addition, computerized docking was performed based on the crystal structure of COX-1. 4-Methylaminoantipyrine (MAA), the active metabolite of dipyrone, largely attenuated or even completely abolished the inhibition of arachidonic acid-induced platelet aggregation, thromboxane formation and P-selectin expression by aspirin. Similar results were obtained for other pyrazolinones, as well as for the conventional NSAIDs ibuprofen and naproxen. Moreover, MAA attenuated the effect of aspirin on COX activity of platelet microsomes, suggesting a competition with aspirin at the COX-1 enzyme. This was confirmed by docking studies, which revealed that MAA forms a strong hydrogen bond with serine 530 within the COX-1, thereby preventing enzyme acetylation by aspirin. This study demonstrates for the first time that dipyrone and other pyrazolinones have a high potential to attenuate or prevent the antiplatelet effect of aspirin. This should be considered if pyrazolinone analgesics are administered to patients with cardiovascular disease requiring antiplatelet aspirin therapy.

  10. An n→π* interaction in aspirin: implications for structure and reactivity.

    Science.gov (United States)

    Choudhary, Amit; Kamer, Kimberli J; Raines, Ronald T

    2011-10-07

    Stereoelectronic effects modulate molecular structure, reactivity, and conformation. We find that the interaction between the ester and carboxyl moieties of aspirin has a previously unappreciated quantum mechanical character that arises from the delocalization of an electron pair (n) of a donor group into the antibonding orbital (π*) of an acceptor group. This interaction affects the physicochemical attributes of aspirin and could have implications for its pharmacology.

  11. An n→π* Interaction in Aspirin: Implications for Structure and Reactivity

    OpenAIRE

    Choudhary, Amit; Kamer, Kimberli J.; Raines, Ronald T.

    2011-01-01

    Stereoelectronic effects modulate molecular structure, reactivity, and conformation. We find that the interaction between the ester and carboxyl moieties of aspirin has a previously unappreciated quantum mechanical character that arises from the delocalization of an electron pair (n) of a donor group into the antibonding orbital (π*) of an acceptor group. This interaction affects the physicochemical attributes of aspirin, and could have implications for its pharmacology.

  12. The analgesic effect of different antidepressants combined with aspirin on thermally induced pain in Albino mice

    Directory of Open Access Journals (Sweden)

    Abdalla S. Elhwuegi

    2012-04-01

    Full Text Available Background:Combination analgesics provide more effective pain relief for a broader spectrum of pain. This research examines the possible potentiation of the analgesic effect of different classes of antidepressants when combined with aspirin in thermal model of pain using Albino mice.Methods:Different groups of six animals each were injected intraperitoneally by different doses of aspirin (50, 100, or 200 mg/kg, imipramine (2.5, 7.5, 15 or 30 mg/kg, fluoxetine (1.25, 2.5, 5 or 7.5 mg/kg, mirtazapine (1.25, 2.5, or 5 mg/kg and a combination of a fixed dose of aspirin (100 mg/kg with the different doses of the three antidepressants. One hour later the analgesic effect of these treatments were evaluated against thermally induced pain. All data were subjected to statistical analysis using unpaired Student's t-test.Results:Aspirin had no analgesic effect in thermally induced pain. The three selected antidepressants produced dose dependent analgesia. The addition of a fixed dose of aspirin to imipramine significantly increased the reaction time (RT of the lowest dose (by 23% and the highest dose (by 20%. The addition of the fixed dose of aspirin to fluoxetine significantly increased RT by 13% of the dose 2.5 mg/Kg. Finally, the addition of the fixed dose of aspirin significantly potentiated the antinociceptive effect of the different doses of mirtazapine (RT was increased by 24, 54 and 38% respectively.Conclusion:Combination of aspirin with an antidepressant might produce better analgesia, increasing the efficacy of pain management and reduces side effects by using smaller doses of each drug.

  13. New Perspectives on Aspirin and the Endogenous Control of Acute Inflammatory Resolution

    Directory of Open Access Journals (Sweden)

    Thea Morris

    2006-01-01

    Full Text Available Aspirin is unique among the nonsteroidal anti-inflammatory drugs in that it has both anti-inflammatory as well as cardio-protective properties. The cardio-protective properties arise form its judicious inhibition of platelet-derived thromboxane A2 over prostacyclin, while its anti-inflammatory effects of aspirin stem from its well-established inhibition of prostaglandin (PG synthesis within inflamed tissues. Thus aspirin and the other NSAIDs have popularised the notion of inhibiting PG biosynthesis as a common anti-inflammatory strategy based on the erroneous premise that all eicosanoids are generally detrimental to inflammation. However, our fascination with aspirin has shown a more affable side to lipid mediators based on our increasing interest in the endogenous control of acute inflammation and in factors that mediate its resolution. Epi-lipoxins (epi-LXs, for instance, are produced from aspirin’s acetylation of inducible cyclooxygenase 2 (COX-2 and together with Resolvins represent an increasingly important family of immuno-regulatory and potentially cardio-protective lipid mediators. Aspirin is beginning to teach us what nature knew all along – that not all lipid mediators are bad. It seems that while some eicosanoids are pathogenic in a variety of diseases, others are unarguable protective. In this review we will re-count aspirin’s colorful history, discuss its traditional mode of action and the controversies associated therewith, as well as highlight some of the new pathways in inflammation and the cardiovascular systems that aspirin has recently revealed.

  14. Gender differences in the activities of aspirin-esterases in rat tissues

    Directory of Open Access Journals (Sweden)

    Benedito M.A.C.

    1998-01-01

    Full Text Available The activities of aspirin (acetylsalicylic acid-esterases were measured in several tissues (liver, kidney, adrenal glands, brain and serum from adult male and female Wistar rats. In males, both aspirin-esterase I (assayed at pH 5.5 and II (assayed at pH 7.4 activities were higher in liver homogenates when compared to females (aspirin-esterase I: males 48.9 ± 4.8 (N = 8 and females 29.3 ± 4.2 (N = 8 nmol of salicylic acid formed min-1 mg protein-1; aspirin-esterase II: males 41.4 ± 4.1 (N = 8 and females 26.1 ± 4.5 (N = 8 nmol of salicylic acid formed min-1 mg protein-1, P<0.001. In serum, enzyme activity was higher in females than in males (aspirin-esterase I: males 0.85 ± 0.06 (N = 6 and females 1.18 ± 0.11 (N = 6 nmol of salicylic acid formed min-1 mg protein-1; aspirin-esterase II: males 1.03 ± 0.13 (N = 6 and females 1.34 ± 0.11 (N = 6 nmol of salicylic acid formed min-1 mg protein-1, P<0.001. In the other tissues assayed, no statistically significant difference between males and females was found. There were no statistically significant differences when the enzymes were assayed in different phases of the estrous cycle in liver and serum. These results show that the differences in aspirin-esterase activity observed between males and females are not due to the estrous cycle. The gender difference obtained in our study may indicate an involvement of gonadal hormones in the control of the hydrolysis of aspirin. This possibility is currently under investigation.

  15. Beneficial effects of low-dose aspirin on aortic stiffness in hypertensive patients.

    Science.gov (United States)

    Pietri, Panagiota; Vlachopoulos, Charalambos; Terentes-Printzios, Dimitris; Xaplanteris, Panagiotis; Aznaouridis, Konstantinos; Petrocheilou, Katerina; Stefanadis, Christodoulos

    2014-12-01

    While treatment with low-dose aspirin has been established as a therapeutic tool for secondary prevention, the role of aspirin on primary prevention remains controversial. Aortic stiffness and wave reflections are independent predictors of cardiovascular events. The aim of the present study was to investigate the effect of low-dose aspirin on aortic stiffness and wave reflections in hypertensive patients. We studied 30 patients with grade I hypertension. Fifteen patients were treated with 160 mg of aspirin and 15 patients with placebo. Aortic stiffness and wave reflections were assessed by measuring carotid-femoral pulse wave velocity (PWV) and heart rate-adjusted augmentation index (AIx75), respectively. All measurements were conducted at baseline and 2 weeks after treatment. In the aspirin group, there was a significant reduction in PWV compared to the placebo group (from 8.9±1.5 to 8.5±1.6 m/s for the aspirin group vs from 8.6±1.4 to 8.7±1.6 m/s for the placebo group, net change: -0.5 m/s; p=0.02). AIx75 showed a marginal decrease (from 28.0±5.4 to 26.2±5.0% for the aspirin group vs from 31.2±9.7 to 30.6±9.2% for the placebo group, net change: -1.2%; p=0.06). In conclusion, a 2-week course of aspirin administration has a favorable effect on aortic stiffness and, to a lesser extent, on wave reflections in hypertensive patients. Whether the reduction in arterial stiffness is translated to fewer cardiovascular events needs to be confirmed by future prospective studies. © The Author(s) 2014.

  16. Preservative effects of Aspirin on Human Hemoglobin glycation in Diabetic Condition

    OpenAIRE

    A Divsalar; J Behroozi; AA Saboury; NN Poursasan

    2013-01-01

    Abstract Background & aim: Diabetes is a common disease which is characterized by hyperglycemia and the increase of protein glycation. The aim of this study was to investigate the effect of aspirin-induced damage in human hemoglobin in diabetic glycation. Materials & Methods: In this study, hemoglobin extracted from the blood of healthy individuals was incubated in the presence and absence of glucose and aspirin for 5 weeks. The rate of haem glycotation was determined in different cond...

  17. Aspirin down-regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro.

    Science.gov (United States)

    Schroecksnadel, K; Winkler, C; Wirleitner, B; Schennach, H; Fuchs, D

    2005-04-01

    Acetylsalicylic acid (aspirin) is one of the most widely used drugs worldwide, due mainly to its broad therapeutic spectrum with anti-inflammatory, antipyretic, antithrombotic and analgesic effects. However, the exact mechanisms by which aspirin influences inflammation, pain and immune system activation are only partly understood. Within activation of the cellular immune system, Th1-type cytokine interferon (IFN)-gamma induces enzyme indoleamine-2,3-dioxygenase (IDO) which converts tryptophan to kynurenine. In parallel, IFN-gamma induces enzyme GTP-cyclohydrolase I, which gives rise to neopterin production by activated human macrophages. Similarly, tryptophan degradation and neopterin formation increase during several disease states involving Th1-type immune activation. Using stimulated human peripheral blood mononuclear cells (PBMC), the effect of aspirin on tryptophan degradation and neopterin production was investigated. Stimulation of PBMC with mitogens concanavalin A, phytohaemagglutinin and pokeweed mitogen induced significant tryptophan catabolism as was reflected by a decline in tryptophan levels and a parallel increase in kynurenine concentrations compared with unstimulated cells. In parallel, neopterin production was enhanced. Treatment of stimulated PBMC with increasing doses of 1-5 mM aspirin significantly decreased stimulation-induced tryptophan degradation and neopterin production as well. All the effects of aspirin were dose-dependent. The parallel influence of aspirin on both biochemical pathways implies that there was no direct inhibitory effect of aspirin on IDO; rather, it inhibits production of IFN-gamma in mitogen-treated PBMC. The influence of aspirin on biochemical pathways induced by IFN-gamma may represent an important part of its broad pharmacological effect.

  18. Aspirin prevents bone loss with little mechanical improvement in high-fat-fed ovariectomized rats.

    Science.gov (United States)

    Lin, Sien; Lee, Wayne Y W; Huang, Meiling; Fu, Ziwei; Liang, Yanlong; Wu, Haiyou; Xu, Liangliang; Suen, Chun Wai; Huang, Jianping; Wu, Tie; Cui, Liao; Li, Gang

    2016-11-15

    Obesity and osteoporosis are often concurrently happened in the menopausal women. Obesity in menopausal women is not only related to a high risk of cardiovascular disease, but also results in a detrimental effect on bone health. This study aimed to investigate the effects of aspirin, a popular anti-thrombosis drug, on bone quantity and quality in the high-fat-fed animal model. Adult female rats were subjected to either sham operations or ovariectomized operations. The ovariectomized rats were orally administered with deionized water or standardized high fat emulsion with or without aspirin. All rats were injected with calcein before killed for the purpose of double in vivo labeling. Biochemistry, histomorphometry, micro-computed tomography analysis, mechanical test, and component analysis were performed after 12 weeks. In vitro cell culture was also performed to observe the effect of aspirin in osteogenesis. We found that high fat remarkably impaired bone formation and bone biomechanics. Aspirin treatment significantly prevented bone loss by increasing bone formation. In vitro studies also validated the enhancement of osteogenic differentiation. However, aspirin presented no significant improvement in bone mechanical properties. Component analysis shown aspirin could significantly increase the content of mineral, but had limited effect on the content of collagen. In conclusion, aspirin is beneficial for the prevention of bone loss; meanwhile, it may cause an imbalance in the components of bone which may weaken the mechanical properties. The current study provided further evidence that aspirin might not be powerful for the prevention of fracture in osteoporotic patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Regular adult aspirin use decreases the risk of non-small cell lung cancer among women.

