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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 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.

  3. 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 ...

  4. 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...

  5. 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.

  6. 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. PMID:27561771

  7. 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 ...

  8. Aspirin Often Wrongly Prescribed for Atrial Fibrillation

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159459.html Aspirin Often Wrongly Prescribed for Atrial Fibrillation Blood thinners -- not aspirin -- dramatically cut the risk of stroke, researchers say ...

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

    NARCIS (Netherlands)

    A. Squizzato; T. Keller; E. Romualdi; S. Middeldorp

    2011-01-01

    Background 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. Objectives To quantify the benefit and harm

  10. [Aspirin suppresses microsatellite instability].

    Science.gov (United States)

    Wallinger, S; Dietmaier, W; Beyser, K; Bocker, T; Hofstädter, F; Fishel, R; Rüschoff, J

    1999-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit cancer preventive effects and have been shown to induce regression of adenomas in FAP patients. In order to elucidate the probable underlying mechanism, the effect of NSAIDs on mismatch repair related microsatellite instability was investigated. Six colorectal cancer cell lines all but one deficient for human mismatch repair (MMR) genes were examined for microsatellite instability (MSI) prior and after treatment with Aspirin or Sulindac. For rapid in vitro analysis of MSI a microcloning assay was developed by combining Laser microdissection and random (PEP-) PCR prior to specific MSI-PCR. Effects of NSAIDs on cell cycle and apoptosis were systematically investigated by using flow cytometry and cell-sorting. MSI frequency in cells deficient of MMR genes (hMSH2, hMLH1, hMSH6) was markedly reduced after long-term (> 10 weeks) NSAID treatment. This effect was reversible, time- and concentration dependent. However, in the hPMS2 deficient endometrial cancer cell line (HEC-1-A) the MSI phenotype kept unchanged. According to cell sorting, non-apoptotic cells were stable and apoptotic cells were unstable. These results suggest that aspirin/sulindac induces a genetic selection for microsatellite stability in a subset of MMR-deficient cells and may thus provide an effective prophylactic therapy for HNPCC related colorectal carcinomas.

  11. Aspirin for the next generation

    OpenAIRE

    Henderson, Nick; Smith, Tom

    2013-01-01

    First used as an analgesic and antipyretic, investigations into aspirin’s anti-inflammatory effects led to its establishment in 1974 as a drug that altered the activity of platelets to influence the course and incidence of myocardial infarction and cerebrovascular disease. It became the standard in treatment and prevention of vascular disorders. The 25th International Scientific Meeting on aspirin held at the Royal College of Physicians in London on 24th October 2012 took aspirin into fresh f...

  12. 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 ...

  13. 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,

  14. Time for aspirin : blood pressure and reactivity

    NARCIS (Netherlands)

    Bonten, Tobias Nicolaas

    2014-01-01

    Aspirine wordt door miljoenen mensen wereldwijd gebruikt ter preventie van hart- en vaatziekten. De meeste mensen nemen aspirine 's ochtends in, maar het optimale inname tijdstip is niet bekend. In dit proefschrift is onderzocht voordelig is om aspirine 's avonds in te nemen in plaats van 's ochtend

  15. 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).

  16. 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 ...

  17. Aspirin in patients undergoing noncardiac surgery

    DEFF Research Database (Denmark)

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

    2014-01-01

    ,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......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...... 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...

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

    OpenAIRE

    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; van Oijen, M.G.H.

    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 volunteers, but at lower cardiovascular doses no beneficial effects were observed. Aim To compare the prevalence of self-reported gastrointestinal symptoms between low-dose plain aspirin and ECC. Methods A...

  19. Talk with Your Doctor about Taking Aspirin Every Day

    Science.gov (United States)

    ... En español Talk with Your Doctor about Taking Aspirin Every Day Browse Sections The Basics Overview Benefits ... and Risks What are the benefits of taking aspirin daily? Aspirin can reduce your risk of heart ...

  20. An evaluation of different doses of soluble aspirin and aspirin tablets in postoperative dental pain.

    Science.gov (United States)

    Holland, I S; Seymour, R A; Ward-Booth, R P; Ord, R A; Lim, K L; Hoare, R C

    1988-01-01

    1. The efficacy of three different single doses (600, 900 and 1200 mg of soluble aspirin and aspirin tablets) was determined in a randomized placebo-controlled parallel study in 140 patients (70 females) with postoperative pain after removal of impacted third molars. 2. Patients treated with soluble aspirin 600 mg, 900 mg, 1200 mg and aspirin tablet 1200 mg reported significantly less pain (P less than 0.01) throughout the investigation period than those treated with placebo. 3. Overall pain scores after treatment with aspirin tablets 600 and 900 mg did not differ significantly from those after treatment with placebo (P greater than 0.05). 4. On a comparative dose basis, soluble aspirin was significantly more potent (P less than 0.05) than aspirin tablets. PMID:3190996

  1. CALCIUM ENHANCES ANTIINFLAMMATORY ACTIVITY OF ASPIRIN

    Directory of Open Access Journals (Sweden)

    Choksi Krishna

    2011-03-01

    Full Text Available The objective of present study is to evaluate the effects of calcium carbonate and calcium gluconate on acute and subacute inflammation and to study their possible interactions with Aspirin. Calcium carbonate (10 mg/kg and calcium gluconate (5 mg/kg were administered individually and also co-administered along with sub therapeutic dose Aspirin (50mg/kg to study their interaction. The inflammation was induced by carrageenan or a foreign body. Both calcium carbonate and calcium gluconate could not show significant anti-inflammatory activity on their own in acute as well as subacute inflammation models. Aspirin at sub-anti-inflammatory dose (50mg/Kg when co-administered along with calcium salts produced the significant anti-inflammatory response which was comparable to anti-inflammatory response of aspirin at therapeutic dose (200mg/Kg. Also co-adminostration minimized the gastro-toxicity of aspirin.

  2. Aspirin and cancer: has aspirin been overlooked as an adjuvant therapy?

    OpenAIRE

    Langley, R E; Burdett, S.; Tierney, J F; Cafferty, F; Parmar, M K B; Venning, G

    2011-01-01

    Aspirin inhibits the enzyme cyclooxygenase (Cox), and there is a significant body of epidemiological evidence demonstrating that regular aspirin use is associated with a decreased incidence of developing cancer. Interest focussed on selective Cox-2 inhibitors both as cancer prevention agents and as therapeutic agents in patients with proven malignancy until concerns were raised about their toxicity profile. Aspirin has several additional mechanisms of action that may contribute to its anti-ca...

  3. Aspirin

    Science.gov (United States)

    ... which the immune system attacks the joints and organs and causes pain and swelling) and certain other ... risk of blood clots in patients who have artificial heart valves or certain other heart conditions and ...

  4. Aspirin

    Science.gov (United States)

    ... LIBRARY Hello, Guest! My alerts Sign In Join Facebook Twitter Home About this Journal Editorial Board General Statistics Circulation Cover Doodle → Blip the Doodle Go Red For Women's Issue Information for Advertisers Author Reprints Commercial Reprints Customer Service and Ordering ...

  5. Tolerabilidad de Aspirina Aspirin tolerability

    Directory of Open Access Journals (Sweden)

    M. R. Moreno-Brea

    2005-09-01

    ácter atero-trombótico. El síndrome de Reye es un cuadro de rara presentación, pero de graves consecuencias, que contraindica el uso de Aspirina en niños o adolescentes con fiebre o ciertas infecciones virales. Dada la extensa utilización de Aspirina, puede ser considerado un fármaco bien tolerado en general, cuyas reacciones adversas más graves deben ser objeto de una especial farmacovigilancia, prestando especial atención a la población de mayor riesgo. Esta situación aconseja, asimismo, la puesta en marcha de programas de educación sanitaria sobre el uso de los analgésicos. En todo caso, Aspirina sigue siendo un fármaco de referencia con una importante potencialidad terapéutica derivada de los beneficios inherentes a su uso.The acetylsalicylic acid (ASA is a widely used drug worldwide, both as prescription and over-the-counter products, and both as the only active drug or associated to other drugs in fixed doses. It is used either occasionally for the management of acute symptomatic conditions, or continuously in prophylactic anti-thrombotic regimes. Its profile of adverse reactions and potential interactions with other drugs makes it very important to have a well-tolerated and safe substance. Both things are particularly relevant when the population exposed to this drug has reached a certain age, since its specific features may increase its susceptibility to side effects and complications. Aspirin shares the general profile of adverse reactions of the NSAIs and it is considered as its prototype. When acutely administered, the incidence of side effects, most of them light, are the same as with other analgesics. Gastrointestinal effects are the most frequent of all and several risk factors have been identify for the development of severe gastrointestinal complications. These risk factors must be considered along with the need to take prophylactic measures in order to reduce the morbi-mortality. In recent years, special attention has been devoted to

  6. CALCIUM ENHANCES ANTIINFLAMMATORY ACTIVITY OF ASPIRIN

    OpenAIRE

    Choksi Krishna; Shenoy Ashoka M; A. R. Shabharaya; Lala Minaxi

    2011-01-01

    The objective of present study is to evaluate the effects of calcium carbonate and calcium gluconate on acute and subacute inflammation and to study their possible interactions with Aspirin. Calcium carbonate (10 mg/kg) and calcium gluconate (5 mg/kg) were administered individually and also co-administered along with sub therapeutic dose Aspirin (50mg/kg) to study their interaction. The inflammation was induced by carrageenan or a foreign body. Both calcium carbonate and calcium gluconate cou...

  7. 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.

  8. Does high serum uric acid level cause aspirin resistance?

    Science.gov (United States)

    Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun

    2016-06-01

    In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage. PMID:26656902

  9. 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

  10. Molecular targets of aspirin and cancer prevention.

    Science.gov (United States)

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

    2014-07-01

    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

  11. Aspirin, cyclooxygenase inhibition and colorectal cancer.

    Science.gov (United States)

    Sostres, Carlos; Gargallo, Carla Jerusalen; Lanas, Angel

    2014-02-01

    Colorectal cancer (CRC) is the third most common type of cancer worldwide. Screening measures are far from adequate and not widely available in resource-poor settings. Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC. Increasing evidence from epidemiological studies, randomized clinical trials and basic science supports the effectiveness of aspirin, as well as other non-steroidal anti-inflammatory drugs, for chemoprevention of several types of cancer, including CRC. This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality. The detectable benefit of daily low-dose aspirin (at least 75 mg), as used to prevent cardiovascular disease events, strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy. Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in 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 (about 20 minutes); nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.

  12. Aspirin, cyclooxygenase inhibition and colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Carlos; Sostres; Carla; Jerusalen; Gargallo; Angel; Lanas

    2014-01-01

    Colorectal cancer(CRC)is the third most common type of cancer worldwide.Screening measures are far from adequate and not widely available in resourcepoor settings.Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC.Increasing evidence from epidemiological studies,randomized clinical trials and basic science supports the effectiveness of aspirin,as well as other non-steroidal anti-inflammatory drugs,for chemoprevention of several types of cancer,including CRC.This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality.The detectable benefit of daily low-dose aspirin(at least 75 mg),as used to prevent cardiovascular disease events,strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy.Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase(COX)-1 in platelets(in pre-systemic circulation)while causing alimited and rapidly reversible inhibitory effect on COX-2and/or COX-1 expressed in nucleated cells.Aspirin has a short half-life in human circulation(about 20 minutes);nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours,while platelets do not.COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.

  13. Aspirin and esophageal squamous cell carcinoma: bedside to bench

    Institute of Scientific and Technical Information of China (English)

    Li Peng; Cheng Rui; Zhang Shutian

    2014-01-01

    Objective To review the advances of studies on clinical results of aspirin's chemopreventive effect against esophageal squamous cell carcinoma (ESCC) and evidences for mechanisms of the antitumoural effects of aspirin in experimental research.Data sources A comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as aspirin and esophageal cancer.Study selection Articles associated with aspirin and esophageal cancer are analyzed.Results This review focuses on the current evidence for use of aspirin as a chemopreventive agent in ESCC.Aspirin is the most widely used among all nonsteroidal anti-inflammatory drugs (NSAIDs),which is cheap and acceptable to patients.Several observational results provide the further investigation of prevention and therapy of aspirin or similar drugs in esophageal cancer.Data from case control studies,cohort studies and randomized controlled trials (RCTs) also give some support of a beneficial role of aspirin on ESCC.Experimental data suggest that aspirin may prevent carcinogenesis of ESCC by favorably affecting proliferation,apoptosis,or other as yet unidentified growth-regulating processes.But the mechanism by which aspirin influence on esophageal squamous cell carcinoma needs further investigation.Conclusion A wealth of evidences ranging from clinical data to experimental results are building to suggest that aspirin has significant effects in reducing both the incidence and mortality of ESCC.

  14. Aspirin metabolism and efficacy in postoperative dental pain.

    Science.gov (United States)

    Seymour, R A; Williams, F M; Ward, A; Rawlins, M D

    1984-01-01

    Aspirin 1200 mg was compared with placebo in a randomised, double-blind, crossover study in 15 patients with postoperative pain after removal of impacted lower third molars. Over a 5 h investigation period, patients reported significantly less pain (P less than 0.01) after treatment with aspirin, than after treatment with placebo. Peak concentrations of aspirin occurred at 15 min after dosage. Significant negative correlations were observed between plasma aspirin esterase activity and both AUC aspirin (r = -0.904, P less than 0.001) and AUC analgesia (r = -0.91, P less than 0.001). Similarly, a significant correlation was observed between AUC aspirin and AUC analgesia (r = 0.96, P less than 0.001). Evidence from this study would suggest that an individual's pain relief in postoperative dental pain is determined by the rate of aspirin hydrolysis to salicylate. PMID:6378231

  15. 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).

  16. 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.

  17. 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

  18. Antiplatelet therapy: aspirin resistance and all that jazz!

    Science.gov (United States)

    Divani, Afshin A; Zantek, Nicole D; Borhani-Haghighi, Afshin; Rao, Gundu H R

    2013-01-01

    Platelets play a crucial role in the pathogenesis of atherosclerosis, thrombosis, and stroke. Aspirin used alone or in combination with other antiplatelet drugs has been shown to offer significant benefit to patients at high risk of vascular events. Resistance to the action of aspirin may decrease this benefit. Aspirin resistance has been defined by clinical and/or laboratory criteria; however, detection by laboratory methods prior to experiencing a clinical event will likely provide the greatest opportunity for intervention. Numerous laboratory methods with different cutoff points have been used to evaluate the resistance. Noncompliance with aspirin treatment has also confounded studies. A single assay is currently insufficient to establish resistance. Combinations of results to confirm compliance and platelet inhibition may identify "at-risk" individuals who truly have aspirin resistance. The most effective strategy for managing patients with aspirin resistance is unknown; however, studies are currently underway to address this issue.

  19. Formulation and evaluation of novel aspirin nanoparticles loaded suppositories

    Institute of Scientific and Technical Information of China (English)

    Ravi Sankar V.; Dhachinamoorthi D.; Chandra Shekar K.B.

    2013-01-01

    The main objective of the present work is to design aspirin nanoparticles loaded suppositories which will reduce the side effects caused by aspirin suppositories.Aspirin nanoparticles were prepared initially based on ionic-gelation mechanism and lyophilized.The prepared nanoparticles were evaluated,and the results confirmed that Fa9 formulation was the best with greater drug entrapment efficiency.Aspirin suppositories were prepared in order to investigate the best base composition.The prepared suppositories were evaluated and FS1,FS3,FS4,FS8,FS11,and FS12 were proved to be the best base compositions based on dissolution performed.The lyophilized aspirin nanoparticles of Fa9 were used to prepare aspirin nanoparticles loaded suppositories.The in vitro results revealed that Fas 11 was the best formulation.

  20. 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 ... any pharmacy, grocery or convenience store and buy aspirin without a prescription. The Drug Facts label on ...

  1. Talk With Your Health Care Provider About Taking Aspirin to Prevent Heart Attack

    Science.gov (United States)

    ... q What are my chances of having a heart attack? q Would I benefit from taking aspirin? q ... Health Care Provider About Taking Aspirin to Prevent Heart Attacks Did you know that aspirin can be an ...

  2. Aspirin as Primary Prevention of Acute Coronary Heart Disease Events

    OpenAIRE

    Glasser, Stephen P.; Hovater, Martha; Brown, Todd M.; Howard, George; Safford, Monika M.

    2014-01-01

    Background/Objective Aspirin for primary prophylaxis is controversial. This study evaluated associations between prophylactic aspirin use and incident acute coronary heart disease (CHD) events. Methods and Results The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study was accessed for aspirin use examining black and white hazards for incident CHD, for men and women, each adjusting incrementally for sampling, sociodemographics, and CHD risk factors. Stratified models exami...

  3. Critical overview of the benefits and harms of aspirin

    OpenAIRE

    Chun Shing Kwok; Loke, Yoon K.

    2010-01-01

    Aspirin is widely used internationally for a variety of indications, with the most prominent one being that of cardiovascular disease. However, aspirin has also been proposed as a treatment option in a diverse range of conditions such as diabetes mellitus, cancer prevention, and obstetrics. In our overview, we critically appraise the current evidence from recent systematic reviews and meta-analyses covering the benefits of aspirin across these conditions. We also look at evidence that some pa...

  4. Interactions of m-xylene and aspirin metabolism in man.

    OpenAIRE

    Campbell, L; Wilson, H.K.; Samuel, A. M.; Gompertz, D

    1988-01-01

    In a series of experiments to investigate interactions between industrial solvents and common medications the interaction between m-xylene and aspirin was studied. As both these substances are metabolised and excreted as glycine conjugates there would possibly be competition for this conjugation pathway. Five male volunteers were exposed on separate occasions to m-xylene by inhalation (100 ppm), aspirin (1500 mg) by mouth, and m-xylene and aspirin together under controlled conditions in an ex...

  5. Phospho-Aspirin (MDC-22) Prevents Pancreatic Carcinogenesis in Mice.

    Science.gov (United States)

    Mattheolabakis, George; Papayannis, Ioannis; Yang, Jennifer; Vaeth, Brandon M; Wang, Ruixue; Bandovic, Jela; Ouyang, Nengtai; Rigas, Basil; Mackenzie, Gerardo G

    2016-07-01

    Pancreatic cancer is a deadly disease with a dismal 5-year survival rate of <6%. The currently limited treatment options for pancreatic cancer underscore the need for novel chemopreventive and therapeutic agents. Accumulating evidence indicates that aspirin use is associated with a decreased risk of pancreatic cancer. However, the anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we developed phospho-aspirin (MDC-22), a novel derivative of aspirin, and evaluated its chemopreventive efficacy in preclinical models of pancreatic cancer. Phospho-aspirin inhibited the growth of human pancreatic cancer cell lines 8- to 12-fold more potently than aspirin; based on the 24-hour IC50 values. In a Panc-1 xenograft model, phospho-aspirin, at a dose of 100 mg/kg/d 5 times per week for 30 days, reduced tumor growth by 78% (P < 0.01 vs. vehicle control). Furthermore, phospho-aspirin prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. In p48-Cre;Kras(G12D) mice, cerulein treatment (6 hourly injections two times per week for 3 weeks) led to a significant increase in ductal metaplasia, replacing the majority of the exocrine compartment. Administration of phospho-aspirin 100 mg/kg/day five times per week for 21 days (starting on the first day of cerulein injection) inhibited the acinar-to-ductal metaplasia, reducing it by 87% (P < 0.01, vs. cerulein-treated control). Phospho-aspirin appeared to be safe, with the animals showing no signs of toxicity during treatment. Mechanistically, phospho-aspirin inhibited EGFR activation in pancreatic cancer, an effect consistently observed in pancreatic cancer cells, primary acinar explants and in vivo In conclusion, our findings indicate that phospho-aspirin has strong anticancer efficacy in preclinical models of pancreatic cancer, warranting its further evaluation. Cancer Prev Res; 9(7); 624-34. ©2016 AACR. PMID:27138793

  6. 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…

  7. 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 reduc...

  8. 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

  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. PMID:26201059

  10. Use of Aspirin postdiagnosis improves survival for colon cancer patients

    NARCIS (Netherlands)

    E. Bastiaannet (Esther); K. Sampieri (K.); O.M. Dekkers (Olaf); A.J. de Craen (Anton); M.P.P. van Herk-Sukel (Myrthe); V.E.P.P. Lemmens (Valery); C.B.M. van den Broek (Colette); J.W.W. Coebergh (Jan Willem); R.M.C. Herings (Ron); C.J.H. van de Velde (Cornelis); R. Fodde (Riccardo); G.-J. Liefers (Gerrit-Jan)

    2012-01-01

    textabstractBackground: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based stud

  11. Critical Overview on the Benefits and Harms of Aspirin

    Directory of Open Access Journals (Sweden)

    Chun Shing Kwok

    2010-05-01

    Full Text Available Aspirin is widely used internationally for a variety of indications, with the most prominent one being that of cardiovascular disease. However, aspirin has also been proposed as a treatment option in a diverse range of conditions such as diabetes mellitus, cancer prevention, and obstetrics. In our overview, we critically appraise the current evidence from recent systematic reviews and meta-analyses covering the benefits of aspirin across these conditions. We also look at evidence that some patients may not derive benefit due to the concept of aspirin resistance. Aspirin is also associated with the potential for significant harm, principally from haemorrhagic adverse events. We critically appraise the threat of haemorrhagic complications, and weigh up these risks against that of any potential benefit.

  12. EFFECT OF EDTA ON GASTRIC MUCOSAL LESION INDUCED BY ASPIRIN

    Directory of Open Access Journals (Sweden)

    M.A FESHARAKI M.A

    2002-06-01

    Full Text Available Introduction. Gastric ulcer is a multifactorial disease, which its pathophysioligy has not been clear yet. The aim of this study was to obtain the prophylactic effects of EDTA on Aspirin induced gastric mucosal lesions. Methods. In fasted male rats the effect of a single oral dose of the EDTA was evaluated in the following test systems: combination of 1 ml EDTA 1.5% + 300 mg/kg aspirin and 1 ml EDTA 1.5%, 2.5%, 5% and 7.5% 30 minutes before 300 mg/kg aspirin. Then the gastric mucosal lesions were assessed microscopically and marcroscopically. Results. EDTA at different doses reduced macroscopic and microscpic gastric mucosal lesion induced by aspirin. Discussion. Combination therapy of EDTA and aspirin has distinct advantages regard to both low gastrointestinal toxicity and restored therapeutic activity.

  13. 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. PMID:25789542

  14. Aspirin Plays Dual Role in Helping Heart

    Institute of Scientific and Technical Information of China (English)

    余玲梅

    2002-01-01

    贵刊多次介绍“百年老药”aspirin(阿斯匹林,解热镇痛药,又称“乙酰水杨酸”)的神奇作用,我读了贵刊的介绍后,也开始服用aspirin,收到了意想不到的效果。现在,我上网时,对aspirin的报道特别留心。今日又在网上读到此文,特地加注后,发你们。文中有两个单词:interleukin-1(IL-1)/endothelialfunction,查阅了许多词典,仍不得其解。好在紧接其后的同谓语对这两个词作了解释。前者的以意思是:a blood of chemical associated with inflammation(一种炎 症有关的血液化学物质);后者是:the ability of the blood vessels to expand(血管扩张的能力)这两个词与新发现的aspirin两个功能有关,一是,能增加抗炎症作用,二是令血管得以扩张。】

  15. CORRELATION OF CLINICAL AND LABORATORY ASPIRIN RESISTANCE: A PILOT STUDY

    Directory of Open Access Journals (Sweden)

    PRASHANT C K,SUDHA,MURALIDHAR, LAXMINARAYANA,ANNAMMA KURIEN,ASHWIN KAMATH

    2013-09-01

    Full Text Available Aspirin resistance may be biochemical or clinical. Data related to the presence of aspirinresistance in the Indian population is scarce. We conducted a cross sectional study toaddress the issue of clinical aspirin non responsiveness and to assess the associationbetween inhibition of platelet aggregation, clinical risk factors and occurrence of vascularevents. We studied platelet aggregation by optical aggregometry in 20 patients on aspirin.No patient was found to be aspirin-resistant on the basis of previously defined criteria.This led us to relook at the current cut offs for resistance, and an analysis of 60 normalpatients showed lower cut off values suggesting ethnic variability. The data wasreanalyzed using these cutoffs. An association between poor clinical aspirin response,older age, male sex, smoking and dyslipidemia was found, suggesting a trend, though notsignificant. 25% of patients had vascular events on aspirin suggesting clinical aspirinresistance. A lower cut off value for aspirin resistance in normal Indians may be neededto detect true prevalence of this entity. In patients with multiple atherothrombotic riskfactors lab detection of resistance may be useful in identifying patients with high risk forrecurrent vascular events. This may help to modify antiplatelet therapy to preventvascular events.

  16. Sex hormones alter the effect of aspirin on bleeding

    Directory of Open Access Journals (Sweden)

    Muhammad Tariq Aftab

    2013-10-01

    Full Text Available Background: Interaction of aspirin and sex hormones was investigated through bleeding time. Methods: Bleeding time in 32 males and 105 unmarried females with previous 6 normal menstrual cycles and all aged between 18 to 21 years was found by Duke’s method before and after 2 hours of aspirin administration. Phase of menstrual cycle of each female was determined by present menstrual history. Results: Bleeding time in 32 male was 69.33± 4.94 seconds and in 105 female was 73.03±1.89 seconds which were not statistically different (P>0.05.This time was increased to 107.66±4.76 seconds in males and 113.65±3.73 seconds in females after aspirin administration which were statistically different (P0.05 difference after aspirin administration with a greater effect in Follicular phase probably due to estradiol. Conclusion: Males respond to aspirin more as compared to females which is likely the effect of the drug and testosterone interaction. Similarly females in the follicular phase respond to aspirin more as compared to females in the luteal phase which may be a result of interaction of estrogen and aspirin. [Int J Basic Clin Pharmacol 2013; 2(5.000: 537-540

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

    OpenAIRE

    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; ,

    2013-01-01

    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...

  18. EFFECT OF EDTA ON GASTRIC MUCOSAL LESION INDUCED BY ASPIRIN

    OpenAIRE

    M.A FESHARAKI M.A; A SHARAITI KAMALABADI; R MOKHTARI

    2002-01-01

    Introduction. Gastric ulcer is a multifactorial disease, which its pathophysioligy has not been clear yet. The aim of this study was to obtain the prophylactic effects of EDTA on Aspirin induced gastric mucosal lesions. Methods. In fasted male rats the effect of a single oral dose of the EDTA was evaluated in the following test systems: combination of 1 ml EDTA 1.5% + 300 mg/kg aspirin and 1 ml EDTA 1.5%, 2.5%, 5% and 7.5% 30 minutes before 300 mg/kg aspirin. Then the gastric mucosal les...

  19. 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 <165 s identified patients not taking aspirin (sensitivity 0.91, specificity 1.00). A good agreement between the PFA-100 method and optical platelet aggregation was found. Within...

  20. 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...

  1. 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.

  2. Pharmacometabolomics Reveals That Serotonin Is Implicated in Aspirin Response Variability

    OpenAIRE

    Ellero-Simatos, S; Lewis, JP; Georgiades, A; Yerges-Armstrong, LM; Beitelshees, AL; Horenstein, RB; Dane, A.; Harms, AC; Ramaker, R; Vreeken, RJ; Perry, CG; Zhu, H.; Sanchez, CL; Kühn, C.; ORTEL, TL

    2014-01-01

    While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways implicated in variation of response to treatment. We profiled serum samples from healthy subjects pre- and postaspirin (14 days, 81 mg/day) using mass spectrometry. We established a strong signature of aspirin exposure independent ...

  3. Aspirin overutilization for the primary prevention of cardiovascular disease

    OpenAIRE

    VanWormer JJ; Miller AW; Rezkalla SH

    2014-01-01

    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 i...

  4. Small bowel injury in low-dose aspirin users.

    Science.gov (United States)

    Endo, Hiroki; Sakai, Eiji; Kato, Takayuki; Umezawa, Shotaro; Higurashi, Takuma; Ohkubo, Hidenori; Nakajima, Atsushi

    2015-04-01

    The use of low-dose aspirin (LDA) is well known to be associated with an increased risk of serious upper gastrointestinal complications, such as peptic ulceration and bleeding. Until recently, attention was mainly focused on aspirin-induced damage of the stomach and duodenum. However, recently, there has been growing interest among gastroenterologists on the adverse effects of aspirin on the small bowel, especially as new endoscopic techniques, such as capsule endoscopy (CE) and balloon-assisted endoscopy, have become available for the evaluation of small bowel lesions. Preliminary CE studies conducted in healthy subjects have shown that short-term administration of LDA can induce mild mucosal inflammation of the small bowel. Furthermore, chronic use of LDA results in a variety of lesions in the small bowel, including multiple petechiae, loss of villi, erosions, and round, irregular, or punched-out ulcers. Some patients develop circumferential ulcers with stricture. In addition, to reduce the incidence of gastrointestinal lesions in LDA users, it is important for clinicians to confirm the differences in the gastrointestinal toxicity between different types of aspirin formulations in clinical use. Some studies suggest that enteric-coated aspirin may be more injurious to the small bowel mucosa than buffered aspirin. The ideal treatment for small bowel injury in patients taking LDA would be withdrawal of aspirin, however, LDA is used as an antiplatelet agent in the majority of patients, and its withdrawal could increase the risk of cardiovascular/cerebrovascular morbidity and mortality. Thus, novel means for the treatment of aspirin-induced enteropathy are urgently needed. PMID:25501289

  5. Prevalence of and risk factors for aspirin resistance in elderly patients with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    Xian-Feng Liu; Jian Cao; Li Fan; Lin Liu; Jian Li; Guo-Liang Hu; Yi-Xin Hu; Xiao-Li Li

    2013-01-01

    Objective To assess the prevalence of and related risk factors for aspirin resistance in elderly patients with coronary artery disease (CAD). Methods Two hundred and forty-six elderly patients (75.9 ± 7.4 years) with CAD who received daily aspirin therapy (≥ 75 mg) over one month were recruited. The effect of aspirin was assessed using light transmission aggregometry (LTA) and thrombelastography platelet mapping assay (TEG). Aspirin resistance was defined as ≥ 20% arachidonic acid (AA)-induced aggregation and ≥ 70% adenosine diphosphate (ADP)-induced aggregation in the LTA assay. An aspirin semi-responder was defined as meeting one (but not both) of the criteria described above. Based on the results of TEG, aspirin resistance was defined as ≥ 50% aggregation induced by AA. Results As determined by LTA, 23 (9.3%) of the elderly CAD patients were resistant to aspirin therapy; 91 (37.0%) were semi-responders. As determined by TEG, 61 patients (24.8%) were aspirin resistant. Of the 61 patients who were aspirin resistant by TEG, 19 were aspirin resistant according to LTA results. Twenty-four of 91 semi-responders by LTA were aspirin resistant by TEG. Multivariate logistic risk factor for aspirin resistance as determined by TEG. Conclusions A significant number of elderly patients with CAD are resistant to aspirin therapy. Fasting blood glucose level is closely associated with aspirin resistance in elderly CAD patients.

  6. 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 infarction, hypertension and diabetes mellitus in the RT group (p infarction and stroke in the ASA resistant RT group compared to the RT patients without ASA resistance (p infarction and hypertension was significantly higher in the non-resistant RT group than in the group of PC patients without ASA resistance (p < 0.05). These results may suggest that the elevated rate of aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

  7. 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 ... care provider can determine whether regular use of aspirin will help to prevent a heart attack or ...

  8. Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer.

    Science.gov (United States)

    Lim, Wei-Yen; Chuah, Khoon Leong; Eng, Philip; Leong, Swan Swan; Lim, Elaine; Lim, Tow Keang; Ng, Alan; Poh, Wee Teng; Tee, Augustine; Teh, Ming; Salim, Agus; Seow, Adeline

    2012-08-01

    There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31-0.81 in non-smokers; OR 0.38, 95%CI 0.16-0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.

  9. 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...

  10. Use of Aspirin postdiagnosis improves survival for colon cancer patients

    Science.gov (United States)

    Bastiaannet, E; Sampieri, K; Dekkers, O M; de Craen, A J M; van Herk-Sukel, M P P; Lemmens, V; van den Broek, C B M; Coebergh, J W; Herings, R M C; van de Velde, C J H; Fodde, R; Liefers, G J

    2012-01-01

    Background: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients. Methods: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998–2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure. Results: In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63–0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50–0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46–0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79–1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70–2.20; P<0.001). Conclusion: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of

  11. 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.

  12. Aspirin May Help Fight Prostate Cancer

    Institute of Scientific and Technical Information of China (English)

    Patricia; Reaney; 吴振华

    2000-01-01

    “阿斯匹林”问世百年,依然活力四射。它的一个新作用最近被发现:help to fight prostate(前列腺的)cancer。但是专家提醒: People should not rush to take aspirin to fight prostate cancer.He said theresearch is the first piece in a large jigsaw puzzle. 你是否能体味上句的哲理及文采?除了rush一词用得生动之外,句末的名词jigsaw puzzle也值得我们品味。jigsaw puzzle的本义是:七巧板,智力拼图玩具。 上句可译: 不要急于用阿斯匹林来治疗前列腺癌。他说目前的研究仅是一个开端而已。 你如觉得遗憾,而改译: 不要急于用阿斯匹林来治疗前列腺癌。他说目前的研究工作正如拼七巧板刚刚拼出了第一块。 读者朋友,你觉得此译美吗?你乐意接受吗?

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

    Science.gov (United States)

    Kanani, Kunal; Gatoulis, Sergio C; Voelker, Michael

    2015-01-01

    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. PMID:26247959

  14. Investigating the Effect of Aspirin on Mercury Toxicity

    Directory of Open Access Journals (Sweden)

    Fatih Polat

    2013-01-01

    Full Text Available The effect of aspirin on the toxicology of mercury was investigated by using fish. The variations between blood parameters of the fish, which were made exposed directly to mercury solutions prepared at certain concentrations (500 μg/L, 250 μg/L, 125 μg/L, 62.5 μg/L, and 31.25 μg/L, and blood parameters of the fish, which were made exposed to mercury at the same concentrations after they had been interacting with aspirin, were investigated. At the end of the study, increases in blood parameters were observed depending on the increases in mercury concentration. Statistically significant variations were observed in blood parameters of the fish, which were made exposed to mercury at the same concentrations after they had been interacting with aspirin, compared to blood parameters of the fish, which were made exposed directly to mercury (. It was found that aspirin has caused significant increases in especially the levels of serum aspartate aminotransferase and alanine aminotranspherase and significant decreases in cortisol and glucose levels among to blood parameters. It was concluded that aspirin alters the toxic effect of mercury.

  15. 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.

  16. Safety of 12 core transrectal ultrasound guided prostate biopsy in patients on aspirin

    OpenAIRE

    Pawan Vasudeva; Niraj Kumar; Anup Kumar; Harbinder Singh; Gaurav Kumar

    2015-01-01

    ABSTRACT Objective: To prospectively assess safety outcome of TRUS guided prostate biopsy in patients taking low dose aspirin. Materials and methods: Consecutive patients, who were planned for 12 core TRUS guided prostate biopsy and satisfied eligibility criteria, were included in the study and divided into two Groups: Group A: patients on aspirin during biopsy, Group B: patients not on aspirin during biopsy, including patients in whom aspirin was stopped prior to the biopsy. Parameters inclu...

  17. 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 recomme

  18. 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...

  19. 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 or of...

  20. Comparison of hyperuricemia in type 2 diabetics on low dose aspirin and not on low dose aspirin

    International Nuclear Information System (INIS)

    Objective: To compare the frequency of hyperuricemia in type 2 diabetes patients who are taking low dose aspirin with those patients who are not taking low dose aspirin. Study design: Quasi experimental study. Place and duration of study: This study was carried out at Military Hospital Rawalpindi for a period of two years (June 2006-May 2008). Patients and Methods: Sixty diabetic patients were selected who were taking low dose aspirin comparing group A and sixty diabetic patients who were not taking aspirin were placed in group B. These patients were selected from the OPD through non probability convenience sampling. All these patients were being followed up in medical outpatient quite regularly on fort-nightly basis. Data had been collected through a carefully designed questionnaire. Results: In group A, 90% of the patients had uric acid less than 445 micro mol/l and 10% of the patients had uric acid more than 445micro mol/l. Whereas in group B 100% of the patients had uric acid less than 445umol/l, there was a statistically significant difference between the two groups (p< 0.05). Conclusion: Aspirin in low doses cause hyperuricemia and regular monitoring of uric acid is mandatory to prevent its adverse effects. (author)

  1. 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.

  2. 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.

  3. Aspirin use for primary prevention in elderly patients.

    Science.gov (United States)

    Terrosu, Pierfranco

    2016-01-01

    The net clinical benefit of aspirin in primary prevention is uncertain as the reduction in occlusive events needs to be balanced against the increase in gastro-intestinal and cerebral bleedings. The meta-analysis of ATT (Anti Thrombotic Trialists) Collaboration in 2009 showed that aspirin therapy in primary prevention was associated with 12% reduction in cardio-vascular events, due mainly to a reduction in non-fatal myocardial infarction (0.18% vs 0.23% per year, pheart attack and stroke. As a consequence, it is important consider both likelihoods of benefits as well as harm within the lifespan and functioning of the person. The older people who most likely benefit from aspirin in primary prevention are those at higher cardio-vascular risk, with preserved functional abilities, low comorbidity, low risk of bleeding and a prolonged life expectancy. PMID:27374042

  4. Investigating the Effect of Aspirin on Mercury Toxicity

    OpenAIRE

    Fatih Polat; Tarık Dal

    2013-01-01

    The effect of aspirin on the toxicology of mercury was investigated by using fish. The variations between blood parameters of the fish, which were made exposed directly to mercury solutions prepared at certain concentrations (500 μg/L, 250 μg/L, 125 μg/L, 62.5 μg/L, and 31.25 μg/L), and blood parameters of the fish, which were made exposed to mercury at the same concentrations after they had been interacting with aspirin, were investigated. At the end of the study, increases in blood paramet...

  5. Impairment of aspirin antiplatelet effects by non-opioid analgesic medication

    Institute of Scientific and Technical Information of China (English)

    Amin; Polzin; Thomas; Hohlfeld; Malte; Kelm; Tobias; Zeus

    2015-01-01

    Aspirin is the mainstay in prophylaxis of cardiovascular diseases. Impaired aspirin antiplatelet effects are associated with enhanced incidence of cardiovascular events. Comedication with non-opioid analgesic drugs has been described to interfere with aspirin,resulting in impaired aspirin antiplatelet effects. Additionally,nonopioid analgesic medication has been shown to enhance the risk of cardiovascular events and death. Pain is very frequent and many patients rely on analgesic drugs to control pain. Therefore effective analgesic options without increased risk of cardiovascular events are desirable. This review focuses on commonly used nonopioid analgesics,interactions with aspirin medication and impact on cardiovascular risk.

  6. 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.

  7. 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.

  8. Endothelial dysfunction in young healthy men is associated with aspirin resistance.

    Science.gov (United States)

    Doroszko, Adrian; Szahidewicz-Krupska, Ewa; Janus, Agnieszka; Jakubowski, Maciej; Turek, Aleksandra; Ilnicka, Paulina; Szuba, Andrzej; Mazur, Grzegorz; Derkacz, Arkadiusz

    2015-01-01

    The aim of this study was to investigate the relation between endothelial dysfunction and aspirin response in a young healthy population (102 men aged 18-40). Initial concentrations of the NO pathway metabolites (ADMA, l-arginine, SDMA), cardiovascular risk markers, oxidative stress markers (MDA, thiol index), sICAM1, sVCAM1, PAI-1, sE-selectin, sP-selectin, VEGF, thromboxane B2, 6-keto-PGF1α and arachidonate-induced platelet aggregation (to separate aspirin resistant from sensitive group) were measured. Flow-mediated-vasodilation (FMD) was measured before and after intravenous infusion of 16.0 g of l-arginine. Measurements were repeated following aspirin administration (75 mg/24 h) for 4 days. Both groups were homogenous regarding demographic and biochemical characteristics reflecting cardiovascular risk. Aspirin resistant subjects were characterized by lower baseline FMD and higher FMD following aspirin and l-arginine treatment, as compared to aspirin sensitive control. MDA and nitrotyrosine were greater, whereas thiol index was lower in aspirin resistant men. The sICAM1, sVCAM1, PAI-1, sE-selectin, sP-selectin and VEGF levels were similar in the analyzed groups. Thromboxane in aspirin resistant subjects was greater both at baseline and following aspirin therapy. However, a significant decrease following aspirin treatment was present in both groups. Aspirin resistance in young men is associated with endothelial dysfunction, which could be due to oxidative stress resulting from lipid peroxidation. PMID:25697550

  9. In vivo prostacyclin biosynthesis and effects of different aspirin regimens in patients with essential thrombocythaemia.

    Science.gov (United States)

    Cavalca, V; Rocca, B; Squellerio, I; Dragani, A; Veglia, F; Pagliaccia, F; Porro, B; Barbieri, S S; Tremoli, E; Patrono, C

    2014-07-01

    Essential thrombocythaemia (ET) is characterised by enhanced platelet generation and thrombosis. Once daily (od) aspirin incompletely inhibits platelet thromboxane (TX)A2 production in ET. A twice daily (bid) dosing is necessary to fully inhibit TXA2. Whether this dosing regimen affects in vivo prostacyclin (PGI2) biosynthesis is unknown. PGI2 biosynthesis was characterised in 50 ET patients on enteric-coated (EC) aspirin 100 mg od, by measuring its urinary metabolite, 2,3-dinor-6-keto-PGF1α (PGI-M). Moreover, in a crossover study 22 patients poorly responsive to standard aspirin based on serum TXB2 levels (≥4 ng/ml) were randomised to different seven-day aspirin regimens: EC aspirin 100 mg od, 100 mg bid, 200 mg od, or plain aspirin 100 mg od. PGI-M measured 24 hours after the last aspirin intake (EC, 100 mg od) was similar in patients and healthy subjects both on (n=10) and off (n=30) aspirin. PGI-M was unrelated to in vivo TXA2 biosynthesis, and not affected by EC aspirin 100 mg bid or 200 mg od as compared to EC 100 mg od. PGI2 biosynthesis in aspirin-treated ET patients appears unrelated to TXA2 biosynthesis, and not affected by an improved aspirin regimen, demonstrating its vascular safety for future trials. PMID:24671522

  10. 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.

  11. 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. PMID:26491233

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

    Institute of Scientific and Technical Information of China (English)

    Yan Wang; Ping-Ping Xu; Xin-Xia Li; Kun Nie; Ming-Fu Tuo; Bin Kong; Jian Chen

    2012-01-01

    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.

  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. SYNTHESIS OF BIOCOMPATIBLE ACRYLIC POLYMERS HAVING ASPIRIN-MOIETIES

    Institute of Scientific and Technical Information of China (English)

    LI Fumian; GU Zhongwei; FENG Xinde(S. T. Voong)

    1983-01-01

    Several new monomers, β-(acetylsalicylyloxy)ethyl methacrylate, β-(acetylsalicylyloxy)propyl methacrylate, β-(acetylsalicylyloxy)ethyl acrylate, β-hydroxy-γ-(acetylsalicylyloxy)propyl methacrylate, β-hydroxy-γ-(acetylsalicylyloxy)propyl acrylate have been synthesized from aspirin with corresponding hydroxyalkyl or glycidyl acrylates, and then polymerized by free radical initiator.

  15. Aspirin in Cardiovascular and Cerebrovascular Events: Does Market Failure Matter?

    Directory of Open Access Journals (Sweden)

    Roger L. Mendoza

    2011-01-01

    Full Text Available Problem statement: Two interrelated questions were raised for investigation in this study: (1 why may government intervene in an otherwise private transaction between physician and patient and between drug manufacturer and buyer? (2 Does government intervention make a difference in what these transacting parties would otherwise have decided or chosen in its absence? Approach: An internet literature search was performed, using query term combinations, to identify aspirin-related studies. The search yielded 51 juried publications that met our predetermined criteria for inclusion and thematic analysis. Results: Some variance exists within the surveyed literature concerning government intervention in aspirin prophylaxis for cardiovascular and cerebrovascular events, particularly heart attacks, strokes and cardiovascular death. This study identified 4 instances of market failure that offer some of the strongest theoretical and practical considerations for public policy intervention in aspirin’s pharmacological information. However, there is also indication that the sense of increased protection arising from safety regulations could stimulate risky behavior that nullifies their net protective effects or benefits. Conclusion: It is not clear either from the surveyed literature or existing economic theory if, ceteris paribus, mandatory safety information is necessary to alter or modify the marginal propensity of a physician to recommend and a patient to purchase, aspirin. The study suggested the need for policy reinforcements to any safety information regulation, if market failures are to be effectively addressed and risk compensating behavior reduced.

  16. The neuroprotection of Aspirin on Cerebral Ischemia-Reperfusion rats

    Institute of Scientific and Technical Information of China (English)

    QiuLi-ying; YuJuan; ChenChong-hong; ZhouYu

    2004-01-01

    AIM: Aspirin (aeetylsalicylic acid, ASA as a nonsteroidal anti-inflammatory drug not only has well-established efficacy in anti-thromboxane, but also has direct neuroprotective effect. In this study, we design to investigate its neuroprotective effect on focal cerebral ischemia-reperfusion injury (CIRI rats, and its effect on ATP level from occluded brain tis-

  17. The role of aspirin in colorectal cancer chemoprevention.

    Science.gov (United States)

    Singh Ranger, Gurpreet

    2016-08-01

    Considerable interest has emerged over the last decade regarding the role of aspirin in prevention of colorectal cancer. This disease is one of the commonest cancers in the Western World, therefore, the existence of a simple "everyday" agent, which could have the ability to prevent the disease, represents an invaluable opportunity clinicians may be able to exploit. Evidence from case-control and cohort studies, and recent updates of randomised controlled trials have been very encouraging-indicating benefit from long term use of aspirin at low dose. Possible mechanisms of chemoprevention include inhibition of the cyclooxygenase (COX) pathway, or COX-independent mechanisms, for example, the PIK3CA pathway, or therapy-induced senescence of cancer cells. The most serious side effect of prolonged aspirin treatment is haemorrhage, especially from the GI tract. This is likely to be less of a problem with chemoprevention at lower doses. One also needs to consider the impact if aspirin resistance, an increasingly recognised clinical entity. PMID:27289249

  18. The utilization status of aspirin for the secondary prevention of ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    KE Xian-jun; YU Yong-fei; GUO Zhen-li; XU Kang; HAl Hong; ZHANG Ai-he; JIANG Hong; PENG Hong

    2009-01-01

    Background The present study was aimed to investigate the usage of aspirin for the secondary prevention of ischemic stroke, evaluate the correlated factors, and analyze the reasons for not taking and irregularly taking aspirin. Methods The patients in this group were all stroke survivors who have formerly been diagnosed with a cerebral infarction or transient ischemic attack (TIA) in our hospital. We investigated their use of aspirin over a three-year periodfollowing their hospitalization. According to the patients' aspirin usage, they were divided into treatment and non-treatment groups. In addition, the reasons for not taking or irregularly taking aspirin were analyzed in the two groups. Results A total of 1240 patients were studied, including 367 (29.60%) in the treatment group and 873 (70.40%) cases in the non-treatment group. In addition, 201 (16.20%) cases in the treatment group had been regularly taking aspirin (50-325 mg of aspirin daily) for 1 to 3 years or longer. The results demonstrated that the main reasons for not taking aspirin in this study were related to patients' concems regarding the side effects of taking aspirin (46.45%), as well as the doctors' inadequacy in informing their patients to take aspirin (38.71%). The major reasons for patients to irregularly take aspirin were that the doctors did not notify the length of aspirin usage to their patients (41.57%), and that doctors did not prescribe aspirin upon the patients' follow-up visit (26.51%). Conclusion The most effective way to increase patient's compliance for aspirin consumption is to promote the guidelines for stroke treatment and to relay these advances in stroke therapy to the patient.

  19. Differential inhibition of tumour cell-induced platelet aggregation by the nicotinate aspirin prodrug (ST0702) and aspirin

    Science.gov (United States)

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

    2012-01-01

    BACKGROUND AND PURPOSE Tumour cell-induced platelet aggregation (TCIPA) facilitates cancer cell invasion, angiogenesis and the formation of metastatic foci. TCIPA can be modulated by pharmacological inhibitors of MMP-2 and ADP; however, the COX inhibitor aspirin did not prevent TCIPA. In this study, we have tested the pharmacological effects of a new group of isosorbide-based aspirin prodrugs on TCIPA. EXPERIMENTAL APPROACH TCIPA was induced in human platelets by mixing with human adenocarcinoma or fibrosarcoma cells under no flow and flow conditions. The release of gelatinases and P-selectin expression during TCIPA were studied by zymography and flow cytometry respectively. KEY RESULTS Tumour cells caused platelet aggregation. This aggregation resulted in the release of MMP-2 and a significant up-regulation of P-selectin on platelets, indicative of platelet activation. Pharmacological modulation of TCIPA revealed that ST0702, one of the aspirin prodrugs, down-regulated TCIPA while aspirin was ineffective. The deacetylated metabolite of ST0702, 5-nicotinate salicylate (ST0702 salicylate), down-regulated both ADP-stimulated platelet aggregation and TCIPA. CONCLUSIONS AND IMPLICATIONS Our results show that ST0702 was an effective inhibitor of TCIPA in vitro. Its deacetylated metabolite may contribute to the effects of ST0702 by inhibiting ADP-mediated TCIPA. PMID:22122360

  20. Poor awareness of preventing aspirin-induced gastrointestinal injury with combined protective medications

    Institute of Scientific and Technical Information of China (English)

    Ling-Ling Zhu; Ling-Cheng Xu; Yan Chen; Quan Zhou; Su Zeng

    2012-01-01

    AIM:To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal (GI) injury with combined protective medications.METHODS:A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital,School of Medicine,Zhejiang University.The hospital has 2300 beds and 2.5 million outpatient visits annually.Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011.Concomitant use of proton-pump inhibitors (PPIs),histamine 2-receptor antagonists (H2RA) and mucoprotective drugs (MPs) were analyzed.A defined daily dose (DDD) methodology was applied to each MP.A further investigation was performed in aspirin users on combination use of GI injurious medicines [non-steoid anti-inflammatory drugs (NSAIDs),corticosteroids and clopidogrel and warfarin] or intestinal protective drugs (misoprostol,rebamipide,teprenone and gefarnate).Data of major bleeding episodes were derived from medical records and adverse drug reaction monitoring records.The annual incidence of major GI bleeding due to low-dose aspirin was estimated for outpatients.RESULTS:Prescriptions for aspirin users receiving PPIs,H2RA and MPs (n =1039) accounted for only 3.46%of total aspirin prescriptions (n =30 015).The ratios of coadministration of aspirin/PPI,aspirin/H2RA,aspirin/MP and aspirin/PPI/MP to the total aspirin prescriptions were 2.82%,0.12%,0.40% and 0.12%,respectively.No statistically significant difference was observed in age between patients not receiving any GI protective medications and patients receiving PPIs,H2RA or MPs.The combined medication of aspirin and PPI was used more frequently than that of aspirin and MPs (2.82% vs 0.40%,P < 0.05) and aspirin/H2RA (2.82% vs 0.12%,P < 0.05).The values of DDDs of MPs in descending order were as follows:gefarnate,hydrotalcite > teprenone > sucralfate oral suspension > L-glutamine and sodium

  1. Aspirin in combination with TACE in treatment of unresectable HCC: a matched-pairs analysis

    Science.gov (United States)

    Li, Jing-Huan; Wang, Yan; Xie, Xiao-Ying; Yin, Xin; Zhang, Lan; Chen, Rong-Xin; Ren, Zheng-Gang

    2016-01-01

    Transarterial chemoembolization (TACE) is the principal therapy for unresectable hepatocellular carcinoma (HCC). However, its efficacy is currently limited owing to tumor progression or treatment failure. It has been shown that aspirin reduces the incidence of multiple malignant tumors including HCC and plays a synergistic role with chemotherapy in the treatment of colon cancer. Therefore, we aimed to investigate the adjuvant effect of aspirin on patients with unresectable HCC who underwent TACE therapy. A retrospective matched-pairs analysis was performed to evaluate the efficacy of aspirin in combination with TACE therapy. A total of 120 patients with HCC, including 60 patients treated with aspirin for treatment of cardiovascular disease, transient ischemic attack, and arthritis, and 60 paired matching HCC patients without aspirin treatment in the same period, were enrolled. Compared with non-aspirin users, patients treated with aspirin showed improved OS (P = 0.050). Specifically, patients treated with a full dose of aspirin showed prolonged OS (P = 0.027), which was an independent factor associated with OS in multivariate analysis (hazard ratio 0.498, 95% confidence interval 0.280-0.888, P = 0.018). Aspirin in combination with TACE might improve OS in patients with unresectable HCC. Thus, the impact of aspirin on patients with HCC warrants further investigation prospectively. PMID:27725915

  2. Risk analysis for aspirin and postoperative intracranial hemorrhage - report of 3 cases

    Institute of Scientific and Technical Information of China (English)

    YU Shu-qing; WANG Ji-sheng; JI Nan; LIU Wei; QIAN Ke

    2009-01-01

    @@ Aspirin has been widely used clinically since 1899.For patients with cerebral ischemia and implanted intravascular stents, aspirin has been used routinely for prevention of intracranial hemorrhage and for anticoagulation treatment. However, many multi-center,large sample, controlled studies have shown that aspirin may actually increase the risk of spontaneous cerebral hemorrhage, and that aspirin was an independent predictor of death shortly after cerebral hemorrhage. Here we report a case series, between July 1 2006 and January 1 2008, of 3 patients who experienced postoperative intracranial hemorrhage after receiving regular aspirin treatment before surgery in the Center of Neurosurgery,Beijing Tiantan Hospital, Capital Medical University.Two of them died. There were 86 patients in all receiving regular aspirin treatment before surgery in the same period. The incidence of intracranial hemorrhage in this group is 3.49%.

  3. 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 < 0.01). Alterations of LG morphology and increased numbers of lipofucsin-like inclusions were observed in diabetic but not in 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 < 0.05, respectively). The findings prevented by 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.

  4. Salicylic acid: a link between aspirin, diet and the prevention of colorectal cancer.

    Science.gov (United States)

    Paterson, J R; Lawrence, J R

    2001-08-01

    Aspirin was introduced into clinical practice more than 100 years ago. This unique drug belongs to a family of compounds called the salicylates, the simplest of which is salicylic acid, the principal metabolite of aspirin. Salicylic acid is responsible for the anti-inflammatory action of aspirin, and may cause the reduced risk of colorectal cancer observed in those who take aspirin. Yet salicylic acid and other salicylates occur naturally in fruits and plants, while diets rich in these are believed to reduce the risk of colorectal cancer. Serum salicylic acid concentrations are greater in vegetarians than non-vegetarians, and there is overlap between concentrations in vegetarians and those taking low-dose aspirin. We propose that the cancer-preventive action of aspirin is due to its principal metabolite, salicylic acid, and that dietary salicylates can have the same effect. It is also possible that natural salicylates contribute to the other recognized benefits of a healthy diet. PMID:11493722

  5. Aspirin Sensitivity and Chronic Rhinosinusitis with Polyps: A Fatal Combination

    Directory of Open Access Journals (Sweden)

    Hendrik Graefe

    2012-01-01

    Full Text Available Aspirin-exacerbated respiratory disease (AERD refers to aspirin sensitivity, chronic rhinosinusitis (CRS, nasal polyposis, asthma, eosinophil inflammation in the upper and lower airways, urticaria, angioedema, and anaphylaxis following the ingestion of NSAIDs. Epidemiologic and pathophysiological links between these diseases are established. The precise pathogenesis remains less defined, even though there is some progress in the understanding of several molecular mechanisms. Nevertheless, these combinations of diseases in patients classified by AERD constitute a fatal combination and may be difficult to treat with standard medical and surgical interventions. This paper reviews in brief the epidemiology, clinical features, diagnosis, molecular pathogenesis, and specific therapies of patients classified by AERD and postulates future attempts to gain new insights into this disease.

  6. 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. PMID:27251704

  7. Aspirin in Cardiovascular and Cerebrovascular Events: Does Market Failure Matter?

    Directory of Open Access Journals (Sweden)

    Roger Lee Mendoza

    2010-01-01

    Full Text Available Problem statement: Against the backdrop of the 2009 scientific studies qualifying the cardiovascular and cerebrovascular benefits of aspirin, two interrelated questions are raised for investigation in this study. First, why may the government intervene in an otherwise private transaction between physician and patient and between drug manufacturer and buyer, when it involves contentious pharmacological information? Second, does government intervention make a difference in what these transacting parties would otherwise have chosen to do in its absence? Approach: An Internet literature search was performed, using query term combinations, to identify relevant aspirin studies. The search yielded 61 juried publications that met our predetermined criteria for inclusion and thematic analysis. Results: Variance exists within the mix of economic and non-economic literature on aspirin information regulation. The study identified 4 instances of market failure that offer some of the most compelling theoretical and practical considerations for public policy intervention in the context of the 2009 findings. However, there is also indication that the sense of increased protection arising from safety regulations could stimulate risky behavior that nullifies their net protective effects or benefits. Conclusion: It is not clear either from the surveyed literature or existing economic theory if, ceteris paribus, regulated information alters or modifies the marginal propensity of a physician to recommend, and a patient to consume, aspirin to prevent cardiovascular and cerebrovascular events, particularly heart attacks, strokes and vascular death. The study suggests the need for policy reinforcements to safety information, if market failures are to be efficiently addressed and risk compensating behavior reduced.

  8. Aspirin treatment exacerbates oral infections by Trypanosoma cruzi.

    Science.gov (United States)

    Cossentini, Luana Aparecida; Da Silva, Rosiane Valeriano; Yamada-Ogatta, Sueli Fumie; Yamauchi, Lucy Megumi; De Almeida Araújo, Eduardo José; Pinge-Filho, Phileno

    2016-05-01

    Oral transmission of the protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas disease, has been documented in Latin American countries. The reported cases of infection were due to the ingestion of contaminated fresh fruit, juices, or sugar cane juice. There have been few studies on the physiopathology of the disease in oral transmission cases. Gastritis is a common ailment that can be caused by poor dietary habits, intake of alcohol or other gastric irritants, bacterial infection, or by the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated in a mouse model whether gastric mucosal injury, induced by aspirin, would affect the course of disease in animals infected with T. cruzi by the oral route. The CL14 and G strains of T. cruzi, both of low infectivity, were used. To this end, groups of BALB/c mice were treated during 5 days with aspirin (100 mg kg(-1)) before oral infection with T. cruzi metacyclic forms (4 × 10(5) or 5 × 10(7) parasites/mouse). Histological analysis and determination of nitric oxide and TNF-α were performed in gastric samples obtained 5 days after infection. Parasitemia was monitored from the thirteenth day after infection. The results indicate that aspirin treatment of mice injured their gastric mucosa and facilitated invasion by both CL14 and G strains of T. cruzi. Strain CL14 caused more severe infection compared to the G strain, as larger numbers of amastigote nests were found in the stomach and parasitemia levels were higher. Our study is novel in that it shows that gastric mucosal damage caused by aspirin, a commonly used NSAID, facilitates T. cruzi infection by the oral route. PMID:26826555

  9. Profile and prevalence of aspirin resistance in patients with metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Zhaoping Liu; Yang Yu; Yuanjie Mao; Xinhua Wang; Jianzhong Wang; Yong Huo

    2008-01-01

    Objective Aspirin has been used extensively in primary and secondary prevention of cardiovascular disease,particularly for subjects at high risk such as metabolic syndrome.However,the responsiveness to aspirin treatment may vary among individuals.The present study was conducted to investigate the profile and prevalence of aspirin resistance in patients with metabolic syndrome.Methods In 221 consecutive patients,platelet aggregation induced by arachidonic acid (0.5mg/ml) was assessed after 10 days of aspirin treatment (200mg/d).Aspirin resistance was defined as mean optical platelet aggregation =20%.Results Aspirin resistance occurred in 39 patients (17.6%).Serum fibrinogen level was higher in patients with than in those without aspirin resistance (2.6_+0.4g/l vs 2.4±0.4g/L,P=0.017).The 2 groups,aspirin resistance group and no aspirin resistance group,did not differ significantly,with regard to gender,age,body mass index,waist-hip ratio,blood pressure level,serum cholesterol level and history of myocardial or cerebral infarction.Multivariate logistic regression analysis revealed that only serum fibrinogen level entered the model (odds ratio 2.973,p=0.023).Subgroup analysis further showed that aspirin resistance occurred more in male patients with myocardial infarction (50% vs14.5%,P=0.02) and in female patients with diastolic blood pressure=85mmHg (34% vs 15.5%,P=0.043).But after multifactor logistic regression,in women blood pressure=85mmHg was not a predictor any more.Conclusions In patients with metabolic syndrome,aspirin resistance is not uncommon,especially for men with history of myocardial infarction.Patients with aspirin resistance have an increased serum fibrinogen level.(J Geriatr Cardio12008;5:7-10)

  10. Aspirin Resistance: A Clinical Review Focused on the Most Common Cause, Noncompliance

    OpenAIRE

    Schwartz, Kenneth A.

