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Sample records for anti-platelet therapy aspirin

  1. PEPTIC ULCER IN PATIENTS WITH ISCHEMIC HEART DISEASE ON CHRONIC ANTI-PLATELET THERAPY WITH ASPIRIN

    OpenAIRE

    松倉, 康夫; 上村, 史朗; 川本, 篤彦; 坂口, 泰弘; 山野, 繁; 藤本, 眞一; 橋本, 俊雄; 土肥, 和紘

    1999-01-01

    Recently, many patients with ischemic heart disease (IHD), including myocardial infarction, angina pectoris, and patients with coronary stent implantation, are receiving chronic aspirin therapy in expectation of its anti-platelet effects. It is well known that, in patients with rheumatic disease on chronic aspirin therapy, aspirin-induced peptic ulcer is frequent and limits its clinical usefulness. In this study, we studied 482 IHD patients after coronary intervention to evaluate the incidenc...

  2. Novel agents for anti-platelet therapy

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    Ji Xuebin

    2011-11-01

    Full Text Available Abstract Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12 receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed.

  3. Is anti-platelet therapy interruption a real clinical issue? Its implications in dentistry and particularly in periodontics

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    Kumar A

    2009-01-01

    Full Text Available The use of anti-platelet therapy has reduced the mortality and morbidity of cardiovascular disease remarkably. A considerable number of patients presenting before a dentist or periodontist give a history of anti-platelet therapy. A clinical dilemma whether to discontinue the anti-platelet therapy or continue the same always confronts the practitioner. Diverse opinions exist regarding the management of such patients. While one group of researchers advise continuation of anti-platelet therapy rather than invite remote, but possible, thromboembolic events, another group encourages discontinuation for variable periods. This study aims at reviewing the current rationale of anti-platelet therapy and the various options available to a clinician, with regard to the management of a patient under anti-platelet therapy. Current recommendations and consensus favour no discontinuation of anti-platelet therapy. This recommendation, however, comes with a rider to use caution and consider other mitigating factors as well. With a large number of patients giving a history of anti-platelet therapy, the topic is of interest and helps a clinician to arrive at a decision.

  4. Pharmacogenomics of anti-platelet therapy: how much evidence is enough for clinical implementation?

    Science.gov (United States)

    Perry, Christina G; Shuldiner, Alan R

    2013-06-01

    Pharmacogenomics, the study of the genomics of drug response and adverse effects, holds great promise for more effective individualized (personalized) medicine. Recent evidence supports a role of loss-of-function (LOF) variants in the cytochrome P450 enzyme CYP2C19 as a determinant of clopidogrel response. Patients given clopidogrel after percutaneous coronary intervention who carry LOF variants do not metabolize clopidogrel, a prodrug, into its active form resulting in decreased inhibition of platelet function and a higher likelihood of recurrent cardiovascular events. Despite a large body of evidence supporting clinical utility, adoption of anti-platelet pharmacogenetics into clinical practice has been slow. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical evidence, identify gaps in knowledge and other barriers that appear to be slowing adoption, and describe CYP2C19 pharmacogenetics implementation projects currently underway. Only when we surmount these barriers will clinicians be able to use pharmacogenetic information in conjunction with the history, physical examination and other medical tests and information to choose the most efficacious anti-platelet therapy for each individual patient.

  5. Aspirin mono-therapy continuation does not result in more bleeding after knee arthroplasty.

    Science.gov (United States)

    Schwab, Pierre-Emmanuel; Lavand'homme, Patricia; Yombi, JeanCyr; Thienpont, Emmanuel

    2017-08-01

    Current clinical practice guidelines sometimes still recommend stopping aspirin five to seven days before knee arthroplasty surgery. Literature regarding multimodal blood management and continuation of anti-platelet therapy in this type of surgery is scant. The study hypothesis was that knee arthroplasty under low-dose aspirin mono-therapy continuation does not cause more total blood loss than knee arthroplasty performed without aspirin. Blood loss would be measured by haemoglobin (Hb) and haematocrit (HTC) levels drop at day 2 or day 4 for patients who benefit from multimodal bleeding control measures. A database of all patients undergoing knee arthroplasty between 2006 and 2014 was analysed. Demographic, surgical and complete blood workup data were collected. A retrospective comparison study analysed both groups in terms of blood loss, by mean calculated blood loss as haemoglobin or haematocrit drop between the preoperative Nadir value and the postoperative day 2 and 4 value. A group of 198 (44 UKA and 154 TKA) patients underwent surgery without interrupting their aspirin therapy for cardiovascular prevention. Mean (SD) age was 71 (8) and the mean (SD) BMI was 29 (5.5) kg/m 2 . The control group consisted of 403 (102 UKA and 301 TKA) patients who were not under aspirin, or any other anti-platelet agent. Mean (SD) age was 65 (10) (p aspirin mono-therapy for cardiovascular prevention. III.

  6. [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.

  7. A short history of anti-rheumatic therapy. II. Aspirin

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

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

  8. Is aspirin still the drug of choice for management of patients with peripheral arterial disease?

    Science.gov (United States)

    Poredos, Pavel; Jezovnik, Mateja K

    2013-03-01

    Antiplatelet drugs represent one of the basic options for management of patients with different atherosclerotic diseases. Aspirin is the oldest and most often prescribed antiplatelet drug. The efficacy of aspirin depends on the clinical characteristics of the treated population and probably also on the type or location of atherosclerotic disease. It seems that it is most effective in coronary patients with clinically unstable disease, less effective in prevention of cerebrovascular incidents, and its efficacy is uncertain in peripheral artery disease (PAD) patients. One of the first meta-analyses (Antithrombotic Trialists' Collaboration - ATC) indicated that antiplatelet drugs also significantly reduce cardiovascular events in patients with PAD. However, only one third of the PAD patients included were treated with aspirin, while the rest received other anti-platelet drugs. The latest ATC meta-analysis of randomized control trials of aspirin therapy involving patients with diabetes and PAD demonstrated no benefit of aspirin in reducing cardiovascular events. Also in patients with preclinical PAD (pathological ankle brachial index) aspirin did not result in a significant reduction of vascular events. The new anti-platelet drugs prasugrel, ticagrelor and picotamide seem to be more effective than aspirin in PAD patients, particularly in diabetic patients with PAD. In conclusion, antiplatelet drugs are effective in prevention of cardiovascular events in different atherosclerotic diseases, including PAD. However, recent studies indicated that in PAD patients aspirin is less effective than in coronary artery disease. New anti-platelet drugs showed marginal superiority over aspirin without definite advantages. Aspirin thus remains the first line of antiplatelet drug for secondary prevention of cardiovascular events in PAD patients and clopidogrel as its effective alternative. Further, new studies on PAD patients are necessary to better define the role of anti-platelet

  9. Aspirin desensitization in patients undergoing percutaneous coronary intervention: a survey of current practice.

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    Chapman, Andrew R; Rushworth, Gordon F; Leslie, Stephen J

    2013-01-01

    Aspirin remains the mainstay of anti-platelet therapy in cardiac patients. However, if a patient is allergic to aspirin and dual anti-platelet therapy is indicated - such as with percutaneous coronary intervention (PCI), then there is no clear guidance. One possibility is aspirin desensitization. A variety of protocols exist for the rapid desensitization of patients with aspirin allergy. The aim of this survey was to assess current knowledge and practice regarding aspirin desensitization in the UK. We conducted a UK wide survey of all UK 116 PCI centers and obtained complete responses from 40 (35.4%) centers. Of these, just 7 (17.5%) centers had previously desensitised patients; 29 (87.9%) centers suggested a lack of a local protocol prevented them from desensitizing, with 10 (30.3%) unsure of how to conduct desensitization. Only 5 (12.5%) centers had a local policy for aspirin desensitization although 25 (64.1%) units had a clinical strategy for dealing with aspirin allergy; the majority (72%) giving higher doses of thienopyridine class drugs. In the UK, there appears to be no consistent approach to patients with aspirin allergy. Patients undergoing PCI benefit from dual anti-platelet therapy (including aspirin), and aspirin desensitization in those with known allergy may facilitate this. Sustained effort should be placed on encouraging UK centers to use desensitization as a treatment modality prior to PCI rather than avoiding aspirin altogether.

  10. Optimal duration of dual anti-platelet therapy after percutaneous coronary intervention: 2016 consensus position of the Italian Society of Cardiology.

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    Barillà, Francesco; Pelliccia, Francesco; Borzi, Mauro; Camici, Paolo; Cas, Livio Dei; Di Biase, Matteo; Indolfi, Ciro; Mercuro, Giuseppe; Montemurro, Vincenzo; Padeletti, Luigi; Filardi, Pasquale Perrone; Vizza, Carmine D; Romeo, Francesco

    2017-01-01

    Definition of the optimal duration of dual anti-platelet therapy (DAPT) is an important clinical issue, given the large number of patients having percutaneous coronary intervention (PCI), the costs and risks of pharmacologic therapy, the consequences of stent thrombosis, and the potential benefits of DAPT in preventing ischaemic outcomes beyond stent thrombosis. Nowadays, the rationale for a prolonged duration of DAPT should be not only the prevention of stent thrombosis, but also the prevention of ischaemic events unrelated to the coronary stenosis treated with index PCI. A higher predisposition to athero-thrombosis may persist for years after an acute myocardial infarction, and even stable patients with a history of prior myocardial infarction are at high risk for major adverse cardiovascular events. Recently, results of pre-specified post-hoc analyses of randomized clinical trials, including the PEGASUS-TIMI 54 trial, have shed light on strategies of DAPT in various clinical situations, and should impact the next rounds of international guidelines, and also routine practice. Accordingly, the 2015 to 2016 the Board of the Italian Society of Cardiology addressed newer recommendations on duration of DAPT based on most recent scientific information. The document states that physicians should decide duration of DAPT on an individual basis, taking into account ischaemic and bleeding risks of any given patient. Indeed, current controversy surrounding optimal duration of DAPT clearly reflects the fact that, nowadays, a one size fits all strategy cannot be reliably applied to patients treated with PCI. Indeed, patients usually have factors for both increased ischaemic and bleeding risks that must be carefully evaluated to assess the benefit/risk ratio of prolonged DAPT. Personalized management of DAPT must be seen as a dynamic prescription with regular re-evaluations of the risk/benefit to the patient according to changes in his/her clinical profile. Also, in order to

  11. 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).

  12. Aspirin

    Science.gov (United States)

    ... to aspirin, other medications for pain or fever, tartrazine dye, or any other medications.tell your doctor ... medications or monitor you more carefully for side effects.if you are taking aspirin on a regular ...

  13. Enhanced ex vivo inhibition of platelet function following addition of dipyridamole to aspirin after transient ischaemic attack or ischaemic stroke: first results from the TRinity AntiPlatelet responsiveness (TrAP) study.

    LENUS (Irish Health Repository)

    Tobin, William Oliver

    2012-02-01

    Ex vivo dipyridamole \\'non-responsiveness\\' has not been extensively studied in ischaemic cerebrovascular disease. Platelet surface marker expression, leucocyte-platelet complex formation and inhibition of platelet function at high shear stress as detected by the PFA-100(R) Collagen-Adenosine-diphosphate (C-ADP) and Collagen-Epinephrine cartridges was assessed in 52 patients within 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke on aspirin, and then 14 d (14 d) and >90 d (90 d) after adding dipyridamole. A novel definition of \\'Dipyridamole non-responsiveness\\' was used. The median C-ADP closure time increased following addition of dipyridamole, remained elevated at 90 d (P <\\/= 0.03), and was unaffected by aspirin dose. 59% at 14 d and 56% at 90 d were \\'dipyridamole non-responders\\' on the PFA-100. The proportion of non-responders at 14 and 90 d was similar (P= 0.9). Compared with baseline (4.6%), median monocyte-platelet complexes increased at 14 d (5.0%, P= 0.03) and 90 d (4.9%, P= 0.04). Low C-ADP closure times were associated with increased monocyte-platelet complexes at 14 d (r= -0.32, P= 0.02) and 90 d (r= -0.33, P = 0.02). Monocyte-platelet complexes increased in the subgroup of dipyridamole non-responders on the PFA-100 (P<\\/= 0.045), but not in responders (P >\\/= 0.5), at 14 and 90 d versus baseline. Additional inhibition of platelet function has been detected with the PFA-100 when dipyridamole is added to aspirin. Elevated monocyte-platelet complexes may contribute to ex vivo dipyridamole non-responsiveness.

  14. Experimental evaluation of analgesic, anti-inflammatory and anti-platelet potential of Dashamoola

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    Reshma R Parekar

    2015-01-01

    Full Text Available Background: Dashamoola, in the form of arishta and kwath, is a commonly used classical Ayurvedic multi-ingredient formulation for management of pain, arthritis and inflammatory disorders. Objective: To study analgesic, anti-inflammatory and anti-platelet activity of Dashamoola and its combination with aspirin. Materials and Methods: Wistar albino rats (180-200 g and Swiss albino mice (20-25 g of either sex were divided randomly into five groups: Distilled water, aspirin (500mg/kg in rats; 722.2 mg/kg in mice, Dashamoolarishta (1.8 mL/kg in rats; 2.5 mL/kg in mice and Dashamoolarishta with aspirin. Anti-inflammatory activity was measured by change in paw volume in carrageenan-induced inflammation, protein content in model of peritonitis and granuloma weight in cotton pellet granuloma. Analgesic effect was evaluated by counting number of writhes in writhing model. Maximum platelet aggregation and percentage inhibition of ADP and collagen-induced platelet aggregation were estimated in vitro. Statistical analysis was done using one way ANOVA (post hoc Tukey′s test and P < 0.05 was considered significant. Results: Dashamoolarishta and its combination with aspirin showed significantly (P < 0.01 less number of writhes. It showed significant (P < 0.001 anti-inflammatory activity by paw edema reduction in rats, decrease in proteins in peritoneal fluid (P < 0.001 and decrease in granuloma weight (P < 0.05 as compared to respective vehicle control groups. Dashamoola kwath alone and in combination with aspirin inhibited maximum platelet aggregation and percent inhibition of platelets as compared to vehicle (P < 0.001. Conclusion: Dashamoola formulation alone and its combination with aspirin showed comparable anti-inflammatory, analgesic and anti-platelet effects to aspirin.

  15. The evaluation of 2,8-disubstituted benzoxazinone derivatives as anti-inflammatory and anti-platelet aggregation agents.

    Science.gov (United States)

    Hsieh, Pei-Wen; Hwang, Tsong-Long; Wu, Chin-Chung; Chang, Fang-Rong; Wang, Tsai-Wei; Wu, Yang-Chang

    2005-06-02

    A series of 2,8-disubstituted benzoxazinones were synthesized and subjected to anti-platelet aggregation, inhibition of superoxide anion generation, and inhibition of neutrophil elastase release assays. Among them, 2-(2'-substituted-phenyl)-benzoxazinones exhibited significant inhibitory effect to target assays. Additionally, all of them were more potent than aspirin on AA-induced platelet aggregation, and these suggested that 2-(2'-substituted-phenyl)-benzoxazinones also possess aspirin-like activity. On the other hand, the compounds 6 and 16 showed inhibitory effects on neutrophil elastase release and superoxide generation.

  16. Application of Feedback System Control Optimization Technique in Combined Use of Dual Antiplatelet Therapy and Herbal Medicines

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    Wang Liu

    2018-05-01

    Full Text Available Aim: Combined use of herbal medicines in patients underwent dual antiplatelet therapy (DAPT might cause bleeding or thrombosis because herbal medicines with anti-platelet activities may exhibit interactions with DAPT. In this study, we tried to use a feedback system control (FSC optimization technique to optimize dose strategy and clarify possible interactions in combined use of DAPT and herbal medicines.Methods: Herbal medicines with reported anti-platelet activities were selected by searching related references in Pubmed. Experimental anti-platelet activities of representative compounds originated from these herbal medicines were investigated using in vitro assay, namely ADP-induced aggregation of rat platelet-rich-plasma. FSC scheme hybridized artificial intelligence calculation and bench experiments to iteratively optimize 4-drug combination and 2-drug combination from these drug candidates.Results: Totally 68 herbal medicines were reported to have anti-platelet activities. In the present study, 7 representative compounds from these herbal medicines were selected to study combinatorial drug optimization together with DAPT, i.e., aspirin and ticagrelor. FSC technique first down-selected 9 drug candidates to the most significant 5 drugs. Then, FSC further secured 4 drugs in the optimal combination, including aspirin, ticagrelor, ferulic acid from DangGui, and forskolin from MaoHouQiaoRuiHua. Finally, FSC quantitatively estimated the possible interactions between aspirin:ticagrelor, aspirin:ferulic acid, ticagrelor:forskolin, and ferulic acid:forskolin. The estimation was further verified by experimentally determined Combination Index (CI values.Conclusion: Results of the present study suggested that FSC optimization technique could be used in optimization of anti-platelet drug combinations and might be helpful in designing personal anti-platelet therapy strategy. Furthermore, FSC analysis could also identify interactions between different

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

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    Iijima, Katsunori; Shimosegawa, Tooru

    2015-01-01

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

  18. Daily Aspirin Therapy: Understand the Benefits and Risks

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    ... aspirin, especially in those with a history of gastritis or ulcers. However, some researchers think there's no ... Aspirin in primary prevention of cardiovascular disease and cancer: A systematic review of the balance of evidence ...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    OBJECTIVE: Low platelet response to aspirin has been reported to be associated with a high incidence of vascular events. The reported prevalence of aspirin low-responsiveness varies, which may be explained by poor reproducibility of the methods used to evaluate aspirin response and low compliance....... The Platelet Function Analyzer-100 (PFA-100) is a commonly used platelet function test. We aimed to assess the reproducibility of the PFA-100 and the agreement with optical platelet aggregometry (OPA) in healthy volunteers and in patients with coronary artery disease (CAD) treated with low-dose aspirin....... MATERIAL AND METHODS: Twenty-one healthy volunteers and 43 patients with CAD took part in the study. During treatment with aspirin 75 mg daily, all participants had platelet function assessed in duplicate with the PFA-100 and OPA on 4 consecutive days. Additionally, platelet function was assessed before...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  1. Anti-platelet aggregation of mixtures of betulinic oleanolic and ...

    African Journals Online (AJOL)

    Original Research Article. Anti-platelet aggregation of mixtures of betulinic oleanolic ... Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, Directory of Open Access Journals. (DOAJ), African Journal Online, Bioline ... antiseptic, aphrodisiac, anti-emetic, anti- inflammatory and carminative properties [5,6].

  2. Anti-platelet aggregation of mixtures of betulinic oleanolic and ...

    African Journals Online (AJOL)

    Anti-platelet aggregation of mixtures of betulinic oleanolic and maslinic acids and derivatives from medicinal plants. Foluso O. Osunsanmi, Babatunji E. Oyinloye, Rebamang A. Mosa, Monisola I. Ikhile, J Catherine Ngila, Francis O. Shode, M Singh, Andy R. Opoku ...

  3. Aspirin inhibits the SHH/GLI1 signaling pathway and sensitizes malignant glioma cells to temozolomide therapy.

    Science.gov (United States)

    Ming, Jianguang; Sun, Bo; Li, Ziwei; Lin, Lin; Meng, Xiangqi; Han, Bo; Wang, Ruijia; Wu, Pengfei; Li, Jianlong; Cai, Jinquan; Jiang, Chuanlu

    2017-04-01

    Aberrant activation of sonic hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) pathway plays an important role in the tumorigenicity of malignant glioma cells and resistance to temozolomide (TMZ). Here we investigated the aspirin's antineoplastic molecular route by targeting SHH/GLI1 pathway and examined the feasibility of aspirin combined with TMZ therapy. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that the activity of the SHH/GLI1 pathway was strongly inhibited by aspirin. Aspirin acted as the glioma growth-inhibitory and pro-apoptosis roles by inhibiting the SHH/GLI1 pathway and reprogramming the epithelial to mesenchymal transition (EMT). The immunofluorescence assay showed aspirin could prevent the nuclear translocation of GLI1 to inhibit its transcriptional regulation. The stable lentiviral overexpression of GLI1 reversed the DNA double strand breaks (DSBs) caused by the GANT61 and TMZ. Furthermore, aspirin combined with TMZ enhanced chemosensitivity and GLI1-induced chemoprotection was partly blocked by aspirin in vitro and in vivo . Collectively, aspirin has a therapeutic potential for SHH/GLI1 targeted therapy against glioma cells. Acquired activation of GLI1 protects glioma cells against TMZ therapy. Impairment of DNA DSBs repair activity might be involved in the route of aspirin-induced chemosensitivity. Combined aspirin with TMZ may be a promising strategy against malignant glioma.

  4. Aspirin and low-molecular weight heparin combination therapy effectively prevents recurrent miscarriage in hyperhomocysteinemic women.

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    Pratip Chakraborty

    Full Text Available The management of recurrent pregnancy loss (RPL still remains a great challenge, and women with polycystic ovarian syndrome (PCOS are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy, insulin resistance (IR and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 women with history of 2 or more consecutive first trimester abortions were screened and 336 were selected for the study. The selected patients were initially divided on the basis of presence or absence of PCOS, while subsequent stratification was based on HHcy, IR and/or obesity. The subjects had treatment with aspirin during one conception cycle and aspirin-LMWH combined anticoagulant therapy for the immediate next conception cycle, if the first treated cycle was unsuccessful. Pregnancy salvage was the sole outcome measure. The overall rate of pregnancy salvage following aspirin therapy was 43.15%, which was mostly represented by normohomocysteinemic women, while the salvage rate was lower in the HHcy populations irrespective of the presence or absence of PCOS, IR, or obesity. By contrast, aspirin-LMWH combined therapy could rescue 66.84% pregnancies in the aspirin-failed cases. Logistic regression analyses showed that HHcy remained a significant factor in predicting salvage rates in the PCOS, IR, and obese subpopulations controlled for other confounding factors. With regard to pregnancy salvage, combined anticoagulant therapy with aspirin and LMWH conferred added benefit to those with HHcy phenotype.

  5. The utility of thrombo-elastography in the monitoring of aspirin therapy

    African Journals Online (AJOL)

    later. After 1 week of aspirin therapy, thrombo-elastogram data failed to demonstrate a significant change in the clotting profile. Platelet aggregometry identified significant changes in the clotting profile in response to stimulation with arachidonic acid, adrenaline and ADP. We conclude that thrombo-elastography may not ...

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

    Science.gov (United States)

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

    2014-01-01

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

  7. Mechanism of platelet functional changes and effects of anti-platelet agents on in vivo hemostasis under different gravity conditions.

    Science.gov (United States)

    Li, Suping; Shi, Quanwei; Liu, Guanglei; Zhang, Weilin; Wang, Zhicheng; Wang, Yuedan; Dai, Kesheng

    2010-05-01

    Serious thrombotic and hemorrhagic problems or even fatalities evoked by either microgravity or hypergravity occur commonly in the world. We recently reported that platelet functions are inhibited in microgravity environments and activated under high-G conditions, which reveals the pathogenesis for gravity change-related hemorrhagic and thrombotic diseases. However, the mechanisms of platelet functional variations under different gravity conditions remain unclear. In this study we show that the amount of filamin A coimmunoprecipitated with GPIbalpha was enhanced in platelets exposed to modeled microgravity and, in contrast, was reduced in 8 G-exposed platelets. Hypergravity induced actin filament formation and redistribution, whereas actin filaments were reduced in platelets treated with modeled microgravity. Furthermore, intracellular Ca2+ levels were elevated by hypergravity. Pretreatment of platelets with the cell-permeable Ca2+ chelator BAPTA-AM had no effect on cytoskeleton reorganization induced by hypergravity but significantly reduced platelet aggregation induced by ristocetin/hypergravity. Two anti-platelet agents, aspirin and tirofiban, effectively reversed the shortened tail bleeding time and reduced the death rate of mice exposed to hypergravity. Furthermore, the increased P-selectin surface expression was obviously reduced in platelets from mice treated with aspirin/hypergravity compared with those from mice treated with hypergravity alone. These data suggest that the actin cytoskeleton reorganization and intracellular Ca2+ level play key roles in the regulation of platelet functions in different gravitational environments. The results with anti-platelet agents not only further confirm the activation of platelets in vivo but also suggest a therapeutic potential for hypergravity-induced thrombotic diseases.

  8. 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

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

    International Nuclear Information System (INIS)

    Zaorsky, Nicholas G.; Buyyounouski, Mark K.; Li, Tianyu; Horwitz, Eric M.

    2012-01-01

    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 χ 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

  10. The influence of aspirin dose and glycemic control on platelet inhibition in patients with type 2 diabetes mellitus

    NARCIS (Netherlands)

    Lemkes, B. A.; Bahler, L.; Kamphuisen, P. W.; Stroobants, A. K.; van den Dool, E. J.; Hoekstra, J. B.; Nieuwland, R.; Gerdes, V. E.; Holleman, F.

    Background: Low-dose aspirin seems to offer no benefit in the primary prevention of cardiovascular disease in type 2 diabetes mellitus (DM2). The anti-platelet effect may be diminished by poor glycemic control or inadequate dosing of aspirin. Objectives: To study the effects of both glycemic control

  11. Influence of aspirin therapy in the ulcer associated with chronic venous insufficiency.

    Science.gov (United States)

    del Río Solá, Ma Lourdes; Antonio, Jose; Fajardo, González; Vaquero Puerta, Carlos

    2012-07-01

    To determine the effect of aspirin on ulcer healing rate in patients with chronic venous insufficiency, and to establish prognostic factors that influence ulcer evolution. Between 2001 and 2005, 78 patients with ulcerated lesions of diameter >2 cm and associated with chronic venous insufficiency were evaluated in our hospital. Of these, 51 patients (22 men, 29 women) with mean age of 60 years (range: 36-86) were included in a prospective randomized trial with a parallel control group. The treatment group received 300 mg of aspirin and the control group received no drug treatment; in both groups, healing was associated with standard compression therapy. During follow-up, held weekly in a blinded fashion, there was ulcer healing as well as cases of recurrence. Results were analyzed by intention-to-treat approach. Cure rate was estimated using Kaplan-Meier survival analysis, and the influence of prognostic factors was analyzed by applying the Cox proportional hazards model. In the presence of gradual compression therapy, healing occurred more rapidly in patients receiving aspirin versus the control subjects (12 weeks in the treated group vs. 22 weeks in the control group), with a 46% reduction in healing time. The main prognostic factor was estimated initial area of injury (P = 0.032). Age, sex, systemic therapy, and infection showed little relevance to evolution. The administration of aspirin daily dose of 300 mg shortens the healing time of ulcerated lesions in the chronic venous insufficiency (CVI). The main prognostic factor for healing of venous ulcerated lesions is the initial surface area of the ulcer. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

  12. Association between Aspirin Therapy and Clinical Outcomes in Patients with Non-Obstructive Coronary Artery Disease: A Cohort Study.

    Science.gov (United States)

    Hwang, In-Chang; Jeon, Joo-Yeong; Kim, Younhee; Kim, Hyue Mee; Yoon, Yeonyee E; Lee, Seung-Pyo; Kim, Hyung-Kwan; Sohn, Dae-Won; Sung, Jidong; Kim, Yong-Jin

    2015-01-01

    Presence of non-obstructive coronary artery disease (CAD) is associated with increased prescription of cardiovascular preventive medications including aspirin. However, the association between aspirin therapy with all-cause mortality and coronary revascularization in this population has not been investigated. Among the cohort of individuals who underwent coronary computed tomography angiography (CCTA) from 2007 to 2011, 8372 consecutive patients with non-obstructive CAD (1-49% stenosis) were identified. Patients with statin or aspirin prescription before CCTA, and those with history of revascularization before CCTA were excluded. We analyzed the differences of all-cause mortality and a composite of mortality and late coronary revascularization (> 90 days after CCTA) between aspirin users (n = 3751; 44.8%) and non-users. During a median of 828 (interquartile range 385-1,342) days of follow-up, 221 (2.6%) mortality cases and 295 (3.5%) cases of composite endpoint were observed. Annualized mortality rates were 0.97% in aspirin users versus 1.28% in non-users, and annualized rates of composite endpoint were 1.56% versus 1.48%, respectively. Aspirin therapy was associated with significantly lower risk of all-cause mortality (adjusted HR 0.649; 95% CI 0.492-0.857; p = 0.0023), but not with the composite endpoint (adjusted HR 0.841; 95% CI 0.662-1.069; p = 0.1577). Association between aspirin and lower all-cause mortality was limited to patients with age ≥ 65 years, diabetes, hypertension, decreased renal function, and higher levels of coronary artery calcium score, low-density lipoprotein cholesterol and high-sensitivity C-reactive protein. Among the patients with non-obstructive CAD documented by CCTA, aspirin is associated with lower all-cause mortality only in those with higher risk.

  13. Association between Aspirin Therapy and Clinical Outcomes in Patients with Non-Obstructive Coronary Artery Disease: A Cohort Study.

    Directory of Open Access Journals (Sweden)

    In-Chang Hwang

    Full Text Available Presence of non-obstructive coronary artery disease (CAD is associated with increased prescription of cardiovascular preventive medications including aspirin. However, the association between aspirin therapy with all-cause mortality and coronary revascularization in this population has not been investigated.Among the cohort of individuals who underwent coronary computed tomography angiography (CCTA from 2007 to 2011, 8372 consecutive patients with non-obstructive CAD (1-49% stenosis were identified. Patients with statin or aspirin prescription before CCTA, and those with history of revascularization before CCTA were excluded. We analyzed the differences of all-cause mortality and a composite of mortality and late coronary revascularization (> 90 days after CCTA between aspirin users (n = 3751; 44.8% and non-users. During a median of 828 (interquartile range 385-1,342 days of follow-up, 221 (2.6% mortality cases and 295 (3.5% cases of composite endpoint were observed. Annualized mortality rates were 0.97% in aspirin users versus 1.28% in non-users, and annualized rates of composite endpoint were 1.56% versus 1.48%, respectively. Aspirin therapy was associated with significantly lower risk of all-cause mortality (adjusted HR 0.649; 95% CI 0.492-0.857; p = 0.0023, but not with the composite endpoint (adjusted HR 0.841; 95% CI 0.662-1.069; p = 0.1577. Association between aspirin and lower all-cause mortality was limited to patients with age ≥ 65 years, diabetes, hypertension, decreased renal function, and higher levels of coronary artery calcium score, low-density lipoprotein cholesterol and high-sensitivity C-reactive protein.Among the patients with non-obstructive CAD documented by CCTA, aspirin is associated with lower all-cause mortality only in those with higher risk.

  14. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. 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.

  16. 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 ...

  17. Aspirin Desensitization

    Science.gov (United States)

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

  18. Anti-platelet effects of chalcones fromAngelica keiskeiKoidzumi (Ashitaba)in vivo.

    Science.gov (United States)

    Ohkura, N; Ohnishi, K; Taniguchi, M; Nakayama, A; Usuba, Y; Fujita, M; Fujii, A; Ishibashi, K; Baba, K; Atsumi, G

    2016-11-02

    Angelica keiskei Koidzumi (Ashitaba) is a traditional folk medicine that is also regarded in Japan as a health food with potential antithrombotic properties. The ability of the major chalcones, xanthoangelol (XA) and 4-hydroxyderricin (4-HD) extracted from Ashitaba roots to inhibit platelet aggregation activity in vitro was recently determined. However, the anti-platelet activities of Ashitaba chalcones in vivo have remained unclear. The present study examines the anti-platelet effects of Ashitaba exudate and its constituent chalcones using mouse tail-bleeding models that reflect platelet aggregation in vivo. Ashitaba exudate and the major chalcone subtype XA, suppressed the lipopolysaccharide (LPS)-induced shortening of mouse tail bleeding. However, trace amounts of other Ashitaba chalcone subtypes including xanthoangelols B (XB), D (XD), E (XE) and F (XF) did not affect tail bleeding. These results suggest that the major chalcone subtype in Ashitaba, XA, has anti-platelet-activities in vivo.

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

    Science.gov (United States)

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

    2017-11-01

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

  20. Association between PTGS1 polymorphisms and functional outcomes in Chinese patients with stroke during aspirin therapy: Interaction with smoking.

    Science.gov (United States)

    Cai, Huan; Cai, Biyang; Sun, Lingli; Zhang, Hao; Zhou, Shuyu; Cao, Liping; Guo, Hongquan; Sun, Wen; Yan, Bernard; Davis, Stephen M; Zhang, Zhizhong; Liu, Xinfeng

    2017-05-15

    Prostaglandin-Endoperoxide Synthase 1 (PTGS1) and smoking may play important roles in aspirin nonresponsiveness, but the effect of their interaction on stroke outcomes remains largely unknown. We examined the effects of PTGS1 polymorphisms, smoking status, and their interaction on functional outcomes in a cohort of Chinese Han patients with stroke during aspirin therapy. A total of 617 ischemic stroke patients taking aspirin were enrolled. Three single nucleotide polymorphisms (SNPs) rs1330344, rs3842788, and rs5788 in PTGS1 were determined for genotyping. Poor functional outcomes were defined as a modified Rankin Scale (mRS) of 3-6 at 90-day follow-up. The influence of PTGS1 gene-smoking interaction on functional outcomes was examined. Poor functional outcomes occurred in 145 (23.5%) patients. When adjusting multiple factors by logistic regression, CC genotype of rs1330344 was associated with poor functional outcomes (risk ratio [RR]=1.73; 95% confidence interval [CI]: 1.17-2.37). A similar connection was found in the CGC haplotype (RR=1.40; 95% CI: 1.08-1.77). Furthermore, we found a significant interaction between rs1330344 and smoking status (P interaction =0.018); the interaction effect between the PTGS1 haplotype and smoking also showed statistical significance (P interaction =0.040). In Chinese Han stroke patients with aspirin therapy, the adverse effect of PTGS1 polymorphisms on functional outcomes may be modulated by the smoking status. PTGS1 gene-smoking interaction might in part reflect the heterogeneity in the prognosis of patients treated with aspirin. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Dentists' approach to patients on anti-platelet agents and warfarin: a survey of practice.

    LENUS (Irish Health Repository)

    Murphy, James

    2010-04-23

    In everyday practice, dentists are confronted with the dilemma of patients on anti-platelet agents and warfarin who require invasive dental procedures and, more pertinently, dental extractions. There may be a divergence of opinion among dentists regarding how they manage these patients. AIMS: To assess general dental practitioners\\' approach to the management of patients taking anti-platelet agents and\\/or warfarin who are undergoing invasive dental procedures. METHODS AND DATA: A semi-structured questionnaire was designed to survey general dental practitioners in a large Irish urban area. RESULTS: A response rate of 89% was achieved in a study population of 54 general dental practitioners. A total of 25% of respondents who carry out extractions on warfarinised patients do not check the INR prior to invasive dental procedures. Some 90% of respondents stop anti-platelet agents prior to extractions. CONCLUSIONS: A significant proportion of respondents fail to check warfarinised patients\\' INR prior to invasive dental procedures. Furthermore, a trend of stopping anti-platelet agents was noted, which is in contrast with current recommendations in the dental literature. Certain practices in this small study population proved alarming and highlight the need for improved awareness of current guidelines. A further large-scale study may be justified, as variation in practice may have clinical and medico-legal repercussions.

  2. Aspirin desensitization for cardiovascular disease.

    Science.gov (United States)

    Woessner, Katharine M

    2015-08-01

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

  3. Aspirin plus dipyridamole has the highest surface under the cumulative ranking curves (SUCRA) values in terms of mortality, intracranial hemorrhage, and adverse event rate among 7 drug therapies in the treatment of cerebral infarction.

    Science.gov (United States)

    Zhang, Jian-Jun; Liu, Xin

    2018-03-01

    The standardization for the clinical use of drug therapy for cerebral infarction (CI) has not yet determined in some aspects. In this paper, we discussed the efficacies of different drug therapies (aspirin, aspirin plus dipyridamole, aspirin plus clopidogrel, aspirin plus warfarin, cilostazol, warfarin, and ticlopidine) for CI. We searched databases of PubMed and Cochrane Library from the inception to April, 2017, randomized controlled trials (RCTs) met the inclusion and exclusion criteria were enrolled in this study. The network meta-analysis integrated evidences of direct and indirect comparisons to assess odd ratios (OR) and surface under the cumulative ranking curves (SUCRA) value. Thirteen eligible RCTs including 7 drug therapies were included into this network meta-analysis. The network meta-analysis results showed that CI patients who received aspirin plus dipyridamole presented lower mortality when compared with those received aspirin plus clopidogrel (OR = 0.46, 95% CI = 0.18-0.99), indicating aspirin plus dipyridamole therapy had better efficacy for CI. As for intracranial hemorrhage (ICH), stroke recurrence, and adverse event (AE) rate, there were no significant differences of efficacy among 7 drug therapies. Besides, SUCRA values demonstrated that in the 7 drug therapies, aspirin plus dipyridamole therapy was more effective than others (mortality: 80.67%; ICH: 76.6%; AE rate: 90.2%). Our findings revealed that aspirin plus dipyridamole therapy might be the optimum one for patients with CI, which could help to improve the survival of CI patients.

  4. Evaluation of aspirin therapy on intracardiac thrombi using indium-111-oxine platelet scintigraphy, two-dimentional echocardiography and left ventriculography

    International Nuclear Information System (INIS)

    Shibuya, Masanori; Irino, Tadayoshi; Yoshioka, Toshiharu; Sugimoto, Tsuyoshi; Tsuji, Kazuo; Naka, Masashi; Arai, Hidekazu.