    Science.gov (United States)

    Van Dyke, Alison L; Cote, Michele L; Prysak, Geoffrey; Claeys, Gina B; Wenzlaff, Angie S; Schwartz, Ann G

    2008-01-01

    Prior studies indicate that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAID) is associated with a decreased risk of non-small cell lung cancer (NSCLC); however, results have been contradictory in part because of variation in study design. Few studies have examined the use of aspirin or other NSAIDs on risk of NSCLC in women. Through a case-control study of African American and Caucasian women with and without NSCLC, we examined the relationship between use of aspirin, NSAIDs, and acetaminophen and risk of NSCLC. Risk was estimated by calculating odds ratios and 95% confidence intervals for ever/never use, duration of use, and duration of use category (never, 1-5 years, >5 years) after adjusting for major risk factors for lung cancer. Risk estimates were stratified by race, age, smoking history, and body mass index. Every use of adult-strength aspirin was associated with a significant reduction in risk of NSCLC (odds ratio, 0.66; 95% confidence interval, 0.46-0.94). Additionally, there was a significant trend toward a reduced risk of NSCLC in adult-strength aspirin users with increasing duration of use (P(trend) = 0.02). In stratified analyses, aspirin use was associated with a significantly reduced risk of lung cancer among Caucasians and 55- to 64-year-olds. Baby aspirin and NSAID use was associated with a significant reduction in risk of NSCLC only among 65- to 74-year-olds. Our results suggest that long-term use of adult-strength aspirin may reduce the risk of NSCLC in women.

  20. Update on Recent Advances in the Management of Aspirin Exacerbated Respiratory Disease

    OpenAIRE

    Palikhe, Nami Shrestha; Kim, Joo-Hee; Park, Hae-Sim

    2009-01-01

    Aspirin intolerant asthma (AIA) is frequently characterized as an aspirin (ASA)-exacerbated respiratory disease (AERD). It is a clinical syndrome associated with chronic severe inflammation in the upper and lower airways resulting in chronic rhinitis, sinusitis, recurrent polyposis, and asthma. AERD generally develops secondary to abnormalities in inflammatory mediators and arachidonic acid biosynthesis expression. Upper and lower airway eosinophil infiltration is a key feature of AERD; howev...

  1. Oxidative stress-related mechanisms affecting response to aspirin in diabetes mellitus.

    Science.gov (United States)

    Santilli, Francesca; Lapenna, Domenico; La Barba, Sara; Davì, Giovanni

    2015-03-01

    Type 2 diabetes mellitus (T2DM) is a major cardiovascular risk factor. Persistent platelet activation plays a key role in atherothrombosis in T2DM. However, current antiplatelet treatments appear less effective in T2DM patients vs nondiabetics at similar risk. A large body of evidence supports the contention that oxidative stress, which characterizes DM, may be responsible, at least in part, for less-than-expected response to aspirin, with multiple mechanisms acting at several levels. This review discusses the pathophysiological mechanisms related to oxidative stress and contributing to suboptimal aspirin action or responsiveness. These include: (1) mechanisms counteracting the antiplatelet effect of aspirin, such as reduced platelet sensitivity to the antiaggregating effects of NO, due to high-glucose-mediated oxidative stress; (2) mechanisms interfering with COX acetylation especially at the platelet level, e.g., lipid hydroperoxide-dependent impaired acetylating effects of aspirin; (3) mechanisms favoring platelet priming (lipid hydroperoxides) or activation (F2-isoprostanes, acting as partial agonists of thromboxane receptor), or aldose-reductase pathway-mediated oxidative stress, leading to enhanced platelet thromboxane A2 generation or thromboxane receptor activation; (4) mechanisms favoring platelet recruitment, such as aspirin-induced platelet isoprostane formation; (5) modulation of megakaryocyte generation and thrombopoiesis by oxidative HO-1 inhibition; and (6) aspirin-iron interactions, eventually resulting in impaired pharmacological activity of aspirin, lipoperoxide burden, and enhanced generation of hydroxyl radicals capable of promoting protein kinase C activation and platelet aggregation. Acknowledgment of oxidative stress as a major contributor, not only of vascular complications, but also of suboptimal response to antiplatelet agents in T2DM, may open the way to designing and testing novel antithrombotic strategies, specifically targeting

  2. Esomeprazole and aspirin fixed combination for the prevention of cardiovascular events.

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    Sylvester, Katelyn W; Cheng, Judy Wm; Mehra, Mandeep R

    2013-01-01

    Low dose aspirin therapy plays a fundamental role in both the primary and secondary prevention of cardiovascular events. Although the evidence using low dose aspirin for secondary prevention is well-established, the decision to use aspirin for primary prevention is based on an evaluation of the patient's risk of cardiovascular events compared to their risk of adverse events, such as bleeding. In addition to the risk of bleeding associated with long term aspirin administration, upper gastrointestinal side effects, such as dyspepsia often lead to discontinuation of therapy, which places patients at an increased risk for cardiovascular events. One option to mitigate adverse events and increase adherence is the addition of esomeprazole to the medication regimen. This review article provides an evaluation of the literature on the concomitant use of aspirin and esomeprazole available through February 2013. The efficacy, safety, tolerability, cost effectiveness, and patient quality of life of this regimen is discussed. A summary of the pharmacokinetic and pharmacodynamic interactions between aspirin and esomeprazole, as well as other commonly used cardiovascular medications are also reviewed. The addition of esomeprazole to low dose aspirin therapy in patients at high risk of developing gastric ulcers for the prevention of cardiovascular disease, significantly reduced their risk of ulcer development. Pharmacokinetic and pharmacodynamic studies suggested that esomeprazole did not affect the pharmacokinetic parameters or the antiplatelet effects of aspirin. Therefore, for those patients who are at a high risk of developing a gastrointestinal ulcer, the benefit of adding esomeprazole likely outweighs the risks of longer term proton pump inhibitor use, and the combination can be recommended. Administering the two agents separately may also be more economical. On the other hand, for those patients at lower risk of developing a gastrointestinal ulcer, both the additional risk

  3. Aspirin: The Mechanism of Action Revisited in the Context of Pregnancy Complications.

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    Cadavid, Angela P

    2017-01-01

    Aspirin is one of the most frequently used and cheapest drugs in medicine. It belongs to the non-steroidal anti-inflammatory drugs with a wide range of pharmacological activities, including analgesic, antipyretic, and antiplatelet properties. Currently, it is accepted to prescribe a low dose of aspirin to pregnant women who are at high risk of preeclampsia (PE) because it reduces the onset of this complication. Another pregnancy alteration in which a low dose of aspirin is recommended is the obstetric antiphospholipid syndrome (APS). The most recognized mechanism of action of aspirin is to inhibit the synthesis of prostaglandins but this by itself does not explain the repertoire of anti-inflammatory effects of aspirin. Later, another mechanism was described: the induction of the production of aspirin-triggered lipoxins (ATLs) from arachidonic acid by acetylation of the enzyme cyclooxygenase-2. The availability of a stable analog of ATL has stimulated investigations on the use of this analog and it has been found that, similar to endogenously produced lipoxins, ATL resolves inflammation and acts as antioxidant and immunomodulator. If we consider that in PE and in the obstetric APS, there is an underlying inflammatory process, aspirin might be used based on the induction of ATL. The objective of this review is to revisit the old and new mechanisms of action of aspirin. In particular, it intends to show other potential uses of this drug to prevent certain pregnancy complications in the light of its ability to induce anti-inflammatory and pro-resolving lipid-derived mediators.

  4. Inhibition of Activator Protein 1 Activity and Neoplastic Transformation by Aspirin*

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    Dong, Zigang; Huang, Chuanshu; Brown, Rhoderick E.; Ma, Wei-Ya

    1997-01-01

    Aspirin, along with its analgesic-antipyretic uses, is now also being considered for prevention of cardiovascular disease, cancer, and treatment of human immunodeficiency virus infection. Although many of aspirin's pharmacological actions are related to its ability to inhibit prostaglandin biosynthesis, some of its beneficial therapeutic effects are not completely understood. Transcription factor activator protein 1 (AP-1) is critical for the induction of neoplastic transformation and inducti...

  5. Aspirin dose for the prevention of cardiovascular disease: a systematic review.

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    Campbell, Charles L; Smyth, Susan; Montalescot, Gilles; Steinhubl, Steven R

    2007-05-09

    More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease, typically either 81 mg/d or 325 mg/d. Controversy remains regarding the most appropriate long-term daily dose. To review the mechanism of action of aspirin and the clinical literature for relationships among aspirin dosage, efficacy, and safety. A systematic review of the English-language literature was undertaken using MEDLINE and EMBASE (searched through February 2007) and the search term aspirin or acetylsalicylic acid and dose. The search was limited to clinical trials and was extended by a review of bibliographies of pertinent reports of original data and review articles. Published prospective studies using different aspirin dosages in the setting of cardiovascular disease were included. Although pharmacodynamic data demonstrate that long-term aspirin dosages as low as 30 mg/d are adequate to fully inhibit platelet thromboxane production, dosages as high as 1300 mg/d are approved for use. In the United States, 81 mg/d of aspirin is prescribed most commonly (60%), followed by 325 mg/d (35%). The available evidence, predominantly from secondary-prevention observational studies, supports that dosages greater than 75 to 81 mg/d do not enhance efficacy, whereas larger dosages are associated with an increased incidence of bleeding events, primarily related to gastrointestinal tract toxicity. Currently available clinical data do not support the routine, long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention. Higher dosages, which may be commonly prescribed, do not better prevent events but are associated with increased risks of gastrointestinal bleeding.

  6. The inhibitory effect of simvastatin and aspirin on histamine responsiveness in human vascular endothelial cells.

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    Absi, Mais; Bruce, Jason I; Ward, Donald T

    2014-04-01

    Statins and aspirin deliver well-established cardiovascular benefits resulting in their increased use as combined polypills to decrease risk of stroke and heart disease. However, the direct endothelial effect of combined statin/aspirin cotreatment remains unclear. Histamine is an inflammatory mediator that increases vascular permeability, and so we examined the effect of treating human umbilical vein endothelial cells (HUVECs) for 24 h with 1 μM simvastatin and 100 μM aspirin on histamine responsiveness. Subsequent histamine (1 μM) challenge increased intracellular calcium (Ca(2+)i) concentration, an effect that was significantly inhibited by combined simvastatin/aspirin pretreatment but not when then the compounds were given separately, even at 10-fold higher concentrations. In contrast, the Ca(2+)i mobilization response to ATP challenge (10 μM) was not inhibited by combined simvastatin/aspirin pretreatment. The H1 receptor antagonist pyrilamine significantly inhibited both histamine-induced Ca(2+)i mobilization and extracellular signal-regulated kinase (ERK) activation, whereas ranitidine (H2 receptor antagonist) was without effect. However, combined simvastatin/aspirin pretreatment failed to decrease H1 receptor protein expression ruling out receptor downregulation as the mechanism of action. Histamine-induced ERK activation was also inhibited by atorvastatin pretreatment, while simvastatin further inhibited histamine-induced vascular endothelial cadherin phosphorylation as well as altered HUVEC morphology and inhibited actin polymerization. Therefore, in addition to the known therapeutic benefits of statins and aspirin, here we provide initial cellular evidence that combined statin/aspirin treatment inhibits histamine responsiveness in HUVECs.