    2011-01-01

    Aspirin is an inexpensive, readily available medication that reduces the risk of subsequent vascular disease by about 25% in patients with known occlusive vascular disease. Aspirin’s beneficial effect is mediated via inhibition of arachidonic acid (AA) activation of platelets and is detected by demonstrating a decrease in platelet function and/or a decrease in prostaglandin metabolites. Patients who are assumed to be taking their aspirin, but who do not demonstrate an aspirin effect are label...

  11. Effect of allopurinol, sulphasalazine, and vitamin C on aspirin induced gastroduodenal injury in human volunteers.

    OpenAIRE

    McAlindon, M E; Muller, A F; Filipowicz, B; Hawkey, C J

    1996-01-01

    BACKGROUND--The mechanisms of aspirin induced gastroduodenal injury are not fully understood. Aspirin induces the release of reactive oxygen metabolites in animal models, which may contribute to mucosal injury. AIMS--To investigate the effects of aspirin administered with placebo or antioxidants on gastric mucosal reactive oxygen metabolite release and gastroduodenal injury in human volunteers. SUBJECTS--Fourteen healthy volunteers participated in the study (seven male; mean age 27 years, ran...

  12. 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.

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

    OpenAIRE

    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...

  14. Critical appraisal of a fixed combination of esomeprazole and low dose aspirin in risk reduction

    OpenAIRE

    Vachhani, Ravi; Bouhaidar, Doumit; Zfass, Alvin; Sandhu, Bimaljit; Nawras, Ali

    2010-01-01

    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, d...

  15. Interactions of aspirin and other potential etiologic factors in an animal model of Reye syndrome.

    OpenAIRE

    Deshmukh, D.R.; Maassab, H. F.; Mason, M.

    1982-01-01

    Recent studies of Reye syndrome (RS) patients have suggested aspirin treatment as a possible factor in the etiology of this often fatal childhood disorder. the relationship of aspirin treatment to other factors that have been strongly implicated (influenza, ammonia toxicity) cannot be examined directly in patients because aspirin treatment is usually initiated by family members in the prodromal period before RS is diagnosed. In this report we describe the use of an animal model for RS in exam...

  16. Cancers prevented in Australia in 2010 through the consumption of aspirin

    OpenAIRE

    Wilson, Louise F.; Green, Adele C.; Kendall, Bradley J; Jordan, Susan J.; Nagle, Christina M; Bain, Christopher J; Neale, Rachel E; Whiteman, David C

    2015-01-01

    Objectives To estimate the proportion and number of cancers in Australia in 2010 that may have been prevented from occurring due to daily use of aspirin in the population. Methods We calculated the Prevented Fraction (PF) of colorectal and oesophageal cancers using standard formulae. The PF is the proportion of the hypothetical total load of cancer in the population that was prevented by exposure to aspirin. The formula incorporates estimates of the prevalence of aspirin use in Australian adu...

  17. Phytoremediation of aspirin and tetracycline by Brassica juncea.

    Science.gov (United States)

    Gahlawat, Sonal; Gauba, Pammi

    2016-09-01

    With the increasing release of pharmaceutical drugs in the environment, research is in progress for investigating alternative methods for their remediation. Various studies have shown the phytoremediation potential of Brassica juncea for metals. The current study was aimed at evaluating the phytoremediation potential of B. juncea for two different pharmaceutical drugs i.e. aspirin and tetracycline in in-vitro conditions. The seeds of B. juncea were germinated and grown for a period of 28 and 24 days for aspirin and tetracycline, respectively. The study analyzed the remediation rate of B. juncea for the selected drugs in three different sets of varying concentration along with any phytotoxic effects exerted by the drugs on the seeds. Preliminary results showed that the average remediation rate of aspirin and tetracycline at the end of experiment was approximately 90% and 71%, respectively. As initial drug concentrations were increased in the media, the remediation rate also improved. However, at higher concentrations, the plants showed phytotoxicity as depicted by the decrease in shoot length of the germinated seeds. These preliminary results indicated that B. juncea could tolerate and remediate pharmaceutical drugs such as analgesics and antibiotics. PMID:26696522

  18. [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.

  19. 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.

  20. Drug/drug interaction of common NSAIDs with antiplatelet effect of aspirin in human platelets.

    Science.gov (United States)

    Saxena, Aaruni; Balaramnavar, Vishal M; Hohlfeld, Thomas; Saxena, Anil K

    2013-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with the anti-platelet activity of aspirin at the level of the platelet cyclooxygenase-1 (COX-1) enzyme. In order to examine the interference of common NSAIDs with the anti-platelet activity of aspirin the human platelet rich plasma from voluntary donors was used for arachidonic acid-induced aggregation and determination of thromboxane synthesis. Further, docking studies were used to explain the molecular basis of the NSAID/aspirin interaction. The experimental results showed that celecoxib, dipyrone (active metabolite), ibuprofen, flufenamic acid, naproxen, nimesulide, oxaprozin, and piroxicam significantly interfere with the anti-platelet activity of aspirin, while diclofenac, ketorolac and acetaminophen do not. Docking studies suggested that NSAIDs forming hydrogen bonds with Ser530, Arg120, Tyr385 and other amino acids of the COX-1 hydrophobic channel interfere with antiplatelet activity of aspirin while non interfering NSAIDs do not form relevant hydrogen bond interactions within the aspirin binding site. In conclusion, docking analysis of NSAID interactions at the COX-1 active site appears useful to predict their interference with the anti-platelet activity of aspirin. The results, demonstrate that some NSAIDs do not interfere with the antiplatelet action of aspirin while many others do and provide a basis for understanding the observed differences among individual non-aspirin NSAIDs. PMID:24075938

  1. Cigarette smoking inhibits the anti-platelet activity of aspirin in patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    LI Wei-ju; ZHANG Hong-yin; MIAO Cheng-long; TANG Ri-bo; DU Xin; SHI Ji-hui; MA Chang-sheng

    2011-01-01

    Objective Tobacco smoking results in increased platelet aggregability, which suggests that low-dose aspirin used in common clinical practice may not effectively inhibit platelet activity in smokers with coronary heart disease (CHD). This review was performed to assess the effect of aspirin on platelet aggregation in patients with CHD.Data sources We performed an electronic literature search of MEDLINE (starting from the beginning to March 15, 2009)using the term "smoking" or "tobacco" paired with the following: "platelet", "aspirin" or "coronary heart disease".Study selection We looked for review articles regarding the effect of tobacco smoking on platelet activity and on the anti-platelet efficacy of aspirin in healthy people and patients with CHD. The search was limited in "core clinical journal".In total, 1321 relevant articles were retrieved, and 36 articles were ultimately cited.Results Tobacco smoking results in increased platelet aggregability, which can be inhibited by low-dose aspirin in the healthy population. However, in patients with CHD, the increased platelet aggregability can not be effectively inhibited by the same low-dose of aspirin. A recent study indicated that clopidogrel or an increased dose of aspirin can effectively inhibit the increased platelet aggregability induced by tobacco smoking in patients with CHD.Conclusions It is important for patients with CHD to quit smoking. For the current smoker, it may be necessary to take larger doses of aspirin than normal or take an adenosine diphosphate receptor inhibitor along with aspirin to effectively inhibit the increased platelet activity.

  2. Aspirin as a risk factor for hemorrhage in patients with head injuries.

    Science.gov (United States)

    Reymond, M A; Marbet, G; Radü, E W; Gratzl, O

    1992-01-01

    The role of aspirin as a risk factor in the occurrence of intracranial bleeding following head injury was investigated. Chronic subdural hematoma appears to be a suitable model for the evaluation of risk factors in the development of hemorrhage. The most common risk factors found in our study were, apart from age, chronic alcohol abuse (28%), consumption of cumarin-derivates (21%), aspirin (13%), and heparin (5%). A patient undergoing aspirin treatment must be considered at risk of development of chronic subdural hematoma. Aspirin should not be prescribed to patients with post-traumatic headaches. PMID:1584433

  3. Gastrointestinal ulcers, role of aspirin, and clinical outcomes: pathobiology, diagnosis, and treatment

    Directory of Open Access Journals (Sweden)

    Cryer B

    2014-03-01

    Full Text Available Byron Cryer,1 Kenneth W Mahaffey2 1University of Texas Southwestern Medical School, Dallas, TX, 2Department of Medicine, Stanford University, Stanford, CA, USA Abstract: Peptic ulcer disease is a major cause of morbidity and mortality in the US with more than six million diagnoses annually. Ulcers are reported as the most common cause of hospitalization for upper gastrointestinal (GI bleeding and are often a clinical concern due to the widespread use of aspirin and nonsteroidal anti-inflammatory drugs, both of which have been shown to induce ulcer formation. The finding that Helicobacter pylori infection (independent of aspirin use is associated with the development of ulcers led to a more thorough understanding of the causes and pathogenesis of ulcers and an improvement in therapeutic options. However, many patients infected with H. pylori are asymptomatic and remain undiagnosed. Complicating matters is a current lack of understanding of the association between aspirin use and asymptomatic ulcer formation. Low-dose aspirin prescriptions have increased, particularly for cardioprotection. Unfortunately, the GI side effects associated with aspirin therapy continue to be a major complication in both symptomatic and asymptomatic patients. These safety concerns should be important considerations in the decision to use aspirin and warrant further education. The medical community needs to continue to improve awareness of aspirin-induced GI bleeding to better equip physicians and improve care for patients requiring aspirin therapy. Keywords: low-dose aspirin, cardioprotection, ulcers, Helicobacter pylori, gastrointestinal bleeding, cardiovascular disease

  4. The effects of aspirin plus cisplatin on SGC7901/CDDP cells in vitro.

    Science.gov (United States)

    Dong, Hanzhang; Liu, Gaogao; Jiang, Biao; Guo, Jiubing; Tao, Guoquan; Yiu, Wei; Zhou, Jingsong; Li, Guoxin

    2014-05-01

    The purpose of this study was to determine the effect of aspirin plus cisplatin (CDDP) in the chemotherapy of gastric cancer. We cultured SGC7901/CDDP cells by long-term exposure of SGC7901 cells to small doses of CDDP in vitro. The cells were treated with aspirin, CDDP or aspirin plus CDDP for 24 h and cell growth was assessed by the MTT assay, the apoptotic rate by flow cytometry, the survivin mRNA expression by RT-PCR and the survivin protein expression by western blotting. The results revealed that the cell growth in the aspirin plus CDDP group was significantly inhibited. The apoptotic rate in the aspirin plus CDDP was significantly higher compared to that in the other groups. The survivin mRNA and protein expression were also significantly reduced in the aspirin plus CDDP group. Our data suggest that the combination of aspirin and CDDP exhibited a higher degree of toxicity against SGC7901/CDDP cells compared to that of aspirin or CDDP alone. Thus, the combination of aspirin plus CDDP may reduce the expression of survivin and induce the apoptosis of SGC7901/CDDP cells. PMID:24748972

  5. 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

  6. Long-term use of ticagrelor in patients with prior heart attack: ticagrelor plus aspirin versus aspirin monotherapy.

    Science.gov (United States)

    Amico, Frank; Schlesinger, Alex; Mazzoni, Jennifer

    2016-01-01

    Review of: Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-1800. This Practice Pearl reviews the recent study Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared With Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54). It challenges the current standard of care of 12 months of dual antiplatelet followed by aspirin indefinitely. The study demonstrated that patients who received ticagrelor, either the 60 mg or 90 mg twice daily plus aspirin, showed a decreased risk of cardiovascular death, myocardial infarction, or stroke. The PEGASUS-TIMI 54 trial also proved that the benefit of ticagrelor was seen early and continued to accrue over time, with a median of 33 months of follow-up, meaning that the benefit persists over time. It is important to note that both doses of the ticagrelor were associated with higher incidence of bleeding, but the rates of fatal bleeding did not show any difference between the ticagrelor or placebo. PMID:26689345

  7. Long-term use of ticagrelor in patients with prior heart attack: ticagrelor plus aspirin versus aspirin monotherapy.

    Science.gov (United States)

    Amico, Frank; Schlesinger, Alex; Mazzoni, Jennifer

    2016-01-01

    Review of: Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-1800. This Practice Pearl reviews the recent study Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared With Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54). It challenges the current standard of care of 12 months of dual antiplatelet followed by aspirin indefinitely. The study demonstrated that patients who received ticagrelor, either the 60 mg or 90 mg twice daily plus aspirin, showed a decreased risk of cardiovascular death, myocardial infarction, or stroke. The PEGASUS-TIMI 54 trial also proved that the benefit of ticagrelor was seen early and continued to accrue over time, with a median of 33 months of follow-up, meaning that the benefit persists over time. It is important to note that both doses of the ticagrelor were associated with higher incidence of bleeding, but the rates of fatal bleeding did not show any difference between the ticagrelor or placebo.

  8. A Markov model to compare the long-term effect of aspirin, clopidogrel and clopidogrel plus aspirin on prevention of recurrent ischemic stroke due to intracranial artery stenosis

    Directory of Open Access Journals (Sweden)

    Jinqiu Yang

    2014-01-01

    Full Text Available Background: Given the importance of intracranial stenosis as a cause of recurrent ischemic stroke and the lack of evidence supporting a clear choice for prevention of recurrent ischemic events, a computer simulation model for prognostic prediction could be used to improve decision making. Aims: The aim of the following study is to compare the long-term effect of aspirin, clopidogrel and clopidogrel plus aspirin for prevention of recurrent stroke due to atherosclerotic intracranial artery stenosis. Setting and Design: The cohort consisted of 206 patients from 2006 to 2011. Materials and Methods: A two-state Markov model was used to predict the prognosis of patients with stroke or transient ischemic attack (TIA caused by angiographically verified 50-99% stenosis of a major intracranial artery to receive aspirin, clopidogrel, or dual therapy. Statistical Analysis: Two tests were used: Pearson Chi-square test or Fisher′s exact test (for percentages and Kruskal Wallis test (for rank order data. Results: In the 10-year Markov cohort analysis, 36.24% of patients who were treated with clopidogrel plus aspirin developed to recurrent stroke while the probability for patients in the aspirin group and clopidogrel group was 42.60% and 48.39% respectively. Patients with clopidogrel plus aspirin had the highest quality-adjusted life years, followed by aspirin and clopidogrel. Conclusion: To prevent recurrent stroke in patients with intracranial artery stenosis, especially in those patients with a history of TIA or coronary artery disease, medical therapy with clopidogrel plus aspirin should be considered in preference to aspirin alone.

  9. Differential Sex Response to Aspirin in Decreasing Aneurysm Rupture in Humans and Mice.

    Science.gov (United States)

    Chalouhi, Nohra; Starke, Robert M; Correa, Tatiana; Jabbour, Pascal M; Zanaty, Mario; Brown, Robert D; Torner, James C; Hasan, David M

    2016-08-01

    We previously found that aspirin decreases the risk of cerebral aneurysm rupture in humans. We aim to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin and confirm these observations in a mouse model of cerebral aneurysm. A nested case-control analysis from the International Study of Unruptured Intracranial Aneurysms was performed to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin. A series of experiments were subsequently performed in a mouse model of cerebral aneurysms. Aneurysms were induced with hypertension and elastase injection into mice basal cisterns. We found that aspirin decreased the risk of aneurysm rupture more significantly in men than in women in the International Study of Unruptured Intracranial Aneurysms. In mice, aspirin and cyclooxygenase-2 inhibitor did not affect cerebral aneurysm formation but significantly decreased the incidence of rupture. The incidence of rupture was significantly lower in male versus female mice on aspirin. Gene expression analysis from cerebral arteries showed higher 15-hydroxyprostaglandin dehydrogenase levels in male mice. The rate of cerebral aneurysm rupture was similar in male mice receiving aspirin and 15-hydroxyprostaglandin dehydrogenase inhibitor compared with females receiving aspirin and 15-hydroxyprostaglandin dehydrogenase agonist, signaling a reversal of the sex-differential response to aspirin. Aspirin decreases aneurysm rupture in human and mice, in part through cyclooxygenase-2 pathways. Evidence from animal and human studies suggests a consistent differential effect by sex. 15-Hydroxyprostaglandin dehydrogenase activation in females reduces the incidence of rupture and eliminates the sex-differential response to aspirin. PMID:27296993

  10. 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 ...

  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

    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...... operating characteristic curves for miR-92a levels and PDW were used to set cut-off values for discrimination between aspirin responding and aspirin resistant patients. RESULTS: When defining aspirin resistance as an ASPItest ≥30U, the optimal cut-off values for discrimination of aspirin responders...

  12. Effects of combined octreotide and aspirin on the growth of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    唐承薇; 王春晖; 汤丽平

    2003-01-01

    Objective To investigate the effects of the combination of octreotide and aspirin on the growth of gastric cancer. Methods Proliferation of gastric cancer cell lines treated with octreotide or aspirin was determined by 3 H-thymidine incorporation. After xenografts of human gastric cancer were implanted orthotropically in the stomach of nude mice, they were administered octreotide plus aspirin for 8 weeks. The mRNA of somatostatin receptor in the tissues of gastric carcinoma was detected by reverse transcription polymerase chain reaction (RT-PCR). Cyclooxygenase-2 in gastric cancer tissues was measured by immuno~histochemistry. Results Both octreotide and aspirin significantly reduced the 3 H-thymidine incorporation of gastric cancer cells. Xenografts in situ were found in all stomachs of nude mice except for two in the combination group. Either size or weight of tumors treated by octreotide, aspirin or in combination was significantly reduced as compared with that of controls. The inhibition rate for tumor was 60.6% (octreotide), 39.3% (aspirin), and 85.6% (in combination) respectively. No severe side effects were observed in any treated groups. Somatostatin receptor-2 and -3 were expressed in the transplanted gastric adenocarcinomas. Aspirin could down-regulate the strong expression of cyclooxygenase-2 in the tissue of gastric adenocarcinomas of nude mice.Conclusion A combination of octreotide and aspirin significantly inhibited proliferation of gastric cancer through mediation of somatosatin receptors and suppression of cyclooxygenase-2.

  13. 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 ant

  14. 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 le

  15. Affordability Calculations on a Health Education Campaign to Promote the Use of Aspirin in Wales

    Science.gov (United States)

    Morgan, Gareth

    2008-01-01

    Aspirin has far-reaching public health potential in reducing the risk of heart attacks, ischemic strokes and possibly cancer. Balanced against this potential are undesirable effects of the drug. It seems reasonable to allow every individual over the age of 50 years to make an informed choice about whether or not to take aspirin. A health education…

  16. 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. Smokers are at increased risk for developing lung and other cancers. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers. |

  17. Study of effects of donepezil and aspirin on working memory in rats using electroconvulsive shock model

    Directory of Open Access Journals (Sweden)

    Rahul M. Manjare

    2014-12-01

    Conclusion: Neuroinflammation plays an important role in the pathophysiology of neurodegenerative disorder like AD. Combination of aspirin with donepezil increased the nootropic and neuroprotective effect of aspirin and thus may hold great clinical significance in such disorders. [Int J Basic Clin Pharmacol 2014; 3(6.000: 1012-1015

  18. Aspirin-intolerant asthma: a comprehensive review of biomarkers and pathophysiology.

    Science.gov (United States)

    Velazquez, Juan R; Teran, Luis M

    2013-08-01

    Aspirin-exacerbated respiratory disease is a tetrad of nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to aspirin. Unawareness of this clinical condition by patients and physicians may have grave consequences because of its association with near-fatal asthma. The pathogenesis of aspirin-intolerant asthma is not related with an immunoglobin E mechanism, but with an abnormal metabolism of the lipoxygenase (LO) and cyclooxygenase (COX) pathways. At present, a diagnosis of aspirin sensitivity can be established only by provocative aspirin challenge, which represents a health risk for the patient. This circumstance has encouraged the search for aspirin intolerance-specific biomarkers. Major attempts have focused on mediators related with inflammation and eicosanoid regulation. The use of modern laboratory techniques including high-throughput methods has facilitated the detection of dozens of biological metabolites associated with aspirin-intolerant asthma disease. Not surprisingly, the majority of these is implicated in the LO and COX pathways. However, substantial amounts of data reveal the participation of many genes deriving from different ontologies. Biomarkers may represent a powerful, noninvasive tool in the diagnosis of aspirin sensitivity; moreover, they could provide a new way to classify asthma phenotypes.

  19. The ADAPTABLE Trial and Aspirin Dosing in Secondary Prevention for Patients with Coronary Artery Disease.

    Science.gov (United States)

    Johnston, Abigail; Jones, W Schuyler; Hernandez, Adrian F

    2016-08-01

    Coronary artery disease (CAD) is the underlying cause of death in one out of seven deaths in the USA. Aspirin therapy has been proven to decrease mortality and major adverse cardiovascular events in patients with CAD. Despite a plethora of studies showing the benefit of aspirin in secondary prevention of cardiovascular events, debate remains regarding the optimal dose due to relatively small studies that had disparate results when comparing patients taking different aspirin dosages. More recently, aspirin dosing has been thoroughly studied in the CAD population with concomitant therapy (such as P2Y12 inhibitors); however, patients in these studies were not randomized to aspirin dose. No randomized controlled trial has directly measured aspirin dosages in a population of patients with established coronary artery disease. In 2015, the Patient-Centered Outcomes Research Institute (PCORI) developed a network, called PCORnet, that includes patient-powered research networks (PPRN) and clinical data research networks (CDRN). The main objective of PCORnet is to conduct widely generalizable observational studies and clinical trials (including large, pragmatic clinical trials) at a low cost. The first clinical trial, called Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE), will randomly assign 20,000 subjects with established coronary heart disease to either low dose (81 mg) or high dose (325 mg) and should be able to finally answer which dosage of aspirin is best for patients with established cardiovascular disease. PMID:27423939

  20. Pharmacokinetic and pharmacodynamic interactions of aspirin with warfarin in beagle dogs.

    Science.gov (United States)

    Shen, Chenlin; Huang, Xiaohui; Li, Jun; Zhang, Ping; Li, Lin; Zhang, Wei; Hu, Tingting; Pappoe, Faustina; Huang, Jihan; Tang, Haiqin

    2016-01-01

    1. Warfarin and aspirin are widely used in a wide spectrum of thromboembolic and atherothrombotic diseases. Despite the potential efficacy of warfarin-aspirin therapy, the safety and side effect of combined therapy remains unclear. 2. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and aspirin in beagles after single and multiple doses. 3. Coadministration of aspirin had no significant effects on the area under the plasma concentration time curve (AUC(0-t)) and maximum plasma concentration (Cmax) of R- and S-warfarin after a single dose of warfarin, but significantly increase the AUC(0-t) and Cmax and dramatically decrease the clearance (CL) of R- and S-warfarin after multiple dose of warfarin. Accordingly, there was a slight increase in the AUEC(0-t) and Emax of activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) after multiple dose of warfarin. 4. Coadministration of warfarin had no markedly effects on the AUC(0-t) and Cmax of aspirin and its metabolite salicylic acid after single or multiple dose of aspirin. Meanwhile, the AUEC(0-t) and Emax of inhibition of platelet aggregation (IPA) were not significantly affected by warfarin. 5. Our animal study indicated that coadministration of aspirin with warfarin can cause significant pharmacokinetic and pharmacodynamic drug-drug interactions in beagles. However, more studies are urgently needed to assess related information of warfarin-aspirin drug interactions in healthy volunteers or patients. PMID:26548565

  1. Aspirin and atenolol enhance metformin activity against breast cancer by targeting both neoplastic and microenvironment cells.

    Science.gov (United States)

    Talarico, Giovanna; Orecchioni, Stefania; Dallaglio, Katiuscia; Reggiani, Francesca; Mancuso, Patrizia; Calleri, Angelica; Gregato, Giuliana; Labanca, Valentina; Rossi, Teresa; Noonan, Douglas M; Albini, Adriana; Bertolini, Francesco

    2016-01-01

    Metformin can induce breast cancer (BC) cell apoptosis and reduce BC local and metastatic growth in preclinical models. Since Metformin is frequently used along with Aspirin or beta-blockers, we investigated the effect of Metformin, Aspirin and the beta-blocker Atenolol in several BC models. In vitro, Aspirin synergized with Metformin in inducing apoptosis of triple negative and endocrine-sensitive BC cells, and in activating AMPK in BC and in white adipose tissue (WAT) progenitors known to cooperate to BC progression. Both Aspirin and Atenolol added to the inhibitory effect of Metformin against complex I of the respiratory chain. In both immune-deficient and immune-competent preclinical models, Atenolol increased Metformin activity against angiogenesis, local and metastatic growth of HER2+ and triple negative BC. Aspirin increased the activity of Metformin only in immune-competent HER2+ BC models. Both Aspirin and Atenolol, when added to Metformin, significantly reduced the endothelial cell component of tumor vessels, whereas pericytes were reduced by the addition of Atenolol but not by the addition of Aspirin. Our data indicate that the addition of Aspirin or of Atenolol to Metformin might be beneficial for BC control, and that this activity is likely due to effects on both BC and microenvironment cells. PMID:26728433

  2. Aspirin After Mini-Stroke May Help Prevent Full-Blown Stroke

    Science.gov (United States)

    ... gov/news/fullstory_158939.html Aspirin After Mini-Stroke May Help Prevent Full-Blown Stroke Study finds risk is reduced by as much ... HealthDay News) -- Taking aspirin immediately after a mini-stroke significantly reduces the risk of a major stroke, ...

  3. 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.

  4. Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats

    Directory of Open Access Journals (Sweden)

    Arijit Ghosh

    2011-01-01

    Full Text Available Objective: To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Materials and Methods: Retention of conditioned avoidance response (CAR and central 5-HT-mediated behavior (lithium-induced head twitches were assessed using repeated electroconvulsive shock (ECS in rats. Rats were divided into eight groups: control (pretreated with distilled water, scopolamine (0.5 mg/kg i.p., ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s pretreated, aspirin (6.75 mg/kg orally pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Results: Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Conclusion: Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions.

  5. 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 inc

  6. Pharmacodynamics Drug Interactions of Metformin with Aspirin and Nifedipine

    Directory of Open Access Journals (Sweden)

    Khidir A. M. Hassan, Mahmoud M. E. Mudawi,Mansour I. Sulaiman

    2016-02-01

    Full Text Available Metformin is now being recognized as the standard therapy in T2D patients who are overweight. Metformin has many drug-disease interactions that can increase the risk of metformin-associated lactic acidosis. Therefore this study was conducted to evaluate any possible pharmacodynamic interactions between metformin and drugs used to treat chronic diseases e.g. Hypertension. The rats were fasted overnight before inducing diabetes with streptozotocin. The rats were given an intraperitoneal injection of streptozotocin (50 mg kg−1 freshly prepared in 0.1M sodium citrate buffer. The diabetic state was confirmed 72 h after streptozotocin injection. Diabetic rats were grouped into seven groups each group of five rats and distributed among the normal control group diabetic control group and the treatment groups. The treatment continued for 10 days. Blood samples were taken before treatment and after 10 days and analyzed for serum glucose, cholesterol, HDL, LDL, and triglycerides. In the diabetic control group which was given STZ alone the blood glucose level decreased significantly (p < 0.05 after 10 days but still above the hyperglycemic level (200mg/dl. The same was observed in the group treated with metformin. The group treated with nifedipine and aspirin showed significant reduction (p < 0.01 in the glucose level below the hyperglycemic level (200mg/dl. While the groups treated with (Metformin + Nifedipine and (Metformin +Aspirin showed highly significant reduction (P<0.001 in blood glucose level. These results conclude that the combination of (metformin +Nifedipine and the combination of (Metformin + Aspirin have highly significant hypoglycemic effect. It also showed that Nifedipine has promising role in reducing blood glucose level, lipid profile especially LDL-cholesterol, and body weight.

  7. Anti-apoptotic effects of aspirin following cerebral ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Liying Qiu; Bin Du; Ying Li; Hongbin Fan; Zhiyong Yang

    2008-01-01

    BACKGROUND: The pharmacological effects of aspirin on apoptosis are complex. The underlying mechanisms have not been properly defined. OBJECTIVE: To observe the effect of different doses of aspirin on brain cell apoptosis following focal cerebral ischemia-reperfusion injury (CIRI) in rats. DESING, TIME AND SETTING: A randomized, controlled, animal experiment, performed at the School of Medicine and Pharmaceutics, Jiangnan University between June and October 2006. MATERIALS: Twenty-six male, adult, Sprague Dawley rats (grade II), weighing 240-290 g, were obtained from Shanghai Experimental Animal Center, Chinese Academy of Sciences. Aspirin was provided by Sigma (USA). METHODS: The rats were randomly divided into four groups: sham-operation (SO), CIRI+ vehicle, CIRI+ aspirin (6 mg/kg), and CIRI + aspirin (60 mg/kg). Rats in the lesion groups were intragastrically administrated saline, aspirin (6 mg/kg), or aspirin (60 mg/kg), respectively. MAIN OUTCOME MEASURES: The number of pyramidal neurons with normal appearance in the cerebral cortex at 2-4 mm from the midline; apoptotic cell death as measured by TUNEL; Bcl-2 and Bax protein localization was determined by immunohistochemistry; maiondiaidehyde (MDA) and super oxidation (SOD) content were determined by biochemistry method; adenosine triphosphate (ATP) content measured by capillary electrophoresis. RESULTS: Following CIRI, the following parameters were altered compared with sham-operated animals: the number of neurons with normal appearance was significantly reduced in the cerebral cortex; the number of apoptotic cells increased; Bax protein expression was enhanced; and the ratio between Bcl-2 and Bax decreased. In addition, MDA content increased significantly, whereas ATP content decreased (P < 0.01 ). Aspirin ameliorated the loss of healthy pyramidal neurons. Both 6 and 60 mg/kg aspirin increased the ratio between Bcl-2 and Bax, with no significant difference between the treatment groups. In addition, 60 mg

  8. Effect of Tamarindus indica L. on the bioavailability of aspirin in healthy human volunteers.

    Science.gov (United States)

    Mustapha, A; Yakasai, I A; Aguye, I A

    1996-01-01

    The influence of Tamarindus indica L. fruit extract incorporated in a traditional meal on the bioavailability of aspirin tablets 600 mg dose was studied in 6 healthy volunteers. There was a statistically significant increase in the plasma levels of aspirin and salicylic acid, respectively, when the meal containing Tamarindus indica fruit extract was administered with the aspirin tablets than when taken under fasting state or with the meal without the fruit extract. The Cmax, AUC0-6h and t1/2 for aspirin increased from 10.04 +/- 0.1 mg/ml to 28.62 +/- 0.21 mg/ml (P Tamarindus indica L. fruit extract significantly increased the bioavailability of aspirin.

  9. 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...

  10. Low-dose aspirin in polycythaemia vera: a pilot study. Gruppo Italiano Studio Policitemia (GISP).

    Science.gov (United States)

    1997-05-01

    In this pilot study, aimed at exploring the feasibility of a large-scale trial of low-dose aspirin in polycythaemia vera (PV), 112 PV patients (42 females, 70 males. aged 17-80 years) were selected for not having a clear indication for, or contraindication to, aspirin treatment and randomized to receive oral aspirin (40 mg/d) or placebo. Follow-up duration was 16 +/- 6 months. Measurements of thromboxane A2 production during whole blood clotting demonstrated complete inhibition of platelet cyclooxygenase activity in patients receiving aspirin. Aspirin administration was not associated with any bleeding complication. Within the limitations of the small sample size, this study indicates that a biochemically effective regimen of antiplatelet therapy is well tolerated in patients with polycythaemia vera and that a large-scale placebo-controlled trial is feasible.

  11. A Markov model to compare the long-term effect of aspirin, clopidogrel and clopidogrel plus aspirin on prevention of recurrent ischemic stroke due to intracranial artery stenosis

    OpenAIRE

    Jinqiu Yang; Lukui Chen; Naveen Chitkara; Qiang Xu

    2014-01-01

    Background: Given the importance of intracranial stenosis as a cause of recurrent ischemic stroke and the lack of evidence supporting a clear choice for prevention of recurrent ischemic events, a computer simulation model for prognostic prediction could be used to improve decision making. Aims: The aim of the following study is to compare the long-term effect of aspirin, clopidogrel and clopidogrel plus aspirin for prevention of recurrent stroke due to atherosclerotic intracranial artery sten...

  12. A Randomized trial comparing ticlopidine with aspirin fof the prevention of ischemic cerebral stroke

    Institute of Scientific and Technical Information of China (English)

    Li Yizhao; Li Danian; Wang Lei

    2000-01-01

    OBJECTIVE To assess the effect and cafety of t iclopidine in the prevention of ischemic cerebral stroke and to compare theeffect of low-dose aspirin with t iclopidine. BACKGROUND The effect and safety of ticlopidine irn the prevention of ischemic cerebral stroke in China has not been reported. METHODS 329 patients with TIA or mild ischemic cevebral stroke wasrandonmly assigned to ticlopidine group(165 case) or aspirin group (164 case) in this study.These patrents were randomly allocated to receive either 250mg trclopidine or 50mg aspirin daily and didnd take any other platelet antiaggregating drugs. Time of eacn follow up visit was one to two months. Follow up lasted for 6 to 18 months. RESULTS The event rate for stroke or death from any cause was 8.3% in ticlopidine group arid 14.9% in aspirin group. This repesented a risk reduction of 44.3%(95% cofidence interval, 0.29-0.94) for ticiopidine group as compared with aspirin group. The event raite for ischemic cerebral stroke or myocarction of ticlopidine group(7.0%)was lower than that cf aspirin group(14.8%)(P<0.05).A riskreduction of 52.7%(95% confidence interval,0.24-0.92) for ticlopidine group compared with aspirin group. The rate of adverse effects of ticlopidine group and aspirin group were 6.9% and 11.0% during the trial ,but this was not statistically significant(P<0.05).DISCUSSION and CONCLUSION Therapeutic efficacy for the prevention oi ischemic stroke of ticlopidine was better than that of aspirin, the rate of side effects in ticlopidine group and aspirin group are not statistically significant. So ticiopidine could serve as a first-line drug for the prevention of ischemic stroke.

  13. Use of Health Care System-Supplied Aspirin by Veterans With Postoperative Heart Attack or Unstable Angina.

    Science.gov (United States)

    Rivera, Cathleen M; Copeland, Laurel A; McNeal, Catherine J; Mortensen, Eric M; Pugh, Mary J; MacCarthy, Daniel J

    2015-10-01

    Evidence-based guidelines for the use of aspirin in secondary prevention of cardiovascular disease events are well established. Despite this, the prevalence of aspirin use for secondary prevention is suboptimal. The study aimed to determine the prevalence of aspirin use for secondary prevention of cardiovascular disease events when it is dispensed as a prescription, as is performed in the Veterans Affairs (VA) managed care system. VA patients who had undergone major surgery and experienced a postoperative myocardial infarction (MI) or unstable angina between the years 2005 and 2009 were identified from administrative databases. VA pharmacy records were used to determine whether a prescription for aspirin was filled after the postoperative MI or unstable angina. Multivariable logistic regression models estimated odd ratios of filling aspirin prescriptions for the predictors of interest. Of the 321,131 men and women veterans who underwent major surgery, 7,700 experienced a postoperative MI or unstable angina. Among those 7,700, 47% filled an aspirin prescription. Only 59% of veterans with no co-pay filled an aspirin prescription. Aspirin fills were more common in younger veterans, Blacks, Hispanics, males, hypertensive veterans, mentally ill patients, those with no co-pay and those prescribed antiplatelets/anticoagulants in addition to aspirin postoperatively. These findings suggest that the impact of dispensing aspirin as a prescription may not be significant in increasing the appropriate use of aspirin for secondary prevention. PMID:26351774

  14. Use of Health Care System-Supplied Aspirin by Veterans With Postoperative Heart Attack or Unstable Angina.

    Science.gov (United States)

    Rivera, Cathleen M; Copeland, Laurel A; McNeal, Catherine J; Mortensen, Eric M; Pugh, Mary J; MacCarthy, Daniel J

    2015-10-01

    Evidence-based guidelines for the use of aspirin in secondary prevention of cardiovascular disease events are well established. Despite this, the prevalence of aspirin use for secondary prevention is suboptimal. The study aimed to determine the prevalence of aspirin use for secondary prevention of cardiovascular disease events when it is dispensed as a prescription, as is performed in the Veterans Affairs (VA) managed care system. VA patients who had undergone major surgery and experienced a postoperative myocardial infarction (MI) or unstable angina between the years 2005 and 2009 were identified from administrative databases. VA pharmacy records were used to determine whether a prescription for aspirin was filled after the postoperative MI or unstable angina. Multivariable logistic regression models estimated odd ratios of filling aspirin prescriptions for the predictors of interest. Of the 321,131 men and women veterans who underwent major surgery, 7,700 experienced a postoperative MI or unstable angina. Among those 7,700, 47% filled an aspirin prescription. Only 59% of veterans with no co-pay filled an aspirin prescription. Aspirin fills were more common in younger veterans, Blacks, Hispanics, males, hypertensive veterans, mentally ill patients, those with no co-pay and those prescribed antiplatelets/anticoagulants in addition to aspirin postoperatively. These findings suggest that the impact of dispensing aspirin as a prescription may not be significant in increasing the appropriate use of aspirin for secondary prevention.

  15. Effects of copper-aspirin complex on platelet-neutrophil interactions

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang SHEN; Peng CHEN; Ling LI; Peng CHEN; Wei-ping LIU

    2004-01-01

    AIM: To investigate the effects of copper-aspirin complex on rat thrombosis and the interaction between platelets and neutrophils. METHODS: The model of electrically stimulated carotid artery thrombosis in Sprague Dawley rats was used; the effects of copper-aspirin complex on rat platelet-neutrophil adhesion and platelet aggregation stimulated by activated neutrophils were observed by rosette assay and Born's method, respectively. RESULTS:Intragastric copper-aspirin complex (5, 7, and 10 mg/kg) dose-dependently prolonged the occlusion time; it significantly decreased the rosette number formed between thrombin-activated platelets and neutrophils; the 50 % of inhibitory concentration (IC50) was (54.6±4.3) μmol/L. Copper-aspirin complex markedly inhibited rat platelet aggregation induced by either cell free supernatant of activated neutrophils or by activated neutrophil suspension.The values of IC50 were (224.5±16.2) μmol/L and (820.5±21.4) μmol/L, whereas aspirin had no influence.CONCLUSION: Copper-aspirin complex inhibited platelet-neutrophil interactions through a different property from aspirin and resulted in a more potent antithrombotic activity.

  16. 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.

  17. 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.

  18. Luteolin supplementation adjacent to aspirin treatment reduced dimethylhydrazine-induced experimental colon carcinogenesis in rats.

    Science.gov (United States)

    Osman, Neamt H A; Said, Usama Z; El-Waseef, Ahmed M; Ahmed, Esraa S A

    2015-02-01

    Previous studies have shown that aspirin is used in colon cancer treatment. However, long-term of Aspirin usage is limited to gastric and renal toxicity. Luteolin (LUT) has cancer prevention and anti-inflammatory effects. The present study was designed to investigate the effect of LUT supplementation and Aspirin treatment in dimethylhydrazine (DMH)-induced carcinogenesis in rats. DMH (20 mg/kg BW/week) treated rats received gavages with Aspirin (50 mg/kg BW/week) and LUT (0.2 mg/kg BW/day) for 15 weeks. DMH injections induce colon polyps and renal bleeding, significantly increasing carcinoembryonic antigen (CEA), cyclooxygenase-2 (COX-2), oxidative stress, and kidney function tests and reducing antioxidant markers. Either Aspirin or LUT gavages alone or combined produce a significant decrease in colon polyp number and size, significantly decreasing CEA, COX-2, and oxidative stress and increasing antioxidant markers. In conclusion, the supplementations of LUT adjacent to Aspirin in the treatment of DMH-induced carcinogenesis in rats reflect a better effect than the use of Aspirin alone. PMID:25342594

  19. Pharmacokinetics of salicylic acid following administration of aspirin tablets and three different forms of soluble aspirin in normal subjects.

    Science.gov (United States)

    Gatti, G; Barzaghi, N; Attardo Parrinello, G; Vitiello, B; Perucca, E

    1989-01-01

    The pharmacokinetic profile of an innovative formulation of soluble aspirin (l-ornithine acetylsalicylate, ldB 1003) was compared with that of conventional tablets and two other soluble dosage forms (d, l-lysine acetylsalicylate and a buffered effervescent formulation of acetylsalicylic acid) after administration of single oral doses in six normal volunteers. All soluble forms showed a rapid absorption profile, peak plasma salicylic acid levels being attained after about 30 min on average and without statistically significant differences among the solutions tested. As compared to the soluble formulations, acetylsalicylic acid given as tablets resulted in slower absorption, with peak plasma salicylic acid levels being reached more than 1 h after dosing. Despite these differences in time course of plasma level profiles, the extent of absorption was similar for all formulations. Apart from the potential advantages in terms of improved gastric tolerability, the increased rate of absorption of aspirin solutions is therapeutically useful whenever a rapid onset of action is required. In this respect, the kinetic pattern of the innovative formulation compares favourably with that of other available soluble dosage forms. PMID:2517497

  20. 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.

  1. Aspirin in polycythemia vera and essential thrombocythemia: current facts and perspectives.

    Science.gov (United States)

    Landolfi, R; Patrono, C

    1996-09-01

    The role of aspirin in the antithrombotic strategy of patients with polycythemia vera (PV) and essential thrombocythemia (ET) is highly controversial. Long considered unsafe on the basis of a single clinical trial testing very high doses in PV patients, aspirin is being increasingly used at lower dosage. The rationale for the use of aspirin in patients with PV and ET is provided by the efficacy of this agent in the treatment of microcirculatory disturbances of thrombocythemic states associated with myeloproliferative disorders and by recent evidence that asymptomatic PV and ET patients have persistently increased thromboxane (TX) A2-biosynthesis. This increase, which most likely reflects enhanced platelet activation in vivo, is independent of the platelet mass and blood viscosity and largely supressed by a short term low-dose aspirin regimen (50 mg/day for 7 days). Since enhanced TXA2 biosynthesis may play a role in transducing the increased thrombotic risk associated with PV and ET, long-term low-dose aspirin administration has been proposed as a possible antithombotic strategy in these subjects. The safety of this treatment in PV patients has been recently reassessed by the Gruppo Italiano per lo Studio della Policitemia Vera (GISP) which has followed for over one year 112 patients randomized to receive 40 mg/day aspirin or placebo. In the same study, serum TXB2 measurements provided evidence that the low-dose aspirin regimen tested was fully effective in inhibiting platelet cyclooxygenase activity. On this basis, a large scale trial aimed at assessing the antithrombotic efficacy of this approach is currently being organized. In patients with ET both the minimal aspirin dose required for complete inhibition of platelet cyclooxygenase and the safety of long-term aspirin administration need to be established prior to extensive clinical evaluation of this strategy.

  2. European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial.

    Science.gov (United States)

    Landolfi, R; Marchioli, R

    1997-01-01

    Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value 50. Randomization will be stratified by participating center. The study is funded by the European Union BIOMED 2 program.

  3. Aspirin use and lung cancer risk: a possible relationship? Evidence from an updated meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hai-yan Jiang

    Full Text Available Growing evidence has emerged and controversial results reported on possible relationship between aspirin use and lung cancer risk. We, therefore, conducted this updated and comprehensive meta-analysis to evaluate this issue, with focus on dose-risk and duration-risk relationships.We searched electronic databases including PUBMED, EMBASE and Cochrane library to identify eligible studies. Relative risk (RR and its 95% confidence interval (CI were used for cohort studies, while odds ratio (OR were employed for case-control studies. The random effects and fixed effects models were used for analyses.18 studies were identified including 19835 lung cancer cases, which were eligible for inclusion in the present meta-analysis. Pooled data from case-control studies showed a significant inverse association between regular aspirin use and lung cancer risk. But for cohort studies, insignificant association was detected with little evidence of heterogeneity (RR: 1.05, 95%CI: 0.95 - 1.16; I2: 10.3%, p value: 0.351. In case-control studies, standard aspirin use (>325mg was related to lower lung cancer incidence, compared with low-dose aspirin use (75-100mg. A similar trend was observed in cohort studies. Besides, when analysis was restricted to long time regular aspirin use (>5 years, insignificant results were reported in both cohort and case-control studies. Finally, regular aspirin use might result in higher reduction of non-small cell lung cancer incidence among men.Our findings do not support the protective effect of regular aspirin use on lung cancer risk. Long time aspirin use, sex, dose and type of lung cancer might alter the effect of aspirin use on lung cancer risk. More well-designed studies are needed to further clarify these associations.

  4. Aspirin increases susceptibility of Helicobacter pylori to metronidazole by augmenting endocellular concentrations of antimicrobials

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Zhang; Wei-Hong Wang; Yu Tian; Wen Gao; Jiang Li

    2009-01-01

    AIM: To investigate the mechanisms of aspirin increasing the susceptibility of Helicobacter pylori ( H pylori) to metronidazole. METHODS: H pylori reference strain 26 695 and two metronidazole-resistant isolates of H pylori were included in this study. Strains were incubated in Brucella broth with or without aspirin (1 mmol/L). The rdxA gene of H pylori was amplified by PCR and sequenced. The permeability of H pylori to antimicrobials was determined by analyzing the endocellular radioactivity of the cells after incubated with [7-3H]-tetracycline. The outer membrane proteins (OMPs) of H pylori 26 695 were depurated and analyzed by SDS-PAGE. The expression of 5 porins (hopA, hopB, hopC, hopD and hopE) and the putative RND efflux system (hefABC) of H pylori were analyzed using real-time quantitative PCR. RESULTS: The mutations in rdxA gene did not change in metronidazole resistant isolates treated with aspirin. The radioactivity of H pylori increased when treated with aspirin, indicating that aspirin improved the permeability of the outer membrane of H pylori. However, the expression of two OMP bands between 55 kDa and 72 kDa altered in the presence of aspirin. The expression of the mRNA of hopA, hopB, hopC, hopD, hopE and hefA, hefB, hefC of H pylori did not change when treated with aspirin. CONCLUSION: Although aspirin increases the susceptibility of H pylori to metronidazole, it has no effect on the mutations of rdxA gene of H pylori. Aspirin increases endocellular concentrations of antimicrobials probably by altering the OMP expression.

  5. 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...

  6. 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.

  7. Trace metal content in aspirin and women's cosmetics via proton induced x-ray emission (PIXE)

    International Nuclear Information System (INIS)

    A multielemental analysis to determine the trace metal content of generic and name-brand aspirins and name-brand lipsticks was done via proton induced x-ray (PIXE) measurements. The Hope College PIXE system is described as well as the target preparation methods. The trace metal content of twelve brands of aspirin and aspirin substitutes and fourteen brands of lipstick are reported. Detection limits for most elements are in the range of 100 parts per billion (ppb) to 10 parts per million

  8. The effects of aspirin plus cisplatin on SGC7901/CDDP cells in vitro

    OpenAIRE

    DONG, HANZHANG; LIU, GAOGAO; Jiang, Biao; GUO, JIUBING; TAO, GUOQUAN; YIU, WEI; Zhou, Jingsong; Li, Guoxin

    2014-01-01

    The purpose of this study was to determine the effect of aspirin plus cisplatin (CDDP) in the chemotherapy of gastric cancer. We cultured SGC7901/CDDP cells by long-term exposure of SGC7901 cells to small doses of CDDP in vitro. The cells were treated with aspirin, CDDP or aspirin plus CDDP for 24 h and cell growth was assessed by the MTT assay, the apoptotic rate by flow cytometry, the survivin mRNA expression by RT-PCR and the survivin protein expression by western blotting. The results rev...

  9. Stress modification of the toxicity of antimotion sickness drugs and Aspirin

    Science.gov (United States)

    Shields, D.; Marra, C.; Goodwin, A.; Vernikos-Danellis, J.

    1975-01-01

    The effect of environmental temperature on the toxicity of cyclizine, trimethobenzamide, and Aspirin were studied in mice. LD-50s were compared at 30 C, 22 C, and 15 C. At 30 C the toxicity of all three drugs increased, with that to Aspirin being affected most. Cooling decreased the toxicity of cyclizine and had no significant effect on that of trimethobenzamide or aspirin. These findings indicate that alterations in environmental temperature markedly affect drug toxicity. They emphasize that such alterations, and particularly increases in temperature, do not have to be particularly drastic, but that 'mild' variations in the environment are effective in altering an animal's sensitivity to a drug.

  10. Aspirin Could Save 40,000 Lives a Year

    Institute of Scientific and Technical Information of China (English)

    Patricia; Reaney; 励蓓蓓

    2002-01-01

    鄙人是服用Aspirin的受益者,所以当我在网上读到此文时,非常兴奋,很想把此短文推荐给我最喜爱的《科技英语学习》的读者们。Aspirin能够稀释人体血液的浓度,因而能有效减少心脏病和中风的危险。服用Aspirin后,体内血液更加流畅,因此,我感到服用Aspirin后,头脑清晰如洗,精神也清朗如浴。 当然,本文的最后一句哲理之言,不能不细读: Aspirin is not an appropriate treatment for everyon but it is important that allthase who might benefit are actually offered it。】

  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. Paroxysmal vascular events in Sturge– Weber syndrome: Role of aspirin

    Directory of Open Access Journals (Sweden)

    Jyoti Sanghvi

    2014-01-01

    Full Text Available Sturge-Weber syndrome (SWS is a rare, sporadically occurring neurocutaneous disorder with a frequency of approximately 1 per 50,000. The hallmark is an intracranial leptomeningeal vascular angioma in association with a port wine nevus, usually involving ophthalmic or maxillary distribution of trigeminal nerve. Other clinical findings associated with SWS are seizures, glaucoma, hemiparesis and mental retardation. The radiological hallmark is "Tram-line" or "Gyri-form" calcification. 25 to 56% of patients experience recurrent episodes of paroxysmal focal neurological deficits in form of transient hemiparesis, which may be due to vascular ischemia or postictal in origin. EEG helps to differentiate the exact etiology, as it is normal in former. Aspirin prophylaxis in those, due to ischemia decreases their recurrences and improves overall neurological prognosis. We report a 25-month-old child of SWS with recurrent episodes of transient hemiparesis and atypical midline location of facial vascular nevus.

  13. 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...... 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...... differences between the two groups with respect to the development of advanced neoplasia (7.4% and 9.9%, respectively; P=0.33). Among the 727 participants receiving resistant starch or placebo, neoplasia developed in 67 participants receiving starch (18.7%), as compared with 68 receiving placebo (18...

  14. 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.

  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. 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.

  17. Aspirin and clopidogrel resistance: possible mechanisms and clinical relevance. Part II: Potential causes and laboratory tests.

    Science.gov (United States)

    Vadász, Dávid; Sztriha, László K; Sas, Katalin; Vécsei, László

    2013-01-30

    Recent meta-analyses have indicated that patients with vascular disease demonstrated by laboratory tests to be aspirin or clopidogrel-resistant are at an increased risk of major vascular events. The suggested mechanisms of aspirin resistance include genetic polymorphism, alternative pathways of platelet activation, aspirin-insensitive thromboxane biosynthesis, drug interactions, or a low aspirin dose. Clopidogrel resistance is likely to develop as a result of a decreased bioavailability of the active metabolite, due to genetic variation or concomitant drug treatment. Additional work is required to improve and validate laboratory tests of platelet function, so that they may become useful tools for selection of the most appropriate antiplatelet therapy for an individual patient. Improvements in antiplatelet treatment strategies in the future should lead to a reduction in premature vascular events. PMID:23607225

  18. Effects of prednisone, aspirin, and acetaminophen on an in vivo biologic response to interferon in humans.

    Science.gov (United States)

    Witter, F R; Woods, A S; Griffin, M D; Smith, C R; Nadler, P; Lietman, P S

    1988-08-01

    In healthy volunteers receiving a single intramuscular dose of 18 X 10(6) U interferon alone or after 24 hours of an 8-day course of prednisone (40 mg/day), aspirin (650 mg every 4 hours), or acetaminophen (650 mg every 4 hours), the magnitude of the biologic response to interferon was quantified by measuring the time course of the induction of 2'-5'-oligoadenylate synthetase and resistance to vesicular stomatitis virus infection in human peripheral blood mononuclear cells. Prednisone decreased the AUC of 2'-5'-oligoadenylate synthetase activity (p less than 0.05), whereas administration of aspirin or acetaminophen did not affect this biologic response. No measurable effect was seen during administration of prednisone, aspirin, or acetaminophen on the duration or intensity of vesicular stomatitis virus yield reduction. The side effects seen with interferon administration at the dose tested were not altered in a clinically meaningful manner by prednisone, aspirin, or acetaminophen. PMID:2456175

  19. Comparative evaluation of antipyretic activity of ibuprofen and aspirin in children with pyrexia of varied aetiology.

    Science.gov (United States)

    Kandoth, P W; Joshi, M K; Joshi, V R; Satoskar, R S

    1984-01-01

    The antipyretic activity of ibuprofen and aspirin was compared in sixteen children with pyrexia due to upper respiratory tract infection and in twelve with fever due to other causes. All 28 children received ibuprofen (7 mg/kg of body-weight) and aspirin (15 mg/kg of body-weight) in a single dose on 2 consecutive days in a crossover manner. Rectal temperature was recorded prior to and at regular intervals up to 8 hours after drug administration. Analysis of the results indicate that ibuprofen and aspirin effectively lower temperature and the two drugs are comparable in their antipyretic activity. In conclusion, significant antipyretic activity, good tolerance profile and availability in syrup form make ibuprofen a useful substitute for aspirin in children with fever. PMID:6500169

  20. 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.

  1. 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....../m(2) increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation...... risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin....

  2. Promising psyllium-based composite containing TiO2 nanoparticles as aspirin-carrier matrix

    Institute of Scientific and Technical Information of China (English)

    Marcela-Corina Rosun; Ioan Bratu

    2014-01-01

    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 1C. 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.

  3. 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

  4. Use of Aspirin Associates with Longer Primary Patency of Hemodialysis Grafts

    OpenAIRE

    Dixon, Bradley S.; Beck, Gerald J.; Dember, Laura M; Vazquez, Miguel A.; Greenberg,Arthur; Delmez, James A.; Allon, Michael; Himmelfarb, Jonathan; Hu, Bo; Greene, Tom; Radeva, Milena K.; Davidson, Ingemar J.; Ikizler, T. Alp; Braden, Gregory L.; Lawson, Jeffrey H.

    2011-01-01

    Extended-release dipyridamole plus low-dose aspirin (ERDP/ASA) prolongs primary unassisted graft patency of newly created hemodialysis arteriovenous grafts, but the individual contributions of each component are unknown. Here, we analyzed whether use of aspirin at baseline associated with primary unassisted graft patency among participants in a randomized trial that compared ERDP/ASA and placebo in newly created grafts. We used Cox proportional hazards regression, adjusting for prespecified b...

  5. 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...

  6. Study of effects of donepezil and aspirin on working memory in rats using electroconvulsive shock model

    OpenAIRE

    Rahul M. Manjare; Abhijit V. Tilak; Bhalchandra T. Rane; Sanjay A. Dabhade; Rahul R. Bhalsinge; Harshal P. Patil

    2014-01-01

    Background: Memory is the most common cognitive ability lost with dementia commonly seen in Alzheimer's disease (AD). Donepezil was the first cholinesterase inhibitor to be licensed in UK for AD. There is preliminary evidence that aspirin decreases the risk and delays the onset of AD. Low dose aspirin users had numerically lower prevalence of Alzheimer's dementia and had better cognitive function than non-users. Methods: Retention of conditioned avoidance response (CAR) was assessed by usi...

  7. ANTI ULCER EFFECT OF BASELLA ALBA LEAF EXTRACT IN ASPIRIN INDUCED ALBINO RATS

    OpenAIRE

    P. Venkatalakshmi et al

    2012-01-01

    The present study was designed to evaluate the anti ulcer effect of Basella alba in aspirin induced ulcerated rats. Aspirin induced ulcer was revealed by increased ulcer index, decreased gastric pH, increase in the levels of pepsin, Thio barbituric acid reactive substance (TBARS). Lipid hydroperoxides and decrease in the levels of enzymatic and non enzymatic antioxidants. Treatment with the plant extract brought back the altered parameters to normal.

  8. ANTI ULCER EFFECT OF BASELLA ALBA LEAF EXTRACT IN ASPIRIN INDUCED ALBINO RATS

    Directory of Open Access Journals (Sweden)

    P. Venkatalakshmi et al

    2012-08-01

    Full Text Available The present study was designed to evaluate the anti ulcer effect of Basella alba in aspirin induced ulcerated rats. Aspirin induced ulcer was revealed by increased ulcer index, decreased gastric pH, increase in the levels of pepsin, Thio barbituric acid reactive substance (TBARS. Lipid hydroperoxides and decrease in the levels of enzymatic and non enzymatic antioxidants. Treatment with the plant extract brought back the altered parameters to normal.

  9. Studies on the hydrolysis of biocompatible acrylic polymers having aspirin-moieties.

    Science.gov (United States)

    Gu, Z W; Li, F M; Feng, X D; Voong, S T

    1983-01-01

    Both the homogeneous and heterogeneous hydrolysis of five new acrylic polymers having aspirin-moieties, i.e. polymers of beta-(acetylsalicylyloxy)ethyl methacrylate, beta-(acetylsalicylyloxy) propyl methacrylate,beta-(acetylsalicylyloxy) ethyl acrylate, beta-hydroxy-gamma-(acetylsalicylyloxy) propyl methacrylate, beta-hydroxy-gamma-(acetylsalicylyloxy) propyl acrylate were investigated in acidic or alkaline medium at 30 degrees C or 60 degrees C, respectively. It was observed that the chief hydrolyzed product is always aspirin with minor amount of salicylic acid.

  10. Aspirin inhibits tumor necrosis factor-α-stimulated fractalkine expression in human umbilical vein endothelial cells

    Institute of Scientific and Technical Information of China (English)

    JIANG De-qian; LIU Hong; ZHANG She-bing; ZHANG Xiao-lian

    2009-01-01

    Background Fractalkine is an important chemokine mediating local monocyte accumulation and inflammatory reactions in the vascular wall. Aspirin inhibits inflammatory cytokine expression closely related to atherosclerosis through the way independent of platelet and cyclooxygenase (COX). There has been no report about the effect of aspirin on fractalkine expression. We aimed to determine the fractalkine expression in human umbilical vein endothelial cell (HUVEC) stimulated by tumor necrosis factor (TNF)-α and the effect of aspirin intervention.Methods Six of 8 HUVEC groups received either different concentrations of aspirin (0.02, 0.2, 1.0, 5.0 mmol/L) or 40 μmol/L pyrrolidinecarbodithioc acid (PDTC) or 0.5 μmol/L NS-398. The other two groups were negative control and positive control (TNF-α-stimulated). After being incubated for 24 hours, cells of the 8 groups except the negative control one were stimulated with TNF-a (4 ng/ml) for another 24 hours. After that, the cells were collected for RNA isolation and protein extraction.Results Both mRNA and protein expressions of fractalkine in HUVEC were upregulated by 4 ng/ml TNF-α stimulation,Aspirin inhibited fractalkine expression in a dose-dependent manner at mRNA and protein levels. Nuclear factor-kappa B inhibitor, PDTC, effectively decreased the fractalkine expression. Fractalkine expression was not influenced by COX-2 selective inhibitor NS-398. COX-1 protein expression was not changed by either TNF-α stimulation or aspirin, PDTC,NS-398 intervention. Both mRNA and protein expression of COX-2 in HUVEC were upregulated by 4 ng/ml TNF-α stimulation. Aspirin decreased COX-2 expression in a dose-dependent manner at mRNA and protein levels.Conclusions TNF-α-stimulated fractalkine expression is suppressed by aspirin in a dose-dependent manner through the nuclear factor-kappa B p65 pathway.