    1984-01-01

    Left ventriculography (LVG), two-dimensional echocardiography (2-DE) and indium-111-oxine platelet scintigraphy were performed in five patients with intracardiac thrombi. Thrombi were visible in 7 sites (5 in the ventricle and 2 in the atrium) by platelet scintigraphy, in 4 sites (3 in the ventricle and 1 in the atrium) by 2-DE, and in 4 sites (4 in the ventricle) by LVG. When aspirin was administered to the patients, platelet scintigraphy had become negative for thrombi in 5 sites and false-negative for them in 2 sites. However, thrombi were detected in 6 sites after the withdrawal of aspirin. On the other hand, thrombi were detected in 4 sites by 2-DE, irrespective of the administration of aspirin. Indium-111-oxine platelet scintigraphy has proved to not only have higher sensitivity for detecting thrombi but also to be capable of observing the coagulation status of platelets on the thrombi. It is therefore considered very helpful in assessing anticoagulation therapy. (Namekawa, K)

  5. Long-term outcome of vincristine-aspirin-ticlopidine (VAT) therapy for vascular tumors associated with Kasabach-Merritt phenomenon.

    Science.gov (United States)

    Fernandez-Pineda, Israel; Lopez-Gutierrez, Juan Carlos; Chocarro, Gloria; Bernabeu-Wittel, Jose; Ramirez-Villar, Gema Lucia

    2013-09-01

    . This study aimed to clarify the combinatorial treatment effect of agents as aspirin and ticlopidine associated with vincristine in the management of Kasabach-Merritt phenomenon (KMP), a severe thrombocytopenic coagulopathy that occurs in the presence of an enlarging vascular tumor such as kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). . A retrospective review was conducted of medical records of all children with diagnosis of KHE or TA associated with KMP treated with vincristine-aspirin-ticlopidine (VAT) therapy at two different institutions in the same country from 1994 to 2011. Clinical features, response to VAT therapy and outcomes were recorded. . Eleven patients (mean age 11 months, range 0-36), including seven females (64%) and four males (36%), were identified. Seven patients underwent incisional biopsy and two different histologies were found, KHE in four patients and TA in three patients. Tumors were located in the head and neck (n = 5), chest wall (n = 2), arm (n = 2) and retroperitoneum (n = 2). Mean platelet level was 10,200/mm(3) (range 4,000-21,000). A plaque-like lesion with ecchymosis was the most common cutaneous manifestation (63%). All patients underwent VAT therapy. Mean duration of treatment was 3.9 months for vincristine, 13.9 months for aspirin, and 13.4 months for ticlopidine. All patients are alive with a mean follow-up of 4.5 years (range, 2-17). . Antiaggregant therapy is helpful in combination with vincristine in the treatment of KMP associated with KHE and TA. Prognosis is excellent if severe thrombocytopenia is controlled despite failure in reduction of tumor size. Copyright © 2013 Wiley Periodicals, Inc.

  6. Vasorelaxant and anti-platelet aggregation effects of aqueous Ocimum basilicum extract.

    Science.gov (United States)

    Amrani, Souliman; Harnafi, Hicham; Gadi, Dounia; Mekhfi, Hassane; Legssyer, Abdelkhaleq; Aziz, Mohammed; Martin-Nizard, Françoise; Bosca, Lisardo

    2009-08-17

    In this work the endothelium-dependant vasorelaxant and anti-platelet aggregation activities of an aqueous extract from Ocimum basilicum were studied. The vasorelaxant effect was undertaken in thoracic aorta from three experimental groups of rats: one of them (NCG) fed with standard diet, the second (HCG) with hypercholesterolemic diet (HCD) and the third (BTG) with hypercholesterolemic diet together with an intragastric administration of Ocimum basilicum extract at a dose of 0.5 g/kg body weight for a period of 10 weeks. The in vitro anti-platelet aggregation of Ocimum basilicum extract was studied using thrombin (0.5 U/ml) and ADP (5 microM) as agonists. The results show that the HCD statistically decreases vascular relaxation in HCG compared to NCG (pOcimum basilicum extract exerts a significant vasorelaxant effect at 10(-5) M (pOcimum basilicum as medicinal plant could be beneficial for cardiovascular system.

  7. Efficacy in Deep Vein Thrombosis Prevention With Extended Mechanical Compression Device Therapy and Prophylactic Aspirin Following Total Knee Arthroplasty: A Randomized Control Trial.

    Science.gov (United States)

    Snyder, Mark A; Sympson, Alexandra N; Scheuerman, Christina M; Gregg, Justin L; Hussain, Lala R

    2017-05-01

    Aspirin at 325 mg twice daily is now included as a nationally approved venous thromboembolism (VTE) prophylaxis protocol for low-risk total knee arthroplasty (TKA) patients. The purpose of this study is to examine whether there is a difference in deep vein thrombosis (DVT) occurrence after a limited tourniquet TKA using aspirin-based prophylaxis with or without extended use of mechanical compression device (MCD) therapy. One hundred limited tourniquet TKA patients, whose DVT risk was managed with aspirin 325 mg twice daily for 3 weeks, were randomized to either using an MCD during hospitalization only or extended use at home up to 6 weeks postoperatively. Lower extremity duplex venous ultrasonography (LEDVU) was completed on the second postoperative day, 14 days postoperatively, and at 3 months postoperatively to confirm the absence of DVT after treatment. The DVT rate for the postdischarge MCD therapy group was 0% and 23.1% for the inpatient MCD group (P aspirin for 3 weeks postoperatively, and on MCD therapy for up to 6 weeks postoperatively experienced superior DVT prophylaxis than patients receiving MCD therapy only as an inpatient (P aspirin and extended-use MCD further validates this type of prophylaxis in low DVT risk TKA patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial

    NARCIS (Netherlands)

    Dewilde, Willem J. M.; Oirbans, Tom; Verheugt, Freek W. A.; Kelder, Johannes C.; de Smet, Bart J. G. L.; Herrman, Jean-Paul; Adriaenssens, Tom; Vrolix, Mathias; Heestermans, Antonius A. C. M.; Vis, Marije M.; Tijsen, Jan G. P.; van 't Hof, Arnoud W.; ten Berg, Jurriën M.; Schölzel, B. E.; van den Branden, B. J.; Plokker, H. W. M.; Bosschaert, M. A.; Slagboom, T.; Vos, J.; Brueren, B. R. G.; Breet, N. J.; Sheikjoesoef, K.; Aarnoudse, W.; Rasoul, S.; van Mieghem, C.; Vandendriessche, T.; Cornelis, K.

    2013-01-01

    If percutaneous coronary intervention (PCI) is required in patients taking oral anticoagulants, antiplatelet therapy with aspirin and clopidogrel is indicated, but such triple therapy increases the risk of serious bleeding. We investigated the safety and efficacy of clopidogrel alone compared with

  9. Oxylipid Profile of Low?Dose Aspirin Exposure: A Pharmacometabolomics Study

    OpenAIRE

    Ellero?Simatos, Sandrine; Beitelshees, Amber L.; Lewis, Joshua P.; Yerges?Armstrong, Laura M.; Georgiades, Anastasia; Dane, Adrie; Harms, Amy C.; Strassburg, Katrin; Guled, Faisa; Hendriks, Margriet M. W. B.; Horenstein, Richard B.; Shuldiner, Alan R.; Hankemeier, Thomas; Kaddurah?Daouk, Rima

    2015-01-01

    Background While aspirin is a well?established and generally effective anti?platelet agent, considerable inter?individual variation in drug response exists, for which mechanisms are not completely understood. Metabolomics allows for extensive measurement of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response. Methods and Results We used a mass?spectrometry?based metabolomics platform to investigate the changes in the serum oxylipid metabolome...

  10. Very late scaffold thrombosis of everolimus-eluting bioresorbable scaffold following implantation in STEMI after discontinuation of dual antiplatelet therapy.

    Science.gov (United States)

    Yahagi, Kazuyuki; Virmani, Renu; Kesavamoorthy, Bhoopalan

    2017-01-01

    A 42-year-old male with a history of smoking and dyslipidemia was admitted due to ST-elevation myocardial infarction. Coronary angiography showed severe stenosis in proximal right coronary artery (RCA) and total occlusion in mid RCA. Absorb everolimus-eluting bioresorbable scaffolds were deployed in mid and proximal RCA. The patient was discharged with dual anti-platelet therapy. Patient was admitted 15-months later due to acute coronary syndrome with scaffold thrombosis. Both aspirin and clopidogrel had been discontinued 1 month prior to the second event because of general malaise. Therefore, either aspirin or clopidogrel should have been continued even after 1 year following stent implantation.

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

    Science.gov (United States)

    Cook, Kevin A; White, Andrew A

    2016-02-01

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

  12. Analgesic, anti-inflammatory and anti-platelet activities of Buddleja crispa.

    Science.gov (United States)

    Bukhari, Ishfaq A; Gilani, Anwar H; Meo, Sultan Ayoub; Saeed, Anjum

    2016-02-25

    Buddleja crispa Benth (Buddlejaceae) is a dense shrub; several species of genus Buddleja have been used in the management of various health conditions including pain and inflammation. The present study was aimed to investigate the analgesic, anti-inflammatory and anti-platelet properties of B. crispa. Male rats (220-270 gm,) and mice (25-30 gm) were randomly divided into different groups (n = 6). Various doses of plant extract of B. crispa, its fractions and pure compounds isolated from the plant were administered intraperitoneally (i.p). The analgesic, anti-inflammatory and anti-platelet activities were assessed using acetic acid and formalin-induced nociception in mice, carrageenan-induced rat paw edema and arachidonic acid-induced platelets aggregation tests. The intraperitoneal administration of the methanolic extract (50 and 100 mg/kg), hexane fraction (10 and 25 mg/kg i.p) exhibited significant inhibition (P < 0.01) of the acetic acid-induced writhing in mice and attenuated formalin-induced reaction time of animals in second phase of the test. Pure compounds BdI-2, BdI-H3 and BH-3 isolated from B. crispa produced significant (P < 0.01) analgesic activity in acetic acid-induced and formalin tests. The crude extract of B. crispa (50-200 mg/kg i.p.) and its hexane fraction inhibited carrageenan-induced rat paw edema with maximum inhibition of 65 and 71% respectively (P < 0.01). The analgesic and anti-inflammatory effect of the plant extract and isolated pure compounds were comparable to diclofenac sodium. B. crispa plant extract (0.5-2.5 mg/mL) produced significant anti-platelet effect (P < 0.01) with maximum inhibition of 78% at 2.5 mg/ml. The findings from our present study suggest that B. crispa possesses analgesic, anti-inflammatory and anti-platelet properties. B. crispa could serve a potential novel source of compounds effective in pain and inflammatory conditions.

  13. Final Results of Cilostazol-Aspirin Therapy against Recurrent Stroke with Intracranial Artery Stenosis (CATHARSIS).

    Science.gov (United States)

    Uchiyama, Shinichiro; Sakai, Nobuyuki; Toi, Sono; Ezura, Masayuki; Okada, Yasushi; Takagi, Makoto; Nagai, Yoji; Matsubara, Yoshihiro; Minematsu, Kazuo; Suzuki, Norihiro; Tanahashi, Norio; Taki, Waro; Nagata, Izumi; Matsumoto, Masayasu

    2015-01-01

    To compare the effect of cilostazol plus aspirin versus aspirin alone on the progression of intracranial arterial stenosis (IAS), and to compare ischemic and hemorrhagic events in patients with symptomatic IAS, an investigator-driven, nationwide multicenter cooperative randomized controlled trial (CATHARSIS; ClinicalTrials.gov Identifier 00333164) was conducted. 165 noncardioembolic ischemic stroke patients with >50% stenosis in the responsible intracranial artery after 2 weeks to 6 months from the onset were randomly allocated to receive either cilostazol 200 mg/day plus aspirin 100 mg/day (n = 83, CA group) or aspirin 100 mg/day alone (n = 82, A group). The primary endpoint was the progression of IAS on magnetic resonance angiography at 2 years after randomization. Secondary endpoints were any vascular events, any cause of death, serious adverse events, new silent brain infarcts, and worsening of the modified Rankin Scale score. Progression of IAS was observed in 9.6% of the CA group patients and in 5.6% of the A group patients, with no significant intergroup difference (p = 0.53). The incidence of the secondary endpoints tended to be lower in the CA group compared with the A group, although the differences were not significant. By using exploratory logistic regression analysis adjusted for patient background characteristics, it was shown that the risk for certain combinations of secondary endpoints was lower in the CA group than in the A group [all vascular events and silent brain infarcts: odds ratio (OR) = 0.37, p = 0.04; stroke and silent brain infarcts: OR = 0.34, p = 0.04; all vascular events, worsening of modified Rankin Scale scores and silent brain infracts: OR = 0.41, p = 0.03]. Major hemorrhage was observed in 4 patients of the CA group and in 3 of the A group. Progression of IAS during the 2-year observation period appears to be less frequent than previously reported in stroke patients on antiplatelet agents after the acute phase, which could be due

  14. 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.

  15. Novel direct factor Xa inhibitory compounds from Tenebrio molitor with anti-platelet aggregation activity.

    Science.gov (United States)

    Lee, Wonhwa; Kim, Mi-Ae; Park, InWha; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup

    2017-11-01

    Tenebrio molitor is an edible insect that has antimicrobial, anticancer, and antihypertensive effects. The aim of this study was to identify the unreported bioactive compounds from T. molitor larvae with inhibitory activities against factor Xa (FXa) and platelet aggregation. Isolated compounds were evaluated for their anti-FXa and anti-platelet aggregation properties by monitoring clotting time, platelet aggregation, FXa activity, and thrombus formation. A diketopiperazine (1, cyclo( L -Pro- L -Tyr)) and a phenylethanoid (2, N-acetyltyramine) were isolated and inhibited the catalytic activity of FXa in a mixed inhibition model and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619. They inhibited ADP- and U46619-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) and the expression of P-selectin and PAC-1 in platelets. They also improved the production of nitric oxide and inhibited the oversecretion of endothelin-1 compared to that of the ADP- or U46619-treated group. In an animal model of arterial and pulmonary thrombosis, the isolated compounds showed enhanced antithrombotic effects. They also elicited anticoagulant effects in mice. Compounds 1-2 inhibited ADP-, collagen-, or U46619-induced platelet aggregation and showed similar anti-thrombotic efficacy to rivaroxaban, a positive control. Therefore, 1-2 could serve as candidates and provide scaffolds for the development of new anti-FXa and anti-platelet drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. EFFECTS OF COMBINATION THERAPY ON PLATELET COUNT IN PATIENTS OF MYOCARDIAL INFARCTION

    Directory of Open Access Journals (Sweden)

    Sadaf Ahmed

    2014-12-01

    Full Text Available Aspirin and clopidogrel are usually used individually to prevent adverse cardiovascular events and stroke. They are used in stabilizing the blood pressure in patients of myocardial infarction while combination therapy of aspirin and Clopidogrel (dual anti-platelet therapy is used for preventing adverse cardiovascular events in myocardial infarction patients. A cross-sectional observational study is conducted through a structured questionnaire from 110 patients of K.I.H.D (Karachi Institute of Heart Disease hospital, Karachi, Pakistan. Indoor/admitted patients with diagnosis of acute coronary syndrome (ACS, non-ST elevation myocardial infarction (NSTE-MI, ST elevation myocardial infarction (STE-MI, supra ventricular tachycardia (SVT were included along with those with previous or current onset of angina pectoris or heart attack. Information from the test reports of these patients was included in the data. Patients without proper test reports were excluded from the study. Combination therapy duration is considered as key tool for evaluation. Out of 100 patients (after exclusion criteria applied almost 18% patients were using the combination therapy for 10 to 25 years while 52% of patients were using the combination therapy for 1 to 10 years. Platelet count of 88% patients was found to be in between 1,50,000–3,50,000/µl. Remaining patients had less than 1,50,000 µl to more than 3,50,000 to 4,50,000 µl. Most frequently reported side effects were chest pain, respiratory issues, headache and depression. On the basis of our data analysis it is concluded that long duration dual anti-platelet therapy will not harm platelet count in human blood but it can create drug dependency in patients. Hypertension is not completely cured with this therapy but can help in stabilizing blood pressure.

  17. The effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder: A randomized clinical trial.

    Science.gov (United States)

    Sepehrmanesh, Zahra; Fahimi, Hosein; Akasheh, Goudarz; Davoudi, Mohamadreza; Gilasi, Hamidreza; Ghaderi, Amir

    2017-11-01

    Different studies have been conducted to find the best adjuvant therapies for depression management. There are controversies over the effects of aspirin as an adjuvant therapy for depression. To determine the effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder. This randomized clinical trial was conducted at Kargarnejad Psychiatric Hospital in Kashan, Isfahan, Iran, from September 1, 2016 to November 1, 2016. The study participants included 100 patients with major depressive disorder who were assigned to aspirin and placebo groups by the use of computer-generated random numbers. Patients in these groups respectively received sertraline-aspirin and sertraline-placebo for eight consecutive weeks. Patients were prescribed 80 milligrams of aspirin twice a day. Also, sertraline was administered at a dose of 50-200 milligrams daily. Beck Depression Inventory was employed for depression severity assessment at four time points, namely before, two, four, and eight weeks after the beginning of the intervention. Medication side effects were also assessed eight weeks after the beginning of the intervention. Data were analyzed by SPSS version 12.0, using Chi-square and the Independent-samples t-test (α=0.05). Both groups were matched in terms of age (p=0.46), gender (p=0.539), and depression severity (p=0.509, with mean score 33.5±4.1 vs. 32.8±5.9) at baseline. However, depression scores were reduced significantly four and eight weeks after initiation of therapy just in the sertraline-aspirin group (pdepression severity among patients with major depressive disorder. Yet, further studies are needed to prove the effectiveness of aspirin and other anti-inflammatory agents in reducing depression severity. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2016082829556N1. The authors received financial support from Research Deputy of Kashan University

  18. MACULAR DEGENERATION AND ASPIRIN USE.

    Science.gov (United States)

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

    2017-09-01

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

  19. Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia

    NARCIS (Netherlands)

    Sonneveld, Myrthe E.; Natunen, Suvi; Sainio, Susanna; Koeleman, Carolien A. M.; Holst, Stephanie; Dekkers, Gillian; Koelewijn, Joke; Partanen, Jukka; van der Schoot, C. Ellen; Wuhrer, Manfred; Vidarsson, Gestur

    2016-01-01

    Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable

  20. Anti-platelet effects of olive oil extract: in vitro functional and proteomic studies.

    Science.gov (United States)

    de Roos, Baukje; Zhang, Xuguang; Rodriguez Gutierrez, Guillermo; Wood, Sharon; Rucklidge, Garry J; Reid, Martin D; Duncan, Gary J; Cantlay, Louise L; Duthie, Garry G; O'Kennedy, Niamh

    2011-10-01

    Platelets play a key role in haemostasis and wound healing, contributing to formation of vascular plugs. They are also involved in formation of atherosclerosic plaques. Some traditional diets, like the Mediterranean diet, are associated with a lower risk of cardiovascular disease. Components in these diets may have anti-platelet functions contributing to their health benefits. We studied the effects of alperujo extract, an olive oil production waste product containing the majority of polyphenols found in olive fruits, through measurement of effects on platelet aggregation and activation in isolated human platelets, and through identification of changes in the platelet proteome. Alperujo extract (40 mg/L) significantly decreased in vitro ADP- (p = 0.002) and TRAP- (p = 0.02) induced platelet activation as measured by the flow cytometry using the antibody for p-selectin (CD62p), but it did not affect the conformation of the fibrinogen receptor as measured by flow cytometry using the antibodies for anti-fibrinogen, CD42a and CD42b. Alperujo extract (100 mg/L) inhibited both collagen- and TRAP-induced platelet aggregation by 5% (p < 0.05), and a combination of hydroxytyrosol and 3,4-dihydroxyphenylglycol were, at least partly, responsible for this effect. Proteomic analysis identified nine proteins that were differentially regulated by the alperujo extract upon ADP-induced platelet aggregation. These proteins represent important mechanisms that may underlie the anti-platelet effects of this extract: regulation of platelet structure and aggregation, coagulation and apoptosis, and signalling by integrin αIIb/β3. Alperujo extract may protect against platelet activation, platelet adhesion and possibly have anti-inflammatory properties.

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

    Science.gov (United States)

    Ta, Von; Simon, Ronald

    2015-01-01

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

  2. Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis

    Directory of Open Access Journals (Sweden)

    Nicholas Schwier

    2016-03-01

    Full Text Available Aspirin (ASA and non-steroidal anti-inflammatory drugs (NSAIDs are a mainstay of therapy for the treatment of idiopathic pericarditis (IP. A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician’s understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts. ASA, ibuprofen, indometacin, and ketorolac relatively have the most evidence in the treatment of IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is the drug of choice in patients with coronary artery disease (CAD, heart failure (HF, or renal disease, but should be avoided in patients with asthma and nasal polyps, who are naïve to ASA therapy. Ibuprofen is an inexpensive and relatively accessible option in patients who do not have concomitant CAD, HF, or renal disease. Indometacin is not available over-the-counter in the USA, and has a relatively higher incidence of central nervous system (CNS adverse effects. Ketorolac is an intravenous option; however, clinicians must be mindful of the maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the disease process of IP, they are part of first-line therapy (along with colchicine, for preventing recurrence of IP. ASA/NSAID choice should be dictated by comorbid conditions, tolerability, and adverse effects. Additionally, the clinician should be mindful of considerations such as tapering, high-sensitivity CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy.

  3. Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis

    Science.gov (United States)

    Schwier, Nicholas; Tran, Nicole

    2016-01-01

    Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of therapy for the treatment of idiopathic pericarditis (IP). A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician’s understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts. ASA, ibuprofen, indometacin, and ketorolac relatively have the most evidence in the treatment of IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is the drug of choice in patients with coronary artery disease (CAD), heart failure (HF), or renal disease, but should be avoided in patients with asthma and nasal polyps, who are naïve to ASA therapy. Ibuprofen is an inexpensive and relatively accessible option in patients who do not have concomitant CAD, HF, or renal disease. Indometacin is not available over-the-counter in the USA, and has a relatively higher incidence of central nervous system (CNS) adverse effects. Ketorolac is an intravenous option; however, clinicians must be mindful of the maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the disease process of IP, they are part of first-line therapy (along with colchicine), for preventing recurrence of IP. ASA/NSAID choice should be dictated by comorbid conditions, tolerability, and adverse effects. Additionally, the clinician should be mindful of considerations such as tapering, high-sensitivity CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy. PMID:27023565

  4. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications.

    Science.gov (United States)

    Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A; Kashfi, Khosrow

    2015-12-15

    Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

    Science.gov (United States)

    Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A.; Kashfi, Khosrow

    2015-01-01

    Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: Nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. PMID:26394025

  6. ASPIRIN RESISTANCE IN NEUROVASCULAR DISEASES

    OpenAIRE

    Martin Vališ; Dagmar Krajíčková; Jaroslav Malý; Radovan Malý; Ilona Fátorová; Oldřich Vyšata; Roman Herzig

    2014-01-01

    Introduction: The issue of resistance to antiplatelet therapy has raised many questions in the area of neurovascular diseases. The first objective of this work was to determine the prevalence of aspirin resistance in neurovascular patients with clinical non-responsiveness to aspirin treatment and a high-risk of atherothrombotic complications using two interpretable and independent methods (aggregation and PFA 100). The second objective was to find the correlation between both assays and to ev...

  7. Aspirin resistance following pediatric cardiac surgery.

    Science.gov (United States)

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

    2010-09-01

    Aspirin is often used to prevent thrombosis in pediatric cardiac surgery. The primary study aim was to assess aspirin resistance in this context. Secondary aims were to evaluate (1) the relationship between elevated inflammatory markers and thrombosis and (2) aspirin's effect on these levels. This was a prospective observational study of children undergoing cardiac surgery managed with and without aspirin. Aspirin response was assessed using the VerifyNow system and urinary 11-dehydrothromboxane B2 (uTxB2) measurements. Laboratory studies of inflammation were also obtained. 101 subjects were studied; 50 received aspirin. Six subjects (5.9%), 5 aspirin-treated, experienced symptomatic thrombosis. When measured by VerifyNow resistance was 43% after aspirin suppositories and 14% after additional days of oral aspirin. There was no correlation with thrombosis. Upper quartile post-operative day (POD) #5 uTxB2 was correlated with thrombosis in aspirin treated subjects (pchildren with high levels of uTxB2 despite aspirin therapy and/or those with elevated preoperative CRP are at increased risk for thrombosis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  8. Bleeding tendency in dual antiplatelet therapy with aspirin/clopidogrel: rescue of the template bleeding time in a single-center prospective study

    Directory of Open Access Journals (Sweden)

    Altman Raul

    2012-01-01

    Full Text Available Abstract Background Patients with heightened platelet reactivity in response to antiplatelet agents are at an increased risk of recurrent ischemic events. However, there is a lack of diagnostic criteria for increased response to combined aspirin/clopidogrel therapy. The challenge is to identify patients at risk of bleeding. This study sought to characterize bleeding tendency in patients treated with aspirin and clopidogrel. Patients/methods In a single-center prospective study, 100 patients under long-term aspirin/clopidogrel treatment, the effect of therapy was assayed by template bleeding time (BT and the inhibition of platelet aggregation (IPA by light transmission aggregometry (LTA. Arachidonic acid (0.625 mmol/L and adenosine diphosphate (ADP; 2, 4, and 8 μmol/L were used as platelet agonists. Results Bleeding episodes (28 nuisance, 2 hematuria [1 severe], 1 severe proctorrhagia, 1 severe epistaxis were significantly more frequent in patients with longer BT. Template BT ≥ 24 min was associated with bleeding episodes (28 of 32. Risk of bleeding increased 17.4% for each 1 min increase in BT. Correlation was found between BT and IPAmax in response to ADP 2 μmol/L but not to ADP 4 or 8 μmol/L. Conclusion In patients treated with dual aspirin/clopidogrel therapy, nuisance and internal bleeding were significantly associated with template BT and with IPAmax in response to ADP 2 μmol/L but not in response to ADP 4 μmol/L or 8 μmol/L.

  9. Is low-dose aspirin therapy to prevent preeclampsia more efficacious in non-obese women or when initiated early in pregnancy?

    Science.gov (United States)

    Cantu, Jessica A; Jauk, Victoria R; Owen, John; Biggio, Joseph R; Abramovici, Adi R; Edwards, Rodney K; Tita, Alan T

    2015-07-01

    Late timing of intervention and maternal obesity are potential explanations for the modest effect of aspirin for preeclampsia prevention. We explored whether low-dose aspirin (LDA) is more effective in women at increased risk when initiated before 16 weeks' gestation or given to non-obese women. Secondary analysis of a trial to evaluate LDA (60 mg/d) for preeclampsia prevention in high-risk women. Participants were randomized to LDA or placebo between 13 and 26 weeks. We stratified the effect of LDA on preeclampsia by (a) timing of randomization (preeclampsia prevention was not more effective when initiated preeclampsia. No particular subgroup of women was more or less likely to benefit from LDA therapy.

  10. Anti-Platelet Aggregation and Vasorelaxing Effects of the Constituents of the Rhizomes of Zingiber officinale

    Directory of Open Access Journals (Sweden)

    Tian-Shung Wu

    2012-07-01

    Full Text Available In the present study, the chemical investigation of the bioactive fractions of the rhizomes of Zingiber officinale has resulted in the identification of twenty-nine compounds including one new compound, O-methyldehydrogingerol (1. Some of the isolates were subjected into the evaluation of their antiplatelet aggregation and vasorelaxing bioactivities. Among the tested compounds, [6]-gingerol (13 and [6]-shogaol (17 exhibited potent anti-platelet aggregation bioactivity. In addition, [10]-gingerol (15 inhibited the Ca2+-dependent contractions in high K+ medium. According to the results in the present research, the bioactivity of ginger could be related to the anti-platelet aggregation and vasorelaxing mechanism.

  11. Vancomycin-induced Immune Thrombocytopenia Proven by the Detection of Vancomycin-dependent Anti-platelet Antibody with Flow Cytometry

    OpenAIRE

    Yamanouchi, Jun; Hato, Takaaki; Shiraishi, Sanshiro; Takeuchi, Kazuto; Yakushijin, Yoshihiro; Yasukawa, Masaki

    2016-01-01

    Vancomycin-induced thrombocytopenia is a rare adverse reaction that may be overlooked because no specific diagnostic test is currently available. We herein report a patient with vancomycin-induced immune thrombocytopenia who was diagnosed by the detection of vancomycin-dependent anti-platelet antibody with flow cytometry. An IgG antibody in the patient's serum reacted with platelets only in the presence of vancomycin. Severe thrombocytopenia gave rise to life-threatening gastrointestinal blee...

  12. Anti-platelet activity of water dispersible curcuminoids in rat platelets.

    Science.gov (United States)

    Maheswaraiah, Anikisetty; Rao, Lingamallu Jaganmohan; Naidu, Kamatham Akhilender

    2015-03-01

    Curcuminoids are active principle of turmeric with plethora of health beneficial properties. In this study, we have evaluated for the first time the effect of water dispersible curcuminoids on rat platelet aggregation. Curcuminoids (10-30 µg/mL) significantly inhibited platelet aggregation induced by agonists viz., collagen, ADP and arachidonic acid. Curcuminoids were found to be two-fold more potent than curcumin in inhibiting platelet aggregation. Intracellular curcuminoid concentration was relatively higher than curcumin in rat platelets. Curcuminoids significantly attenuated thromboxane A2 , serotonin levels in rat platelets which play an important role in platelet aggregation. Curcuminoid treatment increased nitric oxide (NO) levels in platelets treated with agonists. Curcuminoids inhibited free radicals such as superoxide anion released from activated platelets, which ultimately inhibits platelet aggregation. Further, curcuminoids inhibited 12-lipoxygenase activity and formation of 12-hydroperoxyeicosatetraenoic acid (12-HPETE) in activated rat platelets which regulates platelet aggregation. The results suggest that curcuminoids have remarkable anti-platelet activity by modulating multiple mechanisms involved in platelet aggregation. Thus curcuminoids may have a therapeutic potential to prevent platelet activation related disorders. Copyright © 2015 John Wiley & Sons, Ltd.

  13. A prospective randomized trial of aspirin-clopidogrel combination therapy and dose-adjusted warfarin on indices of thrombogenesis and platelet activation in atrial fibrillation.

    Science.gov (United States)

    Kamath, Sridhar; Blann, Andrew D; Chin, Bernard S P; Lip, Gregory Y H

    2002-08-07

    This study was designed to investigate whether or not combination aspirin-clopidogrel therapy would reduce markers of thrombogenesis and platelet activation in atrial fibrillation (AF), in a manner similar to warfarin. Dose-adjusted warfarin is beneficial as thromboprophylaxis in AF, but potentially serious side effects and regular monitoring leave room for alternative therapies. METHODS; We randomized 70 patients with nonvalvular AF who were not on any antithrombotic therapy to either dose-adjusted warfarin (international normalized ratio 2 to 3) (Group I) or combination therapy with aspirin 75 mg and clopidogrel 75 mg (Group II). Plasma indices of thrombogenesis (fibrin D-dimer, prothrombin fragment 1+2) and platelet activation (beta-thromboglobulin [TG] and soluble P-selectin) were quantified, along with platelet aggregation responses to standard agonists, at baseline (pretreatment) and at six weeks posttreatment. RESULTS; Pretreatment levels of fibrin D-dimer (p = 0.001), beta-TG (p = 0.01) and soluble P-selectin (p = 0.03) were raised in patients with AF, whereas plasma prothrombin fragment 1+2 levels and platelet aggregation were not significantly different compared with controls. Dose-adjusted warfarin reduced plasma levels of fibrin D-dimer, prothrombin fragment 1+2 and beta-thromboglobulin levels at six weeks (all p failed to reduce plasma indices of thrombogenesis and platelet activation in AF, although some aspects of ex vivo platelet aggregation were altered. Anticoagulation with warfarin may be superior to combination aspirin-clopidogrel therapy as thromboprophylaxis in AF.

  14. Oxylipid Profile of Low-Dose Aspirin Exposure: A Pharmacometabolomics Study.

    Science.gov (United States)

    Ellero-Simatos, Sandrine; Beitelshees, Amber L; Lewis, Joshua P; Yerges-Armstrong, Laura M; Georgiades, Anastasia; Dane, Adrie; Harms, Amy C; Strassburg, Katrin; Guled, Faisa; Hendriks, Margriet M W B; Horenstein, Richard B; Shuldiner, Alan R; Hankemeier, Thomas; Kaddurah-Daouk, Rima

    2015-10-26

    While aspirin is a well-established and generally effective anti-platelet agent, considerable inter-individual variation in drug response exists, for which mechanisms are not completely understood. Metabolomics allows for extensive measurement of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response. We used a mass-spectrometry-based metabolomics platform to investigate the changes in the serum oxylipid metabolome induced by an aspirin intervention (14 days, 81 mg/day) in healthy subjects (n=156). We observed a global decrease in serum oxylipids in response to aspirin (25 metabolites decreased out of 30 measured) regardless of sex. This decrease was concomitant with a significant decrease in serum linoleic acid levels (-19%, P=1.3×10(-5)), one of the main precursors for oxylipid synthesis. Interestingly, several linoleic acid-derived oxylipids were not significantly associated with arachidonic-induced ex vivo platelet aggregation, a widely accepted marker of aspirin response, but were significantly correlated with platelet reactivity in response to collagen. Together, these results suggest that linoleic acid-derived oxylipids may contribute to the non-COX1 mediated variability in response to aspirin. Pharmacometabolomics allowed for more comprehensive interrogation of mechanisms of action of low dose aspirin and of variation in aspirin response. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  15. Aspirin and Omeprazole

    Science.gov (United States)

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

  16. Pharmacogenomics of Anti-platelet Therapy: How much evidence is enough for clinical implementation?

    OpenAIRE

    Perry, Christina G.; Shuldiner, Alan R.

    2013-01-01

    Pharmacogenomics, the study of the genomics of drug response and adverse effects, holds great promise for more effective individualized (personalized) medicine. Recent evidence supports a role of loss-of-function variants in the cytochrome P450 enzyme CYP2C19 as a determinant of clopidogrel response. Those who carry loss-of-function variants do not metabolize clopidogrel, a prodrug, into its active form resulting in decreased inhibition of platelet function and a higher likelihood of recurren...

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

    OpenAIRE

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

    1984-01-01

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

  18. Reconsidering low-dose aspirin therapy for cardiovascular disease: a study protocol for physician and patient behavioral change

    Directory of Open Access Journals (Sweden)

    Staton Elizabeth W

    2011-06-01

    Full Text Available Abstract Background There are often disparities between current evidence and current practice. Decreasing the gap between desired practice outcomes and observed practice outcomes in the healthcare system is not always easy. Stopping previously recommended or variably recommended interventions may be even harder to achieve than increasing the use of a desired but under-performed activity. For over a decade, aspirin has been prescribed for primary prevention of cardiovascular disease and for patients with the coronary artery disease risk equivalents; yet, there is no substantial evidence of an appropriate risk-benefit ratio to support this practice. This paper describes the protocol of a randomized trial being conducted in six primary care practices in the Denver metropolitan area to examine the effectiveness of three interventional strategies to change physician behavior regarding prescription of low-dose aspirin. Methods All practices received academic detailing, one arm received clinician reminders to reconsider aspirin, a second arm received both clinician and patient messages to reconsider aspirin. The intervention will run for 15 to 18 months. Data collected at baseline and for outcomes from an electronic health record will be used to assess pre- and post-interventional prescribing, as well as to explore any inappropriate decrease in aspirin use by patients with known cardiovascular disease. Discussion This study was designed to investigate effective methods of changing physician behavior to decrease the use of aspirin for primary cardiovascular disease prevention. The results of this study will contribute to the small pool of knowledge currently available on the topic of ceasing previously supported practices. Trial Registration ClinicalTrials.gov: NCT01247454

  19. Protocol for a systematic review of the diagnostic and prognostic utility of tests currently available for the detection of aspirin resistance in patients with established cardiovascular or cerebrovascular disease.

    Science.gov (United States)

    Raichand, Smriti; Moore, David; Riley, Richard D; Lordkipanidzé, Marie; Dretzke, Janine; O'Donnell, Jennifer; Jowett, Sue; Bayliss, Sue; Fitzmaurice, David A

    2013-02-26

    The benefits of aspirin as an anti-platelet agent are well established; however, there has been much debate about the lack of uniformity in the efficacy of aspirin to inhibit platelet function. In some patients, aspirin fails to inhibit platelets even where compliance has been verified, a phenomenon which has been termed "aspirin resistance". These patients may in turn be at a higher risk of future vascular events. The proportion of "resistant" patients identified depends on the type of platelet function test. Therefore, the aim of this systematic review is to determine which, if any, platelet function test has utility in terms of identifying patients with a high risk of vascular events. The review has been registered with PROSPERO (CRD42012002151). Relevant studies will be sought from bibliographic databases. Trials registers will be searched for ongoing studies. Reference lists will be checked and subject experts contacted. There will be no date or language restrictions. Standard reviewing methodology to minimise bias will be employed. Any prospective studies in patients on aspirin therapy and assessing platelet function in relation to relevant clinical outcomes will be included, as will studies reporting prognostic models. Risk of bias assessment will be based on the Quality Assessment of Diagnostic Accuracy Studies guidelines, and suitable criteria for assessing quality of prognostic studies. Data on test accuracy measures, relative risks, odds or hazard ratios will be extracted and meta-analysed, where possible, using a random-effects model to account for between-study heterogeneity. Where appropriate, the causes of heterogeneity will be explored through meta-regression and sub-group or sensitivity analyses. If platelet function testing is demonstrated to have diagnostic/predictive utility in a specific population, the potential for a cost-effectiveness analysis will be considered and, if possible, an economic model constructed. This will be supported by a

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

    DEFF Research Database (Denmark)

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

    2018-01-01

    therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did......, and dipyridamole) with that of guideline-based antiplatelet therapy. METHODS: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using...... was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using...