  7. Aspirin augments IgE-mediated histamine release from human peripheral basophils via Syk kinase activation.

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    Matsuo, Hiroaki; Yokooji, Tomoharu; Morita, Hironobu; Ooi, Mina; Urata, Kana; Ishii, Kaori; Takahagi, Shunsuke; Yanase, Yuhki; Hiragun, Takaaki; Mihara, Shoji; Hide, Michihiro

    2013-12-01

    Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, and food additives (FAs) may exacerbate allergic symptoms in patients with chronic idiopathic urticaria and food-dependent exercise-induced anaphylaxis (FDEIA). Augmentation of histamine release from human mast cells and basophils by those substances is speculated to be the cause of exacerbated allergic symptoms. We sought to investigate the mechanism of action of aspirin on IgE-mediated histamine release. The effects of NSAIDs, FAs or cyclooxygenase (COX) inhibitors on histamine release from human basophils concentrated by gravity separation were evaluated. Benzoate and tartrazine, which have no COX inhibitory activity, augmented histamine release from basophils similar to aspirin. In contrast, ibuprofen, meloxicam, FR122047 and NS-398, which have COX inhibitory activity, did not affect histamine release. These results indicate that the augmentation of histamine release by aspirin is not due to COX inhibition. It was observed that aspirin augmented histamine release from human basophils only when specifically activated by anti-IgE antibodies, but not by A23187 or formyl-methionyl-leucyl-phenylalanine. When the IgE receptor signaling pathway was activated, aspirin increased the phosphorylation of Syk. Moreover, patients with chronic urticaria and FDEIA tended to be more sensitive to aspirin as regards the augmentation of histamine release, compared with healthy controls. Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

  8. Decomposition of aspirin in the solid state in the presence of limited amounts of moisture II: Kinetics and salting-in of aspirin in aqueous acetic acid solutions.

    Science.gov (United States)

    Carstensen, J T; Attarchi, F

    1988-04-01

    The solubility of aspirin in saturated solutions of salicylic acid (and vice versa) was studied in 0 to 16 M aqueous solutions of acetic acid. The solubilities, when expressed in molarity, go through a maximum at an acetic acid concentration of approximately 12 M. The temperature dependence of the solubilities is such that the logarithm of the solubility is linear in reciprocal absolute temperature. The calculated enthalpies are of the order of 11 kcal/mol. The kinetics of aspirin decomposition was also studied at the different acetic acid concentrations, and it was found that the second-order hydrolysis rate constant is fairly independent of acetic acid concentration. Aspirin decomposition follows an Arrhenius equation and has an activation energy of 18 kcal/mol.

  9. Preoperative aspirin use and acute kidney injury after cardiac surgery: A propensity-score matched observational study.

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    Min Hur

    Full Text Available The association between preoperative aspirin use and postoperative acute kidney injury (AKI in cardiovascular surgery is unclear. We sought to evaluate the effect of preoperative aspirin use on postoperative AKI in cardiac surgery.A total of 770 patients who underwent cardiovascular surgery under cardiopulmonary bypass were reviewed. Perioperative clinical parameters including preoperative aspirin administration were retrieved. We matched 108 patients who took preoperative aspirin continuously with patients who stopped aspirin more than 7 days or did not take aspirin for the month before surgery. The parameters used in the matching included variables related to surgery type, patient's demographics, underlying medical conditions and preoperative medications.In the first seven postoperative days, 399 patients (51.8% developed AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO criteria and 128 patients (16.6% required hemodialysis. Most patients took aspirin 100 mg once daily (n = 195, 96.5% and the remaining 75 mg once daily. Multivariable analysis showed that preoperative maintenance of aspirin was independently associated with decreased incidence of postoperative AKI (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.21-0.98, P = 0.048; after propensity score matching: OR 0.39, 95% CI 0.22-0.67, P = 0.001. Preoperative maintenance of aspirin was associated with less incidence of AKI defined by KDIGO both in the entire and matched cohort (n = 44 [40.7%] vs. 69 [63.9%] in aspirin and non-aspirin group, respectively in matched sample, relative risk [RR] 0.64, 95% CI 0.49, 0.83, P = 0.001. Preoperative aspirin was associated with decreased postoperative hospital stay after matching (12 [9-18] days vs. 16 [10-25] in aspirin and non-aspirin group, respectively, P = 0.038. Intraoperative estimated or calculated blood loss using hematocrit difference and estimated total blood volume showed no difference according to aspirin

  10. Critical appraisal of a fixed combination of esomeprazole and low dose aspirin in risk reduction

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    Ravi Vachhani

    2010-06-01

    Full Text Available Ravi Vachhani1, Doumit Bouhaidar1, Alvin Zfass1, Bimaljit Sandhu1, Ali Nawras21Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298–0341, USA; 2Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Toledo Medical Center, Toledo, Ohio 43606-3390, USAAbstract: Low dose aspirin (≤325 mg is routinely used for primary and secondary prophylaxis of cardiovascular and cerebrovascular events. The use of low dose aspirin is associated with two-to four-fold greater risk of symptomatic or complicated peptic ulcers. Risk factors associated with low dose aspirin induced gastrointestinal toxicity includes prior history of ulcer or upper gastrointestinal (GI bleeding, concomitant use of other nonsteroidal anti-inflammatory drugs, corticosteroid or warfarin, dual antiplatelet therapy, Helicobacter pylori (H. pylori infection, and advanced age. Esomeprazole, like other proton pump inhibitors (PPIs is very effective in decreasing the risk of aspirin induced gastrointestinal toxicity. Although evidence to support esomeprazole or other PPIs for primary prophylaxis in aspirin induced gastrointestinal toxicity is limited, its role in secondary prophylaxis is well established.Keywords: esomeprazole, proton pump inhibitors, low dose aspirin, gastrointestinal toxicity, gastrointestinal bleeding

  11. Aspirin for the Primary Prevention of Cardiovascular Disease: In Need of Clarity.

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    Miedema, Michael D; Huguelet, Joseph; Virani, Salim S

    2016-01-01

    Aspirin remains one of the most extensively studied cardiovascular medications in the history of medicine. However, despite multiple, well-designed, large randomized controlled trials evaluating the potential of aspirin to prevent cardiovascular events in individuals without known cardiovascular disease (CVD), the role of aspirin in primary prevention is currently unclear. The initial aspirin trials included largely low-risk individuals with primary outcomes mostly focused on myocardial infarction (MI) and stroke, and showed a significant reduction in these CVD outcomes, especially MI. The more recently conducted trials have focused on older, higher CVD risk populations with high rates of lipid-lowering and antihypertensive medications use. These studies have used broader CVD outcomes as their primary end points and have failed to show a significant benefit of aspirin therapy in primary prevention. The exact reasons for the lack of efficacy in these recent trials are unclear but may be related to low rate of atherothrombotic events relative to other CVD events in the populations studied. Four large randomized controlled trials are currently underway which should provide some clarity in determining the optimal use of aspirin in the primary prevention of CVD.

  12. Which people should take aspirin for primary prevention of cardiovascular disease?

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    Lozano R

    2015-07-01

    Full Text Available Roberto Lozano,1 Maria-Esther Franco21Pharmacy Department, 2Haematology Department, Hospital Real de Nuestra Señora de Gracia, Zaragoza, SpainDear editorA single trial, ISIS-2,1 in 1988, demonstrated the utility of daily aspirin in the setting of acute myocardial infarction, reducing the risk of vascular death by 23%. In addition, aspirin has also proven effective in the setting of acute ischemic stroke.2 Thus, for a subset of the general population, aspirin may help to prevent heart attacks and strokes. In fact, at low doses, in the range of 75 to 100 mg per day, aspirin prevents the progression of existing cardiovascular disease (CVD, including coronary heart disease, stroke and peripheral arterial disease, and reduces the frequency of cardiovascular events in patients with history of CVD,3,4 referred to as secondary prevention.Although the benefits of aspirin for secondary prevention of CVD are well known, its use in primary prevention of CVD, defined as prevention of the first occurrence of CVD for all patients without clinical CVD, including those with diabetes mellitus and those without clinical evidence of atherosclerotic disease who are at higher CVD risk, is less clear and controversial results have been obtained. In fact, the results of several studies using aspirin for primary prevention of CVD have generally shown more modest reductions of major vascular events compared with secondary prevention (12% vs 23%.3,5

  13. Dynamic study of interaction between beta-cyclodextrin and aspirin by the ultrasonic relaxation method.

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    Fukahori, Takanori; Kondo, Minako; Nishikawa, Sadakatsu

    2006-03-09

    A single ultrasonic relaxational phenomenon was observed in aqueous solutions containing both beta-cyclodextrin (beta-CD) as host and nonionized or ionized acetylsalicylic acid (aspirin) as guest. The observed relaxation was responsible for a dynamic complexation reaction between beta-CD and aspirin molecules, concomitant with a volume change during the reaction. The kinetic and equilibrium constants for the complexation in the acid (nonionized) form of the aspirin system were derived from the guest concentration dependence of the relaxation frequency. The equilibrium constant for the carboxylate (ionized) form of aspirin was determined from the concentration dependence of a maximum absorption per wavelength, and the rate constants were calculated by using the determined equilibrium constant and the observed relaxation frequencies, which remained nearly almost constant over the concentration range studied. The results showed that the effect of charge on the aspirin molecule was reflected only in the dissociation process from the beta-CD cavity, while no remarkable change was seen in the association process whose rate was diffusion controlled. The results could be explained on the basis of the difference of the hydrophobic moieties in the two guests that were included in the host cavity. The results of the standard volume change for the complexation reaction were closely related to the number of expelled water molecules originally located in the beta-CD cavity and the volume of the aspirin molecule incorporated into the beta-CD cavity.

  14. THE EFFECTIVENESS OF CLOPIDOGREL AS AN ANTITHROMBOTIC COMPARED TO TICLOPIDINE AND ASPIRIN (META-ANALYSIS

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    Titien Siwi Hartayu

    2017-05-01

    Full Text Available Clopidogrel, an antithrombotic drug, has been proven by FDA as Plavix® was initially used for the prevention of vascular occlusive that cause of myocardial infarction, stroke, and vascular death in patients with atherosclerosis and then it is used to treat Acute Coronary Syndrome (ACS. Aim of the study is to compare the effectiveness of Clopidogrel to aspirin and ticlopidine by meta-analysis of CLASSICS (The Clopidogrel Aspirin Stent International Cooperative Study, MATCH trial dan CAPRIE trial. Results of the study show that the effectiveness of Clopidogrel is significantly higher, however the risk of ischemic and bleeding is lower than aspirin and ticlopidine. Cost-effectiveness of Clopidogrel in avoiding secondary stroke in one episode is approximately US $ 33,000, and aspirin is only US $ 1400.  In Indonesia the price of Clopidogrel  is ranged from US $1.5 to US $3 each tablet, while the price of aspirin ranged from US $ 0.35  to US $ 0.72. However, in Indonesia Clopidogrel is now in the list of National Formulary, this fact might have contributed to the increasing use of Clopidogrel, which has reached around 1000 tablets per day in each hospital while aspirin has reached  almost 1500 tablets per day.

  15. Aspirin and the risk of cardiovascular events in atherosclerosis patients with and without prior ischemic events.

    Science.gov (United States)

    Bavry, Anthony A; Elgendy, Islam Y; Elbez, Yedid; Mahmoud, Ahmed N; Sorbets, Emmanuel; Steg, Philippe Gabriel; Bhatt, Deepak L

    2017-09-01

    The benefit of aspirin among patients with stable atherosclerosis without a prior ischemic event is not well defined. Aspirin would be of benefit in outpatients with atherosclerosis with prior ischemic events, but not in those without ischemic events. Subjects from the Reduction of Atherothrombosis for Continued Health registry were divided according to prior ischemic event (n =21 724) vs stable atherosclerosis, but no prior ischemic event (n = 11 872). Analyses were propensity score matched. Aspirin use was updated at each clinic visit and considered as a time-varying covariate. The primary outcome was the first occurrence of cardiovascular death, myocardial infarction, or stroke. In the group with a prior ischemic event, aspirin use was associated with a marginally lower risk of the primary outcome at a median of 41 months (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.65-1.01, P = 0.06). In the group without a prior ischemic event, aspirin use was not associated with a lower risk of the primary outcome at a median of 36 months (HR: 1.03, 95% CI: 0.73-1.45, P = 0.86). In this observational analysis of outpatients with stable atherosclerosis, aspirin was marginally beneficial among patients with a prior ischemic event; however, there was no apparent benefit among those with no prior ischemic event. © 2017 Wiley Periodicals, Inc.