  11. Effect of low-dose aspirin during pregnancy on fibrinolytic variables before and after parturition

    OpenAIRE

    Bremer, Henk; Rotmans, Nel; Brommer, E.J.Ph.; Wallenburg, Henk

    1995-01-01

    textabstractOBJECTIVE: We assessed the effects of a daily oral dose of 60 to 80 mg of aspirin from 12 weeks gestation until delivery on fibrinolytic variables before and after parturition. STUDY DESIGN: In a prospective controlled study labor was electively induced in 24 patients, eight receiving low-dose aspirin and 16 controls. Levels were determined in maternal and cord plasma of tissue-type plasminogen activator antigen and activity, plasminogen activator inhibitor-1 antigen, plasminogen ...

  12. Aspirin has little additional anti-platelet effect in healthy volunteers receiving prasugrel

    OpenAIRE

    LEADBEATER, P D M; Kirkby, N S; Thomas, S.(Rutgers, The State University of New Jersey, Piscataway, USA); DHANJI, A-R; Tucker, A T; MILNE, G L; Mitchell, J. A.; Warner, T D

    2011-01-01

    Summary Background: Strong P2Y12 blockade, as can be achieved with novel anti-platelet agents such as prasugrel, has been shown in vitro to inhibit both ADP and thromboxane A2-mediated pathways of platelet aggregation, calling into question the need for the concomitant use of aspirin. Objective: The present study investigated the hypothesis that aspirin provides little additional anti-aggregatory effect in a group of healthy volunteers taking prasugrel. Study participants/methods: In all, 9 m...

  13. Assessment of aspirin resistance varies on a temporal basis in patients with ischaemic heart disease

    OpenAIRE

    Muir, A. R.; McMullin, Mary; Patterson, Christopher; McKeown, Pascal

    2009-01-01

    Objective: Laboratory tests including optical platelet aggregometry (OPA), platelet function analyser (PFA-100), and thromboxane B2 (TXB2) metabolite levels have been used to define aspirin resistance. This study characterised the prevalence of aspirin resistance in patients with ischaemic heart disease (IHD) and investigated the concordance and repeatability of these tests. Design, setting and patients: Consecutive outpatients with stable IHD were enrolled. They were commenced on 150 mg aspi...

  14. Genç Bireylerde Aspirin Ve Vitamin C Emiliminin Etkileşimi

    OpenAIRE

    ÖZDENER, H.; AMANVERMEZ, R.; ÇELİK, C.

    2010-01-01

    The Interaction of Aspirin and Ascorbic Acid Absorption in Healthy Young Individuals Aspirin (acetylsalicyclic acid) and vitamin C (ascorbic acid) are commonly used two drugs. Metabolic importance of vitamin C has been risen due to understanding the function of vitamin C on metabolic pathway in human. To known how maintain serum and tissue levels in normal ranges is very crucial to avoid vitamin C deficiency. Therefore vitamin C and drug interaction, particulary for long term use, is ve...

  15. 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

    was twice the prevalence in patients without AMI. METHODS: We included 298 consecutive patients with known cardiovascular disease who were admitted to hospital with symptoms suggestive of an AMI. All had been taking aspirin 150 mg/day for at least 7 days prior to hospital admission. Platelet function...... with symptoms suggestive of an AMI, and aspirin resistance is significantly associated with the diagnosis of a definite AMI....

  16. Aspirin-intolerant asthma in the population : prevalence and important determinants

    OpenAIRE

    Eriksson, Jonas; Ekerljung, Linda; Bossios, Apostolos; Bjerg, Anders; Wennergren, Göran; Rönmark, Eva; Torén, Kjell; Lötvall, Jan; Lundbäck, Bo

    2015-01-01

    BACKGROUND: Population-based studies on aspirin-intolerant asthma are very few and no previous population study has investigated risk factors for the condition. OBJECTIVE: To investigate the prevalence and risk factors of aspirin-intolerant asthma in the general population. METHODS: A questionnaire on respiratory health was mailed to 30 000 randomly selected subjects aged 16-75 years in West Sweden, 29 218 could be traced and 18 087 (62%) responded. The questionnaire included questions on ast...

  17. The inhibitory effect of simvastatin and aspirin on histamine responsiveness in human vascular endothelial cells.

    Science.gov (United States)

    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.

  18. Altered mental status and complete heart block: an unusual presentation of aspirin toxicity

    OpenAIRE

    Aggarwal, Nidhi; Kupfer, Yizhak; Chawla, Kabu; Tessler, Sidney

    2013-01-01

    Aspirin is one of the most commonly used medications. We report a patient who presented with severe weakness, altered mental status and complete heart block requiring temporary pacing. Despite the patient's family denying that the patient used aspirin, an arterial blood gas that revealed a respiratory alkalosis and metabolic acidosis suggested the diagnosis of salicylate toxicity. The salicylate level was extremely elevated and the patient was successfully treated with haemodialysis. Our case...

  19. Clinical evidence for the use of aspirin in the treatment of cancer

    OpenAIRE

    Langley, Ruth E

    2013-01-01

    Although the anti-cancer effects of aspirin were first identified in pre-clinical models four decades ago, a clear role for the drug in either the prevention or treatment of cancer has not been established. Concerns about toxicity, particularly major haemorrhage, and a lack of randomised evidence demonstrating efficacy have limited its use in primary prevention; there was also doubt that a simple aspirin could have a significant therapeutic effect against established malignancy. Three new pie...

  20. The gastrointestinal toxicity of aspirin: an overview of randomised controlled trials.

    OpenAIRE

    Roderick, P. J.; Wilkes, H C; Meade, T W

    1993-01-01

    The proven benefit of aspirin in the secondary prevention of cardiovascular disease and its possible value in primary prevention must be weighted against its potential hazards. This paper is an overview of the gastrointestinal toxicity of aspirin, its most serious complication after intracerebral haemorrhage. Information on toxicity has been drawn only from randomised trials, thus avoiding the potential biases of observational studies. All randomised placebo controlled trials listed in the An...

  1. Psychotropic effects of aspirin, acetylsalicylate cobalt and acetylsalicylate zinc at various doses

    OpenAIRE

    Tatyana V. Yakovchyuk; Oksana V. Katiushyna; Ivan I. Koreniuk; Denis R. Khusainov; Tatyana V. Gamma

    2012-01-01

    For the first time it is shown that psychotropic action of acetylsalicylates at various doses is manifested as a nonmonotonic dependence having its peaks at therapeutic and ultra-low dose zones. It is discovered that development of effects of aspirin resembles that of acetylsalicylate zinc. Acetylsalicylate cobalt at extremely low doses zone showed the highest antidepressant activity, demonstrating toxicity at high doses. Generally, it is revealed that the use of aspirin and its salts at high...

  2. Electrochemical oxidation of drug residues in water by the example of tetracycline, gentamicine and aspirin.

    Science.gov (United States)

    Weichgrebe, D; Danilova, E; Rosenwinkel, K H; Vedenjapin, A A; Baturova, M

    2004-01-01

    Electro-chemical oxidation as a method to destroy drug residues like aspirin, tetracycline or gentamicine in water was investigated with C-anodes (modified by manganese oxides) and Pt anodes. The mechanism of aspirin and tetracycline oxidation and the influence of the biocide effect was observed using GC-MS and three different microbiological tests. In general, the biological availability increases with progressive oxidation of the antibiotics. PMID:15077972

  3. 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.

  4. 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.

  5. 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.

  6. SOX7 is involved in aspirin-mediated growth inhibition of human colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xin Zhou; Shu-Yan Huang; Jing-Xin Feng; Yan-Yan Gao; Li Zhao; Jun Lu; Bai-Qu Huang; Yu Zhang

    2011-01-01

    AIM: To confirm the role of sex-determining region Y-box 7 (Sox7) in aspirin-mediated growth inhibition of COX-independent human colorectal cancer cells.METHODS: The cell survival percentage was examined by MTT (Moto-nuclear cell direc cytotoxicity) assay.SOX7 expression was assessed by using reverse transcription-polymerase chain reaction and Western blotting. SB203580 was used to inhibit the p38MAPK signal pathway. SOX7 promoter activity was detected by Luciferase reporter assay.RESULTS: SOX7 was upregulated by aspirin and was involved in aspirin-mediated growth inhibition of SW480 human colorectal cancer cells. The p38MAPK pathway played a role in aspirin-induced SOX7 expression, during which the AP1 transcription factors c-Jun and c-Fos upregulated SOX7 promoter activities.RESULTS: SOX7 is upregulated by aspirin and is involved in aspirin-mediated growth inhibition of human colorectal cancer SW480 cells.

  7. 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.

  8. 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.

  9. Effect of Aspirin on Cell Growth of Human MG-63 Osteosarcoma Line

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    E. De Luna-Bertos

    2012-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are commonly used in bone tissue repair treatment for their pharmacological action. The objective of this study was to determine the effect of aspirin, on osteoblast growth, using MG63 cell line as osteoblast model. MTT spectrophotometry results showed that 20, 100, and 1000 μM aspirin doses have an inhibitory effect on growth. Cell cycle analysis revealed that aspirin doses of 100 and 1000 μM arrest the cell cycle in phase GO/G1. Parallel apoptosis/necrosis studies showed no changes in comparison to control cells after treatment with 1 or 10 μM aspirin but a significantly increased percentage of cells in apoptosis at doses of 20, 100, and 1000 μM. We highlight that treatment of osteoblast-like cells with 1000 μM aspirin increased not only the percentage of cells in apoptosis but also the percentage of necrotic cells, which was not observed in aspirin treatments at lower doses.

  10. 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

  11. Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Simon, Ronald A

    2004-01-01

    Aspirin-exacerbated respiratory disease (AERD) is an adult-onset condition that manifests as asthma, rhinosinusitis/nasal polyps, and sensitivity to aspirin and other cyclooxygenase-1 (COX-1)-inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs). There is no cross-sensitivity to highly selective COX-2 inhibitors. AERD is chronic and does not improve with avoidance of COX-1 inhibitors. The diagnosis of AERD is made through provocative challenge testing. Following a positive aspirin challenge, patients can be desensitized to aspirin and NSAIDs. The desensitized state can be maintained indefinitely with continued daily administration. After desensitization, there is an approximately 48-hour refractory period to adverse effects from aspirin. The pathogenesis of AERD remains unknown, but these patients have been shown to have multiple abnormalities in arachidonic acid metabolism and in cysteinyl leukotriene 1 receptors. AERD patients can take up to 650 mg of acetaminophen for analgesic or antipyretic relief. Patients can also use weak COX-1 inhibitors, such as sodium salicylate or choline magnesium trisalicylate. Treatment of AERD patients with antileukotriene medications has been helpful but not preferential when compared with non-AERD patients. An alternative treatment for many AERD patients is aspirin desensitization. This is particularly effective in reducing upper-airway mucosal congestion, nasal polyp formation, and systemic steroids. PMID:14680616

  12. The influence of gender on the effects of aspirin in preventing myocardial infarction

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    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.

  13. 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

  14. Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray

    Institute of Scientific and Technical Information of China (English)

    Xue-qin GAO; Jin-xiang HAN; Hai-yan HUANG; Shi YAN; Chang-zheng SONG; Hai-nan HUANG

    2004-01-01

    AIM: To investigate the effect of aspirin on the metastasis-associated gene expression in 3AO ovarian cancer cells.METHODS: 3AO cells were treated with aspirin at the concentration of 1.2 mmol/L for 16 and 48 h, respectively.The total RNA was extracted with Trizol reagents and reverse transcribed with Superscript II and hybridized with cDNA microarray (containing oncogenes, tumor suppressor genes, signal transduction pathway molecules, adhesive molecules, growth factors and ESTs) fabricated in our lab. After normalization, the ratio of gene expression of aspirin treated to untreated 3AO cells being either 2 fold up higher or 0.5 fold down (lower) were defined as differential expression. Semi-quantitative RT-PCR was used to validate the microarray results. RESULTS: Among the 447 metastasis-associated genes, 4 genes were up-regulated and 14 genes were down-regulated in 3AO cells treated with aspirin for 16 h compared with untreated cells. While 24 genes were up-regulated and 10 genes were down-regulated in cells treated with aspirin for 48 h. Several up or down-regulated gene expression changes continued from 16 h to 48 h. CONCLUSION: Aspirin might exert its anti-metastasis effects on ovarian cancer by affecting metastasis-associated gene expression.

  15. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials

    OpenAIRE

    De Berardis, Giorgia; Sacco, Michele; Strippoli, Giovanni F.M.; Pellegrini, Fabio; Graziano, Giusi; Tognoni, Gianni; Nicolucci, Antonio

    2009-01-01

    Objective To evaluate the benefits and harms of low dose aspirin in people with diabetes and no cardiovascular disease. Design Meta-analysis of randomised controlled trials. Data sources Medline (1966-November 2008), the Cochrane central register of controlled trials (Cochrane Library 2008;issue 4), and reference lists of retrieved articles. Review methods Randomised trials of aspirin compared with placebo or no aspirin in people with diabetes and no pre-existing cardiovascular disease were e...

  16. Down-regulation of β-catenin Nuclear Localization by Aspirin Correlates with Growth Inhibition of Jurkat Cell Line

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In this study, we examined the effects of aspirin on the growth rates, subcellar distribution of β-catenin protein, the expression of β-catenin/TCF signaling pathway target gene cyclinD1 mRNA,and cell cycle of Jurkat cell line (Human T-acute lymphoblastic leukemia). Our results showed that the treatment with aspirin inhibited the growth of Jurkat cell line. Jurkat cells treated with 3 mmol/L of aspirin could significantly decrease nuclear localization of β-catenin, and at 5 mmol/L of aspirin,the nuclear localization of β-catenin was undetectable. QRT-PCR showed that the target gene cyclinD1 mRNA expression was gradually decreased with the dosage of aspirin. Aspirin induced G0/G1cell cycle arrest in Jurkat cells. We are led to conclude that aspirin acts through β-catenin-independent mechanisms. The effects of aspirin include down-regulation of β-catenin nuclear localization and G0/G1 cell cycle arrest, which might serve as a means of growth inhibition in aspirin-treated human Jurkat cell line.

  17. Aspirin protected against endothelial damage induced by LDL:role of endogenous NO synthase inhibitors in rats

    Institute of Scientific and Technical Information of China (English)

    Sheng DENG; Pan-yue DENG; Jun-lin JIANG; Feng YE; Jing YU; Tian-lun YANG; Han-wu DENG; Yuan-jian LI

    2004-01-01

    AIM: To study the protective effect of aspirin on damages of the endothelium induced by low-density lipoprotein (LDL), and whether the protective effect of aspirin is related to reduction of nitric oxide synthase inhibitor level.METHODS: Vascular endothelial injury was induced by a single injection of native LDL (4 mg/kg) in rats. Vasodilator responses to acetylcholine (Ach) in the isolated aortic rings were determined, and serum concentrations of asymmetric dimethylarginine (ADMA), malondialdehyde (MDA), tumour necrosis factor-α(TNF-α), and the activity of dimethylaminohydrolase (DDAH) were measured. RESULTS: A single injection of LDL (4 mg/kg)significantly decreased vasodilator responses to Ach, increased the serum level of ADMA, MDA, and TNF-α, and decreased DDAH activity. Aspirin (30 or 100 mg/kg) markedly reduced the inhibition of vasodilator responses to Ach by LDL, and the protective effect of aspirin at the lower dose was greater compared with high-dose aspirin group. Aspirin inhibited the increased level of MDA and TNF-α induced by LDL. Aspirin at the dose of 30 mg/kg,but not at higher dose (100 mg/kg), significantly reduced the concentration of ADMA and increased the activity of DDAH. CONCLUSION: Aspirin at the lower dose (30 mg/kg) protects the endothelium against damages elicited by LDL in vivo, and the protective effect of aspirin on endothelium is related to reduction of ADMA concentration by increasing DDAH activity.

  18. Systems Pharmacogenomics Finds RUNX1 Is an Aspirin-Responsive Transcription Factor Linked to Cardiovascular Disease and Colon Cancer

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    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.

  19. Aspirin At 100, Still A ’Wonderdrug’

    Institute of Scientific and Technical Information of China (English)

    Matt; Karnitschnig; 庄秀琴

    1999-01-01

    1899年3月6日,阿司匹林在德国拜耳公司诞生。今年3月6日,德国拜耳公司举行了庆祝活动,纪念阿司匹林诞生100周年。100年前,拜耳公司的化学家霍夫曼博士提取出具有镇痛和退烧作用的乙酰水杨酸。该公司以阿司匹林的商业名称注册的专利,很快它就成为使用最广泛的常规药品。人们在医学实践中发现,阿司匹林还能抑制血小板聚集,对于冠心病、中风等由于血凝而引发的心血管疾病具有辅助治疗效果。近年来还有一些研究表明它能够防癌,百年老药又展示了它旺盛的生命力。 本文使用了许多精彩的赞誉之词,让读者感到既是夸张,又不是夸张。如: …aspirin, like Coca Cola and Levis(著名牛仔裤的品牌),is one of only a handful of brands to have transcended(超越)cultures, borders and generations to enjoy almost universal recognition. Mentioned in films and fiction, it has become as enduring an element of life in the 20th century as the car and television. …modern man lived in "the age of the aspirin". 让人惊奇的是,对人类作出巨大贡献的阿司匹林,问世之初竟遭“冷遇”: …whose potential was at first doubted by the firm’s management. 因为阿司匹林能够有效防止心脏病的发作,聪明的商人?

  20. Determinants of reduced antiplatelet effect of aspirin in patients with stable coronary artery disease.

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    Sanne Bøjet Larsen

    Full Text Available 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.

  1. CONTRAST ADVERSE EFFECT STUDY OF ASPIRIN AND CLOPIDOGREL IN STROKE PATIENTS USING COMBINATION AND INDIVIDUAL MEDICATION

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    V.S. Giri Prasad

    2012-11-01

    Full Text Available Ischemia and hemorrhage are the conditions which may lead to stroke. As stroke is a medical emergency, treated with medications such as aspirin, clopidogrel and dipyridamole. In the present study the combination and individual adverse effects of aspirin and clopidogrel medication were studied. The study during was around nine months in one of the private hospital at Hyderabad, Andhra Pradesh, India. Adverse effects evaluation was based on WHO guide lines and Naranjo’s Algorithm. Total 69 stroke patients were taken in to studies. 46 (66.66% were males and 23 (33.33% were females. The number of ischemic stroke patients was 39(56.5% and hemorrhage stroke was 30(43.4%. Among 41 patients, 19 patients was on Aspirin (46.34%, 10 patients was on clopidogral (24.34% and 12 patients was on combinations medication (29.26%. Adverse effects reported among the antiplatelate users were 6 patients. Among these 6 patients 4 patients were observed with upper gastrointestinal bleeding (UGI the overall percentage was 66.66% and 2 patients were observed with Vomiting, the overall percentage was 33.33%. In this study, the relative risk reduction for secondary stroke prevention was 37% with use of a combination of extended- release dipyridamole and aspirin. Importantly, the risk of major bleeding attributable to the combination therapy was no greater than that seen with aspirin alone. The benefit of clopidogrel over aspirin for the prevention of vascular events was a relative risk reduction of 8.7%.In addition, there was less major bleeding in the clopidogrel group, yielding a relative net benefit of about 10%. This study revels clopidogrel is the safe drug when compared with Aspirin and as well as combination therapy.

  2. Clinical pharmacology of cyclooxygenase inhibition and pharmacodynamic interaction with aspirin by floctafenine in Thai healthy subjects.

    Science.gov (United States)

    Maenthaisong, R; Tacconelli, S; Sritara, P; Del Boccio, P; Di Francesco, L; Sacchetta, P; Archararit, N; Aryurachai, K; Patrignani, P; Suthisisang, C

    2013-01-01

    Floctafenine, a hydroxyquinoline derivative with analgesic properties, is widely used in Thailand and many other countries. The objectives of this study were to evaluate in Thai healthy volunteers: i) the inhibition of whole blood cyclooxygenase(COX)-2 and COX-1 activity by floctafenine and its metabolite floctafenic acid in vitro and ex vivo after dosing with floctafenine; ii) the possible interference of floctafenine administration with aspirin antiplatelet effects. We performed an open-label, cross-over, 3-period study, on 11 healthy Thai volunteers, who received consecutively floctafenine(200mg/TID), low-dose aspirin(81mg/daily) or their combination for 4 days, separated by washout periods. Floctafenine and floctafenic acid resulted potent inhibitors of COX-1 and COX-2 in vitro (floctafenic acid was more potent than floctafenine) showing a slight preference for COX-1. After dosing with floctafenine alone, whole blood COX-1 and COX-2 activities were inhibited ex vivo in a time-dependent fashion which paralleled floctafenic acid plasma concentrations. Aspirin alone inhibited profoundly and persistently platelet COX-1 activity and AA-induced platelet aggregation throughout 24-h dosing interval which was affected by the co-administration of floctafenine. At 24 h after dosing with aspirin and floctafenine, the inhibition of platelet thromboxane(TX)B2 generation and aggregation were significantly(P less than 0.05) lower than that caused by aspirin alone. Therapeutic dosing with floctafenine profoundly inhibited prostanoid biosynthesis through the rapid conversion to floctafenic acid. Floctafenine interfered with the antiplatelet effect of aspirin. Our results suggest that floctafenine should be avoided in patients with cardiovascular disease under treatment with low-dose aspirin. PMID:23755755

  3. Aspirin augments carotid-cardiac baroreflex sensitivity during muscle mechanoreflex and metaboreflex activation in humans.

    Science.gov (United States)

    Drew, Rachel C; Muller, Matthew D; Blaha, Cheryl A; Mast, Jessica L; Herr, Michael D; Stocker, Sean D; Sinoway, Lawrence I

    2013-10-15

    Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate (HR) control during local metabolite accumulation in humans. However, the contribution of thromboxane A2 (TXA2) toward this response is unknown. Therefore, the effect of inhibiting TXA2 production via low-dose aspirin on CBR-HR sensitivity during muscle mechanoreflex and metaboreflex activation in humans was examined. Twelve young subjects performed two trials during two visits, preceded by 7 days' low-dose aspirin (81 mg) or placebo. One trial involved 3-min passive calf stretch (mechanoreflex) during 7.5-min limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise to accumulate metabolites during CO and stretch (mechanoreflex and metaboreflex). HR (ECG) and mean arterial pressure (Finometer) were recorded. CBR function was assessed using rapid neck pressures ranging from +40 to -80 mmHg. Aspirin significantly decreased baseline thromboxane B2 production by 84 ± 4% (P aspirin, stretch with metabolite accumulation significantly augmented maximal gain (GMAX) and operating point gain (GOP) of CBR-HR (GMAX; -0.71 ± 0.14 vs. -0.37 ± 0.08 and GOP; -0.69 ± 0.13 vs. -0.35 ± 0.12 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively; P aspirin and placebo during stretch with metabolite accumulation. In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in humans. This increased sensitivity appears linked to reduced TXA2 production, which likely plays a role in metabolite sensitization of muscle mechanoreceptors. PMID:23970529

  4. Effects of aspirin on atherosclerosis and the cyclooxygenase-2 expression in atherosclerotic rabbits

    Institute of Scientific and Technical Information of China (English)

    GUO Yi; WANG Qi-zhang; TANG Bing-shan; ZUO Yan-fang; LI Fang-ming; JIANG Xin; WANG Ling; MA Ke-fu

    2006-01-01

    Background Atherosclerosis is a complex vascular inflammatory disease. Aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. In this study, the effectiveness of aspirin in suppressing atherosclerosis and the inflammation process was evaluated in rabbits fed with a high fat diet.Methods Eighteen male New Zealand rabbits were randomly divided into 3 groups: control group, untreated cholesterol-fed group, aspirin treated cholesterol-fed group, which were fed for 12 weeks. After 12 weeks, the aorta was harvested for pathologic morphology observation. Immunohistochemical analysis of cyclooxygenase-2 (COX-2), macrophage and vascular smooth muscle cell (VSMC) was performed. The statistical analysis was performed by the statistical program SPSS 10.0.Results The aorta plaque/intima size (P/I) by pathologic morphology observation was 0%, (59.6± 13.7)% and (36.3± 16.5)% in the control, untreated cholesterol-fed group and aspirin treated group, respectively. The maximum plaque thickness, the degree of artery stenosis and the proportion of the intimal circumference occupied by atheroma of the 3 groups were significantly different from each other (P<0.01). The expression of COX-2 and macrophage in plaque of the aspirin treated group were decreased compared with that in untreated cholesterol-fed group. However, no difference was found in the expression of VSMC between the aspirin treated and the untreated cholesterol-fed group.Conclusion The mechanism of atherosclerosis suppression by aspirin in cholesterol-fed rabbits is related to the inhibition of COX-2 expression together with the reduced inflammation followed by, but not related to the hypolipidemic effects.

  5. SYNTHESIS AND EVALUATION OF MUTUAL PRODRUG OF ASPIRIN AND CHLORZOXAZONE

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    Sandeep Walsangikar

    2013-04-01

    Full Text Available Aspirin chlorzoxazone ester linked mutual prodrug was synthesized with the aim of improving the therapeutic index through prevention of gastrointestinal irritation and bleeding. The structure of the synthesized ester prodrug was confirmed by IR and 1H NMR spectroscopy and their purity was established by elemental analysis, HPLC and TLC. The release of ASP as well as CZX, from the ester prodrug was studied. A validated analytical HPLC method for the estimation of the ASP, and the prodrug was developed. The kinetics of ester hydrolysis was studied in four different non-enzymatic buffer solutions, at pH 3, 4, 5 and 7.4 as well as in experimental plasma. Study of skeletal muscle relaxant and anti-inflammatory properties in comparison with the reference compounds has shown that both skeletal muscle relaxant and anti-inflammatory activities were present at the same doses of the investigated compounds. The ester was found to be less irritating to gastric mucosal membrane than the parent drugs. These results suggest that the synthesized prodrug is characterized by better therapeutic index than the parent drugs.

  6. [Oral exposure testing in non-aspirin-induced analgesic intolerance].

    Science.gov (United States)

    Wiedow, O; Brasch, J; Christophers, E

    1996-12-01

    Although intolerance reaction to analgesics are not uncommon, there is still a lack of standardized procedures to diagnose the problem. We retrospectively analyzed results of scratch tests as well as oral challenges with analgesics in order to evaluate risk and diagnostic relevance of these procedures. In 1987-1992 a total of 650 patients with supposed intolerance to drugs were tested by oral challenge. Among them were 98 patients with a positive history of intolerance to non-aspirin analgesics. In 56 patients the intolerance could be verified by oral challenge. In order of decreasing frequency, the most likely agents were propyphenazone, diclofenac, metamizole, ibuprofen, carbamazepine, indomethacin, phenazone (antipyrine), and paracetamol (acteaminophen). Oral provocation showed clear dose-response relationships. For propyphenazone, the half-effective provocation dose was the same for all symptoms (cutaneous, nasal, bronchial, anaphylactoid). Scratch testing was not of diagnostic significance. Standardized test protocols starting with low dose oral challenges are suitable and helpful in minimizing the risk of severe side effects. PMID:9081936

  7. Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites.

    Science.gov (United States)

    Ai, Guoqiang; Dachineni, Rakesh; Kumar, D Ramesh; Alfonso, Lloyd F; Marimuthu, Srinivasan; Bhat, G Jayarama

    2016-08-01

    Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first reaction in the pentose phosphate pathway, and generates ribose sugars, which are required for nucleic acid synthesis, and nicotinamide adenine dinucleotide phosphate (NADPH), which is important for neutralization of oxidative stress. The expression of G6PD is elevated in several types of tumor, including colon, breast and lung cancer, and has been implicated in cancer cell growth. Our previous study demonstrated that exposure of HCT 116 human colorectal cancer cells to aspirin caused acetylation of G6PD, and this was associated with a decrease in its enzyme activity. In the present study, this observation was expanded to HT‑29 colorectal cancer cells, in order to compare aspirin‑mediated acetylation of G6PD and its activity between HCT 116 and HT‑29 cells. In addition, the present study aimed to determine the acetylation targets of aspirin on recombinant G6PD to provide an insight into the mechanisms of inhibition. The results demonstrated that the extent of G6PD acetylation was significantly higher in HCT 116 cells compared with in HT‑29 cells; accordingly, a greater reduction in G6PD enzyme activity was observed in the HCT 116 cells. Mass spectrometry analysis of aspirin‑acetylated G6PD (isoform a) revealed that aspirin acetylated a total of 14 lysine residues, which were dispersed throughout the length of the G6PD protein. One of the important amino acid targets of aspirin included lysine 235 (K235, in isoform a) and this corresponds to K205 in isoform b, which has previously been identified as being important for catalysis. Acetylation of G6PD at several sites, including K235 (K205 in isoform b), may mediate inhibition of G6PD activity, which may contribute to the ability of aspirin to exert anticancer effects through decreased synthesis of ribose sugars and NADPH.

  8. A prospective study of aspirin use and the risk of gastrointestinal bleeding in men.

    Directory of Open Access Journals (Sweden)

    Edward S Huang

    Full Text Available Data regarding the influence of dose and duration of aspirin use on risk of gastrointestinal bleeding are conflicting.We conducted a prospective cohort study of 32,989 men enrolled in the Health Professionals Follow-up Study (HPFS in 1994 who provided biennial aspirin data. We estimated relative risk of major gastrointestinal bleeding requiring hospitalization or a blood transfusion.During 14 years of follow-up, 707 men reported an episode of major gastrointestinal bleeding over 377,231 person-years. After adjusting for risk factors, regular aspirin use (≥2 times/week had a multivariate relative risk (RR of gastrointestinal bleeding of 1.32 (95% confidence interval [CI], 1.12-1.55 compared to non-regular use. The association was particularly evident for upper gastrointestinal bleeding (multivariate RR, 1.49; 95% CI, 1.16-1.92. Compared to men who denied any aspirin use, multivariate RRs of upper gastrointestinal bleeding were 1.05 (95% CI 0.71-1.52 for men who used 0.5-1.5 standard tablets/week, 1.31 (95% CI 0.88-1.95 for 2-5 aspirin/week, 1.63 (95% CI, 1.15-2.32 for 6-14 aspirin/week and 2.40 (95% CI, 1.10-5.22 for >14 aspirin/week (P(trend<0.001. The relative risk also appeared to be dose-dependent among short-term users <5 years; P(trend<.001 and long-term users (≥5 years; P(trend = 0.015. In contrast, after controlling for dose, increasing duration of use did not appear to be associated with risk (P(trend = 0.749.Regular aspirin use increases the risk of gastrointestinal bleeding, especially from the upper tract. However, risk of bleeding appears to be more strongly related to dose than to duration of use. Risk of bleeding should be minimized by using the lowest effective dose among short-term and long-term aspirin users.

  9. RP-HPLC analysis of aspirin and clopidogrel bisulphate in combination

    Directory of Open Access Journals (Sweden)

    Anandakumar K

    2007-01-01

    Full Text Available A reverse phase high performance liquid chromatography method was developed for the simultaneous estimation of aspirin and clopidogrel bisulphate in formulation. The separation was achieved by octadecyl column (C 18 and acetonitrile:methanol:20 mM phosphate buffer at pH 3 (50:7:43 v/v as eluent, at a flow rate of 1 ml/min. Detection was carried out at 240 nm. Quantitation was done by external standard calibration method. The retention time of aspirin and clopidogrel bisulphate was found to be 2.40 and 9.27 min, respectively. The method has been validated for linearity, accuracy and precision. Linearity for aspirin and clopidogrel bisulphate were in the range of 10-50 µg/ml for both the drugs. The mean recoveries obtained for aspirin and clopidogrel bisulphate were 100.86% and 100.20%, respectively. The developed method was found to be accurate, precise, selective and rapid for the simultaneous estimation of aspirin and clopidogrel bisulphate in capsules.

  10. Does Utilitarian Policy such as Smoking Cessation Lend Support to Wider Aspirin Use?

    Directory of Open Access Journals (Sweden)

    Gareth Morgan

    2015-06-01

    Full Text Available Tobacco control policy seems to be based on a utilitarian principle that public health is best served by a range of measures that will provide overall population benefit. Aspirin may have a potential wider role since meta-analysis of randomized controlled trials shows it reduces the risk of a first vascular event and also cancer. Are smoking cessation and the public health potential of aspirin different? The benefit versus risk balance of aspirin, an inexpensive and easily available medicine, deserves serious consideration as a public health measure in middle age. Smoking cessation and wider aspirin use are not seen as either competing or duplicating policy areas, but complementary. Their comparison has been purposefully selected because of common impacts, namely reduced vascular disease and cancer with increases in undesirable effects, notably gastrointestinal pathology. Part of the driver for this paper is to convey the message that public health policy has benefits and risks and the concept of a universally effective policy is unrealistic. Is it time for public health action to increase the use of aspirin?

  11. Adverse Effects of Subchronic Dose of Aspirin on Reproductive Profile of Male Rats

    Directory of Open Access Journals (Sweden)

    Archana Vyas

    2016-01-01

    Full Text Available Aspirin (acetylsalicylic acid is widely used for cardiovascular prophylaxis and as anti-inflammatory pharmaceutical. An investigation was carried out to evaluate the influence of subchronic dose of aspirin on reproductive profile of male rats, if any. Experimental animals were divided into three groups: control and aspirin subchronic dose of 12.5 mg/kg for 30 days and 60 days, respectively, while alterations in sperm dynamics, testicular histopathological and planimetric investigations, body and organs weights, lipid profiles, and hematology were performed as per aimed objectives. Subchronic dose of aspirin reduced sperm density, count, and mobility in cauda epididymis and testis; histopathology and developing primary spermatogonial cells (primary spermatogonia, secondary spermatogonia, and mature spermatocyte count were also significantly decreased in rats. Hematological investigations revealed hemopoietic abnormalities in 60-day-treated animals along with dysfunctions in hepatic and renal functions. The findings of the present study revealed that administration with subchronic dose of aspirin to male rats resulted in altered reproductive profiles and serum biochemistry.

  12. Quasi-elastic neutron scattering studies of the slow dynamics of supercooled and glassy aspirin

    Science.gov (United States)

    Zhang, Yang; Tyagi, Madhusudan; Mamontov, Eugene; Chen, Sow-Hsin

    2012-02-01

    Aspirin, also known as acetylsalicylic acid (ASA), is not only a wonderful drug, but also a good glass former. Therefore, it serves as an important molecular system to study the near-arrest and arrested phenomena. In this paper, a high-resolution quasi-elastic neutron scattering (QENS) technique is used to investigate the slow dynamics of supercooled liquid and glassy aspirin from 410 down to 350 K. The measured QENS spectra can be analyzed with a stretched exponential model. We find that (i) the stretched exponent β(Q) is independent of the wavevector transfer Q in the measured Q range and (ii) the structural relaxation time τ(Q) follows a power-law dependence on Q. Consequently, the Q-independent structural relaxation time τ0 can be extracted for each temperature to characterize the slow dynamics of aspirin. The temperature dependence of τ0 can be fitted with the mode-coupling power law, the Vogel-Fulcher-Tammann equation and a universal equation for fragile glass forming liquids recently proposed by Tokuyama in the measured temperature range. The calculated dynamic response function χT(Q, t) using the experimentally determined self-intermediate scattering function of the hydrogen atoms of aspirin shows direct evidence of the enhanced dynamic fluctuations as the aspirin is increasingly supercooled, in agreement with the fixed-time mean squared displacement langx2rang and the non-Gaussian parameter α2 extracted from the elastic scattering.

  13. Quasi-Elastic Neutron Scattering Studies of the Slow Dynamics of Supercooled and Glassy Aspirin

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yang [ORNL; Tyagi, M. [NCNR and University of Maryland; Mamontov, Eugene [ORNL; Chen, Sow-hsin H [ORNL

    2011-01-01

    Aspirin, also known as acetylsalicylic acid (ASA), is not only a wonderful drug, but also a good glass former. Therefore, it serves as an important molecular system to study the near-arrest and arrested phenomena. In this paper, a high-resolution quasi-elastic neutron scattering (QENS) technique is used to investigate the slow dynamics of supercooled liquid and glassy aspirin from 410 K down to 350 K. The measured QENS spectra can be analyzed with a stretched exponential model. We find that (i) the stretched exponent (Q) is independent of the wave vector transfer Q in the measured Q-range, and (ii) the structural relaxation time (Q) follows a power law dependence on Q. Consequently, the Q-independent structural relaxation time 0 can be extracted for each temperature to characterize the slow dynamics of aspirin. The temperature dependence of 0 can be fitted with the mode coupling power law, the Vogel-Fulcher-Tammann equation and a universal equation for fragile glass forming liquids recently proposed by M. Tokuyama in the measured temperature range. The calculated dynamic response function T(Q,t) using the experimentally determined self-intermediate scattering function of the hydrogen atoms of aspirin shows a direct evidence of the enhanced dynamic fluctuations as the aspirin is increasingly supercooled, in agreement with the fixed-time mean squared displacement x2 and non-Gaussian parameter 2 extracted from the elastic scattering.

  14. Aspirin-induced small bowel injuries and the preventive effect of rebamipide

    Institute of Scientific and Technical Information of China (English)

    Kazuhiro Mizukami; Kazunari Murakami; Takashi Abe; Kunimitsu Inoue; Masahiro Uchida; Tadayoshi Okimoto; Masaaki Kodama; Toshio Fujioka

    2011-01-01

    AIM: To evaluate the influence of taking low-dose aspirin for 4 wk on small intestinal complications and to examine the preventive effect of rebamipide. METHODS: This study was conducted as a singlecenter, randomized, double-blind, cross-over, placebocontrolled study. Eleven healthy male subjects were enrolled. Each subject underwent video capsule endoscopy after 1 and 4 wk of taking aspirin and omeprazole, along with either rebamipide or placebo therapy. The primary endpoint was to evaluate small bowel damage in healthy subjects before and after taking low-dose aspirin for 4 wk. RESULTS: The number of subjects with mucosal breaks (defined as multiple erosions and/or ulcers) were 1 at 1 wk and 1 at 4 wk on the jejunum, and 6 at 1 wk (P = 0.0061) and 7 at 4 wk on the ileum (P = 0.0019). Rebamipide significantly prevented mucosal breaks on the ileum compared with the placebo group (P = 0.0173 at 1 wk and P = 0.0266 at 4 wk). CONCLUSION: Longer-term, low-dose aspirin administration induced damage in the small bowel. Rebamipide prevented this damage, and may be a candidate drug for treating aspirin-induced small bowel complications.

  15. In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes.

    Science.gov (United States)

    Zaccardi, Francesco; Rizzi, Alessandro; Petrucci, Giovanna; Ciaffardini, Flavia; Tanese, Luigi; Pagliaccia, Francesca; Cavalca, Viviana; Ciminello, Angela; Habib, Aida; Squellerio, Isabella; Rizzo, Paola; Tremoli, Elena; Rocca, Bianca; Pitocco, Dario; Patrono, Carlo

    2016-02-01

    Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation. PMID:26470782

  16. Effect of Glucose or Fat Challenge on Aspirin Resistance in Diabetes

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    Hussein N. Yassine

    2010-01-01

    Full Text Available Aspirin has lower antiplatelet activity in diabetic patients. Our aim is to study the roles of acute hyperglycemia and hyperlipidemia on aspirin function in diabetic subjects with and without cardiovascular disease. Using urine thromboxane (pg/mg creatinine and VerifyNow (Aspirin Resistance Measures-ARU, we investigated diabetic subjects during a 2-hour glucose challenge (n=49 or a 4-hour fat challenge (n=11. All subjects were currently taking aspirin (81 or 325 mg. After fat ingestion, urine thromboxane increased in all subjects (Mean ± SE before: after (1209 ± 336: 1552 ±371, P=.01, while we noted a trend increase in VerifyNow measures (408±8: 431±18, P=.1. The response to glucose ingestion was variable. Diabetic subjects with cardiac disease and dyslipidemia increased thromboxane (1693±364: 2799 ± 513, P<.05 and VerifyNow (457.6 ± 22.3: 527.1 ± 25.8, P<.05 measures after glucose. We conclude that saturated fat ingestion increases in vivo thromboxane production despite aspirin therapy.

  17. Time of taking aspirin can have an effect on the frequency of occurrence of stroke

    Institute of Scientific and Technical Information of China (English)

    Ildiko Csoboth; Anita Matyus; Krisztina Gabara; Imre Boncz

    2009-01-01

    @@ To the Editor: We read the article by Ke et al1 with great interest, in which they investigated the usage of aspirin for the secondary prevention of ischemic stroke. The incidence of ischemic stroke and transient ischemic attack assessed by onset of clinical symptoms exhibits a marked circadian variation with a peak period during the morning. Stroke usually occurs unexpectedly or more frequently in the morning hours, between 7-12 a.m. In this morning period there is a higher aggregability of thrombocytes. Patients usually take aspirin in the morning for prevention as the treatment regimen is one tablet per day to be swallowed without chewing at least 30 minutes before breakfast (Figure). The highest plasma level of the drug occurs after the morning peak-incidence of the thromboembolic event, suggesting lower prophylactic effect of aspirin. Taking aspirin in the morning has its highest protective effect during the day, when normal physical activity exerts a protective action. Furthermore, this method of daily aspirin administration has its lowest protective value against cardio- and cerebrovascular events during the night and early rooming, when the lack of physical activity further augment the cascade of haemorheological events favoring platelet aggregation and subsequent ischemia.2-5

  18. Evaluation of ketorolac, aspirin, and an acetaminophen-codeine combination in postoperative oral surgery pain.

    Science.gov (United States)

    Forbes, J A; Butterworth, G A; Burchfield, W H; Beaver, W T

    1990-01-01

    One-hundred twenty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive oral doses of ketorolac tromethamine 10 mg, aspirin 650 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. The acetaminophen-codeine combination was significantly superior to aspirin for peak analgesia. Ketorolac was significantly superior to aspirin for every measure of total and peak analgesia, and significantly superior to acetaminophen-codeine for measures of total effect. The analgesic effect of ketorolac was significant by hour 1 and persisted for 6 hours. Repeat-dose data also suggested that ketorolac 10 mg was superior to aspirin 650 mg and acetaminophen-codeine on the day of surgery. Differences among the active medications were trivial for the postoperative days 1-6 analyses. The frequency of adverse effects was over 4 times greater for acetaminophen-codeine than for ketorolac or aspirin. PMID:2082317

  19. Combining aspirin with cholecalciferol (vitamin D3--a potential new tool for controlling possum populations.

    Directory of Open Access Journals (Sweden)

    David R Morgan

    Full Text Available The introduced Australian brushtail possum is a major vertebrate pest in New Zealand, with impacts on conservation and agriculture being managed largely through poisoning operations. Cholecalciferol (vitamin D3 is registered for use in controlling possums and despite its many advantages it is expensive and relatively inhumane. Combination of a high proportion of aspirin with a low proportion of cholecalciferol was effective in killing high proportions of groups of acclimatised, caged possums: this is attributed to both an unexpectedly high toxicity of the type of cholecalciferol used, and a proposed synergistic mechanism between the two compounds. Death was caused by localised damage to heart ventricles by aspirin, and inhibition of tissue repair by both aspirin and cholecalciferol. The observed toxicosis had lower impact on the welfare of possums than either compound administered alone, particularly aspirin alone. Residue analyses of bait remains in the GI tract suggested a low risk of secondary poisoning by either compound. The combination of cholecalciferol and aspirin has the potential to meet key requirements of cost-effectiveness and humaneness in controlling possum populations, but the effect of the combination in non-target species has yet to be tested.

  20. PREVENTION OF ONE-YEAR VEIN-GRAFT OCCLUSION AFTER AORTOCORONARY-BYPASS SURGERY - A COMPARISON OF LOW-DOSE ASPIRIN, LOW-DOSE ASPIRIN PLUS DIPYRIDAMOLE, AND ORAL ANTICOAGULANTS

    NARCIS (Netherlands)

    VANDERMEER, J; HILLEGE, HL; KOOTSTRA, GJ; ASCOOP, CAPL; PFISTERER, M; VANGILST, WH; LIE, KI

    1993-01-01

    Aspirin, alone or in combination with dipyridamole, is known to prevent occlusion of aortocoronary vein grafts. The benefit of dipyridamole in addition to aspirin remains controversial, and the efficacy and safety of oral anticoagulants for prevention of vein-graft occlusion have not been establishe

  1. EFFECTS OF LOW-DOSE ASPIRIN (50-MG/DAY), LOW-DOSE ASPIRIN PLUS DIPYRIDAMOLE, AND ORAL ANTICOAGULANT AGENTS AFTER INTERNAL MAMMARY ARTERY BYPASS-GRAFTING - PATENCY AND CLINICAL OUTCOME AT 1 YEAR

    NARCIS (Netherlands)

    VANDERMEER, J; DELARIVIERE, AB; VANGILST, WH; HILLEGE, HL; PFISTERER, M; KOOTSTRA, GJ; DUNSELMAN, PHJM; MULDER, BJM; LIE, KI

    1994-01-01

    Objectives. This study was performed to compare the efficacy and safety of aspirin, aspirin plus dipyridamole, and oral anti coagulant agents in the prevention of internal mammary artery graft occlusion. Background. Antithrombotic drugs increase vein graft patency after coronary artery bypass surger

  2. Otpornost na acetilsalicilnu kiselinu u kasnom poslijeoperacijskom razdoblju nakon kirurške revaskularizacije miokarda [Aspirin resistance in late postoperative period after coronary artery bypass grafting

    OpenAIRE

    Fučkar, Krunoslav

    2016-01-01

    Study goals: In patients after coronary artery bypass grafting during the early postoperative stage there is a higher prevalence of aspirin resistance. Data concerning the issue of aspirin resistance in the late postoperative period are rare. Clinical impact of aspirin resistance has not yet been thoroughly investigated. The primary objective of this dissertation was to assess the prevalence of laboratorically defined aspirin resistance during the late postoperative period afte...

  3. Early outcome in acute ischemic stroke is not influenced by the prophylactic use of low-dose aspirin

    NARCIS (Netherlands)

    DeKeyser, J; Herroelen, L; DeKlippel, N

    1997-01-01

    Aspirin reduces the occurrence of ischemic strokes. In some prophylactic trials it was suggested that aspirin might also lessen stroke severity, and hence improve outcome in patients sustaining an ischemic stroke. We examined stroke severity (by using the Mathew scale) and early outcome (Barthel ind

  4. Effects of aspirin on angiotensin-converting enzyme inhibition and left ventricular dilation one year after acute myocardial infarction

    NARCIS (Netherlands)

    Oosterga, M; Anthonio, RL; de Kam, PJ; Kingma, JH; Crijns, HJGM; van Gilst, WH

    1998-01-01

    There are conflicting reports on the interaction of aspirin with angiotensin-converting enzyme inhibitors in heart failure and systemic hypertension. A past hoc analysis of the Captopril and Thrombolysis Study (CATS) study was conducted. At randomization, 94 patients (31.5%) took aspirin. In patient

  5. 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;

    turnover. Key Words: aspirin; immature platelets; platelet aggregation; platelet function tests; stent thrombosis Abbreviations: ARU, aspirin reaction units; AU, aggregation units; BMS, bare-metal stent(s); DES, drug-eluting stent(s); IPF, immature platelet fraction; MEA, multiple electrode aggregometry...

  6. Low-dose aspirin use and the risk of ovarian cancer in Denmark

    DEFF Research Database (Denmark)

    Baandrup, Lone; Kjaer, S K; Olsen, J H;

    2015-01-01

    BACKGROUND: 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...... were seen for mucinous and endometrioid tumours. CONCLUSION: This nationwide case-control study indicates that low-dose aspirin use may be associated with a reduced risk of epithelial ovarian cancer....... 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. RESULTS: For 4103 ovarian cancer cases and 58 706 population controls, the...

  7. Do Aspirin and Other Antiplatelet Drugs Reduce the Mortality in Critically Ill Patients?

    Directory of Open Access Journals (Sweden)

    Wolfgang Lösche

    2012-01-01

    Full Text Available Platelet activation has been implicated in microvascular thrombosis and organ failure in critically ill patients. In the first part the present paper summarises important data on the role of platelets in systemic inflammation and sepsis as well as on the beneficial effects of antiplatelet drugs in animal models of sepsis. In the second part the data of retrospective and prospective observational clinical studies on the effect of aspirin and other antiplatelet drugs in critically ill patients are reviewed. All of these studies have shown that aspirin and other antiplatelet drugs may reduce organ failure and mortality in these patients, even in case of high bleeding risk. From the data reviewed here interventional prospective trials are needed to test whether aspirin and other antiplatelet drugs might offer a novel therapeutic option to prevent organ failure in critically ill patients.

  8. Chemometric simultaneous estimation of clopidogrel bisulphate and aspirin from combined dosage form

    Directory of Open Access Journals (Sweden)

    Rajput S

    2008-01-01

    Full Text Available Two chemometric methods, inverse least square and classical least square, were applied to simultaneous assay of clopidogrel bisulphate and aspirin in their combined dosage tablet formulation. Twelve mixed solutions were prepared for the chemometric calibration as training set and 10 mixed solutions were prepared as validation set. The absorbance data matrix was obtained by measuring the absorbance at 16 wavelength points, from 220 to 250 nm with the interval of 2 nm (Dl= 2 nm. The developed calibrations were successfully tested for laboratory mixtures as well as commercial tablet formulation for their clopidogrel bisulphate and aspirin concentration. Mean recoveries for clopidogrel bisulphate and aspirin were found to be in good agreement with the label claim.

  9. Low-Dose Aspirin Treatment Alleviates Gamma Irradiation Impaired Fertility in Female Albino Rats

    International Nuclear Information System (INIS)

    Recent experimental evidence suggests that Aspirin (acetylsalicylic acid), the extensively prescribed analgesic, can improve female fertility by suppressing the prostaglandin (PG) biosynthesis and modulating the uterine circulation. Aspirin has also been found to exhibit a protective ability on the radiation induced oxidative stress. Thus the present work aims to investigate the effect of oral low-dose Aspirin treatment on the radiation induced female reproductive disturbance. Adult female rats were used in the current experiment. All rat group treatments started at the onset of the proestrus phase and terminated at the diestrus encompassing 2 complete estrus cycles. Subsequently, the rats were divided into 4 equal groups: Group 1-Control: female rats receiving distilled water via an oral gavage; Group 2- Irradiation: female rats subjected to 6 Gy gamma rays at the proestrus cycle and receiving distilled water; Group 3-Aspirin: rats orally administered a daily dose of 7mg/kg body weight aspirin dissolved in distilled water via an oral gavage and Group 4- Irradiation + Aspirin: female rats irradiated as group 2 and receiving aspirin treatment. A number of rats from each experimental group were allowed to mate following every treatment to serve as Control mated (Subgroup 1), Irradiated mated (Subgroup 2), Aspirin administered mated (Subgroup 3) and Irradiated + Aspirin treated mated (Subgroup 4). At the assigned day of the second estrus cycle completion, blood was collected from Groups 1-4 for subsequent hormonal assay, lipid peroxides and glutathione (GSH) estimation whereas Subgroups 1-4 were carefully monitored for reproduction and infertility rates. Results have shown that the 6 Gy γ- irradiation of the rats at the proestrus cycle (Group 2) caused a decrease in follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and estradiol (E2) levels associated with a drastic increase in the progesterone levels in addition to the significant

  10. Evaluation of antioxidant activity and electronic structure of aspirin and paracetamol

    Science.gov (United States)

    Motozaki, W.; Nagatani, Y.; Kimura, Y.; Endo, K.; Takemura, T.; Kurmaev, E. Z.; Moewes, A.

    2011-01-01

    We present a study of electronic structure, chemical bonding, and antioxidant activity of phenolic antioxidants (aspirin and paracetamol). X-ray photoelectron and emission spectra of the antioxidants have been simulated by deMon density functional theory (DFT) calculations of the molecules. The chemical bonding of aspirin is characterized by the formation of oxygen 'lone-pair' π-orbitals which can neutralize free radicals and thus be related to antioxidant properties of the drug. In the case of paracetamol the additional nitrogen 'lone pair' is formed which can explain toxicity of the drug. We propose an evaluation method of antioxidant activity based on the relationship between experimental half-wave oxidation potential ( Ep/2 ) and calculated ionization potentials ( IP) by the DFT calculations, and can conclude that paracetamol has the higher antioxidant activity than aspirin.

  11. Comparative antiplatelet activity of COX1 NSAIDS versus aspirin, encompassing regimen simplification and gastroprotection: a call for a controlled study

    Directory of Open Access Journals (Sweden)

    B. Rothschild

    2011-09-01

    Full Text Available The cardioprotective/platelet inhibitory role of non-steroidal antiinflammatory drugs (NSAIDs has been controversial, perhaps in contrast to the accepted prophylactic role of aspirin (114. That cardioprotective effect is attributed to the platelet aggregation inhibitory effects of aspirin and COX 1 active NSAIDS (10, 11, 13 and can be studied without requirement for massive numbers of patients. Such cardioprotection, however, has its own risks. Significant gastrointestinal toxicity is still present with the 75-81 mg aspirin dose and appears no less than that found with the higher doses once routinely utilized in treatment of arthritis (2, 8, 9. One study even reported that 4% of patients receiving aspirin had moderate to severe bleeding (14. The challenge with aspirin is that even with a 75 mg dose, the frequency of severe gastrointestinal hemorrhage is double that of placebo (2, 8, 9 and not different from that observed with COX 1 NSAIDs, in the abse

  12. The effect of simvastatin, aspirin, and their combination in reduction of atheroma plaque

    Science.gov (United States)

    Kurniati, Neng Fisheri; Permatasari, Anita

    2015-09-01

    Atherosclerosis is one of the risk factors of cardiovascular disease. Atherosclerosis is a chronic inflammatory disease caused by high level of cholesterol especially low density lipoprotein (LDL) and accumulation of neutrophil and macrophage in the artery wall. Thickness of aortic wall is an early stage of atherosclerosis plaque formation. Identification of atherosclerosis plaque formation was done by measuring level of total cholesterol, triglycerides, HDL, LDL, interleukin-18 (IL-18), myeloperoxidase (MPO) and measuring the thickness of aortic wall. Atherosclerosis's model induced by high fat diet and CCT (cholesterol, cholic acid, and propyltiouracil) oral administration. Rats induced cholesterol divided into positive control, simvastatin 25 mg/kg bw, aspirin 20 mg/kg bw, and combination simvastatin 25 mg/kg and aspirin 20 mg/kg bw group for 3 weeks. In the third week, therapy was given to atherosclerosis's model. Then, in the fourth and fifth week, therapy was given but induction of high cholesterol was stopped due to the massive loss of body weight. Total cholesterol, triglycerides, HDL, LDL, MPO, and IL-18 measured by uv-vis spectrophotometry and ELISA. In the end of therapy, aorta's rats was isolated to identify the thickness of aorta wall. In the fourth week, after 1 week of treatment, only combination group showed significantly higher total cholesterol, LDL and MPO compared to positive control group. Level of triglycerides and HDL in all groups did not significantly differ compared to positive control group. After 2 weeks continuing drug treatment, the level of total cholesterol, MPO, and IL-18 were decreased in all groups, and aspirin group showed the lowest level. The level of triglycerides was decreased in simvastatin and aspirin group, and aspirin group showed the lowest. Only combination group showed the lowest level of LDL. Based on histopathology result, the thickness of aortic wall was reduced in all groups and aspirin group showed the lowest.

  13. Safety of ultrasound-guided transrectal extended prostate biopsy in patients receiving low-dose aspirin

    Directory of Open Access Journals (Sweden)

    Ioannis Kariotis

    2010-06-01

    Full Text Available PURPOSE: To determine whether the peri-procedural administration of low-dose aspirin increases the risk of bleeding complications for patients undergoing extended prostate biopsies. MATERIALS AND METHODS: From February 2007 to September 2008, 530 men undergoing extended needle biopsies were divided in two groups; those receiving aspirin and those not receiving aspirin. The morbidity of the procedure, with emphasis on hemorrhagic complications, was assessed prospectively using two standardized questionnaires. RESULTS: There were no significant differences between the two groups regarding the mean number of biopsy cores (12.9 ± 1.6 vs. 13.1 ± 1.2 cores, p = 0.09. No major biopsy-related complications were noted. Statistical analysis did not demonstrate significant differences in the rate of hematuria (64.5% vs. 60.6%, p = 0.46, rectal bleeding (33.6% vs. 25.9%, p = 0.09 or hemospermia (90.1% vs. 86.9%, p = 0.45. The mean duration of hematuria and rectal bleeding was significantly greater in the aspirin group compared to the control group (4.45 ± 2.7 vs. 2.4 ± 2.6, p = < 0.001 and 3.3 ± 1.3 vs. 1.9 ± 0.7, p < 0.001. Multivariate logistic regression analysis revealed that only younger patients (mean age 60.1 ± 5.8 years with a lower body mass index (< 25 kg/m2 receiving aspirin were at a higher risk (odds ratio = 3.46, p = 0.047 for developing hematuria and rectal bleeding after the procedure. CONCLUSIONS: The continuing use of low-dose aspirin in patients undergoing extended prostatic biopsy is a relatively safe option since it does not increase the morbidity of the procedure.

  14. Safety of 12 core transrectal ultrasound guided prostate biopsy in patients on aspirin

    Directory of Open Access Journals (Sweden)

    Pawan Vasudeva

    2015-12-01

    Full Text Available Objective: To prospectively assess safety outcome of TRUS guided prostate biopsy in patients taking low dose aspirin. Materials and methods: Consecutive patients, who were planned for 12 core TRUS guided prostate biopsy and satisfied eligibility criteria, were included in the study and divided into two Groups: Group A: patients on aspirin during biopsy, Group B: patients not on aspirin during biopsy, including patients in whom aspirin was stopped prior to the biopsy. Parameters included for statistical analysis were: age, serum prostate specific antigen (PSA, prostate volume, hemoglobin (Hb %, number of hematuria episodes, number of patient reporting hematuria, hematuria requiring intervention, number of patient reporting hematospermia and number of patient reporting rectal bleeding. Results: Of 681 eligible patients, Group A and B had 191 and 490 patients respectively. The mean age, prostate volume, serum PSA and pre-biopsy hemoglobin were similar in both Groups with no significant differences noted between them. None of the post-biopsy complications, including number of hematuria episodes (p=0.83, number of patients reporting hematuria (p=0.55, number of patients reporting hematospermia (p=0.36 and number of patients reporting rectal bleeding (p=0.65, were significantly different between Groups A and B respectively. None of the hemorrhagic complication in either group required intervention and were self limiting. Conclusion: Continuing low dose aspirin during TRUS guided prostate biopsy neither alters the minor bleeding episodes nor causes major bleeding complication. So, discontinuation of low dose aspirin prior to TRUS guided prostate biopsy is not required.