  1. Adjuvant Aspirin Therapy Reduces Symptoms of Schizophrenia Spectrum Disorders : Results From a Randomized, Double-Blind, Placebo-Controlled Trial

    NARCIS (Netherlands)

    Laan, Wijnand; Grobbee, Diederick E.; Selten, Jean-Paul; Heijnen, Cobi J.; Kahn, Rene S.; Burger, Huibert

    Objective: Inflammatory processes may play a role in the pathophysiology of schizophrenia. The aim of this study was to determine the efficacy of adjuvant treatment with aspirin (acetylsalicylic acid) in schizophrenia spectrum disorders. Method: This randomized, double-blind, placebo-controlled

  2. Laboratory assessment of anti-thrombotic therapy in heart failure, atrial fibrillation and coronary artery disease: insights using thrombelastography and a micro-titre plate assay of thrombogenesis and fibrinolysis.

    Science.gov (United States)

    Lau, Y C; Xiong, Q; Ranjit, P; Lip, G Y H; Blann, A D

    2016-08-01

    As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk.

  3. A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Hull, Mark A; Sandell, Anna C; Montgomery, Alan A; Logan, Richard F A; Clifford, Gayle M; Rees, Colin J; Loadman, Paul M; Whitham, Diane

    2013-07-29

    The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2×2 factorial 'efficacy' study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55-73 year-old patients, who have been identified as 'high risk' (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and 'advanced') per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as 'intermediate risk' for future surveillance. Exploratory end-points include levels of

  4. Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries.

    Science.gov (United States)

    Mo, Chen; Sun, Gang; Lu, Ming-Liang; Zhang, Li; Wang, Yan-Zhi; Sun, Xi; Yang, Yun-Sheng

    2015-05-07

    To determine the preventive effect and safety of proton pump inhibitors (PPIs) in low-dose aspirin (LDA)-associated gastrointestinal (GI) ulcers and bleeding. We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to December 2013, and checked conference abstracts of randomized controlled trials (RCTs) on the effect of PPIs in reducing adverse GI events (hemorrhage, ulcer, perforation, or obstruction) in patients taking LDA. The preventive effects of PPIs were compared with the control group [taking placebo, a cytoprotective agent, or an H2 receptor antagonist (H2RA)] in LDA-associated upper GI injuries. The meta-analysis was performed using RevMan 5.1 software. We evaluated 8780 participants in 10 RCTs. The meta-analysis showed that PPIs decreased the risk of LDA-associated upper GI ulcers (OR = 0.16; 95%CI: 0.12-0.23) and bleeding (OR = 0.27; 95%CI: 0.16-0.43) compared with control. For patients treated with dual anti-platelet therapy of LDA and clopidogrel, PPIs were able to prevent the LDA-associated GI bleeding (OR = 0.36; 95%CI: 0.15-0.87) without increasing the risk of major adverse cardiovascular events (MACE) (OR = 1.00; 95%CI: 0.76-1.31). PPIs were superior to H2RA in prevention of LDA-associated GI ulcers (OR = 0.12; 95%CI: 0.02-0.65) and bleeding (OR = 0.32; 95%CI: 0.13-0.79). PPIs are effective in preventing LDA-associated upper GI ulcers and bleeding. Concomitant use of PPI, LDA and clopidogrel did not increase the risk of MACE.

  5. Role of Aspirin in Breast Cancer Survival.

    Science.gov (United States)

    Chen, Wendy Y; Holmes, Michelle D

    2017-07-01

    Chemotherapy and hormonal therapy have significantly decreased breast cancer mortality, although with considerable side effects and financial costs. In the USA, over three million women are living after a breast cancer diagnosis and are eager for new treatments that are low in toxicity and cost. Multiple observational studies have reported improved breast cancer survival with regular aspirin use. Furthermore, pooled data from five large randomized trials of aspirin for cardiovascular disease showed that subjects on aspirin had decreased risk of cancer mortality and decreased risk of metastatic cancer. Although the potential mechanism for aspirin preventing breast cancer is not known, possible pathways may involve platelets, inflammation, cyclooxygenase (COX) 2, hormones, or PI3 kinase. This review article summarizes the current epidemiologic and clinical trial evidence as well as possible underlying mechanisms that justify current phase III randomized trials of aspirin to improve breast cancer survival.

  6. Molecular spectroscopic and thermodynamic studies on the interaction of anti-platelet drug ticlopidine with calf thymus DNA

    Science.gov (United States)

    Afrin, Shumaila; Rahman, Yusra; Sarwar, Tarique; Husain, Mohammed Amir; Ali, Abad; Shamsuzzaman; Tabish, Mohammad

    2017-11-01

    Ticlopidine is an anti-platelet drug which belongs to the thienopyridine structural family and exerts its effect by functioning as an ADP receptor inhibitor. Ticlopidine inhibits the expression of TarO gene in S. aureus and may provide protection against MRSA. Groove binding agents are known to disrupt the transcription factor DNA complex and consequently inhibit gene expression. Understanding the mechanism of interaction of ticlopidine with DNA can prove useful in the development of a rational drug designing system. At present, there is no such study on the interaction of anti-platelet drugs with nucleic acids. A series of biophysical experiments were performed to ascertain the binding mode between ticlopidine and calf thymus DNA. UV-visible and fluorescence spectroscopic experiments confirmed the formation of a complex between ticlopidine and calf thymus DNA. Moreover, the values of binding constant were found to be in the range of 103 M- 1, which is indicative of groove binding between ticlopidine and calf thymus DNA. These results were further confirmed by studying the effect of denaturation on double stranded DNA, iodide quenching, viscometric studies, thermal melting profile as well as CD spectral analysis. The thermodynamic profile of the interaction was also determined using isothermal titration calorimetric studies. The reaction was found to be endothermic and the parameters obtained were found to be consistent with those of known groove binders. In silico molecular docking studies further corroborated well with the experimental results.

  7. 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 ...

  8. Aspirin challenge/desensitisation before coronary stenting in subjects with history of hypersensitivity. A pragmatic approach.

    Science.gov (United States)

    Cortellini, G; Testi, S; Severino, M; Chechi, T; Iorno, M L; Santucci, A; Corvetta, A; Piovaccari, G; Santarelli, A; Franco, N; Canonica, G W; Passalacqua, G

    2012-08-01

    Aspirin hypersensitivity may represent a major problem in patients with ischemic coronary disease who need a stenting procedure. In those patients, clinically unsettled reasonably quick desensitisation procedures are needed. In our study we attempted to select the most suitable procedure on the basis of characteristics and severity of ASA hypersensitivity. Thirty patients with a history of mild reactions to anti-inflammatory doses of aspirin (> 325 mg) were considered at low risk and underwent a tolerance test in 5 steps. Thirty-one patients, with a history of severe reactions to anti-platelet doses of aspirin 0 mg) underwent a slow desensitisation in 12 steps, reaching a cumulative dose of 150 mg ASA in 220 minutes. In the first group, 29 patients tolerated the challenge. One developed urticaria, thus underwent challenge/desensitisation and achieved tolerance. In the second group, 3 patients did not tolerate the procedure and had to discontinue. CONCLUSION. Our approach to aspirin hypersensitivity in patients needing coronary stenting, based on a severity stratification, allowed to achieve an effective tolerance to aspirin in the majority of subject in a reasonable short time.

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

    Science.gov (United States)

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

    2015-02-01

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

  10. Comparative anti-platelet and antioxidant properties of polyphenol-rich extracts from: berries of Aronia melanocarpa, seeds of grape and bark of Yucca schidigera in vitro.

    Science.gov (United States)

    Olas, Beata; Wachowicz, Barbara; Tomczak, Anna; Erler, Joachim; Stochmal, Anna; Oleszek, Wieslaw

    2008-02-01

    The aim of the present study was to investigate and compare the anti-platelet action of extracts from three different plants: bark of Yucca schidigera, seeds of grape and berries of Aronia melanocarpa (chokeberry). Anti-platelet action of tested extracts was compared with action of well characterized antioxidative and anti-platelet commercial monomeric polyphenol-resveratrol. The effects of extracts on platelet adhesion to collagen, collagen-induced platelet aggregation and on the production of O2-* in resting platelets and platelets stimulated by a strong platelet agonist-thrombin were studied. The in vitro experiments have shown that all three tested extracts (5-50 microg/ml) rich in polyphenols reduce platelet adhesion, aggregation and generation of O2-* in blood platelets. Comparative studies indicate that all three plant extracts were found to be more reactive in reduction of platelet processes than the solution of pure resveratrol. The tested extracts due to their anti-platelet effects may play an important role as components of human diet in prevention of cardiovascular or inflammatory diseases, where blood platelets are involved.

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  13. 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

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

    Science.gov (United States)

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

    2014-12-02

    There is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke. Retrospective. We conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database. Among 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke. Compared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates. Among patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Paradoxical Effect of Aspirin

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    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.

  16. Esomeprazole alone compared with esomeprazole plus aspirin for the treatment of aspirin-related peptic ulcers.

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    Liu, Chun-Peng; Chen, Wen-Chi; Lai, Kwok-Hung; Mar, Guang-Yuan; Lin, Shyr-Yi; Ger, Luo-Ping; Hsu, Ping-I

    2012-07-01

    Aspirin-related peptic ulcers are a common disorder. However, whether or not aspirin should be continued during treatment for aspirin-related ulcers remains unclear. To compare esomeprazole alone with esomeprazole plus aspirin in the treatment of aspirin-related peptic ulcers and to investigate the independent factors associated with the failure of ulcer healing. From January 2008 to July 2011, patients with aspirin-related peptic ulcers were randomized to receive esomeprazole (40 mg per day) alone or esomeprazole (40 mg per day) plus aspirin (100 mg per day) for 8 weeks. The subjects with Helicobacter pylori infection were treated with standard triple therapy. Follow-up endoscopy was carried out at the end of the 8th week. The primary end point was the healing of peptic ulcers. In all, 178 patients (89 receiving esomeprazole alone and 89 receiving esomeprazole plus aspirin) were enrolled and underwent follow-up endoscopy. The healing rate of ulcers by modified intention-to-treat analysis was 82.5% (95% confidence interval (CI), 74.2-90.8%) among patients treated with esomeprazole alone and 81.5% (95% CI, 73.0-90.0%) among patients treated with esomeprazole plus aspirin (difference, 1.0%; 95% CI, -11.2 to 12.6%). The per-protocol analysis yielded similar results (healing rate: 83.1% vs. 83.8%, respectively; difference, 0.7%; 95% CI, -11.2 to 12.6%). Multivariate analysis disclosed that use of steroids during treatment (odds ratio: 5.6; 95% CI, 1.1-27.7%) was the only independent factor associated with the failure of ulcer healing. The observed ulcer healing rates were comparable in the esomeprazole and esomeprazole-plus-aspirin groups, but the wide CIs do not rule out clinically meaningful differences of more than 10%.

  17. [Aspirin and colorectal cancer].

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

    2018-02-01

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

  18. Aspirin for Primary Prevention.

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    Richman, Ilana B; Owens, Douglas K

    2017-07-01

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

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

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

    2016-01-20

    Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions. 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. 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 Helicobacter pylori infection (OR = 2.242, 95% CI: 1.032-4.870), male gender (OR = 2.211, 95% CI: 1.027-4.760), GG genotype of rs2243086 (OR = 4.516, 95% CI: 1.180-17.278), and AA genotype of rs1330344 (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 of rs2238631 and TT genotype of rs2243100 was higher than in those without upper gastrointestinal bleeding. 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 rs1330344 were possible genetic risk factors. TT genotype of rs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in aspirin users.

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

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    Yun Wu

    2016-01-01

    Full Text Available 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 Helicobacter pylori infection (OR = 2.242, 95% CI: 1.032-4.870, male gender (OR = 2.211, 95% CI: 1.027-4.760, GG genotype of rs2243086 (OR = 4.516, 95% CI: 1.180-17.278, and AA genotype of rs1330344 (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 of rs2238631 and TT genotype of rs2243100 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 rs1330344 were possible genetic risk factors. TT genotype of rs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in

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

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

    2017-12-14

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

  2. Anti-platelet and anti-thrombotic effect of a traditional herbal medicine Kyung-Ok-Ko.

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    Kim, Tae-Ho; Lee, Kyoung Mee; Hong, Nam Doo; Jung, Yi-Sook

    2016-02-03

    Kyung-Ok-Ko (KOK), a traditional herbal prescription, contains six main ingredients; Rehmannia glutinosa var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey. KOK has been widely taken as a traditional oriental medicine for improving blood circulation or age-related symptoms, such as dementia and stroke. However, the effect of KOK on platelet activity has not been clarified. To evaluate the effect of KOK on platelet function, we evaluated its effect on functional markers of platelet activation such as aggregation and shape change. As a mechanism study for the effect of KOK, we examined its effect on granule secretion, intracellular Ca(2+) increase, and PLCγ and Akt activation. To investigate the effect of orally administered KOK (0.5, 1, 2 g/kg), we examined its ex vivo effect on platelet aggregation in rat, and its in vivo anti-thrombotic effect in mice thromboembolism model. Furthermore, the effect of KOK on bleeding time was examined to estimate its potential side effect. KOK (0.3, 1, 3, 10 mg/ml) inhibited collagen-induced platelet aggregation and shape change in rat platelets in a concentration-dependent manner. The mechanism for the anti-platelet effect of KOK seems to involve the inhibition of ATP release, intracellular Ca(2+) elevation, and the phosphorylation of PLCγ and Akt. In rat ex vivo study, KOK (2 g/kg, p.o. for 1 day, and 0.5, 1, 2 g/kg, p.o. for 7 days) also had significant inhibitory effects on collagen-induced platelet aggregation. In addition, KOK showed a significant protective effect against thrombosis attack in mice. The prolongation of bleeding time by KOK was much less than that by ASA, suggesting a beneficial potential of KOK than ASA in view of side effect. These findings suggest that KOK elicits remarkable anti-platelet and anti-thrombotic effects with less side effect of bleeding, and therefore, it may have a therapeutic potential for the prevention of platelet-associated cardiovascular diseases

  3. Tratamiento perioperatorio del paciente con antiagregación o anticoagulación Peri-operative management of patients with anti-platelet or anticoagulation treatment

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    Juan C Déaz M

    2012-10-01

    Full Text Available El tratamiento del paciente que recibe terapias que afectan la hemostasia normal (anticoagulantes y/o antiagregantes plaquetarios y que será sometido a un procedimiento quirúrgico, es uno de los retos que se presentan cada vez con mayor frecuencia en los servicios de cardiología. La toma de la mejor opción terapéutica en este grupo de pacientes requiere un profundo conocimiento sobre los riesgos de sangrado en caso de continuarse el tratamiento, frente a los riesgos de trombosis o embolismo en caso de suspenderlo. Por tradición, esa decisión se ha basado más en el temor al riesgo de sangrado, por lo cual en muchos casos se ha suspendido dicha terapia de manera innecesaria. En los últimos años, la aparición de la evidencia que indica que no sólo no es alto el riesgo de sangrado sino que además la continuación de estos medicamentos en muchos casos disminuye desenlaces adversos mayores, ha llevado a replantear esta conducta. En este artículo se revisará la evidencia actual existente al respecto y se suministrarán pautas que permitan la toma de una decisión adecuada.Treatment of patients receiving therapies that affect normal hemostasis (anticoagulants and / or anti-platelet aggregators and that will undergo surgery, is one of the challenges that arise with increasing frequency in the cardiology services. Making the best therapeutic option in these patients requires a thorough understanding of the risks of bleeding in case of continuing the treatment against the risks of thrombosis or embolism in case of stopping it. By tradition, this decision has been based more on fear to the risk of bleeding, whereby in many cases this therapy has been suspended unnecessarily. In recent years, the emergence of evidence indicates that the risk of bleeding is not high and that continuation of these drugs in many cases reduce major adverse outcomes. This has led to redefine this behavior. In this article we review the current evidence available on

  4. Inhibition of platelet aggregation by prostaglandin E1 (PGE1) in diabetic patients during therapy with clopidogrel and aspirin.

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    Kreutz, Rolf P; Nystrom, Perry; Kreutz, Yvonne; Miao, Jia; Kovacs, Richard; Desta, Zeruesenay; Flockhart, David A; Jin, Yan

    2013-01-01

    Diabetes mellitus (DM) is associated with increased platelet activation and reduced platelet inhibition by clopidogrel. Prostaglandin E1 (PGE1) stimulates adenyl cyclase activity in platelets and increases cyclic AMP concentrations, which inhibit Ca(2+)release and platelet aggregation induced by P2Y1 receptor activation. PGE1 is included in the VerifyNow P2Y12 assay to suppress P2Y1 induced platelet aggregation. We hypothesized that diabetes mellitus may be associated with altered response to PGE1 in subjects treated with clopidogrel. Subjects with established coronary artery disease who were taking clopidogrel 75 mg daily and aspirin for >14 days were enrolled (n = 96). Diabetic (n = 34) were compared with non-diabetic subjects (n = 62). VerifyNow P2Y12 assay and light transmittance aggregometry (LTA) were performed using ADP as agonist with and without addition of PGE1. Genomic DNA was genotyped for common cytochrome P450 (CYP) 2C19 variants using Taqman assays. Residual on-treatment platelet aggregation induced by 20 µM ADP was not significantly different between subjects with and without DM. Addition of 22 nM and 88 nM PGE1 to 20 µM ADP resulted in a significant reduction of maximal platelet aggregation (MPA). Residual LTA platelet aggregation with PGE1 and VerifyNow P2Y12 platelet reactivity were significantly higher in subjects with DM than those without DM and in carriers of CYP 2C19*2 polymorphism. We conclude that an impaired inhibitory response to PGE1 may contribute to the high platelet reactivity phenotype in subjects with DM treated with clopidogrel. Addition of PGE1 to ADP agonist platelet assays may identify subjects with blunted inhibitory response to prostaglandins and result in a higher proportion of subjects with DM being classified as non-responders.

  5. Esomeprazole and rabeprazole did not reduce antiplatelet effects of aspirin/clopidogrel dual therapy in patients undergoing percutaneous coronary intervention: a prospective, randomized, case-control study.

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    Liu, Li-Peng; Wang, Yan; Si, Rui; Yuan, Ming; Cheng, Kang; Guo, Wen-Yi

    2016-01-01

    Controversy has been prompted based on drug interaction between proton pump inhibitors (PPIs) and aspirin/clopidogrel leading to weakened effects. However, whether such interaction was drug-specific or class effect remains controversial. This study predicted the impact of esomeprazole and rabeprazole on efficacy of dual antiplatelet therapy (DAPT). This study, involving 150 patients, evaluated the efficacy of DAPT upon concomitant use of esomeprazole (40 mg/d) or rabeprazole (20 mg/d). Platelet reactivity was assessed by value of ADP-induced light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at day 1, day 3 and day 30 end points after initiation of DAPT. No significance were observed by post-hoc analysis of treatment-by-period interaction in LTA value and VASP-PRI value when compared with non-PPI users, which suggests no carryover effect in both PPIs over the 30-day treatment period. Moreover, no statistical differences was in LTA or VASP-PRI value in esomeprazole group while rabeprazole group showed decreased in antiplatelet function of DAPT at the day 3 and day 30 end points. Although antiplatelet effect of DAPT were not affected upon concomitant use of both PPIs over the 30-day treatment period, esomeprazole exerts much more stable impact on antiplatelet effect than rabeprazole among respective end points.

  6. Aspirin overutilization for the primary prevention of cardiovascular disease

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    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

  7. Aspirin therapy reduces the ability of platelets to promote colon and pancreatic cancer cell proliferation: Implications for the oncoprotein c-MYC

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    Sylman, Joanna L.; Ngo, Anh T. P.; Pang, Jiaqing; Sears, Rosalie C.; Williams, Craig D.; McCarty, Owen J. T.

    2017-01-01

    Aspirin, an anti-inflammatory and antithrombotic drug, has become the focus of intense research as a potential anticancer agent owing to its ability to reduce tumor proliferation in vitro and to prevent tumorigenesis in patients. Studies have found an anticancer effect of aspirin when used in low, antiplatelet doses. However, the mechanisms through which low-dose aspirin works are poorly understood. In this study, we aimed to determine the effect of aspirin on the cross talk between platelets and cancer cells. For our study, we used two colon cancer cell lines isolated from the same donor but characterized by different metastatic potential, SW480 (nonmetastatic) and SW620 (metastatic) cancer cells, and a pancreatic cancer cell line, PANC-1 (nonmetastatic). We found that SW480 and PANC-1 cancer cell proliferation was potentiated by human platelets in a manner dependent on the upregulation and activation of the oncoprotein c-MYC. The ability of platelets to upregulate c-MYC and cancer cell proliferation was reversed by an antiplatelet concentration of aspirin. In conclusion, we show for the first time that inhibition of platelets by aspirin can affect their ability to induce cancer cell proliferation through the modulation of the c-MYC oncoprotein. PMID:27903583

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

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    Isnatin Miladiyah

    2016-01-01

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

  9. Inappropriate combination of warfarin and aspirin.

    Science.gov (United States)

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

    2016-03-01

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

  10. Targeting AMPK, mTOR and β-Catenin by Combined Metformin and Aspirin Therapy in HCC: An Appraisal in Egyptian HCC Patients.

    Science.gov (United States)

    Abdelmonsif, Doaa Ali; Sultan, Ahmed S; El-Hadidy, Wessam F; Abdallah, Dina Mohamed

    2018-02-01

    Hepatocellular carcinoma (HCC) is an expanding health problem with a great impact on morbidity and mortality, both in Egypt and worldwide. Recently, metformin and aspirin showed a potential anticancer effect on HCC, although the mechanism of this effect is not fully elucidated. The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and β-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients. HepG2 cells were exposed to increasing concentrations of metformin, aspirin and combined treatment, and an MTT assay was performed to determine half maximal inhibitory concentration (IC 50 ). Caspase-3 activity, cell cycle analysis, and protein expression of AMPK, phosphorylated AMPK (pAMPK) and mTOR proteins were assessed. Furthermore, the expression and localization of β-catenin protein was assessed by immunocytochemistry, and protein expression of pAMPK, mTOR and β-catenin was assessed in Egyptian HCC and cirrhotic tissue specimens. Metformin/aspirin combined treatment had a synergistic effect on cell cycle arrest at the G2/M phase and apoptosis induction in a caspase-dependent manner via downregulation of pAMPK and mTOR protein expression. Additionally, metformin/aspirin combined treatment enhanced cell-cell membrane localization of β-catenin expression in HepG2 cells, which might inhibit the metastatic potential of HepG2 cells. In Egyptian HCC specimens, pAMPK, mTOR and β-catenin proteins showed a significant increased expression compared with cirrhotic controls. Targeting AMPK, mTOR and β-catenin by combined metformin/aspirin treatment could be a promising therapeutic strategy for Egyptian HCC patients, and possibly other HCC patients.

  11. Incidence, predictors, and outcomes of gastrointestinal bleeding in patients on dual antiplatelet therapy with aspirin and clopidogrel.

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    Alli, Oluseun; Smith, Colin; Hoffman, Micah; Amanullah, Steven; Katz, Philip; Amanullah, Aman M

    2011-01-01

    The benefits of dual antiplatelet therapy are counterbalanced by the increased incidence of gastrointestinal (GI) complications. The aim of this study was to determine the frequency of GI bleeding, identify the predictors associated with the increased bleeding, and determine the short-term and long-term outcomes. This was an observational, case-control cohort study carried out at the Albert Einstein Medical Center. It included all patients who had a drug-eluting stent implanted between May 2003 and April 2007. A total of 1852 patients were identified; of these 50 patients were readmitted for a GI bleed. A control group of 202 patients who did not have any evidence of GI bleeding were compared with the original group. All data were expressed as mean±SD. The baseline clinical characteristics between the 2 groups were compared using the t test and the Fisher exact test. Multivariate analysis was used to determine the predictors of GI bleeding. The rate of GI bleeding was 2.7%. The mean age in the group with GI bleeding was 70.9±12.2 years, whereas in the group without GI bleeding it was 66.5±12.8 years (P<0.05). The majority of the patients presented with melena (40%). Gastritis and gastric ulcers were the most common findings seen in 49% of the patients on endoscopy. On multivariate logistic regression analysis, a history of GI bleeding was the most important independent predictor of future GI bleeding (P<0.001), whereas the use of statins was found to be protective (95% confidence interval, 0.13-0.48; P<0.001) against future GI bleeding. The 30-day mortality rate in the GI bleeding and control groups was 3.7% and 0%, respectively (P<0.01), whereas in the corresponding 1 year the mortality rate was 18.9% and 0%, respectively (P<0.001). The rate of GI bleeding in patients on dual antiplatelet therapy is low. Earlier history of GI bleeding is the most significant multivariate predictor of future GI bleeding whereas statins seemed to be protective. Patients with GI

  12. 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 ...

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

    Science.gov (United States)

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

    2015-05-01

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

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

    OpenAIRE

    Navaratnam, K; Alfirevic, A; Alfirevic, Z

    2016-01-01

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

  15. Comparison of antiplatelet activity of garlic tablets with cardio-protective dose of aspirin in healthy volunteers: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Mojtaba Shafiekhani

    2016-08-01

    Full Text Available Objective: Some of the adverse effects of aspirin including peptic ulcers, gastrointestinal bleeding and aspirin resistance compelled researchers to find a suitable alternative with fewer adverse effects. In this clinical trial, we aimed to find the effective antiplatelet dose of garlic. Materials and Methods: This randomized controlled clinical trial (RCT was conducted on 62 healthy volunteers of 20-50 years old. All volunteers used 80 mg aspirin per day for 1 week and at the end of this time, platelet aggregation (PA induced by 4 agonists acting in aggregation pathway including adenosinediphosphate (20 μmol/l, epinephrine (20 μmol/l, collagen(0.19 mg/ ml and arachidonic acid (0.5mg/ ml was measured by Light Transmittance Aggregometry (LTA in all participants. After one month washout period, volunteers were randomized into 3 groups and each received 1, 2 or 3 garlic tablets (1250 mg a day for 1 month. After one month, PA was examined in all groups. Results: The mean ±SD of the age of all volunteers was 28.60 ± 9.00 years. In addition, 52.00 % of our volunteers were male and 48.00% of them were female. Garlic tablet didnot have significant effect on PA at any dose. However, 30% of volunteers in the group that used 3 garlic tablets/day reported adverse effect (i.e. bleeding. No significant association between sex, age and PA was observed. Conclusion:  In this study, we were unable to determine the effective anti-platelet dose of garlic which that could be equal to that of aspirin anti-platelet activity, as assessed LTA method.

  16. Aspirin-Exacerbated Asthma

    Directory of Open Access Journals (Sweden)

    Varghese Mathew

    2008-06-01

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

  17. Aspirin: yesterday, today, and tomorrow

    OpenAIRE

    Marina Nikołajewna Dołżenko

    2014-01-01

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

  18. PFA-100-measured aspirin resistance is the predominant risk factor for hospitalized cardiovascular events in aspirin-treated patients: A 5-year cohort study.

    Science.gov (United States)

    Chen, H Y; Chou, P

    2018-04-01

    Aspirin therapy is the clinical gold standard for the prevention of cardiovascular events. However, cardiovascular events still develop in some patients undergoing aspirin therapy. Many laboratory methods exist for measuring aspirin resistance. Using the platelet Function Analyzer (PFA)-100 system, we aimed to determine the effect of aspirin resistance on hospitalized cardiovascular events (hCVE) in a 5-year follow-up cohort. We also sought to determine the impact of aspirin resistance on the relationship between common cardiovascular risk factors and cardiovascular hospitalization. Aspirin resistance was evaluated in aspirin-treated patients from the outpatient department. A total of 465 patients during a 5-year follow-up period were included in this study. The primary endpoint of the study was hospitalization for any acute cardiovascular event. The prevalence and associated risk factors of acute cardiovascular events were evaluated. Aspirin resistance was prevalent in 91 (20.0%) of 465 patients. Prior hospitalization history of cardiovascular events was highly associated with aspirin resistance (P = .001). At the 5-year follow-up, cardiovascular events were found to have developed in 11 patients (8 stroke and 3 myocardial infarction) who exhibited aspirin resistance (12.1%) and in 9 (4 stroke and 5 myocardial infarction) patients who did not exhibit aspirin resistance (2.4%) (P resistance and cardiovascular events (adjusted odds ratio 4.28; 95% CI: 1.64-11.20; P = .03). PFA-100 measurements of aspirin resistance correlate with hCVE, as evidenced by both the past medical history and the 5-year follow-up. The logistic regression analysis results showed that aspirin resistance plays a larger role in hospitalized cardiovascular disease than do other cardiovascular risk factors. © 2017 John Wiley & Sons Ltd.

  19. 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.

  20. 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.

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

    International Nuclear Information System (INIS)

    Li, Xiaofei; Zhu, Yanshuang; He, Huabin; Lou, Lianqing; Ye, Weiwei; Chen, Yongxin; Wang, Jinghe

    2013-01-01

    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

  2. Acute pancreatitis complicated by jejunal hematoma in a patient on anti-coagulants and anti-platelets.

    Science.gov (United States)

    Chong, Vui Heng; Basir, Norwani; Yaakub, Aziman Bin

    2010-05-05

    Pancreatitis can be associated with significant complications. Bowel hematoma is a rare complication and the second part of the duodenum is the most commonly affected site. Hematomas affecting other parts of the bowel are extremely rare. A 53-year-old female with a history of atrial fibrillation and ischemic heart disease on anticoagulants and aspirin presented with abdominal pain of a few days duration which had worsened prior to presentation. This was associated with abdominal distension, vomiting and melena. Laboratory investigations showed elevated serum amylase, coagulopathy and severe anemia. Computed tomography imaging showed a jejunal hematoma and pancreatitis with peripancreatic inflammation. She responded to conservative treatment in addition to correction of the coagulopathy and a blood transfusion. Her symptoms were resolved within a few days and a repeat computed tomography scan two months later showed complete resolution of the hematoma and the pancreatitis. Our case demonstrates a rare complication of acute pancreatitis in a patient with risk factors.

  3. Preventive Aspirin and Other Antiplatelet Medication Use Among U.S. Adults Aged ≥40 Years: Data from the National Health and Nutrition Examination Survey, 2011–2012

    Science.gov (United States)

    Dillon, Charles F.; Eberhardt, Mark S.; Wright, Jacqueline D.; Burt, Vicki L.

    2015-01-01

    Objective We estimated the prevalence of preventive aspirin and/or other antiplatelet medication use and the dosage of aspirin use in the U.S. adult population. Methods We conducted cross-sectional analyses of a representative sample (n=3,599) of U.S. adults aged ≥40 years from the National Health and Nutrition Examination Survey, 2011–2012. Results In 2011–2012, one-third of U.S. adults aged ≥40 years reported taking preventive aspirin and/or other antiplatelet medications, 97% of whom indicated preventive aspirin use. Preventive aspirin use increased with age (from 11% of those aged 40–49 years to 54% of those ≥80 years of age, paspirin than non-Hispanic Asian (20%, paspirin. Among those with cardiovascular disease, 76% reported taking preventive aspirin and/or other antiplatelet medications, of whom 91% were taking preventive aspirin. Among adults without cardiovascular disease, 28% reported taking preventive aspirin. Adherence rates to medically recommended aspirin use were 82% overall, 91% for secondary prevention, and 79% for primary prevention. Among current preventive aspirin users, 70% were taking 81 milligrams (mg) of aspirin daily and 13% were taking 325 mg of aspirin daily. Conclusion The vast majority of antiplatelet therapy is preventive aspirin use. A health-care provider's recommendation to take preventive aspirin is an important determinant of current preventive aspirin use. PMID:26556936

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

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

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

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

    Science.gov (United States)

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

    2017-12-05

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

  7. Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect

    Energy Technology Data Exchange (ETDEWEB)

    Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil); Borsato, Débora Maria [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Almeida, Martinha Antunes [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Barboza, Fernanda Malaquias [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zawadzki, Sônia Faria [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Kanunfre, Carla Cristine [Postgraduate Program in Biomedical Science, Department of General Biology, State University of Ponta Grossa (Brazil); Farago, Paulo Vitor, E-mail: pvfarago@gmail.com [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zanin, Sandra Maria Warumby [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil)

    2016-07-01

    This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3 μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects. - Highlights: • Ferulic acid-loaded Eudragit® L100 microparticles with high drug-loading were obtained. • Spray-dried Eudragit® L100 microparticles containing ferulic acid showed improved in vitro cytoprotective effect. • Ferulic acid spray-dried microparticles had potential as in vitro anti-inflammatory and immunomodulatory. • In vivo studies demonstrated an enhanced antiplatelet effect for ferulic acid-loaded Eudragit® L100 microparticles.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    David S. Morris

    2008-06-01

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

  12. Greener Methods for Aspirin Synthesis

    OpenAIRE

    Barilone, Jessica

    2013-01-01

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

  13. Aspirin and the Primary Prevention of Cardiovascular Diseases: An Approach Based on Individualized, Integrated Estimation of Risk.

    Science.gov (United States)

    Volpe, Massimo; Battistoni, Allegra; Gallo, Giovanna; Coluccia, Roberta; De Caterina, Raffaele

    2017-09-01

    While the use of aspirin in the secondary prevention of cardiovascular (CVD) is well established, aspirin in primary prevention is not systematically recommended because the absolute CV event reduction is similar to the absolute excess in major bleedings. Recently, emerging evidence suggests the possibility that the assumption of aspirin, may also be effective in the prevention of cancer. By adding to the CV prevention benefits the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in the primary prevention in favour of the latter and broaden the indication for treatment with in populations at average risk. While prospective and randomized study are currently investigating the effect of aspirin in prevention of both cancer and CVD, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention could be already based on a balanced evaluation of the benefit/risk ratio.