  16. Surface enhanced Raman spectroscopic studies on aspirin : An experimental and theoretical approach

    Science.gov (United States)

    Premkumar, R.; Premkumar, S.; Rekha, T. N.; Parameswari, A.; Mathavan, T.; Benial, A. Milton Franklin

    2016-05-01

    Surface enhanced Raman scattering (SERS) studies on aspirin molecule adsorbed on silver nanoparticles (AgNPs) were investigated by experimental and density functional theory approach. The AgNPs were synthesized by the solution-combustion method and characterized by the X-ray diffraction and high resolution-transmission electron microscopy techniques. The averaged particle size of synthesized AgNPs was calculated as ˜55 nm. The normal Raman spectrum (nRs) and SERS spectrum of the aspirin were recorded. The molecular structure of the aspirin and aspirin adsorbed on silver cluster were optimized by the DFT/ B3PW91 method with LanL2DZ basis set. The vibrational frequencies were calculated and assigned on the basis of potential energy distribution calculation. The calculated nRs and SERS frequencies were correlated well with the observed frequencies. The flat-on orientation was predicted from the nRs and SERS spectra, when the aspirin adsorbed on the AgNPs. Hence, the present studies lead to the understanding of adsorption process of aspirin on the AgNPs, which paves the way for biomedical applications.

  17. Aspirin mono-therapy continuation does not result in more bleeding after knee arthroplasty.

    Science.gov (United States)

    Schwab, Pierre-Emmanuel; Lavand'homme, Patricia; Yombi, JeanCyr; Thienpont, Emmanuel

    2017-08-01

    Current clinical practice guidelines sometimes still recommend stopping aspirin five to seven days before knee arthroplasty surgery. Literature regarding multimodal blood management and continuation of anti-platelet therapy in this type of surgery is scant. The study hypothesis was that knee arthroplasty under low-dose aspirin mono-therapy continuation does not cause more total blood loss than knee arthroplasty performed without aspirin. Blood loss would be measured by haemoglobin (Hb) and haematocrit (HTC) levels drop at day 2 or day 4 for patients who benefit from multimodal bleeding control measures. A database of all patients undergoing knee arthroplasty between 2006 and 2014 was analysed. Demographic, surgical and complete blood workup data were collected. A retrospective comparison study analysed both groups in terms of blood loss, by mean calculated blood loss as haemoglobin or haematocrit drop between the preoperative Nadir value and the postoperative day 2 and 4 value. A group of 198 (44 UKA and 154 TKA) patients underwent surgery without interrupting their aspirin therapy for cardiovascular prevention. Mean (SD) age was 71 (8) and the mean (SD) BMI was 29 (5.5) kg/m 2 . The control group consisted of 403 (102 UKA and 301 TKA) patients who were not under aspirin, or any other anti-platelet agent. Mean (SD) age was 65 (10) (p aspirin mono-therapy for cardiovascular prevention. III.

  18. Ab initio study of aspirin adsorption on single-walled carbon and carbon nitride nanotubes

    Science.gov (United States)

    Lee, Yongju; Kwon, Dae-Gyeon; Kim, Gunn; Kwon, Young-Kyun

    We use ab intio density functional theory to investigate the adsorption properties of acetylsalicylic acid or aspirin on a (10, 0) carbon nanotube (CNT) and a (8, 0) triazine-based graphitic carbon nitride nanotube (CNNT). It is found that an aspirin molecule binds stronger to the CNNT with its adsorption energy of 0.67 eV than to the CNT with 0.51 eV. The stronger adsorption energy on the CNNT is ascribed to the high reactivity of its N atoms with high electron affinity. The CNNT exhibits local electric dipole moments, which cause strong charge redistribution in the aspirin molecule adsorbed on the CNNT than on the CNT. We also explore the influence of an external electric field on the adsorption properties of aspirin on these nanotubes by examining the modifications in their electronic band structures, partial densities of states, and charge distributions. It is found that an electric field applied along a particular direction induces aspirin molecular states in the in-gap region of the CNNT implying a potential application of aspirin detection.

  19. Effect of aspirin on chromosome aberration and DNA damage induced by X-rays in mice

    Science.gov (United States)

    Niikawa, M.; Chuuriki, K.; Shibuya, K.; Seo, M.; Nagase, H.

    In order to reveal the anticlastogenic potency of aspirin, we evaluated the suppressive ability of aspirin on chromosome aberrations induced by X-ray. Aspirin at doses of 0.5, 5 and 50 mg/kg was administrated intraperitoneally or orally at 0.5 h after or before the X-ray irradiation. The anticlastogenic activity of aspirin on chromosome aberrations induced by X-ray was determined in the mouse micronucleus test and alkaline single cell gel electrophoresis (SCG) assay in vivo. The frequency by polychromatic erythrocytes with micronuclei (MNPCEs) was decreased by about 19-61% at 0.5 h after and about 23-62% at 0.5 h before the X-ray irradiation. DNA damage by X-ray was significantly decreased by oral administration of aspirin at 0.5 h after or before the X-ray irradiation for the SCG assay. We consider aspirin can be used as preventive agents against exposure of X-ray.

  20. Surface enhanced Raman spectroscopic studies on aspirin : An experimental and theoretical approach

    Energy Technology Data Exchange (ETDEWEB)

    Premkumar, R.; Premkumar, S.; Parameswari, A.; Mathavan, T.; Benial, A. Milton Franklin, E-mail: miltonfranklin@yahoo.com [Department of Physics, N.M.S.S.V.N College, Madurai-625019, Tamilnadu, India. (India); Rekha, T. N. [PG and Research Department of Physics, Lady Doak College, Madurai-625 002, Tamilnadu, India. (India)

    2016-05-06

    Surface enhanced Raman scattering (SERS) studies on aspirin molecule adsorbed on silver nanoparticles (AgNPs) were investigated by experimental and density functional theory approach. The AgNPs were synthesized by the solution-combustion method and characterized by the X-ray diffraction and high resolution-transmission electron microscopy techniques. The averaged particle size of synthesized AgNPs was calculated as ∼55 nm. The normal Raman spectrum (nRs) and SERS spectrum of the aspirin were recorded. The molecular structure of the aspirin and aspirin adsorbed on silver cluster were optimized by the DFT/ B3PW91 method with LanL2DZ basis set. The vibrational frequencies were calculated and assigned on the basis of potential energy distribution calculation. The calculated nRs and SERS frequencies were correlated well with the observed frequencies. The flat-on orientation was predicted from the nRs and SERS spectra, when the aspirin adsorbed on the AgNPs. Hence, the present studies lead to the understanding of adsorption process of aspirin on the AgNPs, which paves the way for biomedical applications.

  1. Aspirin Inhibits Platelet-Derived Sphingosine-1-Phosphate Induced Endothelial Cell Migration.

    Science.gov (United States)

    Polzin, Amin; Knoop, Betül; Böhm, Andreas; Dannenberg, Lisa; Zurek, Mark; Zeus, Tobias; Kelm, Malte; Levkau, Bodo; Rauch, Bernhard H

    2018-01-01

    Aspirin plays a crucial role in the prevention of cardiovascular diseases. We previously described that aspirin has effects beyond inhibition of platelet aggregation, as it inhibited thrombin-mediated release of sphingosine-1-phosphate (S1P) from human platelets. S1P is a bioactive lipid with important functions on inflammation and apoptosis. In endothelial cells (EC), S1P is a key regulator of cell migration. In this study, we aimed to analyze the effects of aspirin on platelet-induced EC migration. Human umbilical EC migration was measured by Boyden chamber assay. EC migration was induced by platelet supernatants of thrombin receptor-activating peptide-1 (AP1) stimulated platelets. To investigate the S1P receptor subtype that promotes EC migration, specific inhibitors of S1P receptor subtypes were applied. S1P induced EC migration in a concentration-dependent manner. EC migration induced by AP1-stimulated platelet supernatants was reduced by aspirin. S1P1 receptor inhibition almost completely abolished EC migration induced by activated platelets. The inhibition of S1P2 or S1P3 receptor had no effect. Aspirin inhibits EC migration induced by activated platelets that is in part due to S1P and mediated by the endothelial S1P1 receptor. The clinical significance of this novel mechanism of aspirin action has to be investigated in future studies. © 2017 S. Karger AG, Basel.

  2. Metabolism of arachidonic acid in hamster lung microsomes is not completely inhibited by aspirin and indomethacin

    Energy Technology Data Exchange (ETDEWEB)

    Uotila, P.; Paajanen, H.; Schalin, M.; Simberg, N.

    1983-10-01

    Aspirin (100 microM or 1 mM) or indomethacin (10 microM or 100 microM) was incubated with a microsomal preparation of hamster lungs in the presence of NADPH for 10 min. Then 14C-arachidonic acid (20 microM) was added and the incubation was continued for an additional 20 min. The metabolites were extracted with ethyl acetate first at pH 7.4 and then at pH 3.5 and analysed by thin layer chromatography. Both aspirin and indomethacin inhibited dose dependently the formation of all identified prostaglandins, including PGF2 alpha, 6-keto-PGF1 alpha, PGE2 and PGD2. The rate of formation of some unidentified metabolites extracted at pH 7.4 and 3.5 was, however, not changed by aspirin or indomethacin. We have earlier reported that in isolated perfused hamster lungs the formation of all arachidonate metabolites is inhibited by both aspirin and indomethacin. As the present study indicates that in the microsomes of hamster lungs all metabolic pathways of arachidonic acid are not inhibited by aspirin or indomethacin, it is possible that in isolated tissues and in vivo aspirin-like drugs have some other inhibitory effects on arachidonate metabolism than the inhibition of the cyclo-oxygenase enzyme.

  3. Risk of complications with use of aspirin during renal biopsy: A systematic review.

    Science.gov (United States)

    Kumar, Vinayak; Mitchell, Matthew D; Umscheid, Craig A; Berns, Jeffrey S; Hogan, Jonathan J

    2018-02-01

    Bleeding is a well-known complication of percutaneous renal biopsy (PRB). Thus, antiplatelet agents are routinely held for most patients undergoing elective PRB to decrease bleeding risk. In this systematic review, we examine the association between antiplatelet use and bleeding during PRB. MEDLINE and EMBASE were searched from inception to December 2016 using terms that included "renal biopsy", "antiplatelet","aspirin", and "bleeding". Guidelines and systematic reviews were identified primarily through large databases, including the National Guideline Clearinghouse and Cochrane Database of Systematic Reviews. Two authors independently screened the results, and appraised and graded the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Out of 371 guidelines, 40 systematic reviews, and 709 primary studies originally identified, 4 guidelines, 1 systematic review, and 2 primary studies met inclusion criteria. The guidelines recommend halting aspirin for elective PRB. The systematic review found no difference in major outcomes for PRB in patients for whom aspirin was continued versus halted, but was of low quality. The 2 nonrandomized primary studies in PRB patients managed with and without aspirin found no difference in major bleeds but a higher risk of minor bleeds. There is low-quality evidence on the effect of aspirin on bleeding risk from PRB. It is reasonable to discontinue aspirin 7 - 10 days prior to nonemergent biopsies, in accordance with guidelines. Given the results from the primary studies, it is reasonable to perform randomized controlled trials to obtain high-quality evidence to inform clinical practice.
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  4. The influence of gender on the effects of aspirin in preventing myocardial infarction

    Directory of Open Access Journals (Sweden)

    Sin Don D

    2007-10-01

    Full Text Available Abstract Background There is considerable variation in the effect of aspirin therapy reducing the risk of myocardial infarction (MI. Gender could be a potential explanatory factor for the variability. We conducted a systematic review and meta-analysis to determine whether gender mix might play a role in explaining the large variation of aspirin efficacy across primary and secondary MI prevention trials. Methods Randomized placebo-controlled clinical trials that examined the efficacy of aspirin therapy on MI were identified by using the PUBMED database (1966 to October 2006. Weighted linear regression technique was used to determine the relationship between log-transformed relative risk (RR of MI and the percentage of male participants in each trial. The reciprocal of the standard error of the RR in each trial (1/SE was used as the weight. Results A total of 23 trials (n = 113 494 participants were identified. Overall, compared with placebo, aspirin reduced the risk of non-fatal MI (RR = 0.72, 95% confidence interval (CI 0.64–0.81, p Conclusion Gender accounts for a substantial proportion of the variability in the efficacy of aspirin in reducing MI rates across these trials, and supports the notion that women might be less responsive to aspirin than men.