  15. Comparison of Anticoagulant Effects on Vein Grafts between Human TFPI Gene Transfection and Aspirin Oral Administration

    Institute of Scientific and Technical Information of China (English)

    Deguang FENG; Cheng ZHOU; Quan LI; Kailin ZHANG; Xionggang JIANG; Song LENG; Heping DENG; Jiane FENG; Tucheng SUN; Long WU

    2008-01-01

    To develop a more efficient antithrombotic way after coronary artery bypass grafting (CABG), the anticoagulant effects were compared of human tissue factor pathway inhibitor (TFPI) gene transfection and aspirin oral administration (traditional method) on vein grafts. An eukaryotic expression plasmid pCMV-(Kozak) TFPI was prepared. Animal model of carotid artery bypass grafting was constructed. In operation, endothelial cells of vein grafts in TFPI group and empty plasmid control group were transfected with pCMV-(Kozak) TFPI and empty plasmid pCMV respectively, while no transfection was conducted in aspirin control group. After operation, aspirin (2 mg·kg-1·d-1) was administered (I.g.) in aspirin control group. Three days later, grafts (n=10) were harvested for RT-PCR, Western blotting and immunohistochemical analyses of exogenous gone expression and for pathological, scanning electron microscopic observation of thrombus. Thirty days later, the patency rates of remnant grafts (n=10) were recorded by vessel Doppler ultrasonography. Human TFPI gene products were detected in gene transferred vein grafts. Three days later, thrombi were found in 7 animals of aspirin control group and in 8 animals of empty plasmid control group, but in only 1 of TFPI group (P<0.01). Thirty days later, 5 grafts were occluded in empty plasmid control group, but none of grafts was occluded in the other groups (P<0.05). The endothelial surfaces of grafts in both of the control groups were covered with aggregated erythrocytes and platelets, and it were not seen in TFPI group. R was suggested that the anticoagulant effects on vein grafts of human TFPI gene trans- fection are better than those of aspirin.

  16. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice.

    Science.gov (United States)

    Strong, Randy; Miller, Richard A; Astle, Clinton M; Floyd, Robert A; Flurkey, Kevin; Hensley, Kenneth L; Javors, Martin A; Leeuwenburgh, Christiaan; Nelson, James F; Ongini, Ennio; Nadon, Nancy L; Warner, Huber R; Harrison, David E

    2008-10-01

    The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex,with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p=0.0006) and aspirin (p=0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan;neither NDGA (p=0.12) nor aspirin (p=0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on life span in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses,might prove to postpone death and various age-related outcomes reproducibly in mice. PMID:18631321

  17. Role of Helicobacter pylori eradication in aspirin or non-steroidal anti-inflammatory drug users

    Institute of Scientific and Technical Information of China (English)

    George V. Papatheodoridis; Athanasios J. Archimandritis

    2005-01-01

    Helicobacter pylori (H pylori) infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin at any dosage and formulation represent well-established risk factors for the development of uncomplicated and complicated peptic ulcer disease accounting for the majority of such cases. Although the interaction between H pylori and NSAID/aspirin use in the same individuals was questioned in some epidemiological studies, it has now become widely accepted that they are at least independent risk factors for peptic ulcer disease. According to data from randomized intervention trials, naive NSAID users certainly benefit from testing for H pylori infection and, if positive,H pylori eradication therapy prior to the initiation of NSAID. A similar strategy is also suggested for naive aspirin users, although the efficacy of such an approach has not been evaluated yet. Strong data also support that chronic aspirin users with a recent ulcer complication should be tested for H pyloriinfection and, if positive, receive H pylori eradication therapy after ulcer healing, while they appear to benefit from additional long-term therapy with a proton pump inhibitor (PPI).A similar approach is often recommended to chronic aspirin users at a high risk of ulcer complication. H pylori eradication alone does not efficiently protect chronic NSAID users with a recent ulcer complication or those at a high-risk, who certainly should be treated with long-term PPI therapy, but H pylori eradication may be additionally offered even in this setting. In contrast, testing for H pylorior PPI therapy is not recommended for chronic NSAID/aspirin users with no ulcer complications or those at a low risk of complications.

  18. Aspirin may inhibit angiogenesis and induce autophagy by inhibiting mTOR signaling pathway in murine hepatocarcinoma and sarcoma models

    Science.gov (United States)

    Zhao, Qianqian; Wang, Zhaopeng; Wang, Zhaoxia; Wu, Licun; Zhang, Weidong

    2016-01-01

    Aspirin is known to have inhibitory effects on growth development in various types of tumor. In previous studies, it was observed to inhibit angiogenesis by downregulating the expression of vascular endothelial growth factor-A (VEGF-A). In the present study, murine H22 hepatocarcinoma and S180 sarcoma models were used to ascertain whether aspirin could inhibit angiogenesis and promote autophagy in tumors. Tumor-bearing mice were randomly divided into four groups with 10 mice per group: i) no treatment; ii) low-dose aspirin (100 mg/kg); iii) high-dose aspirin (400 mg/kg); iv) everolimus group (4 mg/kg). The effects of high-dose aspirin were validated through preliminary experiments. The drug treatment was administered every day for 14 days. The tumor size was measured every other day and then the tumor growth curve was plotted, and the tumor inhibitory rates were calculated. The expression levels of phosphorylated mammalian target of rapamycin (p-mTOR), hypoxia-inducible factor-1α (HIF-1α), VEGF-A, UNC-51-like kinase-1 (ULK1) and microtubule-associated protein 1 light chain 3A (LC3A) were detected by immunohistochemistry and western blot analysis, respectively. We observed that tumor growth delay was achieved in both H22 hepatocarcinoma and S180 sarcoma models following treatment with aspirin. The tumor growth inhibition rates induced by low and high-dose aspirin and everolimus were 19.6, 33.6 and 53.7% (PHIF-1α and VEGF-A was decreased, while the expression of ULK1 and LC3A was increased following treatment with aspirin and everolimus. The changes were more apparent in the high-dose aspirin and everolimus groups (PHIF-1α and VEGF-A. Alternatively, aspirin may induce autophagy by inhibiting the mTOR signaling target and then increasing ULK1 and LC3A.

  19. The effect of aspirin on atherogenic diet-induced diabetes mellitus.

    Science.gov (United States)

    Sethi, Apoorva; Parmar, Hamendra S; Kumar, Anil

    2011-06-01

    Exploration of atherogenic diet-induced diabetes mellitus and the evaluation of antidiabetic potential of aspirin were carried out in this study. Male albino Wistar rats were divided into three groups of seven each (1, 2 and 3). Animals of groups 2 and 3 received CCT diet (normal rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5%, 2-thiouracil), whereas the animals of group 1 received normal feed and served as control. In addition to CCT, animals of group 3 (CCT + Asp) also received aspirin (8 gm/kg), commencing from day 8 till the end of study (day 15). In another experiment (exp. 2), aspirin-supplemented normal rat chow (Asp) was fed to the animals for 7 days and compared with the normal rat chow-fed control group. In experiment 3, an in vitro nitric oxide radical-scavenging potential of aspirin at three different doses (25, 50 and 100 μg/ml) was evaluated. In response to CCT diet, a decrease in serum insulin, α-amylase activity, hepatic glycogen, pancreatic calcium with a concomitant increase in serum glucose, lipid profile (except high-density lipoprotein cholesterol (HDL-C)), pancreatic nitrite and lipid peroxidation and the size of adipocytes along with macrophages infiltration were observed. Aspirin administration to CCT diet-fed animals (CCT + Asp) reverted all the studied biochemical and histological changes towards normality. In experiment 2, aspirin administration decreased the serum glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and VLDL-C with concomitantly increased HDL-C and insulin; however, it increased hepatic glycogen and pancreatic calcium concentration with a decrease in pancreatic and adipose lipid peroxidation. In vitro assay revealed the nitric oxide radical-scavenging potential of aspirin in all the studied doses. It is concluded that CCT diet-induced diabetes mellitus might be the outcome of nitric oxide radical-induced oxidative stress in pancreatic tissue, as well as diminished

  20. Translational vibrations between chains of hydrogen-bonded molecules in solid-state aspirin form I

    Science.gov (United States)

    Takahashi, Masae; Ishikawa, Yoichi

    2013-06-01

    We perform dispersion-corrected first-principles calculations, and far-infrared (terahertz) spectroscopic experiments at 4 K, to examine translational vibrations between chains of hydrogen-bonded molecules in solid-state aspirin form I. The calculated frequencies and relative intensities reproduce the observed spectrum to accuracy of 11 cm-1 or less. The stronger one of the two peaks assigned to the translational mode includes the stretching vibration of the weak hydrogen bond between the acetyl groups of a neighboring one-dimensional chain. The calculation of aspirin form II performed for comparison gives the stretching vibration of the weak hydrogen bond in one-dimensional chain.

  1. The effect of aspirin on atherogenic diet-induced diabetes mellitus.

    Science.gov (United States)

    Sethi, Apoorva; Parmar, Hamendra S; Kumar, Anil

    2011-06-01

    Exploration of atherogenic diet-induced diabetes mellitus and the evaluation of antidiabetic potential of aspirin were carried out in this study. Male albino Wistar rats were divided into three groups of seven each (1, 2 and 3). Animals of groups 2 and 3 received CCT diet (normal rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5%, 2-thiouracil), whereas the animals of group 1 received normal feed and served as control. In addition to CCT, animals of group 3 (CCT + Asp) also received aspirin (8 gm/kg), commencing from day 8 till the end of study (day 15). In another experiment (exp. 2), aspirin-supplemented normal rat chow (Asp) was fed to the animals for 7 days and compared with the normal rat chow-fed control group. In experiment 3, an in vitro nitric oxide radical-scavenging potential of aspirin at three different doses (25, 50 and 100 μg/ml) was evaluated. In response to CCT diet, a decrease in serum insulin, α-amylase activity, hepatic glycogen, pancreatic calcium with a concomitant increase in serum glucose, lipid profile (except high-density lipoprotein cholesterol (HDL-C)), pancreatic nitrite and lipid peroxidation and the size of adipocytes along with macrophages infiltration were observed. Aspirin administration to CCT diet-fed animals (CCT + Asp) reverted all the studied biochemical and histological changes towards normality. In experiment 2, aspirin administration decreased the serum glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and VLDL-C with concomitantly increased HDL-C and insulin; however, it increased hepatic glycogen and pancreatic calcium concentration with a decrease in pancreatic and adipose lipid peroxidation. In vitro assay revealed the nitric oxide radical-scavenging potential of aspirin in all the studied doses. It is concluded that CCT diet-induced diabetes mellitus might be the outcome of nitric oxide radical-induced oxidative stress in pancreatic tissue, as well as diminished

  2. High performance liquid chromatographic determination of aspirin and clopidogrel in tablets

    Directory of Open Access Journals (Sweden)

    Gandhimathi M

    2007-01-01

    Full Text Available A reverse phase high performance liquid chromatographic method to determine aspirin and clopidogrel in combined dosage form is proposed. The chromatographic resolution of aspirin and clopidogrel was obtained in a mobile phase consisting of 0.1% v/v triethylamine (pH 4.0:acetonitrile in the ratio 25:75% (v/v in an isocratic elution. A detection wavelength of 225 nm and flow rate of 1 ml/min was used in the study. Nimesulide (20 µg/ml was used as an internal standard. The system suitability procedures as precision, accuracy, LOD, LOQ, number of theoretical plates and tailing factor were studied.

  3. Solid-state 17O NMR of pharmaceutical compounds: salicylic acid and aspirin.

    Science.gov (United States)

    Kong, Xianqi; Shan, Melissa; Terskikh, Victor; Hung, Ivan; Gan, Zhehong; Wu, Gang

    2013-08-22

    We report solid-state NMR characterization of the (17)O quadrupole coupling (QC) and chemical shift (CS) tensors in five site-specifically (17)O-labeled samples of salicylic acid and o-acetylsalicylic acid (Aspirin). High-quality (17)O NMR spectra were obtained for these important pharmaceutical compounds under both static and magic angle spinning (MAS) conditions at two magnetic fields, 14.0 and 21.1 T. A total of 14 (17)O QC and CS tensors were experimentally determined for the seven oxygen sites in salicylic acid and Aspirin. Although both salicylic acid and Aspirin form hydrogen bonded cyclic dimers in the solid state, we found that the potential curves for the concerted double proton transfer in these two compounds are significantly different. In particular, while the double-well potential curve in Aspirin is nearly symmetrical, it is highly asymmetrical in salicylic acid. This difference results in quite different temperature dependencies in (17)O MAS spectra of the two compounds. A careful analysis of variable-temperature (17)O MAS NMR spectra of Aspirin allowed us to obtain the energy asymmetry (ΔE) of the double-well potential, ΔE = 3.0 ± 0.5 kJ/mol. We were also able to determine a lower limit of ΔE for salicylic acid, ΔE > 10 kJ/mol. These asymmetrical features in potential energy curves were confirmed by plane-wave DFT computations, which yielded ΔE = 3.7 and 17.8 kJ/mol for Aspirin and salicylic acid, respectively. To complement the solid-state (17)O NMR data, we also obtained solid-state (1)H and (13)C NMR spectra for salicylic acid and Aspirin. Using experimental NMR parameters obtained for all magnetic nuclei present in salicylic acid and Aspirin, we found that plane-wave DFT computations can produce highly accurate NMR parameters in well-defined crystalline organic compounds.

  4. AMPK-mediated up-regulation of mTORC2 and MCL-1 compromises the anti-cancer effects of aspirin

    Science.gov (United States)

    Hua, Hui; Yin, Yancun; Wang, Jiao; Luo, Ting; Jiang, Yangfu

    2016-01-01

    AMP-activated protein kinase (AMPK) is an important energy sensor that may inhibit cell proliferation or promote cell survival during stresses. Besides cyclooxygenase, AMPK is another target of the nonsteroid anti-inflammatory agent aspirin. Preclinical and clinical investigations demonstrate that aspirin can inhibit several types of cancer such as colorectal adenomas and hepatocellular carcinoma (HCC). However, little is known about the cellular response to aspirin that may lead to aspirin resistance. Here, we show that aspirin induces the expression of MCL-1 in HepG2 and SW480 cells through AMPK-mTOR-Akt/ERK axis. Treatment of HepG2 and SW480 cells with aspirin leads to increased MCL-1 expression, Akt and ERK1/2 phosphorylation. Inhibition of Akt/MEK abrogates the induction of MCL-1 by aspirin. Aspirin activates AMPK, which in turn up-regulates mTORC2 activity, Akt, ERK1/2 phosphorylation and MCL-1 expression. MCL-1 knockdown sensitizes cancer cells to aspirin-induced apoptosis. Combination of aspirin and AMPK, Akt or MEK inhibitor results in more significant inhibition of cell proliferation and induction of apoptosis than single agent. Moreover, sorafenib blocks aspirin-induced MCL-1 up-regulation. Combination of aspirin and sorafenib leads to much more cell death and less cell proliferation than each drug alone. Treatment of HCC and colon cancer xenografts with both aspirin and sorafenib results in more significant tumor suppression than single agent. These data demonstrate that AMPK-mediated up-regulation of mTORC2 and MCL-1 may compromise the anticancer effects of aspirin. Combination of aspirin and sorafenib may be an effective regimen to treat HCC and colon cancer. PMID:26918349

  5. Is there an ideal way to initiate antiplatelet therapy with aspirin? A crossover study on healthy volunteers evaluating different dosing schemes with whole blood aggregometry

    Directory of Open Access Journals (Sweden)

    Overbeck Ursula

    2011-04-01

    Full Text Available Abstract Background Guidelines recommend an early initiation of aspirin treatment in patients with acute cerebral ischemia. Comparative studies on the best starting dose for initiating aspirin therapy to achieve a rapid antiplatelet effect do not exist. This study evaluated the platelet inhibitory effect in healthy volunteers by using three different aspirin loading doses to gain a model for initiating antiplatelet treatment in acute strokes patients. Methods Using whole blood aggregometry, this study with a prospective, uncontrolled, open, crossover design examined 12 healthy volunteers treated with three different aspirin loading doses: intravenous 500 mg aspirin, oral 500 mg aspirin, and a course of 200 mg aspirin on two subsequent days followed by a five-day course of 100 mg aspirin. Aspirin low response was defined as change of impedance exceeding 0 Ω after stimulation with arachidonic acid. Results Sufficient antiplatelet effectiveness was gained within 30 seconds when intravenous 500 mg aspirin was used. The mean time until antiplatelet effect was 74 minutes for 500 mg aspirin taken orally and 662 minutes (11.2 hours for the dose scheme with 200 mg aspirin with a high inter- and intraindividual variability in those two regimes. Platelet aggregation returned to the baseline range during the wash-out phase within 4 days. Conclusion Our study reveals that the antiplatelet effect differs significantly between the three different aspirin starting dosages with a high inter- and intraindividual variability of antiplatelet response in our healthy volunteers. To ensure an early platelet inhibitory effect in acute stroke patients, it could be advantageous to initiate the therapy with an intravenous loading dose of 500 mg aspirin. However, clinical outcome studies must still define the best way to initiate antiplatelet treatment with aspirin.

  6. Lack of Pharmacokinetic Interaction between Aspirin and Warfarin.

    Science.gov (United States)

    Fiske, William D.; Connell, Jill M.; Benedek, Irma H.

    1995-06-01

    An open-label, randomized, two-phase crossover study was conducted on 36 healthy male volunteers to identify the effects of coadministration of aspirin (acetylsalicylic acid; ASA) and crystalline warfarin sodium (Coumadin((R))) on the elimination and disposition kinetics of ASA, salicylic acid (SA) and R- and S-warfarin enantiomers. Twenty-four subjects were administered single doses of 325 mg of ASA alone and in combination with 10 mg of crystalline warfarin sodium with a 1-week washout between ASA doses. ASA and SA pharmacokinetic parameters were determined after each dose. Twelve subjects were administered single doses of 10 mg of crystalline warfarin sodium alone and in combination with 325 mg of ASA with a 4-week washout between warfarin doses. R- and S-warfarin enantiomer pharmacokinetic parameters were determined after each dose. Pharmacokinetic parameters were compared using analysis of variance and 90% confidence intervals. ASA and SA AUCs (the area under the plasma concentration versus time curve from time zero to time infinity) respectively were 3.28 plus minus 0.80 and 66.99 plus minus 11.73 &mgr;g h ml(minus sign1) (ASA alone), and 3.22 plus minus 0.61 and 69.48 plus minus 15.79 &mgr;g h ml(minus sign1) (ASA with warfarin). R-warfarin and S-warfarin AUCs respectively were 33.9 plus minus 9.3 and 23.9 plus minus 16.0 &mgr;g h ml(minus sign1) (warfarin alone) and 33.6 plus minus 10.2 and 22.6 plus minus 14.7 &mgr;g h ml(minus sign1) (warfarin with ASA). The only pharmacokinetic parameter which was statistically significantly different when the combination was administered was the S-warfarin elimination rate constant (p < 0.05), but the difference (9.2% increase in the presence of ASA) was small and no significant difference was found in S-warfarin clearance. It is concluded that there is no pharmacokinetic interaction when a single dose of ASA 325 mg is coadministered with a single dose of crystalline warfarin sodium 10 mg. PMID:11850685

  7. High-on-Aspirin Residual Platelet Reactivity Evaluated Using the Multiplate® Point-of-Care Device

    Directory of Open Access Journals (Sweden)

    Mărginean Alina

    2016-03-01

    Full Text Available Objective: The aim of this study was to evaluate the prevalence of aspirin non-responsiveness using whole blood multiple electrode aggregometry and to investigate the role of different clinical and laboratory variables associated with the lack of response. Methods: The present study included 116 aspirin treated patients presented with acute coronary syndromes or stroke. Response to aspirin was assessed by impedance aggregometry using arachidonic acid as agonist, in a final concentration of 0.5 mM (ASPI test. Results: In our data set 81% (n=94 were responders and 19% (n=22 non-responders showing high-on-aspirin platelet reactivity. Correlation analysis showed that the ward of admittance, low-density lipoproteins (LDL, concomitant antibiotic treatment, beta-adrenergic receptor blockers, history of myocardial infarction as well as PCI performed on Cardiology patients have different degrees of association with aspirin response. Conclusion: Concomitant treatment with beta-adrenergic receptor inhibitors, history of myocardial infarction and Cardiology ward admittance significantly increased the chance of responding to aspirin treatment whereas antibiotic therapy and low-density lipoproteins cholesterol seemed to increase the risk of high-on-aspirin residual platelet reactivity.

  8. Association of the Platelet Membrane Glycoprotein Ⅰa C807T Gene Polymorphism with Aspirin Resistance

    Institute of Scientific and Technical Information of China (English)

    SU Guanhua; WANG Zhaohui; DING Yanping; LIU Xiaoqian; WANG Jue

    2007-01-01

    To explore the correlation between the C807T polymorphism of platelet membrane gly- coprotein Ⅰa (GPⅠa) gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin (100 mg/d) for 7 days. Platelet aggregation function was detected using adenosine diphosphate (ADP) and arachidonic acid (AA) before and after the administration of aspi- fin. Then the subjects were divided into three groups according to the results of platelet aggregation function: an aspirin resistant (AR) group, an aspirin semi-responder (ASR) group and an aspi- fin-sensitive (AS) group. Platelet GPⅠa gene 807CT polymorphism was examined by means of po- lymerase chain reaction-sequence specific primers (PCR-SSP). The results showed that T allelic fre- quency in AR group and ASR group were higher that of AS group (P<0.005), and the prevalence of genotypes (TT+TC) of these two groups was significantly higher than that in AS group (P<0.05). Platelet GPⅠa T allele was significantly associated with aspirin resistance as revealed by multiple logistic regression (OR=3.76, 95% CI: 2.87-9.58). The results suggest that inherited platelet GPⅠa variations may have an important impact on aspirin resistance and the presence of GPⅠa T allele may be a marker of genetic susceptibility to aspirin resistance.

  9. Interaction of Acupuncture and Electroacupuncture on the Pharmacokinetics of Aspirin and the Effect of Brain Blood Flow in Rats

    Directory of Open Access Journals (Sweden)

    Ming-Tsang Wu

    2013-01-01

    Full Text Available Acupuncture and electroacupuncture have been used to improve the brain and motor functions of poststroke patients, and aspirin is used for the prevention of stroke recurrence. Our hypothesis is that acupuncture and electroacupuncture treatments may interact with aspirin in terms of pharmacokinetics via affecting the brain blood flow. The aim of this study is to investigate the potential interactions of acupuncture and electroacupuncture on the pharmacokinetics of aspirin. The effects of acupuncture treatments on brain blood flow were measured by the laser Doppler blood flow imager. The parallel pharmacokinetic study design included three groups: control, acupuncture, and electroacupuncture groups. Two acupoints, namely, Quchi (LI 11 and Zusanli (ST 36, were needled and stimulated electronically in anaesthetized rats. The concentrations of aspirin and its metabolite, salicylic acid were determined by microdialysis and HPLC analysis after aspirin administration (30 mg/kg, i.v.. The brain blood flow responded to electroacupuncture treatments, but the pharmacokinetic parameters of aspirin and salicylic acid in blood and brain were not significantly changed by acupuncture and electroacupuncture treatments. This study may, in part, offer some evidence to support the contention that there is no significant interaction for the combination of aspirin with acupuncture or electroacupuncture.

  10. Interaction of acupuncture and electroacupuncture on the pharmacokinetics of aspirin and the effect of brain blood flow in rats.

    Science.gov (United States)

    Wu, Ming-Tsang; Shaw, Lee-Hsin; Wu, Yu-Tse; Tsai, Tung-Hu

    2013-01-01

    Acupuncture and electroacupuncture have been used to improve the brain and motor functions of poststroke patients, and aspirin is used for the prevention of stroke recurrence. Our hypothesis is that acupuncture and electroacupuncture treatments may interact with aspirin in terms of pharmacokinetics via affecting the brain blood flow. The aim of this study is to investigate the potential interactions of acupuncture and electroacupuncture on the pharmacokinetics of aspirin. The effects of acupuncture treatments on brain blood flow were measured by the laser Doppler blood flow imager. The parallel pharmacokinetic study design included three groups: control, acupuncture, and electroacupuncture groups. Two acupoints, namely, Quchi (LI 11) and Zusanli (ST 36), were needled and stimulated electronically in anaesthetized rats. The concentrations of aspirin and its metabolite, salicylic acid were determined by microdialysis and HPLC analysis after aspirin administration (30 mg/kg, i.v.). The brain blood flow responded to electroacupuncture treatments, but the pharmacokinetic parameters of aspirin and salicylic acid in blood and brain were not significantly changed by acupuncture and electroacupuncture treatments. This study may, in part, offer some evidence to support the contention that there is no significant interaction for the combination of aspirin with acupuncture or electroacupuncture. PMID:24371465

  11. Reproducibility over time and effect of low-dose aspirin on soluble P-selectin and soluble CD40 ligand.

    Science.gov (United States)

    Valdes, Vanessa; Nardi, Michael A; Elbaum, Lindsay; Berger, Jeffrey S

    2015-07-01

    Platelet markers [soluble CD40 ligand (sCD40L) and soluble p selectin (sPselectin)] are associated with platelet activation and cardiovascular events. We sought to investigate the reproducibility of these markers over time and the effect of low-dose aspirin on sCD40L and sPselectin in plasma and serum. Following an overnight fast, 40 healthy volunteers had weekly phlebotomy and were administered aspirin 81 mg/day between weeks 3 and 4. Reproducibility over time was assessed by coefficient of variation (CV) and inter-class correlation coefficient. Correlation between markers was assessed using Pearson r statistic. Difference between levels pre- and post-aspirin was measured with Wilcoxon signed-rank test. Data are presented as median (interquartile range). sCD40L and sPselectin measurements were reproducible over time in plasma and serum (CV < 10 %). Measurement of sCD40L and sPselectin in plasma correlated with levels in serum before aspirin and after aspirin. There was no significant correlation between sCD40L and sPselectin. After 1-week of aspirin 81 mg/day, there was a reduction in sCD40L and sPselectin in serum and plasma, respectively. Soluble CD40L and sPselectin are independent markers that are reproducible over time in both plasma and sera and are reduced by 1-week of low-dose aspirin.

  12. Aspirin treatment of the low-dose-endotoxin-treated pregnant rat : Pathophysiologic and immunohistologic aspects

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Baller, JFW; Valkhof, N; Bakker, WW

    1997-01-01

    In the present study, we evaluated the effect of low-dose aspirin (acetylsalicylic acid (ASA); 1.0 mg/kg daily) on blood pressure, albumin excretion, glomerular fibrinogen deposits, and glomerular (basement) membrane-bound adenosine diphosphatase (ecto-ADPase) activity, as well as on glomerular infl

  13. NIH study finds regular aspirin use may reduce ovarian cancer risk

    Science.gov (United States)

    Women who take aspirin daily may reduce their risk of ovarian cancer by 20 percent, according to a study by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health. However, further research is needed before clinical r

  14. Which patients should receive aspirin for primary prevention of cardiovascular disease? An economic evaluation

    NARCIS (Netherlands)

    Annemans, L.; Lamotte, M.; Kubin, M.; Evers, T.; Verheugt, F. W. A.

    2006-01-01

    Low-dose aspirin is a standard care for secondary prevention of cardiovascular disease (CVD). Its use in primary prevention is less widely accepted, however, despite recent meta-analyses and US and European guidelines supporting its use in individuals at increased CVD risk. The aim of this study was

  15. Biphasic effect of aspirin on apoptosis of bovine vascular endothelial cells and its molecular mechanism

    Institute of Scientific and Technical Information of China (English)

    Qing-quan CHEN; Wen-lan LIU; Xun GUO; Yuan-jian LI; Zhao-gui GUO

    2007-01-01

    Aim: To investigate the effect of aspirin on the apoptosis of cultured bovine aortic endothelial cells (BAEC) and the signal pathways involved in this process.Methods: BAEC were cultured and passaged in Dulbecco's modified Eagle's medium culture medium. Morphologic changes and quantification of apoptotic cells were determined using fluorescence microscope after staining the cells with Hoechst 33258. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method. DNA fragmentation was visualized by agarose gel electrophoresis. Phospho-p38 mitogen-activated protein kinase(MAPK) expression was detected by Western blotting. Results: Aspirin at low concentrations from 1×10-10 mol/L to 1×10-8 mol/L decreased the apoptosis and p38 MAPK phosphorylation induced by H2O2 in BAEC, while high doses of aspi-fin (1×10-7-1×10-4 mol/L) induced typical apoptotic changes in BAEC and stimu-lated the expression of phospho-p38 MAPK in a concentration-dependent manner.SB203580, a specific p38 MAPK inhibitor, blocked such effects. Conclusion:Aspirin exhibits a biphasic effect on the apoptosis in BAEC, reducing apoptosis at low concentration and inducing apoptosis at high concentration, p38 MAPK may be an important signal molecule mediating the effects of aspirin.

  16. APROTININ PRESERVES HEMOSTASIS IN ASPIRIN-TREATED PATIENTS UNDERGOING CARDIOPULMONARY BYPASS

    NARCIS (Netherlands)

    TABUCHI, N; HUET, RCG; STURK, A; EIJSMAN, L; WILDEVUUR, CRH

    1994-01-01

    Various clinical trials have shown that hemostasis is improved by the administration of aprotinin during cardiopulmonary bypass. However, this effect has not been proved for those patients treated preoperatively with aspirin. Therefore, a double-blind, placebo-controlled study was conducted to test

  17. Correlation between erosive esophagitis and low-dose aspirin in elderly patients

    Institute of Scientific and Technical Information of China (English)

    于雪

    2013-01-01

    Objective To investigate the correlation between erosive esophagitis (EE) and low dose aspirin in elderly patients.Methods From January 2009 to August 2012,a total of 304 patients to undergo upper gastrointestinal endoscopy in our hospital without history of upper gastrointestinal operation,malignant tumor,liver cirrhosis and

  18. Aspirin in the prevention of cardiovascular disease in type 2 diabetes

    NARCIS (Netherlands)

    Hovens, Marcel Maria Christiaan

    2010-01-01

    In the first of this thesis, results are summarized of a randomised crossover trial on the effects of aspirin on markers of inflammation, coagulation and number of endothelial progenitor cells in type 2 diabetic patients without cardiovascular disease. In the second part, results of two systematic r

  19. Low-dose aspirin and rupture of abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Wemmelund, Holger; Jørgensen, Trine M M; Høgh, Annette;

    2016-01-01

    OBJECTIVE: The use of low-dose aspirin (acetylsalicylic acid [ASA]) has been suggested to attenuate growth of abdominal aortic aneurysms (AAAs), yet solid clinical evidence of this hypothesis is still missing. This study aimed to investigate whether preadmission ASA use influenced the risk of...

  20. Aspirin induced asthma accompanied with allergic bronchopulmonary aspergillosis: a case report

    Institute of Scientific and Technical Information of China (English)

    TANG Rui; ZHANG Hong-yu

    2010-01-01

    @@ In this paper, we describe a patient with a rather severe form of aspirin-induced asthma (AIA) and allergic bronchopulmonary aspergillosis (ABPA). The patient is a man born in 1948, who first presented with rhinorrhea,nasal congestion and chronic urticaria, and had an episode of asthma after ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) for the further eight years.

  1. Repurposing of Aspirin and Ibuprofen as Candidate Anti-Cryptococcus Drugs.

    Science.gov (United States)

    Ogundeji, Adepemi O; Pohl, Carolina H; Sebolai, Olihile M

    2016-08-01

    The usage of fluconazole and amphotericin B in clinical settings is often limited by, among other things, drug resistance development and undesired side effects. Thus, there is a constant need to find new drugs to better manage fungal infections. Toward this end, the study described in this paper considered the repurposing of aspirin (acetylsalicylic acid) and ibuprofen as alternative drugs to control the growth of cryptococcal cells. In vitro susceptibility tests, including a checkerboard assay, were performed to assess the response of Cryptococcus neoformans and Cryptococcus gattii to the above-mentioned anti-inflammatory drugs. Next, the capacity of these two drugs to induce stress as well as their mode of action in the killing of cryptococcal cells was determined. The studied fungal strains revealed a response to both aspirin and ibuprofen that was dose dependent, with ibuprofen exerting greater antimicrobial action. More importantly, the MICs of these drugs did not negatively (i) affect growth or (ii) impair the functioning of macrophages; rather, they enhanced the ability of these immune cells to phagocytose cryptococcal cells. Ibuprofen was also shown to act in synergy with fluconazole and amphotericin B. The treatment of cryptococcal cells with aspirin or ibuprofen led to stress induction via activation of the high-osmolarity glycerol (HOG) pathway, and cell death was eventually achieved through reactive oxygen species (ROS)-mediated membrane damage. The presented data highlight the potential clinical application of aspirin and ibuprofen as candidate anti-Cryptococcus drugs. PMID:27246782

  2. Relief of Dental Pain: A Controlled 12-Hour Comparison of Etodolac, Aspirin, and Placebo

    Science.gov (United States)

    Nelson, Sharon L.; Bergman, Stewart A.

    1985-01-01

    Single doses of the study drugs were evaluated for 12 hours by 201 out-patients reporting moderate or severe pain following oral surgery. The results of this double-blind study indicated that 50, 100, and 200 mg of etodolac as well as 650 mg of aspirin were significantly more effective than placebo. A dose-response relationship was found for the three doses of etodolac, which was significant for summed pain relief scores for up to 8 hours. In terms of total analgesic effect, etodolac 200 mg was significantly superior to placebo for 8 hours, while aspirin and the two lower doses of etodolac were similarly effective in the range of 3-6 hours postdrug. All doses showed a favorable onset of analgesia (½-1 hour). Etodolac 200 mg resulted in a duration of action which was approximately twice as long as aspirin's and also produced a peak pain relief which was significantly greater than the lower doses of etodolac and aspirin. All study medications were well tolerated with no reports of significant adverse side effects. No dose-related effects were observed with etodolac PMID:2934008

  3. Effect of low-dose aspirin during pregnancy on fibrinolytic variables before and after parturition

    NARCIS (Netherlands)

    H.A. Bremer (Henk); N. Rotmans (Nel); E.J.Ph. Brommer; H.C.S. Wallenburg (Henk)

    1995-01-01

    textabstractOBJECTIVE: We assessed the effects of a daily oral dose of 60 to 80 mg of aspirin from 12 weeks gestation until delivery on fibrinolytic variables before and after parturition. STUDY DESIGN: In a prospective controlled study labor was electively induced in 24 patients, eight receiving l

  4. Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding.

    Directory of Open Access Journals (Sweden)

    Akiko Shiotani

    Full Text Available BACKGROUND: Aspirin-induced enteropathy is now increasingly being recognized although the pathogenesis of small intestinal damage induced by aspirin is not well understood and related risk factors have not been established. AIM: To investigate pharmacogenomic profile of low dose aspirin (LDA-induced small bowel bleeding. METHODS: Genome-wide analysis of single nucleotide polymorphisms (SNPs was performed using the Affymetrix DMET™ Plus Premier Pack. Genotypes of candidate genes associated with small bowel bleeding were determined using TaqMan SNP Genotyping Assay kits and direct sequencing. RESULTS: In the validation study in overall 37 patients with small bowel bleeding and 400 controls, 4 of 27 identified SNPs: CYP4F11 (rs1060463 GG (p=0.003, CYP2D6 (rs28360521 GG (p=0.02, CYP24A1 (rs4809957 T allele (p=0.04, and GSTP1 (rs1695 G allele (p=0.04 were significantly more frequent in the small bowel bleeding group compared to the controls. After adjustment for significant factors, CYP2D6 (rs28360521 GG (OR 4.11, 95% CI. 1.62 -10.4 was associated with small bowel bleeding. CONCLUSIONS: CYP4F11 and CYP2D6 SNPs may identify patients at increased risk for aspirin-induced small bowel bleeding.

  5. Reduction of aspirin-induced fecal blood loss with low-dose misoprostol tablets in man

    International Nuclear Information System (INIS)

    Misoprostol (SC-29333), a synthetic prostaglandin E1 methyl ester analog, was given simultaneously with acetylsalicylic acid in a double-blind, placebo-controlled randomized prospective study of 32 healthy human male subjects. Fecal blood loss was measured for eight days using the 51Cr-labeled red blood cell technique. Aspirin (650 mg qid) and misoprostol (25 micrograms qid) or placebo were given during days 3, 4, and 5. There was a significant (P less than 0.05) increase in median blood loss (modified Friedman test) from 0.81 to 6.05 ml/day in the aspirin with placebo group (N = 16). Median blood loss was increased (from 0.75 to 3.75 ml/day) in the aspirin with misoprostol group (N = 16), but this was significantly less (Mann-Whitney U test, P less than 0.01) than the placebo group. Mean serum salicylate concentrations in the placebo and misoprostol groups were similar (7.8 and 6.8 micrograms/ml, respectively). There were no significant changes in laboratory values in any of the subjects studied, nor were any major side-effects encountered. This study demonstrates that oral misoprostol reduces aspirin-induced gastrointestinal bleeding even when administered simultaneously and at a dose level below its threshold for significant acid inhibition. This indicates a potential role for misoprostol in the prevention of gastric mucosal damage in selected patients

  6. Prevention of Aspirin against Recurrence of Polyposis after Operation on Patients with Familial Polyposis Coli

    Institute of Scientific and Technical Information of China (English)

    Zhou Jia-zhen; Liu Tao; Jin Jia-gui; Hu Xian-dian

    2006-01-01

    Objective To investigate how well a combined therapy prevents and treats familial polyposis coli and to observe whether aspirin prevents duodenal polyp development after operation.Methods Aspirin was started one month after the operation on 6 patients with familial polyposis coli. It was given 60 mg once a day for one month, and then was discontinued for one month, then used again for one month, and then discontinued for one month; in this way, aspirin was used every two months for the patient's life. The follow-up was performed for 17 years. Results The combined therapy, which consisted of a surgical operation of cutting the superior mesenteric artery & vein and making anastomosis of the ileum pouch and the anal canal within the muscular sheath of the rectum and an internal medical therapy of nonsteroidal antiinflammatory drugs, had a good therapeutic effect on familial polyposis coli and no duodenal polyp occurred in the 6 patients. Conclusion Our combined therapy can effectively treat familial polyposis coli, and aspirin can prevent duodenal polyp development after the operation.

  7. Sustained release of aspirin and vitamin C from titanium nanotubes: An experimental and stimulation study.

    Science.gov (United States)

    Yang, Weihu; Deng, Conghui; Liu, Peng; Hu, Yan; Luo, Zhong; Cai, Kaiyong

    2016-07-01

    Anodization is a promising method to change the topography and wettability of titanium (Ti) implant. The formed TiO2 nanotubes (TiNTs) arrays could enhance the biological properties of Ti implants. In this study, to investigate the possibility of TiNTs arrays on a Ti implant surface as nano-reservoirs for small molecular drugs when using in orthopedic and dental prosthesis, TiNTs on a Ti implant surface were prepared. Then, aspirin and/or vitamin C were loaded into TiNTs as model drugs. Meanwhile, low molecular weight polylactic acid (PLA, Mw=3000) was synthesized and loaded alternately along with aspirin or vitamin C. The release rates of aspirin and vitamin C with/or without PLA loading were investigated by using a UV-Vis spectrometer. The results showed that when loading without PLA, drugs released quickly with presence of burst release. However, when loading with PLA, the cumulative release duration of aspirin and vitamin C was prolonged to over 240h. Molecular dynamics (MD) simulation and dissipative particle dynamics (DPD) simulation results proved that when loading with PLA, PLA molecules aggregated gradually and formed clusters or micelles in these nanotubes. Meanwhile, drug molecules were captured and distributed inside the PLA matrix, which retarding the release of drugs. Only when PLA micelles degrade gradually in body fluid, drugs could be released slowly from nanotubes. These knowledge laid ground basis for the following biological experiments. PMID:27127038

  8. Analgesic effect of fendosal, ibuprofen and aspirin in postoperative oral surgery pain.

    Science.gov (United States)

    Forbes, J A; Barkaszi, B A; Ragland, R N; Hankle, J J

    1984-01-01

    The analgesic efficacy of a single 200-mg dose of fendosal, a nonnarcotic, nonsteroidal antiinflammatory analgesic, was compared, in a double-blind study, with aspirin 650 mg, ibuprofen 400 mg and placebo in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medicating. Each active medication was significantly superior to placebo. The peak analgesic effect of fendosal 200 mg was similar to that of the aspirin 650-mg standard. Although fendosal's onset of action was slow (3 hours), its effect persisted for 8 hours, substantially longer than that of aspirin. Ibuprofen 400 mg was statistically significantly superior to aspirin 650 mg and fendosal 200 mg for most measures of peak and total analgesia, and its effect persisted for 8 hours. The results of this study raise some questions concerning the comparability of data from studies that employ different criteria for remedication and/or different criteria for the inclusion of data in the analyses of efficacy.

  9. Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, K.K.; Sanduja, R.; Tsai, A.L.; Ferhanoglu, B.; Loose-Mitchell, D.S. (Univ. of Texas Medical School, Houston (United States))

    1991-03-15

    Prostaglandin H (PGH) synthase is a key enzyme in the biosynthesis of prostaglandins, thromboxane, and prostacyclin. In cultured human umbilical vein endothelial cells, interleukin 1 (IL-1) is known to induce the synthesis of this enzyme, thereby raising the level of PGH synthase protein severalfold over the basal level. Pretreatment with aspirin at low concentrations inhibited more than 60% of the enzyme mass and also the cyclooxygenase activity in IL-1-induced cells with only minimal effects on the basal level of the synthase enzyme in cells without IL-1. Sodium salicylate exhibited a similar inhibitory action whereas indomethacin had no apparent effect. Similarly low levels of aspirin inhibited the increased L-({sup 35}S)methionine incorporation into PGH synthase that was induced by IL0-1 and also suppressed expression of the 2.7-kilobase PGH synthase mRNA. These results suggest that in cultured endothelial cells a potent inhibition of eicosanoid biosynthetic capacity can be effected by aspirin or salicylate at the level of PGH synthase gene expression. The aspirin effect may well be due to degradation of salicylate.

  10. Evaluation of small bowel blood flow in healthy subjects receiving low-dose aspirin

    Institute of Scientific and Technical Information of China (English)

    Urara Nishida; Mototsugu Kato; Mutsumi Nishida; Go Kamada; Takeshi Yoshida; Shouko Ono; Yuichi Shimizu; Masahiro Asaka

    2011-01-01

    AIM: To investigate the relationship between low-dose aspirin-induced small bowel mucosal damage and blood flow, and the effect of rebamipide.METHODS: Ten healthy volunteers were enrolled in this study. The subjects were divided into two groups:a placebo group given low-dose aspirin plus placebo and a rebamipide group given low-dose aspirin plus rebamipide for a period of 14 d. Capsule endoscopy and contrast-enhanced ultrasonography were performed before and after administration of drugs. Areas under the curves and peak value of time-intensity curve were calculated.RESULTS: Absolute differences in areas under the curves were -1102.5 (95% CI: -1980.3 to -224.7, P = 0.0194) in the placebo group and -152.7 (95% CI:-1604.2 to 641.6, P = 0.8172) in the rebamipide group.Peak values of time intensity curves were -148.0 (95%CI: -269.4 to -26.2, P = 0.0225) in the placebo group and 28.3 (95% CI: -269.0 to 325.6, P = 0.8343) in the rebamipide group. Capsule endoscopy showed mucosal breaks only in the placebo group.CONCLUSION: Short-term administration of low-dose aspirin is associated with small bowel injuries and blood flow.

  11. The incidence of aspirin resistance and relevant influencing factors in patients on maintenance hemodialysis

    Institute of Scientific and Technical Information of China (English)

    张春华

    2014-01-01

    Objective To explore aspirin resistance(AR)and its relevant influencing factors in patients on maintenance hemodialysis(MHD).Methods Patients on MHD who visited Beijing Chaoyang Hospital from June 1 to 30,2011 were enrolled in this study.A total of 150 age and gender matched individuals with normal renal function were taken as control group.Anthropometric data,bio-

  12. Aspirin in Alzheimer's Disease Increased Risk of Intracerebral Hemorrhage: Cause for Concern?

    NARCIS (Netherlands)

    H. Thoonsen; E. Richard; P. Bentham; R. Gray; N. van Geloven; R.J. de Haan; W.A. van Gool; P.J. Nederkoorn

    2010-01-01

    Background and Purpose-In a randomized controlled trial in Alzheimer's disease (AD), we found a higher number of intracerebral hemorrhages (ICHs) in patients randomized to aspirin treatment. Here, we evaluate the literature on the risk of ICH as a complication in patients with AD treated with aspiri

  13. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin

    Directory of Open Access Journals (Sweden)

    Yuan Li

    2016-01-01

    Full Text Available The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin’s related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71 and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed.

  14. Effect of aspirin on glucose-D transport in intestine of rat

    Institute of Scientific and Technical Information of China (English)

    Mazhar Mushtaq; Farah Deeba Khan; M. Naeem Akhtar; Saghir Ahmad Jafri; Mehboob Bari

    2009-01-01

    Objective: The present study was designed to evaluate the effect a commonly prescribed Non Steroidal Anti In-flammatory Drug (NSAID) i.e. aspirin on brush border membrane in terms of changes in the intestinal transport level of glucose which is monosaccharide with absolute requirement in the body and hence its absorption is directly proportional on the morphology of the intestinal mucosa. Method: Albino rats (Rattus Norvegicus) were divided into two different groups, Group Ⅰ (Control), Group Ⅱ ( aspirin-treated, 50 mg aspirin/kg of body weight). The treatment was continued for 28 days. On the 29th day after o-, vernight fasting, intestine was removed from animals of both groups. Changes in transport of glucose-D in intestine were studied. Result: The results indicated a significant decrease in the transport of glucose-D in aspirin treated group as compared to the con-trol group. Conclusion: Cautious use of NSAID is recommended in commonly observed symptom such as headache and to those patients who are given as a prophylaxis for thrombosis.

  15. Should All Patients with Risk Factors for Ischemic Heart Disease Receive Aspirin?

    OpenAIRE

    Willerson, James T.; Mueller, Susan D.; Ferguson, James J.

    1992-01-01

    Unstable angina appears to be caused by relatively brief, repetitive episodes of myocardial oxygen impairment secondary to platelet aggregation and dynamic vasoconstriction at sites of coronary stenosis and endothelial injury. With chronic endothelial injury, the accumulation of thromboxane A2, serotonin, and other mediators may contribute to platelet aggregation and dynamic vasoconstriction. Aspirin acetylates the platelet enzyme, cyclooxygenase, thereby inhibiting the formation of thromboxa...

  16. Aspirin Has Antitumor Effects via Expression of Calpain Gene in Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sang Koo Lee

    2008-01-01

    Full Text Available Aspirin and other nonsteroidal anti-inflammatory drugs show efficacy in the prevention of cancers. It is known that they can inhibit cyclooxygenases, and some studies have shown that they can induce apoptosis. Our objective in this study was to investigate the mechanism by which aspirin exerts its apoptosis effects in human cervical cancer HeLa cells. The effect of aspirin on the gene expression was studied by differential mRNA display RT-PCR. Among the isolated genes, mu-type calpain gene was upregulated by aspirin treatment. To examine whether calpain mediates the antitumor effects, HeLa cells were stably transfected with the mammalian expression vector pCR3.1 containing mu-type calpain cDNA (pCRCAL/HeLa, and tumor formations were measured in nude mice. When tumor burden was measured by day 49, HeLa cells and pCR/HeLa cells (vector control produced tumors of 2126 mm3 and 1638 mm3, respectively, while pCRCAL/HeLa cells produced markedly smaller tumor of 434 mm3 in volume. The caspase-3 activity was markedly elevated in pCRCAL/HeLa cells. The increased activity levels of caspase-3 in pCRCAL/HeLa cells, in parallel with the decreased tumor formation, suggest a correlation between caspase-3 activity and calpain protein. Therefore, we conclude that aspirin-induced calpain mediates an antitumor effect via caspase-3 in cervical cancer cells.

  17. Aspirin and Statin Nonuse Associated With Early Biochemical Failure After Prostate Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zaorsky, Nicholas G. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Buyyounouski, Mark K., E-mail: mark.buyyounouski@fccc.edu [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Li, Tianyu [Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Horwitz, Eric M. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States)

    2012-09-01

    Purpose: To present the largest retrospective series investigating the effect of aspirin and statins, which are hypothesized to have antineoplastic properties, on biochemical failure (nadir plus 2 ng/mL) after prostate radiation therapy (RT). Methods and Materials: Between 1989 and 2006, 2051 men with clinically localized prostate cancer received definitive RT alone (median dose, 76 Gy). The rates of aspirin use and statin use (defined as any use at the time of RT or during follow-up) were 36% and 34%, respectively. The primary endpoint of the study was an interval to biochemical failure (IBF) of less than 18 months, which has been shown to be the single strongest predictor of distant metastasis, prostate cancer survival, and overall survival after RT. Patient demographic characteristics and tumor staging factors were assessed with regard to associations with the endpoint. Univariate analysis was performed with the {chi}{sup 2} test for categorical variables and the Wilcoxon test for continuous variables. Multivariable analysis was performed with a multiple logistic regression. Results: The median follow-up was 75 months. Univariate analysis showed that an IBF of less than 18 months was associated with aspirin nonuse (P<.0001), statin nonuse (P<.0001), anticoagulant nonuse (P=.0006), cardiovascular disease (P=.0008), and prostate-specific antigen (continuous) (P=.008) but not with Gleason score, age, RT dose, or T stage. On multivariate analysis, only aspirin nonuse (P=.0012; odds ratio, 2.052 [95% confidence interval, 1.328-3.172]) and statin nonuse (P=.0002; odds ratio, 2.465 [95% confidence interval, 1.529-3.974]) were associated with an IBF of less than 18 months. Conclusions: In patients who received RT for prostate cancer, aspirin or statin nonuse was associated with early biochemical failure, a harbinger of distant metastasis and death. Further study is needed to confirm these findings and to determine the optimal dosing and schedule, as well as the relative

  18. Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1

    Energy Technology Data Exchange (ETDEWEB)

    Rimon, Gilad; Sidhu, Ranjinder S.; Lauver, D. Adam; Lee, Jullia Y.; Sharma, Narayan P.; Yuan, Chong; Frieler, Ryan A.; Trievel, Raymond C.; Lucchesi, Benedict R.; Smith, William L. (Michigan)

    2010-02-11

    Pain associated with inflammation involves prostaglandins synthesized from arachidonic acid (AA) through cyclooxygenase-2 (COX-2) pathways while thromboxane A{sub 2} formed by platelets from AA via cyclooxygenase-1 (COX-1) mediates thrombosis. COX-1 and COX-2 are both targets of nonselective nonsteroidal antiinflammatory drugs (nsNSAIDs) including aspirin whereas COX-2 activity is preferentially blocked by COX-2 inhibitors called coxibs. COXs are homodimers composed of identical subunits, but we have shown that only one subunit is active at a time during catalysis; moreover, many nsNSAIDS bind to a single subunit of a COX dimer to inhibit the COX activity of the entire dimer. Here, we report the surprising observation that celecoxib and other coxibs bind tightly to a subunit of COX-1. Although celecoxib binding to one monomer of COX-1 does not affect the normal catalytic processing of AA by the second, partner subunit, celecoxib does interfere with the inhibition of COX-1 by aspirin in vitro. X-ray crystallographic results obtained with a celecoxib/COX-1 complex show how celecoxib can bind to one of the two available COX sites of the COX-1 dimer. Finally, we find that administration of celecoxib to dogs interferes with the ability of a low dose of aspirin to inhibit AA-induced ex vivo platelet aggregation. COX-2 inhibitors such as celecoxib are widely used for pain relief. Because coxibs exhibit cardiovascular side effects, they are often prescribed in combination with low-dose aspirin to prevent thrombosis. Our studies predict that the cardioprotective effect of low-dose aspirin on COX-1 may be blunted when taken with coxibs.

  19. Aspirin delays mesothelioma growth by inhibiting HMGB1-mediated tumor progression.

    Science.gov (United States)

    Yang, H; Pellegrini, L; Napolitano, A; Giorgi, C; Jube, S; Preti, A; Jennings, C J; De Marchis, F; Flores, E G; Larson, D; Pagano, I; Tanji, M; Powers, A; Kanodia, S; Gaudino, G; Pastorino, S; Pass, H I; Pinton, P; Bianchi, M E; Carbone, M

    2015-01-01

    High-mobility group box 1 (HMGB1) is an inflammatory molecule that has a critical role in the initiation and progression of malignant mesothelioma (MM). Aspirin (acetylsalicylic acid, ASA) is the most widely used nonsteroidal anti-inflammatory drug that reduces the incidence, metastatic potential and mortality of many inflammation-induced cancers. We hypothesized that ASA may exert anticancer properties in MM by abrogating the carcinogenic effects of HMGB1. Using HMGB1-secreting and -non-secreting human MM cell lines, we determined whether aspirin inhibited the hallmarks of HMGB1-induced MM cell growth in vitro and in vivo. Our data demonstrated that ASA and its metabolite, salicylic acid (SA), inhibit motility, migration, invasion and anchorage-independent colony formation of MM cells via a novel HMGB1-mediated mechanism. ASA/SA, at serum concentrations comparable to those achieved in humans taking therapeutic doses of aspirin, and BoxA, a specific inhibitor of HMGB1, markedly reduced MM growth in xenograft mice and significantly improved survival of treated animals. The effects of ASA and BoxA were cyclooxygenase-2 independent and were not additive, consistent with both acting via inhibition of HMGB1 activity. Our findings provide a rationale for the well documented, yet poorly understood antitumorigenic activity of aspirin, which we show proceeds via HMGB1 inhibition. Moreover, the use of BoxA appears to allow a more efficient HMGB1 targeting while eluding the known gastrointestinal side effects of ASA. Our findings are directly relevant to MM. Given the emerging importance of HMGB1 and its tumor-promoting functions in many cancer types, and of aspirin in cancer prevention and therapy, our investigation is poised to provide broadly applicable information. PMID:26068794

  20. Aspirin's Active Metabolite Salicylic Acid Targets High Mobility Group Box 1 to Modulate Inflammatory Responses.

    Science.gov (United States)

    Choi, Hyong Woo; Tian, Miaoying; Song, Fei; Venereau, Emilie; Preti, Alessandro; Park, Sang-Wook; Hamilton, Keith; Swapna, G V T; Manohar, Murli; Moreau, Magali; Agresti, Alessandra; Gorzanelli, Andrea; De Marchis, Francesco; Wang, Huang; Antonyak, Marc; Micikas, Robert J; Gentile, Daniel R; Cerione, Richard A; Schroeder, Frank C; Montelione, Gaetano T; Bianchi, Marco E; Klessig, Daniel F

    2015-01-01

    Salicylic acid (SA) and its derivatives have been used for millennia to reduce pain, fever and inflammation. In addition, prophylactic use of acetylsalicylic acid, commonly known as aspirin, reduces the risk of heart attack, stroke and certain cancers. Because aspirin is rapidly de-acetylated by esterases in human plasma, much of aspirin's bioactivity can be attributed to its primary metabolite, SA. Here we demonstrate that human high mobility group box 1 (HMGB1) is a novel SA-binding protein. SA-binding sites on HMGB1 were identified in the HMG-box domains by nuclear magnetic resonance (NMR) spectroscopic studies and confirmed by mutational analysis. Extracellular HMGB1 is a damage-associated molecular pattern molecule (DAMP), with multiple redox states. SA suppresses both the chemoattractant activity of fully reduced HMGB1 and the increased expression of proinflammatory cytokine genes and cyclooxygenase 2 (COX-2) induced by disulfide HMGB1. Natural and synthetic SA derivatives with greater potency for inhibition of HMGB1 were identified, providing proof-of-concept that new molecules with high efficacy against sterile inflammation are attainable. An HMGB1 protein mutated in one of the SA-binding sites identified by NMR chemical shift perturbation studies retained chemoattractant activity, but lost binding of and inhibition by SA and its derivatives, thereby firmly establishing that SA binding to HMGB1 directly suppresses its proinflammatory activities. Identification of HMGB1 as a pharmacological target of SA/aspirin provides new insights into the mechanisms of action of one of the world's longest and most used natural and synthetic drugs. It may also provide an explanation for the protective effects of low-dose aspirin usage. PMID:26101955

  1. Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial.

    Science.gov (United States)

    Souza, E V; Torloni, M R; Atallah, A N; Santos, G M S dos; Kulay, L; Sass, N

    2014-05-01

    Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.

  2. Trace metal content in aspirin and women's cosmetics via proton induced x-ray emission (PIXE)

    Energy Technology Data Exchange (ETDEWEB)

    Hichwa, B.P.; Pun, D.D.; Wang, D.

    1981-04-01

    A multielemental analysis to determine the trace metal content of generic and name-brand aspirins and name-brand lipsticks was done via proton induced x-ray (PIXE) measurements. The Hope College PIXE system is described as well as the target preparation methods. The trace metal content of twelve brands of aspirin and aspirin substitutes and fourteen brands of lipstick are reported. Detection limits for most elements are in the range of 100 parts per billion (ppb) to 10 parts per million (ppm).

  3. 载体MCM-41对Tb(aspirin)3phen发光性能的影响%Effect of Host MCM-41 on the Luminescence Properties of Tb (aspirin)3phen

    Institute of Scientific and Technical Information of China (English)

    彭春佳; 魏长平; 祝翠梅

    2008-01-01

    在室温下,乙二胺环境中合成了高度有序的介孔材料MCM-41,并将经热处理的发光客体Tb(aspi-rin)3phen组装进其孔道,通过激发发射光谱对其光致发光性能进行了研究.结果表明,Tb(aspirin)3phen240~375 nm区间的宽激发峰归属于配体aspirin羰基n→π*跃迁、苯环,π→π*跃迁,和phen的杂菲基团吸收,Tb3+的特征发射是由于Antenna效应引起的.相对于纯Tb(aspirin)3phen,Tb(aspirin)3phen-MCM-41B和Tb(aspirin)3phen/MCM-41A的激发谱带出现了明显的分裂,而Tb(aspirin)3phen-MCM-41A只在353nm处剩下了相对较窄的单峰.Tb(aspirin)3phen-MCM-41B,Tb(aspirin)3phen/MCM-41A和Tb(aspirin)3phen-MCM-41A的短波段激发峰依次减弱消失,长波段激发峰逐渐增强,而405 nm发射峰强度IL和544 nm发射峰强度Iln的比值I(I=IL/Iln)依次减小.MCM-41骨架与Tb(aspirin)3phen成键后,不同程度降低了配体aspirin和phen单重态S1和三重态T1能级,且对phen的影响大于aspirin.不同的MCM-41表面晶格场对配体能级的影响顺序为:MCM-41B外表面>MCM-41A外表面>MCM-41A内表面.I值可定性表示MCM-41表面晶格场对配体能级影响程度和MCM-41表面Tb(aspirin)3phen的含量.

  4. Impacts of metformin and aspirin on life history features and longevity of crickets: trade-offs versus cost-free life extension?

    Science.gov (United States)

    Hans, Harvir; Lone, Asad; Aksenov, Vadim; Rollo, C David

    2015-01-01

    We examined the impacts of aspirin and metformin on the life history of the cricket Acheta domesticus (growth rate, maturation time, mature body size, survivorship, and maximal longevity). Both drugs significantly increased survivorship and maximal life span. Maximal longevity was 136 days for controls, 188 days (138 % of controls) for metformin, and 194 days (143 % of controls) for aspirin. Metformin and aspirin in combination extended longevity to a lesser degree (163 days, 120 % of controls). Increases in general survivorship were even more pronounced, with low-dose aspirin yielding mean longevity 234 % of controls (i.e., health span). Metformin strongly reduced growth rates of both genders (aspirin only slightly reduced the growth rate of females and slightly increased that of males. Both drugs delayed maturation age relative to controls, but metformin had a much greater impact (>140 % of controls) than aspirin (~118 % of controls). Crickets maturing on low aspirin showed no evidence of a trade-off between maturation mass and life extension. Remarkably, by 100 days of age, aspirin-treated females were significantly larger than controls (largely reflecting egg complement). Unlike the reigning dietary restriction paradigm, low aspirin conformed to a paradigm of "eat more, live longer." In contrast, metformin-treated females were only ~67 % of the mass of controls. Our results suggest that hormetic agents like metformin may derive significant trade-offs with life extension, whereas health and longevity benefits may be obtained with less cost by agents like aspirin that regulate geroprotective pathways. PMID:25833406

  5. Airway responsiveness to leukotriene C4 (LTC4), leukotriene E4 (LTE4) and histamine in aspirin-sensitive asthmatic subjects.