  14. Phenomenology, pathogenesis, diagnosis and treatment of aspirin-sensitive rhinosinusitis.

    Science.gov (United States)

    Schapowal, A G; Simon, H U; Schmitz-Schumann, M

    1995-01-01

    Aspirin-sensitive rhinosinusitis is a non-allergic, non-infectious perennial eosinophilic rhinitis starting in middle age and rarely seen in children. It may also been seen in atopic patients who have developed a mixed type rhinitis with recurrent airway infections. There is an intolerance to aspirin and most other NSAID. An intolerance to tartrazine, food additives, alcohol, narcotics and local anaesthetics can follow. Most aspirin-sensitive patients develop nasal polyps. Untreated, it can lead to asthma. The frequency of aspirin intolerance is 6.18% in patients with perennial rhinitis and 14.68% in patients with nasal polyps. Immunologic studies of the blood and the nasal polyps show a hyperreactive immune system with an activation of the eosinophil granulocytes due to a TH1-lymphocyte-activation. In atopic subjects with a mixed type rhinitis, we found a TH2- and B-lymphocyte-activation as well. Inhibition of eosinophil apoptosis might be a second remarkable change in the immune system of aspirin-sensitive patients. A key pathogenic event for aspirin sensitivity is the change of the leukotriene pathway for arachidonic acid metabolism releasing high amounts of leukotrienes LTC4, LTD4 and LTE4, effective chemoattractants and activators of inflammatory cells. For the diagnosis of aspirin intolerance, nasal, bronchial and oral challenge are available. The sensitivity of nasal challenge with lysine-aspirin for the diagnosis of aspirin-sensitive rhinitis is 0.93, the specificity 0.97. It is the safest test in aspirin-sensitive asthmatics causing bronchial side effects only in 0.45%. Therapy of aspirin-sensitive rhinosinusitis includes avoidance of aspirin and NSAID. A general down regulation of the immune response with glucocorticosteroids is an effective means. We prefer a maintenance dose of budesonid 400 micrograms a day. Systemic steroids for a reversibility test or in exacerbation due to viral infection are given in a dose of 50 mg a day for one week. If steroids

  15. A novel hybrid aspirin-NO-releasing compound inhibits TNFalpha release from LPS-activated human monocytes and macrophages

    Directory of Open Access Journals (Sweden)

    Fox Sarah

    2008-07-01

    Full Text Available Abstract Background The cytoprotective nature of nitric oxide (NO led to development of NO-aspirins in the hope of overcoming the gastric side-effects of aspirin. However, the NO moiety gives these hybrids potential for actions further to their aspirin-mediated anti-platelet and anti-inflammatory effects. Having previously shown that novel NO-aspirin hybrids containing a furoxan NO-releasing group have potent anti-platelet effects, here we investigate their anti-inflammatory properties. Here we examine their effects upon TNFα release from lipopolysaccharide (LPS-stimulated human monocytes and monocyte-derived macrophages and investigate a potential mechanism of action through effects on LPS-stimulated nuclear factor-kappa B (NF-κB activation. Methods Peripheral venous blood was drawn from the antecubital fossa of human volunteers. Mononuclear cells were isolated and cultured. The resultant differentiated macrophages were treated with pharmacologically relevant concentrations of either a furoxan-aspirin (B8, B7; 10 μM, their respective furazan NO-free counterparts (B16, B15; 10 μM, aspirin (10 μM, existing nitroaspirin (NCX4016; 10 μM, an NO donor (DEA/NO; 10 μM or dexamethasone (1 μM, in the presence and absence of LPS (10 ng/ml; 4 h. Parallel experiments were conducted on undifferentiated fresh monocytes. Supernatants were assessed by specific ELISA for TNFα release and by lactate dehydrogenase (LDH assay for cell necrosis. To assess NF-κB activation, the effects of the compounds on the loss of cytoplasmic inhibitor of NF-κB, IκBα (assessed by western blotting and nuclear localisation (assessed by immunofluorescence of the p65 subunit of NF-κB were determined. Results B8 significantly reduced TNFα release from LPS-treated macrophages to 36 ± 10% of the LPS control. B8 and B16 significantly inhibited monocyte TNFα release to 28 ± 5, and 49 ± 9% of control, respectively. The B8 effect was equivalent in magnitude to that of

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

    African Journals Online (AJOL)

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

  17. Taking Aspirin to Protect Your Heart

    Science.gov (United States)

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

  18. Pathophysiologic, rather than laboratory-defined resistance drives aspirin failure in ischemic stroke.

    Science.gov (United States)

    Agayeva, Nergiz; Gungor, Levent; Topcuoglu, Mehmet Akif; Arsava, Ethem Murat

    2015-04-01

    A significant proportion of ischemic strokes occur while using aspirin and therefore can be considered as clinical aspirin resistance. Apart from this clinical description, aspirin resistance can be defined by laboratory tests of in vitro platelet reactivity. The correlation between clinical and laboratory-defined resistance, however, is far from perfect, and the heterogenous nature of stroke pathophysiology might play a role in this discrepancy. The level of in vitro platelet inhibition by aspirin was prospectively evaluated using the VerifyNow Aspirin Assay (Accumetrics, San Diego, CA) in patients presenting with ischemic stroke while using aspirin (n = 78). Demographic and clinical features, including stroke etiology, were compared among patients with and without sufficient level of platelet inhibition and an additional set of patients suffering from stroke while not using aspirin (n = 257). Similar analyses were performed in a separate validation cohort. Laboratory evidence of insufficient platelet inhibition was detected in 16 of 78 patients (21%) with clinical aspirin resistance. On the other hand, 30 patients (38%) had stroke etiologies well known to be inadequately responsive to aspirin therapy. Overall, laboratory-defined resistance by itself could be considered to be accountable for the ischemic event in only 15% of these patients. The corresponding figure was 9% in validation cohort. Patients with sufficient level of platelet inhibition were more likely to harbor an anticoagulant responsive etiology compared with aspirin naive patients (odds ratio, 2.0; P = .033). Our findings highlight that laboratory aspirin resistance because of insufficient platelet inhibition is relatively uncommon, whereas pathophysiologic resistance, signifying the presence of etiologies that cannot be efficiently treated with aspirin treatment, is a major contributor of clinical resistance in ischemic stroke. Copyright © 2015 National Stroke Association. Published by

  19. Platelets, aspirin, and cardiovascular disease.

    Science.gov (United States)

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

    1998-10-01

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

  20. Aspirin resistance may be identified by miR-92a in plasma combined with platelet distribution width

    DEFF Research Database (Denmark)

    Binderup, Helle Glud; Houlind, Kim; Madsen, Jonna Skov

    2016-01-01

    OBJECTIVE: Aspirin is a widely used drug for prevention of thrombotic events in cardiovascular patients, but approximately 25% of patients experience insufficient platelet inhibition due to aspirin, and remain in risk of cardiovascular events. This study aimed to investigate the value...... of circulating miR-92a and platelet size as biomarkers of the individual response to aspirin therapy. METHODS: Blood samples were collected from 50 healthy blood donors without antithrombotic medication and 50 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic...... acid stimulated aggregation test on Multiplate®analyzer (ASPItest), patients were defined as aspirin resistant (n=10) or aspirin responders (n=40). Plasma levels of miR-92a were evaluated by RT-qPCR analysis and platelet distribution width (PDW) was used to assess platelet size variability. Receiver...

  1. Platelets, aspirin, and cardiovascular disease.

    OpenAIRE

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

    1998-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

  3. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

  5. The effect of concurrent aspirin upon plasma concentrations of tenoxicam.

    OpenAIRE

    Day, R O; Paull, P D; Lam, S; Swanson, B R; Williams, K M; Wade, D N

    1988-01-01

    1. The effect of chronic, high-dose aspirin therapy upon the disposition of a single dose and multiple doses of tenoxicam was examined in normal volunteers. 2. Aspirin caused a 24% drop in the t1/2 (P less than 0.005), a 49% rise in the volume of distribution (P less than 0.0003) and a 98% increase in the clearance (P less than 0.0001) of tenoxicam after a single dose of the tenoxicam. 3. Steady-state concentrations of tenoxicam decreased significantly from 10.4 +/- 1.5 to 4.5 +/- 1.6 microgr...

  6. Initial experience with aspirin use during robotic radical prostatectomy.

    Science.gov (United States)

    Nowfar, Sepehr; Kopp, Ryan; Palazzi-Churas, Kerrin; Derweesh, Ithaar H; Kane, Christopher J

    2012-04-01

    New cardiology guidelines recommend antiplatelet therapy for some patients with cardiac stents. Aspirin use is relatively contraindicated during urologic surgery because of increased bleeding risk. We sought to review the outcomes of patients who continued aspirin during robot-assisted radical prostatectomy. Between October 2007 and February 2010, 249 patients underwent robot-assisted radical prostatectomy by a single surgeon. After consultation with the patients' cardiologists, 6 patients had coronary artery stents and continued aspirin perioperatively (Group 1), and 7 patients had coronary artery stents but did not continue aspirin perioperatively (Group 2). The remaining 236 patients had no coronary artery stents and did not require continued aspirin (Group 3). We analyzed our patients' preoperative characteristics, including age, prostate-specific antigen volume, and D'Amico risk, as well as operative time, blood loss, hematocrit changes, transfusion requirements, length of hospital stay, and complications. We found no differences in operative time, estimated blood loss, changes in hematocrit, or length of hospital stay. No patients with any type of cardiac stent required a postoperative blood transfusion or had complications requiring more than simple anti-emetics, analgesics, or electrolyte correction. Nine patients in Group 3 required interventions for significant complications. Larger studies need to be performed to validate these observations.

  7. The effect of concurrent aspirin upon plasma concentrations of tenoxicam.

    Science.gov (United States)

    Day, R O; Paull, P D; Lam, S; Swanson, B R; Williams, K M; Wade, D N

    1988-01-01

    1. The effect of chronic, high-dose aspirin therapy upon the disposition of a single dose and multiple doses of tenoxicam was examined in normal volunteers. 2. Aspirin caused a 24% drop in the t1/2 (P less than 0.005), a 49% rise in the volume of distribution (P less than 0.0003) and a 98% increase in the clearance (P less than 0.0001) of tenoxicam after a single dose of the tenoxicam. 3. Steady-state concentrations of tenoxicam decreased significantly from 10.4 +/- 1.5 to 4.5 +/- 1.6 micrograms ml-1 in the presence of chronic, high-dose aspirin treatment. 4. Tenoxicam percentage free measured in plasma from a normal volunteer was 0.56 +/- 0.05% over the tenoxicam concentration range 1-20 micrograms ml-1 and rose to 1.24 +/- 0.07% in the presence of aspirin 150 micrograms ml-1. 5. The effect of aspirin upon the disposition of tenoxicam was consistent with a competitive protein binding interaction. PMID:3190995

  8. 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.

  9. 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.

  10. 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 diabetes mellitus in the RT group (p < 0.05). The subgroup analysis revealed significantly higher incidence of infarction and stroke in the ASA resistant RT group compared to the RT patients without ASA resistance (p < 0.05). Furthermore, the incidence of myocardial 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.

  11. Yosprala: A Fixed Dose Combination of Aspirin and Omeprazole.

    Science.gov (United States)

    Veltri, Keith T

    Cardiovascular disease is the leading cause of morbidity and mortality in the United States. Patients who survive a primary cerebrovascular or cardiovascular event are at increased risk of a subsequent occurrence. Antiplatelet therapy plays an essential role for secondary prevention in individuals with stroke, transient ischemic attack, acute or chronic artery disease, or peripheral arterial disease. Maintaining high-risk patients on low-dose aspirin therapy is a fundamental component of management. However, poor adherence, secondary to the drug's gastrointestinal side effects, has been associated with negative cardiovascular outcomes. Numerous studies have indicated that proton-pump inhibitors significantly reduce the risk of upper gastrointestinal adverse events in aspirin-treated patients. The US Food and Drug Administration approved Yosprala (Aralez Pharmaceuticals), a fixed-dose combination of delayed-release aspirin and immediate-release omeprazole, on September 15, 2016. It is the first product to become available in the United States that combines these 2 pharmacologic drug classes, and represents a new therapeutic option for patients and healthcare providers who strive to improve adherence to daily aspirin therapy.

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

    Science.gov (United States)

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

    2017-07-10

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

  13. Low-dose aspirin and upper gastrointestinal damage: epidemiology, prevention and treatment.

    Science.gov (United States)

    Lanas, Angel; Scheiman, James

    2007-01-01

    Low-dose aspirin (75-325 mg/day) is widely used for the prevention of cardiovascular disease. However, due to its action on cyclo-oxygenase (COX), aspirin is associated with upper gastrointestinal (GI) side effects including ulcers and bleeding. This was a comprehensive review of the literature available on the side effects associated with low-dose aspirin, together with the available treatment and prevention options, which was based on the authors' expertise in the field and a supplementary PubMed search limited to papers published in English during the last 10 years, up to November 2006. Although the risk of upper GI side effects is smaller with low-dose aspirin compared with non-selective, non-steroidal anti-inflammatory drugs (NSAIDs), it is nevertheless a substantial healthcare issue. Factors associated with an increased risk of upper GI complications during low-dose aspirin therapy include aspirin dose, history of ulcer or upper GI bleeding, age > 70 years, concomitant use of NSAIDs (including COX-2-selective NSAIDs), and Helicobacter pylori infection. Co-administration of a gastroprotective agent such as proton pump inhibitors (PPIs) may be useful for alleviating the upper GI side effects associated with use of low-dose aspirin. Eradication of H. pylori also appears to reduce the risk of these side effects, especially in those at high risk. The use of other antiplatelet agents such as clopidogrel does not seem to provide a safer alternative to low-dose aspirin in at-risk patients. Prophylactic low-dose aspirin therapy is associated with an increased risk of developing upper GI side effects. Administration of a PPI seems the most effective therapy for the prevention and/or relief of such side effects in at-risk patients. H. pylori eradication therapy further reduces the risk of upper GI bleeding in these patients.

  14. 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.

  15. Aspirin and aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

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

    2014-12-01

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

  16. Incidence of and risk factors for upper gastrointestinal complications in patients taking low-dose aspirin in Japan.

    Science.gov (United States)

    Fujisawa, Nobutaka; Inamori, Masahiko; Endo, Hiroki; Uchiyama, Takashi; Hosono, Kunihiro; Akiyama, Tomoyuki; Tomimoto, Ayako; Koyama, Sigeru; Sawabe, Aya; Tanida, Emiko; Yanagisawa, Shogo; Hata, Yasuo; Okada, Kazuhisa; Atsukawa, Kazuhiro; Watanabe, Seitaro; Kawamura, Harunobu; Higurashi, Takuma; Nagase, Hajime; Akimoto, Keiko; Matsuhashi, Nobuyuki; Nakajima, Atsushi

    2011-01-01

    Low-dose aspirin is widely used for the prevention of cardiovascular and cerebrovascular diseases. However, administration of low-dose aspirin is associated with an increased risk of upper gastrointestinal complications, such as upper gastrointestinal erosions, ulcers and bleeding. The aim of this study was to clarify the prevalence and various clinical factors of upper gastrointestinal complications associated with low-dose aspirin treatment. A total of 1213 patients taking low-dose aspirin were evaluated with upper endoscopic examinations. We studied retrospectively the incidence of and risk factors for upper gastrointestinal complications associated with low-dose aspirin use. Of the 1213 patients taking low-dose aspirin, 598 patients and 72 patients were found to have gastroduodenal erosions (57.3%) and peptic ulcers (5.9%), respectively. Of these 72 peptic ulcers, 27 were diagnosed as hemorrhagic ulcers. Previous ulcer history was identified as a risk factor for peptic ulcer and upper gastrointestinal bleeding during low-dose aspirin therapy. Upper gastrointestinal symptoms and no use of gastroprotective agents were also identified as risk factors for peptic ulcers. In this study, the use of a histamine-2 receptor antagonist was indicated as a protective factor for peptic ulcers. Low-dose aspirin therapy is associated with an increased risk of developing upper gastrointestinal complications. Administration of a histamine-2 receptor antagonist was effective for the prevention of low-dose aspirin induced peptic ulcers.

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

    Science.gov (United States)

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

    2017-11-24

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

  18. Measurement of platelet function to determine the prevalence of aspirin non-responsiveness among Saudi type II diabetic patients

    Directory of Open Access Journals (Sweden)

    Saeed Alahmari

    2016-01-01

    Conclusion: The relationship between the levels of glucose in the blood and aspirin resistance relates the importance of controlling blood glucose in diabetic patients to guarantee better aspirin action. Regular examining of type II diabetic patients to determine the sensitivity of platelet to the antiplatelet therapy is necessary to protect them from the risks of cardiovascular complications.

  19. cDNA cloning of a snake venom metalloproteinase from the eastern diamondback rattlesnake (Crotalus adamanteus), and the expression of its disintegrin domain with anti-platelet effects

    Science.gov (United States)

    Suntravat, Montamas; Jia, Ying; Lucena, Sara E.; Sánchez, Elda E.; Pérez, John C.

    2013-01-01

    A 5′ truncated snake venom metalloproteinase was identified from a cDNA library constructed from venom glands of an eastern diamondback rattlesnake (Crotalus adamanteus). The 5′-rapid amplification of cDNA ends (RACE) was used to obtain the 1865 bp full-length cDNA sequence of a snake venom metalloproteinase (CamVMPII). CamVMPII encodes an open reading frame of 488 amino acids, which includes a signal peptide, a pro-domain, a metalloproteinase domain, a spacer, and an RGD-disintegrin domain. The predicted amino acid sequence of CamVMPII showed a 91%, 90%, 83%, and 82% sequence homology to the P-II class enzymes of C. adamanteus metalloproteinase 2, C. atrox CaVMP-II, Gloydius halys agkistin, and Protobothrops jerdonii jerdonitin, respectively. Disintegrins are potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. Therefore, the disintegrin domain (Cam-dis) of CamVMPII was amplified by PCR, cloned into a pET-43.1a vector, and expressed in Escherichia coli BL21. Affinity purified recombinantly modified Cam-dis (r-Cam-dis) with a yield of 8.5 mg/L culture medium was cleaved from the fusion tags by enterokinase cleavage. r-Cam-dis was further purified by two-step chromatography consisting of HiTrap™ Benzamidine FF column, followed by Talon Metal affinity column with a final yield of 1 mg/L culture. r-Cam-dis was able to inhibit all three processes of platelet thrombus formation including platelet adhesion with an estimated IC50 of 1 nM, collagen- and ADP-induced platelet aggregation with the estimated IC50s of 18 and 6 nM, respectively, and platelet function on clot retraction. It is a potent anti-platelet inhibitor, which should be further investigated for drug discovery to treat stroke patients or patients with thrombotic disorders. PMID:23313448

  20. Aspirin resistant patients with recent ischemic stroke.

    Science.gov (United States)

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

    2014-04-01

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

  1. Aspirin: past, present and future.

    Science.gov (United States)

    Elwood, P C

    2001-01-01

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

  2. Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term low-dose aspirin therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial.

    Science.gov (United States)

    Sugano, Kentaro; Matsumoto, Yasushi; Itabashi, Tsukasa; Abe, Sumihisa; Sakaki, Nobuhiro; Ashida, Kiyoshi; Mizokami, Yuji; Chiba, Tsutomu; Matsui, Shigeyuki; Kanto, Tatsuya; Shimada, Kazuyuki; Uchiyama, Shinichiro; Uemura, Naomi; Hiramatsu, Naoki

    2011-06-01

    The efficacy of low-dose lansoprazole has not been established for the prevention of recurrent gastric or duodenal ulcers in those receiving long-term low-dose aspirin (LDA) for cardiovascular and cerebrovascular protection. This study sought to examine the efficacy of low-dose lansoprazole (15 mg once daily) for the secondary prevention of LDA-associated gastric or duodenal ulcers. Patients were randomized to receive lansoprazole 15 mg daily (n = 226) or gefarnate 50 mg twice daily (n = 235) for 12 months or longer in a prospective, multicenter, double-blind, randomized active-controlled trial, followed by a 6-month follow-up study with open-label lansoprazole treatment. The study utilized 94 sites in Japan and 461 Japanese patients with a history of gastric or duodenal ulcers who required long-term LDA therapy for cardiovascular and cerebrovascular disease. The primary endpoint was the development of gastric or duodenal ulcers. The cumulative incidence of gastric or duodenal ulcers on days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 1.5, 2.1, and 3.7%, respectively, in the lansoprazole group versus 15.2, 24.0, and 31.7%, respectively, in the gefarnate group. The risk of ulcer development was significantly (log-rank test, P lansoprazole group than in the gefarnate group, with the hazard ratio being 0.099 (95% confidence interval [CI] 0.042-0.230). Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term LDA therapy.

  3. 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,

  4. HMG-CoA reductase inhibitors, other lipid-lowering medication, antiplatelet therapy, and the risk of venous thrombosis

    NARCIS (Netherlands)

    Ramcharan, A.S.; van Stralen, K.J.; Snoep, J.D.; Mantel-Teeuwisse, A.K.; Doggen, Catharina Jacoba Maria

    2009-01-01

    Background: Statins [3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors] and antiplatelet therapy reduce the risk of atherosclerotic disease. Besides a reduction of lipid levels, statins might also have antithrombotic and anti-inflammatory properties, and anti-platelet

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

    Science.gov (United States)

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

    2017-04-01

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

  6. Efficacy of aspirin (325 mg) + omeprazole (40 mg) in treating coronary artery disease.

    Science.gov (United States)

    Sharma, Tushar; Bliden, Kevin; Chaudhary, Rahul; Tantry, Udaya; Gurbel, Paul A

    2017-01-01

    Aspirin is indicated for primary and secondary prevention of cardiovascular diseases (CVD) by major guidelines. However, its use may be associated with gastrointestinal (GI) toxicities, including, but not limited to, GI bleeding. This may lead to increased morbidity and mortality, as well as diminished compliance, which again leads to increased risk of major cardiovascular events. Modified formulations of aspirin often have comparable risks of GI toxicity despite their dose or formulation and have had limited success to prevent GI toxicities. Simultaneous treatment with Proton pump inhibitors (PPIs) has been used successfully to prevent GI toxicities from aspirin. However, addition of an extra medication may lead to lower compliance and hence ineffective or less than optimal treatment. Areas covered: After a selective literature search, a brief review of the available evidence regarding GI toxicity of aspirin and the protective effects of PPIs was conducted. The concept of combination tablets, and the available data about Aralez Pharmaceuticals' YOSPRALA (aspirin (81 mg or 325 mg) and omeprazole (40 mg) fixed dose combination tablet being evaluated for secondary prevention of cardiovascular and cerebrovascular events in patients at risk for GI complications of aspirin therapy) is also presented. Expert opinion: The available evidence suggests that PPIs are the best option to prevent aspirin-related GI toxicities, but compliance is low in people who are prescribed both aspirin and PPI. Combination tablets containing both aspirin and a PPI may be a good option for providing protection against GI toxicities in people who require aspirin for secondary prevention of cardiovascular diseases.

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

    Science.gov (United States)

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

    2015-01-01

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

  8. A multicentre retrospective study to understand anti-platelet treatment patterns and outcomes of acute coronary syndrome patients in India (TRACE

    Directory of Open Access Journals (Sweden)

    Upendra Kaul

    2014-05-01

    Conclusion: This pilot study conducted in tertiary care centers in India showed that patients with ACS were more often diagnosed with UA/NSTEMI as compared to STEMI and reported maximum compliance to statins, clopidogrel and aspirin after discharge over 1 year follow-up. More ACS patients were lost to follow up that resulted in low reporting of clinical outcomes, following discharge upto 1 year.

  9. 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).

  10. The Effect of Combined Aspirin and Clopidogrel Treatment on Cancer Incidence.

    Science.gov (United States)

    Leader, Avi; Zelikson-Saporta, Ravit; Pereg, David; Spectre, Galia; Rozovski, Uri; Raanani, Pia; Hermoni, Doron; Lishner, Michael

    2017-07-01

    Multiple studies have shown an association between aspirin treatment and a reduction in newly diagnosed cancer. Conversely, there are conflicting clinical and laboratory data on the effect of combined clopidogrel and aspirin therapy on cancer incidence, including analyses suggesting an increased cancer risk. No large-scale cohort study has been performed to address this issue in a heterogeneous real-world scenario. We investigated the effect of clopidogrel and aspirin on cancer incidence compared with aspirin alone and no antiplatelet therapy. A population-based historical cohort study of subjects aged ≥50 years covered by Clalit Health Services, an Israeli health maintenance organization, was performed. Patients treated with the newer antiplatelet drugs, prasugrel or ticagrelor, which, like clopidogrel, inhibit adenosine diphosphate receptors, and those with prior cancer were excluded. Prescription records of antiplatelet medication were retrieved. The cohort included 183,912 subjects diagnosed with 21,974 cancer cases based upon the International Classification of Diseases, Ninth Revision. Dual aspirin and clopidogrel was prescribed in 9.6%, while 49% received aspirin alone and 41% used neither. Compared with nonusers, there was a lower risk of cancer in subjects exposed to aspirin with (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.44-0.49) or without clopidogrel (HR 0.54; 95% CI, 0.52-0.56), on long-term follow-up. Combined treatment was associated with a lower cancer risk than the aspirin-only group (HR 0.92; 95% CI, 0.86-0.97). Dual clopidogrel and aspirin treatment is safe regarding the cancer risk. This study generates the hypothesis that clopidogrel may reduce cancer incidence. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 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 ...

  12. Uso de rTPA e aspirina no tratamento de trombose intracardíaca em recém-nascido Combined rTPA and aspirin therapy for intracardiac thrombosis in neonates

    Directory of Open Access Journals (Sweden)

    Fernanda Almeida Tardin

    2007-05-01

    Full Text Available Descreve-se o caso de um recém-nascido prematuro de peso muito baixo, gemelar, com trombose intracardíaca. O recém-nascido apresentou quadro compatível com sepse neonatal, sendo submetido a suporte avançado de vida, terapia com antibióticos, nutrição parenteral, uso de hemoderivados e cateterismo venoso profundo. Evoluiu com suspeita de endocardite infecciosa, sendo realizada ecocardiografia bidimensional com Doppler, quando foi evidenciado volumoso trombo intracavitário. Pela alta letalidade e pela dificuldade técnica da cirurgia, que, em alguns casos, é contra-indicada, optou-se pelo uso do trombolítico ativador de plasminogênio tecidual recombinante humano (rTPA associado a aspirina, obtendo-se dissolução total do trombo sem efeitos adversos.We describe a case of a very low birth weight premature female twin with intracardiac thrombosis. Her condition was consistent with neonatal sepsis, and she was treated with advanced life support, antibiotic therapy, parenteral nutrition, blood transfusion, and central venous catheterization. Infective endocarditis was suspected, and a large intracavitary thrombus was detected by two-dimensional Doppler echocardiography. Surgical procedure was not only technically difficult but also highly lethal, being contraindicated in some cases. Consequently, the use of the thrombolytic recombinant tissue-plasminogen activator (rTPA associated with aspirin was the treatment of choice, and complete dissolution of the thrombus was achieved without adverse effects.

  13. 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.

  14. An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

    Science.gov (United States)

    Chen, Justin R; Buchmiller, Brett L; Khan, David A

    2015-01-01

    Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. Esomeprazole and aspirin fixed combination for the prevention of cardiovascular events.

    Science.gov (United States)

    Sylvester, Katelyn W; Cheng, Judy Wm; Mehra, Mandeep R

    2013-01-01

    Low dose aspirin therapy plays a fundamental role in both the primary and secondary prevention of cardiovascular events. Although the evidence using low dose aspirin for secondary prevention is well-established, the decision to use aspirin for primary prevention is based on an evaluation of the patient's risk of cardiovascular events compared to their risk of adverse events, such as bleeding. In addition to the risk of bleeding associated with long term aspirin administration, upper gastrointestinal side effects, such as dyspepsia often lead to discontinuation of therapy, which places patients at an increased risk for cardiovascular events. One option to mitigate adverse events and increase adherence is the addition of esomeprazole to the medication regimen. This review article provides an evaluation of the literature on the concomitant use of aspirin and esomeprazole available through February 2013. The efficacy, safety, tolerability, cost effectiveness, and patient quality of life of this regimen is discussed. A summary of the pharmacokinetic and pharmacodynamic interactions between aspirin and esomeprazole, as well as other commonly used cardiovascular medications are also reviewed. The addition of esomeprazole to low dose aspirin therapy in patients at high risk of developing gastric ulcers for the prevention of cardiovascular disease, significantly reduced their risk of ulcer development. Pharmacokinetic and pharmacodynamic studies suggested that esomeprazole did not affect the pharmacokinetic parameters or the antiplatelet effects of aspirin. Therefore, for those patients who are at a high risk of developing a gastrointestinal ulcer, the benefit of adding esomeprazole likely outweighs the risks of longer term proton pump inhibitor use, and the combination can be recommended. Administering the two agents separately may also be more economical. On the other hand, for those patients at lower risk of developing a gastrointestinal ulcer, both the additional risk

  16. Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis.

    Science.gov (United States)

    Berger, Jeffrey S; Brown, David L; Becker, Richard C

    2008-01-01

    Many recommendations for aspirin in stable cardiovascular disease are based on analyses of all antiplatelet therapies at all dosages and in both stable and unstable patients. Our objective was to evaluate the benefit and risk of low-dose aspirin (50-325 mg/d) in patients with stable cardiovascular disease. Secondary prevention trials of low-dose aspirin in patients with stable cardiovascular disease were identified by searches of the MEDLINE database from 1966 to 2006. Six randomized trials were identified that enrolled patients with a prior myocardial infarction (MI) (n=1), stable angina (n=1), or stroke/transient ischemic attack (n=4). A random effects model was used to combine results from individual trials. Six studies randomized 9853 patients. Aspirin therapy was associated with a significant 21% reduction in the risk of cardiovascular events (nonfatal MI, nonfatal stroke, and cardiovascular death) (95% confidence interval [CI], 0.72-0.88), 26% reduction in the risk of nonfatal MI (95% CI, 0.60-0.91), 25% reduction in the risk of stroke (95% CI, 0.65-0.87), and 13% reduction in the risk of all-cause mortality (95% CI, 0.76-0.98). Patients treated with aspirin were significantly more likely to experience severe bleeding (odds ratio 2.2, 95% CI, 1.4-3.4). Treatment of 1000 patients for an average of 33 months would prevent 33 cardiovascular events, 12 nonfatal MIs, 25 nonfatal strokes, and 14 deaths, and cause 9 major bleeding events. Among those with ischemic heart disease, aspirin was most effective at reducing the risk of nonfatal MI and all-cause mortality; however, among those with cerebrovascular disease, aspirin was most effective at reducing the risk of stroke. In patients with stable cardiovascular disease, low-dose aspirin therapy reduces the incidence of adverse cardiovascular events and all-cause mortality, and increases the risk of severe bleeding.

  17. Impact of aspirin and statins on long-term survival in patients hospitalized with acute myocardial infarction complicated by heart failure

    DEFF Research Database (Denmark)

    Lewinter, Christian; Bland, John M; Crouch, Simon

    2014-01-01

    AIMS: Aspirin and statins are established therapies for acute myocardial infarction (MI), but their benefits in patients with chronic heart failure (HF) remain elusive. We investigated the impact of aspirin and statins on long-term survival in patients hospitalized with acute MI complicated by HF...... by HF, prescription of aspirin and statins either alone or together was associated with better long-term survival....

  18. Effect of Aspirin on Spinal Cord Injury: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Hamed Reihani Kermani

    2016-05-01

    Full Text Available Aspirin is an anti-inflammatory drug, peroxyl radical scavenger, and antioxidant agent that inhibits phospholipases, nitric oxide synthetases, and cyclooxygenase enzymes. The existing literature contains no studies on the effects of various doses of aspirin on spinal cord injury (SCI. Therefore, we sought to investigate the putative effects of aspirin on experimental SCI. The weight-drop injury model was used to produce SCI in 100 albino Wistar rats. The animals were allocated to five groups: a control group, where the rats did not undergo any surgical or medical intervention except for anesthesia; a sham-treated group, where laminectomy was performed without SCI and no further therapy was administered; and three other groups, where the rats with SCI received low-dose aspirin [20 mg/kg], high-dose aspirin [80 mg/kg], and a vehicle, respectively. Half of the rats were sacrificed 24 hours later, and their spinal cords were excised for biochemical studies. The other rats were subjected to Basso, Beattie, and Bresnahan (BBB locomotor rating scale scoring once a week for 6 consecutive weeks. Aspirin decreased lipid peroxidation following SCI as the mean (± standard error catalase level was significantly higher in the high-dose aspirin group (46.10±12.01 than in the sham-treated group (16.07±2.42 and the vehicle-treated group (15.31±3.20 (P<0.05; P<0.05, respectively. Both of the groups treated with high-dose and low-dose aspirin demonstrated a higher mean BBB score than did the control group (P<0.001 and the sham-treated group (P<0.001. Our data provide evidence in support of the potential effects of aspirin in biochemical and neurobehavioral recovery after SCI.

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

    OpenAIRE

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

    2007-01-01

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

  20. Prognostic and therapeutic implications of statin and aspirin therapy in individuals with nonobstructive coronary artery disease: Results from the confirm (coronary CT angiography evaluation for clinical outcomes: An international multicenter registry) registry

    NARCIS (Netherlands)

    B.J.W. Chow (Benjamin); G.R. Small (Gary); Y. Yam (Yeung); L. Chen (Li); R. McPherson (Ruth); S. Achenbach (Stephan); M. Al-Mallah (Mouaz); D.S. Berman (Daniel); M.J. Budoff (Matthew J.); F. Cademartiri (Filippo); T.Q. Callister (Tracy); H.-J. Chang (Hyuk-Jae); V.Y. Cheng (Victor Y.); K. Chinnaiyan (Kavitha); R.C. Cury (Ricardo); A. Delago (Augustin); A. Dunning (Allison); G. Feuchtner (Gundrun); M. Hadamitzky (Martin); J. Hausleiter (Jörg); R.P. Karlsberg (Ronald); P.A. Kaufmann (Philipp A.); Y.-J. Kim (Yong-Jin); J. Leipsic (Jonathon); T.M. LaBounty (Troy); F.Y. Lin (Fay); E. Maffei (Erica); G.L. Raff (Gilbert); L.J. Shaw (Leslee J.); T.C. Villines (Todd); J.K. Min (James)

    2015-01-01

    textabstractObjective - We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality. Approach and Results - Coronary computed tomographic angiography permits direct visualization

  1. Aspirin in venous leg ulcer study (ASPiVLU): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Weller, Carolina D; Barker, Anna; Darby, Ian; Haines, Terrence; Underwood, Martin; Ward, Stephanie; Aldons, Pat; Dapiran, Elizabeth; Madan, Jason J; Loveland, Paula; Sinha, Sankar; Vicaretti, Mauro; Wolfe, Rory; Woodward, Michael; McNeil, John

    2016-04-11

    Venous leg ulceration is a common and costly problem that is expected to worsen as the population ages. Current treatment is compression therapy; however, up to 50 % of ulcers remain unhealed after 2 years, and ulcer recurrence is common. New treatments are needed to address those wounds that are more challenging to heal. Targeting the inflammatory processes present in venous ulcers is a possible strategy. Limited evidence suggests that a daily dose of aspirin may be an effective adjunct to aid ulcer healing and reduce recurrence. The Aspirin in Venous Leg Ulcer study (ASPiVLU) will investigate whether 300-mg oral doses of aspirin improve time to healing. This randomised, double-blinded, multicentre, placebo-controlled, clinical trial will recruit participants with venous leg ulcers from community settings and hospital outpatient wound clinics across Australia. Two hundred sixty-eight participants with venous leg ulcers will be randomised to receive either aspirin or placebo, in addition to compression therapy, for 24 weeks. The primary outcome is time to healing within 12 weeks. Secondary outcomes are ulcer recurrence, wound pain, quality of life and wellbeing, adherence to study medication, adherence to compression therapy, serum inflammatory markers, hospitalisations, and adverse events at 24 weeks. The ASPiVLU trial will investigate the efficacy and safety of aspirin as an adjunct to compression therapy to treat venous leg ulcers. Study completion is anticipated to occur in December 2018. Australian New Zealand Clinical Trials Registry, ACTRN12614000293662.

  2. Aspirin is associated with low oral pH levels and antacid helps to increase oral pH.

    Science.gov (United States)

    Ediriweera, Dileepa Senajith; Dilina, Nuwani; Saparamadu, Vipula; Fernando, Inoka; Kurukulasuriya, Buddhika; Fernando, Deepika; Kurera, Janakie

    2018-02-20

    Aspirin is a commonly used medicine for primary and secondary prevention of cardiovascular diseases. It is an acidic medicine associated with gastric irritation and acid reflux, which in turn can lead to low oral pH levels. Therefore, it is important to understand the association between aspirin and oral pH levels in order to achieve an optimum oral health condition among patients who take aspirin on prescription. Out of 373 patients, 162 (44%) were males and 245 (66%) were on aspirin. 71% of aspirin taking patients and 29% of non-aspirin taking patients had oral pH less than 6.5 (P pH levels (odds ratio = 1.91, 95% CI 1.23-2.99, P pH and the improvement was marked in the group who had oral pH between 5.5-6.0 compared to the group who had oral pH between 6.0-6.5 (P = 0.03). The results show that aspirin therapy is associated with low oral pH and administration of an antacid with aspirin helps to increase the oral pH level.

  3. Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement.

    Science.gov (United States)

    Cuzick, Jack; Otto, Florian; Baron, John A; Brown, Powel H; Burn, John; Greenwald, Peter; Jankowski, Janusz; La Vecchia, Carlo; Meyskens, Frank; Senn, Hans Jörg; Thun, Michael

    2009-05-01

    Evidence clearly shows a chemopreventive effect for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer and probably other cancer types; however, data on the risk-benefit profile for cancer prevention are insufficient and no definitive recommendations can be made. Aspirin has emerged as the most likely NSAID for use in chemoprevention because of its known cardiovascular benefit and available safety and efficacy data. Other traditional NSAIDs, particularly sulindac, and selective COX-2 inhibitors are now given to patients at high risk of colorectal cancer, although these drugs do not provide cardioprotection. More studies of aspirin and cancer prevention are needed to define the lowest effective dose, the age at which to initiate therapy, the optimum treatment duration, and the subpopulations for which the benefits of chemoprevention outweigh the risks of adverse side-effects. Although it might be possible to answer some of these questions with longer follow-up of existing clinical trials, randomised controlled trials with new study designs will be needed. Future projects should investigate the effects of aspirin treatment on multiple organ systems. Cancers of interest are colorectal, breast, prostate, lung, stomach, and oesophageal. The main side-effect of aspirin is peptic ulcers; therefore coadministration of aspirin with a proton-pump inhibitor is an attractive option and is under investigation in the AspECT trial.

  4. Aspirin for the Primary Prevention of Cardiovascular Disease: In Need of Clarity.

    Science.gov (United States)

    Miedema, Michael D; Huguelet, Joseph; Virani, Salim S

    2016-01-01

    Aspirin remains one of the most extensively studied cardiovascular medications in the history of medicine. However, despite multiple, well-designed, large randomized controlled trials evaluating the potential of aspirin to prevent cardiovascular events in individuals without known cardiovascular disease (CVD), the role of aspirin in primary prevention is currently unclear. The initial aspirin trials included largely low-risk individuals with primary outcomes mostly focused on myocardial infarction (MI) and stroke, and showed a significant reduction in these CVD outcomes, especially MI. The more recently conducted trials have focused on older, higher CVD risk populations with high rates of lipid-lowering and antihypertensive medications use. These studies have used broader CVD outcomes as their primary end points and have failed to show a significant benefit of aspirin therapy in primary prevention. The exact reasons for the lack of efficacy in these recent trials are unclear but may be related to low rate of atherothrombotic events relative to other CVD events in the populations studied. Four large randomized controlled trials are currently underway which should provide some clarity in determining the optimal use of aspirin in the primary prevention of CVD.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    1976-10-01

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

  7. Role of p38 MAPK in enhanced human cancer cells killing by the combination of aspirin and ABT-737

    Science.gov (United States)

    Zhang, Chong; Shi, Jing; Mao, Shi-ying; Xu, Ya-si; Zhang, Dan; Feng, Lin-yi; Zhang, Bo; Yan, You-you; Wang, Si-cong; Pan, Jian-ping; Yang, You-ping; Lin, Neng-ming

    2015-01-01

    Regular use of aspirin after diagnosis is associated with longer survival among patients with mutated-PIK3CA colorectal cancer, but not among patients with wild-type PIK3CA cancer. In this study, we showed that clinically achievable concentrations of aspirin and ABT-737 in combination could induce a synergistic growth arrest in several human PIK3CA wild-type cancer cells. In addition, our results also demonstrated that long-term combination treatment with aspirin and ABT-737 could synergistically induce apoptosis both in A549 and H1299 cells. In the meanwhile, short-term aspirin plus ABT-737 combination treatment induced a greater autophagic response than did either drug alone and the combination-induced autophagy switched from a cytoprotective signal to a death-promoting signal. Furthermore, we showed that p38 acted as a switch between two different types of cell death (autophagy and apoptosis) induced by aspirin plus ABT-737. Moreover, the increased anti-cancer efficacy of aspirin combined with ABT-737 was further validated in a human lung cancer A549 xenograft model. We hope that this synergy may contribute to failure of aspirin cancer therapy and ultimately lead to efficacious regimens for cancer therapy. PMID:25388762

  8. High-dose aspirin in addition to daily low-dose aspirin decreases platelet activation in patients before and after percutaneous coronary intervention.