  5. Post-diagnosis aspirin use and overall survival in patients with melanoma.

    Science.gov (United States)

    Rachidi, Saleh; Wallace, Kristin; Li, Hong; Lautenschlaeger, Tim; Li, Zihai

    2018-01-06

    Mouse studies show that tumor-derived prostaglandins and platelets promote melanoma progression and immune-evasion. Determine if aspirin confers longer survival in patients with melanoma. A retrospective cohort study of 1,522 patients at Indiana University Health (IUH) diagnosed with melanoma between 2000 and 2014 and followed up through September, 2016. Aspirin use was associated with longer overall survival in univariate analysis and after controlling for age, sex, stage, and treatment modalities (HR 0.58, 95% CI [0.45-0.75]). Aspirin use was not associated with survival in patients with in situ and stage I melanoma, but was associated with better survival in stages II (HR 0.45, 95% CI [0.24-0.82]) and III (HR 0.57, 95% CI [0.34-0.96]). No statistical significance was observed in stage IV patients (HR 0.55, 95% CI [0.27-1.13]). In turn, patients using aspirin before diagnosis were less likely to be diagnosed in stages III or IV disease. Observational study. Aspirin could provide a survival advantage in melanoma. Clinical trials investigating the therapeutic potential of aspirin are warranted. Copyright © 2018. Published by Elsevier Inc.

  6. Impact of aspirin and clopidogrel interruption on platelet function in patients undergoing major vascular surgery.

    Directory of Open Access Journals (Sweden)

    Yannick Le Manach

    Full Text Available AIMS: To investigate functional platelet recovery after preoperative withdrawal of aspirin and clopidogrel and platelet function 5 days after treatment resumption. METHODS/RESULTS: We conducted an observational study, which prospectively included consecutive patients taking aspirin, taking clopidogrel, and untreated controls (15 patients in each group. The antiplatelet drugs were withdrawn five days before surgery (baseline and were reintroduced two days after surgery. Platelet function was evaluated by optical aggregation in the presence of collagen, arachidonic acid (aspirin and ADP (clopidogrel and by VASP assay (clopidogrel. Platelet-leukocyte complex (PLC level was quantified at each time-point. At baseline, platelet function was efficiently inhibited by aspirin and had recovered fully in most patients 5 days after drug withdrawal. PLC levels five days after aspirin reintroduction were similar to baseline (+4±10%; p = 0.16, in line with an effective platelet inhibition. Chronic clopidogrel treatment was associated with variable platelet inhibition and its withdrawal led to variable functional recovery. PLC levels were significantly increased five days after clopidogrel reintroduction (+10±15%; p = 0.02, compared to baseline. CONCLUSIONS: Aspirin withdrawal 5 days before high-bleeding-risk procedures was associated with functional platelet recovery, and its reintroduction two days after surgery restored antiplaletet efficacy five days later. This was not the case of clopidogrel, and further work is therefore needed to define its optimal perioperative management.

  7. [Analysis of saccharin and aspirin tasting ability among Mongolians of Xinjiang].

    Science.gov (United States)

    Rahman, Erkin; Omer, Zibirnisa; Lawook, Ahsheeka; Mamut, Hajinisa

    2002-07-01

    The saccharin and aspirin tasting abilities have been detected and analyzed in 710 individuals (328men, 382women) of Xinjiang Mongol. It is showed that the saccharin taste-blindness ratio among Mongolians was 4.648%,frequency of the recessive gene determining taste-blindness and the dominant gene determining taste ability was 0.2156, and 0.7844 respectively,and its mean testable threshold was 8.00+/-1.34 (0.108mol/L). Distribution of aspirin tasting threshold appeared a distinct curve with double peaks and single bottom,and demonstrated the aspirin tasting ability was a monogenic character. Solution NO.7 (3.00x10(-4)mol/L) at the bottom in the curve was the boundary of taste-blindness. The peak of taste-blindness was at the solution NO.1 (1.7x10(-2)mol/L), and the peak of tasters was at the solution NO.11 (1.25x10(-5)mol/L), The ratio of aspirin taste-blindness was 90.28%. The chi2 test has been used to evaluate the statistical difference in aspirin taste-blindness ratio between male and female, the result showed that there was no significant difference (P>0.90), and the gene determining for aspirin tasting ability located on autosomes.

  8. [Resistance to aspirin: prevalence, mechanisms of action and association with thromboembolic events. A narrative review].

    Science.gov (United States)

    Cañivano Petreñas, L; García Yubero, C

    2010-01-01

    The purpose of this study is to review the prevalence of aspirin resistance in patients with a high risk of cardiovascular events, and secondly, to investigate its epidemiology and mechanism of action, and the clinical consequences it can provoke. A search was run on PubMed, EMBASE and Reviews Database for English or Spanish articles on aspirin resistance published up to November 2008. Additional studies were obtained by searching the reference lists in the selected articles for articles relevant to our secondary objectives. Aspirin resistance is described as affecting 0 to 57% of the population, and is related to a decreased protective effect against strokes and cardiovascular events. Many modifiable and unmodifiable factors can affect the efficacy of antiplatelet drugs. Possible strategies for overcoming this decreased antiaggregant effect include increasing the aspirin dosage or dual therapy with another antiplatelet agent. Lack of response to aspirin decreases its protective effects. However, lack of a standard definition for aspirin resistance, the absence of diagnostic reference methods to identify resistant patients, and the different mechanisms of action involved in platelet aggregation call the clinical importance of this fact into question. Additional well-designed studies are needed to detect patients with real resistance in order to have more effective prevention of cardiovascular morbidity and mortality. Copyright (c) 2009 SEFH. Published by Elsevier Espana. All rights reserved.

  9. Mechanism of action by which aspirin alleviates detrusor hyperactivity in rats.

    Science.gov (United States)

    Tsukimi, Yasuhiro; Mizuyachi, Kaori; Matsumoto, Hiroko; Sato, Masako; Ng, Betty; Tajimi, Masaomi

    2004-05-01

    We examined the effect of aspirin on urodynamic parameters in normal and cyclophosphamide-induced cystitic rats and compared them in rats with or without sensory denervation. Cystometry was performed under urethane anesthesia; and volume threshold for micturition (VT), micturition frequency (MF), micturition pressure (MP), and micturition volume (MV) were determined. Cystitis was induced by pretreatment with cyclophosphamide and sensory denervation was performed by pretreating animals with a large dose of capsaicin. PGE(2) and 6-keto-PGF(1alpha) contents in the bladder were determined by ELISA. Sensory intact, cystitic rats showed decrement of VT and increment of MF. Aspirin increased VT and decreased MF in the cystitic condition. Both PGE(2) and 6-keto-PGF(1alpha) contents in the bladder were significantly increased in cystitic rats, but such increases were completely inhibited by aspirin. In sensory denervated rats, aspirin showed a marginal tendency of increment of VT. Cystitic rats showed overflow micturition in the sensory denervated condition, but VT was the same as that of normal rats. Furthermore, following capsaicin pretreatment, aspirin had no effect on the cystometrogram in cystitic rats. From these findings, it is concluded that suppression of sensory C-fiber via inhibition of PGs synthesis in the bladder is involved in the pharmacological action of aspirin in the detrusor hyperactivity.

  10. Hypothesis formulation from subgroup analyses: nonadherence or nonsteroidal anti-inflammatory drug use explains the lack of clinical benefit of aspirin on first myocardial infarction attributed to "aspirin resistance".

    Science.gov (United States)

    Hennekens, Charles H; Schneider, Wendy R; Hebert, Patricia R; Tantry, Udaya S; Gurbel, Paul A

    2010-05-01

    "Aspirin resistance" has been defined as the occurrence of cardiovascular events despite regular intake of aspirin. One major analytic study suggesting that "aspirin resistance" is a clinical reality was unable to control for confounding by nonadherence or nonsteroidal anti-inflammatory drugs (NSAIDs). We formulated a hypothesis from subgroup analyses in the Physicians' Health Study, a randomized double-blind placebo-controlled trial testing 325 mg of aspirin every other day among 22,071 apparently healthy US male physicians. We classified participants by nonadherence or NSAIDs and used time-varying Cox proportional hazard models to adjust for confounding. After 5 years, the blinded aspirin component was terminated early based on the unanimous recommendation of the Data and Safety Monitoring Board. Of 378 confirmed first myocardial infarctions (139 aspirin and 239 placebo), the relative risk (RR) was 0.56 (95% CI 0.45-0.70, P aspirin 60 days per year (RR = 1.54, 95% CI 0.68-3.47, P = .31). There was a statistically significant reduction among aspirin >150/180 pills/y and NSAID users aspirin 60 days/y (RR of 3.43, 95% CI 1.41-8.33, P = .007). In subgroup analyses useful to formulate hypotheses from a large randomized trial in apparently healthy men, aspirin nonadherence or NSAID use explained the lack of clinical benefit of aspirin on first myocardial infarction that has been attributed to "aspirin resistance." Direct randomized comparisons are necessary in trials designed a priori to test this hypothesis. 2010 Mosby, Inc. All rights reserved.

  11. Aspirin resistance may be identified by miR-92a in plasma combined with platelet distribution width

    DEFF Research Database (Denmark)

    Binderup, Helle Glud; Houlind, Kim; Madsen, Jonna Skov

    2016-01-01

    OBJECTIVE: Aspirin is a widely used drug for prevention of thrombotic events in cardiovascular patients, but approximately 25% of patients experience insufficient platelet inhibition due to aspirin, and remain in risk of cardiovascular events. This study aimed to investigate the value...... of circulating miR-92a and platelet size as biomarkers of the individual response to aspirin therapy. METHODS: Blood samples were collected from 50 healthy blood donors without antithrombotic medication and 50 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic...... acid stimulated aggregation test on Multiplate®analyzer (ASPItest), patients were defined as aspirin resistant (n=10) or aspirin responders (n=40). Plasma levels of miR-92a were evaluated by RT-qPCR analysis and platelet distribution width (PDW) was used to assess platelet size variability. Receiver...

  12. Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity.

    Science.gov (United States)

    Fujiwara, T; Ikeda, M; Esumi, K; Fujita, T D; Kono, M; Tokushige, H; Hatoyama, T; Maeda, T; Asai, T; Ogawa, T; Katsumata, T; Sasaki, S; Suzuki, E; Suzuki, M; Hino, F; Fujita, T K; Zaima, H; Shimada, M; Sugawara, T; Tsuzuki, Y; Hashimoto, Y; Hishigaki, H; Horimoto, S; Miyajima, N; Yamamoto, T; Imagawa, K; Sesoko, S; Fujisawa, Y

    2007-12-01

    Aspirin prevents the production of thromboxane A2 (TXA2) by irreversibly inhibiting platelet cyclooxygenase, exhibiting antiplatelet actions. This agent has been reported to prevent relapse in patients with ischemic heart disease or cerebral infarction via this action mechanism. However, there are individual differences in this action, and aspirin is not effective in some patients, which is referred to as 'aspirin resistance'. In this study, we analyzed laboratory aspirin resistance by platelet aggregation in 110 healthy adult Japanese males using 24 single-nucleotide polymorphisms (SNPs) of nine genes involved in platelet aggregation/hemorrhage. Among SNPs involved in platelet aggregation, aspirin was less effective for 924T homozygote of a TXA2 receptor, 924T>C, and 1018C homozygote of a platelet membrane glycoprotein GPIbalpha, 1018C>T, suggesting that 924T and 1018C alleles are involved in aspirin resistance.

  13. Could Aspirin and Diets High in Fiber Act Synergistically to Reduce the Risk of Colon Cancer in Humans?

    OpenAIRE

    Pan Pan; Yi-Wen Huang; Kiyoko Oshima; Martha Yearsley; Jianying Zhang; Jianhua Yu; Mark Arnold; Li-Shu Wang

    2018-01-01

    Early inhibition of inflammation suppresses the carcinogenic process. Aspirin is the most commonly used non-steroid anti-inflammatory drugs (NSAIDs), and it irreversibly inhibits cyclooxygenase-1 and -2 (COX1, COX2). Multiple randomized clinical trials have demonstrated that aspirin offers substantial protection from colon cancer mortality. The lower aspirin doses causing only minimal gastrointestinal disturbance, ideal for long-term use, can achieve only partial and transitory inhibition of ...