    Science.gov (United States)

    Christie, P E; Schmitz-Schumann, M; Spur, B W; Lee, T H

    1993-11-01

    We wanted to determine whether the airway response to inhaled leukotriene C4 (LTC4) is similar to inhaled leukotriene E4 (LTE4) in aspirin-sensitive asthma and, therefore, determined airway responsiveness to histamine, LTC4 and LTE4 in seven aspirin-sensitive subjects and 13 control asthmatic subjects, who were tolerant of aspirin. The concentration of inhaled lysine-aspirin which produced a 15% fall in forced expiratory volume in one second (FEV1) (PC15) was determined in aspirin-sensitive asthmatic subjects. The dose of histamine, LTC4 and LTE4 which produced a 35% fall in specific airways conductance (PD35sGaw) was determined by linear interpolation from the log dose response curve. There was no correlation between the PC15 for lysine-aspirin and the airway reactivity to inhaled LTC4 or LTE4. There was no difference in airway response to histamine and LTC4 between any of the groups of asthmatic subjects. There was a rank order of potency LTC4 > LTE4 > histamine in both groups, with LTC4 approximately 1,000 fold more potent than histamine in both groups. Aspirin-sensitive asthmatic subjects were significantly more responsive to LTE4 (p = 0.02) than aspirin-tolerant asthmatic subjects. The relative responsiveness of LTE4 to histamine (PD35 histamine/PD35 LTE4) was significantly greater in aspirin-sensitive asthmatic subjects compared to aspirin-tolerant asthmatic subjects (p = 0.05). There was no difference in relative responsiveness of LTC4 to histamine between aspirin-sensitive or aspirin-tolerant asthmatic subjects. We conclude that the airways of aspirin-sensitive asthmatic subjects demonstrate a selective hyperresponsiveness to LTE4, which is not observed for LTC4. PMID:8112440

  6. Use of Aspirin in normalization of recombinant human erythropoietin-mediated hyper-reactivity of platelets in rats

    Directory of Open Access Journals (Sweden)

    Hitesh M Soni

    2014-01-01

    Conclusions: These findings suggest that rHuEPO increases platelet reactivity and aspirin normalizes the hyper-reactive platelet and may reduce the cardiovascular events associated with rHuEPO in CKD patients.

  7. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT) : a randomised controlled trial

    NARCIS (Netherlands)

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

    2007-01-01

    BACKGROUND: Oral anticoagulants are better than aspirin for secondary prevention after myocardial infarction and after cerebral ischaemia in combination with non-rheumatic atrial fibrillation. The European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) aimed to determine wheth

  8. Clopidogrel plus long-term aspirin after femoro-popliteal stenting. The CLAFS project: 1- and 2-year results

    Energy Technology Data Exchange (ETDEWEB)

    Strecker, Ernst-Peter K.; Boos, Irene B.L.; Goettmann, Dieter; Vetter, Sylvia [Department of Imaging, Interventional Radiology, and Nuclear Medicine, Diakonissen Hospital, Diakonissenstrasse 28, 76199, Karlsruhe (Germany)

    2004-02-01

    The aim of this study was to determine the patency rate after femoro-popliteal stenting followed by oral clopidogrel plus long-term aspirin. In a prospective trial, 31 patients with a total of 33 femoro-popliteal artery lesions (21 stenoses, 12 occlusions; 24 femoral, 9 popliteal) were treated with flexible tantalum stents after unsuccessful percutaneous transluminal angioplasty (PTA) preceded by local fibrinolysis in 5 of 12 patients with total occlusion. Post-interventionally, oral aspirin 100 mg was started simultaneously for the long term and was combined with an oral loading dose of 300 mg clopidogrel, followed by 75 mg clopidogrel daily for 28 days. Patients were followed for at least 12 months (maximum 34 months) by clinical examination, Doppler pressure measurement, color and duplex sonography, and angiography in case of suspicion of restenosis. In a retrospective analysis, the results were compared with those of historical groups of patients having received aspirin only (41 patients) or a long-term high-dose low molecular weight heparin (LMWH)+aspirin treatment (42 patients). Three small puncture aneurysms were treated successfully by conservative means and were categorized as minor bleeding complication. Cumulative primary patency rate (PPR) was 76{+-}7.5% (1 year), and 70{+-}9.6% (2 years) in the clopidogrel+aspirin group, thus being tendentiously better than in the aspirin-only group showing 75{+-}4.6% (1 year), and 50{+-}8.1% (2 years). Long-term high-dose LMWH+aspirin treatment showed 87{+-}5.8% (1 year), and 72{+-}9.1% (2 years), thus being superior to the other treatment regimes, with a statistically significant difference (p<0.05) between the LMWH+aspirin and the aspirin group. Clopidogrel plus aspirin is a safe medication regimen and may be effective in the prevention of early stent thrombosis. Mid- and long-term patency rate seems to be intermediate as compared with other therapeutic regimens. The LMWH+aspirin seems to be superior compared with

  9. Effect of polymorphism and type Ⅱ diabetes on aspirin resistance in patients with unstable coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    GAO Fei; WANG Zan-xin; MEN Jian-long; REN Jing; WEI Min-xin

    2011-01-01

    Background Aspirin is widely used in the secondary prevention of coronary artery diseases, including myocardial infarction, stroke, and vascular related deaths. However, the antiplatelet effect of aspirin appears to be variable and aspirin resistance (AR) is currently still controversial for Chinese patients. The aim of this study was to describe the prevalence of AR, and identify possible risk factors associated with a lack of response to aspirin treatments in patients with unstable coronary artery disease.Methods Platelet function tests with arachidonic acid (ARA) and urinary 11-dehydro-thromboxane B2 (11-DH-TXB2) concentrations were performed in 262 patients with unstable coronary artery disease who had not been taking aspirin before admission. ARA induced platelet aggregation and 11-DH-TXB2 were detected to evaluate the functional and biochemical responses to aspirin before and on days 1, 4, and 10 after aspirin administration. Six-month follow-up was completed in patients who developed AR to evaluate the effect of aspirin in a long-term treatment. GP1 Bα (C1018T), PI(A1/A2), P2Y1(A1622G), TBXA2R (T924C) were also detected to evaluate the influence of genetic variant on aspirin responsiveness.Results A total of 8.8% of patients were indentified as AR at the first day after aspirin treatment. The level of urine 11-DH-TXB2 in the AR group was higher compared to non-AR group (P <0.05). There was no relationship between ARA induced platelet aggregation and urinary 11-DH-TXB2 levels (r=0.038, P=0.412). The results of DNA sequencing showed that TBXA2R-924TT homozygotes had a significantly high rate of AR. Logistic regression demonstrated that diabetes was an independent risk factor of AR.Conclusions In the beginning period of administration, aspirin was not a sufficient factor that inhibits platelet aggregation. TBXA2R-g24T allele was involved in AR. Diabetes was an independent risk factor of AR.

  10. Study of Clinical and Genetic Risk Factors for Aspirin-induced Gastric Mucosal Injury

    Institute of Scientific and Technical Information of China (English)

    Yun Wu; Ying Hu; Peng You; Yu-Jing Chi; Jian-Hua Zhou; Yuan-Yuan Zhang; Yu-Lan Liu

    2016-01-01

    Background:Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions.Methods:We recruited aspirin takers as the exposed group and healthy volunteers as the control group.The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy,including erosion,ulcer or bleeding of the esophagus,stomach,or duodenum;subgroup B as no injury of the gastric mucosa was detected by gastroscopy.Clinical information was collected,and 53 single nucleotide polymorphisms were evaluated.Results:Among 385 participants,234 were in the aspirin-exposed group.According to gastroscopy,82 belonged to subgroup A,91 belonged to subgroup B,and gastroscopic results of 61 participants were not available.Using the Chi-square test and logistic regression,we found that peptic ulcer history (odds ratio [OR] =5.924,95% confidence intervals [CI]:2.115-16.592),dual anti-platelet medication (OR =3.443,95% CI:1.154-10.271),current Helicobacterpylori infection (OR =2.242,95% CI:1.032-4.870),male gender (OR =2.211,95% CI:1.027-4.760),GG genotype ofrs2243086 (OR =4.516,95% CI:1.180-17.278),and AA genotype ofrs 1330344 (OR =2.178,95% CI:1.016-4.669) were more frequent in subgroup A than subgroup B.In aspirin users who suffered from upper gastrointestinal bleeding,the frequency of the TT genotype ofrs2238631 and TT genotype ofrs2243100 was higher than in those without upper gastrointestinal bleeding.Conclusions:Peptic ulcer history,dual anti-platelet medication,H.pylori current infection,and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury.GG genotype of rs2243086 and AA genotype of rs 1330344 were possible genetic risk factors.TT genotype ofrs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in aspirin users.

  11. Effects of Pranlukast, a Cysteinyl Leukotriene Antagonist, on Bronchial Responsiveness to Methacholine in Aspirin-Intolerant Asthmatics Treated with Corticosteroids

    OpenAIRE

    ISHIOKA Shinichi; Hozawa, Soichiro; Haruta, Yoshinori; Maeda, Akihiro; Tamagawa, Kotaro; Watanabe, Tetsuya; Hiyama, Keiko; Yamakido, Michio

    2000-01-01

    Cysteinyl leukotrienes (cysLTs) are considered to be the most important mediator involved in the pathogenesis of aspirin-intolerant asthma (AIA). However, the role of cysLTs in the baseline condition of the pathophysiology of AIA when not exposed to non-steroidal antiinflammatory drugs (NSAIDs) as well as that in the pathophysiology of aspirin-tolerant asthma remains to be elucidated. Therefore, we evaluated the effect of pranlukast, a potent, selective cysLT receptor antagonist, on bronchial...

  12. Mechanisms underlying aspirin-mediated growth inhibition and apoptosis induction of cyclooxygenase-2 negative colon cancer cell line SW480

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the effects of aspirin (acetylsalicylic acid) on proliferation and apoptosis of colorectal can- cer cell line $W480 and its mechanism. METHODS: Cyclooxygenase (COX)-2 negative colorec- tal cancer cell line SW480 was treated with aspirin at concentrations of 2.5 retool/L, 5.0 retool/L, 10.0 mmol/L for different periods in vitro. Anti-proliferation effect of aspirin on SW480 was detected by 3-(4,5-dimeth- ylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and apoptosis were observed by flow cytometry (FCM). Transmission electron microscope (TEM) was used for morphological study. Apoptosis-as- sociated genes were detected by immunohistochemical staining and Western blotting. RESULTS: Aspirin inhibited SW480 proliferation and induced apoptosis in a dose- and time-dependent manner. Treatment with different concentrations of aspirin significantly increased the proportions of cells at the G0/G1 phase and decreased the proportions of cells at the S- and G2/M phases in a concentration- dependent manner. Aspirin not only induced apoptosis but also caused cell necrosis at a high concentration as well. After treatment with aspirin, SW480 cells displayed typically morphological features of apoptosis and necrosis under TEM, and increased the Bcl-2 expression in cells, but the expression of Bax was down regulated. CONCLUSION: Aspirin inhibits proliferation and induces apoptosis of SW480 cells. Its anti-tumor mechanism may arrest cell cycle and shift Bax/Bcl-2 balance in cells.

  13. Prevention of venous thromboembolism after total knee replacement by high-dose aspirin or intermittent calf and thigh compression.

    OpenAIRE

    McKenna, R; Galante, J; Bachmann, F.; Wallace, D.L.; Kaushal, P S; Meredith, P.

    1980-01-01

    A prospective study of patients undergoing total knee replacement was carried out by using a combination of 125I-fibrinogen scanning and phlebography, and showed a high incidence of venous thromboembolic disease (TE). Ventilation-perfusion lung scanning was performed to detect pulmonary emboli in most patients. High doses of aspirin and an intermittent low-pressure pneumatic compression device (IPCD) were effective, even in women, in preventing TE. Low doses of aspirin and placebo were equall...

  14. Statins but not aspirin reduce thrombotic risk assessed by thrombin generation in diabetic patients without cardiovascular events: the RATIONAL trial.

    Directory of Open Access Journals (Sweden)

    Alejandro Macchia

    Full Text Available BACKGROUND: The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG among patients with type II diabetes mellitus and no previous cardiovascular events. METHODOLOGY/PRINCIPAL FINDINGS: Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks, assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018. On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716. The effects of treatments on measurements of TG using other agonists were consistent. CONCLUSIONS/SIGNIFICANCE: While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG. TRIAL REGISTRATION: ClinicalTrials.gov NCT00793754.

  15. NAC Attenuates LPS-Induced Toxicity in Aspirin-Sensitized Mouse Macrophages via Suppression of Oxidative Stress and Mitochondrial Dysfunction

    OpenAIRE

    Raza, Haider; John, Annie; Shafarin, Jasmin

    2014-01-01

    Bacterial endotoxin lipopolysaccharide (LPS) induces the production of inflammatory cytokines and reactive oxygen species (ROS) under in vivo and in vitro conditions. Acetylsalicylic acid (ASA, aspirin) is a commonly used anti-inflammatory drug. Our aim was to study the effects of N-acetyl cysteine (NAC), an antioxidant precursor of GSH synthesis, on aspirin-sensitized macrophages treated with LPS. We investigated the effects of LPS alone and in conjunction with a sub-toxic concentration of A...

  16. Comparative antiplatelet activity of COX1 NSAIDS versus aspirin, encompassing regimen simplification and gastroprotection: a call for a controlled study

    OpenAIRE

    B. Rothschild

    2011-01-01

    The cardioprotective/platelet inhibitory role of non-steroidal antiinflammatory drugs (NSAIDs) has been controversial, perhaps in contrast to the accepted prophylactic role of aspirin (114). That cardioprotective effect is attributed to the platelet aggregation inhibitory effects of aspirin and COX 1 active NSAIDS (10, 11, 13) and can be studied without requirement for massive numbers of patients. Such cardioprotection, however, has its own risks. Significant gastrointestinal toxicity is stil...

  17. Electrochemical oxidation of drug residues in water by the example of tetracycline, gentamicin and Aspirin {sup trademark}

    Energy Technology Data Exchange (ETDEWEB)

    Weichgrebe, D.; Danilova, E.; Rosenwinkel, K.H. [Inst. of Water Quality and Waste Management, Univ. of Hannover, Hannover (Germany); Vedenjapin, A.; Baturova, M. [Inst. of Organic Chemistry, Russian Academy of Science, Moscow (Russian Federation)

    2003-07-01

    The electrochemical oxidation as a method to destroy drug residues like Aspirin {sup trademark}, tetracycline or gentamicin in water was investigated with C-Anode (modified by manganese oxides) and Pt Anode. The mechanism of Aspirin {sup trademark} and tetracycline oxidation and the influence of the biocide effect was observed using GC-MS and three different microbiological tests. In general the biological availability increases with progressive oxidation of the antibiotics. (orig.)

  18. Lack of effect of multiple doses of vortioxetine on the pharmacokinetics and pharmacodynamics of aspirin and warfarin.

    Science.gov (United States)

    Chen, Grace; Zhang, Wencan; Serenko, Michael

    2015-06-01

    Vortioxetine is an antidepressant with multimodal activity approved for the treatment of major depressive disorder. Two separate randomized, placebo-controlled trials evaluated the effects of multiple doses of vortioxetine (10 mg/day) on the pharmacokinetics and pharmacodynamics of aspirin and warfarin in healthy volunteers. In the aspirin study, subjects received vortioxetine 10 mg or placebo once daily for 14 days, followed by coadministration with aspirin 150 mg once daily for 6 days, in 2 periods with a crossover design. In the warfarin study, subjects were randomized after reaching target international normalized ratio (INR) values on warfarin to receive vortioxetine 10 mg or matching placebo once daily for 14 days, with all subjects receiving a maintenance dose of warfarin (1-10 mg). Vortioxetine had no effect on the steady-state pharmacokinetic parameters of aspirin or its metabolite salicylic acid, and no statistically significant effect on the inhibition of arachidonic acid-, adenosine-5'-diphosphate-, or collagen-induced platelet aggregation at any time points. Coadministration of vortioxetine did not alter the pharmacokinetics of (R)- and (S)-warfarin enantiomers, or the mean coagulation parameters of warfarin treatment alone. Coadministration of vortioxetine doses in healthy volunteers had no effect on aspirin or warfarin pharmacokinetics or pharmacodynamics. Vortioxetine was well tolerated when coadministered with aspirin or warfarin. PMID:25641606

  19. Dietary nitrate and reductive polyphenols may potentiate the vascular benefit and alleviate the ulcerative risk of low-dose aspirin.

    Science.gov (United States)

    McCarty, Mark F

    2013-02-01

    The recent revelation that daily low-dose aspirin not only lowers risk for vascular events, but also can notably decrease risk for a range of adenocarcinomas, decreasing total cancer mortality by about 20%, makes it highly desirable to implement this protective strategy on a population-wide basis. Nonetheless, the fact that low-dose aspirin approximately doubles risk for serious gastrointestinal bleeding may impede health authorities from recommending its use by people judged to be at low cardiovascular risk. Nitric oxide (NO) exerts gastroprotective effects by boosting blood flow and mucus production in the gastric mucosa - effects which demonstrably oppose the pro-ulcerative impact of aspirin and other NSAIDs. A nitrate-rich diet, as well as ingestion of reductive catechol-bearing polyphenols, can collaborate in promoting NO generation in gastric juice, and they are protective in rodent models of gastric ulceration. Moreover, a high-nitrate diet, as well as certain reductive polyphenols such as epicatechin and quercetin, can exert platelet-stabilizing effects complementary to those of aspirin, and act in other ways to preserve vascular health. Hence, diets rich in nitrate and reductive polyphenols have the potential to amplify the vascular-protective benefits of low-dose aspirin, while diminishing its pro-ulcerative risk. Low-dose aspirin may be more unequivocally recommendable within the context of such a dietary strategy.

  20. 阿司匹林抵抗的相关临床研究%Clinical correlation study on aspirin resistance

    Institute of Scientific and Technical Information of China (English)

    何清; 焦洁茹; 赵雅洁; 王学锋; 吴方

    2012-01-01

    Objective To study the aspirin resistance phenomenon in our patient group and to assess the value of various aspirin resistance tests in judging the therapeutic efficacy of aspirin. Methods In 264 patients taking aspirin orally, platelet aggregation test (PAgT),thrombelastography (TEG),levels of serum and urinary 11-dehydro thromboxane B2 (11-DH-TXB2) and P-selectin were determined,and the frequency of aspirin resistance, relevant risk factors and correlation between aspirin resistance and clinical end point were analyzed. Results The detection rates of aspirin resistance by various tests were basically the same (P>0.05). The trend of aspirin resistance and aspirin semi-resistance was higher in patients with diabetics than in other patient groups. High low density lipoprotein and fasting blood glucose were the risk factors of aspirin resistance. Correlation was found between these tests (r:0.408-0.709,P<0.01).TEG was more sensitive (89.29%) and specific (92.31%)than other tests and more in consistent with P-selectin (K = 0.904, P<0.001) . Conclusions High low density lipoprotein and fasting blood glucose are the risk factors of aspirin resistance. The occurrence of thrombotic events is higher in cardiovascular patients with aspirin resistance than those without aspirin resistance. TEG is more sensitive and specific, and more in consistent with P-selectin.%目的:探讨我国患病人群中阿司匹林抵抗(aspirin resistance,AR)现象,比较不同AR实验检测法对阿司匹林疗效的判断及其临床应用价值.方法:对264例口服阿司匹林的患者(高血压、糖尿病等)分别进行光学法血小板聚集率(platelet aggregation test,PagT)、血栓弹力图(thrombelastography,TEG)、血和尿11-脱氢-血栓素B2(11-dehydro thromboxane B2,11-DH-TXB2)及P-选择蛋白表达检测,并对比分析患者的AR发生率、相关危险因素及AR与临床终点事件间的相关性.结果:口服阿司匹林患者采用各种方法检测

  1. A case of aspirin-resistance probably related to glycemic excursion

    Directory of Open Access Journals (Sweden)

    Ilaria Fava

    2010-12-01

    Full Text Available Diabetes is characterised by development of specific microvascular complications and by a high incidence of accelerated atherosclerosis. Several Authors demonstrated that post-prandial hyperglycaemia is certainly an independent risk factor of vascular complications in type 2 diabetes. The endothelial dysfunction, the oxidative stress, the post-prandial hyperglycaemia and the haemostatic and thrombotic parameters alterations are the principal causes for the cardiovascular risk increase in diabetic patient. For this reason many studies on anti-platelet therapy have been made in order to reduce thrombotic complication of diabetes mellitus. However, data suggest that the clinical efficacy of low-dose aspirin in patients with diabetes is substantially lower than in individuals without diabetes. Indeed, several evidences support the hypothesis that diabetes might represent a case of “aspirin resistance”.

  2. The Potential Mechanisms Underlying Aspirin-induced Inhibition of Ovarian Tumor Cell Growth

    Institute of Scientific and Technical Information of China (English)

    Yu LIU; Jin KE; Shi-Quan LIU; Fu-Xiang ZHOU; Cong-Hua XIE; Yun-Feng ZHOU

    2005-01-01

    @@ 1 Introduction Ovarian cancer remains the most lethal disease of the gynecological cancers. Owing to the lack of an effective screening approach combined with inadequate therapeutic approach for advanced disease, fewer than 25% of ovarian cancers are identified at an early curable stage. Thus these make ovarian cancer a strong candidate for chemoprevention. In 2001, Akhmedkhanov et al. demonstrated a 2-3 folds decrease in epithelial ovarian cancer associated with Aspirin use. These epidemiological observations suggest that an improved understanding of the mechanisms by which NSAID may decrease the development of ovarian cancer could lead to improved approaches for chemoprevention of this deadly disease. In this research, we explored the potential mechanism underlying epidemiological observations that ovarian cancer occurs at a lower frequency in women exposed to Aspirin(ASP).

  3. Novel application of hydrotropic solubilizing additives in the estimation of aspirin in tablets

    Directory of Open Access Journals (Sweden)

    Maheshwari R

    2010-01-01

    Full Text Available Highly concentrated aqueous solutions of various hydrotropic agents like sodium benzoate, sodium salicylate, sodium acetate, sodium citrate, nicotinamide and sodium ascorbate have been observed to enhance aqueous solubilities of a large number of poorly water-soluble drugs. In the present investigation hydrotropic solubilization technique has been employed to solubilize poorly water-soluble aspirin (analgesic and antipyretic drug by 0.5 M ibuprofen sodium solution to carry out titrimetric analysis of aspirin in tablet dosage form. Results of analysis by proposed method and Phamacopoeial method are very comparable. Proposed method is new, rapid, simple, accurate, and reproducible. Statistical data proved the accuracy, reproducibility and the precision of proposed method.

  4. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

    DEFF Research Database (Denmark)

    Sacco, Ralph L; Diener, Hans-Christoph; Yusuf, Salim;

    2008-01-01

    BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly...... assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes....... Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel...

  5. Do Aspirin and Other Antiplatelet Drugs Reduce the Mortality in Critically Ill Patients?

    OpenAIRE

    Wolfgang Lösche; Janina Boettel; Björn Kabisch; Johannes Winning; Claus, Ralf A.; Michael Bauer

    2011-01-01

    Platelet activation has been implicated in microvascular thrombosis and organ failure in critically ill patients. In the first part the present paper summarises important data on the role of platelets in systemic inflammation and sepsis as well as on the beneficial effects of antiplatelet drugs in animal models of sepsis. In the second part the data of retrospective and prospective observational clinical studies on the effect of aspirin and other antiplatelet drugs in critically ill patients ...

  6. Establishing a predictive model for aspirin resistance in elderly Chinese patients with chronic cardiovascular disease

    Science.gov (United States)

    Cao, Jian; Hao, Wei-Jun; Gao, Ling-Gen; Chen, Tian-Meng; Liu, Lin; Sun, Yu-Fa; Hu, Guo-Liang; Hu, Yi-Xin; Fan, Li

    2016-01-01

    Background Resistance to anti-platelet therapy is detrimental to patients. Our aim was to establish a predictive model for aspirin resistance to identify high-risk patients and to propose appropriate intervention. Methods Elderly patients (n = 1130) with stable chronic coronary heart disease who were taking aspirin (75 mg) for > 2 months were included. Details of their basic characteristics, laboratory test results, and medications were collected. Logistic regression analysis was performed to establish a predictive model for aspirin resistance. Risk score was finally established according to coefficient B and type of variables in logistic regression. The Hosmer–Lemeshow (HL) test and receiver operating characteristic curves were performed to respectively test the calibration and discrimination of the model. Results Seven risk factors were included in our risk score. They were serum creatinine (> 110 μmol/L, score of 1); fasting blood glucose (> 7.0 mmol/L, score of 1); hyperlipidemia (score of 1); number of coronary arteries (2 branches, score of 2; ≥ 3 branches, score of 4); body mass index (20–25 kg/m2, score of 2; > 25 kg/m2, score of 4); percutaneous coronary intervention (score of 2); and smoking (score of 3). The HL test showed P ≥ 0.05 and area under the receiver operating characteristic curve ≥ 0.70. Conclusions We explored and quantified the risk factors for aspirin resistance. Our predictive model showed good calibration and discriminative power and therefore a good foundation for the further study of patients undergoing anti-platelet therapy. PMID:27594876

  7. The Potential Mechanisms Underlying Aspirin-induced Inhibition of Ovarian Tumor Cell Growth

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionOvarian cancer remains the most lethal disease of the gynecological cancers. Owing to the lack of an effective screening approach combined with inadequate therapeutic approach for advanced disease, fewer than 25% of ovarian cancers are identified at an early curable stage. Thus these make ovarian cancer a strong candidate for chemoprevention. In 2001, Akhmedkhanov et al. demonstrated a 2-3 folds decrease in epithelial ovarian cancer associated with Aspirin use. These epidemiological observatio...

  8. Clinical Risk Factors for Gastroduodenal Ulcer in Romanian Low-Dose Aspirin Consumers.

    Science.gov (United States)

    Negovan, Anca; Iancu, Mihaela; Moldovan, Valeriu; Voidazan, Septimiu; Bataga, Simona; Pantea, Monica; Sarkany, Kinga; Tatar, Cristina; Mocan, Simona; Banescu, Claudia

    2016-01-01

    Background. Aspirin use for cardiovascular or cancer prevention is limited due to its gastrointestinal side effects. Objective. Our prospective, observational case-control study aims to identify the predictive factors for ulcers in low-dose aspirin consumers (75-325 mg/day). Methods. The study included patients who underwent an upper digestive endoscopy and took low-dose aspirin treatment. Results. We recruited 51 patients with ulcer (ulcer group) and 108 patients with no mucosal lesions (control group). In univariate analysis, factors significantly associated with ulcers were male gender (p = 0.001), anticoagulants (p = 0.029), nonsteroidal anti-inflammatory drugs (p = 0.013), heart failure (p = 0.007), liver (p = 0.011) or cerebrovascular disease (p = 0.004), diabetes mellitus (p = 0.043), ulcer history (p = 0.044), and alcohol consumption (p = 0.018), but not Helicobacter pylori infection (p = 0.2). According to our multivariate regression analysis results, history of peptic ulcer (OR 3.07, 95% CI 1.06-8.86), cotreatment with NSAIDs (OR 8, 95% CI 2.09-30.58) or anticoagulants (OR 4.85, 95% CI 1.33-17.68), male gender (OR 5.2, 95% CI 1.77-15.34), and stroke (OR 7.27, 95% CI 1.40-37.74) remained predictors for ulcer on endoscopy. Conclusions. Concomitant use of NSAIDs or anticoagulants, comorbidities (cerebrovascular disease), and male gender are the most important independent risk factors for ulcer on endoscopy in low-dose aspirin consumers, in a population with a high prevalence of H. pylori infection. PMID:27579036

  9. Economic Evaluation of Triflusal and Aspirin in the Treatment of Acute Myocardial Infarction

    OpenAIRE

    Josep Darba; Inaki Izquierdo; Caridad Pontes; Carlos Navas; Joan Rovira

    2002-01-01

    Objective: To compare the costs to the Spanish healthcare system of 35 days' treatment with triflusal (600 mg/day) and aspirin (300 mg/day) in patients with confirmed acute myocardial infarction within 24 hours of onset of symptoms. Design: A cost minimisation analysis based on the results of the Triflusal in Acute Myocardial Infarction study (TIM) was conducted. The hypothesis was that despite a higher acquisition cost of triflusal, savings would result because of differences in efficacy and...

  10. Effects of aspirin, prednisolone and indomethacin on nephrotoxic serum nephritis in the rat.

    OpenAIRE

    Kurokawa, H; Sakamoto, K.

    1982-01-01

    1 The effects of aspirin, prednisolone, and indomethacin on nephrotoxic serum nephritis in rats was studied. The nephritis was induced by a single intravenous injection of nephrotoxic serum (NTS, rabbit anti-serum against the water-soluble renal antigen of the rat). The injection of NTS induced the heterologous phase of proteinuria (within a day after NTS injection) and then the autologous phase (5 to 7 days after NTS injection). The effect of drugs given before the NTS (i.e. prophylactically...

  11. Regulation effect of Aspirin Eugenol Ester on blood lipids in Wistar rats with hyperlipidemia

    OpenAIRE

    Karam, Isam; Ma, Ning; Liu, Xi-Wang; Li, Shi-Hong; Kong, Xiao-Jun; Li, Jian-Yong; Yang, Ya-Jun

    2015-01-01

    Background Aspirin eugenol ester (AEE) is a promising drug candidate for treatment of inflammation, pain and fever and prevention of cardiovascular diseases with less side effects. The experiment will be conducted to investigate the efficacy of AEE on curing hyperlipidemia in Wistar rats. The rats were fed with high fat diet (HFD) for 8 weeks to induce hyperlipidemia. Results Compared with the model group, the results showed that AEE at 54 mg/kg dosage could significantly decrease the hyperli...

  12. Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment

    Directory of Open Access Journals (Sweden)

    Bratseth Vibeke

    2012-08-01

    Full Text Available Abstract Background Cardiovascular disease with disturbances in the haemostatic system, might lead to thrombotic complications with clinical manifestations like acute myocardial infarction (AMI and stroke. Activation of the coagulation cascade with subsequent increased thrombin generation, characterizes a prothrombotic phenotype. In the present study we investigated whether prothrombotic markers were associated with risk factors and clinical subgroups in a cohort of patients with angiographically verified coronary artery disease (CAD. The patients were randomized to long-term treatment with the antiplatelet drugs aspirin or clopidogrel, and we further investigated the effect on hypercoagulability of such treatment for 1 year, of which limited data exists. Methods Venous blood samples were collected in fasting condition between 08:00 and 10:30 am, at baseline when all patients were on aspirin therapy (n = 1001 and in 276 patients after 1 year follow-up on aspirin or clopidogrel. In vivo thrombin generation was assessed by prothrombin fragment 1 + 2 (F1+2 and D-dimer, and the endogenous thrombin potentiale (ETP in the calibrated automated thrombogram (CAT assay, representing ex vivo thrombin generation. In addition soluble tissue factor (sTF and free- and total tissue factor pathway inhibitor (TFPI were measured. Results We found age to be significantly associated with F1+2 and D-dimer (β = 0.229 and β =0.417 respectively, p Conclusions In the present population of stable CAD, we could demonstrate a more hypercoagulable profile among women, smokers and patients on RAS medication, assessed by the prothrombotic markers F1+2, D-dimer and ETP. Long-term antiplatelet treatment with aspirin alone seems to attenuate thrombin generation to a greater extent than with clopidogrel alone. The study is registered at http://www.clinicaltrials.gov: NCT00222261.

  13. Aspirin Use and Lung Cancer Risk: A Possible Relationship? Evidence from an Updated Meta-Analysis

    OpenAIRE

    Hai-yan Jiang; Tian-bao Huang; Lei Xu; Jing Yu; Yan Wu; Jiang Geng; Xu-dong Yao

    2015-01-01

    Background and Purpose Growing evidence has emerged and controversial results reported on possible relationship between aspirin use and lung cancer risk. We, therefore, conducted this updated and comprehensive meta-analysis to evaluate this issue, with focus on dose-risk and duration-risk relationships. Methods We searched electronic databases including PUBMED, EMBASE and Cochrane library to identify eligible studies. Relative risk (RR) and its 95% confidence interval (CI) were used for cohor...

  14. Early ultrastructural changes of antral mucosa with aspirin in the absence of Helicobacter pylori.

    OpenAIRE

    McCarthy, C J; Sweeney, E; O'Morain, C

    1995-01-01

    AIMS--To describe the ultrastructural changes that occur in human antral mucosa following direct application of aspirin in volunteers without Helicobacter pylori infection. METHODS--Ten healthy male volunteers without H pylori infection underwent three consecutive endoscopies (at zero, one and five hours). At the first endoscopy, two biopsy specimens were obtained (one for histology and the other for electron microscopy (EM)). At subsequent endoscopies, a single biopsy specimen was obtained f...

  15. The Effects of EPA, DHA, and Aspirin Ingestion on Plasma Lysophospholipids and Autotaxin

    OpenAIRE

    Block, RC; Duff, R; Lawrence, P.; Kakinami, L.; Brenna, JT; Shearer, GC; Meednu, N; Mousa, S; Friedman, A.; Harris, WS; Larson, Mark; Georas, S

    2010-01-01

    Lysophophatidylcholine (LPC) and lysophosphatidic acid (LPA) are potent lysolipid mediators increasingly linked with atherosclerosis and inflammation. A current model proposing that plasma LPA is produced when LPC is hydrolyzed by the enzyme autotaxin has not been rigorously investigated in human subjects. We conducted a clinical trial of eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) and aspirin ingestion in normal volunteers. Fasting blood samples were drawn at baseline and after 4-we...

  16. Role of Aspirin and Dexamethasone against Experimentally Induced Depression in Rats.

    Science.gov (United States)

    Bhatt, Shailendra; Shukla, Priyanka; Raval, Jibril; Goswami, Sunita

    2016-07-01

    A large number of current studies indicate that inflammatory mediators may contribute to depression in experimental models as well as in human beings. Nevertheless, the subject, whether anti-inflammatory treatments can prevent depression still remains controversial. In the present study, a chronic mild stress (CMS) model of male Sprague Dawley rats was used to investigate the role of anti-inflammatory drugs in the treatment of depression. All the animals in different groups, except the normal control group, were exposed to CMS procedure for 28 days and concurrently treated with aspirin (10 mg/kg, p.o.), dexamethasone (1 mg/kg p.o.) and amitriptyline (10 mg/kg p.o., reference standard), respectively. Amitriptyline was also used in combination with aspirin and dexamethasone to inspect any synergistic effects. Tests performed towards the end of the study included sucrose preference test, behavioural tests like forced swim test, elevated plus-maze, light/dark box, locomotor activity and biochemical estimations like serum cortisol and brain neurotransmitters. Disease control group (CMS-treated) produced significant depressive behaviour in rats. The animals treated with aspirin showed increased sucrose preference, decreased immobility time in forced swim test, decreased serum cortisol and increased brain serotonin levels signifying antidepressant action. In contrast, there was aggravation of depressive behaviour in rats treated with dexamethasone. Together, these findings suggest that aspirin can serve as a potential antidepressant both individually and as adjunctive agent in the treatment of depression. Inhibition of the inflammatory mediators during stress procedures or any other potential physiological and biochemical mechanisms may be involved in its antidepressant effect. PMID:26645736

  17. A novel aspirin prodrug inhibits NFκB activity and breast cancer stem cell properties

    OpenAIRE

    Kastrati, Irida; Litosh, Vladislav A.; Zhao, Shuangping; Alvarez, Manuel; Thatcher, Gregory R.J.; Frasor, Jonna

    2015-01-01

    Introduction Activation of cyclooxygenase (COX)/prostaglandin and nuclear factor κB (NFκB) pathways can promote breast tumor initiation, growth, and progression to drug resistance and metastasis. Thus, anti-inflammatory drugs have been widely explored as chemopreventive and antineoplastic agents. Aspirin (ASA), in particular, is associated with reduced breast cancer incidence but gastrointestinal toxicity has limited its usefulness. To improve potency and minimize toxicity, ASA ester prodrugs...

  18. Building a better aspirin: gaseous solutions to a century-old problem

    OpenAIRE

    Wallace, J. L.

    2007-01-01

    The gastrointestinal adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) have been recognized since shortly after the introduction of aspirin to the marketplace over a century ago. However, the underlying pathogenesis of NSAID-induced gastropathy remains incompletely understood. Advances in understanding some of the factors that contribute to the mucosal injury have provided clues for the development of safer NSAIDs. The inhibitory effects of nitric oxide (NO) on NSAID-induced le...

  19. Combining Aspirin with Cholecalciferol (Vitamin D3) – A Potential New Tool for Controlling Possum Populations

    OpenAIRE

    Morgan, David R.; Arrow, Jane; Smith, Mark P.

    2013-01-01

    The introduced Australian brushtail possum is a major vertebrate pest in New Zealand, with impacts on conservation and agriculture being managed largely through poisoning operations. Cholecalciferol (vitamin D3) is registered for use in controlling possums and despite its many advantages it is expensive and relatively inhumane. Combination of a high proportion of aspirin with a low proportion of cholecalciferol was effective in killing high proportions of groups of acclimatised, caged possums...

  20. Critical appraisal of a fixed combination of esomeprazole and low dose aspirin in risk reduction

    OpenAIRE

    Ravi Vachhani; Doumit Bouhaidar; Alvin Zfass; et al.

    2010-01-01

    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 a...

  1. Effect of Bark Extract and Gum Exudate of Commiphora Caudata on Aspirin Induced Ulcer in Rats

    OpenAIRE

    R Nanthakumar; Ambrose S Stephen; E Sriram; Babu, G.; K Chitra; C Uma maheswara Reddy

    2009-01-01

    Commiphora caudata is used in Indian folk medicine as an antiulcerogenic agent. Despite of its promising use, there has been no scientific report present regarding its antiulcer activity. Therefore, this study was designed to evaluate the antiulcer activity of bark extract and gum exudate of commiphora caudata on aspirin induced ulcer in rats. Acute toxicity study was performed and 200 mg/kg was selected as an effective dose. Four groups of Albino Swiss rats were included in this study. Aspir...

  2. ASPIRIN AND NICOTINIC ACID AS TWO FACES OF SAME COIN IN THE TREATMENT OF DYSLIPIDEMIA

    Directory of Open Access Journals (Sweden)

    RK Mohamed Mutahar

    2011-03-01

    Full Text Available Globally cardiovascular diseases are believed to be the no.1 cause of death. According to the current estimates of World Health Organisation, approximately one-third of all deaths (16.7 million people around the globe resulted from cardiovascular diseases. Eighty percent of these deaths were reported from low and middle income countries. The main intention of writing this review article is that, India being the second most highly populated country characterized by a majority of low and middle income population, the need for an effective treatment for this devastating disease both cost and efficacy wise is most desired. Since a long time, antidislipidemic agent nicotinic acid has been continuously under consideration to tackle the cardiovascular diseases by treating dyslipidemia. But its use has been limited due to its notorious yet harmless side effect of flushing. Now the focus of attention would be to use nicotinic acid by cleverly handling the flush. At this adjuncture the entry of acetyl salicylic acid (Aspirin has been taken to give the best result. No doubt the major intention to take aspirin (low dose with the combination of major drug nicotinic acid is to reduce nicotinic acid -induced flushing, but its associated properties or remedies as you may tell are more equally supportive to the very treatment of cardiovascular diseases itself. Hence it may be construed that aspirin and nicotinic acid are nothing but the two sides of the same coin in the treatment of dyslipidemia. Hence the hypothesis “People with heart disease should be on aspirin anyway”.

  3. Aromatic hydroxylation of salicylic acid and aspirin by human cytochromes P450.

    Science.gov (United States)

    Bojić, Mirza; Sedgeman, Carl A; Nagy, Leslie D; Guengerich, F Peter

    2015-06-20

    Aspirin (acetylsalicylic acid) is a well-known and widely-used analgesic. It is rapidly deacetylated to salicylic acid, which forms two hippuric acids-salicyluric acid and gentisuric acid-and two glucuronides. The oxidation of aspirin and salicylic acid has been reported with human liver microsomes, but data on individual cytochromes P450 involved in oxidation is lacking. In this study we monitored oxidation of these compounds by human liver microsomes and cytochrome P450 (P450) using UPLC with fluorescence detection. Microsomal oxidation of salicylic acid was much faster than aspirin. The two oxidation products were 2,5-dihydroxybenzoic acid (gentisic acid, documented by its UV and mass spectrum) and 2,3-dihydroxybenzoic acid. Formation of neither product was inhibited by desferrioxamine, suggesting a lack of contribution of oxygen radicals under these conditions. Although more liphophilic, aspirin was oxidized less efficiently, primarily to the 2,5-dihydroxy product. Recombinant human P450s 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 all catalyzed the 5-hydroxylation of salicylic acid. Inhibitor studies with human liver microsomes indicated that all six of the previously mentioned P450s could contribute to both the 5- and 3-hydroxylation of salicylic acid and that P450s 2A6 and 2B6 have contributions to 5-hydroxylation. Inhibitor studies indicated that the major human P450 involved in both 3- and 5-hydroxylation of salicylic acid is P450 2E1.

  4. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Jin Young [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2011-05-06

    Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  5. Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress, arterial oxidation-specific epitopes, and atherogenesis in hypercholesterolemic mice

    Science.gov (United States)

    Napoli, Claudio; Ackah, Eric; de Nigris, Filomena; Del Soldato, Piero; D'Armiento, Francesco P.; Crimi, Ettore; Condorelli, Mario; Sessa, William C.

    2002-01-01

    The effects of chronic treatment with nitric oxide-containing aspirin (NO-aspirin, NCX-4016) in comparison with regular aspirin or placebo on the development of a chronic disease such as atherosclerosis were investigated in hypercholesterolemic low-density lipoprotein (LDL)-receptor-deficient mice. Male mice were assigned randomly to receive in a volume of 10 ml/kg either placebo (n = 10), 30 mg/kg/day NO-aspirin (n = 10), or 18 mg/kg/day of regular aspirin (n = 10). After 12 weeks of treatment, the computer-assisted imaging analysis revealed that NO-aspirin reduced the aortic cumulative lesion area by 39.8 ± 12.3% compared with that of the placebo (P < 0.001). Regular aspirin did not reduce significantly aortic lesions (−5.1 ± 2.3%) compared with the placebo [P = 0.867, not significant (NS)]. Furthermore, NO-aspirin reduced significantly plasma LDL oxidation compared with aspirin and placebo, as shown by the significant reduction of malondialdehyde content (P < 0.001) as well as by the prolongation of lag-time (P < 0.01). Similarly, systemic oxidative stress, measured by plasma isoprostanes, was significantly reduced by treatment with NCX-4016 (P < 0.05). More importantly, mice treated with NO-aspirin revealed by immunohistochemical analysis of aortic serial sections a significant decrease in the intimal presence of oxidation-specific epitopes of oxLDL (E06 monoclonal antibody, P < 0.01), and macrophages–derived foam cells (F4/80 monoclonal antibody, P < 0.05), compared with placebo or aspirin. These data indicate that enhanced NO release by chronic treatment with the NO-containing aspirin has antiatherosclerotic and antioxidant effects in the arterial wall of hypercholesterolemic mice. PMID:12209007

  6. New insights into the anti-inflammatory actions of aspirin-induction of nitric oxide through the generation of epi-lipoxins

    OpenAIRE

    Gilroy, Derek W.

    2005-01-01

    Aspirin has always remained an enigmatic drug. Not only does it present with new benefits for treating an ever-expanding list of apparently unrelated diseases at an astounding rate but also because aspirin enhances our understanding of the nature of these diseases processe. Originally, the beneficial effects of aspirin were shown to stem from its inhibition of cyclooxygenase-derived prostaglandins, fatty acid metabolites that modulate host defense. However, in addition to inhibiting cyclooxyg...

  7. Phospho-aspirin (MDC-22) inhibits breast cancer in preclinical animal models: an effect mediated by EGFR inhibition, p53 acetylation and oxidative stress

    OpenAIRE

    Huang, Liqun; WONG, CHI C.; Mackenzie, Gerardo G; Sun, Yu; Cheng, Ka Wing; Vrankova, Kvetoslava; Alston, Ninche; Ouyang, Nengtai; Rigas, Basil

    2014-01-01

    Background The anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we synthesized phospho-aspirin (PA-2; MDC-22), a novel derivative of aspirin, and evaluated its chemotherapeutic and chemopreventive efficacy in preclinical models of triple negative breast cancer (TNBC). Methods Efficacy of PA-2 was evaluated in human breast cancer cells in vitro, and in orthotopic and subcutaneous TNBC xenografts in nude mice. Mechanistic stud...

  8. Amelioration of Aspirin Induced Oxidative Impairment and Apoptotic Cell Death by a Novel Antioxidant Protein Molecule Isolated from the Herb Phyllanthus niruri

    OpenAIRE

    Bhattacharyya, Sudip; Ghosh, Shatadal; Sil, Parames C.

    2014-01-01

    Aspirin has been used for a long time as an analgesic and anti-pyretic drug. Limitations of its use, however, remain for the gastro-intestinal side effects and erosions. Although the role of aspirin on gastro-intestinal injury has been extensively studied, the molecular mechanisms underlying aspirin-induced liver and spleen pathophysiology are poorly defined. The present study has been conducted to investigate whether phyllanthus niruri protein (PNP) possesses any protective role against aspi...

  9. Gastroduodenal Mucosal Injury in Patients Taking Low-Dose Aspirin and the Role of Gastric Mucoprotective Drugs: Possible Effect of Rebamipide

    OpenAIRE

    Yamamoto, Takatsugu; Isono, Akari; Mishina, Yuji; Ebato, Tadahisa; Shirai, Tsuguru; Nakayama, Shin; Nagasawa, Kunitaka; Abe, Koichiro; Hattori, Kengo; Ishii, Taro; Kuyama, Yasushi

    2010-01-01

    The present study was conducted to investigate the prevalence of mucosal injury in patients taking low-dose aspirin in Japan and examine the effect of gastric mucoprotective drugs on aspirin-related gastroduodenal toxicity. We selected 530 patients who had taken low-dose aspirin for 1 month or more after undergoing esophagogastroduodenoscopy from 2005 through 2006 at Teikyo University Hospital, Tokyo, Japan. Endoscopic records were retrospectively reviewed to determine the presence of massive...

  10. Cardiovascular risks associated with non-aspirin non-steroidal anti-inflammatory drug use

    DEFF Research Database (Denmark)

    Schmidt, Morten

    2015-01-01

    whether use of non-aspirin NSAIDs was associated with risk of major adverse cardiovascular events (MACE) after coronary stent implantation (study I), risk of venous thromboembolism (study II), risk of atrial fibrillation (study III), and 30-day stroke mortality (study IV). We conducted two cohort studies...... coronary intervention with stent implantation in Western Denmark. Compared with non-users of NSAIDs, the adjusted incidence rate ratio (IRR) for MACE was 1.04 (95% CI: 0.83-1.31) for users of nonselective NSAIDs and 1.00 (95% CI: 0.81-1.25) for users of COX-2 inhibitors. Consistently, current use of non-aspirin...... COX-2 inhibitors, the MRR was driven by new use of older traditional COX-2 inhibitors (1.30, 95% CI: 1.12-1.52), being 1.51 (95% CI: 1.16-1.98) for etodolac and 1.21 (95% CI: 1.01-1.45) for diclofenac. Mortality from hemorrhagic strokes was not associated with preadmission use of non-aspirin NSAIDs...

  11. Probing Vitamine C, Aspirin and Paracetamol in the Gas Phase: High Resolution Rotational Studies

    Science.gov (United States)

    Mata, S.; Cabezas, C.; Varela, M.; Pena, I.; Nino, A.; López, J. C.; Alonso, J. L.; Grabow, J.-U.

    2011-06-01

    A solid sample of Vitamin C (m.p. 190°C) vaporized by laser ablation has been investigated in gas phase and characterized through their rotational spectra. Two spectroscopy techniques has been used to obtain the spectra: a new design of broadband chirped pulse Fourier transform microwave spectroscopy with in-phase/quadrature-phase-modulation passage-acquired-coherence technique (IMPACT) and conventional laser ablation molecular beam Fourier transform microwave spectroscopy (LA-MB-FTMW). Up to now, two low-energy conformer have been observed and their rotational constants determined. Ab initio calculations at the MP2/6-311++G (d,p) level of theory predicted rotational constants which helped us to identify these conformers unequivocally. Among the molecules to benefit from the LA-MB-FTMW technique there are common important drugs never observed in the gas phase through rotational spectroscopy. We present here the results on acetyl salicylic acid and acetaminophen (m.p. 136°C), commonly known as aspirin and paracetamol respectively. We have observed two stable conformers of aspirin and two for paracetamol. The internal rotation barrier of the methyl group in aspirin has been determined for both conformers from the analysis of the A-E splittings due to the coupling of internal and overall rotation. J. L. Alonso, C. Pérez, M. E. Sanz, J. C. López, S. Blanco, Phys. Chem. Chem. Phys. 11,617-627 (2009)and references therein

  12. Effect of Bark Extract and Gum Exudate of Commiphora Caudata on Aspirin Induced Ulcer in Rats

    Directory of Open Access Journals (Sweden)

    R Nanthakumar

    2009-01-01

    Full Text Available Commiphora caudata is used in Indian folk medicine as an antiulcerogenic agent. Despite of its promising use, there has been no scientific report present regarding its antiulcer activity. Therefore, this study was designed to evaluate the antiulcer activity of bark extract and gum exudate of commiphora caudata on aspirin induced ulcer in rats. Acute toxicity study was performed and 200 mg/kg was selected as an effective dose. Four groups of Albino Swiss rats were included in this study. Aspirin suspended in 0.5 % carboxymethyl cellulose (CMC was given orally to group 1 rats as a negative control group. Group 2 and group 3 animals received methanolic extract and gum exudate of commiphora caudata respectively. Sucralfate was given orally to group 4 animals as a positive control. The methanolic extract of commiphora caudata has been found to reduce total acidity as much as by sucralfate. However, it has not changed the fluid secretion. The gum preparation not only reduced the total acidity but also considerably reduce the gastric fluid secretion. In case of ulcer score sucralfate, methanolic extract and the gum have produced the low ulcer score compared to aspirin. Increased gastric mucosal protective mechanism by bark extract and gum exudate is probably due to the presence of some active principles present in the plant. However, further investigations are required to elucidate their exact mechanism of anti-ulcer activity.

  13. Low-Dose Aspirin-Associated Upper and Mid Gastrointestinal Tract Damage and Gene Polymorphism.

    Science.gov (United States)

    Shiotani, Akiko; Fujita, Yoshihiko; Nishio, Kazuto

    2015-01-01

    The risk of gastrointestinal (GI) bleeding is increased in association with the use of low-dose aspirin (LDA). There are few studies of the association between genetic polymorphisms and the risks of aspirin-induced ulcer or its complications. Individuals with two single nucleotide polymorphisms (SNPs) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibit increased sensitivity to aspirin and lower prostaglandin synthesis capacity but the polymorphism lacked statistical significance in relation to an association with bleeding peptic ulcer. In our previous Japanese study, SLCO1B1 521TT genotype and the SLCO1B1 *1b haplotype were significantly associated with the risk of peptic ulcer and ulcer bleeding in patients taking LDA, especially in the patients with angiotensin converting enzyme inhibitor (ACEI), angiotensin type 1 receptor blocker (ARB), or statin co-treatment. Protonpump inhibitors (PPIs) are recommended for patients who require antiplatelet therapy and have a history of upper GI bleeding. The interaction between PPIs and consequent impaired effectiveness of clopidogrel has caused concern regarding the effect of genetic polymorphisms of the CYP2C19 which mediates conversion of clopidogrel to its active metabolite. The later recent genome-wide analysis of SNPs indicated the association of several SNPs with small bowel bleeding in Japanese patients taking LDA. The data are still lacking and further prospective studies are needed to identify the specific gene polymorphisms as risk or protective factors for GI bleeding associated with LDA. PMID:26369686

  14. Fatty acid binding protein 1 is related with development of aspirin-exacerbated respiratory disease.

    Directory of Open Access Journals (Sweden)

    Tae-Hoon Kim

    Full Text Available BACKGROUND: Aspirin-exacerbated respiratory disease (AERD refers to the development of bronchoconstriction in asthmatics following the ingestion of aspirin. Although alterations in eicosanoid metabolites play a role in AERD, other immune or inflammatory mechanisms may be involved. We aimed to identify proteins that were differentially expressed in nasal polyps between patients with AERD and aspirin-tolerant asthma (ATA. METHODOLOGY/PRINCIPAL FINDINGS: Two-dimensional electrophoresis was adopted for differential display proteomics. Proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS. Western blotting and immunohistochemical staining were performed to compare the amount of fatty acid-binding protein 1 (FABP1 in the nasal polyps of patients with AERD and ATA. Fifteen proteins were significantly up- (seven spots or down-regulated in the nasal polyps of patients with AERD (n = 5 compared to those with ATA (n = 8. LC-MS revealed an increase in seven proteins expression and a decrease in eight proteins expression in patients with AERD compared to those with ATA (P = 0.003-0.045. FABP1-expression based on immunoblotting and immunohistochemical analysis was significantly higher in the nasal polyps of patients with AERD compared to that in patients with ATA. FABP1 was observed in epithelial, eosinophils, macrophages, and the smooth-muscle cells of blood vessels in the polyps. CONCLUSIONS/SIGNIFICANCE: Our results indicate that alterations in 15 proteins, including FABP1, may be related to the development of AERD.

  15. NSAIDs, Mitochondria and Calcium Signaling: Special Focus on Aspirin/Salicylates

    Directory of Open Access Journals (Sweden)

    Yoshihiro Suzuki

    2010-05-01

    Full Text Available Aspirin (acetylsalicylic acid is a well-known nonsteroidal anti-inflammatory drug (NSAID that has long been used as an anti-pyretic and analgesic drug. Recently, much attention has been paid to the chemopreventive and apoptosis-inducing effects of NSAIDs in cancer cells. These effects have been thought to be primarily attributed to the inhibition of cyclooxygenase activity and prostaglandin synthesis. However, recent studies have demonstrated unequivocally that certain NSAIDs, including aspirin and its metabolite salicylic acid, exert their anti-inflammatory and chemopreventive effects independently of cyclooxygenase activity and prostaglandin synthesis inhibition. It is becoming increasingly evident that two potential common targets of NSAIDs are mitochondria and the Ca2+ signaling pathway. In this review, we provide an overview of the current knowledge regarding the roles of mitochondria and Ca2+ in the apoptosis-inducing effects as well as some side effects of aspirin, salicylates and other NSAIDs, and introducing the emerging role of L-type Ca2+ channels, a new Ca2+ entry pathway in non-excitable cells that is up-regulated in human cancer cells.

  16. Radiochromium (chromium-51) evaluation of gastrointestinal blood loss associated with placebo, aspirin, and nabumetone

    Energy Technology Data Exchange (ETDEWEB)

    Lussier, A.; LeBel, E.

    1987-10-30

    Gastrointestinal blood loss is one of the most serious clinical events induced by drugs. To date, almost no nonsteroidal anti-inflammatory drug has been shown to be devoid of that side effect in a strictly controlled study. The objective of this study was to assess quantitatively, by use of radioactive chromium (chromium-51)-labeled red blood cells, gastrointestinal blood loss associated with nabumetone (1000 mg daily), aspirin (3.6 g daily), and placebo. A total of 37 normal subjects, divided among the three treatment groups and a fourth group that received no treatment, were assessed clinically and quantitatively for gastrointestinal blood loss over a period of 28 days of active treatment. The results with chromium-51, analyzed on a logarithmic scale, revealed no statistically significant differences between the nabumetone, placebo, and control groups. Gastrointestinal blood loss in the aspirin group, however, was elevated when compared with all other groups at a high level of statistical significance (p less than 0.001). It is concluded that, under conditions in which aspirin causes substantial gastrointestinal microbleeding, nabumetone is not significantly different from placebo.

  17. Amelioration of aspirin induced oxidative impairment and apoptotic cell death by a novel antioxidant protein molecule isolated from the herb Phyllanthus niruri.

    Directory of Open Access Journals (Sweden)

    Sudip Bhattacharyya

    Full Text Available Aspirin has been used for a long time as an analgesic and anti-pyretic drug. Limitations of its use, however, remain for the gastro-intestinal side effects and erosions. Although the role of aspirin on gastro-intestinal injury has been extensively studied, the molecular mechanisms underlying aspirin-induced liver and spleen pathophysiology are poorly defined. The present study has been conducted to investigate whether phyllanthus niruri protein (PNP possesses any protective role against aspirin mediated liver and spleen tissue toxicity, and if so, what signaling pathways it utilizes to convey its protective action. Aspirin administration in mice enhanced serum marker (ALP levels, reactive oxygen species (ROS generation, reduced antioxidant power and altered oxidative stress related biochemical parameters in liver and spleen tissues. Moreover, we observed that aspirin intoxication activated both the extrinsic and intrinsic apoptotic pathways, as well as down regulated NF-κB activation and the phosphorylation of p38 and JNK MAPKs. Histological assessments and TUNEL assay also supported that aspirin induced tissue damages are apoptotic in nature. PNP treatment after aspirin exposure effectively neutralizes all these abnormalities via the activation of survival PI3k/Akt pathways. Combining all results suggest that PNP could be a potential protective agent to protect liver and spleen from the detrimental effects of aspirin.

  18. Healthy older humans exhibit augmented carotid-cardiac baroreflex sensitivity with aspirin during muscle mechanoreflex and metaboreflex activation.