    NARCIS (Netherlands)

    Berg, J.M. ten; Gerritsen, W.B.M.; Haas, F.J.L.M.; Kelder, J.C.; Verheugt, F.W.A.; Plokker, H.W.M.

    2002-01-01

    BACKGROUND: Activated platelets play a major role in acute vessel closure after coronary angioplasty. Although aspirin is the routine therapy during angioplasty, it only incompletely prevents acute closure. This might be due to suboptimal dosing. OBJECTIVE: First, to study the effect of additional

  9. 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; Abildstrom, Steen Z

    2009-01-01

    . Numbers needed to harm were 81.2 for aspirin plus clopidogrel, 45.4 for aspirin plus vitamin K antagonist, 15.2 for clopidogrel plus vitamin K antagonist, and 12.5 for triple therapy. 702 (37.9%) of 1852 patients with non-fatal bleeding had recurrent myocardial infarction or died during the study period......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...

  10. Aspirin in patients undergoing noncardiac surgery

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10,010...

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

    African Journals Online (AJOL)

    LIVINGSTON

    Sankarkumar T. used cryotherapy of the palpebral conjunctiva with oral aspirin in mixed type active vernal kerato-conjunctivitis. Patients received oral Aspirin 0.50 to 1.50g in three divided doses daily over six weeks and the result showed that the relief from symptoms was statistically significant (p<0.001) and objective.

  12. Contemporary Reflections on the Safety of Long-Term Aspirin Treatment for the Secondary Prevention of Cardiovascular Disease

    Science.gov (United States)

    Fanaroff, Alexander C.; Roe, Matthew T.

    2018-01-01

    Aspirin has been the cornerstone of therapy for the secondary prevention treatment of patients with cardiovascular disease since landmark trials were completed in the late 1970s and early 1980s that demonstrated the efficacy of aspirin for reducing the risk of ischemic events. Notwithstanding the consistent benefits demonstrated with apirin for both acute and chronic cardiovascular disease, there are a number of toxicities associated with aspirin that have been showcased by recent long-term clinical trials that have included an aspirin monotherapy arm. As an inhibitor of cyclooxygenase, aspirin impairs gastric mucosal protective mechanisms. Prior trials have shown that up to 15–20% of patients developed gastrointestinal symptoms with aspirin monotherapy and roughly 1% of patients per year had a clinically significant bleeding event, including 1 in 1000 patients who suffered an intracranial or fatal bleed. These risks have been shown to be compounded for patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), who are also treated with other anti-thrombotic agents during the acute care/procedural period, as well as for an extended time period afterwards. Given observations of substantial increases in bleeding rates from many prior long-term clinical trials that have evaluated aspirin together with other oral platelet inhibitors or oral anti-coagulants, the focus of contemporary research has pivoted towards tailored anti-thrombotic regimens that attempt to either shorten the duration of exposure to aspirin or replace aspirin with an alternative anti-thrombotic agent. While these shifts are occurring, the safety profile of aspirin when used for the secondary prevention treatment of patients with established cardiovascular disease deserves further consideration. PMID:27028617

  13. Inhibition of camel lens zeta-crystallin by aspirin and aspirin-like analgesics.

    Science.gov (United States)

    Bazzi, Mohammad D; Rabbani, Nayyar; Duhaiman, Ali S

    2002-01-01

    Camel lens zeta-crystallin was reversibly inhibited to various degrees by aspirin (acetyl salicylic acid) and the aspirin-like analgesics: paracetamol (acetaminophen) and ibuprofen (2-(4-isobutyl phenyl)-propionic acid). Among these, aspirin was the most potent inhibitor, causing nearly complete inhibition in a dose-dependent, but time-independent manner. Analysis of inhibition kinetics revealed that aspirin was uncompetitive inhibitor (K(i) 0.64 mM) with respect to NADPH and non-competitive inhibitor (K(i) 1.6 mM) with respect to the substrate, 9,10-phenanthrenequinone (PQ). Multiple-inhibition analysis showed that aspirin and pyridoxal 5' phosphate (PAL-P), a lysine specific reagent, simultaneously bound to a critical lysine residue located towards the NADPH binding region. Consistent with this, NADPH was able to substantially protect zeta-crystallin against aspirin, whereas PQ did not provide any protection. The results suggested that an essential lysine residue was the locus of aspirin binding. The inhibition of zeta-crystallin by aspirin and aspirin-like analgesics was reversible thus eliminating acetylation as a mechanism for inhibition. Reversible binding of aspirin to this lysine may cause steric hindrance resulting in uncompetitive inhibition with respect to NADPH.

  14. Effect of aspirin on nasal resistance to airflow.

    OpenAIRE

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

    1985-01-01

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

  15. Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels

    DEFF Research Database (Denmark)

    Lundberg Slingsby, Martina Helena; Gliemann, Lasse; Thrane, Mette Nørmark

    2018-01-01

    into 3 groups; untrained, moderately- and well-trained. Their platelet reactivity (agonist-induced %aggregation) was investigated in platelet rich plasma at rest and after inhibition with aspirin and ticagrelor and/or prostacyclin and nitric oxide added to the blood in vitro, and after physiological......The current guidelines following an acute coronary syndrome recommend dual anti-platelet therapy (aspirin plus a P2Y12 antagonist) alongside lifestyle modifications, including more regular physical activity. It is currently unknown if regular exercise affects the pharmacology of dual anti-platelet...... therapy. AIM: To explore how exercise-induced improvements in vascular and platelet function affect the efficacy of dual anti-platelet therapy, in a cross-sectional study of men with different physical activity level (training status). METHODS: 42 healthy, normal-weight, middle-aged men were divided...

  16. 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.

  17. Comparison of VerifyNow-P2Y12 test and Flow Cytometry for monitoring individual platelet response to clopidogrel. What is the cut-off value for identifying patients who are low responders to clopidogrel therapy?

    Directory of Open Access Journals (Sweden)

    Castelli Alfredo

    2009-05-01

    Full Text Available Abstract Background Dual anti-platelet therapy with aspirin and a thienopyridine (DAT is used to prevent stent thrombosis after percutaneous coronary intervention (PCI. Low response to clopidogrel therapy (LR occurs, but laboratory tests have a controversial role in the identification of this condition. Methods We studied LR in patients with stable angina undergoing elective PCI, all on DAT for at least 7 days, by comparing: 1 Flow cytometry (FC to measure platelet membrane expression of P-selectin (CD62P and PAC-1 binding following double stimulation with ADP and collagen type I either in the presence of prostaglandin (PG E1; 2 VerifyNow-P2Y12 test, in which results are reported as absolute P2Y12-Reaction-Units (PRU or % of inhibition (% inhibition. Results Thirty controls and 52 patients were analyzed. The median percentage of platelets exhibiting CD62P expression and PAC-1 binding by FC evaluation after stimulation in the presence of PG E1 was 25.4% (IQR: 21.4–33.1% and 3.5% (1.7–9.4%, respectively. Only 6 patients receiving DAT (11.5% had both values above the 1st quartile of controls, and were defined as LR. Evaluation of the same patients with the VerifyNow-P2Y12 test revealed that the area under the receiver-operating-characteristic (ROC curve was 0.94 (95% CI: 0.84–0.98, p 213 PRU gave the maximum accuracy for the detection of patients defined as having LR by FC. Conclusion In conclusion our findings show that a cut-off value of ≤ 15% inhibition or > 213 PRU in the VerifyNow-P2Y12 test may provide the best accuracy for the identification of patients with LR.

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

    OpenAIRE

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

    2014-01-01

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

  19. Aspirin

    Science.gov (United States)

    ... Jeremy S. Paikin , John W. Eikelboom Download PDF https://doi.org/10.1161/CIRCULATIONAHA.111.046243 Circulation. 2012; 125: ... e439-e442 , originally published March 12, 2012 https://doi.org/10.1161/CIRCULATIONAHA.111.046243 Citation Manager Formats ...

  20. Aspirin induces IL-4 production: augmented IL-4 production in aspirin-exacerbated respiratory disease

    Science.gov (United States)

    Kong, Su-Kang; Soo Kim, Byung; Gi Uhm, Tae; Soo Chang, Hun; Sook Park, Jong; Woo Park, Sung; Park, Choon-Sik; Chung, Il Yup

    2016-01-01

    Aspirin hypersensitivity is a hallmark of aspirin-exacerbated respiratory disease (AERD), a clinical syndrome characterized by the severe inflammation of the respiratory tract after ingestion of cyclooxygenase-1 inhibitors. We investigated the capacity of aspirin to induce interleukin-4 (IL-4) production in inflammatory cells relevant to AERD pathogenesis and examined the associated biochemical and molecular pathways. We also compared IL-4 production in peripheral blood mononuclear cells (PBMCs) from patients with AERD vs aspirin-tolerant asthma (ATA) upon exposure to aspirin. Aspirin induced IL-4 expression and activated the IL-4 promoter in a report assay. The capacity of aspirin to induce IL-4 expression correlated with its activity to activate mitogen-activated protein kinases, to form DNA–protein complexes on P elements in the IL-4 promoter and to synthesize nuclear factor of activated T cells, critical transcription factors for IL-4 transcription. Of clinical importance, aspirin upregulated IL-4 production twice as much in PBMCs from patients with AERD compared with PBMCs from patients with ATA. Our results suggest that IL-4 is an inflammatory component mediating intolerance reactions to aspirin, and thus is crucial for AERD pathogenesis. PMID:27534531

  1. Epidemiology of Upper Gastrointestinal Damage Associated with Low-Dose Aspirin.

    Science.gov (United States)

    Hsu, Ping-I; Tsai, Tzung-Jiun

    2015-01-01

    Low-dose aspirin, commonly defined as 75-325 mg daily, is widely used for cardiovascular (CV) protection. It reduced the risk of CV events and death in patients with coronary and cerebrovascular diseases and has the advantages of both low cost and long duration of antiplatelet action. However, low-dose aspirin therapy is associated with upper gastrointestinal (GI) side effects, which range from dyspepsia (point prevalence: 31%), gastroduodenal erosions (point prevalence: 60%), endoscopic peptic ulcer (3-month incidence: 7%) to symptomatic or complicated ulcers (annual incidence of upper GI bleeding: 0.6%; relative risk of upper GI bleeding: 2.6). The important factors that increase the risk of low-dose aspirin-related ulcer complications include a history of bleeding peptic ulcer, prior peptic ulcer, age > 70 years, H pylori infection, and concomitant drug therapy with non-steroidal anti-inflammatory drugs, other antiplatelet agents (e.g., clopidogrel) or anticoagulants. The use of enteric-coated or buffered preparations do not reduce the risk of upper GI complications. Assessment of GI risk for patients is a crucial step in preventing complications of antiplatelet agents. Patients with a high GI risk should prevent peptic ulcer or ulcer complications by co-therapy with an antisecretory agent, especially proton pump inhibitors. H pylori eradication is recommended for patients requiring long-term low-dose aspirin therapy who have a prior history of peptic ulcer or GI bleeding.

  2. Aspirin desensitization in patients undergoing planned or urgent coronary stent implantation. A single-center experience

    NARCIS (Netherlands)

    Luca, G. De; Verdoia, M.; Binda, G.; Schaffer, A.; Suryapranata, H.; Marino, P.

    2013-01-01

    INTRODUCTION: Dual antiplatelet therapy (aspirin and ADP-antagonists) is mandatory after stent implantation in order to avoid stent thrombosis, especially in the era of DES. In fact, a delayed re-endothelization process may enlarge the window of occurrence of stent thrombosis beyond 1-year after

  3. Impact of aspirin according to type of stable coronary artery disease: insights from a large international cohort.

    Science.gov (United States)

    Bavry, Anthony A; Gong, Yan; Handberg, Eileen M; Cooper-DeHoff, Rhonda M; Pepine, Carl J

    2015-02-01

    Aspirin is recommended in stable coronary artery disease based on myocardial infarction and stroke studies. However, benefit among stable coronary artery disease patients who have not suffered an acute ischemic event is uncertain. The objective of this study was to evaluate the impact of aspirin in stable coronary artery disease. We hypothesized that aspirin's benefit would be attenuated among individuals with stable coronary artery disease but no prior ischemic event. An observational study was conducted from the INternational VErapamil-SR/Trandolapril STudy cohort. Ambulatory patients ≥ 50 years of age with clinically stable coronary artery disease requiring antihypertensive drug therapy (n = 22,576) were classified "ischemic" if they had a history of unstable angina, myocardial infarction, transient ischemic attack, or stroke at the baseline visit. All others were classified "non-ischemic." Aspirin use was updated at each clinic visit and considered as a time-varying covariate in a Cox regression model. The primary outcome was first occurrence of all-cause mortality, myocardial infarction, or stroke. At baseline, 56.7% of all participants used aspirin, which increased to 69.3% at study close out. Among the "non-ischemic" group (n = 13,091), aspirin was not associated with a reduction in risk (hazard ratio [HR] 1.11; 95% confidence interval [CI], 0.97-1.28; P = .13); however, among the "ischemic" group (n = 9485), aspirin was associated with a reduction in risk (HR 0.87; 95% CI, 0.77-0.99; P = .033). In patients with stable coronary artery disease and hypertension, aspirin use was associated with reduced risk for adverse cardiovascular outcomes among those with prior ischemic events. Among patients with no prior ischemic events, aspirin use was not associated with a reduction in risk. Published by Elsevier Inc.

  4. Analysis of the Interaction between Clopidogrel, Aspirin, and Proton Pump Inhibitors Using the FDA Adverse Event Reporting System Database.

    Science.gov (United States)

    Suzuki, Yukiya; Suzuki, Honami; Umetsu, Ryogo; Uranishi, Hiroaki; Abe, Junko; Nishibata, Yuri; Sekiya, Yasuaki; Miyamura, Nobuteru; Hara, Hideaki; Tsuchiya, Teruo; Kinosada, Yasutomi; Nakamura, Mitsuhiro

    2015-01-01

    Clopidogrel is an antiplatelet agent widely used in combination with aspirin to limit the occurrence of cardiovascular (embolic/thrombotic) events. Consensus guidelines recommend proton pump inhibitors (PPIs) as a gastrointestinal (GI) prophylactic measure for all patients receiving dual antiplatelet therapy with clopidogrel and aspirin. The objective of this study was to analyze the effect of the simultaneous use of clopidogrel, aspirin, and PPIs on hemorrhagic and embolic/thrombotic events using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Reports of hemorrhagic and embolic/thrombotic events between 2004 and 2013 were analyzed with a reporting odds ratio (ROR) algorithm and logistic regression methods. The Medical Dictionary for Regulatory Activities Preferred Terms was used to identify such events. Regarding hemorrhagic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 4.40 (95% confidence interval [CI], 4.02-4.81) and 3.40 (95% CI, 2.84-4.06), respectively. For embolic/thrombotic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 2.37 (95% CI, 2.16-2.59) and 2.38 (95% CI, 2.00-2.84), respectively. Among patients included in the FAERS database, the concurrent use of aspirin and clopidogrel with PPIs reduced the adjusted ROR of GI hemorrhagic events. PPIs had little influence on the adjusted ROR of embolic/thrombotic events. These results support the use of PPIs as a preventive measure against GI hemorrhagic events for patients receiving clopidogrel and aspirin.

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

    Science.gov (United States)

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

    2017-12-01

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

  6. Management of low-dose aspirin and clopidogrel in clinical practice: a gastrointestinal perspective.

    Science.gov (United States)

    Lanas, Angel; Gargallo, Carla J

    2015-06-01

    Low-dose aspirin, alone or combined with other antiplatelet agents, is increasingly prescribed for cardiovascular prevention. However, the cardiovascular benefits should be evaluated together with the gastrointestinal risks. Low-dose aspirin is associated with upper and lower gastrointestinal injury, although lower gastrointestinal effects are poorly characterized. This gastrointestinal risk differs among antiplatelets drugs users. The most important risk factors are history of peptic ulcer, older age, and concomitant use of non-steroidal anti-inflammatory drugs or dual antiplatelet therapy. Effective upper gastrointestinal prevention strategies are available and should be used in at-risk patients taking low-dose aspirin or clopidogrel. Proton pump inhibitors seem to be the best gastroprotective agents, whereas the benefits of Helicobacter pylori eradication are still unclear. Low-dose aspirin has additional effects in the gastrointestinal tract. A large body of evidence indicates that it can protect against different cancers, in particular colorectal cancer. This effect could modify the future indications for use of low-dose aspirin and the risk-benefit balance.

  7. 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

    : Platelet inhibition declined significantly during the 24-hour dosing interval in aspirin-treated patients with previous definite ST or stable coronary artery disease and in healthy individuals. Increased levels of immature platelets and thrombopoietin were observed in patients with previous definite ST....... through 24 h in patients with previous definite ST. Furthermore, we explored whether increased levels of immature platelets and thrombopoietin are associated with a particularly rapid recovery of platelet function. METHODS: This case-control study included 50 patients with previous definite ST matched...... with 100 patients with stable coronary artery disease and 50 healthy volunteers. All participants were on aspirin 75 mg/day mono antiplatelet therapy. Platelet aggregation was measured 1 and 24 h after aspirin intake using platelet aggregometry (Multiplate® Analyzer). Cyclooxygenase-1 activity, platelet...

  8. Oxylipin studies expose aspirin as antifungal.

    Science.gov (United States)

    Kock, Johan L F; Sebolai, Olihile M; Pohl, Carolina H; van Wyk, Pieter W J; Lodolo, Elizabeth J

    2007-12-01

    The presence of aspirin-sensitive 3-hydroxy fatty acids (i.e. 3-OH oxylipins) in yeasts was first reported in the early 1990s. Since then, these oxidized fatty acids have been found to be widely distributed in yeasts. 3-OH oxylipins may: (1) have potent biological activity in mammalian cells; (2) act as antifungals; and (3) assist during forced spore release from enclosed sexual cells (asci). A link between 3-OH oxylipin production, mitochondria and aspirin sensitivity exists. Research suggests that: (1) 3-OH oxylipins in some yeasts are probably also produced by mitochondria through incomplete beta-oxidation; (2) aspirin inhibits mitochondrial beta-oxidation and 3-OH oxylipin production; (3) yeast sexual stages, which are probably more dependent on mitochondrial activity, are also characterized by higher 3-OH oxylipin levels as compared to asexual stages; (4) yeast sexual developmental stages as well as cell adherence/flocculation are more sensitive to aspirin than corresponding asexual growth stages; and (5) mitochondrion-dependent asexual yeast cells with a strict aerobic metabolism are more sensitive to aspirin than those that can also produce energy through an alternative anaerobic glycolytic fermentative pathway in which mitochondria are not involved. This review interprets a wide network of studies that reveal aspirin to be a novel antifungal.

  9. Post Hoc Analyses of Randomized Clinical Trial for the Effect of Clopidogrel Added to Aspirin on Kidney Function.

    Science.gov (United States)

    Ikeme, Jesse C; Pergola, Pablo E; Scherzer, Rebecca; Shlipak, Michael G; Benavente, Oscar R; Peralta, Carmen A

    2017-07-07

    Despite the high burden of CKD, few specific therapies are available that can halt disease progression. In animal models, clopidogrel has emerged as a potential therapy to preserve kidney function. The effect of clopidogrel on kidney function in humans has not been established. The Secondary Prevention of Small Subcortical Strokes Study randomized participants with prior lacunar stroke to treatment with aspirin or aspirin plus clopidogrel. We compared annual eGFR decline and incidence of rapid eGFR decline (≥30% from baseline) using generalized estimating equations and interval-censored proportional hazards regression, respectively. We also stratified our analyses by baseline eGFR, systolic BP target, and time after randomization. At randomization, median age was 62 (interquartile range, 55-71) years old; 36% had a history of diabetes, 90% had hypertension, and the median eGFR was 81 (interquartile range, 65-94) ml/min per 1 m 2 . Persons receiving aspirin plus clopidogrel had an average annual change in kidney function of -1.39 (95% confidence interval, -1.15 to -1.62) ml/min per 1.73 m 2 per year compared with -1.52 (95% confidence interval, -1.30 to -1.74) ml/min per 1.73 m 2 per year among persons receiving aspirin only ( P =0.42). Rapid kidney function decline occurred in 21% of participants receiving clopidogrel plus aspirin compared with 22% of participants receiving aspirin plus placebo (hazard ratio, 0.94; 95% confidence interval, 0.79 to 1.10; P =0.42). Findings did not vary by baseline eGFR, time after randomization, or systolic BP target (all P values for interaction were >0.3). We found no effect of clopidogrel added to aspirin compared with aspirin alone on kidney function decline among persons with prior lacunar stroke. Copyright © 2017 by the American Society of Nephrology.

  10. 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.

  11. Treatment with aspirin, NSAID, corticosteroids, and colchicine in acute and recurrent pericarditis.

    Science.gov (United States)

    Imazio, Massimo; Adler, Yehuda

    2013-05-01

    Empiric anti-inflammatory therapy for acute and recurrent pericarditis is warranted for viral and idiopathic cases that represent most cases of pericarditis in developed countries. For specific uncomplicated etiologies, such as systemic autoimmune diseases and postpericardiotomy syndromes, the same drugs are also indicated. Aspirin and non-steroidal anti-inflammatory drugs (NSAID) are mainstay of therapy with the possible adjunct of colchicine, especially for recurrences. Corticosteroids are a second choice for difficult cases requiring multi-drug therapies and specific medical conditions (i.e., specific cases with systemic autoimmune diseases, postpericardiotomy syndrome, and pregnancy). Medical therapy of pericarditis should be individualized as much as possible providing the attack dose every 8 h to ensure full daily control of symptoms and till remission and C-reactive protein normalization, and then tapering should be considered. The present paper will review current evidence for the treatment of acute and recurrent pericarditis with aspirin, NSAID, corticosteroids, and colchicine.

  12. 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)

    Chen, Wei; Zhu, Hong; Jia, Zhenquan; Li, Jianrong; Misra, Hara P.; Zhou, Kequan; Li, Yunbo

    2009-01-01

    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.

  13. 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.

  14. Aspirin disrupts the mTOR-Raptor complex and potentiates the anti-cancer activities of sorafenib via mTORC1 inhibition.

    Science.gov (United States)

    Sun, Danni; Liu, Hongchun; Dai, Xiaoyang; Zheng, Xingling; Yan, Juan; Wei, Rongrui; Fu, Xuhong; Huang, Min; Shen, Aijun; Huang, Xun; Ding, Jian; Geng, Meiyu

    2017-10-10

    Aspirin is associated with a reduced risk of cancer and delayed progression of malignant disease. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mTOR signaling is believed to partially contribute to these anticancer effects, although the mechanism is unclear. In this study, we revealed the mechanism underlying the effects of aspirin on AMPK-mTOR signaling, and described a mechanism-based rationale for the use of aspirin in cancer therapy. We found that aspirin inhibited mTORC1 signaling through AMPK-dependent and -independent manners. Aspirin inhibited the AMPK-TSC pathway, thus resulting in the suppression of mTORC1 activity. In parallel, it directly disrupted the mTOR-raptor interaction. Additionally, the combination of aspirin and sorafenib showed synergetic effects via inhibiting mTORC1 signaling and the PI3K/AKT, MAPK/ERK pathways. Aspirin and sorafenib showed synergetic anticancer efficacy in the SMMC-7721 model. Our study provides mechanistic insights and a mechanism-based rationale for the roles of aspirin in cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The safety and efficacy of aspirin intake in photoselective vaporization laser treatment of benign prostate hyperplasia

    Directory of Open Access Journals (Sweden)

    Shao IH

    2013-03-01

    Full Text Available I-Hung Shao,1,* Chen-Pang Hou,1,* Shao-Ming Chen,3 Chien-Lun Chen,1,2 Yu-Hsiang Lin,1 Phei-Lang Chang,1,2 Ke-Hung Tsui1,2 1Department of Urology, 2Bioinformation Center, Chang Gung Memorial Hospital-Linko and Chang Gung University College of Medicine, 3Department of Urology, Taipei City Hospital, Heping Campus, Taipei, Taiwan, People's Republic of China *These authors contributed equally to this work Abstract: Endoscopic surgical treatment has become an option to treat benign prostate hyperplasia. We evaluated the safety and effectiveness of photoselective vaporization of the prostate (PVP in patients. We evaluated preoperative and perioperative parameters, functional outcomes, and adverse events up to 12 months postoperatively of patients on oral anticoagulation therapy undergoing PVP, and compared the results with patients who did not take anticoagulation therapy. A total of 89 patients who received photoselective vaporization laser for benign prostate hyperplasia from May 2006 to February 2011 in our hospital were enrolled in our study. The patients were divided into two groups based on whether or not they were taking oral aspirin; 23 (25.8% patients were taking aspirin derivatives (aspirin group, and 66 (74.2% were not taking aspirin derivatives (control group. The mean prostate volume (58.8 mL vs 51 mL; P = 0.16 and mean energy consumption (235,268 J vs 289,793 J; P = 0.097 were comparable between the aspirin group and control group. The average postoperative results of hemoglobin were 13.4 mg/dL for the aspirin group versus 13.9 mg/dL for the control group (P = 0.327. A significantly higher maximum flow rates and 80% improved post-void residual urine were noted during the followup. Postoperatively all variable showed significant improvement starting at month 1 of followup and remained improved for the 12 month followup. Postoperative complications were low and comparable between groups. PVP was characterized by excellent hemostatic

  16. Anti-platelet drugs in patients with femoral neck fractures undergoing cemented hip hemiarthroplasty surgery. A study of complications and mortality.

    Science.gov (United States)

    Agudo Quiles, M; Sanz-Reig, J; Alcalá-Santaella Oria de Rueca, R

    2015-01-01

    To assess complications and factors predicting one-year mortality in patients on antiplatelet agents presenting with femoral neck fractures undergoing hip hemiarthroplasty surgery. A review was made on 50 patients on preoperative antiplatelet agents and 83 patients without preoperative antiplatelet agents. Patients in both groups were treated with cemented hip hemiarthroplasty. A statistical comparison was performed using epidemiological data, comorbidities, mental state, complications and mortality. There was no lost to follow-up. The one-year mortality was 20.3%. In patients without preoperative antiplatelet agents it was 14.4% and in patients with preoperative antiplatelet agents was 30%. Age, ASA grade, number of comorbidities and antiplatelet agent therapy were predictors of one-year mortality. The one-year mortality of patients on clopidogrel was 46.1%, versus 24.3% in patients on acetylsalicylic acid. Patients with preoperative antiplatelet therapy were older and had greater number of comorbidities, ASA grade, delayed surgery, and a longer length of stay than patients without antiplatelet therapy. The one-year mortality was higher in patients with preoperative antiplatelet therapy. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  17. Talk with Your Doctor about Taking Aspirin Every Day

    Science.gov (United States)

    ... safe to take with aspirin. If you drink alcohol, drink only in moderation . This means no more than ... day for women and no more than 2 drinks a day for men. Alcohol can increase some risks of taking daily aspirin. ...

  18. Aspirin suppresses growth in PI3K-mutant breast cancer by activating AMPK and inhibiting mTORC1 signaling

    Science.gov (United States)

    Henry, Whitney S.; Laszewski, Tyler; Tsang, Tiffany; Beca, Francisco; Beck, Andrew H.; McAllister, Sandra S.; Toker, Alex

    2016-01-01

    Despite the high incidence of oncogenic mutations in PIK3CA, the gene encoding the catalytic subunit of phosphoinositide 3-kinase (PI3K), PI3K inhibitors have yielded little clinical benefit for breast cancer patients. Recent epidemiological studies have suggested a therapeutic benefit from aspirin intake in cancers harboring oncogenic PIK3CA. Here we show that mutant PIK3CA-expressing breast cancer cells have greater sensitivity to aspirin-mediated growth suppression than their wild-type counterparts. Aspirin decreased viability and anchorage-independent growth of mutant PIK3CA breast cancer cells independently of its effects on cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB). We ascribed the effects of aspirin to AMP-activated protein kinase (AMPK) activation, mammalian target of rapamycin complex 1 (mTORC1) inhibition, and autophagy induction. In vivo, oncogenic PIK3CA-driven mouse mammary tumors treated daily with aspirin resulted in decreased tumor growth kinetics, while combination therapy of aspirin and a PI3K inhibitor further attenuated tumor growth. Our study supports evaluation of aspirin and PI3K pathway inhibitors as combination therapy for targeting breast cancer. PMID:27940576

  19. A critical appraisal of the phenomenon of aspirin resistance

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  20. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Science.gov (United States)

    2010-04-01

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

  1. Mechanisms of aspirin-sensitive asthma

    Directory of Open Access Journals (Sweden)

    Sun Ying

    2004-01-01

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

  2. [Milestones of cardivascular pharmacotherapy: salicylates and aspirin].

    Science.gov (United States)

    Jerie, P

    2006-01-01

    The analgesic and antipyretic effect of the bark of willow has been known in Egypt and Greece for canturies. The modem era of salicylates starts with a letter sent 1758 by Reverend Edward Stone to The Royal Society in London. He described "an account of the success of the bark of willow in the cure of agues". His report. erroneously attributed to Edmond Stone. was published five years later. The active ingredient of willow bark. "salicine". was first isolated 1828 by Joseph Buchner, then by Henri Leroux, and also prepared from the oil of wintergreen (Gaultheria) and meadowsweet (Spirea ulmaria) by J. W. Lowig 1833. and called "Spirsäure", which was already pure acetylsalicylic acid. It was also synthetised 1853 by Ch. Gerhardt and finally 1897 in Bayer's laboratoires by Felix Hoffman, who also demonstrated its antiinflammatory efficacy. After two years of clinical trials with low doses, Bayer's management decided to start the productions and launched Aspirin as an analgetic worldwide in summer 1899. The first ASPIRIN ERA bagun. A completely new epoch started when J. N. Vane and Priscilla Piner demonstrated 1971 that the main mechanism of action of aspirin-like drugs is the inhibition of prostaglandin synthesis. In later studies the potency to inhibit platelet aggregation with small doses of aspirin (30-125 mg) was demonstrated. The Physicians'Health Study 1988 confirmed this effect: aspirin significantly reduced the risk of both, fatal and non-fatal myocardial infarction. and is now used in primary and secondary prevention of atherosclerosis. However the idea was not new: The use of salicylates and aspirin was throughly discussed more than 50 years ago: Paul C. Gibson published 1949 a well-documented case report on efficacy of aspirin in patients with angina, and Kl. Weber and P. Klein in Prague used Gibson's mixture successfully for patients with acute myocardial infarction (1951). Recently, the efficacy and security, the interactions and side-effects of low

  3. ESR investigation of gamma-irradiated Aspirin

    International Nuclear Information System (INIS)

    Cozar, O.; Chis, V.; David, L.; Damian, G.; Barbur, I.

    1997-01-01

    Electron spin resonance spectroscopy was used to investigate the radiation damage in a powder of 2-acetoxybenzoic acid (Aspirin). Three types of radicals occur by γ-irradiation of Aspirin at room temperature. Two of them are result of hydrogen abstraction while the third is produced by hydrogen addition at one of the carbon atoms of the ring. The relative yielding of the free radicals as a function of absorbed dose in the range of 2.4 kGy to 160 kGy is also discussed. (author)

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

    International Nuclear Information System (INIS)

    Ibrahim, M.F.

    2013-01-01

    elevated malondialdehyde (MDA) and reduced glutathione (GSH) levels compared to the related serum control values. The radiation effect was extended to Subgroup 2 that revealed apparent infertility. Moreover, Aspirin oral daily administration caused a remarkable reduction in both FSH and LH hormones alongside with elevated progesterone and PRL levels with no noted E2 level changes (Group 3). However the same treatment accelerated both the fertility and re productivity rates of Subgroup 3. However, the results of the present study revealed the potency of the anti-inflammatory drug Aspirin when administered post radiation exposure (Group 4) in ameliorating the abrupt irradiation induced hormonal imbalance and the significant elevation in serum MDA in addition to its ability in alleviating the radiation induced reproductive disorders (Subgroup 4). In conclusion, oxidative stress caused by radiation exposure of cycling female rats induced marked disturbance in their hormonal balance leading to negative fertility outcomes that has been ameliorated by Aspirin therapy.

  5. Are the current recommendations for the use of aspirin in primary prevention of cardiovascular disease applicable in low-income countries?

    Directory of Open Access Journals (Sweden)

    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

  6. Age-related macular degeneration in a randomized controlled trial of low-dose aspirin: Rationale and study design of the ASPREE-AMD study

    Directory of Open Access Journals (Sweden)

    Liubov Robman

    2017-06-01

    Conclusion: The study findings will be of significant clinical and public interest due to a potential to identify a possible low cost therapy for preventing AMD worldwide and to determine risk/benefit balance of the aspirin usage by the AMD-affected elderly. The ASPREE-AMD study provides a unique opportunity to determine the effect of aspirin on AMD incidence and progression, by adding retinal imaging to an ongoing, large-scale primary prevention randomized clinical trial.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    .g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian...... or endometrial cancer risk and prognosis are warranted. In the present review, we discuss the importance of comprehensive exposure definitions (i.e., duration, timing, consistency and intensity/dose) and evaluation of potential effect modification according to user characteristics, with the aim of identifying......Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin...

  8. Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).

    Science.gov (United States)

    Easton, J Donald; Aunes, Maria; Albers, Gregory W; Amarenco, Pierre; Bokelund-Singh, Sara; Denison, Hans; Evans, Scott R; Held, Peter; Jahreskog, Marianne; Jonasson, Jenny; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence; Johnston, S Claiborne

    2017-09-05

    Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2

  9. Acetyl salicyclic acid (aspirin) improves synthesis of maspin and lowers incidence of metastasis in breast cancer patients

    International Nuclear Information System (INIS)

    Bhattacharyya, M.; Girish, G.V.; Ghosh, R.; Chakraborty, S.; Sinha, A.K.

    2010-01-01

    Maspin, a 42 kDa protein produced in normal breast cells, has been shown to inhibit the invasion and metastasis of breast cancer in an animal model. Ingestion of acetylsalicylic acid (aspirin) by breast cancer patients has been reported to restore the systemic synthesis of maspin through the stimulation of systemic nitric oxide production. Studies were carried out to determine the effect of aspirin on the incidence of breast cancer metastasis, which is reported to occur in 50% of patients who have previously received chemotherapy, radiation, and/or surgery. Thirty-five female patients (aged 41-65 years) with breast cancer who had previously received these therapies took one 75 mg/70 kg body weight enteric-coated aspirin tablet every 24 h, after an adequate meal, for 3 years. Their plasma nitric oxide and maspin levels were measured. The occurrence of metastasis was ascertained monthly by a qualified oncologist, and confirmed, if necessary, by biopsy. Daily ingestion of aspirin by participants resulted in an increase in maspin levels from 0.95±0.04 to 4.63±0.05 nM after 24 h. These levels were maintained for 3 years. These studies suggest that daily ingestion of aspirin might significantly reduce the incidence of breast cancer metastasis in patients who have previously received anticancer therapies. (author)

  10. Rivaroxaban with or without aspirin in stable cardiovascular disease

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  11. Aspirin treatment reduces platelet resistance to deformation.