  14. Suboptimal inhibition of platelet cyclo-oxygenase-1 (COX-1) by aspirin in lupus erythematosus: Association with metabolic syndrome

    Science.gov (United States)

    Kawai, Vivian K.; Avalos, Ingrid; Oeser, Annette; Oates, John A.; Milne, Ginger L.; Solus, Joseph F.; Chung, Cecilia P.; Stein, C. Michael

    2013-01-01

    Objectives Low-dose aspirin prevents platelet aggregation by suppressing thromboxane A2 synthesis. However, in some individuals thromboxane A2 suppression by aspirin is impaired, indicating suboptimal inhibition of platelet COX-1 by aspirin. Because patients with systemic lupus erythematosus (SLE) have increased risk of thrombotic events, many receive aspirin; however, the efficacy of aspirin in SLE has not been determined. We examined the hypothesis that aspirin response is impaired in SLE. Methods We assessed the effect of aspirin by measuring concentrations of the stable metabolite of thromboxane A2 - serum thromboxane B2 (sTxB2), before and after treatment with 81 mg daily aspirin for 7 days in 34 patients with SLE and 36 control subjects. The inability to suppress sTxB2 synthesis to aspirin. Results Aspirin almost completely suppressed sTXB2 in control subjects to 1.5, [0.8–2.7] ng/ml (median and interquartile ranges [IQR]), but had less effect in patients with SLE (3.1, [2.2–5.3] ng/ml) (P=0.002). A suboptimal effect of aspirin was present in 15% (5/34) of the patients with SLE but not in control subjects (0/36) (P=0.023). Incomplete responders were more likely to have metabolic syndrome (P=0.048), obesity (P=0.048) and higher concentrations of CRP (P=0.018). Conclusion The pharmacologic effect of aspirin is suboptimal in 15% of patients with SLE but in none of the control subjects, and the suboptimal response was associated with metabolic syndrome, obesity, and higher CRP concentrations. PMID:24022862

  15. Effect of atorvastatin on platelet thromboxane A(2) synthesis in aspirin-treated patients with acute myocardial infarction.

    Science.gov (United States)

    Santos, M Teresa; Fuset, M Paz; Ruano, Miguel; Moscardó, Antonio; Valles, Juana

    2009-12-15

    Inhibition of platelet thromboxane A(2) (TXA(2)) by aspirin is critical in patients with acute myocardial infarction (AMI), but some patients have persistent platelet TXA(2) production within 48 hours of the onset of AMI. Statins are known to reduce TXA(2) in aspirin-free patients with hypercholesterolemia. We hypothesized that treatment with aspirin plus atorvastatin could reduce persistent TXA(2) synthesis and aspirin resistance in patients with AMI. We evaluated platelet function in 184 aspirin-treated patients within 48 hours of the onset of AMI. Patients were divided into group A (treated with aspirin alone, n = 139) and group B (treated with aspirin plus atorvastatin, n = 45). We studied collagen-induced platelet TXA(2) synthesis, serotonin ((14)C-5HT) release and recruitment, and adenosine diphosphate-, arachidonic acid-, and collagen-induced platelet aggregation. Persistent TXA(2) synthesis was detected in 25% and 9% of groups A and B, respectively (p = 0.03). TXA(2), arachidonic acid-aggregation, and collagen-induced responses were significantly reduced in patients receiving dual treatment compared to those receiving aspirin monotherapy. Atorvastatin did not modify platelet reactivity in patients with efficiently blocked TXA(2) synthesis. These results strongly suggest a direct effect of the statin on platelet eicosanoid synthesis. This was confirmed in vitro by incubating washed aspirin-free and aspirin (1 muM)-treated platelets from normal subjects with 1 to 20 microM atorvastatin. Atorvastatin in vitro significantly reduced platelet TXA(2) synthesis and collagen-induced aggregation. In conclusion, atorvastatin combined with aspirin early in the onset of the acute event significantly reduced persistent TXA(2) and TXA(2)-dependent aspirin resistance. This could contribute to the clinical benefit of atorvastatin in patients with AMI.

  16. De Novo Post-Diagnosis Aspirin Use and Mortality in Women with Stage I-III Breast Cancer.

    Science.gov (United States)

    Barron, Thomas I; Murphy, Laura M; Brown, Chris; Bennett, Kathleen; Visvanathan, Kala; Sharp, Linda

    2015-06-01

    Aspirin use has been associated with significant reductions in breast cancer-related mortality in some observational studies. However, these studies included women who initiated aspirin use before breast cancer diagnosis. It is unclear whether initiating aspirin use after diagnosis is associated with similar reductions in mortality. This study investigates associations between de novo post-diagnostic aspirin use and all cause, breast cancer-specific mortality. Women, ages 50 to 80, with a diagnosis of stage I-III breast cancer were identified from Ireland's National Cancer Registry (N = 4,540). Initiation of de novo post-diagnostic aspirin use was identified from linked national prescription refill data (N = 764). Adjusted HRs were estimated for associations between de novo aspirin use and all-cause, breast cancer-specific mortality. The median time from diagnosis to aspirin initiation was 1.8 years. The mean number of days' supply of aspirin received was 631, and 95% of users were taking less than 150 mg/d. We found no association between de novo aspirin use and breast cancer-specific mortality [HR, 0.98; 95% confidence interval (CI), 0.74-1.30]. Similar null associations were found in women taking aspirin at high-intensity (HR, 1.03; 95% CI, 0.72-1.47) and women initiating use in the 1.5 years after diagnosis (HR, 1.04; 95% CI, 0.77-1.40). There was no effect modification by estrogen (Pinteraction = 0.81) or progesterone (Pinteraction = 0.41) receptor status. Initiating aspirin use after a breast cancer diagnosis was not associated with a reduction in breast cancer-specific mortality. On the basis of our findings, we suggest that a clearer understanding of aspirin's mechanism of action is needed to help inform the design of future studies in breast cancer. ©2015 American Association for Cancer Research.

  17. Role of gastric blood flow, neutrophil infiltration, and mucosal cell proliferation in gastric adaptation to aspirin in the rat.

    OpenAIRE

    Konturek, S J; Brzozowski, T; Stachura, J.; Dembinski, A; Majka, J

    1994-01-01

    Gastric mucosa exhibits the ability to adapt to ulcerogenic action of aspirin but the mechanism of this phenomenon is unknown. In this study, acute gastric lesions were produced by single or repeated doses of acidified aspirin in rats with intact or resected salivary glands and with intact or suppressed synthase of nitric oxide. A single oral dose of aspirin produced a dose dependent increase in gastric lesions accompanied by considerable blood neutrophilia and mucosal neutrophil infiltration...

  18. FREQUENCY OF ASPIRIN RESISTANCE IN PATIENTS WITH TYPE 1 AND 2 DIABETES MELLITUS AND ITS ASSOCIATION WITH METABOLIC PARAMETERS

    Directory of Open Access Journals (Sweden)

    Deniz Gokalp

    2016-08-01

    Full Text Available Objectives: In the present study, we aimed to determine the prevalence of aspirin resistance in patients with Type 1 and 2 diabetes and to study its association with metabolic parameters. Methods: Aspirin resistance of patients (n=158 with Type 2 Diabetes Mellitus (DM who presented to the center after 7 days of regular aspirin use were compared to age-mathced (55±19 healthy controls (n=164. Similarly, aspirin resistance of patients (n=30 diagnosed with Type 1 DM were compared to age-matched (27±7 healthy subjects (n=41 as the control group. Platelet Function Analyzer (PFA-100 was used to evaluate the efficacy of aspirin. Results: Aspirin resistance was identified in 72 of 158 patients with Type 2 DM (45.6% and in 47 of 164 healthy controls (28.6% (p=0.001. Aspirin resistance had a prevalence of 50% in patients with Type 1 DM and was significantly higher compared to the control group of 41 healthy subjects (12.2% (p=0.001. No correlations were noted between aspirin resistance and sex, smoking, HbA1c, hypertension and aspirin dose. There was a significant relation between aspirin resistance and LDL-cholesterol in patients with Type 2 DM (p=0.020. Conclusion: Patients with Type 1 and Type 2 DM had a higher frequency of aspirin resistance than the control group. Therefore, treatment choices including administering higher doses of aspirin or using other antiplatelet agents such as clopidogrel should be considered to prevent thrombocytic events in diabetes mellitus.

  19. Systems Pharmacogenomics Finds RUNX1 Is an Aspirin-Responsive Transcription Factor Linked to Cardiovascular Disease and Colon Cancer

    Directory of Open Access Journals (Sweden)

    Deepak Voora, MD

    2016-09-01

    Full Text Available Aspirin prevents cardiovascular disease and colon cancer; however aspirin's inhibition of platelet COX-1 only partially explains its diverse effects. We previously identified an aspirin response signature (ARS in blood consisting of 62 co-expressed transcripts that correlated with aspirin's effects on platelets and myocardial infarction (MI. Here we report that 60% of ARS transcripts are regulated by RUNX1 – a hematopoietic transcription factor - and 48% of ARS gene promoters contain a RUNX1 binding site. Megakaryocytic cells exposed to aspirin and its metabolite (salicylic acid, a weak COX-1 inhibitor showed up regulation in the RUNX1 P1 isoform and MYL9, which is transcriptionally regulated by RUNX1. In human subjects, RUNX1 P1 expression in blood and RUNX1-regulated platelet proteins, including MYL9, were aspirin-responsive and associated with platelet function. In cardiovascular disease patients RUNX1 P1 expression was associated with death or MI. RUNX1 acts as a tumor suppressor gene in gastrointestinal malignancies. We show that RUNX1 P1 expression is associated with colon cancer free survival suggesting a role for RUNX1 in aspirin's protective effect in colon cancer. Our studies reveal an effect of aspirin on RUNX1 and gene expression that may additionally explain aspirin's effects in cardiovascular disease and cancer.

  20. Patients with previous definite stent thrombosis have a larger fraction of immature platelets and a reduced antiplatelet effect of aspirin

    DEFF Research Database (Denmark)

    Würtz, Morten; Grove, Erik; Wulff, Lise Nielsen

    Objectives This study sought to evaluate the platelet response to aspirin and the immature platelet fraction in patients with previous stent thrombosis (ST). Background ST is a potentially fatal complication of coronary stenting. A reduced platelet response to aspirin increases the risk of cardio......Objectives This study sought to evaluate the platelet response to aspirin and the immature platelet fraction in patients with previous stent thrombosis (ST). Background ST is a potentially fatal complication of coronary stenting. A reduced platelet response to aspirin increases the risk...

  1. Low-dose aspirin use and the risk of ovarian cancer in Denmark.

    Science.gov (United States)

    Baandrup, L; Kjaer, S K; Olsen, J H; Dehlendorff, C; Friis, S

    2015-04-01

    A comprehensive body of evidence has shown that aspirin has cancer-preventive effects, particularly against gastrointestinal cancer, but its effects on the risk of ovarian cancer are less well established. This nationwide case-control study examined the association between low-dose aspirin and the risk of ovarian cancer. We identified all patients in the Danish Cancer Registry aged 30-84 years old with a histologically verified first diagnosis of epithelial ovarian cancer during 2000-2011. Each patient was sex- and age-matched to 15 population controls using risk-set sampling. Prescription use, comorbidity, reproductive history, and demographic characteristics data were obtained from nationwide registries. The use of low-dose (75-150 mg) aspirin was defined according to the dose as well as the duration and consistency of use. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between low-dose aspirin use and the risk of epithelial ovarian cancer, both overall and for specific histological types. For 4103 ovarian cancer cases and 58 706 population controls, the adjusted OR for epithelial ovarian cancer associated with ever use (≥2 prescriptions) of low-dose aspirin was 0.94 (95% CI 0.85-1.05). ORs for epithelial ovarian cancer were lower with the use of 150 mg aspirin tablets (OR = 0.82; 95% CI 0.68-0.99) and with long-term use (≥5 years) of low-dose aspirin (OR = 0.77; 95% CI 0.55-1.08). Continuous long-term use of low-dose aspirin, defined as close consecutive prescriptions, was associated with a further reduction in OR (0.56; 95% CI 0.32-0.97). For histological types of epithelial ovarian cancer, the strongest inverse associations with low-dose aspirin use were seen for mucinous and endometrioid tumours. This nationwide case-control study indicates that low-dose aspirin use may be associated with a reduced risk of epithelial ovarian cancer. © The Author 2014. Published by Oxford

  2. [Effect of aspirin administration for the treatment of osteoporosis in ovariectomized rat model].