    Science.gov (United States)

    Drew, Rachel C; Blaha, Cheryl A; Herr, Michael D; Stocker, Sean D; Sinoway, Lawrence I

    2015-10-01

    Low-dose aspirin inhibits thromboxane production and augments the sensitivity of carotid baroreflex (CBR) control of heart rate (HR) during concurrent muscle mechanoreflex and metaboreflex activation in healthy young humans. However, it is unknown how aging affects this response. Therefore, the effect of low-dose aspirin on carotid-cardiac baroreflex sensitivity during muscle mechanoreflex with and without metaboreflex activation in healthy older humans was examined. Twelve older subjects (6 men and 6 women, mean age: 62 ± 1 yr) performed two trials during two visits preceded by 7 days of low-dose aspirin (81 mg) or placebo. One trial involved 3 min of passive calf stretch (mechanoreflex) during 7.5 min of limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise (mechanoreflex and metaboreflex). HR (ECG) and mean arterial blood pressure (MAP; Finometer) were recorded. CBR function was assessed using rapid neck pressure application (+40 to -80 mmHg). Aspirin significantly decreased baseline thromboxane B2 production by 83 ± 4% (P aspirin, CBR-HR maximal gain and operating point gain were significantly higher during stretch with metabolite accumulation compared with placebo (maximal gain: -0.23 ± 0.03 vs. -0.14 ± 0.02 and operating point gain: -0.11 ± 0.03 vs. -0.04 ± 0.01 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively, P aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in healthy older humans. This increased sensitivity appears linked to reduced thromboxane sensitization of muscle mechanoreceptors, which consequently improves CBR-HR control. PMID:26371168

  19. Aspirin and salicylic acid decrease c-Myc expression in cancer cells: a potential role in chemoprevention.

    Science.gov (United States)

    Ai, Guoqiang; Dachineni, Rakesh; Muley, Pratik; Tummala, Hemachand; Bhat, G Jayarama

    2016-02-01

    Epidemiological studies have demonstrated a significant correlation between regular aspirin use and reduced colon cancer incidence and mortality; however, the pathways by which it exerts its anti-cancer effects are still not fully explored. We hypothesized that aspirin's anti-cancer effect may occur through downregulation of c-Myc gene expression. Here, we demonstrate that aspirin and its primary metabolite, salicylic acid, decrease the c-Myc protein levels in human HCT-116 colon and in few other cancer cell lines. In total cell lysates, both drugs decreased the levels of c-Myc in a concentration-dependent fashion. Greater inhibition was observed in the nucleus than the cytoplasm, and immunofluorescence studies confirmed these observations. Pretreatment of cells with lactacystin, a proteasome inhibitor, partially prevented the downregulatory effect of both aspirin and salicylic acid, suggesting that 26S proteasomal pathway is involved. Both drugs failed to decrease exogenously expressed DDK-tagged c-Myc protein levels; however, under the same conditions, the endogenous c-Myc protein levels were downregulated. Northern blot analysis showed that both drugs caused a decrease in c-Myc mRNA levels in a concentration-dependent fashion. High-performance liquid chromatography (HPLC) analysis showed that aspirin taken up by cells was rapidly metabolized to salicylic acid, suggesting that aspirin's inhibitory effect on c-Myc may occur through formation of salicylic acid. Our result suggests that salicylic acid regulates c-Myc level at both transcriptional and post-transcription levels. Inhibition of c-Myc may represent an important pathway by which aspirin exerts its anti-cancer effect and decrease the occurrence of cancer in epithelial tissues. PMID:26314861

  20. Effect of aspirin plus clopidogrel on inflammatory markers in patients with non-ST-segment elevation acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Aspirin can inhibit inflammatory reactions and platelet aggregation, but little is known about the effects of the combination of aspirin plus clopidogrel, a new antiplatelet agent, on inflammation. The purpose of this study was to determine whether aspirin plus clopidogrel can further suppress inflammation in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Methods One hundred and fifteen patients with NSTEACS were randomized into two groups: group A (aspirin alone, n=58) and group B (aspirin plus clopidogrel, n=57). Patients in group A received a loading dose of 300 mg aspirin, then 100 mg per day. The patients in group B received a loading dose of 300 mg aspirin and 300 mg clopidogrel, then 100 mg aspirin and 75 mg clopidogrel per day. Serum high sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α(TNF-α) were measured in all patients at baseline prior to any drug treatment after admission, and at 7 and 30 days after beginning drug treatment. Thirty healthy volunteers on no medications were enrolled as controls (group C).Results Baseline levels of hs-CRP and TNF-αin group A and group B were significantly higher than those in group C. Seven days after administration, the levels of hs-CRP in both group A and group B decreased significantly [Group A: (6.15 ± 1.39) mg/L vs (9.18 ± 1.62) mg/L, P <0.01; Group B:(4.99 ± 1.62) mg/L vs (10.29 ± 1.47) mg/L, P<0.01]. Similarly, levels of TNF-αin both groups decreased at 7 days compared to baseline [Group A: (90.99 ± 28.91) pg/ml vs (117.20 ± 37.13) pg/ml, P <0.01; Group B: (74.32± 21.83) pg/ml vs (115.27 ± 32.11) pg/ml, P <0.01]. Thirty days after administration, the levels of hs-CRP in both group A and group B decreased further to (3.49 ± 1.53) mg/L, and (2.40 ± 1.17) mg/L respectively (P <0.01 for both comparisons). Levels of TNF-αin groups A and B also decreased significantly between 7 and 30 days, to 63.28 ± 29.01 pg/ml (group A) and (43.95 ± 17.10) pg

  1. Aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of pentose phosphate pathway.

    Science.gov (United States)

    Su, Ying-Fang; Yang, Shih-Huang; Lee, Yu-Hsien; Wu, Buor-Chang; Huang, Shu-Ching; Liu, Chia-Ming; Chen, Shiow-Ling; Pan, Ya-Fang; Chou, Shih-Shen; Chou, Ming-Yung; Yang, Hui-Wen

    2014-09-01

    Obesity has become a major public health problem of global significance. Today, aspirin remains the most commonly used medication for the treatment of pyrexia, pain, inflammation and antiplatelet. The present study aims at evaluating the possible existence of a putative p53-dependent pathway underlying the aspirin-induced inhibition of adipogenesis. Cell migration assay was identified by the ability to migrate through Transwell insert. Oil Red O staining was employed to quantify adipose accumulation. The concentration of glucose and triglyceride were measured by using assay kits. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques. Aspirin significantly inhibited preadipocyte migration and adipose accumulation. The p53-p21 signaling and the expression of differentiation marker glycerol-3-phosphate dehydrogenase were increased in a dose-dependent manner. It indicated that aspirin induced adipocyte differentiation through p53-p21 pathway. The oncogenic ERK 1/2 MAPK signaling was induced, whereas, the expression of adipogenic markers peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid-binding protein (A-FABP) and inflammatory factors cyclooxygenase-2 (Cox-2), tumor necrosis factor α (TNFα) and inducible nitric oxide synthase (iNOS) were inhibited. Aspirin negatively regulated the pentose phosphate pathway (PPP) by inhibiting the expression of rate-limiting enzyme glucose-6-phosphate dehydrogenase. Knockdown the expression of oncogenic ERK 1/2 MAPK by using 10 μM PD98059 significantly increased triglyceride synthesis, adipose accumulation and activated PPP, however, decreased glucose uptake. Diverted the glucose flux to PPP, rather than increased glucose uptake, was associated with adipogenesis. Down-regulated the expression of tumor suppressor p53 by 10 μM pifithrin-α (PFTα) alone had no effect on adipose accumulation. However, administration

  2. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data

    DEFF Research Database (Denmark)

    Sørensen, Rikke; Hansen, Morten L; Abildstrøm, Steen;

    2009-01-01

    BACKGROUND: Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We examined the risk of hospital admission for bleeding associated with different antithrombotic regimens...... according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding...... was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios...

  3. Effect of pretreatment with aspirin and ticlopidine on the change of platelet aggregability after radiofrequency catheter ablation

    Institute of Scientific and Technical Information of China (English)

    王利宏; 陈君柱; 郑良荣; 陶谦民

    2002-01-01

    Eighty-two patients with supraventricular tachycardia undergoing radi o frequency catheter ablation (RFCA) were studied to observe the inhibition effect of aspirin and ticlopidine on platelet aggregability (PAG) and thromboxane B2 (T XB2) of the blood samples. Patients were divided into aspirin group A, ticlopi di ne group B, aspirin+ticlopidine group C and control group D. PAG and TXB2 were i ncreased clearly after RFCA in all groups (P<0.001). Treatment with aspirin or t iclopidine before operation could reduce the platelet aggregability caused by RF CA and the joint effect of two drugs(change rate of group A:52.51±12.51%; group B:54.78±11.27%;group C: 30.51±10.59%;group D:91.75±21.43%; P<0.05)was st udie d. The much decreased platelet aggregability after antiplatelet therapy was evid ence of the potential benefit of the treatment in preventing thromboembolism aft er ablation. Pretreatment with aspirin and ticlopidine together is a good way to decrease palatelet aggregability after RFCA.

  4. Correlation between long-term aspirin use and F-fluorodeoxyglucose uptake in colorectal cancer measured by PET/CT.

    Directory of Open Access Journals (Sweden)

    Binbin Su

    Full Text Available The aim of this study was to evaluate the relationship between long-term aspirin use with pretreatment 18 Fluorodeoxyglucose (FDG uptake of primary lesions of Colorectal cancer (CRC and evaluate their clinical significance.We enrolled 84 patients with CRC who underwent 18F-FDG PET/CT scanning before surgery between 1st July 2008 and 1st March 2013 and followed up until 1st March 2014. Maximum standardized uptake value (SUVmax of the primary tumor was measured by 18F-FDG PET/CT. The history of aspirin taken and other clinicopathogical factors were also obtained and their relationships were examined by Mann-Whitney or χ2 tests. Progression-free survival (PFS was determined by standard Kaplan-Meier survival analysis. Cox proportional hazards regression was performed to determine whether history of aspirin taken, pretreatment SUVmax, age, gender, TNM stage, tumor sizes and differentiation influenced outcomes.CRC Patients with long-term history of aspirin use had lower SUVmax of primary lesions than control group (9.74±2.62 vs. 13.91±6.18 and showed a trend towards improved PFS after curative surgery. However, pretreatment of SUVmax showed no prognostic value in patients with CRC.Long-term aspirin use is associated with lower pretreatment SUVmax of CRC and is a promising prognostic factor for predicting PFS in patients with CRC.

  5. Effect of pretreatment with aspirin and ticlopidine on the change of platelet aggregability after radiofrequency catheter ablation

    Institute of Scientific and Technical Information of China (English)

    王利宏; 陈君柱; 郑良荣; 陶谦民

    2002-01-01

    Eighty-two patients with supraventricular tachycardia undergoing radiofrequency catheter ablation (RFCA) were studied to observe the inhibition effect of aspirin and ticlopidine on platelet aggregability(PAG) and thromboxane B2(TXB2) of the blood samples.Patients were divided into aspirin group A.ticlopidine group B.aspirin+ticlopidine group C and control group D.PAG and TXB2 were increased clearly after RFCA in all groups(P<0.001).Treatment with aspirin or ticlopidine before operation could reduce the patelet aggregability caused by RFCA and the joint effect of two drugs(change rate of group A:52.51±12.51%;group B:54.78±11.27%;group C:30.51±10.59%;group D:91.75±21.43%;(P<0.05)was studied .The much decreased platelet aggregability after antiplatelet therapy was evidence of the potential benefit of the treatment in preventing thromboembolism after ablation.Pretreatment with aspirin and ticlopidine together is a good way to decrease palateler aggregability after RFCA.

  6. Aspirin decreases systemic exposure to clopidogrel through modulation of P-glycoprotein but does not alter its antithrombotic activity.

    Science.gov (United States)

    Oh, J; Shin, D; Lim, K S; Lee, S; Jung, K-H; Chu, K; Hong, K S; Shin, K-H; Cho, J-Y; Yoon, S H; Ji, S C; Yu, K-S; Lee, H; Jang, I-J

    2014-06-01

    Decreased oral clopidogrel absorption caused by induction of intestinal permeability glycoprotein (P-gp) expression after aspirin administration was observed in rats. This study evaluated the effect of aspirin coadministration on the pharmacokinetics/pharmacodynamics of clopidogrel in humans. A single 75-mg dose of clopidogrel was orally administered before and after 2 and 4 weeks of once-daily 100-mg aspirin administration in 18 healthy volunteers who were recruited based on CYP2C19 and PON1 genotypes. Plasma concentrations of clopidogrel and its active metabolite, H4, and relative platelet inhibition (RPI) were determined. The P-gp microRNA miR-27a increased by up to 7.67-fold (P = 0.004) and the clopidogrel area under the concentration-time curve (AUC) decreased by 14% (P > 0.05), but the AUC of H4 remained unchanged and RPI increased by up to 15% (P = 0.002) after aspirin administration. These findings indicate low-dose aspirin coadministration may decrease clopidogrel bioavailability but does not decrease its efficacy. PMID:24566733

  7. Effects of Grape Seed Extract, Vitamin C, and Vitamin E on Ethanol- and Aspirin-Induced Ulcers

    Science.gov (United States)

    Cuevas, Vivian Molina; Calzado, Yazmín Ravelo; Guerra, Yohani Pérez; Yera, Ambar Oyarzábal; Despaigne, Sonia Jiménez; Ferreiro, Rosa Mas; Quintana, Daisy Carbajal

    2011-01-01

    Effects of GSE and vitamins C and E on aspirin- and ethanol-induced gastric ulcer and associated increases of lipid peroxidation in rats were compared. Two experiments were conducted. Rats were randomized into eight groups: a negative control and seven groups that received aspirin or ethanol for ulcer induction: one positive control (vehicle) and six with VC, VE, or GSE (25 and 250 mg/kg). Ulcer indexes and gastric levels of malondialdehyde (MDA) were quantified. VC, VE, and GSE (25 and 250 mg/kg) decreased aspirin, and ethanol-induced ulcers and MDA values compared with positive control group. The magnitude of aspirin ulcer reduction was comparable for all treatments, and MDA decrease with GSE was higher than with VC and tended to be greater, albeit none significantly, than with VE. GSE was more effective than VC and VE for lowering the ethanol ulcers, while the decrease of MDA levels with GSE was greater than with VC, but comparable to that achieved with VE. GSE protected against ethanol-induced gastric ulcers more effectively than VC or VE, while its protection against aspirin ulcers was comparable for all treatments. GSE produced the greatest reductions of gastric MDA in both models. PMID:22162675

  8. Effects of Grape Seed Extract, Vitamin C, and Vitamin E on Ethanol- and Aspirin-Induced Ulcers

    Directory of Open Access Journals (Sweden)

    Vivian Molina Cuevas

    2011-01-01

    Full Text Available Effects of GSE and vitamins C and E on aspirin- and ethanol-induced gastric ulcer and associated increases of lipid peroxidation in rats were compared. Two experiments were conducted. Rats were randomized into eight groups: a negative control and seven groups that received aspirin or ethanol for ulcer induction: one positive control (vehicle and six with VC, VE, or GSE (25 and 250 mg/kg. Ulcer indexes and gastric levels of malondialdehyde (MDA were quantified. VC, VE, and GSE (25 and 250 mg/kg decreased aspirin, and ethanol-induced ulcers and MDA values compared with positive control group. The magnitude of aspirin ulcer reduction was comparable for all treatments, and MDA decrease with GSE was higher than with VC and tended to be greater, albeit none significantly, than with VE. GSE was more effective than VC and VE for lowering the ethanol ulcers, while the decrease of MDA levels with GSE was greater than with VC, but comparable to that achieved with VE. GSE protected against ethanol-induced gastric ulcers more effectively than VC or VE, while its protection against aspirin ulcers was comparable for all treatments. GSE produced the greatest reductions of gastric MDA in both models.

  9. Inhibition of peroxynitrite-mediated DNA strand cleavage and hydroxyl radical formation by aspirin at pharmacologically relevant concentrations: Implications for cancer intervention

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wei [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035 (China); Department of Food Science and Technology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Zhu, Hong; Jia, Zhenquan [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); Li, Jianrong [College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035 (China); Misra, Hara P. [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States); Zhou, Kequan, E-mail: kzhou@wayne.edu [Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202 (United States); Li, Yunbo, E-mail: yli@vcom.vt.edu [Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA 24060 (United States)

    2009-12-04

    Epidemiological studies have suggested that the long-term use of aspirin is associated with a decreased incidence of human malignancies, especially colorectal cancer. Since accumulating evidence indicates that peroxynitrite is critically involved in multistage carcinogenesis, this study was undertaken to investigate the ability of aspirin to inhibit peroxynitrite-mediated DNA damage. Peroxynitrite and its generator 3-morpholinosydnonimine (SIN-1) were used to cause DNA strand breaks in {phi}X-174 plasmid DNA. We demonstrated that the presence of aspirin at concentrations (0.25-2 mM) compatible with amounts in plasma during chronic anti-inflammatory therapy resulted in a significant inhibition of DNA cleavage induced by both peroxynitrite and SIN-1. Moreover, the consumption of oxygen caused by 250 {mu}M SIN-1 was found to be decreased in the presence of aspirin, indicating that aspirin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy using 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap demonstrated the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from authentic peroxynitrite, and that aspirin at 0.25-2 mM potently diminished the radical adduct formation in a concentration-dependent manner. Taken together, these results demonstrate for the first time that aspirin at pharmacologically relevant concentrations can inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. These results may have implications for cancer intervention by aspirin.

  10. Aspirin inhibits osteoclastogenesis by suppressing the activation of NF-κB and MAPKs in RANKL-induced RAW264.7 cells.

    Science.gov (United States)

    Zeng, Yan-Ping; Yang, Chao; Li, Yuan; Fan, Yong; Yang, Hong-Jun; Liu, Bin; Sang, Hong-Xun

    2016-09-01

    Aspirin is a commonly used medicine as an effective antipyretic, analgesic and anti-inflammatory drug. Previous studies have demonstrated its potential effects of anti-postmenopausal osteoporosis, while the molecular mechanisms remain unclear. The effects of aspirin on receptor‑activator of nuclear factor κB (NF‑κB) ligand (RANKL)‑induced osteoclasts were investigated in RAW264.7 cells in the current study. Using tartrate‑resistant acid phosphatase (TRAP) staining, it was observed that aspirin inhibited the differentiation of RANKL‑induced RAW264.7 cells. The mRNA expression of osteoclastic marker genes, including cathepsin K, TRAP, matrix metalloproteinase 9 and calcitonin receptor, were suppressed by aspirin as identified using reverse transcription‑quantitative polymerase chain reaction analysis. The immunofluorescence assay indicated that aspirin markedly inhibited NF‑κB p65 translocation to the nucleus in RANKL‑induced RAW264.7 cells. In addition, aspirin also suppressed the phosphorylation of mitogen‑activated protein kinases (MAPKs), observed by western blot analysis. Taken together, these data identified that aspirin inhibits osteoclastogenesis by suppressing the activation of NF‑κB and MAPKs in RANKL‑induced RAW264.7 cells, implying that aspirin may possess therapeutic potential for use in the prevention and treatment of osteoporosis. PMID:27430169

  11. Inhibition of peroxynitrite-mediated DNA strand cleavage and hydroxyl radical formation by aspirin at pharmacologically relevant concentrations: Implications for cancer intervention

    International Nuclear Information System (INIS)

    Epidemiological studies have suggested that the long-term use of aspirin is associated with a decreased incidence of human malignancies, especially colorectal cancer. Since accumulating evidence indicates that peroxynitrite is critically involved in multistage carcinogenesis, this study was undertaken to investigate the ability of aspirin to inhibit peroxynitrite-mediated DNA damage. Peroxynitrite and its generator 3-morpholinosydnonimine (SIN-1) were used to cause DNA strand breaks in φX-174 plasmid DNA. We demonstrated that the presence of aspirin at concentrations (0.25-2 mM) compatible with amounts in plasma during chronic anti-inflammatory therapy resulted in a significant inhibition of DNA cleavage induced by both peroxynitrite and SIN-1. Moreover, the consumption of oxygen caused by 250 μM SIN-1 was found to be decreased in the presence of aspirin, indicating that aspirin might affect the auto-oxidation of SIN-1. Furthermore, EPR spectroscopy using 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap demonstrated the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from authentic peroxynitrite, and that aspirin at 0.25-2 mM potently diminished the radical adduct formation in a concentration-dependent manner. Taken together, these results demonstrate for the first time that aspirin at pharmacologically relevant concentrations can inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. These results may have implications for cancer intervention by aspirin.

  12. Safety and efficacy of multimodal thromboprophylaxis following total knee arthroplasty: a comparative study of preferential aspirin vs. routine coumadin chemoprophylaxis.

    Science.gov (United States)

    Gesell, Mark W; González Della Valle, Alejandro; Bartolomé García, Sergio; Memtsoudis, Stavros G; Ma, Yan; Haas, Steven B; Salvati, Eduardo A

    2013-04-01

    Multimodal thromboprophylaxis encompasses preoperative VTE risk stratification, regional anesthesia, mechanical prophylaxis, and early mobilization. We determined if aspirin can be safely used for adjuvant chemoprophylaxis in patients who have a low thromboembolic risk. 1016 consecutive patients undergoing TKA received multimodal thromboprophylaxis. Aspirin was used in 67% of patients and Coumadin 33% (high risk patients, or who were on Coumadin before surgery). This study group was compared to 1001 consecutive patients who received multimodal thromboprophylaxis and routine Coumadin chemoprophylaxis. There was no significant difference in rates of VTE, PE, bleeding, complications, readmission and 90-day mortality between the two groups. There was a significantly higher rate of wound related complications in the control group (p=0.03). Multimodal thromboprophylaxis with aspirin given to the majority of patients at a low VTE risk is safe and effective in patients undergoing primary TKA.

  13. Effect of long-term low dose of aspirin on severity of disease following onset of acute cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Jun Xu; Lili Cao; Xiaomei Deng; Enji Han

    2006-01-01

    BACKGROUND: Aspirin can decrease the incidence risk of high-risk crowdgroup of cerebral infarction, but there are still controversy if it might decrease the degree of disease in degree of patients with acute cerebral infarction.OBJECTIVE: To observe the effect of lower dose of aspirin during taking for a long time on disease degree of disease following onset of acute cerebral infarction.DESIGN: Grouping according to the admission time and 1:1 paired observation.SETTING: Department of Neurology, Qilu Hospital of Shandong University.PARTICIPANTS: The participants in present study were 321 patients with acute cerebral infarction who received treatments in the Department of Neurology, Qilu Hospital of Shandong University from January 1999 to June 2000. There were 190 male and 131 female ,with mean (65±11 )years of age. Inclusive criteria: ① A focal neurological disturbance occurred suddenly and had lasted for more than 24 hours, patients were admitted within 3 days after onset of disease; ② A computed tomography of the brain was performed and excluded hemorrhage in all patients; ③ The patients were proved internal carotid occlusions by clinical features and image findings; ④ The functions of limbs were normal (before the first stroke) or almost normal (before the second stroke). Exclusive criteria: ①The patients who had have cardiogenic cerebral embolism; ②The patients who had taken warfarin orally and other platelet agglutination drugs.METHODS: ①All the patients were divided into 2 groups according to whether they had taken aspirin before: aspirin-treated group (n=110) and blank control group (n=211). There were 70 male and 40 female in aspirin-treated group, with average(65±10) years of age.All patients had taken 50-100 mg/d aspirin for 6 months to 10 years before onset. There were 120 male and 91 female in blank control group, with average (65±13)years of age. Patients received a clinical scoring within 3 days and similar therapeutic measures (such

  14. 阿司匹林与肿瘤防治%Prevention and treatment of aspirin on tumor

    Institute of Scientific and Technical Information of China (English)

    米登海; 王燕慧

    2010-01-01

    动物实验及流行病学研究发现阿司匹林有一定的抗肿瘤作用,长期规律服用阿司匹林可以明显降低结直肠癌、食管癌和胃癌风险,对前列腺癌、膀胱癌、卵巢癌、胰腺癌也有一定的抗癌作用,但仍存在争议.%It has been suggested that aspirin may have anti-tumor effect based on animal experiments and epidemiological investigation, however, it remains controversial whether aspirin has certain effects on prostatic cancer, bladder cancer, ovarian cancer and pancreatic cancer whereas it has been well documented that long-term regular use of aspirin can significantly reduce risks of colorectal cancer, esophageal cancer and gastric cancer.

  15. Aspirin is associated with an increased risk of subdural hematoma in normal-pressure hydrocephalus patients following shunt implantation

    DEFF Research Database (Denmark)

    Birkeland, Peter; Lauritsen, Jens; Poulsen, Frantz Rom

    2015-01-01

    OBJECT: In this paper the authors investigate whether shunt-treated patients with normal-pressure hydrocephalus receiving aspirin therapy are at increased risk of developing subdural hematoma (SDH). METHODS: Records from 80 consecutive patients who had undergone implantation of a cerebrospinal...... fluid shunt for the treatment of normal-pressure hydrocephalus were retrospectively reviewed. RESULTS: Eleven cases of symptomatic SDH occurred, all among patients receiving aspirin or clopidogrel. The 5-year survival estimate was 0.3 (p ...% CI 3.1-53). CONCLUSIONS: Patients on an aspirin therapy regimen have a markedly increased risk of SDH after a shunt has been implanted for the treatment of normal-pressure hydrocephalus. Users of clopidogrel may have an even greater risk....

  16. Theoretical modeling of infrared spectra of the hydrogen and deuterium bond in aspirin crystal

    Science.gov (United States)

    Ghalla, Houcine; Rekik, Najeh; Michta, Anna; Oujia, Brahim; Flakus, Henryk T.

    2010-01-01

    An extended quantum theoretical approach of the ν IR lineshape of cyclic dimers of weakly H-bonded species is proposed. We have extended a previous approach [M.E.-A. Benmalti, P. Blaise, H.T. Flakus, O. Henri-Rousseau, Chem. Phys. 320 (2006) 267] by accounting for the anharmonicity of the slow mode which is described by a "Morse" potential in order to reproduce the polarized infrared spectra of the hydrogen and deuterium bond in acetylsalicylic acid (aspirin) crystals. From comparison of polarized IR spectra of isotopically neat and isotopically diluted aspirin crystals it resulted that centrosymmetric aspirin dimer was the bearer of the crystal main spectral properties. In this approach, the adiabatic approximation is performed for each separate H-bond bridge of the dimer and a strong non-adiabatic correction is introduced into the model via the resonant exchange between the fast mode excited states of the two moieties. Within the strong anharmonic coupling theory, according to which the X-H→⋯Y high-frequency mode is anharmonically coupled to the H-bond bridge, this model incorporated the Davydov coupling between the excited states of the two moieties, the quantum direct and indirect dampings and the anharmonicity for the H-bond bridge. The spectral density is obtained within the linear response theory by Fourier transform of the damped autocorrelation functions. The evaluated spectra are in fairly good agreement with the experimental ones by using a minimum number of independent parameters. The effect of deuteration has been well reproduced by reducing simply the angular frequency of the fast mode and the anharmonic coupling parameter.

  17. Low-dose aspirin use does not diminish the immune response to monovalent H1N1 influenza vaccine in older adults.

    Science.gov (United States)

    Jackson, M L; Bellamy, A; Wolff, M; Hill, H; Jackson, L A

    2016-03-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) may inhibit antibody production by peripheral blood mononuclear cells; one consequence of this could be decreased effectiveness of vaccines in NSAID users. Because many older adults use low-dose aspirin for primary or secondary prevention of coronary events, any inhibitory effect of aspirin on vaccine immune response could reduce the benefits of vaccination programmes in older adults. We tested whether immune response to vaccination differed between users vs. non-users of low-dose aspirin, using data from four randomized trials of monovalent 2009 pandemic influenza A(H1N1) vaccine. Geometric mean haemagglutination inhibition antibody titres were not significantly lower in low-dose aspirin users compared to non-users. Our results provide reassurance that influenza vaccination effectiveness is probably not reduced in older adults taking chronic low-dose aspirin. PMID:26330204

  18. Low-dose aspirin use does not diminish the immune response to monovalent H1N1 influenza vaccine in older adults.

    Science.gov (United States)

    Jackson, M L; Bellamy, A; Wolff, M; Hill, H; Jackson, L A

    2016-03-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) may inhibit antibody production by peripheral blood mononuclear cells; one consequence of this could be decreased effectiveness of vaccines in NSAID users. Because many older adults use low-dose aspirin for primary or secondary prevention of coronary events, any inhibitory effect of aspirin on vaccine immune response could reduce the benefits of vaccination programmes in older adults. We tested whether immune response to vaccination differed between users vs. non-users of low-dose aspirin, using data from four randomized trials of monovalent 2009 pandemic influenza A(H1N1) vaccine. Geometric mean haemagglutination inhibition antibody titres were not significantly lower in low-dose aspirin users compared to non-users. Our results provide reassurance that influenza vaccination effectiveness is probably not reduced in older adults taking chronic low-dose aspirin.

  19. 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

    a 100% risk of colorectal cancer and early death. We conducted an international, multicenter, randomized, placebo-controlled trial of aspirin (600 mg/d) and/or RS (30 g/d) for from 1 to 12 years to prevent disease progression in FAP patients from 10 to 21 years of age. In a 2 × 2 factorial design......, patients were randomly assigned to the following four study arms: aspirin plus RS placebo; RS plus aspirin placebo; aspirin plus RS; RS placebo plus aspirin placebo; they were followed with standard annual clinical examinations including endoscopy. The primary endpoint was polyp number in the rectum...... and sigmoid colon (at the end of intervention), and the major secondary endpoint was size of the largest polyp. A total of 206 randomized FAP patients commenced intervention, of whom 133 had at least one follow-up endoscopy and were therefore included in the primary analysis. Neither intervention...

  20. Damage to cellular and isolated DNA induced by a metabolite of aspirin

    Energy Technology Data Exchange (ETDEWEB)

    Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan)], E-mail: s-oikawa@doc.medic.mie-u.ac.jp; Kobayashi, Hatasu; Tada-Oikawa, Saeko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); JSPS Research Fellow (Japan); Isono, Yoshiaki [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Kawanishi, Shosuke [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 (Japan)

    2009-02-10

    Aspirin has been proposed as a possible chemopreventive agent. On the other hand, a recent cohort study showed that aspirin may increase the risk for pancreatic cancer. To clarify whether aspirin is potentially carcinogenic, we investigated the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is correlated with the incidence of cancer, in cultured cells treated with 2,3-dihydroxybenzoic acid (2,3-DHBA), a metabolite of aspirin. 2,3-DHBA induced 8-oxodG formation in the PANC-1 human pancreatic cancer cell line. 2,3-DHBA-induced DNA single-strand breaks were also revealed by comet assay using PANC-1 cells. Flow cytometric analyses showed that 2,3-DHBA increased the levels of intracellular reactive oxygen species (ROS) in PANC-1 cells. The 8-oxodG formation and ROS generation were also observed in the HL-60 leukemia cell line, but not in the hydrogen peroxide (H{sub 2}O{sub 2})-resistant clone HP100 cells, suggesting the involvement of H{sub 2}O{sub 2}. In addition, an hprt mutation assay supported the mutagenicity of 2,3-DHBA. We investigated the mechanism underlying the 2,3-DHBA-induced DNA damage using {sup 32}P-labeled DNA fragments of human tumor suppressor genes. 2,3-DHBA induced DNA damage in the presence of Cu(II) and NADH. DNA damage induced by 2,3-DHBA was enhanced by the addition of histone peptide-6 [AKRHRK]. Interestingly, 2,3-DHBA and histone peptide-6 caused base damage in the 5'-ACG-3' and 5'-CCG-3' sequences, hotspots of the p53 gene. Bathocuproine, a Cu(I) chelator, and catalase inhibited the DNA damage. Typical hydroxyl radical scavengers did not inhibit the DNA damage. These results suggest that ROS derived from the reaction of H{sub 2}O{sub 2} with Cu(I) participate in the DNA damage. In conclusion, 2,3-DHBA induces oxidative DNA damage and mutations, which may result in carcinogenesis.

  1. Neuroprotection by Aspirin and Sodium Salicylate Through Blockade of NF-kappaB Activation

    Science.gov (United States)

    Grilli, Mariagrazia; Pizzi, Marina; Memo, Maurizio; Spano, Pierfranco

    1996-11-01

    Aspirin (acetylsalicylic acid) is a commonly prescribed drug with a wide pharmacological spectrum. At concentrations compatible with amounts in plasma during chronic anti-inflammatory therapy, acetylsalicylic acid and its metabolite sodium salicylate were found to be protective against neurotoxicity elicited by the excitatory amino acid glutamate in rat primary neuronal cultures and hippocampal slices. The site of action of the drugs appeared to be downstream of glutamate receptors and to involve specific inhibition of glutamate-mediated induction of nuclear factor kappa B. These results may contribute to the emerging theme of anti-inflammatory drugs and neurodegeneration.

  2. Gender differences of low-dose aspirin-associated gastroduodenal ulcer in Japanese patients

    Institute of Scientific and Technical Information of China (English)

    Kazuhisa; Okada; Masahiko; Inamori; Kento; Imajyo; Hideyuki; Chiba; Takashi; Nonaka; Tadahiko; Shiba; Takashi; Sakaguchi; Kazuhiko; Atsukawa; Hisao; Takahashi; Etsuo; Hoshino; Atsushi; Nakajima

    2010-01-01

    AIM:To clarify the gender differences about the clini-cal features and risk factors of low-dose aspirin (LDA) (81-100 mg daily)-associated peptic ulcer in Japanese patients.METHODS: There were 453 patients under treatment with LDA (298 males, 155 females) who underwent esophagogastroduodenoscopy at the Department of Gastroenterology and Hepatology of Hiratsuka City Hospital between January 2003 and December 2007. They had kept taking the LDA or started treatmentduring the study period and kept taking LDA du...

  3. Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats

    OpenAIRE

    Arijit Ghosh; V R Dhumal; A V Tilak; Nina Das; Amarinder Singh; Bondekar, Abhijit A.

    2011-01-01

    Objective: To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Materials and Methods: Retention of conditioned avoidance response (CAR) and central 5-HT-mediated behavior (lithium-induced head twitches) were assessed using repeated electroconvulsive shock (ECS) in rats. Rats were divided into eight groups: control (pretreated with distilled water), scopolamine (0.5 mg/kg i.p.), ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s) pretreated, as...

  4. Gastroprotective Effect of Rubia cordifolia Linn. on Aspirin Plus Pylorus-Ligated Ulcer

    Directory of Open Access Journals (Sweden)

    R. S. Deoda

    2011-01-01

    Full Text Available The present study was designed to investigate the effect of Rubia cordifolia (Rubiaceae against experimentally induced gastric ulcer and compare activity with its fractions by employing aspirin plus pylorus-ligated ulcer screening model in Wistar rats. Total acidity, volume of gastric acid secretion, total acid output, and pepsin activity show significant reduction, when compared with the control group. The present study confirmed that chloroform fraction showed the significant activity at lower doses compared to parent extract. The mechanism can be attributed to decrease in gastric acid secretary activity along with strengthening of mucosal defensive mechanism by prostaglandin synthesis and antioxidant potential.

  5. Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xianwei, E-mail: XWang2@UAMS.edu; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L., E-mail: MehtaJL@UAMS.edu

    2012-03-15

    Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22{sup phox}, p47{sup phox}, p67{sup phox}, NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H{sub 2}O{sub 2}. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac

  6. Impact of aspirin dose on adenosine diphosphate-mediated platelet activities. Results of an in vitro pilot investigation.

    Science.gov (United States)

    Tello-Montoliu, Antonio; Thano, Estela; Rollini, Fabiana; Patel, Ronakkumar; Wilson, Ryan E; Muñiz-Lozano, Ana; Franchi, Francesco; Darlington, Andrew; Desai, Bhaloo; Guzman, Luis A; Bass, Theodore A; Angiolillo, Dominick J

    2013-10-01

    Different aspirin dosing regimens have been suggested to impact outcomes when used in combination with adenosine diphosphate (ADP) P2Y12 receptor antagonists. Prior investigations have shown that not only aspirin, but also potent ADP P2Y12 receptor blockade can inhibit thromboxane A2-mediated platelet activation. The impact of aspirin dosing on ADP mediated platelet activities is unknown and represents the aim of this in vitro pilot pharmacodynamic (PD) investigation. Twenty-six patients with stable coronary artery disease on aspirin 81 mg/day and P2Y12 naïve were enrolled. PD assessments were performed at baseline, while patients were on 81 mg/day aspirin and after switching to 325 mg/day for 7 ± 2 days with and without escalating concentrations (vehicle, 1, 3, and 10 μM) of prasugrel's active metabolite (P-AM). PD assays included flow cytometric assessment of VASP to define the platelet reactivity index (PRI) and the Multiplate Analyzer (MEA) using multiple agonists [ADP, ADP + prostaglandin (PGE1), arachidonic acid (AA), and collagen]. Escalating P-AM concentrations showed incremental platelet P2Y12 inhibition measured by VASP-PRI (paspirin dosing regimen at any P-AM concentration (vehicle: p=0.899; 1 μM: p=0.888; 3 μM: p=0.524; 10 μM: p=0.548). Similar findings were observed in purinergic markers assessed by MEA (ADP and ADP+PGE1). P-AM addition significantly reduced AA and collagen induced platelet aggregation (paspirin dose. In conclusion, aspirin dosing does not appear to affect PD measures of ADP-mediated platelet reactivity irrespective of the degree of P2Y12 receptor blockade. P2Y12 receptor blockade modulates platelet reactivity mediated by alternative activators. PMID:23884248

  7. COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance.

    Science.gov (United States)

    Poorani, R; Bhatt, Anant N; Dwarakanath, B S; Das, Undurti N

    2016-08-15

    Polyunsaturated fatty acids (PUFAs) are vital for normal growth and development and physiological function of various tissues in humans. PUFAs have immunomodulatory actions in addition to their ability to modulate inflammation, vascular reactivity, neurotransmission and stem cell biology. PUFAs and their metabolites possess both pro- and anti-inflammatory properties that underlie their actions and involvement in several diseases. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), possesses both cyclo-oxygenase (COX) and lipoxygenase (LOX) inhibitory action and enhances the production of anti-inflammatory lipoxin A4 {(called as epi-lipoxin A4, aspirin-triggered lipoxins (ATLs))}. In addition, at low doses aspirin may not interfere with the production of prostacyclin (PGI2). Both lipoxin A4 and PGI2 have vasodilator, platelet anti-aggregator and anti-inflammatory actions that may underlie the beneficial actions of aspirin. Paradoxically, other NSAIDs may not have the same actions as that of aspirin on PUFA metabolism. Similar anti-inflammatory compounds are formed from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by the action of aspirin termed as resolvins (from EPA and DHA) and protectins and maresins from DHA. PUFAs: arachidonic acid (AA), EPA and DHA and their various products modulate not only inflammation and immune response but also possess actions on various genes, nuclear factors, cyclic AMP and GMP, G-protein coupled receptors (GPRs), hypothalamic neurotransmitters, hormones, cytokines and enzymes, and interact with nitric oxide, carbon monoxide, and hydrogen sulfide to regulate their formation and action and to form new compounds that have several biological actions. These pleiotropic actions of PUFAs and their metabolites may explain their ability to play a role in several physiological actions and diseases. The big challenge is to harness these actions to prevent and manage clinical conditions. PMID:26335394

  8. Inhibition of Pancreatic Intraepithelial Neoplasia Progression to Carcinoma by Nitric Oxide-Releasing Aspirin in p48Cre/+-LSL-KrasG12D/+ Mice

    Directory of Open Access Journals (Sweden)

    Chinthalapally V. Rao

    2012-09-01

    Full Text Available Nitric oxide-releasing aspirin (NO-aspirin represents a novel class of promising chemopreventive agents. Unlike conventional nonsteroidal anti-inflammatory drugs, NO-aspirin seems to be free of adverse effects while retaining the beneficial activities of its parent compound. The effect of NO-aspirin on pancreatic carcinogenesis was investigated by assessing the development of precursor pancreatic lesions and adenocarcinomas in KrasG12D/+ transgenic mice that recapitulate human pancreatic cancer progression. Six-week-old male p48Cre/+-LSL-KrasG12D/+ transgenic mice (20 per group were fed diets containing 0, 1000, or 2000 ppm NO-aspirin. The development of pancreatic tumors was monitored by positron emission tomography imaging. All mice were killed at the age of 41 weeks and assessed for pancreatic intraepithelial neoplasia (PanIN and pancreatic ductal adenocarcinoma (PDAC and for molecular changes in the tumors. Our results reveal that NO-aspirin at 1000 and 2000 ppm significantly suppressed pancreatic tumor weights, PDAC incidence, and carcinoma in situ (PanIN-3 lesions. The degree of inhibition of PanIN-3 and carcinoma was more pronounced with NO-aspirin at 1000 ppm (58.8% and 48%, respectively than with 2000 ppm (47% and 20%, respectively. NO-aspirin at 1000 ppm significantly inhibited the spread of carcinoma in the pancreas (∼97%; P < .0001. Decreased expression of cyclooxygenase (COX; with ∼42% inhibition of total COX activity, inducible nitric oxide synthase, proliferating cell nuclear antigen, Bcl-2, cyclin D1, and β-catenin was observed, with induction of p21, p38, and p53 in the pancreas of NO-aspirin-treated mice. These results suggest that low-dose NO-aspirin possesses inhibitory activity against pancreatic carcinogenesis by modulating multiple molecular targets.

  9. The History of Antithrombotic Therapy: The Discovery of Heparin, the Vitamin K Antagonists, and the Utility of Aspirin.

    Science.gov (United States)

    Handin, Robert I

    2016-10-01

    The administration of intravenous heparin to postoperative patients by Barritt and Jordan reduced the incidence of fatal and nonfatal pulmonary embolism and established heparin as the standard for parenteral anticoagulation. The coumarin family of vitamin K antagonists quickly became the standard for long-term oral anticoagulation. Aspirin became a widely used antithrombotic agent after the discovery that chronic oral administration reduced the incidence of secondary strokes and myocardial infarction. This article gives a brief history of antithrombotic therapy, including the discovery of heparin, the vitamin k antagonists, and the utility of aspirin. PMID:27637302

  10. Protective effect of ginger oil on aspirin and pylorus ligation-induced gastric ulcer model in rats

    Directory of Open Access Journals (Sweden)

    Khushtar M

    2009-01-01

    Full Text Available The present investigation was performed in aspirin and pylorus ligation-induced ulcer model in Wistar rats, in which ability of ginger oil to provide gastric protection was studied at two different doses, 0.5 and 1 g/kg po. Gastric protection was evaluated by measuring the ulcer index, serum λ- GTP levels, total acidity of gastric juice and gastric wall mucus thickness. The results obtained in the present study indicated that ginger oil has a protective action against gastric ulcers induced by aspirin plus pylorus ligation in Wistar rats.

  11. Aspirin and other non-steroidal anti-inflammatory drugs and risk of colorectal cancer: A Danish cohort study

    DEFF Research Database (Denmark)

    Friis, Søren; Poulsen, Aslak H; Sørensen, Henrik Toft;

    2009-01-01

    The optimal duration and dose of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) in the potential prevention of colorectal cancer (CRC) have not been established. We examined this issue in the Danish Diet, Cancer, and Health Study. Self-reported NSAID use at entry (January...... 1995-May 1997) was updated through June 2006, using a nationwide prescription database. CRC incidence was ascertained from nationwide registers. Cox proportional hazards regression was used to compute confounder-adjusted incidence rate ratios (RRs) and 95% confidence intervals (CIs). From 51,053 cohort...

  12. The effects of aspirin on platelet function and lysophosphatidic acids depend on plasma concentrations of EPA and DHA

    OpenAIRE

    Block, Robert C.; Abdolahi, Amir; Tu, Xin; Georas, Steve N.; Brenna, J. Thomas; Phipps, Richard P.; Lawrence, Peter; Mousa, Shaker A.

    2014-01-01

    Aspirin’s prevention of cardiovascular disease (CVD) events in individuals with type 2 diabetes mellitus is controversial. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and aspirin all affect the cyclooxygenase enzyme. The relationship between plasma EPA and DHA and aspirin’s effects has not been determined. Thirty adults with type 2 diabetes mellitus ingested aspirin (81 mg/day) for 7 days, then EPA+DHA (2.6 g/day) for 28 days, then both for another 7 days. Lysophosphatidic acid...

  13. Successful outcome from empirical use of heparin and aspirin in unexplained pregnancy loss

    Institute of Scientific and Technical Information of China (English)

    Babita Panda; Sasmita Das; Lita Mohapatra; Mahesh C Sahu; Rabindra N Padhy

    2012-01-01

    Success in pregnancy of a 42-years old woman with a history of unexplained recurrent miscarriages is described. She had a sub-septate uterus with free spillage bilaterally, based on hysterosalpingogram, and it was corrected by hysteroscopy in October 2009, which was followed by transcervical septal resection (TCRS). Clomiphene citrate was given ovulation. She was treated with folic acid supplementation, aspirin 75 mg, micronized progesterone 400 mg/d, and low molecular heparin 2500 IU/d, from the diagnosis of pregnancy at 5 weeks, until the delivery. However, at 28 weeks glucose tolerance test with 100 g glucose revealed mild derangement in first (159 mg/dL) and second (164 mg/dL) hour values;metformin was given for the control of sugar. Heparin injections were given to the patient continuously during the antenatal period. No major bleeding episode was noted during pregnancy or delivery. A male child weighing 3.2 kg with a good APGAR score was delivered at the end of the term. Both anatomical abnormality and advanced maternal age had determinative role in pregnancy loss, but TCRS and antithrombotic heparin and aspirin treatment had the blithesome effect.

  14. The in vitro effect of aspirin on increased whole blood platelet aggregation in oral contraceptive users.

    Science.gov (United States)

    Norris, L A; Bonnar, J

    1994-05-01

    The effects of triphasic oral contraceptives on whole blood platelet aggregation in 36 Italian women are reported here. Aspirin's effects on platelet aggregation were also studied. 18 women took a triphasic oral contraceptive; 10 women took Trinordiol, while 8 took Trinovum for at least 90 days. The remaining 18 women took nothing and served as controls. The study was aligned with each woman's birth control pill cycle. Blood was taken daily on days 15-21 of their cycle. Either saline solution or acetylsalicylic acid was added to the blood samples and compared. All data was statistically analyzed using unpaired student's t-test. Effects of 3 aggregating agents, ADP, PAF, and EDTA, on platelet aggregation were studied. Arachidonic acid and adrenalin bitartrate were also studied in this manner. An increase in platelet aggregation was observed in women taking oral contraceptives. No difference was found between patients taking Trinordiol and those taking Trinovum. The results of this study indicate an increase in whole blood platelet sensitivity to collagen, adrenalin, and arachidonic acid when using oral contraceptives. Aspirin, at low doses, may have a role in preventing early thrombus formation in women taking oral contraceptives. PMID:8042198

  15. Effect of aspirin on the metabolism of exogenous arachidonic acid in human polymorphonuclear leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Punnonen, K.; Uotila, P.

    1984-08-01

    When human polymorphonuclear leukocytes (PMNL) were incubated with exogenous /sup 14/C-arachidonic acid (/sup 14/C-AA), both lipoxygenase and cyclo-oxygenase metabolites were detected. The amount of the 5-lipoxygenase metabolites formed, including 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), was small. The amount of other mono-HETE's (migrating in the vicinity of 12-HETE) was greater, but this was obviously mainly due to the small amount of contaminating platelets. In the presence of calcium ionophore A23187 the rate of formation of 5-HETE was increased, but the formation of other metabolites remained unchanged. When PMNL were incubated with aspirin in the presence of A23187 the formation of the cyclo-oxygenase products was decreased but that of 5-HETE was unchanged. The present study indicates that the calcium ionophore A23187 stimulates specifically the 5-lipoxygenase in human PMNL and that aspirin has no effect on the formation of the 5-lipoxygenase metabolites of arachidonic acid in human PMNL.

  16. Risk and preventive factors of low-dose aspirin-induced gastroduodenal injuries: a comprehensive review.

    Science.gov (United States)

    Shiotani, Akiko; Manabe, Noriaki; Kamada, Tomoari; Fujimura, Yoshinori; Sakakibara, Takashi; Haruma, Ken

    2012-04-01

    The risk of peptic ulcer complications, particularly bleeding, is increased in association with the use of low-dose aspirin (LDA). Risk factors for upper gastrointestinal (GI) ulcer or bleeding among LDA users include a history of prior GI events, older age, chronic renal failure, combined antithrombotic therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). Helicobacter pylori and aspirin seem to be independent risk factors for peptic ulcer and bleeding. The studies report conflicting findings about the effect of H. pylori infection on NSAID-related ulcers, and proton-pump inhibitors (PPIs) seem to be superior to eradication only to prevent recurrent ulcer bleeding with LDA. Previous studies indicate that hypoacidity related to corpus atrophy, as well as taking PPIs and co-treatment with angiotensin type 1 receptor blockers (ARBs) and statins seem to reduce peptic ulcer among LDA users. In addition, the interleukin-1β (IL-1β)-511 T allele and angiotensinogen (AGT)-20 CC, which work as the high-producer allele of IL-1β and AGT, are significantly associated with ulcer or ulcer bleeding. The SLCO1B1*1b haplotype, which has the highest transport activity, may diminish the preventive effect of statins or ARBs. The data are still lacking and further prospective studies are needed to identify the specific risk or protective factors for upper GI ulcer and its complications associated with LDA. PMID:22486865

  17. Aspirin use is associated with lower prostate cancer risk in male carriers of BRCA mutations.

    Science.gov (United States)

    Cossack, Matthew; Ghaffary, Cameron; Watson, Patrice; Snyder, Carrie; Lynch, Henry

    2014-04-01

    Previous studies have shown that male BRCA mutation carriers stand at increased risk of developing prostate cancer and have concerns about developing cancer. Genetic counseling practitioners often discuss strategies for reducing the risk of cancer for patients at high risk due to their genetic background. Addressing modifiable health habits is one such strategy. Unfortunately, modifiable risk factors for prostate cancer have only been documented in the general population and have not yet been studied in the BRCA carrier subpopulation. Therefore, this study aimed to identify modifiable risk factors for prostate cancer in BRCA carriers. We examined prostate cancer risk factors in 74 men who were part of families with a BRCA mutation. This study examined nine dichotomous variables including: exercise, history of vasectomy, smoking history, alcohol use, finasteride use, statin use, aspirin use, coffee use, and vitamin use. The survey was sent to all cases of prostate cancer in the Hereditary Cancer Center Database at Creighton University with a known BRCA status. This study confirmed the protective benefits of daily aspirin use, which have been observed in previous studies of the general population, and suggests its benefit in BRCA carriers. Protective benefits from regular vigorous exercise and daily coffee use trended towards significance, but neither factor withstood the Bonferroni Correction for multiple comparisons. PMID:23881471

  18. Design and evaluation of famotidine mucoadhesive nanoparticles for aspirin induced ulcer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Dhaval J., E-mail: dhaval6668@gmail.com [Department of Pharmaceutics, Saraswati Institute of Pharmaceutical Sciences, Gujarat (India); Patel, Jayvadan K. [Department of Pharmaceutics, Nootan Pharmacy College, Visnagar (India)

    2013-03-15

    The present study was performed to design and evaluate the famotidine loaded mucoadhesive nanosuspension for aspirin induced ulcer. A 3-factor, 3-level Box-Behnken design was applied to study the effects of amount of the beads (X{sub 1}), PVPK-30(X{sub 2}) and Tween-80 (X{sub 3}) on the particle size (Y{sub 1}), and cumulative percentage drug released after 1h (Y{sub 2}). The optimization was performed using the desirability function and contour plots. The scanning electron microscopy (SEM) showed the nanoparticles as spherical in shape. The differential scanning calorimetry (DSC) analysis indicated that there was substantial crystallinity change in the nanoparticle compared with the pure drug. Ex-vivo mucoadhesion study showed that famotidine mucoadhesive nanoparticles possessed higher mucoadhesion than the famotidine nanoparticles. The in vivo studies on aspirin-induced rats indicated the lowering in ulcer index for famotidine mucoadhesive nanoparticles was 0.46 {+-}0.011, which was significantly better than the effect of traditional famotidine suspension (0.66{+-}0.035). Famotidine mucoadhesive nanosuspension could be prepared using the media milling technique and allowing significant reduction in ulcer index compared to famotidine suspension. (author)

  19. Survival of heparins, oral anticoagulants, and aspirin after the year 2010.

    Science.gov (United States)

    Fareed, Jawed; Hoppensteadt, Debra A; Fareed, Daniel; Demir, Muzaffer; Wahi, Rakesh; Clarke, Melaine; Adiguzel, Cafer; Bick, Rodger

    2008-02-01

    The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants, and aspirin. Despite remarkable progress in life sciences, these drugs still remain a challenge and a mystery to us, and their use is far from optimized. The development of low-molecular-weight heparins and the synthesis of heparinomimetics, such as the chemically synthesized pentasaccharide, represent a refined use of heparin. Additional drugs from this knowledge will continue to develop; however, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, glycoprotein IIb/IIIa inhibitors, and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains as the approach of choice to manage thrombotic disorders. The new anticoagulant targets, including specific sites in the hemostatic network such as tissue factor, individual clotting factors (IIa, VIIa, IXa, Xa, XIIa, and XIIIa), recombinant forms of serpins (antithrombin, heparin cofactor II, and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin, and site-specific serine protease inhibitor complexes have also been developed. There is a major thrust on the development of orally bioavailable anticoagulant drugs (anti-Xa and anti-IIa agents), which are slated to replace oral anticoagulants. Both the anti-factor Xa and antithrombin agents have been developed for oral use and have provided impressive clinical outcomes in sponsor trials for the postsurgical prophylaxis of venous thrombosis; however, safety concerns related to liver enzyme elevations and

  20. Thrombelastographic haemostatic status and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial: assessing and monitoring the antithrombotic effect of clopidogrel and aspirin versus aspirin alone in hypercoagulable patients: study protocol for a randomized controlled trial

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    Rafiq Sulman

    2012-04-01

    Full Text Available Abstract Background Hypercoagulability, assessed by the thrombelastography (TEG assay, has in several observational studies been associated with an increased risk of post-procedural thromboembolic complications. We hypothesize that intensified antiplatelet therapy with clopidogrel and aspirin, as compared to aspirin alone, will improve saphenous vein graft patency in preoperatively TEG-Hypercoagulable coronary artery bypass surgery (CABG patients and reduce their risk for thromboembolic complications and death postoperatively. Methods/Design This is a prospective randomized clinical trial, with an open-label design with blinded evaluation of graft patency. TEG-Hypercoagulability is defined as a TEG maximum amplitude above 69 mm. Two hundred and fifty TEG-Hypercoagulable patients will be randomized to either an interventional group receiving clopidogrel 75 mg daily for three months (after initial oral bolus of 300 mg together with aspirin 75 mg or a control group receiving aspirin 75 mg daily alone. Monitoring of antiplatelet efficacy and on-treatment platelet reactivity to clopidogrel and aspirin will be conducted with Multiplate aggregometry. Graft patency will be assessed with Multislice computed tomography (MSCT at three months after surgery. Conclusions The present trial is the first randomized clinical trial to evaluate whether TEG-Hypercoagulable CABG patients will benefit from intensified antiplatelet therapy after surgery. Monitoring of platelet inhibition from instituted antithrombotic therapy will elucidate platelet resistance patterns after CABG surgery. The results could be helpful in redefining how clinicians can evaluate patients preoperatively for their postoperative thromboembolic risk and tailor individualized postoperative antiplatelet therapy. Trial registration Clinicaltrials.gov Identifier NCT01046942

  1. DEVELOPMENT AND VALIDATION OF HPTLC METHOD FOR SIMULTANEOUS ESTIMATION OF ROSUVASTATIN CALCIUM AND ASPIRIN IN CAPSULE DOSAGE FORM

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    Pallavi H. Tank et al

    2012-10-01

    Full Text Available This paper described validated high performance thin layer liquid chromatographic (HPTLC method for estimation of Rosuvastatin Calcium (ROSU and Aspirin (ASP in capsule dosage form. The method involved separation of components by TLC on a precoated silica gel 60 F254 using a mixture of n-Hexane: Acetone: Ethyl acetate: Formic acid (6:3:1:0.2 v/v as a mobile phase. Detection of spots was carried out at 240 nm for Rosuvastatin Calcium and Aspirin both. The mean retardation factor for Rosuvastatin Calcium and Aspirin were found to be 0.31±0.02 and 0.60±0.02, respectively. The linear regression data for the calibration plots showed good linear relationship with r2 value 0.995 and 0.995 in the concentration range of 500-1000 ng/spot and 3750-7500 ng/spot for Rosuvastatin calcium and Aspirin, respectively. The developed method was validated as per ICH Guidelines.

  2. Clopidogrel plus long-term aspirin after femoro-popliteal stenting. The CLAFS project: 1- and 2-year results

    NARCIS (Netherlands)

    Strecker, E.P.; Boos, I.B.; Gottmann, D.; Vetter, S.

    2004-01-01

    The aim of this study was to determine the patency rate after femoro-popliteal stenting followed by oral clopidogrel plus long-term aspirin. In a prospective trial, 31 patients with a total of 33 femoro-popliteal artery lesions (21 stenoses, 12 occlusions; 24 femoral, 9 popliteal) were treated with

  3. Targeting FLIP and Mcl-1 using a combination of aspirin and sorafenib sensitizes colon cancer cells to TRAIL

    NARCIS (Netherlands)

    Pennarun, Bodvael; Kleibeuker, Jan H.; Boersma-van Ek, Wytske; Kruyt, Frank A. E.; Hollema, Harry; de Vries, Elisabeth G. E.; de Jong, Steven

    2013-01-01

    The multikinase inhibitor sorafenib is highly effective against certain types of cancer in the clinic and prevents colon cancer cell proliferation in vitro. Non-steroidal anti-inflammatory drugs, such as acetylsalicylic acid (aspirin), have shown activity against colon cancer cells. The aims of this

  4. The postulated mechanism of the protective effect of ginger on the aspirin induced gastric ulcer: Histological and immunohistochemical studies.

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    Salah Khalil, Mahmoud

    2015-07-01

    There are many available drugs for treating gastric ulcer, but they have various side effects. Ginger is a folk, herbal medicine, which is used for treatment of various diseases including gastric ulcer. This study investigates the possible mechanism of the protective effect of ginger on aspirin induced gastric ulcer. Forty adult male albino rats were randomized into four groups (10 animal per each group) and orally received the followings once daily for 5 days: Group I: 3 ml of 1% carboxymethyl cellulose; Group II: ginger powder (200 mg/kg body weight) suspended in 3 mL of 1% carboxymethylcellulose; Group III: aspirin (400 mg/kg body weight) suspended in 3 ml of 1% carboxymethylcellulose in water. Group IV: ginger and 30 minutes later, received aspirin suspended in 1% carboxymethylcellulose, in similar doses as received in groups II and III. On day 6, rats were sacrificed. The animals were anesthetized and the stomach was removed for the macroscopic, histological (Haematoxylin & Eosin and Periodic Acid Shiff) and immunohistochemical investigations (Bax, inducible nitric oxide synthase and heat shock protein 70). Aspirin induced a significant increase of the macroscopic ulcer score, shed and disrupted epithelium, mucosal hemorrhage, submucosal edema and leukocyte infiltration, loss of the mucus of the mucosal surface significantly increased expression of apoptosis regulator Bax, inducible nitric oxide synthase (iNOS) and heat shock protein 70 (HSP70). Ginger ameliorated the histological changes by reducing Bax and iNOS and increasing HSP70 expressions.

  5. Cost-Effectiveness Comparison of Breast Cancer Screening and Vascular Event Primary Prevention with Aspirin in Wales

    Science.gov (United States)

    Morgan, Gareth

    2011-01-01

    Aim: For the first time, this article presents a cost-effectiveness comparison of a breast cancer screening programme with a possible health education programme with aspirin for vascular event primary prevention. Background: Breast cancer screening is a well established part of cancer control programmes yet recent evidence on this intervention has…

  6. Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet.

    NARCIS (Netherlands)

    Diepen, J.A. van; Vroegrijk, I.O.; Berbee, J.F.; Shoelson, S.E.; Romijn, J.A.; Havekes, L.M.; Rensen, P.C.; Voshol, P.J.

    2011-01-01

    Systemic inflammation is strongly involved in the pathophysiology of the metabolic syndrome, a cluster of metabolic risk factors that includes hypertriglyceridemia. Aspirin treatment lowers inflammation via inhibition of NF-kappaB activity but also reduces hypertriglyceridemia in humans. The aim of

  7. PREOPERATIVE THERAPY OF LOW-DOSE ASPIRIN IN INTERNAL MAMMARY ARTERY BYPASS OPERATIONS WITH AND WITHOUT LOW-DOSE APROTININ

    NARCIS (Netherlands)

    SCHONBERGER, JPAM; BREDEE, JJ; VANOEVEREN, W; VANZUNDERT, AAJ; VERKROOST, M; TERWOORST, J; BAVINCK, JH; BERREKLOUW, E; WILDEVUUR, CRH

    1993-01-01

    The effect of preoperative low-dose aspirin (1 mg/kg of body weight) and intraoperative low-dose aprotinin (2 million kallikrein inactivator units) treatment on perioperative blood loss and blood requirements in patients who undergo internal mammary artery bypass operations is unknown. Therefore, we

  8. Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet

    NARCIS (Netherlands)

    Diepen, J.A. van; Vroegrijk, I.O.C.M.; Berbée, J.F.P.; Shoelson, S.E.; Romijn, J.A.; Havekes, L.M.; Rensen, P.C.N.; Voshol, P.J.

    2011-01-01

    Systemic inflammation is strongly involved in the pathophysiology of the metabolic syndrome, a cluster of metabolic risk factors that includes hypertriglyceridemia. Aspirin treatment lowers inflammation via inhibition of NF-?B activity but also reduces hypertriglyceridemia in humans. The aim of this

  9. Patient-level analysis of five international cohorts further confirms the efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies.