    Science.gov (United States)

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

    1987-01-01

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

  12. Van der Waals Interactions in Aspirin

    Science.gov (United States)

    Reilly, Anthony; Tkatchenko, Alexandre

    2015-03-01

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

  13. Aspirin augments hyaluronidase induced adhesion inhibition ...

    African Journals Online (AJOL)

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

  14. Aspirin for Venous Ulcers: Randomised Trial (AVURT): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Tilbrook, Helen; Forsythe, Rachael O; Rolfe, Debbie; Clark, Laura; Bland, Martin; Buckley, Hannah; Chetter, Ian; Cook, Liz; Dumville, Jo; Gabe, Rhian; Harding, Keith; Layton, Alison; Lindsay, Ellie; McDaid, Catriona; Moffatt, Christine; Phillips, Ceri; Stansby, Gerard; Vowden, Peter; Williams, Laurie; Torgerson, David; Hinchliffe, Robert J

    2015-11-10

    Venous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs - it is estimated that the cost of treatment for 1 ulcer is up to £1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is often prolonged and up to one quarter of venous leg ulcers do not heal despite standard care. Two previous trials have suggested that low-dose aspirin, as an adjunct to standard care, may hasten healing, but these trials were small and of poor quality. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established. AVURT is a phase II randomised double blind, parallel-group, placebo-controlled efficacy trial. The primary objective is to examine whether aspirin, in addition to standard care, is effective in patients with chronic VLUs (i.e. over 6 weeks in duration or a history of VLU). Secondary objectives include feasibility and safety of aspirin in this population. A target of 100 participants, identified from community leg ulcer clinics and hospital clinics, will be randomised to receive either 300 mg of aspirin once daily or placebo. All participants will receive standard care with compression therapy. The primary outcome will be time to healing of the reference ulcer. Follow-up will occur for a maximum of 27 weeks. The primary analysis will use a Cox proportional hazards model to compare time to healing using the principles of intention-to-treat. Secondary outcomes will include ulcer size, pain evaluation, compliance and adverse events. The AVURT trial will investigate the efficacy and safety of aspirin as a treatment for VLU and will inform on the feasibility of proceeding to a larger phase III study. This study will address the paucity of information currently available regarding aspirin therapy to treat VLU. The study is registered on a public database with

  15. [Diagnosis and treatment of aspirin--and NSAID-induced peptic ulcers].

    Science.gov (United States)

    Satoh, Kiichi; Tanabe, Hiroki; Ichiishi, Eiichiro; Ando, Katsuyoshi

    2015-07-01

    A Japanese case-control study showed the odds ratio of upper gastrointestinal bleeding was 5.5 for aspirin and 6.1 for other NSAIDs. A Japanese cohort study showed that peptic ulcers were found in 6.5% of 1,454 patients receiving low-dose aspirin (LDA). Some endoscopic studies reported that NSAID users often had antral, multiple, and irregular ulcers, irrespective of Helicobacter pylori status. Proton-pump inhibitor (PPI) and misoprostol should be used for therapy for NSAID-ulcers. Maintenance therapy with PPI should be given for prevention of relapse of ulcers of NSAIDs and LDA users. PPI and histamine 2-recetor antagonist were effective for prevention of upper GI mucosal injury in patients receiving LDA.

  16. Role of Aspirin in Patients with Bladder Cancer Receiving Intravesical Bacillus Calmette-Guerin: A Prospective, Observational Study

    Directory of Open Access Journals (Sweden)

    Rupesh Gupta

    2017-10-01

    Full Text Available Introduction: High-Risk Non-Muscle Invasive Bladder Cancers (HR NMIBC are prone to recur and progress even with intravesical Bacillus Calmette-Guerin (BCG therapy. Aim: To investigate the role of aspirin in prevention of early recurrence and progression in patients with HR NMIBC receiving intravesical BCG. Materials and Methods: This was a prospective, single centre, observational study that included patients with HR NMIBC {Ta, T1 or Carcinoma in situ (CIS} from February 2015 to January 2017. Patients were screened for eligibility based on clinical, radiological and risk factor profile assessment, history of treatment with aspirin and medical records. Eligible patients were grouped into Group 1 and Group 2 based on aspirin (for minimum of three months or non-aspirin consumption respectively. Both groups received similar induction, maintenance and intravesical BCG therapy; according to Southwest Oncology Group (SWOG protocol. Follow up cystoscopy was done every three months for up to two years. Results: A total of 152 patients were screened and 103 patients were included in the study (Group 1, n=15; Group 2, n=88. Binary progression analysis revealed that focality was the only significant predictor variable for the recurrence (OR, 5.064; p=0.001. Aspirin intake was not related to stage (p=0.595, grade (p=0.558, recurrence (p=0.508 and progression (p=0.621 of the tumour. Kaplan-Meier analysis showed that 12-month recurrence (64.2% versus 64.7%, p=0.566 and progression free survival rate (66.7% versus 57.3%, p=0.640 were same in both groups. Conclusion: Results showed that aspirin does not affect the recurrence and progression of HR NMIBC in patients receiving BCG therapy.

  17. 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...

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

    Directory of Open Access Journals (Sweden)

    Kok-Yong Chin

    2017-01-01

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

  19. Aspirin resistance: effect of clinical, biochemical and genetic factors.

    Science.gov (United States)

    Fitzgerald, Richard; Pirmohamed, Munir

    2011-05-01

    Aspirin is one of the cornerstones of treatment for cardiovascular disease. However, some patients may be 'resistant' to its effect: this is associated with adverse cardiovascular outcomes and increased mortality. Measuring response to aspirin is often difficult and there is no accepted definition of aspirin resistance. Many assays are available to test aspirin sensitivity but most are not specific to aspirin and the degree of agreement between different assays is poor. Each assay has its own advantages and disadvantages, and there is currently no one assay that can be recommended for routine clinical practise. There are also many potential modifiers of aspirin response including aspirin dose, non-compliance, disease severity, genetic factors, inflammation, diabetes mellitus, hyperlipidaemia, smoking and interacting drugs. Treating the underlying cause may improve aspirin sensitivity but current data are contradictory with no large clinical trials that have addressed this. Further work is required in this area to determine whether and how aspirin resistance is important clinically, what the best measurement is phenotypically and how this should be used in clinical practise, and whether there are any genetic predisposing factors. This will require well designed prospective studies which take into account the numerous confounding factors that can modify aspirin resistance. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Trends in early aspirin use among patients with acute myocardial infarction in China, 2001-2011: the China PEACE-Retrospective AMI study.

    Science.gov (United States)

    Gao, Yan; Masoudi, Frederick A; Hu, Shuang; Li, Jing; Zhang, Haibo; Li, Xi; Desai, Nihar R; Krumholz, Harlan M; Jiang, Lixin

    2014-10-10

    Aspirin is an effective, safe, and inexpensive early treatment of acute myocardial infarction (AMI) with few barriers to administration, even in countries with limited healthcare resources. However, the rates and recent trends of aspirin use for the early treatment of AMI in China are unknown. Using data from the China Patient-centered Evaluative Assessment of Cardiac Events Retrospective Study of Acute Myocardial Infarction (China PEACE-Retrospective AMI Study), we identified a cohort of 14 041 patients with AMI eligible for early aspirin therapy. Early use of aspirin for AMI increased over time (78.4% in 2001, 86.5% in 2006, and 90.0% in 2011). However, about 15% of hospitals had a rate of use of <80% in 2011. Treatment was less likely in patients who were older, presented with cardiogenic shock at admission, presented without chest discomfort, had a final diagnosis of non-ST-segment elevation acute myocardial infarction, or did not receive reperfusion therapy. Hospitalization in rural regions was also associated with aspirin underuse. Despite improvements in early use of aspirin for AMI in China, there remains marked variation in practice and opportunities for improvement that are concentrated in some hospitals and patient groups. ClinicalTrials.gov Unique identifier: NCT01624883. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  1. Microparticle Shedding by Erythrocytes, Monocytes and Vascular Smooth Muscular Cells Is Reduced by Aspirin in Diabetic Patients.

    Science.gov (United States)

    Chiva-Blanch, Gemma; Suades, Rosa; Padró, Teresa; Vilahur, Gemma; Peña, Esther; Ybarra, Juan; Pou, Jose M; Badimon, Lina

    2016-07-01

    Diabetes mellitus is associated with an enhanced risk for cardiovascular disease and its prevalence is increasing. Diabetes induces metabolic stress on blood and vascular cells, promoting platelet activation and vascular dysfunction. The level of vascular cell activation can be measured by the number and phenotype of microparticles found in the circulation. The aim of this study was to investigate the effect of a platelet-inhibitory dose of aspirin on the number and type of microparticles shed to the circulation. Forty-three diabetic patients were enrolled in the study and received a daily dose of 100mg of aspirin for 10 days to cover the average platelet life-span in the circulation. Before and after the intervention period, circulating microparticles were characterized and quantified by flow cytometry. Type 1 diabetic patients had about twice the number of tissue factor-positive circulating microparticles (derived both from platelets and monocytes) and endothelial-derived E-selectin positive microparticles than type 2 diabetic patients. Aspirin therapy significantly inhibited platelets since cyclooxygenase 1 derived thromboxane generation levels were reduced by 99%. Microparticles derived from erythrocytes, activated monocytes, and smooth muscle cells were significantly reduced after 10 days of aspirin administration. These results indicate that: a) vascular and blood cells in type 1 diabetic patients are exposed to more sustained stress shown by their specific microparticle origin and levels; b) aspirin therapy inhibits vascular wall cell activation and microparticle shedding, and c) the effects of aspirin are similar in type 1 and 2 diabetes. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  2. 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 ...

  3. Aspirin: a history, a love story.

    Science.gov (United States)

    Wick, Jeannette Y

    2012-05-01

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

  4. Aspirin resistance: Prevalence and clinical outcome in Egypt

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-10-05

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

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

    Science.gov (United States)

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

  7. Aspirin-induced asthma in children.

    Science.gov (United States)

    Botey, J; Navarro, C; Marín, A; Eseverri, J L

    1988-01-01

    Since Cooke first described bronchospasm induced by acetyl salicylic acid in asthmatic patients in 1919, numerous studies have been done with the objective of understanding the pathology, treatment and incidence of aspirin-induced asthma. The incidence is difficult to establish but according to two recent studies, the percentage in the infantile asthmatic population was estimated at 13% and 28%. This prevalence is greater than that suspected at first and reveals the necessity of reviewing this problem. In this study we present 4 pediatric patients, 2 atopics and 2 non-atopics affected with aspirin-induced asthma. A detailed clinical history, oral provocation test to acetyl salicylic acid, other non-steroid anti-inflammatory analgesics and additives was performed. The oral provocation test with acetyl salicylic acid was positive in all 4 cases. The oral provocation with non-steroid anti-inflammatory analgesics and other additives was negative in 2 patients. In the remaining 2 patients, one demonstrated sensitivity only to tartrazine and the other to tartrazine, red coccine, mefenamic acid and benorylate. In conclusion, aspirin-induced asthma is not infrequent in infancy. Therefore, it is important to bear it always in mind and to diagnose it through oral provocation besides looking for possible cross reactions.

  8. Aspirin Recapitulates Features of Caloric Restriction

    Directory of Open Access Journals (Sweden)

    Federico Pietrocola

    2018-02-01

    Full Text Available The age-associated deterioration in cellular and organismal functions associates with dysregulation of nutrient-sensing pathways and disabled autophagy. The reactivation of autophagic flux may prevent or ameliorate age-related metabolic dysfunctions. Non-toxic compounds endowed with the capacity to reduce the overall levels of protein acetylation and to induce autophagy have been categorized as caloric restriction mimetics (CRMs. Here, we show that aspirin or its active metabolite salicylate induce autophagy by virtue of their capacity to inhibit the acetyltransferase activity of EP300. While salicylate readily stimulates autophagic flux in control cells, it fails to further increase autophagy levels in EP300-deficient cells, as well as in cells in which endogenous EP300 has been replaced by salicylate-resistant EP300 mutants. Accordingly, the pro-autophagic activity of aspirin and salicylate on the nematode Caenorhabditis elegans is lost when the expression of the EP300 ortholog cpb-1 is reduced. Altogether, these findings identify aspirin as an evolutionary conserved CRM.

  9. Effect of misoprostol on patients with aspirin-exacerbated respiratory disease undergoing aspirin challenge and desensitization.

    Science.gov (United States)

    Walters, Kristen M; Simon, Ronald A; Woessner, Katharine M; Wineinger, Nathan E; White, Andrew A

    2017-07-01

    Prostaglandin E 2 (PGE 2 ) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE 2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE 2 stabilizes inflammatory mediator release. To examine whether misoprostol (oral prostaglandin E 1 analogue) use during aspirin challenge and desensitization might decrease the severity of aspirin-induced symptoms and make desensitization safer for patients with AERD. Forty-five patients undergoing aspirin challenge and/or desensitization were randomized to misoprostol (n = 30) or placebo (n = 15) and compared with a group of historical controls (n = 31). Misoprostol (200 μg) was administered at 30 minutes, 90 minutes, and 4 hours after the first dose of nasal ketorolac. Measured end points included change in forced expiratory volume in 1 second (FEV 1 ), peak nasal inspiratory flow rate (PNIF), number of treatments received for induced reactions, and adverse gastrointestinal effects. A difference in FEV 1 and PNIF reduction was detected between misoprostol and placebo (P = .03) and misoprostol and historical controls (P = .01), respectively, during nasal ketorolac challenge. No difference was detected among aspirin reactors. Among all reactors, no difference in magnitude was found for FEV 1 (P = .13) or PNIF (P = .07) reduction across all 3 groups. Total treatment requirement was similar (P = .14). Patients receiving misoprostol were more likely to report adverse gastrointestinal effects (P = .02). The addition of misoprostol to current aspirin challenge and/or desensitization protocols reveals no protective effect in reducing the intensity of nonsteroidal anti-inflammatory drug-induced symptoms and is not recommended based on the findings in this study. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. 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

    2014-09-05

    of aspirin accompanied with PFTα abolished aspirin-induced inhibition of adipogenesis. We demonstrated that aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of PPP. Blockade PPP may be a novel strategy for obesity prevention and therapy. Moreover, when use aspirin in therapeutic strategy, the p53 status should be considered. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Ticagrelor Versus Aspirin in Acute Embolic Stroke of Undetermined Source.

    Science.gov (United States)

    Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Hill, Michael D; Jonasson, Jenny; Kasner, Scott E; Ladenvall, Per; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence; Johnston, S Claiborne

    2017-09-01

    Ticagrelor is an effective antiplatelet therapy among patients with atherosclerotic disease and, therefore, could be more effective than aspirin in preventing recurrent stroke and cardiovascular events among patients with embolic stroke of unknown source (ESUS), which includes patients with ipsilateral stenosis stroke or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90) within 24 hours of symptom onset. In all patients, investigators informed on the presence of ipsilateral stenosis ≥50%, small deep infarct stroke, myocardial infarction, or death within 90 days. ESUS was identified in 4329 (32.8%) patients. There was no treatment-by-ESUS category interaction ( P =0.83). Hazard ratio in ESUS patients was 0.87 (95% confidence interval, 0.68-1.10; P =0.24). However, hazard ratio was 0.51 (95% confidence interval, 0.29-0.90; P =0.02) in ESUS patients with ipsilateral stenosis <50% or aortic arch atherosclerosis (n=961) and 0.98 (95% confidence interval, 0.76-1.27; P =0.89) in the remaining ESUS patients (n=3368; P for heterogeneity =0.04). In this post hoc, exploratory analysis, we found no treatment-by-ESUS category interaction. ESUS subgroups have heterogeneous response to treatment (Funded by AstraZeneca). URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720. © 2017 American Heart Association, Inc.

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

    Science.gov (United States)

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

    2013-02-01

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

  13. Hemostatic effects of the ticagrelor antidote MEDI2452 in pigs treated with ticagrelor on a background of aspirin.

    Science.gov (United States)

    Pehrsson, S; Johansson, K J; Janefeldt, A; Sandinge, A-S; Maqbool, S; Goodman, J; Sanchez, J; Almquist, J; Gennemark, P; Nylander, S

    2017-06-01

    Essentials MEDI2452 is a specific antidote of the platelet P2Y 12 receptor antagonist ticagrelor. Hemostatic effects of MEDI2452 were evaluated in pigs treated with ticagrelor and aspirin. MEDI2452 eliminated free ticagrelor within 5 min and gradually normalized platelet aggregation. Improvements in blood pressure (significant) and in blood-loss and survival (non-significant) were observed. Background Ticagrelor, a P2Y 12 antagonist, is approved for the prevention of thromboembolic events. However, antiplatelet therapies carry a risk of bleeding. Objective To explore the hemostatic effects of MEDI2452, an antidote for ticagrelor. Methods Pigs, pre-treated with aspirin, were given an intravenous infusion of ticagrelor or vehicle. At the end of the infusion, a piece of a liver lobe was cut off and a bolus of MEDI2452 or vehicle was administered intravenously. Blood was collected to monitor blood loss, mean arterial blood pressure (MAP) was recorded and survival time was observed over 4 h. Blood samples for drug plasma exposures and platelet aggregation were collected. Results MEDI2452 eliminated the free concentrations of ticagrelor and its active metabolite AR-C124910XX within 5 min. ADP-induced platelet aggregation was close to normal at 60 min, which was not significantly different from aspirin alone. MEDI2452 numerically reduced ticagrelor-mediated effects: body-weight-adjusted blood loss in the 15- to 90-min interval, 12 (confidence interval [CI] 95% 7-28] vs. 17 (CI 95% 5-31) (ticagrelor and aspirin) vs. 5 (CI 95% 3-9) mL kg -1 (aspirin alone), survival 70% (CI 95% 47-100) vs. 45% (CI 95% 21-92) (ticagrelor and aspirin) vs. 100% (CI 95% 100-100) (aspirin alone), and median survival time, 240 (CI 95% 180-240) vs. 169 (CI 95% 64-240) (ticagrelor and aspirin) vs. 240 (CI 95% 240-240) min (aspirin alone). Finally, MEDI2452 significantly attenuated the decline in MAP, 0.08 (CI 95% 0.07-0.09) vs. 0.141 (CI 95% 0.135-0.148) (ticagrelor and aspirin) vs. 0.04 (CI 95% 0

  14. Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells.

    Science.gov (United States)

    Cheng, Ran; Liu, Ya-Jing; Cui, Jun-Wei; Yang, Man; Liu, Xiao-Ling; Li, Peng; Wang, Zhan; Zhu, Li-Zhang; Lu, Si-Yi; Zou, Li; Wu, Xiao-Qin; Li, Yu-Xia; Zhou, You; Fang, Zheng-Yu; Wei, Wei

    2017-05-02

    Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Antiplatelet Regimen for Patients With Breakthrough Strokes While on Aspirin: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Lee, Meng; Saver, Jeffrey L; Hong, Keun-Sik; Rao, Neal M; Wu, Yi-Ling; Ovbiagele, Bruce

    2017-09-01

    Optimal antiplatelet therapy after an ischemic stroke or transient ischemic attack while on aspirin is uncertain. We, therefore, conducted a systematic review and meta-analysis. We searched PubMed (1966 to August 2016) and bibliographies of relevant published original studies to identify randomized trials and cohort studies reporting patients who were on aspirin at the time of an index ischemic stroke or transient ischemic attack and reported hazard ratio for major adverse cardiovascular events or recurrent stroke associated with a switch to or addition of another antiplatelet agent versus maintaining aspirin monotherapy. Estimates were combined using a random effects model. Five studies with 8723 patients with ischemic stroke or transient ischemic attack were identified. Clopidogrel was used in 4 cohorts, and ticagrelor was used in 1 cohort. Pooling results showed that addition of or a switch to another antiplatelet agent, versus aspirin monotherapy, was associated with reduced risks of major adverse cardiovascular events (hazard ratio, 0.68; 95% confidence interval, 0.54-0.85) and recurrent stroke (hazard ratio, 0.70; 95% confidence interval, 0.54-0.92). Each of the strategies of addition of and switching another antiplatelet agent showed benefit versus continued aspirin monotherapy, and studies with regimen initiation in the first days after index event showed more homogenous evidence of benefit. Among patients who experience an ischemic stroke or transient ischemic attack while on aspirin monotherapy, the addition of or a switch to another antiplatelet agent, especially in the first days after index event, is associated with fewer future vascular events, including stroke. © 2017 American Heart Association, Inc.

  19. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease

    NARCIS (Netherlands)