    Science.gov (United States)

    Chen, Zhi-wen; Wu, Zi-xiang; Sang, Hong-xun; Qin, Guo-liang; Wang, Li-song; Feng, Jing; Wang, Jun; Li, Xiao-juan; Wang, Jian-chao; Zhang, Da

    2011-04-05

    To explore the therapeutic effects of aspirin on postmenopausal osteoporosis and understand its action mechanism. Forty three-month-old female SD rats were randomly divided into 5 groups (n = 8 each): sham group, OVX group and aspirin groups (A1, A2 & A3). The OVX and aspirin groups were ovariectomized (OVX). All rats underwent BMD (bone mineral density) scan at the time of OVX and 3 months after OVX. After the animal model of osteoporosis was established, aspirin groups were intragastrically administered at a dose of 8.93 mg×kg(-1)×d(-1) (A1), 26.79 mg×kg(-1)×d(-1) (A2) and 80.36 mg×kg(-1)×d(-1) (A3) daily in OVX rats. Three months later, the BMD and micro-architecture of vertebrae were measured by dual-energy X-ray absorptiometry and microtomography. Alkaline phosphatase and osteocalcin were measured in peripheral blood. The trabecular architecture changes were observed by histomorphology. Axial compression tests were used to evaluate the mechanical properties of vertebral specimens and three-point bending tests used for femur shaft. Three months after ovariectomy, BMD was significantly lower than preoperative. BMD in aspirin treated groups was significantly higher than that in OVX group. Alkaline phosphatase in peripheral blood decreased significantly in aspirin groups than those in OVX, but osteocalcin had no significant difference between aspirin and OVX groups. The microtomography reconstruction analysis also showed that the trabecular thickness, trabecular number and BMD increased significantly in aspirin groups than those in OVX. And there was no significant difference between A3 and sham groups. The results of biomechanical test showed that the maximum compression load of lumbar spine and three-point bending load of femur shaft were significantly higher in aspirin groups than those in OVX group. Aspirin can promote trabecular bone remodeling, improve three-dimensional structure of trabecular bone and increase bone density of cancellous in

  3. Assessment of platelet function in acute ischemic stroke patients previously treated with aspirin.

    Science.gov (United States)

    Lago, Aida; Parkhutik, Vera; Tembl, Jose Ignacio; Vallés, Juana; Santos, Maria Teresa; Moscardó, Antonio

    2014-01-01

    Platelet inhibition measured by platelet function tests could be critical to understand the reasons for early recurrence and to guide therapeutic recommendations. We assess the platelet function during the acute phase of ischemic stroke in patients pretreated with aspirin who continue their treatment with aspirin only, are started on clopidogrel only, or add clopidogrel to aspirin. Sixty-four patients were taking aspirin before the stroke. Depending on the administered antiplatelet, 3 groups were defined: ASA: patients who continued on aspirin orally or intravenous acetylsalicylate of lysine, n = 30; CLO: patients who discontinued aspirin and were started on clopidogrel, n = 16; and ASA + CLO: patients who were prescribed both aspirin and clopidogrel, n = 10. Collagen-induced thromboxane A2 (TXA2) synthesis, ADP (adenosine diphosphate)-induced aggregation, and occlusion time (PF-100) were measured. CLO group only had a marked elevation of TXA2 (17.44 ± 15.62 ng/mL, P = .000) and a shortening of the platelet function analyzer (PFA)-100 closure time (157.13 ± 88 seconds, P = .047) compared with the other 2 groups (ASA: TXA2, .62 ± 1.59 ng/mL; ASA + CLO: TXA2 1.79 ± 4.59 ng/mL). They achieved a small (13%) but significant reduction of ADP-induced aggregation (87.00 ± 23.06 mm, P = .008) compared with the ASA group (102.82 ± 22.38 seconds). Stopping aspirin intake within the first 72 hours of the acute stroke drastically increases TXA2 synthesis. During the same time window, the freshly prescribed clopidogrel manages to reduce the ADP-induced aggregation only slightly (13%). This study offers analytic proof that the common practice of replacing aspirin with clopidogrel does not leave stroke patients fully protected during the first days after an ischemic stroke. Possible solutions could be to preserve aspirin during a few days or to use loading doses of clopidogrel at hospital admission. Copyright © 2014 National Stroke Association. Published by Elsevier Inc

  4. Contemporary patterns of discharge aspirin dosing after acute myocardial infarction in the United States: results from the National Cardiovascular Data Registry (NCDR).

    Science.gov (United States)

    Hall, Hurst M; de Lemos, James A; Enriquez, Jonathan R; McGuire, Darren K; Peng, S Andrew; Alexander, Karen P; Roe, Matthew T; Desai, Nihar; Wiviott, Stephen D; Das, Sandeep R

    2014-09-01

    Accumulated data suggest that low-dose aspirin after myocardial infarction (MI) may offer similar efficacy to higher dose aspirin with reduced risk of bleeding. Few data are available on contemporary aspirin dosing patterns after MI in the United States Aspirin dosing from 221 199 patients with MI (40.2% ST-segment-elevation MI) from 525 US hospitals enrolled in the National Cardiovascular Data Registry's (NCDR's) Acute Coronary Treatment and Intervention Outcomes Network Registry-Get with the Guidelines were described, overall and in clinically relevant subgroups. High-dose aspirin was defined as 325 mg and low dose as 81 mg. Between January 2007 and March 2011, 60.9% of patients with acute MI were discharged on high-dose aspirin, 35.6% on low-dose aspirin, and 3.5% on other doses. High-dose aspirin was prescribed at discharge to 73.0% of patients treated with percutaneous coronary intervention and 44.6% of patients managed medically. Among 9075 patients discharged on aspirin, thienopyridine, and warfarin, 44.0% were prescribed high-dose aspirin. Patients with an in-hospital major bleeding event were also frequently discharged on high-dose aspirin (56.7%). A 25-fold variation in the proportion prescribed high-dose aspirin at discharge was observed across participating centers. Most US patients with MI continue to be discharged on high-dose aspirin. Although aspirin dosing after percutaneous coronary intervention largely reflected prevailing guidelines before 2012, high-dose aspirin was prescribed with similar frequency in medically managed patients and to those in categories expected to be at high risk for bleeding. Wide variability in the proportional use of high-dose aspirin across centers suggests significant influence from local practice habits and uncertainty about appropriate aspirin dosing. © 2014 American Heart Association, Inc.

  5. Update on aspirin in the treatment and prevention of cardiovascular disease.

    Science.gov (United States)

    Hennekens, Charles H

    2002-12-01

    Antiplatelet therapy, most notably aspirin, has been well documented to reduce risks of subsequent cardiovascular disease (CVD) in secondary prevention, acute myocardial infarction (MI), acute occlusive stroke, as well as in primary prevention. In secondary prevention, the most recent Antithrombotic Trialists' Collaboration reviewed 194 published randomized trials of antiplatelet therapy, mostly aspirin, involving more than 212 000 patients (ie, 135 000 using antiplatelet therapy or control and 77 000 using different antiplatelet regimens). In a very wide range of patients who have survived a prior occlusive vascular event-including MI, transient ischemic attacks, occlusive stroke, unstable and stable angina, percutaneous coronary interventions, and coronary artery bypass graft-aspirin prevents about 25% of serious vascular events. Among patients suffering acute Ml or acute occlusive stroke, aspirin begun promptly and continued long-term reduces risks of subsequent MI, stroke, and vascular death. In acute coronary syndromes, clopidogrel added to aspirin further reduces the risk of important vascular events, but not mortality, and causes more side effects, especially bleeding. For patients undergoing percutaneous coronary interventions, the addition of a short-term infusion of a glycoprotein IIb/IIIa receptor antagonist to aspirin prevents additional vascular events during the early in-hospital period but also increases the risk of major bleeding. Ongoing research is investigating other combinations of different antiplatelet drugs. In all these high-risk patients, there is a small excess of major bleeding among those assigned at random to aspirin, which is far outweighed by the magnitude of benefits on CVD. During an acute MI, after a loading dose of 160 mg to 325 mg aspirin, daily doses ranging from 75 to 150 mg daily are as effective as higher doses. For long-term treatment, the effects of doses 325 mg daily, no antiplatelet regimen is more effective than aspirin

  6. Review of aspirin and clopidogrel resistance in peripheral arterial disease.

    Science.gov (United States)

    Guirgis, Mina; Thompson, Peter; Jansen, Shirley

    2017-11-01

    Aspirin resistance (AR) and clopidogrel resistance (CR) are terms used to describe a reduction in the medication's efficacy in inhibiting platelet aggregation despite regular dosing. This review gives context to the clinical role and implications of antiplatelet resistance in peripheral arterial disease (PAD). A review of English-language literature on AR and CR in PAD involving human subjects using PubMed and MEDLINE databases was performed in April 2017. A total of 2075 patients in 22 relevant studies were identified. To give this issue context, a review of the larger, more established literature on antiplatelet resistance in coronary disease was undertaken, identifying significant research associating resistance to major adverse cardiovascular events (MACEs). Studies in the coronary arterial disease literature have strongly associated antiplatelet resistance with increased MACE. Prevalence of AR or CR in coronary disease appears to be >55% for each in some studies. Meta-analyses of >50 studies revealed that AR and CR are significantly associated with MACE (relative risk of 2.09 and 2.8, respectively). This adds further weight to the literature reporting antiplatelet resistance as an independent predictor of and a threefold risk factor for major adverse cardiovascular events. The prevalence of resistance in PAD in this review was comparable to that in the coronary disease literature, with AR and CR prevalence up to 60% and 65%, respectively. There is evidence that the adverse effects of antiplatelet resistance are significant in PAD. In fact, research directly studying stent thrombosis populations with either coronary arterial disease or PAD revealed more significantly impaired platelet responsiveness to clopidogrel and aspirin in PAD compared with similar individuals with coronary disease. AR in PAD was found in studies to be a significant risk factor for iliofemoral stent reocclusion (P = .0093) and stroke in patients with symptomatic carotid disease (P

  7. General practitioner attitudes towards prescribing aspirin to carriers of Lynch Syndrome: findings from a national survey.

    Science.gov (United States)

    Smith, Samuel G; Foy, Robbie; McGowan, Jennifer; Kobayashi, Lindsay C; Burn, John; Brown, Karen; Side, Lucy; Cuzick, Jack

    2017-10-01

    A dose non-inferiority study comparing 100 mg, 300 mg and 600 mg of aspirin for cancer prevention among Lynch Syndrome carriers is underway (Colorectal Adenoma/Carcinoma Prevention Programme trial 3, CaPP3). To guide implementation of the findings, we investigated general practitioner (GP) attitudes towards aspirin prescribing for Lynch Syndrome carriers. We surveyed 1007 UK GPs (9.6% response rate). Using a within-subjects design, GPs read a statement on harms and benefits of aspirin and indicated their willingness to prescribe aspirin at three doses (100 mg, 300 mg, 600 mg). Approximately two-thirds (70.8%) of GPs had heard of Lynch Syndrome or its associated names, and among those 46.7% were aware of the cancer preventive effects of aspirin among carriers. Two-thirds (68.1%) of GPs reported feeling comfortable discussing harms and benefits of aspirin with a Lynch Syndrome patient. Willingness to prescribe was 91.3% at 100 mg, and declined to 81.8% at 300 mg and 62.3% at 600 mg (p Lynch Syndrome patient in practice (OR 1.44, 95% CI 1.01-2.05, p = 0.045). GPs report limited awareness of Lynch Syndrome and the preventive effects of aspirin among carriers. To ensure the optimal dose identified in the CaPP3 trial is readily available to patients, prescribing guidance and strategies to educate GPs should be developed.

  8. Challenge-proven aspirin hypersensitivity in children with chronic spontaneous urticaria.

    Science.gov (United States)

    Cavkaytar, Ozlem; Arik Yilmaz, Ebru; Buyuktiryaki, Betul; Sekerel, Bulent E; Sackesen, Cansin; Soyer, Ozge U

    2015-02-01

    Nonsteroidal anti-inflammatory drug (NSAID) exacerbated cutaneous disease is defined as the exacerbation of wheals and/or angioedema in patients with a history of chronic spontaneous urticaria (CSU). The objective of this study was to define 'aspirin-hypersensitive' children and adolescents in a clearly defined group of patients with CSU and to describe their clinical features. Eighty-one children with a history of CSU were enrolled over a 3-year period. The daily or almost daily (>4 days a week) presence of urticaria was defined as 'chronic persistent urticaria' (CPU), while the presence of urticaria for 2-4 days a week was defined as 'chronic recurrent urticaria' (CRU). Single-blind, placebo-controlled provocation tests (SBPCPTs) with aspirin were performed for children with CSU. Patients with CRU had a longer duration of cutaneous symptoms [1.6 (0.5-4) vs 0.6 (0.3-1.5) years], and stress was less frequently experienced as an eliciting factor in patients with CRU compared with the patients with CPU (P aspirin revealed that 14 of 58 patients (24%) with CPU and one of 10 patients with CRU (10%) were aspirin hypersensitive. Aspirin hypersensitivity rate was 26.5% in patients aspirin-hypersensitive patients (aged between 6.6 and 17.4 years), except for three, experienced an unequivocal angioedema of the lips as a positive reaction in SBPCPT. Nearly a quarter of children and adolescents with CSU were hypersensitive to aspirin. For children with chronic urticaria, determination of NSAID hypersensitivity in a well-controlled clinical setting will help to avoid severe drug hypersensitivity reactions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Determinants of reduced antiplatelet effect of aspirin in patients with stable coronary artery disease.