    Science.gov (United States)

    Arnaud, Laurent; Mathian, Alexis; Devilliers, Hervé; Ruffatti, Amelia; Tektonidou, Maria; Forastiero, Ricardo; Pengo, Vittorio; Lambert, Marc; Lefevre, Guillaume; Martinez-Zamora, Maria Angeles; Balasch, Juan; Wahl, Denis; Amoura, Zahir

    2015-03-01

    We performed an individual patient meta-analysis to determine whether aspirin has a significant protective effect on the risk of first thrombosis among patients with antiphospholipid antibodies (aPL). Five international cohort studies with available individual patient-level data, reporting on primary prophylaxis with continuous treatment with low-dose aspirin in patients with aPL were included. The main outcome was the occurrence of a first thrombotic in patients with aPL treated with low-dose aspirin compared to those not treated with low-dose aspirin. Pooled Hazard Ratios (HRs) and 95%CIs were calculated using frailty models. We pooled data from 497 subjects and 79 first thrombotic events (3469 patient-years of follow-up). After adjustment on cardiovascular risk factors, aPL profiles, and treatment with hydroxychloroquine, the HR for the risk of a first thrombosis of any type in aPL carriers treated with low-dose aspirin versus those not treated with aspirin was 0.43 (95%CI 0.25-0.75). Subgroup analysis showed a protective effect of aspirin against arterial (HR: 0.43 [95%CI: 0.20-0.93]) but not venous (HR: 0.49 [95%CI: 0.22-1.11]) thrombosis. Subgroup analysis according to underlying disease revealed a protective effect of aspirin against arterial thrombosis for systemic lupus erythematosus (SLE) (HR: 0.43 [95%CI: 0.20-0.94]) and asymptomatic aPL carriers (HR: 0.43 [95%CI 0.20-0.93]). We found no independent protective effect of hydroxychloroquine. This individual patient data meta-analysis shows that the risk of first thrombotic event as well of first arterial thrombotic event is significantly decreased among SLE patients and asymptomatic aPL individuals treated by low-dose aspirin.

  10. The utility of Aspirin in dukes C and high risk dukes B colorectal cancer - The ASCOLT study: study protocol for a randomized controlled trial

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    Ali Raghib

    2011-12-01

    Full Text Available Abstract Background High quality evidence indicates that aspirin is effective in reducing colorectal polyps; and numerous epidemiological studies point towards an ability to prevent colorectal cancer. However the role of Aspirin as an adjuvant agent in patients with established cancers remains to be defined. Recently a nested case-control study within the Nurses Health cohort suggested that the initiation of Aspirin after the diagnosis of colon cancer reduced overall colorectal cancer specific mortality. Although this data is supportive of Aspirin's biological activity in this disease and possible role in adjuvant therapy, it needs to be confirmed in a randomized prospective trial. Methods/Design We hypothesize through this randomized, placebo-controlled adjuvant study, that Aspirin in patients with dukes C or high risk dukes B colorectal cancer (ASCOLT can improve survival in this patient population over placebo control. The primary endpoint of this study is Disease Free Survival and the secondary Endpoint is 5 yr Overall Survival. This study will randomize eligible patients with Dukes C or high risk Dukes B colorectal cancer, after completion of surgery and standard adjuvant chemotherapy (+/- radiation therapy for rectal cancer patients to 200 mg Aspirin or Placebo for 3 years. Stratification factors include study centre, rectal or colon cancer stage, and type of adjuvant chemotherapy (exposed/not exposed to oxaliplatin. After randomization, patient will be followed up with 3 monthly assessments whilst on study drug and for a total of 5 years. Patients with active peptic ulcer disease, bleeding diathesis or on treatment with aspirin or anti-platelet agents will be excluded from the study. Discussion This study aims to evaluate Aspirin's role as an adjuvant treatment in colorectal cancer. If indeed found to be beneficial, because aspirin is cheap, accessible and easy to administer, it will positively impact the lives of many individuals in Asia

  11. Are the current recommendations for the use of aspirin in primary prevention of cardiovascular disease applicable in low-income countries?

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    Noubiap JJ

    2015-08-01

    Full Text Available Jean Jacques N Noubiap,1,2 Jobert Richie N Nansseu3,41Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa; 2Medical Diagnostic Center, Yaoundé, Cameroon; 3Sickle Cell Disease Unit, Mother and Child Centre, Chantal BIYA Foundation, Yaoundé, Cameroon; 4Department of Public Health, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, CameroonAbstract: Although evidence has accumulated that long-term aspirin therapy is beneficial in secondary prevention of cardiovascular disease (CVD, a lot of controversies persist regarding the benefit of aspirin use in primary prevention of CVD. In low-income countries (LIC specifically, the decision to prescribe aspirin for primary CVD prevention is more problematic, as there is a dearth of evidence in this regard. Aspirin has been shown to have relative beneficial effects in preventing a first myocardial infarction, but not stroke. However, as stroke is the prevailing CVD in many LIC, especially in Africa, the benefit of aspirin in these settings is therefore questionable. Indeed, there is no published trial that has evaluated the benefits and risks of continuous aspirin therapy in populations of LIC. Furthermore, though cardiovascular risk assessment is crucial in decision-making for the use of aspirin in primary prevention of CVD, there are no risk assessment tools that have been validated in African populations. Studies are urgently warranted, to determine the usefulness of aspirin in primary prevention of CVD in low-income settings where the drug is highly available and affordable, as CVD is becoming the leading cause of deaths in LIC.Keywords: aspirin, cardiovascular disease, primary prevention, low-income countries

  12. Aspirin Compared to Low Intensity Anticoagulation in Patients with Non-Valvular Atrial Fibrillation. A Systematic Review and Meta-Analysis.

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    Fernando J Vazquez

    Full Text Available Despite its lack of efficacy, aspirin is commonly used for stroke prevention in atrial fibrillation. Since prior studies have suggested a benefit of low-intensity anticoagulation over aspirin in the prevention of vascular events, the aim of this systematic review was to compare the outcomes of patients with non-valvular atrial fibrillation treated with low-intensity anticoagulation with Vitamin K antagonists or aspirin.We conducted a systematic review searching Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, from 1946 to October 14th, 2015. Randomized controlled trials were included if they reported the outcomes of patients with non-valvular atrial fibrillation treated with a low-intensity anticoagulation compared to patients treated with aspirin. The primary outcome was a combination of ischemic stroke or systemic embolism. The random-effects model odds ratio was used as the outcome measure.Our initial search identified 6309relevant articles of which three satisfied our inclusion criteria and were included. Compared to low-intensity anticoagulation, aspirin alone did not reduce the incidence of ischemic stroke or systemic embolism OR 0.94 (95% CI 0.57-1.56, major bleeding OR 1.06 (95% CI 0.42-2.62 or vascular death OR 1.04 (95% CI 0.61-1.75. The use of aspirin was associated with a significant increase in all-cause mortality OR 1.66 (95% CI 1.12-2.48.In patients with non-valvular atrial fibrillation, aspirin provides no benefits over low-intensity anticoagulation. Furthermore, the use of aspirin appears to be associated with an increased risk in all-cause mortality. Our study provides more evidence against the use aspirin in patients with non-valvular atrial fibrillation.

  13. Bleeding after tooth extraction in patients taking aspirin and clopidogrel (Plavix®) compared with healthy controls.

    Science.gov (United States)

    Sadeghi-Ghahrody, Mohsen; Yousefi-Malekshah, Seyed Hamid; Karimi-Sari, Hamidreza; Yazdanpanah, Hamid; Rezaee-Zavareh, Mohammad Saeid; Yavarahmadi, Mohammadhosein

    2016-06-01

    The risk of perioperative bleeding is high in patients who take aspirin and clopidogrel after a percutaneous coronary intervention, and whether to stop the drugs is a matter of concern for dentists. The aim of this study was to answer the specific question: should aspirin and clopidogrel bisulphate (Plavix®) be discontinued during a conventional forceps extraction? We studied 64 patients during the first year after percutaneous insertion of coronary stents who were taking aspirin (ASA) 80mg and clopidogrel (Plavix(®)) 75mg, and 50 healthy patients who were to have a conventional forceps extraction at this polyclinic in 2013-2014 and acted as controls. Clinical details (underlying diseases; number of roots; type of tooth; type of haemostasis; and bleeding immediately, 30minutes, and 48hours after intervention) were compared. We evaluated 114 patients with the mean (range) age of 56 (43-76) years, and there were no significant differences in demographic data, underlying diseases, type of tooth, number of roots, and dose of anaesthetic between the groups. There were also no significant differences in the number of bleeds immediately and 30minutes after intervention (P=0.310 and 0.205). The time that the last dose of aspirin had been taken correlated with 30-minute haemostasis (20 compared with 12hours, p=0.037). During the 48hours after the intervention, there were no uncontrolled bleeds or emergency referrals. We conclude that using aspirin and Plavix® simultaneously has no considerable effect on the risk of bleeding in patients having conventional forceps extraction of a single tooth. PMID:26975576

  14. Attenuation of gastric mucosal inflammation induced by aspirin through activation of A2A adenosine receptor in rats

    Institute of Scientific and Technical Information of China (English)

    Masaru Odashima; Reina Ohba; Sumio Watanabe; Joel Linden; Michiro Otaka; Mario Jin; Koga Komatsu; Isao Wada; Youhei Horikawa; Tamotsu Matsuhashi; Natsumi Hatakeyama; Jinko Oyake

    2006-01-01

    AIM: To determine whether a specific adenosine A2A receptor agonist (ATL-146e) can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil accumulation and production of pro-inflammatory cytokines.METHODS: Gastric lesions were produced by oral gavage of aspirin (200 mg/kg) and HCl (0.15 mol/L,8.0 mL/kg). 4-{3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester (ATL-146e,2.5-5 μg/kg, IP) was injected 30 min before the administration of aspirin. Tissue myeloperoxidase (MPO) concentration in gastric mucosa was measured as an index of neutrophil infiltration. Gastric mucosal concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by ELISA. Also, we examined the effect of ATL-146e on tissue prostaglandin E2 (PGE2) production and gastric secretion.RESULTS: Intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. The total length of gastric erosions (ulcer index) in control rats was 29.8±7.75 mm and was reduced to 3.8±1.42 mm after pretreatment with 5.0 g/kg ATL-146e (P< 0.01).The gastric contents of MPO and pro-inflammatory cytokines were all increased after the administration of aspirin and reduced to nearly normal levels by ATL-146e.Gastric mucosal PGE2 concentration was not affected by intraperitoneal injection of ATL-146e.CONCLUSION: The specific adenosine A2A receptor agohist, ATL-146e, has potent anti-ulcer effects presumably mediated by its anti-inflammatory properties.

  15. Effects of aspirin on number,activity and inducible nitric oxide synthase of endothelial progenitor cells from peripheral blood

    Institute of Scientific and Technical Information of China (English)

    Tu-gang CHEN; Jun-zhu CHEN; Xu-dong XIE

    2006-01-01

    Aim:To investigate whether aspirin has an influence on endothelial progenitor cells (EPC).Methods:Total mononuclear cells (MNC) were isolated from peripheral blood by Ficoll density gradient centrifugation,then cells were plated on fibronectin-coated culture dishes.After 7 d of culture,attached cells were stimulated with aspirin (to achieve final concentrations of 1,2,5,and 10 mmol/L) for 3,6,12,and 24 h.EPC were characterized as adherent cells that were double positive for 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine low density lipoprotein (DiLDL) uptake and lectin binding by direct fluorescent staining.EPC proliferation and migration were assayed using a 3- (4,5-dimethyl-2 thiazoyl) -2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and a modified Boyden chamber assay.respectively.An EPC adhesion assay was performed by replating the EPC on fibronectin-coated dishes,and then adherent cells were counted.In vitro vasculogenesis activity was assayed by using an in vitro vasculogenesis kit. Inducible nitric oxide synthase (iNOS) was assayed by Westem blotting.Results:Incubation of isolated human MNC with aspirin decreased the number of EPC.Aspirin also decreased the proliferative,migratory,adhesive,and in vitro Vasculogenesis capacity of EPC,and also their iNOS levels in a concentration-and time-dependent manner.Conclusion:Aspirin decreases (1) the number of EPC; (2) the proliferative,migratory,adhesive and in vitro vasculogenesis capacities of EPC;and (3) iNOS levels in EPC.

  16. Impact of aspirin use in the incidence of thromboembolic events after bioprosthesis replacement in patients with rheumatic disease

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    André Rodrigues Durães

    2013-09-01

    Full Text Available INTRODUCTION: There is still much debate regarding the kind of antithrombotic therapy in the immediate postoperative period of bioprosthesis replacement (first three months. Thus, the authors consider relevant to determine the contemporary incidence of thromboembolic events in rheumatic patients early after implantation of aortic and mitral bioprosthesis replacement (first 90 days in the post-operative period and perform a comparison between isolated Aspirin uses versus no-antiplatelet therapy, in this same context. METHODS: Between the period of January 2010 to July 2012, all consecutive rheumatic patients, with basal sinus rhythm, who performed mitral and aortic valve replacement with bioprosthesis (pericardial bovine, were included in this prospective cohort study, 184 patients in total. The primary endpoint evaluated were the rate of embolic events. RESULTS: In the first 30 days, there were three cerebral ischemic events among patients treated in Aspirin group (5.2% compared with two events in patients without Aspirin therapy (1.7%, HR = 3.18; 95% CI 0.5 to 19.6; P=0.33. Between 31 and 90 days postoperatively, no patient had a primary outcome. The embolism-free survival, bleeding events and the overall survival were not statistically significant between the aspirin and no-antiplatelet groups. CONCLUSION: In conclusion, in this prospective cohort of rheumatic patients, we found a low and very rare incidence rate of embolic events during the first 90 days postoperative period in mitral and isolated aortic position, respectively. The use of aspirin did not significantly reduce the rate of thromboembolism.

  17. Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin.

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    Yu Lai

    Full Text Available The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage.BALB/c mice were administered aspirin (200 mg/kg/d for 5 days to induce acute small intestinal injury (SII. Subsequently, SII mice were treated with rebamipide (320 mg/kg/d for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2 levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively.COX expression was significantly down-regulated in aspirin induced SII (P < 0.05. In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05.Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.

  18. Implications of altered glutathione metabolism in aspirin-induced oxidative stress and mitochondrial dysfunction in HepG2 cells.

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    Haider Raza

    Full Text Available We have previously reported that acetylsalicylic acid (aspirin, ASA induces cell cycle arrest, oxidative stress and mitochondrial dysfunction in HepG2 cells. In the present study, we have further elucidated that altered glutathione (GSH-redox metabolism in HepG2 cells play a critical role in ASA-induced cytotoxicity. Using selected doses and time point for ASA toxicity, we have demonstrated that when GSH synthesis is inhibited in HepG2 cells by buthionine sulfoximine (BSO, prior to ASA treatment, cytotoxicity of the drug is augmented. On the other hand, when GSH-depleted cells were treated with N-acetyl cysteine (NAC, cytotoxicity/apoptosis caused by ASA was attenuated with a significant recovery in oxidative stress, GSH homeostasis, DNA fragmentation and some of the mitochondrial functions. NAC treatment, however, had no significant effects on the drug-induced inhibition of mitochondrial aconitase activity and ATP synthesis in GSH-depleted cells. Our results have confirmed that aspirin increases apoptosis by increased reactive oxygen species production, loss of mitochondrial membrane potential and inhibition of mitochondrial respiratory functions. These effects were further amplified when GSH-depleted cells were treated with ASA. We have also shown that some of the effects of aspirin might be associated with reduced GSH homeostasis, as treatment of cells with NAC attenuated the effects of BSO and aspirin. Our results strongly suggest that GSH dependent redox homeostasis in HepG2 cells is critical in preserving mitochondrial functions and preventing oxidative stress associated complications caused by aspirin treatment.

  19. Influencia de la aspirina sobre el sangrado al sondaje Influence of aspirin on the bleeding on probing

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    C.M. Ardila Medina

    2011-08-01

    Full Text Available La presencia de sangrado es un signo de inflamación en los tejidos gingivales y periodontales. Aun cuando el sangrado puede ser causado por eventos inflamatorios hiperémicos, otras variables como una función defectuosa de las plaquetas también pueden ocasionar hemorragia. El uso de la aspirina comúnmente ocasiona disfunción adquirida de las plaquetas. Las indicaciones de la aspirina incluyen la reducción del riesgo de varias enfermedades cerebrovasculares y cardiovasculares debido a su actividad antitrombolítica. La aspirina en bajas concentraciones inhibe preferencialmente la síntesis de tromboxanos responsable en la agregación de plaquetas. De esta forma, la aspirina tiene el potencial de alterar la aparición de sangrado valorado por algunos índices empleados en la evaluación clínica periodontal.The presence of bleeding is a sign of inflammation in gingival and periodontal tissues. Although bleeding can be caused by hyperemic inflammatory events, other variables such as defective platelet function can also cause bleeding. The acquired platelet dysfunction is most commonly caused by the use of aspirin. The indication of aspirin include risk reduction for various cerebrovascular and cardiovascular diseases, these benefits derive from aspirin's anti-thromobolytic activity. Aspirin at low concentrations preferentially inhibits the synthesis of thromboxanes responsible for the aggregation of platelets. Thus, aspirin has the potential to alter the appearance of bleeding on some indices used in clinical periodontal evaluation.

  20. Resolution of Ternary Mixture of Aspirin, Atorvastatin, and Clopidogrel by Chemometric-Assisted UV Spectroscopic and Liquid Chromatography Methods

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    Mahmoud Mohamed Issa

    2013-01-01

    Full Text Available Two chemometrics-assisted UV spectrophotometric methods were proposed for the resolution of ternary mixtures without any chemical pretreatment. The first method is based on modification of H-point standard addition method which permits simultaneous analysis of three species from a unique calibration set by making the simultaneous addition of the three analytes. Quotient between the spectra of aspirin, atorvastatin, and clopidogrel was obtained and the results showed that simultaneous determination of aspirin, atorvastatin, and clopidogrel can be obeyed in the linear range 2.5–20 μg mL−1 of aspirin, 2.5–17.5 μg mL−1 of atorvastatin, and 2.5–20 μg mL−1 of clopidogrel in ternary mixture. The second method is based on the combination of the first derivative spectra and Cramer's matrix rule. In the matrix calculation, clopidogrel has zero crossing point at 316.8 and 212 nm, while for atorvastatin the zero crossing point at 250 nm where the matrix is greatly simplified and easily solved. The linear concentration ranges were 2.5–20 μg mL−1 aspirin, 2.5–17.5 μg mL−1 atorvastatin and 2.5–20 μg mL−1 clopidogrel in ternary mixtures. The results proved that the simultaneous determination of aspirin, atorvastatin, and clopidogrel could be obeyed. Both methods were applied for capsules containing the three ingredients and results were in good concordance with alternative liquid chromatography.

  1. Different effects of cytoprotective drugs on ethanol- and aspirin-induced gastric mucosal injury in pylorus-ligated rats

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, K.; Nishiwaki, H.; Niida, H.; Okabe, S. (Kyoto Pharmaceutical Univ. (Japan))

    1990-02-01

    In anesthetized rats oral administration (2 ml) of both ethanol (50% in 150 mM HCl) and aspirin (80 mM in 150 mM HCl) produced bandlike lesions in the stomach, while more generalized lesions occurred in the pylorus-ligated stomach when the irritant was given intragastrically through the fistula prepared in the rumen and the mucosal folds were removed by stomach distension. The bandlike lesions induced in the intact stomach by both irritants were significantly and dose-dependently prevented by 16,16-dimethyl PGE2 (dmPGE2: 3 and 10 micrograms/kg, subcutaneously), cysteamine (30 and 100 mg/kg, subcutaneously) or timoprazole (10 and 30 mg/kg, per os) at the doses which significantly inhibited gastric motility. In the pylorus-ligated stomach, however, neither of these agents showed any protection against the generalized lesions induced by ethanol, but such lesions caused by aspirin were significantly prevented only by dmPGE2. These agents also showed similar effects against the reduction of transmucosal PD in the pylorus-ligated stomach exposed to ethanol and aspirin. These results suggest that (1) the formation of bandlike lesions caused by ethanol and aspirin depends on the presence of mucosal folds and may be prevented by the agents that inhibit gastric motility, (2) the pathogenesis of the lesions induced by aspirin and ethanol may be different in the pylorus-ligated stomach, and (3) dmPGE2 has a unique protective ability that is not shared by usual cytoprotective agents.

  2. EFFECT OF AN ISOLATED COMPPOUND (AS-1 FROM THE LEAVES OF Amaranthus spinosus L. ON ASPIRIN INDUCED GASTRIC ULCER IN ALBINO RATS

    Directory of Open Access Journals (Sweden)

    DEBIPRASAD GHOSH

    2014-05-01

    Full Text Available Objective: Effect of AS-1, a compound isolated from the leaves of Amaranthus spinosus L., was studied on aspirin induced gastric ulcer in albino rats. Method: Gastric ulcer was produced in rats by aspirin and effect of AS-1 was studied. Result: Result showed that the compound could decrease ulcer index in rats induced by aspirin. The compound produced gastric anti secretory effect by decreasing gastric volume and acidity. It further increased gastric mucin which showed gastric cytoprotective effect. Results were comparable to that of ranitidine, a standard anti ulcer drug. Conclusion: AS-1 thus provides a scientific rationale for the use as anti gastric ulcer drug.

  3. Everted Intestinal Sacs As In vitro Model For Assessing Absorptivity Of L Histidine Under The Effect Of Aspirine And Gum Acacia In Male Rats

    Directory of Open Access Journals (Sweden)

    Mahmoud Rabeh Mahmoud

    2004-09-01

    Full Text Available The purpose of this study was to characterize intestinal permeability changes over a range of physiologically relevant intestinal injury. The experiments were performed in 80 rats subdivided into four groups as aspirin (400 mg/kg b.w., gum Acacia ( 1g./day and aspirin with gum Acacia groups for 21 days compared with control group. Relative reabsorption of L-Histidine was greater(p<0.001 in the aspirin in 10 min of incubation compared with that of the control rats. In aspirin in combination with gum Acacia, the relative reabsorption were significantly (p<0.001 decrease in 10, 20 and 30 min. of incubation compared with that of the control rats. Moreover, the relative reabsorption of L-histidine was significantly (p<0.01 reduced by the aspirin at 45 min of time of the incubation buffer compared with that of the control. However, gum acacia treatment was increased at 10 min (p<0.01 ,30 min (p<0.01 and 45 min (p<0.001 respectively compared with that of the control rats. Relative reabsorption of L-histidine record a nonsignificant increase of aspirin at 20 min and 30 min of incubation compared with that of the control. Gum and aspirin with gum at 20min and 45min of incubation resulted an increase and decrease in relative reabsorption of L-histidine respectively compared with that of the control. Aspirin and aspirin in combination with gum acacia treatment increased body, intestinal weights and mucosal total protein significantly with percent changes ranged from 8% to 40% compared with that of the control. On the other hand, gum treatment decreased body, intestinal weights and mucosal total protein significantly with percent changes ranged from 8% to 35% compared with that of the control. These results demonstrated that L-histidine is actively taken up by a gum Acacia system in intestinal everted sac mechanism of rat with energy supplied by glucose and Na+in incubation buffer. Moreover, aspirin system had an inhibitory effect on L-histidine uptake in

  4. Comparative bioavailability studies of citric acid and malonic acid based aspirin effervescent tablets

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    Anju Gauniya

    2010-01-01

    Full Text Available Purpose: The present investigation is aimed at comparing the pharmacokinetic profile (Bioavailability of aspirin in tablet formulations, which were prepared by using different effervescent excipients such as citric acid and malonic acid. Materials and Methods: The relative bioavailability and pharmacokinetics of citric acid based aspirin effervescent tablet (Product A and malonic acid based aspirin effervescent tablet (Product B formulations were evaluated for an in-vitro dissolution study and in-vivo bioavailability study, in 10 normal healthy rabbits. The study utilized a randomized, crossover design with a one-week washout period between doses. Blood samples were collected at 0, 1, 2, 4, 6, 8, 12 and 24 hours following a 100 mg/kg dose. Plasma samples were assayed by High Performance Liquid Chromatography. T max , C max , AUC 0-24 , AUC 0- ∞, MRT, K a, and relative bioavailability were estimated using the traditional pharmacokinetic methods and were compared by using the paired t-test. Result: In the present study, Products A and B showed their T max , C max , AUC 0-24 , AUC 0- ∞, MRT, and K a values as 2.5 h, 2589 ± 54.79 ng/ml, 9623 ± 112.87 ng.h/ml, 9586 ± 126.22 ng.h/ml, 3.6 ± 0.10 h, and 0.3698 ± 0.003 h -1 for Product A and 3.0 h, 2054 ± 55.79 ng/ml, 9637 ± 132.87 ng.h/ml, 9870 ± 129.22 ng.h/ml, 4.76 ± 0.10 h, and 0.3812 ± 0.002 h -1 for Product B, respectively. Conclusion: The results of the paired t-test of pharmacokinetics data showed that there was no significant difference between Products A and B. From both the in vitro dissolution studies and in vivo bioavailability studies it was concluded that products A and B had similar bioavailability.

  5. Polymorphs of Aspirin Solid-state IR-LD spectroscopic and quantitative determination in solid mixtures

    Science.gov (United States)

    Koleva, Bojidarka B.

    2006-12-01

    Solid-state linear-dichroic infrared (IR-LD) spectroscopy, using an orientation technique as a suspension in nematic liquid crystal, has been carried out of Aspirin polymorphs (forms I and II). Reducing-difference procedure for polarized IR-spectra interpretation has been applied for structural analysis of both modifications and the data have been compared with known crystallographic ones. A vibration assignment of forms I and II has been included and on this basis, a quantitative determination by FT-IR spectra for form I in mixtures with second one has been presented, using intensity ratio of 1606 cm -1 peak (characteristic for both forms) to 599 cm -1 one (attributed to form I). The obtained reliability is 99.78%.

  6. Esophageal mucosal lesion with low-dose aspirin and prasugrel mimics malignancy: A case report

    Institute of Scientific and Technical Information of China (English)

    Gui-Fen Ma; Hong Gao; Shi-Yao Chen

    2011-01-01

    Dual antiplatelet therapy consisting of low-dose aspirin (LDA) and other antiplatelet medications is recommended in patients with coronary heart disease, but it may increase the risk of esophageal lesion and bleeding.We describe a case of esophageal mucosal lesion that was difficult to distinguish from malignancy in a patient with a history of ingesting LDA and prasugrel after implantation of a drug-eluting stent. Multiple auxiliary examinations were performed to make a definite diagnosis. The patient recovered completely after concomitant acid-suppressive therapy. Based on these findings, we strongly argue for the evaluation of the risk of gastrointestinal mucosal injury and hemorrhage if LDA therapy is required, and we stress the paramount importance of using drug combinations in individual patients.

  7. Inhibition by indomethacin and aspirin of 15 hydroxy prostaglandin dehydrogenase in vitro

    DEFF Research Database (Denmark)

    Hansen, Harald S.

    1974-01-01

    15 Hydroxyprostaglandin dehydrogenase from bovine lung was purified 7.4 times to a specific activity of 1.4 mU/mg of protein. The isoelectric point was estimated at 5.4 and the molecular weight by gel filtration at 40,000. K(m) for prostaglandin E and for NAD was found to be 3.4 µM and 1.1 x 10M...... respectively. The enzyme was inhibited by indomethacin and aspirin. The indomethacin inhibition was found to be non competitive to prostaglandin E having a K(i) = 1.4 x 10M and a K'(i) = 1.6 x 10M....

  8. Network reconstruction of platelet metabolism identifies metabolic signature for aspirin resistance

    Science.gov (United States)

    Thomas, Alex; Rahmanian, Sorena; Bordbar, Aarash; Palsson, Bernhard Ø.; Jamshidi, Neema

    2014-01-01

    Recently there has not been a systematic, objective assessment of the metabolic capabilities of the human platelet. A manually curated, functionally tested, and validated biochemical reaction network of platelet metabolism, iAT-PLT-636, was reconstructed using 33 proteomic datasets and 354 literature references. The network contains enzymes mapping to 403 diseases and 231 FDA approved drugs, alluding to an expansive scope of biochemical transformations that may affect or be affected by disease processes in multiple organ systems. The effect of aspirin (ASA) resistance on platelet metabolism was evaluated using constraint-based modeling, which revealed a redirection of glycolytic, fatty acid, and nucleotide metabolism reaction fluxes in order to accommodate eicosanoid synthesis and reactive oxygen species stress. These results were confirmed with independent proteomic data. The construction and availability of iAT-PLT-636 should stimulate further data-driven, systems analysis of platelet metabolism towards the understanding of pathophysiological conditions including, but not strictly limited to, coagulopathies.

  9. Newly Identified Targets of Aspirin and Its Primary Metabolite, Salicylic Acid.

    Science.gov (United States)

    Klessig, Daniel F

    2016-04-01

    Salicylic acid (SA) is a plant hormone, which influences several physiological processes, and is a critical modulator of multiple levels of immunity in plants. Several high-throughput screens, which were developed to identify SA-binding proteins through which SA mediates its many physiological effects in plants, uncovered several novel targets of aspirin and its primary metabolite, SA, in humans. These include glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and high mobility group box 1 (HMGB1), two proteins associated with some of the most prevalent and devastating human diseases. In addition, natural and synthetic SA derivatives were discovered, which are much more potent than SA at inhibiting the disease-associated activities of these targets. PMID:26954428

  10. Aspirin, Calcitriol, and Calcium Do Not Prevent Adenoma Recurrence in a Randomized Controlled Trial

    DEFF Research Database (Denmark)

    Pommergaard, Hans Christian; Burcharth, Jakob; Rosenberg, Jacob;

    2016-01-01

    , and calcium carbonate could prevent colorectal adenoma recurrence. METHODS: We included 1107 patients with 1 or more sporadic adenoma(s) removed from the colon or rectum at centers in Europe, Russia, or the United States, from 2004 through 2010. Inclusion criteria were 1 adenoma greater than 1 cm in diameter......BACKGROUND & AIMS: Chemopreventive strategies might be used to reduce the recurrence of colorectal adenomas and the incidence of colorectal cancer. We performed a randomized, double-blind, placebo-controlled trial to determine whether a combination of acetylsalicylic acid (aspirin), calcitriol......, more than 1 adenoma of any size, or an adenoma of any size and first-degree relatives with colorectal cancer. Subjects were assigned randomly to groups given 0.5 μg calcitriol, 75 mg acetylsalicylic acid, and 1250 mg calcium carbonate (n = 209), or placebo (n = 218), each day for 3 years. The primary...

  11. Intragastric inulin as a measure of mucosal damage caused by aspirin

    Energy Technology Data Exchange (ETDEWEB)

    Wittmers, L.E. Jr.; Anderson, L.A.; Fall, M.M.; Alich, A.A. (Univ. of Minnesota-Duluth School of Medicine (USA))

    1990-11-01

    In an attempt to find a method of gastric mucosal damage assessment that yields consistent results, the experiments presented here employed the measurement of the movement of inulin out of the gastric contents into the stomach wall and vascular compartment as an estimate of mucosal damage. Anesthetized male Sprague-Dawley rats were functionally nephrectomized and were administered a control or test solution containing 3H-inulin. The test solutions contained one of three doses of aspirin. Blood samples were taken at 15-min intervals over a 90-min exposure period. The stomach was removed from the animal and full-thickness tissue samples taken for measurement of 3H-inulin content. When the gastric mucosa was exposed to the test agents, there was a significantly greater accumulation of inulin in the body and antrum as well as in the plasma when compared to controls. We conclude that intragastric inulin can be employed to estimate gastric mucosal damage.

  12. Aspirin for cancer is no mere antiplatelet prototype. There is potential in its ancient roots.

    Science.gov (United States)

    Lawrence, James R; Baxter, Gwendoline J; Paterson, John R

    2016-09-01

    Aspirin (ASA), increasingly accepted as predominantly a cyclooxygenase (COX)-1 inhibitor, is a prodrug for salicylic acid (SA) which has no such activity. SA is widespread in nature, vital in plants, and present in drug free serum from animals and man. Evolutionary conserved SA receptors are found in human tissues. Very low doses of ASA will, on repeat dosing, produce near maximal platelet COX-1 inhibition. Evidence for cancer prophylaxis is based on ASA doses of at least 75mg/day. Pleiotropic mechanisms underlie low dose ASA's undoubted efficacy in preventive medicine but the key barrier to its more widespread use is gastrointestinal toxicity. ASA/SA combination formulations may improve the current risk/benefit ratio of chemo-prophylactic preparations. There is well established methodology for, and should be few regulatory barriers to, their evaluation. PMID:27515206

  13. In Vitro Cytotoxic Effects of Celecoxib, Mefenamic Acid, Aspirin and Indometacin on Several Cells Lines

    Science.gov (United States)

    Hashemipour, Maryam Alsadat; Mehrabizadeh Honarmand, Hoda; Falsafi, Farideh; Tahmasebi Arashlo, Mehrnaz; Rajabalian, Saied; Gandjalikhan Nassab, Sayed Amir Hossein

    2016-01-01

    Statement of the Problem Use of cyclooxygenase inhibitors as chemotherapy agents has attracted the attention of a large number of investigators in recent years. Given the importance of cancer therapy, only a limited number of studies have been carried out to investigate the effects of cyclooxygenase inhibitors on specific cell lines. Purpose This research aimed to determine the in vitro cytotoxic effects of cyclooxygenase inhibitors (COX-1 and COX-2 inhibitors) on KB, Saos-2, 1321N, U-87MG, SFBF-PI 39 cell lines. Materials and Method Powders of celecoxib, mefenamic acid, aspirin and indometacin were dissolved in the appropriate solvent. The viability of cell lines was carried out by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay technique. Data gathered from four separate experiments were expressed as mean±SD. Statistical significance was defined at p< 0.05 by using analysis of variance. Significant treatment mean values were subjected to post-hoc Tukey’s test. Results Celecoxib showed marked cytotoxic effects on KB, Saos-2, and 1321N cells, which was significant in comparison with the control group. Celecoxib was not effective in killing U-87MG cell line. Mefenamic acid exerted cytotoxic effects on KB, Saos-2, and 1321N cells, where the viability was approximately 75%. U-87MG cells were resistant to mefenamic acid. Indometacin had the highest rate of activity on U-87MG cells, which was significant in comparison with the control group. Aspirin did not exhibit any activity on these cell lines and was not effective in killing U-87MG, KB, Saos-2, and 1321N cells. Conclusion This research showed that celecoxib, indometacin, and mefenamic acid have the cytotoxic effects on KB, Saos-2, 1321N and U-87MG cell lines. Therefore, it appears that these drugs can be considered as anti-neoplastic agents in the experimental phase. PMID:27602398

  14. New insights into the mechanisms of action of aspirin and its use in the prevention and treatment of arterial and venous thromboembolism

    Directory of Open Access Journals (Sweden)

    Mekaj YH

    2015-09-01

    Full Text Available Ymer H Mekaj,1,2 Fetije T Daci,2 Agon Y Mekaj3 1Institute of Pathophysiology, Faculty of Medicine, University of Prishtina, 2Department of Hemostasis and Thrombosis, National Blood Transfusion Center of Kosovo, 3Clinic of Neurosurgery, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo Abstract: The antithrombotic action of aspirin has long been recognized. Aspirin inhibits platelet function through irreversible inhibition of cyclooxygenase (COX activity. Until recently, aspirin has been mainly used for primary and secondary prevention of arterial antithrombotic events. The aim of this study was to review the literature with regard to the various mechanisms of the newly discovered effects of aspirin in the prevention of the initiation and development of venous thrombosis. For this purpose, we used relevant data from the latest numerous scientific studies, including review articles, original research articles, double-blinded randomized controlled trials, a prospective combined analysis, a meta-analysis of randomized trials, evidence-based clinical practice guidelines, and multicenter studies. Aspirin is used in the prevention of venous thromboembolism (VTE, especially the prevention of recurrent VTE in patients with unprovoked VTE who were treated with vitamin K antagonists (VKAs or with non-vitamin K antagonist oral anticoagulants (NOACs. Numerous studies have shown that aspirin reduces the rate of recurrent VTE in patients, following cessation of VKAs or NOACs. Furthermore, low doses of aspirin are suitable for long-term therapy in patients recovering from orthopedic or other surgeries. Aspirin is indicated for the primary and secondary prevention as well as the treatment of cardiovascular diseases, including acute coronary syndrome, myocardial infarction, peripheral artery disease, acute ischemic stroke, and transient ischemic attack (especially in atrial fibrillation or mechanical heart valves. Aspirin can prevent or treat

  15. Aspirin combined with mechanical measures to prevent venous thromboembolism after total knee arthroplasty: a randomized controlled trial

    Institute of Scientific and Technical Information of China (English)

    Jiang Yi; Du Hui; Liu Jian; Zhou Yixin

    2014-01-01

    Background Venous thromboembolism (VTE) is an important complication after major orthopedic surgery.Pharmaceutical methods represent the main strategy of VTE prevention.The use of aspirin in VTE prevention is still controversial worldwide,especially in China.The purpose of this study was to evaluate the role of aspirin combined with mechanical measures in the prevention of VTE after total knee arthroplasty (TKA).Methods Between January 2012 and May 2013 and in accordance with the inclusion criteria,120 patients undergoing TKA were randomly allocated to two groups.To prevent VTE,patients in group A received aspirin combined with mechanical measures postoperatively,while patients in group B received low-molecular-weight heparin (LMWH) sodium and rivaroxaban sequentially in combination with mechanical measures postoperatively.All surgeries were performed by one surgeon using a posterior-stabilized cemented prosthesis.The two groups were followed up and compared for the incidence of deep vein thrombosis (DVT) by duplex ultrasound scan and clinical VTE events.The adverse events,the blood loss index,and the cost of VTE prevention were also compared.Results DVT was detected in 10 of 60 patients in group A (16.7%,95% CI:7.3%-26.1%) compared with 11 of 60 in group B (18.3%,95% CI:8.5%-27.8%) (P=0.500).There is no statistical evidence supporting the inferior effect of aspirin in preventing DVT as compared with the other medications.There were no cases of symptomatic VTE or death during the follow-up period.Area of ecchymosis was lower in group A than in group B,and the differences were statistically significant.Patients in group A had the lower blood loss index as compared with patients in group B.No transfusion cases were found in both groups.The differences were statistically significant.The cost of VTE prevention analysis indicated a cost reduction using aspirin in group A compared with using LMWH and rivaroxaban in group B.Conclusion Aspirin combined with

  16. Aspirin inhibits the proliferation of tobacco-related esophageal squamous carcinomas cell lines through cyclooxygenase 2 pathway

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qiao-Zhi; LIU Hai-bo; DING Xin-chun; LI Peng; ZHANG Shu-tian; YU Zhong-lin

    2007-01-01

    Background Cigarette smoking has been verified as the risk factor of esophageal squamous cell carcinoma(ESCC).Overexpression of cyclooxygenase 2(COX-2)is shown in ESCC.The objective of this study was to investigate the effects of cigarette smoking ethanol extract(EE)on the proliferation of the human ESCC cell Iines,and to explore the correlation between the proliferation rate of human ESCC cell lines and the expression pattern of COX-2.Whether aspirin can inhibit the proliferation of the ESCC cell lines pretreated with EE.and regulate the mRNA expression levels of COX-2 are also examined.Methods Two human ESCC cell Iines were selected.EC109 was poorly differentiated and EC9706 was highly differentiated.EC109 and EC9706 were treated with EE and aspirin for different time course.The cell growth of ESCC was measured by MTT reduction assay and the expression of COX-2 was measured by RT-PCR and Western blot analysis.Results EE promoted the proliferation of EC109 and EC9706 in dose- and time-dependent manners.In the concentration range (10-100 μg/ml for EE)and in the time range(24-72 hours)after addition of EE,the cell proliferation was prominent in an up-scaled manner respectively.Aspirin could inhibit the proliferation of cell lines EC109 and EC9706.pretreated with EE for 5 hours,in a dose-dependent manner.In the concentration range (0.5-8.0 mmol/L for aspirin),the cell growth inhibition was prominent in an up-scaled manner accordingly (P<0.05).The effect of EE on cell proliferation was correlated with the up-regulation of COX-2 gene.However,the cell growth inhibition of aspirin was correlated with the down-regulation of COX-2 gene.Conclusions EE can stimulate the proliferation of human ESCC cell lines EC109 and EC9706,most likely through up-regulating the expression of COX-2.Aspirin can inhibit the proliferation of ESCC cell lines induced by EE,which suggests it may be advantageous in the chemoprevention and therapy of human tobacco-related ESCC.And its effect is

  17. Can Airway Tolerance be Promoted Immunopharmacologically with Aspirin in Aspirin-insensitive Allergic Bonchial Asthmatics by T Regulatory Cells (Tregs-directed Immunoregulatory Therapy?

    Directory of Open Access Journals (Sweden)

    Muzammal Hussain

    2012-07-01

    Full Text Available The pathobiology of allergic bronchial asthma is mediated by over-expressed T helper type 2 (Th2-biased immune responses to harmless environmental antigens, leading to airway inflammation and hyper-responsiveness. These Th2 responses are normally suppressed by functional T regulatory cells (Tregs, which maintain the airway tolerance. However, the Tregs activity is conceived to be compromised in allergic asthmatics. The curative therapy to counteract this immune dysregulation is not available so far, and to devise such a remedy is the current research impetus in allergic asthma therapeutics. One of the novel insights is to consider a Tregs-directed immunoregulatory therapy that could harness endogenous Tregs to redress the Th2/Tregs imbalance, thus enhancing the airway tolerance. Aspirin or acetylsalicylic acid (ASA is a prototype non-steroidal anti-inflammatory drug that possesses intriguing immunopharmacological attributes. For example, it can enhance the number or the frequency of functional Tregs, especially natural CD4+ CD25+ FoxP3+ Tregs, either directly or by inducing tolerogenic activity in dendritic cells (DCs. It is also considered to be beneficial for the induction of immunological tolerance in autoimmunity and graft rejection. This raises the question whether ASA, if exploited optimally, may be used to induce and harness endogenous Tregs activity for redressing Th2/Tregs imbalance in allergic asthma. In this paper, we hypothesise that ASA may help to counteract the underlying immune dysregulation in allergic asthma by promoting airway tolerance. Nevertheless, the future research in this regard will selectively need to be targeted to allergic asthma models, which are ASA insensitive, as ASA has some adverse background and is contraindicated in asthmatics who are sensitive to it.

  18. Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production.

    Directory of Open Access Journals (Sweden)

    Chia-Chien Hsieh

    Full Text Available Breast cancer is one of the most common cancers in women worldwide. The obesity process is normally accompanied by chronic, low-grade inflammation. Infiltration by inflammatory cytokines and immune cells provides a favorable microenvironment for tumor growth, migration, and metastasis. Epidemiological evidence has shown that aspirin is an effective agent against several types of cancer. The aim of this study is to investigate the anti-inflammatory and anti-cancer effects of aspirin on 3T3-L1 adipocytes, 4T1 murine breast cancer cells, and their crosstalk. The results showed that aspirin treatment inhibited differentiation and lipid accumulation by 3T3-L1 preadipocytes, and decreased the secretion of the inflammatory adipokine MCP-1 after stimulation with tumor necrosis factor (TNF-α or conditioned medium from RAW264.7 cells. In 4T1 cells, treatment with aspirin decreased cell viability and migration, possibly by suppressing MCP-1 and VEGF secretion. Subsequently, culture of 4T1 cells in 3T3-L1 adipocyte-conditioned medium (Ad-CM and co-culture of 3T3-L1 and 4T1 cells using a transwell plate were performed to clarify the relationship between these two cell lines. Aspirin exerted its inhibitory effects in the transwell co-culture system, as well as the conditioned-medium model. Aspirin treatment significantly inhibited the proliferation of 4T1 cells, and decreased the production of MCP-1 and PAI-1 in both the Ad-CM model and co-culture system. Aspirin inhibited inflammatory MCP-1 adipokine production by 3T3-L1 adipocytes and the cell growth and migration of 4T1 cells. It also broke the crosstalk between these two cell lines, possibly contributing to its chemopreventive properties in breast cancer. This is the first report that aspirin's chemopreventive activity supports the potential application in auxiliary therapy against obesity-related breast cancer development.

  19. Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production.

    Science.gov (United States)

    Hsieh, Chia-Chien; Huang, Yu-Shan

    2016-01-01

    Breast cancer is one of the most common cancers in women worldwide. The obesity process is normally accompanied by chronic, low-grade inflammation. Infiltration by inflammatory cytokines and immune cells provides a favorable microenvironment for tumor growth, migration, and metastasis. Epidemiological evidence has shown that aspirin is an effective agent against several types of cancer. The aim of this study is to investigate the anti-inflammatory and anti-cancer effects of aspirin on 3T3-L1 adipocytes, 4T1 murine breast cancer cells, and their crosstalk. The results showed that aspirin treatment inhibited differentiation and lipid accumulation by 3T3-L1 preadipocytes, and decreased the secretion of the inflammatory adipokine MCP-1 after stimulation with tumor necrosis factor (TNF)-α or conditioned medium from RAW264.7 cells. In 4T1 cells, treatment with aspirin decreased cell viability and migration, possibly by suppressing MCP-1 and VEGF secretion. Subsequently, culture of 4T1 cells in 3T3-L1 adipocyte-conditioned medium (Ad-CM) and co-culture of 3T3-L1 and 4T1 cells using a transwell plate were performed to clarify the relationship between these two cell lines. Aspirin exerted its inhibitory effects in the transwell co-culture system, as well as the conditioned-medium model. Aspirin treatment significantly inhibited the proliferation of 4T1 cells, and decreased the production of MCP-1 and PAI-1 in both the Ad-CM model and co-culture system. Aspirin inhibited inflammatory MCP-1 adipokine production by 3T3-L1 adipocytes and the cell growth and migration of 4T1 cells. It also broke the crosstalk between these two cell lines, possibly contributing to its chemopreventive properties in breast cancer. This is the first report that aspirin's chemopreventive activity supports the potential application in auxiliary therapy against obesity-related breast cancer development.

  20. In vitro release of arachidonic acid metabolites, glutathione peroxidase, and oxygen-free radicals from platelets of asthmatic patients with and without aspirin intolerance.

    OpenAIRE

    Plaza, V.; J. Prat; Rosellò, J.; Ballester, E; Ramis, I; Mullol, J; Gelpí, E; Vives-Corrons, J. L.; Picado, C.

    1995-01-01

    BACKGROUND--An abnormal platelet release of oxygen-free radicals has been described in acetylsalicylic acid (aspirin)-induced asthma, a finding which might suggest the existence of an intrinsic, specific platelet abnormality of arachidonic acid metabolism in these patients. The objective of this study was to evaluate platelet arachidonic acid metabolism in asthmatic patients with or without intolerance to aspirin. METHODS--Thirty subjects distributed into three groups were studied: group 1, 1...

  1. Simultaneous determination of carisoprodol and aspirin in human plasma using liquid chromatography-tandem mass spectrometry in polarity switch mode: application to a human pharmacokinetic study.

    Science.gov (United States)

    Sreenivasulu, Vudagandla; Ramesh, Mullangi; Kumar, Inamadugu Jaswanth; Babu, Ravi Vasu; Pilli, Nageswara Rao; Krishnaiah, Abburi

    2013-02-01

    A simple, sensitive and rapid LC-MS/MS-ESI method has been developed and validated for simultaneous quantification of the carisoprodol and aspirin in human plasma. Carisoprodol was detected in positive ion mode, whereas aspirin was detected in negative ion mode. Carbamazepine and furosemide were used as internal standards (IS) for quantification of carisoprodol and aspirin, respectively. The extraction procedure involves a liquid-liquid extraction method with ter-butyl methyl ether. Chromatographic separation was achieved on a Zorbax XDB-Phenyl (4.6 × 75 mm, 3.5 µm) column using an isocratic mobile phase (5 mm ammonium acetate:methanol, 20:80, v/v) at a flow rate of 0.8 mL/min with a total run time of 2.2 min. A detailed method validation was performed as per the FDA guidelines. The standard curves found to be linear in the range of 25.5-4900 and 15.3-3000 ng/mL for carisoprodol and aspirin, respectively. The results met the acceptance criteria. Carisoprodol and aspirin were found to be stable in various stability studies. The validated method was successfully applied to a pharmacokinetic study following co-administration of carisoprodol (250 mg) and aspirin (75 mg) tablets by oral route to human volunteers. PMID:22674769

  2. Aspirin-induced increase in intestinal paracellular permeability does not affect the levels of LPS in venous blood of healthy women.

    Science.gov (United States)

    Gnauck, Anne; Lentle, Roger G; Kruger, Marlena C

    2015-07-01

    The presence of subclinical levels of LPS from Gram-negative bacteria, also referred to as endotoxin, in the circulation may induce a pro-inflammatory immune response that leads to the development of obesity and insulin resistance. Recent data indicate that high-fat meals may elevate circulating levels of LPS. However, it is currently unclear how the LPS transits from the gut lumen to the general circulation. We determined whether aspirin-induced damage of the small intestinal mucosa, evidenced by an increase in the paracellular permeability, allows greater transit of LPS into the systemic circulation. The 3-h cumulative excretion of lactulose was significantly increased after the consumption of aspirin solution relative to that after the consumption of an equal volume of water in 15 healthy women (median after aspirin 0.09% of dose vs. median after water 0.03% of dose; P = 0.004). Dosage with aspirin also significantly increased the lactulose : mannitol ratio (median after aspirin 0.014 vs. median after water 0.005; P = 0.017). However, serum LPS levels after the consumption of the aspirin solution were not significantly different from those after consumption of the control (plain water). Further, there was no correlation between body fat content and circulating levels of LPS.

  3. New insights into the anti-inflammatory actions of aspirin- induction of nitric oxide through the generation of epi-lipoxins

    Directory of Open Access Journals (Sweden)

    Derek W Gilroy

    2005-03-01

    Full Text Available Aspirin has always remained an enigmatic drug. Not only does it present with new benefits for treating an ever-expanding list of apparently unrelated diseases at an astounding rate but also because aspirin enhances our understanding of the nature of these diseases processe. Originally, the beneficial effects of aspirin were shown to stem from its inhibition of cyclooxygenase-derived prostaglandins, fatty acid metabolites that modulate host defense. However, in addition to inhibiting cyclooxygenase activity aspirin can also inhibit pro-inflammatory signaling pathways, gene expression and other factors distinct from eicosanoid biosynthesis that drive inflammation as well as enhance the synthesis of endogenous protective anti-inflammatory factors. Its true mechanism of action in anti-inflammation remains unclear. Here the data from a series of recent experiments proposing that one of aspirin's predominant roles in inflammation is the induction of nitric oxide, which potently inhibits leukocyte/endothelium interaction during acute inflammation, will be discussed. It will be argued that this nitric oxide-inducing effects are exclusive to aspirin due to its unique ability, among the family of traditional anti-inflammatory drugs, to acetylate the active site of inducible cyclooxygenase and generate a family of lipid mediators called the epi-lipoxins that are increasingly being shown to have profound roles in a range of host defense responses.

  4. In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Shen, Youming; Liu, Xiwang; Yang, Yajun; Li, Jianyong; Ma, Ning; Li, Bing

    2015-01-01

    Aspirin eugenol ester (AEE) is a promising drug candidate for treatment of inflammation, pain and fever and prevention of cardiovascular diseases with fewer side effects than its precursor, aspirin. Investigation into its metabolic process in target animal species will help to illustrate its mechanism of action and to establish its residual mark compound to formulate its dosage. Six beagle dogs were orally given a dose of 20 mg kg(-1) of AEE and one dog was used to prepare blank liver microsomes. Their liver microsomes were prepared for in vitro study and their plasma and urine were collected for in vivo metabolic analysis using liquid chromatography tandem mass spectrometry. In this study we identified 10 metabolites, M1, M2, M3, M4, M5 in phase I and M6, M7, M8, M9, M10 in phase II. Based on the metabolites of AEE, the pathways of AEE metabolism in dog were demonstrated.

  5. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin.

    Science.gov (United States)

    Bozzi, Laura M; Mitchell, Braxton D; Lewis, Joshua P; Ryan, Kathy A; Herzog, William R; O'Connell, Jeffrey R; Horenstein, Richard B; Shuldiner, Alan R; Yerges-Armstrong, Laura M

    2016-01-01

    Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti-platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days. One hour after the last dose of clopidogrel, 325 mg of aspirin was given. Ex vivo platelet aggregometry was performed at baseline, post-clopidogrel, and post-DAPT. Platelet aggregation measurements were significantly lower after both interventions for all agonists tested (p pharmacogenomics studies.

  6. Deep vein thrombosis in a patient of adenomatous polyposis coli treated successfully with aspirin: A case report

    Science.gov (United States)

    Agrawal, Neha; Santra, Tuhin; Kar, Arnab; Guha, Pradipta; Bar, Mita; Adhikary, Apu; Datta, Sumana

    2016-01-01

    Background: Deep vein thrombosis is an important cause of morbidity and mortality. However, its association with adenomatous polyposis coli is extremely rare. Here we present an interesting case of deep vein thrombosis associated with adenomatous polyposis coli. Case Presentation: A 15 year old female who was having fever and diarrhea for 5 months developed bilateral asymmetric painful swelling of lower limbs for 1 month. Doppler ultrasound of lower limbs revealed presence of thrombosis from inferior vena cava up to popliteal vein. Colonoscopy and biopsy were suggestive of adenomatous polyposis coli. However, she could not tolerate anticoagulant therapy and was put on aspirin therapy for 6 months to which she responded well with the resolution of thrombus. Conclusion: Role of aspirin therapy may be considered whenever a patient of venous thrombosis cannot tolerate anticoagulant therapy.

  7. Deep vein thrombosis in a patient of adenomatous polyposis coli treated successfully with aspirin: A case report

    Science.gov (United States)

    Agrawal, Neha; Santra, Tuhin; Kar, Arnab; Guha, Pradipta; Bar, Mita; Adhikary, Apu; Datta, Sumana

    2016-01-01

    Background: Deep vein thrombosis is an important cause of morbidity and mortality. However, its association with adenomatous polyposis coli is extremely rare. Here we present an interesting case of deep vein thrombosis associated with adenomatous polyposis coli. Case Presentation: A 15 year old female who was having fever and diarrhea for 5 months developed bilateral asymmetric painful swelling of lower limbs for 1 month. Doppler ultrasound of lower limbs revealed presence of thrombosis from inferior vena cava up to popliteal vein. Colonoscopy and biopsy were suggestive of adenomatous polyposis coli. However, she could not tolerate anticoagulant therapy and was put on aspirin therapy for 6 months to which she responded well with the resolution of thrombus. Conclusion: Role of aspirin therapy may be considered whenever a patient of venous thrombosis cannot tolerate anticoagulant therapy. PMID:27386068

  8. The Helicobacter Eradication Aspirin Trial (HEAT: A Large Simple Randomised Controlled Trial Using Novel Methodology in Primary Care

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    Jennifer S. Dumbleton

    2015-09-01

    Discussion: HEAT is important medically, because aspirin is so widely used, and methodologically, as a successful trial would show that large-scale studies of important clinical outcomes can be conducted at a fraction of the cost of those conducted by industry, which in turn will help to ensure that trials of primarily medical rather than commercial interest can be conducted successfully in the UK.

  9. Preventive Effect of Aspirin Eugenol Ester on Thrombosis in κ-Carrageenan-Induced Rat Tail Thrombosis Model.

    Science.gov (United States)

    Ma, Ning; Liu, Xi-Wang; Yang, Ya-Jun; Li, Jian-Yong; Mohamed, Isam; Liu, Guang-Rong; Zhang, Ji-Yu

    2015-01-01

    Based on the prodrug principle, aspirin eugenol ester (AEE) was synthesized, which can reduce the side effects of aspirin and eugenol. As a good candidate for new antithrombotic and anti-inflammatory medicine, it is essential to evaluate its preventive effect on thrombosis. Preventive effect of AEE was investigated in κ-carrageenan-induced rat tail thrombosis model. AEE suspension liquids were prepared in 0.5% sodium carboxymethyl cellulose (CMC-Na). AEE was administrated at the dosage of 18, 36 and 72 mg/kg. Aspirin (20 mg/kg), eugenol (18 mg/kg) and 0.5% CMC-Na (30 mg/kg) were used as control drug. In order to compare the effects between AEE and its precursor, integration of aspirin and eugenol group (molar ratio 1:1) was also designed in the experiment. After drugs were administrated intragastrically for seven days, each rat was injected intraperitoneally with 20 mg/kg BW κ-carrageen dissolved in physiological saline to induce thrombosis. The length of tail-thrombosis was measured at 24 and 48 hours. The blank group just was given physiological saline for seven days without κ-carrageenan administrated. The results indicated that AEE significantly not only reduced the average length of thrombus, PT values and FIB concentration, but also reduced the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT) and platelet (PLT). The effects of AEE on platelet aggregation and anticoagulant in vitro showed that AEE could inhibit adenosine diphosphate (ADP)-induced platelet aggregation as dose-dependence but no notable effect on blood clotting. From these results, it was concluded that AEE possessed positive effect on thrombosis prevention in vivo through the reduction of FIB, PLT, inhibition of platelet aggregation and the change of TT and PT values.

  10. Adherence to the preventive strategies for nonsteroidal anti-inflammatory drug- or low-dose aspirin-induced gastrointestinal injuries

    OpenAIRE

    Fujita, Tsuyoshi; Kutsumi, Hiromu; Sanuki, Tsuyoshi; Hayakumo, Takanobu; Azuma, Takeshi

    2013-01-01

    As the aging of the population advances, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or low-dose aspirin (LDA) is increasing. Their use is accompanied by a risk of serious complications, such as hemorrhage or perforation of the gastrointestinal tract. Therefore, gastroprotective strategies upon the prescription of NSAIDs/LDA are outlined in several guidelines or recommendations. Because all NSAIDs including cyclooxygenase (COX)-2 inhibitors have cardiovascular (CV) toxicity, ...

  11. Antiulcer activity of water soaked Glycine max L. grains in aspirin induced model of gastric ulcer in Wistar rats

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    Dushyant Kumar

    2013-01-01

    Full Text Available Introduction: Glycine max L. with Drakshasava, widely used by traditional healers as a formulation for the treatment of peptic ulcer in rural northern Karnataka in India, appears to be effective as assessed by patients and in our previously published research work of traditionally used formulation. Aim: The present study was undertaken to evaluate the safety and efficacy of the overnight water soaked G. max grains. This is one of the components of traditional formulation. The study, approved by Institutional Animal Ethics Committee was carried out in male Wistar rats after assessing its toxicity in mice. Materials and Methods: Four groups of rats (n = 6 in each group were treated with aspirin 200 mg/kg oral. In addition to aspirin control group received normal saline, standard group received 20 mg/kg omeprazole and 3 rd and 4 th group received G. max 250 and 500 mg/kg, respectively. All treatments were administered orally every 24 h for 7 days. After 24 hours fasting, on the 8 th day stomach contents were aspirated under anesthesia to estimate free and total acidity. Stomachs were opened along the greater curvature to calculate ulcer index and subjected to histopathology studies. Statistics: The results were analyzed by one-way analysis of variance followed-by Dunnett′s post hoc test. P ≤0.05 was considered as significant. Results: The severity of aspirin induced ulceration was found significantly (P < 0.05 decreased in test groups compared with the control group. Free and total acidity was significantly reduced in 500 mg/kg treated group, compared with the control group and was inferior to omeprazole treated group. Conclusion: The grain of G. max was found to be effective against aspirin induced ulcers.

  12. Assessment of the Prophylactic Role of Aspirin and/or Clopidogrel on Experimentally Induced Acute Myocardial Infarction in Hypercholesterolemic Rats

    OpenAIRE

    Mohamed, Adham R.; Wessam F. El-Hadidy; Mannaa, Hazem F.

    2014-01-01

    Introduction Hyperlipidemia is a risk factor for cardiovascular diseases such as acute infarction. Inflammation and platelet activation are critical phenomena in acute myocardial infarction (AMI). Aim The aim of the study was to assess potential protective effects of aspirin and/or clopidogrel on AMI in hypercholesterolemic rats. Methods Forty adult male Wistar rats were divided into five groups (eight rats in each). Group I included normal healthy rats. The other 32 rats were subjected to in...