    Eikelboom, John W.; Connolly, Stuart J.; Bosch, Jackie; Dagenais, Gilles R.; Hart, Robert G.; Shestakovska, Olga; Diaz, Rafael; Alings, Marco; Lonn, Eva M.; Anand, Sonia S.; Widimsky, Petr; Hori, Masatsugu; Avezum, Alvaro; Piegas, Leopoldo S.; Branch, Kelley R. H.; Probstfield, Jeffrey; Bhatt, Deepak L.; Zhu, Jun; Liang, Yan; Maggioni, Aldo P.; Lopez-Jaramillo, Patricio; O'Donnell, Martin; Kakkar, Ajay K.; Fox, Keith A. A.; Parkhomenko, Alexander N.; Ertl, Georg; Störk, Stefan; Keltai, Matyas; Ryden, Lars; Pogosova, Nana; Dans, Antonio L.; Lanas, Fernando; Commerford, Patrick J.; Torp-Pedersen, Christian; Guzik, Tomek J.; Verhamme, Peter B.; Vinereanu, Dragos; Kim, Jae-Hyung; Tonkin, Andrew M.; Lewis, Basil S.; Felix, Camilo; Yusoff, Khalid; Steg, P. Gabriel; Metsarinne, Kaj P.; Cook Bruns, Nancy; Misselwitz, Frank; Chen, Edmond; Leong, Darryl; Yusuf, Salim; Aboyans, V.; Ha, J.; Keltai, K.; Lamy, A.; Liu, L.; Moayyedi, P.; Sharma, M.; Stoerk, S.; Varigos, J.; Bhagirath, V.; Bogaty, P.; Botto, F.; Catanese, L.; Donato Magno, J.; Fabbri, G.; Gabizon, I.; Gosselin, G.; Halon, D.; Heldmann, M.; Lamelas, P.; Lauw, M.; Leong, Y.; Liang, D.; Lutay, Y.; Maly, M.; Mikulik, R.; Nayar, S.; Ng, K.; Perera, K.; Pirvu, O.; Ronner, E.; Sato, S.; Smyth, A.; Sokolova, E.; Wiendl, M.; Winkelmann, B.; Yang, X.; Yufereva, Y.; Cairns, J.; Sleight, P.; deMets, D.; Momomura, S. I.; Prins, M. [=Martin H.; Ramsay, T.; Goto, S.; Rouleau, J. L.; Schumi, J.; Thabane, L.; Casanova, A.; Bangdiwala, S.; Deng, E.; Dyal, L.; Khatun, R.; Marsden, T.; Pogue, J.; Tang, C.; Wong, G.; Yuan, F.; Aman, S.; Ariz, A.; Ashton, H.; Belanger, J.; Belanger, M.; Brettell, K.; Chandra, J.; Choppick, C.; Cisternino, D.; Cuncins-Hearn, A.; Di Marino, M.; Diao, L.; Dwomoh, S.; Dykstra, A.; Galatsis, E.; Gasic, T.; Gutierrez, J.; Hamilton, L.; Irwin, L.; Lapensee, C.; Li, A.; Lu, X.; MacRae, L.; Malik, S.; Malvestiti, A.; Mastrangelo, J.; Maystrenko, A.; O'Donnell, L.; Reeh, K.; Szymkow, P.; Thomas, S.; Thrasher, D.; Tyrwhitt, J.; White, L.; Bastone, R.; Berkowitz, S.; Dias, A.; Ho, K.; Keller, L.; Lanius, V.; Lister, K.; Merten, C.; Muehlhofer, E.; Schmidt, K.; Tasto, C.; Tsihlias, E.; Woroniecka-Osio, A.; Orlandini, A.; Niemann, G.; Pascual, A.; Toscanelli, S.; Cabezón, M.; Debaveye, B.; Meeusen, K.; Luys, C.; Broos, K.; Vandenberghe, K.; Luyten, A.; Oliveira, G. B. F.; Vila Nova, D. C.; Konishi, M. Y. N.; Lonn, A.; Turbide, G.; Cayer, M.; Rovito, C.; Standen, D.; Li, J.; Lopez Pico, M.; Dusek, R.; Buzalka, V.; Larsen, J.; Paucar, M. J.; Saarinen, M.; Simon, T.; Bezault, M.; Le Lay, M.; Epstein, L.; Fajardo-Moser, M.; Röser, C.; Putz-Todd, G.; Scheidemantel, F.; Poehler, D.; Renner, J.; Hargitai, A.; Doherty, A. O.; Duffy, N.; Roarty, C.; Nolan, A.; Power, A.; Yuval, R.; Ben Ari, M.; Greenblatt, S.; Marmor, Y.; Lucci, D.; Ceseri, M.; Baldini, E.; Cipressa, L.; Miccoli, M.; Goto, M.; Yamasowa, H.; Kajiwara, M.; Takase, D.; Ikeguchi, K.; Matsumoto, M.; Ishii, M.; Asai, J.; Nozaki, D.; Akatsuka, T.; Yoshida, T.; Shahadan, S.; Md Nasir, N.; Schut, Astrid; Vinck, Leonie; van Leeuwen, Marjelle; Sanchez, J.; Aquino, M. R.; Mararac, T.; Benedyk, K.; Iordache, A.; Ciobanu, A.; Rimbas, R.; Dragoi Galrinho, R.; Magda, S.; Mihaila, S.; Mincu, R.; Suran, B.; Cotoban, A.; Matei, L.; Kursakov, A.; Rusnak, P.; Zakharova, A.; Demidova, E.; Commerford, A.; Lee, S.; Ju, I.; Gunolf, M.; Lorimer, A.; Parkhomenko, L.; Johnson, J.; Anderson, J.; Norby-Slycord., C.; Sala, J.; Sicer, M.; Rasmussen, M.; Luciani, C.; Cartasegna, L.; Beltrano, C.; Medek, G.; Vico, M.; Lanchiotti, P.; Martella, C.; Hominal, M.; Castoldi, M.; Casali, W.; Raimondi, S.; Hasbani, E.; Prado, A.; Paterlini, G.; Waisman, F.; Leonard, M.; Caccavo, A.; Alarcon, V.; Zaidman, C.; Guerlloy, F.; Vogel, D.; Imposti, H.; Dominguez, A.; Hrabar, A.; Fernandez, A.; Schygiel, P.; Sokn, F.; Cuneo, C.; Gutierrez Carrillo, N.; Martinez, G.; Luquez, H.; Costantino, M.; Ruiz, M.; Beccetti, N.; Mackinnon, I.; Cluigt, N.; Ahuad Guerrero, R.; Fanuele, M.; Campisi, V.; Costabel, J.; Romanelli, M.; Bartolacci, I.; Echeverria, M.; Pedrotti, M.; Montaña, O.; Camino, A.; Crespo, C.; Barbieri, M.; Lopez Santi, R.; Tonin, H.; Heffes, R.; Gomez Vilamajo, O.; Vanesio, F.; Allegrini, E.; Garcia Duran, R.; Garcia, C.; Garcia Duran, L.; Schiavi, L.; Mana, M.; Bordonava, A.; Rodriguez, M.; Gutierrez, M.; Garrido, M.; Rodriguez, C.; Ingaramo, A.; Costamagna, O.; Almagro, S.; Gerbaudo, C.; Pelagagge, M.; Bustamante Labarta, M.; Novaretto, L.; Maldini, A.; Lopez, L.; Albisu Di Gennero, J.; Ibanez Saggia, L.; Garcia Vilkas, A.; Alvarez, M.; Stoermann, W.; Vita, N.; Vottero, E.; Macin, S.; Cocco, M.; Onocko, M.; Dran, R.; Gimenez, C.; Cardona, M.; Guzman, L.; Guzman, P.; Martinez, D.; Sarjanovich, R.; Huerta, C.; Scaro, G.; Cuadrado, J.; Rodriguez, G.; Nani, S.; Guardiani, F.; Litvak Bruno, M.; Ceconi, G.; Chacon, C.; Casado, M.; Fernandez Moutin, M.; Maffei, L.; Sassone, S.; Yantorno, M.; Grinfeld, D.; Vensentini, N.; Rolandi, F.; Fallabrino, L.; Majul, C.; Paez, O.; Visser, M.; Luciardi, H.; Mansilla, V.; Gonzalez Colaso, P.; Ferre Pacora, F.; Jure, H.; Parody, M.; Espeche, E.; Whelan, A.; Boyle, A.; Collins, N.; Roberts-Thomson, P.; Rogers, J.; Caroll, P.; Colquhoun, D.; Williams, L.; Shaw, J.; Blombery, P.; Amerena, J.; Lee, C.; Hii, C.; Royse, A.; Royse, C.; Singh, B.; Selvanayagam, J.; Jansen, S.; Thompson, P.; Lo, W.; Hammett, C.; Poulter, R.; Graves, S.; Narasimhan, S.; van den Heuvel, P.; Wollaert, B.; Sinnaeve, P.; Fourneau, I.; Meuris, B.; Vanassche, T.; Ector, B.; Janssens, L.; Debonnaire, P.; Vandekerckhove, Y.; van de Borne, P.; Wautrecht, J.; Motte, S.; Leroy, J.; Schroë, H.; Vrolix, M.; Ferdinande, B.; Vranckx, P.; Benit, E.; Elegeert, I.; Lerut, P.; Wallaert, P.; Hoffer, E.; Borgoens, P.; Dujardin, K.; Brasil, C. K. O. I.; del Monaco, M. I.; Uint, L.; Pavanello, R.; Precoma, D. B.; Vianna, H. S.; Abrantes, J.; Morelli, J.; Manenti, E.; Jaeger, C.; Reis, G.; Giorgeto, F. E.; França, C. C. B.; Quadros, T. F. S.; Saraiva, J.; Costa, M.; de Camargo, O.; Marson Lopes, M.; Silva, J.; Maia, L. N.; Nakazone, M. A.; Mouco, O. M. C. C.; Lemos, M. A. B. T.; Hernandes, M. E.; Pântano, G. S.; de Castro, J. C. M.; Rossi, P. R. F.; Guedes, A. A. M.; Dos Santos, L. B.; dos Santos, F. R.; Vidotti, M. H.; Zimmermann, S. L.; Rech, R.; Nunes, C.; Abib, E.; Oliveira, K. L. C.; Leaes, P. E.; Botelho, R. V.; Navarro, A. L. C.; Silva, R. A.; Arantes, F. B. B.; Dutra, O.; Vaz, R.; Souza, W. K. S. B.; Souza, A. S. B.; Queiroz, W. C. B.; Braile, M.; Ferreira, V.; Izukawa, N. M.; Prakasan, A. K.; Nicolau, J. C.; Dalçóquio, T. F.; Tanajura, L. F. L.; Serrano, C. V.; Hueb, W. A.; Minelli, C.; Borsetti Neto, F. A.; Nasi, L. A.; Martins, S. C. O.; Oliveira, L. F. A.; Silva, M. A. V.; Ferreira, J. O.; de Carvalho Cantarelli, M. J.; Tytus, R.; Pasyk, E.; Pandey, A. S.; Rowe, A.; Cha, J.; Vizel, S.; Babapulle, M.; Semelhago, L.; Saunders, K.; Haligowski, D.; Berlingieri, J.; Nisker, W.; Kiaii, B.; Romsa, J.; Chu, M.; Nagpal, D.; Guo, R.; Mckenzie, N.; Quantz, M.; Bhargava, R.; Bhargava, M.; Mehta, P.; Hill, L.; Heslop, W.; Fell, D.; Hess, A.; Zadra, R.; Zeman, P.; Srivamadevan, M.; Lam, A.; Tai, S.; Al-Qoofi, F.; Spence, F.; Anderson, T.; Kieser, T.; Kidd, W.; Fedak, P.; Smith, E.; Har, B.; Brown, C.; Forgie, R.; Hassan, A.; Pelletier, M.; Searles, G.; Marr, D.; Bessoudo, R.; Douglas, G.; Legare, J.; Petrella, R.; Pavlosky, W.; Ricci, J.; Galiwango, P.; Janmohamed, A.; Kassam, S.; Mukherjee, A.; Vijayaraghavan, R.; Burstein, J.; D'Mello, N.; Glanz, A.; Noiseux, N.; Stevens, L. M.; Basile, F.; Prieto, I.; Normandin, L.; Helou, J.; Do, Q. B.; Bainey, K.; Tymchak, W.; Welsh, R.; Merali, F.; Pandith, V.; Heffernan, M.; Orfi, J.; Mcconachie, D.; Jedrzkiewicz, S.; Della Siega, A.; Robinson, S.; Nadra, I.; Poirier, P.; Dagenais, F.; Voisine, P.; Mohammadi, S.; Doyle, D.; Baillot, R.; Charbonneau, E.; Dumont, E.; Kalavrouziotis, D.; Perron, J.; Jacques, F.; Laflamme, M.; Brulotte, S.; Crete, M.; Degrâce, M.; Delage, F.; Grondin, F.; Lemieux, A.; Michaud, N.; Saulnier, D.; Ross, M. K.; Nguyen, M.; Harvey, R.; Daneault, B.; Hartleib, M.; Guzman, R.; Nguyen, T.; Singal, R.; Bourgeois, R.; Landry, D.; Kamel, S.; Rupka, D.; Kuritzky, R.; Khaykin, Y.; Phaneuf, D. C.; Desjardins, V.; Coll, X.; Huynh, T.; Pilon, C.; Mansour, S.; Lemire, F.; Kokis, A.; Potvin, J.; Campeau, J.; Audet, M.; Boulianne, M.; Dupuis, R.; Lauzon, C.; Pruneau, G.; Senay, B.; Pichette, F.; Cieza, T.; Breton, R.; Belisle, P.; Barabas, M.; Diaz, A.; Costa, R.; Absi, F.; Garand, M.; Rheault, A.; Lemay, C.; Gisbert, A.; Raymond, A.; Barrero, M.; Gagne, C. E.; Rheault, P.; Pepin-Dubois, Y.; Johnston, J.; Mundi, A.; Cohen, G.; Shukle, P.; Baskett, R.; Hirsch, G.; Ali, I.; Stewart, K.; Fenton, J.; Pudupakkam, S.; Willoughby, R.; Czarnecki, W.; Roy, A.; Montigny, M.; Descarries, L.; Mayrand, H.; Comtois, H.; Essiambre, R.; Ringuette, G.; Boutros, G.; Gendreau, R.; Pham, L.; Nguyen, V.; Nguyen-Thanh, H. K.; Ben-Yedder, N.; Nawaz, S.; Fremes, S.; Moussa, F.; Shukla, D.; Labonte., R.; Jano, G.; Bobadilla, B.; Saavedra, J.; Bahamondes, J.; Cobos, J.; Grunberg, E.; Corbalan, R.; Verdejo, H.; Medina, M.; Vega, M.; Nahuelpan, L.; Castañia, F.; Raffo, C.; Vargas, A.; Reyes, T.; Vargas, D.; Perez, L.; Arriagada, G.; Potthoff, S.; Godoy, J.; Stockins, B.; Larenas, G.; Quiñinao, F.; Sepulveda, P.; Trucco, V.; Pincetti, C.; Saavedra, S.; Silva, P.; Vejar, M.; Rodríguez, T.; Rodriguez, J.; Tian, H.; Zhang, J.; Meng, Y.; Wu, X.; Wu, Q.; Wang, Q.; Mu, Y.; Yang, J.; Wang, F.; Zhang, W.; Ke, Y.; Jiang, H.; Yin, P.; Jia, K.; Chen, C.; Wang, Z.; Qi, B.; Yu, L.; Feng, G.; Li, L.; Jiang, L.; Wu, S.; Yu, H.; Wu, Z.; Ding, R.; Liu, S.; Xu, H.; Cao, H.; Bai, X.; Zheng, Y.; Liu, Z.; Sun, H.; Yang, P.; Li, B.; Feng, Z.; Yang, Y.; Xu, Z.; Wu, W.; Meng, Q.; Ge, J.; Dai, Y.; Yang, H.; Chen, X.; Tian, X.; Shi, Y.; Hu, T.; Zhang, R.; Zhao, Q.; Quan, W.; Zhu, Y.; Zheng, Z.; Zhang, S.; Zhao, Y.; Zhao, C.; Wang, R.; Tao, L.; Hu, D.; Wang, Y.; Fan, F.; Huang, W.; Xia, X.; Fu, G.; Jiang, D.; Wang, M.; Li, C.; Xu, K.; Dong, Y.; Chen, Y.; Wu, D.; Wang, C.; Sun, X.; Lu, S.; Zhou, X.; Kong, Y.; Zhang, B.; Sotomayor, A.; Suarez, M.; Ripoll, D.; Herrera, O.; Accini Mendoza, J.; Saad Cure, C.; Reyes, M.; Vidal, T.; Donado Beltran, P.; Hernandez Jaimes, E.; Castillo, H.; Rocha, C.; Forero, L.; Zarate Bernal, D.; Vanstrrahle Gonzalez, L.; Urina Triana, M.; Quintero, A.; Ramirez, N.; Balaguera Mendoza, J.; Aroca Martinez, G.; Cotes, C.; Mercado, A.; Lastra Percy, X.; Perez Mayorga, M.; Rodriguez, N.; Molina de Salazar, D.; Perez Agudelo, J.; Lopez Villegas, L.; Agudelo Ramos, L.; Melo Polo, M.; Esparza Albornoz, A.; Forero Gomez, J.; Sanchez Vallejo, G.; Aristizabal, J.; Gallego, A.; Contreras, C.; Yepez, J.; Angel Escobar, J.; Manzur J, F.; Cohen, L.; Boneu, D.; Garcia Lozada, H.; Barrios, L.; Celemin, C.; Diego, M.; Garcia Ortiz, L.; Montoya, C.; Ramirez, E.; Arcos Palma, E.; Ceron, J.; Acosta, G.; Gomez Mesa, J.; Velasquez, J.; Barreto, D.; Trujillo Dada, F.; Trujillo Accini, F.; Cano, R.; Corredor de La Cruz, K.; Maria, V.; Palmera, J.; Vesga, B.; Hernandez, H.; Moreno Silgado, G.; Aruachan Vesga, S.; Burgos Martinez, E.; Quintero Villareal, G.; Solano Ayazo, F.; Porto Valiente, J.; Zidkova, E.; Krupicka, P.; Bultas, J.; Mandysova, E.; Lubanda, J.; Horak, J.; Belohlavek, J.; Kovarnik, T.; Gorican, K.; Rucka, D.; Smid, O.; Dostalova, G.; Skalicka, H.; Karetova, D.; Pavlinak, V.; Kuchynkova, S.; Marek, J.; Rob, D.; Ravlykova, K.; Prochazka, P.; Siranec, M.; Urbanec, T.; Vareka, T.; Nesvadbova, P.; Kaletova, M.; Indrakova, J.; Kryza, R.; Heczko, M.; Hanak, P.; Jancar, R.; Kocurkova, L.; Marcinek, G.; Cermak, O.; Drasnar, T.; Richter, M.; Kaspar, J.; Spinar, J.; Parenica, J.; Parenicova, I.; Schildberger, J.; Toman, O.; Ludka, O.; Poloczek, M.; Musil, V.; Miklik, R.; Labrova, R.; Lokaj, P.; Felsoci, M.; Bocek, O.; Kanovsky, J.; Zatocil, T.; Jerabek, P.; Matuska, J.; Jankovic, M.; Jankovicova, H.; Tesak, M.; Sulc, D.; Svacinova, H.; Radvan, M.; Bednar, J.; Motovska, Z.; Petr, R.; Fischerova, M.; Branny, M.; Vodzinska, A.; Cerny, J.; Indrak, J.; Sknouril, L.; Maly, J.; Vacek, T.; Prazak, O.; Broulikova, K.; Hajsl, M.; Jarkovsky, P.; Kamenik, L.; Kotik, I.; Krcova, E.; Sedlon, P.; Skvaril, J.; Cernohous, M.; Kohoutek, J.; Levcik, M.; Holek, M.; Hajdusek, P.; Foltynova Caisova, L.; Novak, V.; Kladivkova, M.; Slaby, J.; Houra, M.; Vojtisek, P.; Novotny, V.; Lazarak, T.; Pliva, M.; Pirk, J.; Barciakova, L.; Jandova, R.; Adamkova, V.; Galovcova, M.; Peterkova, L.; Turek, D.; Prochazka, J.; Belohoubek, J.; Spinarova, L.; Panovsky, R.; Novotny, P.; Krejci, J.; Hude, P.; Ozabalova, E.; Godava, J.; Honek, T.; Kincl, V.; Benesova, M.; Buckova, J.; Canadyova, J.; Mokracek, A.; Homza, M.; Stverka, P.; Florian, J.; Lukac, B.; Polasek, R.; Kucera, P.; Seiner, J.; Karasek, J.; Coufal, Z.; Stastny, J.; Cernicek, V.; Skalnikova, V.; Jiresova, E.; Brat, R.; Sieja, J.; Gloger, J.; Berger, P.; Prochazkova, I.; Samlik, J.; Brtko, M.; Tuna, M.; Polansky, P.; Omran, N.; Myjavec, A.; Hrdinova, M.; Jansky, P.; Kratochvilova, R.; Burkert, J.; Koubek, F.; Fiala, R.; Paulasova Schwabova, J.; Lindner, J.; Hlubocky, J.; Spacek, M.; Marcian, P.; Hanak, V.; Pozdisek, Z.; Lonsky, V.; Santavy, P.; Troubil, M.; Straka, Z.; Budera, P.; Fojt, R.; Talavera, D.; Tretina, M.; Nemec, P.; Orban, M.; Bedanova, H.; Wiggers, H.; Tougaard, R.; Larsen, A.; Nielsen, H.; Mattsson, N.; Gunnar, G.; Bruun, N.; Folke, F.; Soendergaard, K.; Koeber, L.; Frydland, M.; Fuchs, A.; Bang, L.; Houlind, K.; Olsen, M.; Soerensen, V.; Overgaard Andersen, U.; Dixen, U.; Refsgaard, J.; Moeller, D.; Zeuthen, E.; Lund, J.; Soegaard, P.; Jensen, S.; Duarte, Y.; Duarte, W.; Cáceres, S.; Pow Chon Long, F.; Peñaherrera, C.; Anzules, N.; Sánchez, M.; Zuleta, I.; López, J.; Villota, M.; Sánchez, H.; Perugachi, C.; Gómez, S.; Morejón, P.; Mármol, R.; Guamán, S.; Trujillo, F.; Escobar, M.; Carrera, F.; Ponce, F.; Terán, P.; Carrasco, S.; Tuomilehto, J.; Humaloja, K.; Lindberg, L.; Tuomilehto, H.; Tuominen, M.-L.; Kantola, I.; Juliard, J.; Feldman, L.; Ducrocq, G.; Boulogne, C.; Petitalot, V.; Leclercq, F.; Roubille, F.; Agullo, A.; Ferrari, E.; Chiche, O.; Moceri, P.; Boccara, F.; Charbonnier, M.; Azeddine, B.; Ederhy, S.; Soulat Dufour, L.; Cohen, A.; Etienney, A.; Messas, E.; Calvalido, A.; Galloula, A.; Zarka, S.; Courtois, M.-C.; Mismetti, P.; Accassat, S.; Buchmuller, A.; Moulin, N.; Bertoletti, L.; Seffert, B.; Sevestre, M.; Samy Modeliar Remond, S.; Dupas, S.; Mardyla, J.; Le Gloan, S.; Cayla, G.; Cornillet, L.; Schmutz, L.; Motreff, P.; Souteyrand, G.; Amonchot, A.; Barber-Charmoux, N.; Combaret, N.; Malcles, G.; Brenner, S.; Christa, M.; Duengen, H.; Krackhardt, F.; Bobenko, A.; Hashemi, D.; Stellbrink, C.; Stellbrink, E.; Köster, C.; Guerocak, O.; Bourhaial, H.; Oumbe Tiam, S.; Kemala, E.; Froemke, J.; Kadel, C.; Moellinger, H.; Friedrich, K.; Rafoud, K.; Braun-Dullaeus, R.; Herold, J.; Ganzer, M.; Jeserich, M.; Kimmel, S.; Haggenmiller, S.; Schoengart, H.; Voehringer, H.; Opitz, C.; Appel, K.; Appel, S.; Utech, A.; Finger, C.; Duersch, M.; Dorsel, T.; Wistorf, N.; Grude, M.; Nikol, S.; Ueberschaer, D.; Kast, P.; Darius, H.; Sommer, S.; Girke, F.; Oeztuerk, C.; Ranft, J.; Mikalo, A.; Schellong, S.; Voigts, B.; Mueller, C.; Jungmair, W.; Davierwala, P.; Misfeld, M.; Bomke, K.; Akhavuz, O.; Haensig, M.; Vorpahl, M.; Blem, A.; Langer, G.; Nover, I.; Koehler, T.; Bajnok, L.; Marton, Z.; Laszlo, Z.; Noori, E.; Veress, G.; Fogarassy, G.; Aradi, D.; Kelemen, B.; Vertes, A.; Davidovits, Z.; Zsary, A.; Kis, E.; Hepp, T.; Koranyi, L.; Peterfai, E.; Bezzegh, K.; Bakai, J.; Agardi, I.; Boda, Z.; Razso, K.; Poor, F.; Varallyay, Z.; Jarai, Z.; Sallai, L.; Dudas, M.; Barton, J.; Mahmood, K.; Makki, H.; McAdam, B.; Salim, T.; Murphy, A.; Crean, P.; Liddy, A. M.; Mahon, N.; Khan, I.; Hassan, S.; Curtin, R.; McFadden, E.; MacNeill, B.; Kyvelou, S.; Canavan, M.; Veerasingam, D.; Dinneen, S.; Halabi, M.; Rosenfeld, I.; Levinas, T.; Goldberg, A.; Khateeb, A.; Zimlichman, R.; Ben-Aharon, J.; Beniashvili, A.; Betsalel, A.; Zeltser, D.; Rogowski, O.; Mardi, T.; Rozenbaum, Z.; Turgeman, Y.; Or, T.; Rabkin, Y.; Klainman, E.; Halabi, S.; Halon, D. A.; Katz, A.; Plaev, T.; Drogenikov, T.; Atar, S.; Kilimnik, M.; Wishniak, A.; Merei, M.; Zvi, Y.; Nikolsky, E.; Zukermann, R.; Petcherski, S.; Bosi, S.; Gaitani, S.; Naldi, M.; Barbieri, A.; Faggiano, P.; Guidetti, F.; Adamo, M.; D’Aloia, A.; Magatelli, M.; Robba, D.; Mos, L.; Vriz, O.; Sinagra, G.; Maras, P.; Doimo, S.; Cosmi, F.; D'Orazio, S.; Oltrona Visconti, L.; Leonardi, S.; Vullo, E.; Sbaffi, A.; Azzara, G.; Mauri, S.; Gianni, U.; de Matteis, C.; Campidonico, U.; Di Pasquale, G.; Di Niro, M.; Riva, L.; Filippini, E.; Di Biase, M.; Ieva, R.; Martone, A.; Mandorla, S.; Regni, O.; Capponi, E. 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Yuba, K.; Miyajima, H.; Tobetto, Y.; Yoneda, K.; Ogura, R.; Kobayashi, H.; Takamura, T.; Enkou, K.; Ochi, Y.; Yamada, D.; Kuramochi, T.; Misumi, K.; Iiduka, D.; Hirose, M.; Tone, K.; Taniguchi, Y.; Ebihara, T.; Makino, M.; Yokota, M.; Nitta, M.; Udo, A.; Shimizu, S.; Fujii, K.; Iwakura, K.; Okamura, A.; Inoue, K.; Nagai, H.; Hirao, Y.; Tanaka, K.; Tanaka, N.; Yamasaki, T.; Oka, T.; Iwamoto, M.; Tanaka, T.; Nakamaru, R.; Okada, M.; Takayasu, K.; Sumiyoshi, A.; Inoue, H.; Kitagaki, R.; Ninomiya, Y.; Mizutomi, K.; Koizumi, I.; Funada, A.; Tagawa, S.; Kamide, S.; Saku, K.; Ideishi, M.; Ogawa, M.; Uehara, Y.; Iwata, A.; Nishikawa, H.; Ike, A.; Sugihara, M.; Imaizumi, S.; Fujimi, K.; Kawamura, A.; Sako, H.; Morito, N.; Morii, J.; Fukuda, Y.; Yahiro, E.; Matsunaga, A.; Matsumoto, N.; Noda, K.; Shiga, Y.; Nagata, Y.; Kimura, K.; Ebina, T.; Hibi, K.; Iwahashi, N.; Maejima, N.; Konishi, M.; Matsushita, K.; Minamimoto, Y.; Kawashima, C.; Nakahashi, H.; Kimura, Y.; Takahashi, H.; Matsuzawa, Y.; Kirigaya, J.; Sato, R.; Kikuchi, S.; Ogino, Y.; Kirigaya, H.; Kashiwase, K.; Hirata, A.; Takeda, Y.; Amiya, R.; Higuchi, Y.; Sakaguchi, T.; Nakano, T.; Matsusaki, N.; Suzuki, S.; Hayashi, T.; Nakatani, S.; Koide, M.; Kobayashi, T.; Hamanaka, Y.; Makino, N.; Sotomi, Y.; Abe, M.; Fujieda, H.; Hashimoto, K.; Teratani, Y.; Abe, Y.; Yokoyama, Y.; Higashino, H.; Okuda, H.; Yamazato, M.; Noda, T.; Arai, M.; Ono, K.; Hirose, T.; Iwama, M.; Warita, S.; Goto, Y.; Abe, S.; Kojima, T.; Yoshizane, T.; Tanihata, S.; Fujii, T.; Yagasaki, H.; Miwa, H.; Ishiguro, M.; Kato, T.; Watanabe, R.; Horio, S.; Mita, T.; Hirayama, A.; Watanabe, I.; Hiro, T.; Nakai, T.; Takayama, T.; Yoda, S.; Yajima, Y.; Okubo, K.; Okumura, Y.; Kato, M.; Fukamachi, D.; Aizawa, Y.; Sonoda, K.; Iida, K.; Sasaki, N.; Iso, K.; Takahashi, K.; Kougo, T.; Haruta, H.; Kurokawa, S.; Mano, H.; Nagashima, K.; Onaka, H.; Doi, H.; Hirano, N.; Okamoto, F.; Mori, K.; Ri, G.; Zushi, R.; Otsuka, K.; Inoko, M.; Haruna, T.; Nakane, E.; Miyamoto, S.; Izumi, T.; Honjo, S.; Ikeda, H.; Wada, Y.; Funasako, M.; Hayashi, H.; Hamasaki, A.; Sasaki, K.; Seko, Y.; Nakasone, K.; Hanyu, M.; Iwasaki, Y.; Iwasaki, K.; Ayano, S.; Hirokami, M.; Omoto, Y.; Sasaki, H.; Sato, H.; Yuda, S.; Okubo, M.; Matsuo, H.; Tsuchiya, K.; Kawase, Y.; Miyake, T.; Kondo, H.; Hattori, A.; Kikuchi, J.; Okamoto, S.; Hirata, T.; Kawamura, I.; Ota, H.; Omori, H.; Tanigaki, T.; Kamiya, H.; Sobue, Y.; Komoda, T.; Akatsuka, Y.; Yamamoto, M.; Isegawa, K.; Takanezawa, M.; Kataoka, C.; Imamaki, M.; Shibata, Y.; Yasuda, K.; Shimano, M.; Ozaki, R.; Morishita, Y.; Okabe, K.; Kondo, K.; Miura, A.; Manita, M.; Tabata, K.; Asahi, T.; Mashidori, T.; Higa, N.; Nakata, M.; Himi, T.; Matsudo, Y.; Sekine, T.; Hou, K.; Tonoike, N.; Hama, Y.; Tanaka, S.; Ge, B.; Takahara, M.; Ishimura, M.; Shikada, T.; Ueno, H.; Amemiya, H.; Hisamatsu, Y.; Sada, K.; Sato, T.; Harada, K.; Nakamura, T.; Ako, J.; Tojo, T.; Shimohama, T.; Kishihara, J.; Ishii, S.; Fukaya, H.; Meguro, K.; Nishino, Y.; Inoue, M.; Matsui, Y.; Omura, Y.; Kawakami, H.; Matsuoka, H.; Oshita, A.; Seike, F.; Kondo, N.; Miyoshi, T.; Yamada, Y.; Uchiya, T.; Kikuchi, Y.; Koretsune, Y.; Abe, H.; Shinouchi, K.; Nishida, H.; Yasumura, K.; Date, M.; Ueda, Y.; Iida, Y.; Idemoto, A.; Toriyama, C.; Yokoi, K.; Mishima, T.; Yamada, T.; Fukunami, M.; Morita, T.; Furukawa, Y.; Kawasaki, M.; Kikuchi, A.; Tamaki, S.; Seo, M.; Shirakawa, Y.; Ikeda, I.; Fukuhara, E.; Kawai, T.; Kayama, K.; Kawahira, M.; Tanabe, K.; Nakamura, J.; Shimomura, H.; Kudo, T.; Morisaki, S.; Ogura, Y.; Chazono, N.; Onoue, Y.; Matsumuro, Y.; Shirakawa, T.; Nishi, M.; Kinoshita, N.; Nakamura, R.; Miyai, N.; Ohta, K.; Sawanishi, T.; Takahashi, A.; Hada, T.; Nakajima, S.; Taniguchi, N.; Mizuguchi, Y.; Takahashi, Y.; Hashimoto, S.; Machida, M.; Hirabayashi, K.; Morimoto, S.; Higashino, Y.; Otsuji, S.; Takiuchi, S.; Yabuki, M.; Hasegawa, K.; Shishikura, D.; Ibuki, M.; Ishibuchi, K.; Nagayama, S.; Ishii, R.; Tamaru, H.; Yamamoto, W.; Utsu, N.; Miyakoshi, K.; Nakashima, D.; Tsukuda, K.; Ueda, K.; Nakano, A.; Fukuda, T.; Ikeda, S.; Tsuchiya, H.; Toshima, S.; Tateno, R.; Ishikubo, T.; Suguta, M.; Nakamura, S.; Funatsu, A.; Mizobuchi, M.; Tanaka, M.; Nagai, T.; Hirano, S.; Hashimoto, T.; Doi, T.; Shirasaka, A.; Takeda, S.; Sasaki, Y.; Ohya, H.; Hosokawa, A.; Nishina, N.; Koki, B.; Ando, K.; Hiramori, S.; Soga, Y.; Tomoi, Y.; Tohoku, S.; Shirai, S.; Hyodo, M.; Isotani, A.; Domei, T.; Kuramitsu, S.; Morinaga, T.; Hayashi, M.; Hiromasa, T.; Nagae, A.; Yamaji, Y.; Nakao, K.; Sakamoto, T.; Taguchi, E.; Tsurugi, T.; Tanaka, Y.; Suzuyama, H.; Koyama, J.; Nagano, M.; Okamatsu, H.; Kodama, K.; Nakamura, M.; Horibata, Y.; Sone, M.; Tsunemori, M.; Bando, M.; Nakayama, T.; Tanigaito, Y.; Nomoto, M.; Sawamura, T.; Unoki, T.; Lim, C. W.; Zainal Rashid, R.; Najme Khir, R.; Ibrahim, K. S.; Wan Azman, W. A.; Sridhar, G. S.; Watson, T.; Abu Kassim, Z.; Mahmood Zuhdi, A. S.; Abdul Hafidz, M. I.; Abu Hassan, M. R.; Wan Rahimi Shah, W. F.; Karthikesan, D.; Mohd Suan, M. A.; Md Ali, S. M.; Kasim, S.; Mohd Arshad, M. K.; Ismail, J. R.; Ibrahim, Z. O.; Chua, N. Y. L.; Abdul Rahim, A. A.; Rusani, B. I.; Yap, L. B.; Zamrin, D. M.; Amir, M. A.; Ismail, N. I.; Mohammad Razi, A. A.; Prins, F.; Bendermacher, P.; Burg, M.; Lok, D.; van der Sluis, A.; Martens, F.; Badings, E.; Milhous, J.; van Rossum, P.; Viergever, E.; van Hessen, M.; Willems, F.; Tjon Joe Gin, R.; Swart, H.; Oomen, A.; Kromhout, S.; Lauwerijssen, I.; Daalmans, M.; Breedveld, R.; de Vries, K.; Feenema Aardema, M.; Hofma, S.; van der Borgh, R.; van Nes, E.; Göbel, E.; Oei, F.; Dorman, H.; Bos, R.; Zoet-Nugteren, S.; Emans, M.; Kragten, H.; Lenderink, T.; Feld, R.; Herrman, J.; van Bergen, P.; Gosselink, M.; Elvan, A.; Hoekstra, E.; The, S.; de Vries, R.; Zegers, E.; Oude Ophuis, T.; Remmen, J.; Bech, J.; Kooistra, J.; den Hartog, F.; Oosterhof, T.; Bartels, G.; Posma, J.; Nierop, P.; Liem, A.; van der Zwaan, C.; Asselman, M.; van Eck, J.; Gevers, R.; van Gorselen, E.; van Hal, J.; Terpstra, W.; Groenemeijer, B.; Jerzewski, A.; Hoogslag, P.; Geertman, J.; de Groot, M.; Dijkstra, B.; Loyola, A.; Sulit, D.; Mercado, M. J.; Rey, N.; Evangelista, L.; Abola, M.; Padua, L.; Morales, D.; Palomares, E.; Abat, M.; Santos, R.; Rogelio, G.; Chua, P.; Baello, R.; del Pilar, J.; Alianza, M.; Alcaraz, J.; Alcaraz, L.; Ebo, G.; Guido-Saliot, I.; Tirador, L.; Estoce, E.; Ygpuara, M.; Cruz, J.; Anonuevo, J.; Pitargue, A.; Janion, M.; Drewniak, Z.; Guzik, B.; Nowak, M.; Nosal, M.; Niewiara, Ł; Gajos, G.; Bury, K.; Czubek, U.; Misztal, M.; Grzybczak, R.; Zalewski, J.; Kruszelnicka-Kwiatkowska, O.; Żabówka, M.; Rynkiewicz, A.; Grzybowski, A.; Szałkowski, P.; Broncel, M.; Gorzelak, P.; Możdżan, M.; Olszewska Banaszczyk, M.; Szuba, A.; Tabin, M.; Chachaj, A.; Czarnecka, D.; Terlecki, M.; Klocek, M.; Maga, P.; Coman, I.; Tarlea, M.; Ghionea, M.; Gavrila, C.; Dimulescu, D.; Popescu, A.; Stoicescu, C.; Vintila, V.; Florescu, M.; Baghilovici Cretu, D.; Suran, M.; Mihalcea, D.; Lungeanu Juravle, L.; Cinteza, M.; Calin, I.; Bicescu, G.; Vasile Toma, N.; Udroiu, C.; Gherghinescu, C.; Darabont, R.; Patrascu, N.; Constantinescu, C.; Popescu, I.; Sinescu, C.; Andrei, C.; Axente, L.; Arsenescu, C.; Statescu, C.; Ardeleanu, I.; Anghel, L.; Benedek, I.; Benedek, T.; Kinga, P.; Banga, D. K.; Bobescu, E.; Doka, B.; Dobreanu, D.; Sirbu, V.; Rudzik, R.; Kantor, K.; Sus, I.; Gaita, D.; Maximov, D.; Brie, D.; Mosteoru, S.; Olariu, I.; Iancu, A.; Marc, M.; Hagiu, R.; Manole, V.; Molnar, A.; Dregoesc, I.; Iliesiu, A.; Armean, P.; Parvu, I.; Deleanu, A.; Lighezan, D.; Buzas, R.; Petrescu, L.; Nicola, R.; Dan, R.; Crisan, S.; Trasca, L.; Teodorescu, I.; Zara, O.; Tiron, T.; Tesloianu, D.; Spiridon, M.; Vintila, M.; Baluta, M.; Chioncel, O.; Stoica, E.; Kulcsar, I.; Antohi, L.; Strazhesko, I.; Tkacheva, O.; Sharashkina, N.; Pykhtina, V.; Vasyuk, Y.; Shkolnik, E.; Khadzegova, A.; Sadulaeva, I.; Ivanova, S.; Nesterova, E.; Nesvetov, V.; Shupenina, E.; Shcherbak, M.; Sizova, Z.; Beloborodova, A.; Pozdnyakov, Y.; Tarasov, A.; Shvedov, I.; Zabashta, S.; Ryzhikova, I.; Barbarash, O.; Pecherina, T.; Vatutin, M.; Inozemceva, A.; Kazachek, Y.; Mineeva, E.; Kupriyanova, T.; Voevoda, M.; Gafarov, V.; Gromova, E.; Panov, D.; Voevoda, E.; Kovalkova, N.; Ragino, Y.; Poponina, T.; Poponina, Y.; Garganeeva, N.; Repin, A.; Vershinina, E.; Borodina, E.; Kalashnikova, T.; Safyanova, O.; Osipova, I.; Antropova, O.; Pyrikova, N.; Polyakova, I.; Efremushkina, A.; Guryanova, N.; Kiseleva, E.; Lomteva, E.; Shtyrova, T.; Novikova, N.; Parfenov, D.; Volovchenko, A.; Averkov, O.; Pavlikova, E.; Vaulina, L.; Pletnikova, I.; Mishchenko, L.; Saranin, S.; Tsupko, I.; Kuznetsova, N.; Zateyshchikov, D.; Dankovtseva, E.; Vlazneva, Y.; Tolokonnikova, N.; Zhurina, M.; Zubova, E.; Aseycheva, O.; Sigalovich, E.; Vertkin, A.; Rodiukova, I.; Komissarov, S.; Sokolova, R.; Ausheva, A.; Salbieva, A.; Yusubova, A.; Isakova, S.; Hranai, M.; Obona, P.; Cisar, P.; Semetko, J.; Vanova, P.; Ferencikova, Z.; Vykoukalova, T.; Gaspar, L.; Caprnda, M.; Bendzala, M.; Pella, D.; Fedacko, J.; Hatalova, K.; Drozdakova, E.; Peter, O.; Ntsekhe, M.; de Andrade, M.; Seedat, S.; Gani, M.; van Zyl, L.; Naude, M.; Cronje, T.; van Zyl, F.; Engelbrecht, J.; Jansen, J.; Roos, J.; Makotoko, E.; Pretorius, C.; Mirna, S.; Nell, H.; Pretorius, M.; Basson, M.; Njovane, X.; Mohamed, Z.; Pillay, T.; Dawood, S.; Horak, A.; Lloyd, E.; Hitzeroth, J.; Mabin, T.; Abelson, M.; Klug, E.; Gebka, M.; Hellig, F.; Alison, M.; Bae, J.; Kim, C.; Kim, D.; Joo, S.; Park, C.; Kim, Y.; Jarnert, C.; Rydén, L.; Mooe, T.; Binsell-Gerdin, E.; Dellborg, M.; Torstensson, I.; Albertsson, P.; Hiller, M.; Perers, E.; Johansson, L.; Jansson, J. H.; Al-Khalili, F.; Almroth, H.; Andersson, T.; Eriksson Östman, M.; Pantev, E.; Utter, F.; Tengmark, B. O.; Olsson, Å; Liu, B.; Rasmanis, G.; Wahlgren, C. M.; Thott, O.; Moccetti, T.; Rossi, M. 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M.; Tremblay, H.; Bergeron, A.; Dumont, J.; Keilani, S.; Landry, P.; Deneufbourg, I.; Breton, C.; Bilodeau, N.; Côté, M.; Dumont, F.; Dufort, L.; Marcoux, D.; David, M.; Otis, R.; Parks, J.; Cepidoza, C.; Janz, W.; Weighell, W.; Yaworski, S.; Boyd, K.; Lambert, J.; Shea-Landry, G.; Reid, K.; Thiessen, S.; Nemtean, D.; Futers, S.; Drouin, K.; Masson, C.; Arseneault, M. C.; Lachance, N.; Bergeron, C.; Boudreault, C.; Perkins, L.; Barnett, A.; Fortin, J.; Duclos, R.; Vallières, C.; Bouchard-Pilote, C.; Ouimet, F.; Roberge, B.; Couture, M. L.; Deshaies, D.; Bastien, A.; Chartrand, M. J.; Gagné, N. L.; Desbiens, K.; Alarie, P.; Cassan, J.; Ducharme, Y.; Roy D Tapps, I.; Bolduc, H.; Laliberté, J.; Hickey, L.; Spero, M.; Bernstein, M.; Clement, J.; Pawluch, A.; Ricci-Bonzey, M.; Richer, J.; Vaillancourt, J.; Ward, B.; Mostafai Rad, P.; Oleski, L.; Karkhanis, R.; Hartleib, V.; Poirier, R.; Hidalgo, J.; Hernandez, C.; Obreque, C.; Quilapi, D.; Villa, F.; Iturriaga, C.; Ferrada, M.; Navarrete, S.; Becerra, E.; Vargas, C.; Roque, C.; Alarcon, J.; Diaz, D.; Sepulveda, M.; Villan, C.; Garcia, N.; Lara, C.; Lezana, B.; Basso, N.; Torres, G.; Pasmino, C.; Gonzalez, S.; Medina, D.; Rodriguez, T.; Guo, T.; Chen, S.; Han, W.; Shi, D.; Zhang, Q.; Li, W.; Cui, L.; Huang, Z.; Gong, X.; Liu, D.; Tan, S.; Caicedo, L.; Rodriguez, A.; Mejia, I.; Escalante Ruiz, J.; Camera Ochoa, C.; Conrrado Ortega, Y.; Accini Diaz, A.; Rodriguez, B.; Lopez-Lopez, J.; Di Stefano, K.; Florez, L.; Manco, T.; Rodriguez, D.; Urina, A.; de La Hoz, L.; Almendrales, L.; Bello, O.; Urrea Valencia, H.; Correa Rivera, P.; Perdomo, I.; Alzate, J.; Rivera, E.; Jimenez, N. 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L.; Savoldi, D.; Fiorini, M.; Ramani, F.; Mariottoni, B.; Rizzotti, D.; Di Matteo, C.; Musio, S.; Pieroni Minciaroli, S.; Serani, S.; Aloisi, A.; Attanasio, C.; Tricoli, M.; Giordano, V.; Andrioli, V.; Biundo, V.; Tullio, L.; Schiff, D.; Trovarelli, P.; Chiodi, R.; Sampaolesi, S.; Cina, M. T.; Abatello, M.; de Tora, M.; Pietrucci, F.; Pezzetta, S.; Chiminelli, E.; Dall’Asta, A.; Bennati, M.; Elia, A.; Bizzoco, M.; Iaquaniello, A.; Spigarelli, R.; Cremonesi, C.; Gagliardi, M.; Torricelli, L.; Ijichi, N.; Shiraiwa, K.; Murakami, M.; Takeshita, K.; Sato, M.; Shiratori, A.; Kinjo, K.; Tomita, K.; Mizuno, M.; Kurihara, F.; Tachibana, M.; Nitta, Y.; Unno, K.; Hiramatsu, H.; Sano, A.; Nanatsumura, M.; Tanikawa, I.; Uesugi, K.; Banno, S.; Miyata, T.; Kujuji, A.; Kawai, K.; Maegawa, A.; Koseki, T.; Watanabe, Y.; Aoki, S.; Maesawa, M.; Suzuki, A.; Itose, Y.; Konishi, K.; Fujieda, K.; Nakade, S.; Minami, M.; Yoneda, J.; Akiyama, R.; Sakai, S.; Nakatani, K.; Yamazaki, A.; Funama, M.; Kaneko, E.; Morii, S.; Onishi, M.; Sone, A.; Sagawa, N.; Iwai, F.; Kawahara, A.; Hasimoto, C.; Ueki, M.; Kamiji, M.; Ando, M.; Yokoo, M.; Okada, Y.; Yamada, H.; Matsushige, N.; Nagato, A.; Matsumoto, R.; Nishikawa, M.; Oka, I.; Kitou, S.; Tachiuchi, M.; Nakagawa, M.; Yoneda, S.; Iwasa, K.; Matsuda, J.; Oda, A.; Tokudome, S.; Kaneyuki, Y.; Higaki, M.; Yoneda, H.; Kajita, C.; Suwa, K.; Sato, E.; Nagata, T.; Kubo, Y.; Umesu, A.; Ohashi, K.; Takeuchi, M.; Tanaka, I.; Nobehara, T.; Yamano, R.; Yumiba, A.; Hamada, M.; Nishihata, T.; Ohashi, Y.; Morita, M.; Endo, M.; Matsugi, M.; Tateishi, H.; Nakamori, R.; Yamashita, Y.; Okabe, M.; Matsuo, M.; Ono, T.; Shigeyama, Y.; Ichiyanagi, M.; Sugimori, K.; Ohmura, C.; Igarashi, M.; Aotsuka, S.; Komoda, N.; Watanabe, M.; Enomoto, Y.; Suzuki, Y.; Kawaguchi, A.; Kasahara, A.; Koide, A.; Sakatani, T.; Kurihara, T.; Yokota, S.; Futagi, R.; Amemiya, Y.; Ono, E.; Maeda, A.; Kadono, K.; Ishiguchi, Y.; Kikuchi, R.; Kuramatsu, M.; Nakamura, E.; Chiba, S.; Higa, A.; Kitahashi, M.; Tanaka, H.; Ito, T.; Oba, M.; Tsubouchi, M.; Toshima, M.; Morishita, M.; Miyano, A.; Kondo, M.; Watanabe, K.; Shibata, R.; Tosaki, Y.; Ito, Y.; Saoda, M.; Yamasaki, E.; Kadosaki, S.; Motooka, S.; Akiyoshi, H.; Morio, S.; Nemoto, H.; Yoshizawa, S.; Okabe, N.; Semba, K.; Yoshida, A.; Lee, Y.; Yoshida, M.; Iwashita, Y.; Takeda, A.; Maezato, M.; Kawahira, K.; Yoshikawa, M.; Okamoto, N.; Nishimura, M.; Matsuura, K.; Fukunaga, M.; Fukai, K.; Osakabe, Y.; Yamamura, K.; Koike, M.; Shibuya, S.; Shiramata, M.; Ono, Y.; Tsujimoto, Y.; Tadokoro, T.; Morishita, N.; Matsuo, Y.; Yumoto, I.; Sakazaki, S.; Atarashi, A.; Nabata, Y.; Okuda, N.; Fujita, A.; Matsuo, A.; Ishizawa, Y.; Shibata, H.; Ootsuka, M.; Taimatsu, R.; Takeuchi, A.; Sumi, Y.; Yamamoto, F.; Araki, Y.; Tanaka, A.; Kuroda, S.; Sakata, R.; Okada, N.; Sawada, Y.; Miyata, M.; Asayama, H.; Koga, N.; Miki, T.; Yamaguchi, N.; Hashimoto, A.; Fukuike, C.; Kubo, A.; Yamasaki, M.; Mori, Y.; Nakayama, S.; Kobayashi, Y.; Takenaka, S.; Mashima, M.; Katsuta, H.; Matsumura, T.; Yanagida, S.; Watanabe, N.; Kodama, S.; Kusano, M.; Yamamoto, N.; Kamada, R.; Suzuki, K.; Itami, K.; Hasebe, Y.; Fujita, N.; Kubota, S.; Usuki, A.; Okamoto, M.; Uno, S.; Chikuma, A.; Kishikawa, H.; Yano K Nakano, C.; Otaguro, M.; Kayashima, Y.; Shinoda, M.; Jaafar, S. M.; Baharuddin, S.; Gembor, J.; Ahmad, H.; Syed Mansor, S. M.; Abdullah, W. M.; Shafie, Z.; Muhamad Yunus, S.; Alwi, S. M.; Hussin, N.; Basri, N. A.; Ling Ling, L.; Naem, N. S.; Rutten, R.; Rademaker, H.; van Buijsen, M.; Scholten, M.; Stuij, S.; van Zeijst, M.; van Houwelingen, K.; Engelen, W.; Kramer, H.; Maassen, E.; Verhoeven, P.; Awater, J.; Terwisscha van Scheltinga, C.; Meijlis, P.; Blom, L.; Bos, M.; van der Wal, M.; van Laerhoven, G.; Jacobs, T.; Tan-Urgert, B.; van de Gaag, J.; den Boer, P.; Verlek, E.; Lardinois, R.; Coenjaerds, C.; Hendrick, R.; Schoep, J.; Froma, E.; van Nes, C.; Beuving, D.; Krikken, J.; Drent, I.; Geerlings, F.; Buvelot, S.; Wissenburg, A.; Dijkshoorn, A.; van Setten van der Meer, L.; Singerling, M.; van Wijk, D.; Bor, A.; Aukema-Wouda, Z.; Hendriks-van Woerden, M.; Kort, I.; Danse, I.; van der Knaap, M.; de Jong, C.; Temminck, M.; Schaefer, T.; van der Ven, N.; Drost, I.; Mulder, R.; de Vos, A.; de Hoop, M.; Post, G.; Wielandt, D.; Edorot, N.; de Castro, K.; Flotildes, M.; Mulingtapang, T.; Vasquez, S.; Facundo, S.; Peralta, M.; Jose, M.; Bandiez, J.; Sulit, P.; Joaquin, F.; Arbis, M. G.; Silva, C.; Delgado, D.; de Leon, R.; Maglasang, P.; Sian, A.; Alagban, C.; Alcorano, J.; Marcelo, M. J.; Dela Pena, C.; Hyra, I.; Malkiewicz, B.; Mosakowska, K.; Cana, I.; Dobrin, I.; Lautaru, A.; Manescu, G.; Samoila, N.; Lacatus, M.; Apostoie, A.; Prunoiu, M.; Tilinca, M.; Budeanu, A.; Nedelcu, C.; Dumitrache, N.; Boeru, L.; Zhuravleva, E.; Gundova, M.; Hoffmannova, J.; Svitkova, M.; Pekarova, T.; Ujacka, K.; Zsoriova, T.; Kubincova, K.; Jankovicova, Z.; Talliard, C.; Tyumbu, N.; Mngoma, N.; Kannemeyer, M.; Mostert, J.; Page, A.; Krahenbuhl, C.; Tredoux, C.; Hendricks, L.; Oliver, S.; Le Grange, M.; Naidoo, V.; Bae, Y.; Kim, H.; Lee, J.; Yu, N.; An, S.; Kim, E.; Yang, K.; Woo, J.; Kim, S.; Rasck, J.; Smetana, S.; Ajax, K.; Bylander, L.; Lindberg, A.; Dellborg, H.; Hultsberg-Olsson, G.; Harsmar, K.; Knutsson, A.; Håkansson, L.; Kåveryd-Holmström, M.; Lundmark, L. M.; Norrfors, B.; Löf, P.; Skoglund, K.; Torgersruud, M.; Johansson, K.; Mattsson, A.; Quist, M.; Haglund, P.; Lundell, L.; Gunvasdotter, S.; Rangman, B.; Liu, R.; Shi, J.; Förstedt, G.; Nylund, L.; Welin-Berger, B.; Nilsson, O.; Garcia-Värlid, A.; Forlenza, R.; Kaminska, K.; Nagorna, T.; Cottam, V.; Harper, R.; Gilchrist, M.; Musanhu, R.; Mackin, A.; Turner, A.; Willetts, S.; Cadd, A.; Evans, J.; Young, G.; Sevillano, A.; Brodie, K.; Eccles, A.; Kelly, S.; Doughty, A.; Gray, J.; Gibson, M.; Finlayson, M.; Domingo, D.; Brazee, L.; Renaud, K.; Doman, A.; Meyer, R.; Beatty, J.; Morgan, T.; Rodas, E.; Campbell, D.; Mcquarrie, M.; Battistelli, E.; Eisenbraun, P.; Farley, R.; Park, H.; Dwyer, J.; Adams, K.; Schneider, W.; Barbour, C.; Whyne, E.; Budzinski, S.; Craig, M.; Gilley Elmore, J.; Scott, D.; Bellini, S.; Pepper, M.; Gunderson, K.; Stipek, I.; Schwarz, L.; Watkins, K.; Moore, V.; Palao, A.; Keane-Richmond, P.; Franklin, L.; Ward, L.; Kostedt, G.; Bailey, S.; Hollenweger, L.; Solomon, A.; Johnson, D.; Gloer, K.; Meyer, M.; Boleyn, M.; Nieters, D.; Humphrey, K.; Bohn, A.; Mueller, G.; Mckenzie, H.; Edwards, T.; Velky, J.; Cole, C.; Diederick, M.; Burg, S.; Coulson, T.; Karunaratne, K.; Gunasekera, R.; Cook, S.; Fisher, S.; Garrison, K.; Passey, L.; Kuykendall, K.; Luck, K.; Ramia, L.; Joan, H.; Reynoso, F.; Farley, M.; Shuman, S.; Santana-Fernandes, E.; Ventimiglia, A.; Steele, V.; Gers, L.; Brown, P.; Wilson, J.; Freebersyser, J.; Reno, M.; Buettner, N.; McGovern, M.; Hubbard, T.; Elmore, H.; Payne, D.; Mccann, M.; Decker, S.; Sharp, A.; Forgey, E.; Broussard, E.; Juett, U.; Siddiqui, A.