    Science.gov (United States)

    Larsen, Sanne Bøjet; Grove, Erik Lerkevang; Neergaard-Petersen, Søs; Würtz, Morten; Hvas, Anne-Mette; Kristensen, Steen Dalby

    2015-01-01

    Aspirin is a cornerstone in management of coronary artery disease (CAD). However, considerable variability in the antiplatelet effect of aspirin has been reported. To investigate independent determinants of reduced antiplatelet effect of aspirin in stable CAD patients. We performed a cross-sectional study including 900 stable, high-risk CAD patients. Among these, 795 (88%) had prior myocardial infarction, 250 (28%) had type 2 diabetes, and 170 (19%) had both. All patients received 75 mg aspirin daily as mono antiplatelet therapy. The antiplatelet effect of aspirin was assessed by measurement of platelet aggregation employing 1) multiple electrode aggregometry (MEA, Multiplate Analyzer) in whole blood anticoagulated with citrate or hirudin using arachidonic acid (AA) or collagen as agonists, and 2) VerifyNow Aspirin Assay. Compliance was assessed by measurement of serum thromboxane B2. Platelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased AA-induced MEA platelet aggregation in citrate and hirudin anticoagulated blood (p-values ≤ 0.045). Similar results were found with VerifyNow. Prior coronary artery bypass grafting, age, smoking (MEA, AA/citrate) and female gender (MEA, AA/hirudin) were also independent determinants of increased platelet aggregation (p-values ≤ 0.038). Compliance was confirmed by low serum thromboxane B2 levels in all patients (median [25%;75%]: 0.97 [0.52;1.97], range 0.02-26.44 ng/ml). Platelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased platelet aggregation, indicating that these characteristics may be key factors in reduced antiplatelet effect of aspirin in stable CAD patients.

  10. Aspirin Exposure Reveals Novel Genes Associated with Platelet Function and Cardiovascular Events

    Science.gov (United States)

    Voora, Deepak; Cyr, Derek; Lucas, Joseph; Chi, Jen-Tsan; Dungan, Jennifer; McCaffrey, Timothy A.; Katz, Richard; Newby, L. Kristin; Kraus, William E; Becker, Richard C.; Ortel, Thomas L.; Ginsburg, Geoffrey S.

    2013-01-01

    Objectives To develop RNA profiles that could serve as novel biomarkers for the response to aspirin. Background Aspirin reduces death and myocardial infarction (MI) suggesting that aspirin interacts with biological pathways that may underlie these events. Methods We administered aspirin, followed by whole blood RNA microarray profiling, in a discovery cohort of healthy volunteers (HV1,n=50), and two validation cohorts of volunteers (HV2,n=53) or outpatient cardiology patients (OPC, n=25). Platelet function was assessed by platelet function score (PFS; HV1/HV2) or VerifyNow Aspirin (OPC). Bayesian sparse factor analysis identified sets of coexpressed transcripts, which were examined for association with PFS in HV1 and validated in HV2 and OPC. Proteomic analysis confirmed the association of validated transcripts in platelet proteins. Validated gene sets were tested for association with death/MI in two patient cohorts (n=587, total) from RNA samples collected at cardiac catheterization. Results A set of 60 co-expressed genes named the “aspirin response signature” (ARS) was associated with PFS in HV1 (r = −0.31, p = 0.03), HV2 (r = −0.34, Bonferroni p = 0.03), and OPC (p = 0.046). Corresponding proteins for 17 ARS genes were identified in the platelet proteome, of which, six were associated with PFS. The ARS was associated with death/MI in both patient cohorts (odds ratio = 1.2, p = 0.01 and hazard ratio = 1.5, p = 0.001), independent of cardiovascular risk factors. Compared with traditional risk factors, reclassification (net reclassification index = 31 - 37%, p ≤ 0.0002) was improved by including the ARS or one of its genes, ITGA2B. Conclusions RNA profiles of platelet-specific genes are novel biomarkers for identifying those do not response adequately to aspirin and who are at risk for death/MI. PMID:23831034

  11. The effect of prostaglandin synthase inhibitor, aspirin on the rat intestinal membrane structure and function.

    Science.gov (United States)

    Kaur, G; Kaur, J; Mittal, N; Nath Sanyal, S

    2010-01-01

    Aspirin at a dose of 50 mg/kg body weight was found to decrease the activity of the rat intestinal brush border membrane (BBM) - associated enzymes such as the sucrase, lactase, maltase and alkaline phosphatase. Aspirin treatment also led to a decrease in the microviscosity in the native as well as the benzyl alcohol treated membrane which might be due to the lipid peroxidative damage in the membrane. Physical correlation of the membrane oxidative damage was evident as the Fourier Transformation Infra Red (FTIR) study of the Aspirin treated membrane, which include an increased proportion of gauche to trans conformer, shift in the methylene C-H asymmetric and symmetric stretching frequencies, C = O double bond stretching, NH bending, antisymmetric (N)-CH3 bending, C-N stretching and antisymmetric CNC stretching while there was no change in the CH2 wagging and twisting as well as in NH-bending amide bond I and II. Aspirin treatment also caused an alteration in the glucose and histidine transport, as evident by a decreased Vmax value while the apparent Km remaining unchanged in the control and Aspirin-treated animals confirming that there was no change in the substrate affinity constant of the membrane transport proteins for the glucose and the basic amino acid, although the rate of transport decreased considerably. There was a decrease noted in the energy of activation of glucose and histidine transport when studied at different temperature but no change in the temperature of phase transition in the BBM with Aspirin treatment, thus implying that perhaps the thermotropic phase transition in the membrane may have relatively little effect on the transport processes. The result suggests an underlying molecular mechanism indicating the implied membrane damage by Aspirin, an important member of the non-steroidal antiinflammatory drug (NSAID) family which could possibly through an oxidative damage may lead to an altered molecular structure, physical state and biological

  12. The role of aspirin in post-polypectomy bleeding – a retrospective survey

    Directory of Open Access Journals (Sweden)

    Pan Antony

    2012-10-01

    Full Text Available Abstract Background Bleeding following colonoscopic polypectomy is a common complication and has been reported to occur in up to 6.1% of patients. Several risk factors have been discussed but their overall contribution to post-polypectomy bleeding remains controversial. The aim of the study was to determine the rate of post polypectomy bleeding and to analyse the role of potential risk factors especially the role of aspirin. Methods We conducted a retrospective cohort study of all patients who underwent polypectomy at Dunedin Hospital, New Zealand between January 2007 and June 2009. Results During the study period, 514 patients underwent colonoscopy with polypectomy and a total of 1502 polyps were removed. From further analysis we excluded 21 patients; 15 patients had surgery immediately after colonoscopy for the diagnosis of colorectal carcinoma and 6 patients presented with symptoms of an acute lower gastrointestinal bleed prior to colonoscopy. Of the remaining 493 patients, 11 patients (2.2% presented with post-polypectomy bleeding within 30 days of the investigation of which 8 were on aspirin. In total 145 patients were taking aspirin prior to colonoscopy and 348 patients were not taking aspirin. The use of aspirin was associated with an increased prevalence of post-polypectomy bleeding (OR=6.72, 95% C.I. 1.76 to 25.7. Interestingly, the use of non-steroidal anti-inflammatory drugs (NSAIDs was not associated with risk of bleeding after polypectomy (OR=2.82, 95% C.I, 0.34 to 23.3. Conclusion Our study confirmed a significantly increased risk of lower gastrointestinal bleeding following polypectomy in patients taking aspirin. We would recommend approaching the patient on aspirin coming forward for a colonoscopy with potential polypectomy with caution.

  13. Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study.

    Science.gov (United States)

    Mc Menamin, Úna C; Cardwell, Chris R; Hughes, Carmel M; Murray, Liam J

    2017-04-01

    Preclinical evidence from breast cancer cell lines and animal models suggest that aspirin could have anti-cancer properties. In a large breast cancer patient cohort, we investigated whether post-diagnostic low-dose aspirin use was associated with a reduction in the risk of breast cancer-specific mortality. We identified 15,140 newly diagnosed breast cancer patients within the Scottish Cancer Registry. Linkages to the Scottish Prescribing Information System provided data on dispensed medications and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% CIs for breast cancer-specific and all-cause mortality by post-diagnostic low-dose aspirin use. HRs were adjusted for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of statins. Secondary analysis investigated the association between pre-diagnostic low-dose aspirin use and breast cancer-specific and all-cause mortality. Post-diagnostic users of low-dose aspirin appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.44, 95% CI 1.26, 1.65) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.92, 95% CI 0.75, 1.14). Findings were similar in analysis by increasing duration of use and in analysis of pre-diagnostic low-dose aspirin use. In this large nationwide study of breast cancer patients, we found little evidence of an association between post-diagnostic low-dose aspirin use and cancer-specific mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Aspirin therapy discontinuation and intraoperative blood loss in spinal surgery: a systematic review.

    Science.gov (United States)

    Cheng, Ann; Poon, Michael T C; Demetriades, Andreas K

    2018-01-23

    The purpose of this study was to determine the effect of aspirin therapy discontinuation on intraoperative blood loss in spinal surgery. We searched Medline and Google Scholar 1946 to January 2017 inclusive for case-control studies, cohort studies, and controlled trials reporting intraoperative blood loss during spinal surgery in patients on pre-operative aspirin. Other outcome measures reported in the eligible studies were collected as secondary outcomes. Two reviewers independently screened and extracted data from each study. Five retrospective cohort and two case-control studies were eligible for inclusion. Of the 1173 patients identified, 587 patients were never on aspirin (Ax), 416 patients had aspirin discontinued before surgery (Ad), ranging from 3 to 10 days, and 170 patients had aspirin continued until surgery (Ac). Six out of seven studies reported no statistically significant difference in intraoperative blood loss irrespective of aspirin discontinuation. Meta-analysis was not possible due to high risk of bias. Of the secondary outcome measures, operative time and postoperative complications were most commonly reported. One of six studies evaluating operative time reported a significantly longer operative time in the Ad group compared with the Ac group. The overall risk of postoperative haematoma in Ax, Ad, and Ac groups is 0.2% (n/N = 1/587), 0.2% (n/N = 1/416), and 1.2% (n/N = 2/170), respectively. No study reported a statistically significant difference in postoperative complications. There is no strong evidence demonstrating a difference in intraoperative blood loss, operation time, and postoperative complications, irrespective of aspirin discontinuation. This is, however, based on a limited number of studies and higher-quality research is required to answer this question with a higher degree of confidence.

  15. Aspirin and clopidogrel high on-treatment platelet reactivity and genetic predictors in peripheral arterial disease.

    Science.gov (United States)

    Yeo, Khung-Keong; Armstrong, Ehrin J; López, Javier E; Chen, Debbie C; Westin, Gregory G; Li, Chin-Shang; Anderson, David; Hua, Amy; Singapuri, Anil; Amsterdam, Ezra A; Chiamvimonvat, Nipavan; Laird, John R

    2018-02-07

    Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse cardiovascular outcomes in patients with peripheral arterial disease (PAD). The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear. This is a prospective cohort study of patients with angiographically documented PAD involving carotid and lower extremity arteries. Aspirin and clopidogrel HoTPR (using the VerifyNow Assay) and associated genetic predictors were compared to clinical outcomes. The primary end-point was a composite of major adverse cardiovascular events: all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb-loss in patients who underwent extremity intervention. The study was stopped prematurely due to slow patient enrolment. Of 195 patients enrolled, the primary analysis was performed in 154 patients taking both drugs. Aspirin HoTPR was present in 31 (20%) and clopidogrel HoTPR in 76 (49%) patients. There was a trend toward more primary composite outcome events with PRU ≥ 235 (52% freedom-from-event rate vs. 70% for PRU < 235; P = 0.09). TVR was higher in those with PRU ≥ 235 (20 vs. 6%, unadjusted P = 0.02). There was no association between aspirin HoTPR and combined outcomes. Single nucleotide polymorphisms in serum paraoxonase/arylesterase 1 (PON1) gene was associated with aspirin HoTPR (P = 0.005) while SNP in phospholipase A2, group III (PLA2G3) gene was associated with clopidogrel HoTPR (P = 0.002). Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD. © 2018 Wiley Periodicals, Inc.

  16. Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to