  13. A novel porous aspirin-loaded (GO/CTS-HA)n nanocomposite films: Synthesis and multifunction for bone tissue engineering.

    Science.gov (United States)

    Ji, Mingxiang; Li, Han; Guo, Hailin; Xie, Anjian; Wang, Shaohua; Huang, Fangzhi; Li, Shikuo; Shen, Yuhua; He, Jiacai

    2016-11-20

    A novel porous graphene oxide (GO)/chitosan (CTS)-hydroxyapatite (HA) nanocomposite film was successfully prepared for the first time by combining layer-by-layer (LBL) assembly technology with biomimetic mineralization method. The LBL technology was used to control the thickness of film as well as induce the biomimetic mineralization of biocompatible HA. The obtained (GO/CTS-HA)n film provided ideal platform for the proliferation of mouse mesenchymal stem cells (mMSCs). The pore size in the film is about 300nm, and the porous architecture made the film have high aspirin loading efficiency. Also the accumulated loading dosage could be adjusted by the film thickness, and the sustained release of aspirin could ensure well anti-inflammatory effect. The above advantages may alleviate the pain of patients and give the better environment for bone regeneration. This multifunctional aspirin-loaded (GO/CTS-HA)n film provided an inspiration for the synthesis of novel porous inorganic/biomacromolecule nanocomposite films as the biocoatings applied in bone tissue engineering. PMID:27561479

  14. DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR THE SIMULTANEOUS ESTIMATION OF ROSUVASTATIN CALCIUM AND ASPIRIN IN MARKETED FORMULATION

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    Godavariya Vijay D

    2012-08-01

    Full Text Available A simple, specific, accurate and precise reverse phase high pressure liquid chromatographic method has been developed for the simultaneous determination of Rosuvastatin calcium and Aspirin from Capsule dosage forms using C18 column (¬Grace Smart (250mm x 4.6mm, 5 µm. The sample was analyzed using Water (0.5 ml tri-ethyl amine in 100mL of double distilled water: Acetonitrile in the ratio of 50:50(% v/v pH adjusted to 4.0 with orthophosphoric acid, as a mobile phase at a flow rate of 1.0 mL/min and detection at 243 nm. The retention time for Rosuvastatin calcium and Aspirin was found to be 4.30 and 3.44 min respectively. The method can be used for estimation of combination of these drugs in capsules. The method was validated as per ICH guidelines. The linearity of developed method was achieved in the range of 6 – 14 μg/mL (r2=0.9997 for Rosuvastatin calcium and 45 – 105 μg/mL (r2=0.9989 for Aspirin and assay of capsules were between 98.0-102.0%. Due to these attributes, the proposed method could be used for routine quality control analysis of these drugs in combined dosage forms.

  15. Effect of atorvastatin combine with aspirin on flammatory factors, endothelial function and the cardiovascular complications with diabetic patients

    Institute of Scientific and Technical Information of China (English)

    Hong Wang; Ping Gong

    2016-01-01

    Objective:To investigate the effect of atorvastatin combine with aspirin on flammatory factors, endothelial function and the cardiovascular complications with diabetic patients.Methods:A total of 85 type 2 diabetic patients were randomly divided into observation group (43 cases) and control group (42 cases). All patients recieved routine treatment of hypoglycemic drug, while patients in observation group also received atorvastatin and aspirin. Levels of blood lipid, flammatory factors (hs-CRP, TNF-α, IL-6) endothelial function(ET-1,NO), and incidence of cardiovascular complications were tested and compared.Results:Blood lipid have statistical significance after treatment between two groups, TC, TG, LDL-C were significantly lower in observation group, HDL-C was significantly higher in observation group (P <0.05). Observation group flammatory factors (hs-CRP, TNF-α, IL-6) levels decreased significantly after treatment (P<0.05); Observation group ET-1 level decreased significantly, NO level increased significantly after treatment (P<0.05); Incidence of cardiovascular complications was lower than control group in observation group.Conclusions:Atorvastatin combine with aspirin treatment has reliable curative effect in diabetic patients, which can regulate flammatory factors, endothelial function and incidence of cardiovascular complications.

  16. Decision-making in an era of cancer prevention via aspirin: New Zealand needs updated guidelines and risk calculators.

    Science.gov (United States)

    Wilson, Nick; Selak, Vanessa; Blakely, Tony; Leung, William; Clarke, Philip; Jackson, Rod

    2016-03-11

    Based on new systematic reviews of the evidence, the US Preventive Services Task Force has drafted updated guidelines on the use of low-dose aspirin for the primary prevention of both cardiovascular disease (CVD) and cancer. The Task Force generally recommends consideration of aspirin in adults aged 50-69 years with 10-year CVD risk of at least 10%, in who absolute health gain (reduction of CVD and cancer) is estimated to exceed absolute health loss (increase in bleeds). With the ongoing decline in CVD, current risk calculators for New Zealand are probably outdated, so it is difficult to be precise about what proportion of the population is in this risk category (roughly equivalent to 5-year CVD risk ≥5%). Nevertheless, we suspect that most smokers aged 50-69 years, and some non-smokers, would probably meet the new threshold for taking low-dose aspirin. The country therefore needs updated guidelines and risk calculators that are ideally informed by estimates of absolute net health gain (in quality-adjusted life-years (QALYs) per person) and cost-effectiveness. Other improvements to risk calculators include: epidemiological rigour (eg, by addressing competing mortality); providing enhanced graphical display of risk to enhance risk communication; and possibly capturing the issues of medication disutility and comparison with lifestyle changes. PMID:27005878

  17. Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily). Effects on platelet aggregation and thromboxane formation.

    Science.gov (United States)

    Lorenz, R L; Schacky, C V; Weber, M; Meister, W; Kotzur, J; Reichardt, B; Theisen, K; Weber, P C

    1984-06-01

    Prevention of aortocoronary bypass occlusion by aspirin (ASA, 1 X 100 mg per day) was studied in a prospective double-blind trial of 83 patients. 60 (72%) were randomly allocated to ASA or placebo starting 24 h after operation. 90% of grafts in the ASA group and 68% in the placebo group were patent at four months. At least one anastomosis was occluded in 62% of the patients on placebo and in 27% of those on aspirin. Ventricular arrhythmias increased after surgery in more patients on placebo (12/18) than in patients on ASA (5/17). Platelet thromboxane formation on collagen tested before operation was significantly higher in patients in whom bypass occlusion developed (occlusion: 40 +/- 19, no occlusion: 25 +/- 13 ng/ml). A 100 mg dose of ASA per day effectively blocked platelet thromboxane formation and thromboxane-supported aggregation on collagen and was safe in the postoperative phase. No side effects were reported throughout the trial. The reduced toxicity with full efficacy favours a low and infrequent dosage of aspirin. PMID:6144975

  18. Effects of combining low‑dose aspirin with a Chinese patent medicine on follicular blood flow and pregnancy outcome.

    Science.gov (United States)

    Zhao, Yue; Du, Botao; Jiang, Xiaoying; Ma, Mingxing; Shi, Liqing; Zhang, Qinxi; Zhou, Lili

    2014-11-01

    The aim of the present study was to investigate the clinical value of low‑dose aspirin in combination with Tiao Jing Cu Yun pills in patients with polycystic ovary syndrome (PCOS) by measuring follicular peripheral blood flow parameters and the clinical efficacy. The study involved 78 infertile females with PCOS who were randomly divided into experimental (n=38) and control (n=40) groups. The subjects in the experimental group were treated with letrozole in combination with aspirin and Tiao Jing Cu Yun pills, and the control group was treated with letrozole alone. Transvaginal color Doppler ultrasonography was used to measure the endometrial thickness, pulsatility index (PI), resistance index (RI), peak systolic velocity and end diastolic velocity (EDV) of the follicular peripheral artery on the day of human chorionic gonadotropin administration. The patients who failed to become pregnant in the control group were reintegrated into the experimental group in the subsequent cycle and the clinical effect was observed. In the experimental group, subject perifollicular blood flow was more plentiful, and the PI and RI of the perifollicular blood flow were significantly reduced, while the EDV of the perifollicular blood flow and the rate of clinical pregnancy were markedly elevated compared with the subjects in the control group. Low‑dose aspirin combined with Tiao Jing Cu Yun pills effectively improved perifollicular artery blood flow, and enhanced the oocyte quality and rate of clinical pregnancy. PMID:25230733

  19. Aspirin for primary prevention of cardiovascular events: meta-analysis of randomized controlled trials and subgroup analysis by sex and diabetes status.

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    Manling Xie

    Full Text Available To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status.We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12.Fourteen trials (107,686 participants were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85-0.95, myocardial infarction (0.86; 0.75-0.93, ischemic stroke (0.86; 0.75-0.98 and all-cause mortality (0.94; 0.89-0.99. There were also increases in hemorrhagic stroke (1.34; 1.01-1.79 and major bleeding (1.55; 1.35-1.78 with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59-0.85 and ischemic stroke among women (0.77; 0.63-0.93. Aspirin use was associated with a reduction (0.65; 0.51-0.82 in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day were as large as those obtained with higher doses (650 mg/day.The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials.

  20. The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2 with aspirin insensitivity: a meta-analysis.

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    Zhiyuan Weng

    Full Text Available OBJECTIVE: Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643 from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2 with aspirin insensitivity via a meta-analysis. METHODS AND RESULTS: In total, there were 4 (353/595, 6 (344/698, 10 (588/878 and 7 (209/676 articles (patients/controls qualified for rs3842787, rs20417, rs20118426 and rs1126643, respectively. The data were extracted in duplicate and analyzed by STATA software (Version 11.2. The risk estimate was expressed as odds ratio (OR and 95% confidence interval (95% CI. Analyses of the full data set indicated significant associations of rs20417 (OR; 95% CI; P: 1.86; 1.44-2.41; <0.0005 and rs1126643 (2.37; 1.44-3.89; 0.001 with aspirin insensitivity under allelic model. In subgroup analyses, the risk estimate for rs1126643 was greatly potentiated among patients with aspirin semi-resistance relative to those with aspirin resistance, especially under dominant model (aspirin semi-resistance: 5.44; 1.42-20.83; 0.013 versus aspirin resistance: 1.96; 1.07-3.6; 0.03. Further grouping articles by ethnicity observed a stronger prediction of all, but rs20417, examined polymorphisms for aspirin insensitivity in Chinese than in Caucasians. Finally, meta-regression analyses observed that the differences in percentage of coronary artery disease (P = 0.034 and averaged platelet numbers (P = 0.012 between two groups explained a large part of heterogeneity for rs20417 and rs1126643, respectively. CONCLUSION: Our findings provide strong evidence that COX-2 and ITGA2 genetic defects might increase the risk of having aspirin insensitivity, especially for aspirin semi-resistance and in Chinese populations.

  1. 氯吡格雷对阿司匹林抵抗的影响%Clopidogrel influence on Aspirin Resistance

    Institute of Scientific and Technical Information of China (English)

    黄壮光; 陈亮波

    2009-01-01

    目的 研究所氯吡格雷对冠心病患者阿司匹林抵抗的影响.方法 筛选出冠心病患者中发生阿司匹林抵抗的患者58例入选本研究,随机分为对照组和氯吡格雷组,分别给予阿司匹林100 mg+安慰剂每天和阿司匹林100mg+氯吡格雷75mg每天,14天后采用全血电阻法检测血小板聚集功能.结果 与对照组相比,氯吡格雷组使ADP(二磷酸腺苷)诱导的血小板聚集功能显著抑制[(1.3±0.48)Ω比(12.8±2.5)Ω],P0.05.结论 合用氯吡格雷不能完全改善冠心痛患者的阿斯匹林抵抗,对这部分患者应加强综合治疗.%Objective To study effects of clopidogrel on aspirin resistance of patients with coronary atherosclerotic heart disease.Methods 58 patients with coronary atherosclerotic heart disease who were diagnosed aspirin resistance were randomly divided into control group and clopidogrel group,which were given aspirin 100mg +placebo per day and aspirin 100mg+clopigrel 75mg per day respectively.The platelet aggregation was ana-lyzed by the method of whole blood electric resistance.Results The platelet aggregation function induced by adenosine diphosphate (ADP) was suppressed significantly by clopdogrel group contrast to control group [(1.3±0.48) Ω vs (12.8±2.5) Ω,PO.O5].Conclusions Clopidogrel can't retrieve aspirin resistance of patients with coronary heart disease completely,they should be strengthened combination therapy.

  2. Association Between the P2RY12 Receptor Gene Polymorphism and Aspirin Resistance in Patients with Coronary Artery Disease

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    Ludmila Karazhanova

    2014-12-01

    Full Text Available Introduction. Platelet activation and aggregation are key elements in the development of coronary atherosclerosis. Recent studies have shown that the two polymorphisms of platelet ADP receptor P2RY12 (haplotypes H2 and 34T are associated with increased platelet aggregation and atherothrombotic risk. It was shown that these polymorphisms promote reduced body response to antiplatelet therapy.Aim. We investigated the association of P2RY12 gene polymorphisms with aspirin resistance in patients with coronary artery disease (CAD.Methods. This case-control study included 100 cases with CAD (mean age 57.6 ± 2.8 years treated in the cardiology department of the city hospital Semey, Kazakhstan, 90 of whom suffered from myocardial infarction. The control group (n = 100 were healthy people without a history of CAD, matched on sex and age. Genotyping of polymorphisms H1/H2 in P2RY12 gene was performed by PCR. Statistical analysis was performed using SPSS v.19.0.Results. The distribution of H1/H2 genotypes P2RY12 was 42%, 34%, and 24%, respectively, in cases and 42%, 58%, and 0%, respectively, in controls. All allele frequencies were consistent with the Hardy Weinberg equilibrium (p = 0.0036 and p = 0.0001 in cases and controls, respectively. Genotype H2 was associated with risk of CAD with aspirin resistance (co-dominant model: OR = 3.75, 95% CI 0.14 - 99.88, p = 0.05 and dominant model: OR = 2.78, 95% CI 0.11 - 70.93, p = 0.05. We found significant differences in the distribution of the mutant genotype H2 between CAD patients with aspirin resistance and healthy controls (χ2 = 30.3, p < 0.05.Conclusion. We found an association of H2 haplotype in P2RY12 gene with aspirin resistance in patients with CAD. However, in order to obtain definitive conclusions about the role of genetic variants with the development of aspirin resistance in patients with CAD, there is a need for further research with a larger sample size as well as the use of selective thromboxane

  3. Incidence and predictors of upper gastrointestinal bleeding in patients receiving low-dose aspirin for secondary prevention of cardiovascular events in patients with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    William Ng; Xi Cheng; Chu-Pak Lau; Wai-Man Wong; Wai-Hong Chen; Hung-Fat Tse; Pui-Yin Lee; Kam-Chuen Lai; Sheung-Wai Li; Matthew Ng; Kwok-Fai Lam

    2006-01-01

    AIM: The use of low-dose aspirin to prevent cardiovascular disease events is well established. However,the incidence and predictors of upper gastrointestinal bleeding (UGIB) with its use are unknown. We studied prospectively the incidence and outcome of peptic ulceration in low-dose aspirin users.METHODS: A total of 991 patients with coronary artery disease (CAD) on low-dose aspirin were prospectively followed-up for two years for the occurrence and clinical features of first hospitalized episode of UGIB.RESULTS: UGIB had a bimodal presentation with 45% occurring within four months of aspirin initiation and had an overall prevalence of 1.5% per year. There was no UGIB-related death. Hypertension (OR = 4.6, 95%CI 1.5 - 14.7, P = 0.009), history of peptic ulceration (OR = 3.1,95%CI 1.1 - 9.0, P = 0.039), tertiary education (OR =3.08, 95%CI 1.1 - 9.0, P = 0.039) and higher lean body mass (P = 0.016) were independent factors associated with UGIB. Use of nitrate did not reduce UGIB.CONCLUSION: The incidence of UGIB in patients with CAD on long-term low-dose aspirin is low, but is accompanied with significant morbidity. With prolonged use of aspirin, UGIB continues to be a problem for those with risk factors and especially in patients with a history of peptic ulcers, in which UGIB tends to occur early after aspirin therapy.

  4. Cooperative antiproliferative signaling by aspirin and indole-3-carbinol targets microphthalmia-associated transcription factor gene expression and promoter activity in human melanoma cells.

    Science.gov (United States)

    Poindexter, Kevin M; Matthew, Susanne; Aronchik, Ida; Firestone, Gary L

    2016-04-01

    Antiproliferative signaling of combinations of the nonsteroidal anti-inflammatory drug acetylsalicylic acid (aspirin) and indole-3-carbinol (I3C), a natural indolecarbinol compound derived from cruciferous vegetables, was investigated in human melanoma cells. Melanoma cell lines with distinct mutational profiles were sensitive to different extents to the antiproliferative response of aspirin, with oncogenic BRAF-expressing G361 cells and wild-type BRAF-expressing SK-MEL-30 cells being the most responsive. I3C triggered a strong proliferative arrest of G361 melanoma cells and caused only a modest decrease in the proliferation of SK-MEL-30 cells. In both cell lines, combinations of aspirin and I3C cooperatively arrested cell proliferation and induced a G1 cell cycle arrest, and nearly ablated protein and transcript levels of the melanocyte master regulator microphthalmia-associated transcription factor isoform M (MITF-M). In melanoma cells transfected with a -333/+120-bp MITF-M promoter-luciferase reporter plasmid, treatment with aspirin and I3C cooperatively disrupted MITF-M promoter activity, which accounted for the loss of MITF-M gene products. Mutational analysis revealed that the aspirin required the LEF1 binding site, whereas I3C required the BRN2 binding site to mediate their combined and individual effects on MITF-M promoter activity. Consistent with LEF1 being a downstream effector of Wnt signaling, aspirin, but not I3C, downregulated protein levels of the Wnt co-receptor LDL receptor-related protein-6 and β-catenin and upregulated the β-catenin destruction complex component Axin. Taken together, our results demonstrate that aspirin-regulated Wnt signaling and I3C-targeted signaling pathways converge at distinct DNA elements in the MITF-M promoter to cooperatively disrupt MITF-M expression and melanoma cell proliferation. PMID:27055402

  5. Aspirin Modulates Innate Inflammatory Response and Inhibits the Entry of Trypanosoma cruzi in Mouse Peritoneal Macrophages

    Directory of Open Access Journals (Sweden)

    Aparecida Donizette Malvezi

    2014-01-01

    Full Text Available The intracellular protozoan parasite Trypanosoma cruzi causes Chagas disease, a serious disorder that affects millions of people in Latin America. Cell invasion by T. cruzi and its intracellular replication are essential to the parasite’s life cycle and for the development of Chagas disease. Here, we present evidence suggesting the involvement of the host’s cyclooxygenase (COX enzyme during T. cruzi invasion. Pharmacological antagonist for COX-1, aspirin (ASA, caused marked inhibition of T. cruzi infection when peritoneal macrophages were pretreated with ASA for 30 min at 37°C before inoculation. This inhibition was associated with increased production of IL-1β and nitric oxide (NO∙ by macrophages. The treatment of macrophages with either NOS inhibitors or prostaglandin E2 (PGE2 restored the invasive action of T. cruzi in macrophages previously treated with ASA. Lipoxin ALX-receptor antagonist Boc2 reversed the inhibitory effect of ASA on trypomastigote invasion. Our results indicate that PGE2, NO∙, and lipoxins are involved in the regulation of anti-T. cruzi activity by macrophages, providing a better understanding of the role of prostaglandins in innate inflammatory response to T. cruzi infection as well as adding a new perspective to specific immune interventions.

  6. Variability in the pharmacokinetics and pharmacodynamics of low dose aspirin in healthy male volunteers.

    Science.gov (United States)

    Benedek, I H; Joshi, A S; Pieniaszek, H J; King, S Y; Kornhauser, D M

    1995-12-01

    Data describing the pharmacokinetics and pharmacodynamics of low dose aspirin (acetylsalicylic acid; ASA) are limited. This single-center study was designed to determine the rate and extent of oral absorption of 80-mg ASA tablets in healthy, young male subjects and to assess the intra- and inter-subject variability of ASA pharmacokinetics and platelet aggregation effects. Ten subjects each received a single, open-label, oral 80-mg ASA dose on three separate days. Each dose was separated by a 2-week washout interval. Blood samples for pharmacokinetic determinations of ASA and its metabolite, salicylic acid (SA) and platelet aggregation studies were obtained at scheduled timepoints before and up to 24 hours after each dose. Peak plasma ASA levels of 1 microgram/mL were achieved within 30 minutes. Peak plasma SA levels of approximately 4 micrograms/mL were attained in 1 hour. The terminal half-lives (t1/2) of ASA and SA were 0.4 and 2.1 hours, respectively. Both ASA and SA pharmacokinetics and the platelet aggregation response to ASA exhibited considerable intra- and inter-subject variability. Inhibition of platelet aggregation was found to relate with ASA area under the plasma concentration versus time curve (AUC). PMID:8750369

  7. β-Cyclodextrin inclusion complex: preparation, characterization, and its aspirin release in vitro

    Science.gov (United States)

    Zhou, Hui-Yun; Jiang, Ling-Juan; Zhang, Yan-Ping; Li, Jun-Bo

    2012-09-01

    In this work, the optimal clathration condition was investigated for the preparation of aspirin-β-cyclodextrin (Asp-β-CD) inclusion complex using design of experiment (DOE) methodology. A 3-level, 3-factor Box-Behnken design with a total of 17 experimental runs was used. The Asp-β-CD inclusion complex was prepared by saturated solution method. The influence on the embedding rate was investigated, including molar ratio of β-CD to Asp, clathration temperature and clathration time, and the optimum values of such three test variables were found to be 0.82, 49°C and 2.0 h, respectively. The embedding rate could be up to 61.19%. The formation of the bonding between -COOH group of Asp and O-H group of β-CD might play an important role in the process of clathration according to FT-IR spectra. Release kinetics of Asp from inclusion complex was studied for the evaluation of drug release mechanism and diffusion coefficients. The results showed that the drug release from matrix occurred through Fickian diffusion mechanism. The cumulative release of Asp reached only 40% over 24 h, so the inclusion complex could potentially be applied as a long-acting delivery system.

  8. Structure, molecular simulation, and release of aspirin from intercalated Zn-Al-layered double hydroxides.

    Science.gov (United States)

    Meng, Zilin; Li, Xiaowei; Lv, Fengzhu; Zhang, Qian; Chu, Paul K; Zhang, Yihe

    2015-11-01

    Aspirin or acetylsalicylic acid (AA), a non-steroidal anti-inflammatory drug, is intercalated into Zn-Al-layered double hydroxides (ZnAl-LDHs) by co-precipitation and reconstruction methods. The composition, structure, and morphology of the intercalated products as well as their release behavior are determined experimentally and theoretically by Material Studio 5.5. Experimental results disclose the strong interaction between the LDHs sheets and AA in the intercalated ZnAl-LDHs produced by co-precipitation and slow release of AA from the intercalated ZnAl-LDHs in both phosphate buffered saline (PBS) and borate buffered saline (BBS) solutions. The percentage of AA released from the ZnAl-LDHs prepared by both methods in PBS (96.87% and 98.12%) are much more than those in BBS (68.59% and 81.22%) implying that both H4BO4(-) and H2PO4(-) can exchange with AA in the ZnAl-LDHs. After AA is released to PBS, ZnAl-LDHs break into small pieces. The experimental results are explained theoretically based on the calculation of the bonding energy between the anions and LDHs sheets as well as the AlO bond length change in the LDHs sheets. PMID:26263219

  9. Chinese Herbal Medicine for Aspirin Resistance: A Systematic Review of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Ai-ju Liu

    2014-01-01

    Full Text Available Aspirin resistance (AR is a prevalent phenomenon and leads to significant clinical consequences, but the current evidence for effective interventional strategy is insufficient. The objective of this systematic review is thus to assess the efficacy and safety of Chinese herbal medicine (CHM for AR. A systematical literature search was conducted in 6 databases until December 2012 to identify randomized controlled trials (RCTs of CHM for AR. As a result, sixteen RCTs with a total of 1011 subjects were identified, suggesting that the interests of the medical profession and the public in the use of CHM for AR have grown considerably in the recent years. Tongxinluo capsule and Danshen-based prescriptions were the most frequently used herbal prescriptions, while danshen root, milkvetch root, Leech, and Rosewood were the most frequently used single herbs. Despite the apparent reported positive findings, it is premature to determine the efficacy and safety of CHM for the treatment of AR due to poor methodological quality and insufficient safety data. However, CHMs appeared to be well tolerated in all included studies. Thus, CHM as a promising candidate is worthy of improvement and development for further clinical AR trials. Large sample-size and well-designed rigorous RCTs are needed.

  10. Human GAPDH Is a Target of Aspirin's Primary Metabolite Salicylic Acid and Its Derivatives.

    Science.gov (United States)

    Choi, Hyong Woo; Tian, Miaoying; Manohar, Murli; Harraz, Maged M; Park, Sang-Wook; Schroeder, Frank C; Snyder, Solomon H; Klessig, Daniel F

    2015-01-01

    The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA's multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson's drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA) and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice), glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death.

  11. Insights into and relative effect of chitosan-krill oil, chitosan-H-aspirin, chitosan-H-krill oil-nystatin and chitosan-H-krill oil-aspirin-nystatin on dentin bond strength and functional drug delivery capacity: In-vitro studies

    Directory of Open Access Journals (Sweden)

    Victoria Tamara Perchyonok

    2014-01-01

    Full Text Available Background: Restorative materials in the new era aim to be "bio-active" and long-lasting. The purpose of this study was to design and to evaluate a novel chitosan hydrogels containing krill oil (antioxidant containing material, nystatin (antifungal, aspirin (pain relieve medication and free radical scavengers and combinations thereof (chitosan-H-krill oil, chitosan-H-krill oil-nystatin and chitosan-H-aspirin, chitosan-H-aspirin-nystatin, chitosan-H-krill oil-aspirin and chitosan-H-krill oil-aspirin-nystatin as functional additive prototypes for further development of "dual function restorative materials," and secondly to determine their effect on the dentin bond strength of a composite. Materials and Methods: The above-mentioned hydrogels were prepared by dispersion the corresponding component in glycerol and acetic acid with the addition of chitosan gelling agent. The surface morphology (scanning electron microscope (SEM, release behaviors (physiological pH and also in acidic conditions, stability of the therapeutic agent-antioxidant-chitosan and the effect of the hydrogels on the shear bond strength of dentin were also evaluated. Results: The release of nystatin and aspirin confer the added benefit of synergistic action of a functional therapeutic delivery when comparing the newly designed chitosan-based hydrogel restorative materials to the commercially available products alone. Neither the release of nystatin and aspirin nor the antioxidant stability was affected by storage over a 6 month period. The hydrogel formulations have a uniform distribution of drug content, homogenous texture and yellow color (SEM study. All chitosan dentin treated hydrogels gave significantly (P<0.05; non-parametric ANOVA test higher shear bond values (P<0.05 than dentin treated or not treated with phosphoric acid. Conclusion: The added benefits of the chitosan treated hydrogels involved positive influence on the nystatin and aspirin release as well as increased

  12. Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639

    Directory of Open Access Journals (Sweden)

    Gasparovic Hrvoje

    2012-08-01

    Full Text Available Abstract Background Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive. The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events. Methods Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology as well as bleeding events will be recorded. Discussion This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management. This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639.

  13. Competing intermolecular interactions of artemisinin-type agents and aspirin with membrane phospholipids: Combined model mass spectrometry and quantum-chemical study

    Energy Technology Data Exchange (ETDEWEB)

    Pashynska, Vlada, E-mail: vlada@vl.kharkov.ua [B.Verkin Institute for Low Temperature Physics and Engineering of the National Academy of Sciences of Ukraine, Lenin Ave., 47, 61103 Kharkov (Ukraine); Stepanian, Stepan [B.Verkin Institute for Low Temperature Physics and Engineering of the National Academy of Sciences of Ukraine, Lenin Ave., 47, 61103 Kharkov (Ukraine); Gömöry, Agnes; Vekey, Karoly [Institute of Organic Chemistry of Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Magyar tudosok korutja, 2, Budapest H-1117 (Hungary); Adamowicz, Ludwik [University of Arizona, Department of Chemistry and Biochemistry, Tucson, AZ 85721 (United States)

    2015-07-09

    Highlights: • Competitive binding of artemisinin agents and aspirin with phospholipids is shown. • Complexation between the antimalarial drugs and aspirin molecules is also found. • Energetically favorable structures of the model complexes are identified by DFT. • Membranotropic activity of the studied drugs can be modified under joint usage. - Abstract: Study of intermolecular interactions of antimalarial artemisinin-type drugs and aspirin with membrane phospholipids is important in term of elucidation of the drugs activity modification under their joint usage. Combined experimental and computational study of the interaction of dihydroartemisinin, α-artemether, and artesunate with aspirin (ASP) and dipalmitoylphosphatidylcholine (DPPC) is performed by electrospray ionization (ESI) mass spectrometry and by DFT B3LYP/aug-cc-pVDZ methods. The results of the ESI investigation of systems containing artemisinin-type agent, ASP and DPPC, reveal a competition between the antimalarial agents and ASP for binding with DPPC molecules. The complexation between the antimalarial drugs and ASP is also found. Observed phenomena suggest that membranotropic activity of artemisin-type agents and aspirin is modified under their combined usage. To elucidate structure-energy characteristics of the non-covalent complexes studied the model DFT calculations are performed for dihydroartemisinin · ASP complex and complexes of the each drug with phosphatidylcholine head of DPPC in neutral and cationized forms.

  14. Competing intermolecular interactions of artemisinin-type agents and aspirin with membrane phospholipids: Combined model mass spectrometry and quantum-chemical study

    International Nuclear Information System (INIS)

    Highlights: • Competitive binding of artemisinin agents and aspirin with phospholipids is shown. • Complexation between the antimalarial drugs and aspirin molecules is also found. • Energetically favorable structures of the model complexes are identified by DFT. • Membranotropic activity of the studied drugs can be modified under joint usage. - Abstract: Study of intermolecular interactions of antimalarial artemisinin-type drugs and aspirin with membrane phospholipids is important in term of elucidation of the drugs activity modification under their joint usage. Combined experimental and computational study of the interaction of dihydroartemisinin, α-artemether, and artesunate with aspirin (ASP) and dipalmitoylphosphatidylcholine (DPPC) is performed by electrospray ionization (ESI) mass spectrometry and by DFT B3LYP/aug-cc-pVDZ methods. The results of the ESI investigation of systems containing artemisinin-type agent, ASP and DPPC, reveal a competition between the antimalarial agents and ASP for binding with DPPC molecules. The complexation between the antimalarial drugs and ASP is also found. Observed phenomena suggest that membranotropic activity of artemisin-type agents and aspirin is modified under their combined usage. To elucidate structure-energy characteristics of the non-covalent complexes studied the model DFT calculations are performed for dihydroartemisinin · ASP complex and complexes of the each drug with phosphatidylcholine head of DPPC in neutral and cationized forms

  15. Decoupling the effects of surface chemistry and humidity on solid-state hydrolysis of aspirin in the presence of dicalcium phosphate dihydrate.

    Science.gov (United States)

    Cassidy, Andrew M; Gardner, Catherine E; Auffret, Tony; Aldous, Barry; Jones, William

    2012-04-01

    Atomic force microscopy (AFM) cantilevers were functionalized with particles of dicalcium phosphate dihydrate (DCP), and AFM, in force-displacement mode, was used to bring these probes into contact with aspirin (100) and (001) surfaces in order to investigate the effect of aspirin surface chemistry on the interaction between the two materials as a function of relative humidity (RH). The force of adhesion measurements showed a strong dependence on RH for the interactions between DCP and the aspirin (100) surface, with stronger interactions occurring at higher humudities. Relatively much weaker interactions were measured between DCP and the aspirin (001) surface under all RH conditions. Topographic imaging showed that contact between DCP and the aspirin (100) surface at high RH led to localised development of etch pits and, in some cases, growth normal to the surface. The methodology allows for the creation of a localised solid-solid interface between pharmaceutically relevant materials, providing a means of studying solid-state excipient-active ingredient decomposition reactions.

  16. Aspirin or Nonsteroidal Anti-inflammatory Drug-Exacerbated Chronic Rhinosinusitis.

    Science.gov (United States)

    Ledford, Dennis K; Lockey, Richard F

    2016-01-01

    Aspirin (ASA)-exacerbated respiratory disease (AERD) is characterized by upper airway congestion due to eosinophilic inflammation of the nasal and sinus membranes and nasal polyposis, associated with increased leukotriene production that is further accentuated by ASA or other nonsteroidal anti-inflammatory drug (NSAID) ingestion. It occurs in 5% to 10% of subjects with chronic rhinosinusitis (CRS) and in 15% to 40% of those with nasal polyposis. Although AERD with CRS is usually associated with asthma, this is not always the case. The eosinophilic airway inflammation and symptoms precede clinical reactions to ASA or other NSAIDs, but ultimately affected subjects experience worsening of symptoms with ingestion of ASA/NSAIDs. The endotypic mechanism for this worsening is related to a chronic increase in leukotriene and a decrease in prostaglandin production, particularly prostaglandin E2, that is further aggravated by the inhibition of cycloxgenase I. IgE does not likely play a role in the pathogenesis of the disease although nasal and sinus staphylococcal infection increases local IgE level and may increase total IgE and specific IgE levels. Genetic studies suggest that multiple genes may be involved, but the genetic abnormalities may differ in affected subjects from different ethnicities and candidate genes have not been confirmed in multiple studies. Genome-wide association studies have not been revealing. The phenotype is recognized by the mucosal inflammation and worsening of symptoms acutely with ASA/NSAID. There is clinical improvement with ASA desensitization followed by regular ingestion of ASA or other NSAIDs. Further understanding of this unique phenotype and endotype of CRS will likely improve the understanding of other eosinophilic airway diseases. PMID:27393773

  17. Human GAPDH Is a Target of Aspirin's Primary Metabolite Salicylic Acid and Its Derivatives.

    Science.gov (United States)

    Choi, Hyong Woo; Tian, Miaoying; Manohar, Murli; Harraz, Maged M; Park, Sang-Wook; Schroeder, Frank C; Snyder, Solomon H; Klessig, Daniel F

    2015-01-01

    The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA's multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson's drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA) and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice), glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death. PMID:26606248

  18. Human GAPDH Is a Target of Aspirin's Primary Metabolite Salicylic Acid and Its Derivatives.

    Directory of Open Access Journals (Sweden)

    Hyong Woo Choi

    Full Text Available The plant hormone salicylic acid (SA controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA's multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs. Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH from plants (Arabidopsis thaliana was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson's drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice, glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death.

  19. A spectroscopic study of phenylbutazone and aspirin bound to serum albumin in rheumatoid diseases

    Science.gov (United States)

    Maciążek-Jurczyk, M.; Sułkowska, A.; Bojko, B.; Równicka-Zubik, J.; Sułkowski, W. W.

    2011-11-01

    Interaction of phenylbutazone (PBZ) and aspirin (ASA), two drugs recommended in rheumatoid diseases (RDs), when binding to human (HSA) and bovine (BSA) serum albumins, has been studied by quenching of fluorescence and proton nuclear magnetic resonance ( 1HNMR) techniques. On the basis of spectrofluorescence measurements high affinity binding sites of PBZ and ASA on albumin as well as their interaction within the binding sites were described. A low affinity binding site has been studied by proton nuclear magnetic resonance spectroscopy. Using fluorescence spectroscopy the location of binding site in serum albumin (SA) for PBZ and ASA was found. Association constants Ka were determined for binary (i.e. PBZ-SA and ASA-SA) and ternary complexes (i.e. PBZ-[ASA]-SA and ASA-[PBZ]-SA). PBZ and ASA change the affinity of each other to the binding site in serum albumin (SA). The presence of ASA causes the increase of association constants KaI of PBZ-SA complex. Similarly, PBZ influences KaI of ASA-SA complex. This phenomenon shows that the strength of binding and the stability of the complexes increase in the presence of the second drug. The decrease of KaII values suggests that the competition between PBZ and ASA in binding to serum albumin in the second class of binding sites occurs. The analysis of 1HNMR spectral parameters i.e. changes of chemical shifts and relaxation times of the drug indicate that the presence of ASA weakens the interaction of PBZ with albumin. Similarly PBZ weakens the interaction of ASA with albumin. This conclusion points to the necessity of using a monitoring therapy owning to the possible increase of uncontrolled toxic effects.

  20. Potential of prescription registries to capture individual-level use of aspirin and other nonsteroidal anti-inflammatory drugs in Denmark

    DEFF Research Database (Denmark)

    Schmidt, Morten; Hallas, Jesper; Friis, Søren

    2014-01-01

    BACKGROUND: Due to over-the-counter availability, no consensus exists on whether adequate information on nonsteroidal anti-inflammatory drug (NSAID) use can be obtained from prescription registries. OBJECTIVES: To examine utilization of aspirin and nonaspirin NSAIDs in Denmark between 1999 and 2012...... and to quantify the proportion of total sales that was sold on prescription. METHOD: Based on nationwide data from the Danish Serum Institute and the Danish National Prescription Registry, we retrieved sales statistics for the Danish primary health care sector to calculate 1-year prevalences of...... prescription users of aspirin or nonaspirin NSAIDs, and to estimate the corresponding proportions of total sales dispensed on prescription. RESULTS: Both low-dose aspirin and nonaspirin NSAIDs were commonly used in the Danish population between 1999 and 2012, particularly among elderly individuals. The 1-year...

  1. Evaluative comparison of systemic aspirin therapy effects on gingival bleeding in post non-surgical periodontal therapy individuals

    Directory of Open Access Journals (Sweden)

    Elanchezhiyan Sundram

    2012-01-01

    Full Text Available Background: Gingival bleeding is considered as an important clinical sign for diagnosis of periodontal disease pathogenesis. Immune inflammatory reactions caused by local factors are considered as essential reasons for gingival bleeding, as also for the systemic bleeding disorders. In disease-free conditions of gingiva, the bleeding disorders are considered to be the main contender for bleeding. Other than these variables, many systemic drugs including systemic aspirin could also cause gingival bleeding. The main aim of the study was to evaluate the effect of buffered aspirin therapy on gingival bleeding. Materials and Methods: Totally, 36 systemically healthy individuals were included in the 15-day randomized, double-blinded, placebo-controlled clinical trial. The 15 days were divided as: control period for the first 7 days and study period for the following 7 days. On the 1 st day, all individuals were given oral prophylaxis after recording gingival parameters such as Plaque Index, probing depth, and Bleeding Index, and then blood samples were collected for hematological investigations. Then, all individuals were administered placebo capsules for 1 week as once daily dose. On the 8 th day, all procedures were repeated and the individuals were prescribed with 325 coated aspirin capsules for 1 week. On the 15 th day, all parameters were repeated and the results were statistically analyzed. Results: In the study period, the parameters such as Bleeding Index, bleeding time, and prothrombin time were increased significantly, compared to the control period. Conclusion: The variables such as systemic drug therapy should be considered for the examination of gingiva while the diagnosis is considered mainly based on gingival bleeding.

  2. NCX 4016, a nitric oxide-releasing aspirin, modulates adrenergic vasoconstriction in the perfused rat tail artery

    Science.gov (United States)

    Rossoni, Giuseppe; Manfredi, Barbara; Soldato, Piero Del; Berti, Ferruccio

    2002-01-01

    The ability of the nitric oxide (NO)-releasing aspirin, NCX 4016, to control vasoconstrictor responses induced by electrical field stimulation (TNS) or by exogenous norepinephrine (NE) was investigated in perfused rat tail artery with intact endothelium. NCX 4016 (25, 50 and 100 μM) dose-dependently antagonized the vasoconstriction caused by TNS (from 0.5 to 64 Hz) and by NE (from 0.01 to 10 μM). The vasorelaxant activity of NCX 4016 (100 μM) in NE-precontracted arteries was concomitant with a marked increase of tissue cyclic GMP (4.9 fold, P<0.001) and was significantly antagonized by the inhibitors of soluble guanylate cyclase, methylene blue and 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one. The effect of NCX 4016 was endothelium NO-independent since, in preparations perfused with NG-monomethyl-L-arginine (10 μM), this compound prevented the rise in basal perfusion pressure and reversed the accentuation of vasoconstrictor responses caused by NO synthase inhibition. Aspirin-moiety released by NCX 4016 inhibited the 6-keto-PGF1α formation without interfering with the vasorelaxant activity of NCX 4016, while aspirin (100 μM) was devoid of any activity against vasoconstriction induced by both TNS and NE in perfused rat tail artery. NCX 4016 moderated adrenergic vasoconstriction in perfused rat tail arteries by a direct donation of NO without involving the relaxant factors such as PGI2 and NO from endothelial cells. The results obtained with NCX 4016 in perfused rat tail artery bears some therapeutical potential in conditions associated with vascular smooth muscle hyperreactivity to adrenergic stimulation. PMID:12208780

  3. DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR THE SIMULTANEOUS ESTIMATION OF ROSUVASTATIN CALCIUM AND ASPIRIN IN MARKETED FORMULATION

    OpenAIRE

    Godavariya Vijay D; Prajapati Pintu B; Marolia Bhavin P.; Shah Sailesh A

    2012-01-01

    A simple, specific, accurate and precise reverse phase high pressure liquid chromatographic method has been developed for the simultaneous determination of Rosuvastatin calcium and Aspirin from Capsule dosage forms using C18 column (¬Grace Smart (250mm x 4.6mm, 5 µm). The sample was analyzed using Water (0.5 ml tri-ethyl amine in 100mL of double distilled water): Acetonitrile in the ratio of 50:50(% v/v) pH adjusted to 4.0 with orthophosphoric acid, as a mobile phase at a flow rate of 1.0...

  4. Novel role of antiplatelet agents (aspirin plus clopidogrel in an incoagulable blood of a victim of russell's viper snakebite

    Directory of Open Access Journals (Sweden)

    H. S. Bawaskar

    2006-01-01

    Full Text Available Snake antivenom is a specific antidote to the venom action, neutralizing the circulating venom. However, it fails to neutralize the venom fixed to target organs such as platelets, renal tubules, etc. Russell's viper venom initiates rapid coagulation in a victim by activating blood platelets, factors V, X, and anticoagulant cofactors. Activation of thrombin, resulting in formation of micro-thrombi, fibrinolysis, and a vicious cascade, sets in. Inhibition of activated platelets by aspirin (cyclooxygenase inhibitor and clopidogrel (ADP receptor inhibitor helps to break this vicious circle induced by Russell's venom and may initiate the natural physiological clotting mechanism. They can be utilized as an adjuvant treatment.

  5. Implications of Altered Glutathione Metabolism in Aspirin-Induced Oxidative Stress and Mitochondrial Dysfunction in HepG2 Cells

    OpenAIRE

    Raza, Haider; John, Annie

    2012-01-01

    We have previously reported that acetylsalicylic acid (aspirin, ASA) induces cell cycle arrest, oxidative stress and mitochondrial dysfunction in HepG2 cells. In the present study, we have further elucidated that altered glutathione (GSH)-redox metabolism in HepG2 cells play a critical role in ASA-induced cytotoxicity. Using selected doses and time point for ASA toxicity, we have demonstrated that when GSH synthesis is inhibited in HepG2 cells by buthionine sulfoximine (BSO), prior to ASA tre...

  6. Long term clinical outcome of coronary surgery and assessment of the benefit obtained with postoperative aspirin and dipyridamole.

    OpenAIRE

    Gershlick, A H; Lyons, J. P.; Wright, J. E.; Sturridge, M. F.; Layton, C A; Balcon, R

    1988-01-01

    Three hundred and twenty patients originally entered into a randomised study to assess the effect of aspirin and dipyridamole on the patency of coronary bypass grafts one year after operation were clinically reassessed a mean of 6.6 years (range 4.3-8.6) after operation. Patients were recruited between 1978 and 1982 after the present policy of total revascularisation had been adopted. During the follow up period there were 25 deaths of which 17 were due to cardiac causes (average annual cardi...

  7. Selective and rapid monitoring of dual platelet inhibition by aspirin and P2Y12 antagonists by using multiple electrode aggregometry

    Directory of Open Access Journals (Sweden)

    Lorenz Reinhard

    2010-05-01

    Full Text Available Abstract Background Poor platelet inhibition by aspirin or clopidogrel has been associated with adverse outcomes in patients with cardiovascular diseases. A reliable and facile assay to measure platelet inhibition after treatment with aspirin and a P2Y12 antagonist is lacking. Multiple electrode aggregometry (MEA, which is being increasingly used in clinical studies, is sensitive to platelet inhibition by aspirin and clopidogrel, but a critical evaluation of MEA monitoring of dual anti-platelet therapy with aspirin and P2Y12 antagonists is missing. Design and Methods By performing in vitro and ex vivo experiments, we evaluated in healthy subjects the feasibility of using MEA to monitor platelet inhibition of P2Y12 antagonists (clopidogrel in vivo, cangrelor in vitro and aspirin (100 mg per day in vivo, and 1 mM or 5.4 mM in vitro alone, and in combination. Statistical analyses were performed by the Mann-Whitney rank sum test, student' t-test, analysis of variance followed by the Holm-Sidak test, where appropriate. Results ADP-induced platelet aggregation in hirudin-anticoagulated blood was inhibited by 99.3 ± 1.4% by in vitro addition of cangrelor (100 nM; p 95% and 100 ± 3.2%, respectively (p in vitro or ex vivo. Oral intake of clopidogrel did not significantly reduce AA-induced aggregation, but P2Y12 blockade by cangrelor (100 nM in vitro diminished AA-stimulated aggregation by 53 ± 26% (p Conclusions Selective platelet inhibition by aspirin and P2Y12 antagonists alone and in combination can be rapidly measured by MEA. We suggest that dual anti-platelet therapy with these two types of anti-platelet drugs can be optimized individually by measuring platelet responsiveness to ADP and AA with MEA before and after drug intake.

  8. Induction of lung lesions in Wistar rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate

    International Nuclear Information System (INIS)

    The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by suitable laboratory animal models, such as animals treated with the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the current study, we established a novel lung cancer model in Wistar rats treated with NNK. Using this model, we assessed the effects of two chemopreventive agents, aspirin and phenethyl isothiocyanate (PEITC), on tumor progression. First, rats were treated with a single-dose of NNK by intratracheal instillation; control rats received iodized oil. The animals were then sacrificed on the indicated day after drug administration and examined for tumors in the target organs. PCNA, p63 and COX-2 expression were analyzed in the preneoplastic lung lesions. Second, rats were treated with a single-dose of NNK (25 mg/kg body weight) in the absence or presence of aspirin and/or PEITC in the daily diet. The control group received only the vehicle in the regular diet. The animals were sacrificed on day 91 after bronchial instillation of NNK. Lungs were collected and processed for histopathological and immunohistochemical assays. NNK induced preneoplastic lesions in lungs, including 33.3% alveolar hyperplasia and 55.6% alveolar atypical dysplasia. COX-2 expression increased similarly in alveolar hyperplasia and alveolar atypical dysplasia, while PCNA expression increased more significantly in the latter than the former. No p63 expression was detected in the preneoplastic lesions. In the second study, the incidences of alveolar atypical dysplasia were reduced to 10%, 10% and 0%, respectively, in the aspirin, PEITC and aspirin and PEITC groups, compared with 62.5% in the carcinogen-treated control group. COX-2 expression decreased after dietary aspirin or aspirin and PEITC treatment. PCNA expression was significantly reduced in the aspirin and PEITC group. (1) A single dose of 25 mg/kg body weight

  9. Reduction in fever and symptoms in young adults with influenza A/Brazil/78 H1N1 infection after treatment with aspirin or amantadine.

    OpenAIRE

    Younkin, S W; Betts, R F; Roth, F K; Douglas, R G

    1983-01-01

    During an outbreak of influenza A/Brazil/78 H1N1 infection, 47 volunteers with clinical and virological influenza of less than 2 days duration were treated in a randomized double-blind fashion for 5 days with 100 or 200 mg of amantadine daily or with 3.25 g of aspirin daily. The aspirin treatment group defervesced more rapidly (10.3 h versus 21.5 h and 23.6 h; P less than 0.01), but by the second daily follow-up visit, both groups of amantadine recipients exhibited greater symptomatic improve...

  10. Gender differences of aspirin resistance in patients with coronary heart disease%冠心病患者阿司匹林抵抗的性别差异

    Institute of Scientific and Technical Information of China (English)

    蒋志丽; 李艳芳; 王乐; 郭彦青

    2012-01-01

    目的 探讨冠心病患者阿司匹林抵抗(aspirin resistance,AR)的性别差异.方法 选取北京安贞医院行冠状动脉造影证实的冠心病患者312例,其中男204例,女108例.入院前已口服阿司匹林75~100 mg/d 1个月以上.静脉取血,采用光比浊法测定花生四烯酸和二磷酸腺苷诱导的血小板聚集率等指标.根据对阿司匹林的反应分为AR,阿司匹林半抵抗(aspirin semi resistance,ASR)和阿司匹林敏感(aspirin sensitive,AS).AR 37例,ASR 161例,AS 183例.比较冠心病患者发生AR、ASR、AS的性别差异和影响因素.结果 女性AR、ASR、AR+ ASR、AS分别占冠心病患者AR、ASR、AR+ASR、AS的60.5%、60.4%、60.5%、16.5%.与男性比较,女性患者更易发生AR和ASR.logistic回归分析,AR与性别、年龄显著相关.结论 冠心病女性患者较男性更容易发生AR,年龄增长是阿司匹林抵抗的危险因素.%Objective To investigate the gender differences of aspirin resistance in patients with coronary heart disease. Methods A total of 312 patients with coronary heart disease(CHD) were diagnosed by coronary angiography in Beijing Anzhen Hospital. There were 204 male and 108 female patients. They took aspirin 75 to 100 mg per day more than one month before hospitaliza-tion. Nephelometry was used to evaluate aspirin resistance with detection of platelet aggregation induced by arachidonic acid and adenosine diphosthate, which was divided into aspirin resistant (AR) , semi-resistant to aspirin(ASR) and aspirin sensitive(AS) according to the response to aspirin. We tried to investigate the gender differences and influential factors of aspirin resistance in patients with CHD. Results Women CHD patients with AR, ASR, AR + ASR and AS accounted for 60. 5%, 60. 4%, 60. 5%, 16. 5% of the CHD patients, respectively. Compared with men, women were more susceptible to AR and ASR. Logistic regression analysis showed that AR and ASR significantly correlated with gender and age

  11. The Use of Multi-Walled Carbon Nanotubes as Possible Carrier in Drug Delivery System for Aspirin

    Science.gov (United States)

    Yusof, Alias Mohd.; Buang, Nor Aziah; Yean, Lee Sze; Ibrahim, Mohd. Lokman

    2009-06-01

    Carbon nanotubes (CNTs) have raised great interest in a number of applications, including field emission, energy storage, molecular electronics, sensors, biochips and drug delivery systems. This is due to their remarkable mechanical properties, chemical stability and biofunctionalizability. This nanomaterial is low in weight, has high strength and a high aspect ratio (long length compared to a small diameter). This paper will present a brief overview of drugs adsorbed onto the surface of carbon nanotubes via sonication method. The surface area of carbon nanotubes was measured by methylene blue method, Carbon nanotubes synthesized by catalytic chemical vapor deposition (CCVD) method were purified and functionalized in a mixture of concentrated acids (H2SO4:HNO3 = 3:1) at room temperature (25° C) via sonication in water bath, yielding carboxylic acid group on the CNTs' surface. CNT was successfully loaded with 48 %(w/w) aspirin molecules by suspending CNTs in a solution of aspirin in alcohol. Analysis of loaded CNTs by Field Emission-Scanning Electron Microscope (FESEM), Fourier Transform Infrared Spectrum (FITR) and UV-visible Spectroscopy confirmed the loading of the drug onto the CNTs. The work presented is a prelude to the direction of using carbon nanotubes as a drug delivery system to desired sites in human body.

  12. Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental animal models of ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Bing Chun Yan

    Full Text Available Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA, decursinol (DA and new synthetic aspirin-decursinol adduct (ASA-DA against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.

  13. Automated Dissolution for Enteric-Coated Aspirin Tablets: A Case Study for Method Transfer to a RoboDis II.

    Science.gov (United States)

    Ibrahim, Sarah A; Martini, Luigi

    2014-08-01

    Dissolution method transfer is a complicated yet common process in the pharmaceutical industry. With increased pharmaceutical product manufacturing and dissolution acceptance requirements, dissolution testing has become one of the most labor-intensive quality control testing methods. There is an increased trend for automation in dissolution testing, particularly for large pharmaceutical companies to reduce variability and increase personnel efficiency. There is no official guideline for dissolution testing method transfer from a manual, semi-automated, to automated dissolution tester. In this study, a manual multipoint dissolution testing procedure for an enteric-coated aspirin tablet was transferred effectively and reproducibly to a fully automated dissolution testing device, RoboDis II. Enteric-coated aspirin samples were used as a model formulation to assess the feasibility and accuracy of media pH change during continuous automated dissolution testing. Several RoboDis II parameters were evaluated to ensure the integrity and equivalency of dissolution method transfer from a manual dissolution tester. This current study provides a systematic outline for the transfer of the manual dissolution testing protocol to an automated dissolution tester. This study further supports that automated dissolution testers compliant with regulatory requirements and similar to manual dissolution testers facilitate method transfer.

  14. A Molecular Dynamics Approach to Ligand-Receptor Interaction in the Aspirin-Human Serum Albumin Complex

    Directory of Open Access Journals (Sweden)

    H. Ariel Alvarez

    2012-01-01

    Full Text Available In this work, we present a study of the interaction between human serum albumin (HSA and acetylsalicylic acid (ASA, C9H8O4 by molecular dynamics simulations (MD. Starting from an experimentally resolved structure of the complex, we performed the extraction of the ligand by means of the application of an external force. After stabilization of the system, we quantified the force used to remove the ASA from its specific site of binding to HSA and calculated the mechanical nonequilibrium external work done during this process. We obtain a reasonable value for the upper boundary of the Gibbs free energy difference (an equilibrium thermodynamic potential between the complexed and noncomplexed states. To achieve this goal, we used the finite sampling estimator of the average work, calculated from the Jarzynski Equality. To evaluate the effect of the solvent, we calculated the so-called “viscous work,” that is, the work done to move the aspirin in the same trajectory through the solvent in absence of the protein, so as to assess the relevance of its contribution to the total work. The results are in good agreement with the available experimental data for the albumin affinity constant for aspirin, obtained through quenching fluorescence methods.

  15. Modulation of alpha-interferon's antiviral and clinical effects by aspirin, acetaminophen, and prednisone in healthy volunteers.

    Science.gov (United States)

    Hendrix, C W; Petty, B G; Woods, A; Kuwahara, S K; Witter, F R; Soo, W; Griffin, D E; Lietman, P S

    1995-10-01

    The magnitude and duration of the antiviral and clinical effect of alpha-interferon was measured in healthy volunteers. A single 3 million unit intramuscular dose of interferon was given either alone (controls) or after 72 h of concomitant medications. These medications included either aspirin (650 mg every 4 h), acetaminophen (650 mg every 4 h), or prednisone (40 mg per day). Peripheral blood mononuclear cells were assayed for resistance to vesicular stomatitis virus infection and induction of 2'-5'-oligoadenylate synthetase activity as evidence of interferon's antiviral effect. Co-administration of acetaminophen increased both antiviral parameters by more than 70% (P acetaminophen, aspirin, and prednisone reduced the clinical symptoms by 47% compared to controls (P = 0.03) after interferon dosing, although individual drug comparisons failed to reach statistical significance. Independent of treatment group, the changes in antiviral markers after interferon dosing correlated closely with each other (r = 0.72, P 0.05). Acetaminophen enhances the antiviral effects of a single intramuscular dose of alpha-interferon, considering the parameters measured in these healthy volunteers. PMID:8585766

  16. Modifications produced by selective inhibitors of cyclooxygenase and ultra low dose aspirin on platelet activity in portal hypertension

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To study the mechanism involved in the potentially beneficial effect of ultra low dose aspirin (ULDA) in prehepatic portal hypertension, rats were pretreated with selective COX 1 or 2 inhibitors (SC-560 or NS-398 respectively), and subsequently injected with ULDA or placebo.METHODS: Portal hypertension was induced by portal vein ligation. Platelet activity was investigated with an in-vivo model of laser induced thrombus production in mesenteric circulation and induced hemorrhagic time (IHT). Platelet aggregation induced by ADP and dosing of prostanoid products 6-keto-PGF1α, TXB2, PGE2 and LTB4 were also performed.RESULTS: The portal hypertensive group receiving a placebo showed a decreased in vivo platelet activity with prolonged IHT, an effect that was normalized by ULDA. SC-560 induced a mild antithrombotic effect in the normal rats, and an unmodified effect of ULDA. NS-398 had a mild prothrombotic action in portal hypertensive rats, similar to ULDA, but inhibited a further effect when ULDA was added. An increased 6-keto-PGF1α was observed in portal hypertensive group that was normalised after ULDA administration. TXA2 level after ULDA, remained unchanged.CONCLUSION: These results suggest that the effect of ULDA on platelet activity in portal hypertensive rats,could act through a COX 2 pathway more than the COX 1,predominant for aspirin at higher doses.

  17. Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial

    Directory of Open Access Journals (Sweden)

    Sushma S. Thomas

    2015-12-01

    Full Text Available Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133+2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2 levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO – accession number GSE71571 – was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9].

  18. Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.

    Science.gov (United States)

    Thomas, Sushma S; Makar, Karen W; Li, Lin; Zheng, Yingye; Yang, Peiying; Levy, Lisa; Rudolph, Rebecca Y; Lampe, Paul D; Yan, Min; Markowitz, Sanford D; Bigler, Jeannette; Lampe, Johanna W; Potter, John D

    2015-12-01

    Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) - accession number GSE71571 - was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9]).

  19. Low-molecular-weight heparin added to aspirin in the prevention of recurrent early-onset pre-eclampsia in women with inheritable thrombophilia : the FRUIT-RCT

    NARCIS (Netherlands)

    De Vries, J. I. P.; Van Pampus, M. G.; Hague, W. M.; Bezemer, P. D.; Joosten, J. H.

    2012-01-01

    . Background: Early-onset hypertensive disorders (HD) of pregnancy and small-for-gestational age infants (SGA) are associated with placental vascular thrombosis, these often recur and are also associated with inheritable thrombophilia. Aspirin reduces the recurrence risk. Objectives: Adding low-mole

  20. Low-Dose Aspirin in Early Gestation for Prevention of Preeclampsia and Small-for-Gestational-Age Neonates: Meta-analysis of Large Randomized Trials.

    Science.gov (United States)

    Roberge, Stéphanie; Sibai, Baha; McCaw-Binns, Affette; Bujold, Emmanuel

    2016-07-01

    Objectives Meta-analyses of small to moderate size randomized controlled trials (RCTs) suggested that aspirin started before 17 weeks' gestation reduces the risk of preeclampsia and small-for-gestational-age (SGA) neonates. We evaluated data from large randomized trials originally excluded from meta-analyses. Methods We performed meta-analyses of RCTs including more than 350 participants that compared aspirin to placebo during pregnancy. Corresponding authors were contacted to obtain data according to gestational age. Outcomes included preeclampsia, severe preeclampsia, and SGA. Relative risks (RRs) with their 95% confidence intervals (CIs) were calculated. Results Data for women recruited before 17 weeks' gestation were obtained for three (50%) of the six eligible trials for a total of 11,949 participants including 3,293 recruited before 17 weeks' gestation with available data. We observed no impact of low-dose aspirin (60 mg) started before 17 weeks' gestation on the risk of preeclampsia (RR: 0.93; 95% CI: 0.75-1.15), severe preeclampsia (RR: 0.96; 95% CI: 0.71-1.28), or SGA (RR: 0.84; 95% CI: 0.56-1.26) and it was not statistically different than when started at or after 17 weeks' gestation. Conclusion Data from large randomized trials do not support greater benefits of low-dose aspirin (at 60 mg daily) when started before 17 weeks' gestation for the prevention of preeclampsia or SGA. PMID:26906184