    2017-01-01

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

    Dr J. T. Ekanem

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

  2. 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

  3. Aspirin and lipid mediators in the cardiovascular system.

    Science.gov (United States)

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

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

  4. 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…

  5. Aspirin-Exacerbated Respiratory Disease: Evaluation and Management

    Science.gov (United States)

    2011-01-01

    maintained and stable on antihistamines , topical steroids, leu- kotriene modifiers and immunotherapy. Sometimes omali- zumab needs to be added to...that patients discontinue their antihistamines , decongestants and short-acting inhaled beta- agonists prior to aspirin challenge. These medications...10 mg daily – Oral corticosteroids if necessary – Stop antihistamines and decongestants 48hr prior to aspirin challenge – Stop short acting

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

    International Nuclear Information System (INIS)

    Mackey, W.C.; Connolly, R.J.; Callow, A.D.

    1984-01-01

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

  7. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

    Tang, Yu; Singh, Jagdish

    2008-06-05

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

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

    Science.gov (United States)

    Hademenos, George

    2005-01-01

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

  11. Aspirin for Primary Prevention of Cardiovascular Events: Meta-Analysis of Randomized Controlled Trials and Subgroup Analysis by Sex and Diabetes Status

    Science.gov (United States)

    Zhang, Yan; Chen, Sijing; Yang, Wei; Bao, Wei; Rong, Ying; Yu, Xuefeng; Hu, Frank B.; Liu, Liegang

    2014-01-01

    Objective 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. Methods 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. Results 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). Conclusions 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

  12. Prevalence of Aspirin Resistance in Diabetic Patients and its Associated Factors

    OpenAIRE

    HABIZAL, Nor Halwani; ABDUL HALIM, Sanihah; BHASKAR, Shalini; WAN BEBAKAR, Wan Mohamed; ABDULLAH, Jafri Malin

    2015-01-01

    Background: Aspirin resistance has posed a major dilemma in the prevention of cardiovascular disease and stroke. There have been many factors that have been associated with aspirin resistance. Among these factors, the inflammatory processes of diabetes and glycaemic control have been significantly associated with aspirin resistance. Our study evaluated the prevalence of aspirin resistance and its associated factors.

  13. Aspirin and the prevention of colorectal cancer.

    Science.gov (United States)

    Ferrández, Angel; Piazuelo, Elena; Castells, Antoni

    2012-04-01

    A large body of evidence from basic science, epidemiologic observations and population-based studies demonstrates that aspirin, as well as other non-steroidal anti-inflammatory drugs, has a chemopreventive effect on several cancer types and, more specifically, in CRC. This protective effect includes prevention of adenoma recurrence and reduction of CRC incidence and mortality. Although the protective effect appears to depend on the dose and the drug, the most important factor is the duration of exposure. However, the lowest effective dose, treatment duration, specific target populations, and effects on survival have not been defined yet. More important, data on the risk-benefit profile for cancer prevention are insufficient and, accordingly, no definitive recommendation can be made at present. In this article, besides reviewing current knowledge of the mechanisms involved in aspirin-based CRC chemoprevention, we will be focused on randomized controlled studies assessing its efficacy in high-, moderate- and average-risk populations. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-03-01

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

  15. Different impact of aspirin on renal progression in patients with predialysis advanced chronic kidney disease with or without previous stroke.

    Science.gov (United States)

    Hsiao, Kuang-Chih; Huang, Jing-Yang; Lee, Chun-Te; Hung, Tung-Wei; Liaw, Yung-Po; Chang, Horng-Rong

    2017-04-01

    The benefit of reducing the risk of stroke against increasing the risk of renal progression associated with antiplatelet therapy in patients with advanced chronic kidney disease (CKD) is controversial. We enrolled 1301 adult patients with advanced CKD treated with erythropoiesis stimulating agents from January 1, 2002 to June 30, 2009 from the 2005 Longitudinal Health Insurance Database in Taiwan. All of the patients were followed until the development of the primary or secondary endpoints, or the end of the study (December 31, 2011). The primary endpoint was the development of ischemic stroke, and the secondary endpoints included hospitalization for bleeding events, cardiovascular mortality, all-cause mortality, and renal failure. The adjusted cumulative probability of events was calculated using multivariate Cox proportional regression analysis. Adjusted survival curves showed that the usage of aspirin was not associated with ischemic stroke, hospitalization for bleeding events, cardiovascular mortality or all-cause mortality, however, it was significantly associated with renal failure. In subgroup analysis, aspirin use was associated with renal failure in the patients with no history of stroke (HR, 1.41; 95% CI, 1.14-1.73), and there was a borderline interaction between previous stroke and the use of aspirin on renal failure (interaction p=0.0565). There was no significant benefit in preventing ischemic stroke in the patients with advanced CKD who received aspirin therapy. Furthermore, the use of aspirin was associated with the risk of renal failure in the patients with advanced CKD without previous stroke. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  16. Variation and importance of aspirin resistance in patients with known cardiovascular disease

    DEFF Research Database (Denmark)

    Poulsen, Tina Svenstrup; Kristensen, Søren Risom; Korsholm, Lars

    2007-01-01

    AIM: To investigate whether aspirin resistance is a persistent condition, and to evaluate if aspirin resistance affects one-year clinical outcome. METHODS AND RESULTS: Previously we studied 298 patients admitted to hospital with symptoms suggestive of an acute myocardial infarction (MI) despite...... treatment with aspirin, and 70 patients (23.5%) were aspirin resistant. In the present study, platelet function was reassessed by use of a Platelet Function Analyzer-100 one year later. A total of 187 patients were re-examined, and 17 (9.1%) demonstrated aspirin resistance. Of these 17 patients, 12 also...... exhibited aspirin resistance at baseline resulting in a 6% (12/187) prevalence of persistent aspirin resistance. A total of 34 patients had changed from aspirin resistant at baseline to aspirin sensitive at follow-up. We found a significant decrease in the prevalence of aspirin resistance from baseline (43...

  17. Enhancement of aspirin capsulation by porous particles including iron hydrous oxide

    International Nuclear Information System (INIS)

    Saito, Kenji; Koishi, Masumi; Hosoi, Fumio; Makuuchi, Keizo.

    1986-01-01

    Polymer-coated porous particles containing aspirin as a drug were prepared and the release of rate of aspirin was studied. The impregnation of aspirin was carried out by post-graft polymerization, where methyl methacrylate containing aspirin was treated with porous particles including iron oxide, pre-irradiated with γ-ray form Co-60. Release of aspirin from modified particles was examined with 50 % methanol solution. The amount of aspirin absorbed in porous particles increased by grafting of methyl methacrylate. The particles treated with iron hydrous oxide sols before irradiation led to the increment of aspirin absorption. Diffusion of aspirin through the polymer matrix and the gelled layer was the limiting process in the aspirin release from particles. The rate of aspirin released from modified particles including iron hydrous oxide wasn't affected by the grafting of methyl methacrylate. (author)

  18. Prevention of cardiovascular complications of diabetes mellitus by aspirin.

    Science.gov (United States)

    Nobles-James, Candi; James, Erskine A; Sowers, James R

    2004-01-01

    Eighteen million Americans have type 2 Diabetes Mellitus (DM) while another 40 million have impaired glucose tolerance. Atherosclerotic heart disease is the leading cause of death in patients with diabetes mellitus. In addition to the increased risk for CardioVascular Disease (CVD), patients with diabetes have a worse prognosis than nondiabetics when they suffer an ischemic event. Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Hyperinsulinemia has been proposed as the forerunner of hypertension, low high-density lipoprotein cholesterolemia, hypertriglyceridemia, abdominal obesity, and altered glucose tolerance, linking all these abnormalities to the development of coronary vascular disease. Atherosclerosis and insulin resistance share similar pathophysiological mechanisms, due to the actions of proinflammatory cytokines. The dynamic inflammatory milieu found in diabetes explains the susceptibility of diabetics to CVD and the potential mechanism by which aspirin may prevent CVD in diabetics. Aspirin decreases the risk for CVD in diabetic patients by a variety of established and novel mechanisms. Therapeutic strategies that lesson the CVD risk in diabetic patients, including the use of aspirin for primary and secondary prevention, are potentially very important. This review article addresses the antiatherosclerotic effects of aspirin, the potential anti-diabetic effects of aspirin, and the clinical trial evidence for CVD prevention by aspirin in diabetics. We also present recommendations for the use of aspirin in the diabetic population and the current guidelines put forth by the American Heart Association and by the American Diabetes Association.

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

    OpenAIRE

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

    2017-01-01

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

  20. Aspirin and clonidine in non-cardiac surgery

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  2. Review of aspirin and clopidogrel resistance in peripheral arterial disease.

    Science.gov (United States)

    Guirgis, Mina; Thompson, Peter; Jansen, Shirley

    2017-11-01

    Aspirin resistance (AR) and clopidogrel resistance (CR) are terms used to describe a reduction in the medication's efficacy in inhibiting platelet aggregation despite regular dosing. This review gives context to the clinical role and implications of antiplatelet resistance in peripheral arterial disease (PAD). A review of English-language literature on AR and CR in PAD involving human subjects using PubMed and MEDLINE databases was performed in April 2017. A total of 2075 patients in 22 relevant studies were identified. To give this issue context, a review of the larger, more established literature on antiplatelet resistance in coronary disease was undertaken, identifying significant research associating resistance to major adverse cardiovascular events (MACEs). Studies in the coronary arterial disease literature have strongly associated antiplatelet resistance with increased MACE. Prevalence of AR or CR in coronary disease appears to be >55% for each in some studies. Meta-analyses of >50 studies revealed that AR and CR are significantly associated with MACE (relative risk of 2.09 and 2.8, respectively). This adds further weight to the literature reporting antiplatelet resistance as an independent predictor of and a threefold risk factor for major adverse cardiovascular events. The prevalence of resistance in PAD in this review was comparable to that in the coronary disease literature, with AR and CR prevalence up to 60% and 65%, respectively. There is evidence that the adverse effects of antiplatelet resistance are significant in PAD. In fact, research directly studying stent thrombosis populations with either coronary arterial disease or PAD revealed more significantly impaired platelet responsiveness to clopidogrel and aspirin in PAD compared with similar individuals with coronary disease. AR in PAD was found in studies to be a significant risk factor for iliofemoral stent reocclusion (P = .0093) and stroke in patients with symptomatic carotid disease (P

  3. Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a systematic review

    DEFF Research Database (Denmark)

    Teo, Koon K; Yusuf, Salim; Pfeffer, Marc

    2002-01-01

    -Yusuf method to undertake a systematic overview of data for 22060 patients from six long-term randomised trials of ACE inhibitors to assess whether aspirin altered the effects of ACE inhibitor therapy on major clinical outcomes (composite of death, myocardial infarction, stroke, hospital admission......BACKGROUND: Results from a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) study suggest that angiotensin-converting-enzyme (ACE) inhibitors may be less effective in patients receiving aspirin. We aimed to confirm or refute this theory. METHODS: We used the Peto...

  4. 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.

  5. Aspirin resistance: Prevalence and clinical outcome in Egypt

    Directory of Open Access Journals (Sweden)

    Ahmed Salah

    2015-04-01

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

  6. The Role of Platelet and its Interaction with Aspirin

    Directory of Open Access Journals (Sweden)

    Luisa Fernanda Zúñiga Cerón

    2016-04-01

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

  7. 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...

  8. An Efficient Microscale Procedure for the Synthesis of Aspirin

    Science.gov (United States)

    Pandita, Sangeeta; Goyal, Samta

    1998-06-01

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

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

    OpenAIRE

    Chin, Kok-Yong

    2017-01-01

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

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

    OpenAIRE

    Pignone, Michael; Williams, Craig D.

    2010-01-01

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

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

    African Journals Online (AJOL)

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

  12. Trace element impurity determination in aspirin tablets by INAA

    International Nuclear Information System (INIS)

    Miyoshi, E.K.; Saiki, M.

    2009-01-01

    Instrumental neutron activation analysis (INAA) was applied to assess trace element concentrations in six samples of aspirin tablets acquired in Sao Paulo city, Brazil. Concentrations of the elements Br, Ca, Co, Cr, Fe, K, La, Na, Sc and Zn were determined. Comparisons were made between the results obtained with published data for aspirins from foreign countries. Certified reference materials, INCT-MPH-2 Mixed Polish Herbs were analyzed for quality control of the analytical results. (author)

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

    Science.gov (United States)

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

    2015-08-27

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

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

    Science.gov (United States)

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

    2013-01-01

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

  15. Can We Select Patients for Colorectal Cancer Prevention with Aspirin?

    Science.gov (United States)

    Kraus, Sarah; Sion, Daniel; Arber, Nadir

    2015-01-01

    Aspirin has been extensively investigated in the context of the prevention of cardiovascular disease. It has one of the strongest cumulative evidence supporting its use in colorectal cancer (CRC) chemoprevention. Epidemiological, clinical, and observational studies have demonstrated that aspirin and non-steroidal antiinflammatory drugs (NSAIDs), including COX-2 inhibitors, can protect against CRC and significantly reduce its incidence. Moreover, prospective randomized controlled trials of colorectal polyp recurrence and in patients with hereditary CRC syndromes have shown that aspirin can produce regression of existing colorectal adenomas and prevent the formation of new polyps. However, the lowest effective doses, treatment duration, target populations, and the effects on survival are not entirely clear. Although not common serious side effects and in particular gastrointestinal and intracerebral hemorrhage do occur, better selection of individuals who might benefit the most from aspirin use must be carefully performed in order to maximize their risk/benefit ratio. In the era of precision medicine, genetic information, blood and/or urinary biomarkers, could potentially help in tailoring chemopreventive therapeutic strategies, based on aspirin use, while limiting adverse toxic effects. The current review will cover the use of aspirin for the prevention of colorectal adenomas and CRC, potential markers for chemoprevention, and patient stratification.

  16. TRIAL OF ASPIRIN AND CALCIUM ON PREVENTION OF PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    ALI AKBA TAHERIAN

    2002-06-01

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

  17. Antithrombotic and Thrombolytic Therapy for Ischemic Stroke

    Science.gov (United States)

    Lansberg, Maarten G.; O’Donnell, Martin J.; Khatri, Pooja; Lang, Eddy S.; Nguyen-Huynh, Mai N.; Schwartz, Neil E.; Sonnenberg, Frank A.; Schulman, Sam; Vandvik, Per Olav; Spencer, Frederick A.; Alonso-Coello, Pablo; Guyatt, Gordon H.

    2012-01-01

    Objectives: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA). Methods: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence. Results: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B). Conclusions: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. PMID:22315273

  18. 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 ...

  19. 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...

  20. Contemporary management of chronic rhinosinusitis with nasal polyposis in aspirin exacerbated respiratory disease: an evidence-based review with recommendations

    Science.gov (United States)

    Levy, Joshua M.; Rudmik, Luke; Peters, Anju T.; Wise, Sarah K.; Rotenberg, Brian W.; Smith, Timothy L.

    2016-01-01

    Background Chronic rhinosinusitis (CRS) in aspirin exacerbated respiratory disease (AERD) represents a recalcitrant form of sinonasal inflammation for which a multidisciplinary consensus on patient management has not been reached. Several medical interventions have been investigated, but a formal comprehensive evaluation of the evidence has never been performed. The purpose of this article is to provide an evidence-based approach for the multidisciplinary management of CRS in AERD. Methods A systematic review of the literature was performed and the guidelines for development of an evidence-based review with recommendations were followed. Study inclusion criteria included: adult population>18 years old; CRS based on published diagnostic criteria and a presumptive diagnosis of AERD. We focused on reporting higher-quality studies (level 2 or higher) when available, but reported lower-quality studies if the topic contained insufficient evidence. Treatment recommendations were based on American Academy of Otolaryngology guidelines, with defined grades of evidence and evaluation of research quality and risk/benefits associated with each treatment. Results This review identified and evaluated the literature on 3 treatment strategies for CRS in AERD: dietary salicylate avoidance, leukotriene modification and desensitization with daily aspirin therapy. Conclusion Based on the available evidence, dietary salicylate avoidance and leukotriene modifying drugs are options following appropriate treatment with nasal corticosteroids and saline irrigation. Desensitization with daily aspirin therapy is recommended following revision ESS. PMID:27480830

  1. Aspirin Intolerance: Experimental Models for Bed-to-Bench

    Science.gov (United States)

    Yamashita, Masamichi

    2016-01-01

    Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents leads to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms. As the bed-to-bench approach, to confirm the clinical discussion in experimental cellular models, we have tried to develop a cellular model of AERD using activated RBL-2H3 cells, a rat mast cell like cell line. Indomethacin (another NSAID and also causes AERD), enhances in vitro cysLTs production by RBL-2H3 cells, while there is no induction of cysLTs production in the absence of inflammatory activation. Since this suggests that all inflammatory cells with activation of prostaglandin and cysLT metabolism should respond to NSAIDs, and then I have concluded that aspirin intolerance should be separated from subsequent bronchoconstriction. Evidence about the cellular mechanisms of NSAIDs may be employed for development of in vitro AERD models as the approach from bench-to-bed. PMID:27719658

  2. Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice.

    Science.gov (United States)

    Zhu, Kun; Hu, Ming; Yuan, Bo; Liu, Jian-Xin; Liu, Yong

    2017-08-01

    Neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy, and could be implicated in the neuronal hyperexcitability. Aspirin represents one of the non-selective nonsteroidal anti-inflammatory drugs with fewer side effects in long-term application. This study was carried out to assess the anti-epileptic effects of aspirin when administered during the chronic stage of temporal lobe epilepsy [TLE] in mice. The alteration of hippocampal neurogenesis was also examined for raising a possible mechanism underlying the protective effect of anti-inflammatory treatment in the TLE. Two months after pilocarpine-induced status epilepticus, the chronically epileptic mice were treated with aspirin (20 mg, 60 mg or 80 mg/kg) once a day for 10 weeks. Spontaneous recurrent seizures were monitored by video camera for 2 weeks. To evaluate the profile of hippocampal neurogenesis, the newly generated cells in the dentate gyrus were labeled by the proliferation marker BrdU. The newborn neurons that extended axons to CA3 area were visualized by cholera toxin B subunit retrograde tracing. Administration of aspirin with a dosage of 60 mg or 80 mg/kg initiated at 2 months after pilocarpine-induced status epilepticus significantly reduced the frequency and duration of spontaneous recurrent seizures. Aspirin treatment also increased the number of newborn neurons with anatomic integration through improving the survival of the newly generated cells. Aspirin treatment during the chronic stage of TLE could attenuate the spontaneous recurrent seizures in mice. Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to this anti-epileptic effect. Highlights • Aspirin attenuates spontaneous recurrent seizures of chronically epileptic mice • Aspirin increases neurogenesis of chronically epileptic hippocampus by improving the survival of newly generated cells • Promotion of hippocampal neurogenesis and inhibition

  3. NIH Study Finds Regular Aspirin Use May Reduce Ovarian Cancer Risk

    Science.gov (United States)

    ... daily aspirin use include upper gastrointestinal bleeding and hemorrhagic stroke. Therefore, a daily aspirin regimen should only be ... translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. ...

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    International Nuclear Information System (INIS)

    Gao Lin; Sun Jihong; Li Yuzhen

    2011-01-01

    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 f t =kt n 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. - Graphical abstract: Loading (A) and release profiles (B) of aspirin in N-BMMs and N-MCM-41 indicated that BMMs have more drug loading capacity and faster release rate than that MCM-41. Highlights: → Bimodal mesoporous silicas (BMMs) and MCM-41 modified with amino group via post-treatment procedure. → Loading and release profiles of aspirin in modified BMMs and MCM-41. → Modified BMMs have more drug loading capacity and faster release rate than that modified MCM-41.

  6. Salicylate Food Intolerance and Aspirin Hypersensitivity in Nasal Polyposis.

    Science.gov (United States)

    Esmaeilzedeh, Hossein; Esmaeilzadeh, Elmira; Faramarzi, Mohammad; Nabavi, Mohammad; Farhadi, Mohammad

    2017-03-01

    A clear association between allergy and nasal polyposis (NP) is not determined and the role of food intolerance in patients with NP is not investigated by oral food challenge (OFC). To investigate the relation of salicylate food intolerance and atopy in patients with NP according to recurrence and aspirin sensitivity. A cross sectional multicenter study was done in two tertiary centers for allergy in Iran. Adult patients with NP were selected for the study that had been referred to allergy clinics. The oral aspirin challenge (OAC) test was performed to identify aspirin exacerbated respiratory disease (AERD) and the OFC test was used to investigate food intolerance. Atopic evaluation was performed by skin-prick tests, nasal smear and blood eosinophil count as well as serum total IgE. One hundred and nineteen Iranian patients (female to male ratio 1.05) with NP were enrolled (mean age, 38 ± 11 years). Recurrence of nasal polyposis was 64.7%. OAC was performed in all cases; 43.79% cases had aspirin hypersensitivity. In addition, OFC tests determined that 69.9% of patients had salicylate food allergy. Salicylate food intolerance was significantly higher in NP cases with AERD than in aspirin tolerant patients (pfood intolerance was associated with AERD in nasal polyposis.

  7. 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.

  8. Practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation

    DEFF Research Database (Denmark)

    Barbui, Tiziano; Barosi, Giovanni; Gugliotta, Luigi

    2004-01-01

    to their internal validity and quality. Using the Delphi technique, the EP was asked to answer the key questions according to the available evidence. From September 2002 to March 2003, four Consensus Conferences were held in accordance with the Nominal Group Technique with the goal of solving residual disagreement...... on recommendations. RESULTS: The EP provided recommendations on when to start platelet-lowering therapy, the most appropriate platelet-lowering agent, the use of anti-platelet therapy, and the management of women in childbearing age and of pregnant women. INTERPRETATION AND CONCLUSIONS: By using evidence...

  9. The Effect of Xuefuzhuyu Oral Liquid on Aspirin Resistance and Its Association with rs5911, rs5787, and rs3842788 Gene Polymorphisms

    Directory of Open Access Journals (Sweden)

    Mei Xue

    2015-01-01

    Full Text Available Aspirin should be continued indefinitely in patients after interventional therapy, but 10% to 40% of patients experience recurrent vascular events despite adequate aspirin therapy, a condition known as aspirin resistance (AR. Xuefuzhuyu oral liquid, derived from the classic recipe Xuefuzhuyu decoction, has been well documented to inhibit platelet aggregation and to improve hemorheology. The aims of this study were to investigate the effects of Xuefuzhuyu oral liquid on AR in patients with chronic stable angina after percutaneous coronary intervention (PCI and the possible genetic markers related to the drug response. 43 patients diagnosed as having aspirin resistance or semi-resistance were randomly divided into control and treatment groups after screening 207 stable CHD patients. Platelet aggregation rate was determined using turbidimetry. Three single nucleotide polymorphisms in COX-1 (rs5787, rs3842788 and GP IIb (rs5911 were genotyped in whole blood samples using ABI PRISM 7900 HT Fast Real-Time instrument and ABI PRISM 3730 DNA Sequencer. The results showed that Xuefuzhuyu oral liquid could effectively improve blood stasis syndrome and AR by inhibiting ADP-induced platelet aggregation and that patients with the rs5911 genetic variant exhibited better drug response upon treatment with Xuefuzhuyu oral liquid, which suggests Xuefuzhuyu oral liquid as a new possible drug for the prevention of AR.

  10. Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism. Rationale for and design of the EINSTEIN CHOICE study.

    Science.gov (United States)

    Weitz, Jeffrey I; Bauersachs, Rupert; Beyer-Westendorf, Jan; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Davidson, Bruce L; Holberg, Gerlind; Kakkar, Ajay; Lensing, Anthonie W A; Prins, Martin; Haskell, Lloyd; van Bellen, Bonno; Verhamme, Peter; Wells, Philip S; Prandoni, Paolo

    2015-08-31

    Patients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6-12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).

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

    Science.gov (United States)

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

    2016-07-01

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

  12. 75 FR 61503 - Determination That AZDONE (Hydrocodone Bitartrate and Aspirin) Tablet, 5 Milligrams/500...

    Science.gov (United States)

    2010-10-05

    ...] Determination That AZDONE (Hydrocodone Bitartrate and Aspirin) Tablet, 5 Milligrams/500 Milligrams, Was Not... bitartrate and aspirin) Tablet, 5 milligrams (mg)/ 500 mg, was not withdrawn from sale for reasons of safety... (ANDAs) for hydrocodone bitartrate and aspirin tablet, 5 mg/500 mg, if all other legal and regulatory...

  13. 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

  14. A computational prospect to aspirin side effects: aspirin and COX-1 interaction analysis based on non-synonymous SNPs.

    Science.gov (United States)

    Marjan, Mojtabavi Naeini; Hamzeh, Mesrian Tanha; Rahman, Emamzadeh; Sadeq, Vallian

    2014-08-01

    Aspirin (ASA) is a commonly used nonsteroidal anti-inflammatory drug (NSAID), which exerts its therapeutic effects through inhibition of cyclooxygenase (COX) isoform 2 (COX-2), while the inhibition of COX-1 by ASA leads to apparent side effects. In the present study, the relationship between COX-1 non-synonymous single nucleotide polymorphisms (nsSNPs) and aspirin related side effects was investigated. The functional impacts of 37 nsSNPs on aspirin inhibition potency of COX-1 with COX-1/aspirin molecular docking were computationally analyzed, and each SNP was scored based on DOCK Amber score. The data predicted that 22 nsSNPs could reduce COX-1 inhibition, while 15 nsSNPs showed increasing inhibition level in comparison to the regular COX-1 protein. In order to perform a comparing state, the Amber scores for two Arg119 mutants (R119A and R119Q) were also calculated. Moreover, among nsSNP variants, rs117122585 represented the closest Amber score to R119A mutant. A separate docking computation validated the score and represented a new binding position for ASA that acetyl group was located within the distance of 3.86Å from Ser529 OH group. This could predict an associated loss of activity of ASA through this nsSNP variant. Our data represent a computational sub-population pattern for aspirin COX-1 related side effects, and provide basis for further research on COX-1/ASA interaction. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Malik, M.I.

    2013-01-01

    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)

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

    DEFF Research Database (Denmark)

    Gaist, D; 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...

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

    Science.gov (United States)

    Laidlaw, Tanya M; Cahill, Katherine N

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

  18. 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.

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

    Science.gov (United States)

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

    2015-02-01

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

  20. Regular use of aspirin and pancreatic cancer risk

    Directory of Open Access Journals (Sweden)

    Mahoney Martin C

    2002-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Cristina Pellegrino Baena

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

  2. Efficacy and safety of apixaban compared with aspirin in patients who previously tried but failed treatment with vitamin K antagonists: results from the AVERROES trial.

    Science.gov (United States)

    Coppens, Michiel; Synhorst, David; Eikelboom, John W; Yusuf, Salim; Shestakovska, Olga; Connolly, Stuart J

    2014-07-21

    The AVERROES double-blinded, randomized trial demonstrated that apixaban reduces the risk of stroke or systemic embolism (SSE) by 55% compared with aspirin without an increase in major bleeding in patients with atrial fibrillation either who previously tried but failed vitamin K antagonists (VKA) therapy or who were expected to be unsuitable for VKA therapy. In this pre-specified analysis, we explored the consistency of the results in the subgroup of patients who tried but failed VKA therapy. Of 5599 patients, 2216 (40%) had previously failed VKA treatment [main reasons: poor international normalized ratio (INR) control 42%, refusal 37%, bleeding on VKA 8%]. Compared with those expected to be unsuitable for VKA therapy, those who had previously failed were older, more often male, had higher body mass index, more likely to have moderate renal impairment and a history of stroke and less likely to have heart failure or to be medically undertreated. The effects of apixaban compared with aspirin were consistent in those who previously failed and those who were expected to be unsuitable, for both SSE (P interaction 0.13) and major bleeding (P interaction 0.74) and were also consistent among different subgroups of patients who had previously failed VKA therapy defined by reasons for unsuitability, age, sex, renal function, CHADS2 score, aspirin dose, duration, indication, and quality of INR control of prior VKA use. The efficacy and safety of apixaban compared with aspirin is consistent in subgroups of patients who have previously attempted but failed VKA therapy, irrespective of the reason for discontinuation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

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

    Science.gov (United States)

    Desborough, Michael J R; Keeling, David M

    2017-06-01

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

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

    Science.gov (United States)

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

    2017-12-06

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

  5. Thrombotic Management of Antiphospholipid Syndrome: Towards Novel Targeted Therapies.

    Science.gov (United States)

    Islam, Md Asiful; Alam, Fahmida; Wong, Kah Keng; Kamal, Mohammad Amjad; Gan, Siew Hua

    2017-01-01

    Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity with persistent levels of antiphospholipid antibodies (aPLs). The development of thrombosis in APS is mediated by aPLs and contributes to the high mortality rate in APS patients. However, although APS has been reported for more than 30 years, there has been no optimal regimen for its prevention or for the management of thrombosis, mainly because the mainstay treatment strategies for managing APS are not targeted towards aPL-mediated thrombotic pathophysiology. Instead, the treatments commonly used are aimed at general thrombotic disorders. Warfarin is the most commonly used vitamin K antagonist (VKA), in addition to anti-platelet medications, such as aspirin and clopidogrel. Over the last decade, novel non-VKA oral anticoagulants, including rivaroxaban, apixaban and dabigatran, as well as immunomodulatory agents, such as rituximab, eculizumab, hydroxychloroquine, statins and sirolimus, have also been used. In this review, we discuss the current treatment strategies and future treatment outlook for thrombotic APS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Evaluation of the uses of aspirin, statins and ACEIs/ARBs in a diabetes outpatient population in southern Thailand.

    Science.gov (United States)

    Pongwecharak, J; Maila-ead, C; Sakulthap, J; Sripanitkulchai, N

    2007-04-01

    To evaluate the uses of aspirin, statins and angiotensin converting enzymes inhibitors/angiotensin receptor blockers (ACEIs/ARBs) in a diabetes population in southern Thailand. A review of outpatient medical records at the diabetic clinics of the regional hospital (n=304) and a community hospital (n=313), and a review of pharmacy computerized diabetes prescribing data (n=398) of the teaching hospital. All were in the province of Songkhla, southern Thailand. A total of 1015 diabetes patients, mean age (SD) 60.1 (12.1) years, were identified, with type 2 diabetes being most prevalent (93%). Females constituted 69%. Hypertension was a co-morbidity in almost half. Mean time (SD) since diagnosis was 5.8 (4.7) years. Where lipid profiles were available, less than one-third achieved the target LDL-C of <2.6 mmol L(-1). Almost all patients (96%) were candidates for treatment with a statin according to the American Diabetes Association (ADA) recommendation, whereas only 6.6 and 38.5% were actually taking one in the regional and the teaching hospital, respectively. Over 90% should have been taking primary prophylactic aspirin, whereas only 5.7-29% were actually prescribed one. A few had existing cardiovascular/cerebrovascular disease, and all were taking aspirin. There was no documented proteinuria status; however, 30-50% were on a ACEI/ARB, most likely as part of an antihypertensive regimen. Aspirin as a primary prophylaxis of cardiovascular disease in diabetes is remarkably underused. Screening for albuminuria was apparently lacking. Statin therapy also presented a major deficiency. ACEI/ARB was probably prescribed for hypertension rather than in relation to proteinuria.

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

    Science.gov (United States)

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

    1987-07-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  9. Health issues in the Arab American community. The use of glucose-lowering agents and aspirin among Arab Americans with diabetes.

    Science.gov (United States)

    Berlie, Helen D; Hammad, Adnan; Jaber, Linda A

    2007-01-01

    Little is known about the health outcomes or the quality of care among Arab American patients with diabetes. The objective of this study is to examine the use of glucose-lowering agents and aspirin therapy in this population compared to the drug utilization patterns reported in nationally representative surveys. A random sample of adult Arab American patients with self-reported diabetes was selected. Complete medication histories were recorded during a face-to-face interview. Medication utilization of the glucose-lowering agents and aspirin were compared to data from the Third National Health and Nutrition Examination Survey (NHANES) and the Behavioral Risk Factor Surveillance System (BRFSS). The study sample consisted of 53 participants (20 males, 33 females) with mean age +/- SD of 59.4 +/- 12 years and A1C levels of 8.0 +/- 2%. Compared to US adults, Arab American patients with diabetes were less likely to be treated with insulin (27% vs 17%) and more likely to receive oral hypoglycemic agents (65% vs 81%). Similar proportions of participants were maintained on insulin-oral hypoglycemic-combined therapy (10% US adults vs 9% Arab Americans). Aspirin use was significantly lower among the study participants (23%) compared to the reported national prevalence of aspirin intake (64%). The therapeutic management of diabetes in the Arab-American patients with diabetes is suboptimal. The use of insulin and aspirin was lower than that reported by participants in the NHANES and BRFSS national databases. More aggressive approaches for the management of hyperglycemia and the prevention of cardiovascular diseases are needed to improve health outcomes in the Arab-American community.

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

    Science.gov (United States)

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

    2012-01-01

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

  11. The role of low-dose aspirin in the prevention of colorectal cancer.

    Science.gov (United States)

    Avivi, Doran; Moshkowitz, Menachem; Detering, Elmar; Arber, Nadir

    2012-03-01

    Colorectal cancer (CRC) is a prevalent disease that is associated with considerable morbidity and mortality. The progression of normal mucosa through adenomatous polyps to overt cancer can span for 10 - 15 years, making early detection, as well as the use of chemopreventive agents such as aspirin, an attractive option. The effects of aspirin in reducing CRC incidence and mortality have consistently been demonstrated in a number of studies. However, a greater understanding of how aspirin exerts its anti-cancer effects is warranted. The aim of this non-systematic review, which was developed using published randomized and epidemiological studies, as well as key references known to the authors, was to consider the role of aspirin in CRC prevention. Areas covered include the effects of aspirin on cardiovascular disease, CRC and colorectal adenoma (CRA) prevention, mode of action of aspirin and the benefit-to-risk of aspirin in disease prevention. Incorporating CRC and CRA benefits into coronary heart disease (CHD) risk scores would be particularly useful for determining the benefit-to-risk ratio for aspirin use in borderline cases. For instance, patients with an annual CHD risk around 0.7 - 1.4%, but with a high risk of colorectal neoplasm may benefit from aspirin. The strong association between CRC and age may also be useful for re-examining the benefit-to-risk ratio for aspirin use in older patients. However, it has to be noted that a cancer prevention indication for aspirin is not approved regulatory-wise anywhere.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

    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- 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

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

    Science.gov (United States)

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

    2013-01-01

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

  15. 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.

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

    Science.gov (United States)

    Jacob, James N; Tazawa, Makio J

    2012-05-01

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

  17. Aspirin effects on lymphocyte cyclic AMP levels in normal human subjects.

    Science.gov (United States)

    Snider, D E; Parker, C W

    1976-01-01

    In purified lymphocytes from the peripheral blood of healthy human subjects who had ingested therapeutic doses of aspirin, there was a significant decrease in resting cyclic AMP levels as well as a partial inhibition of the rise in cyclic AMP with isoproterenol or prostaglandin E1. These changes were seen as early as 30 min after aspirin ingestion and did not appear to result from aspirin effects on lymphocyte recovery, purity, viability, or relative number of thymus- or bone marrow-derived lymphocytes. In contrast, the direct addition of aspirin to suspensions of purified peripheral lymphocytes did not significantly alter their cyclic AMP levels. However, an effect of aspirin could be obtained in vitro if aspirin was added to unprocessed whole blood during the dextran sedimentation phase of the cell purification. Thus the effect of aspirin on lymphocyte cyclic AMP metabolism, may be indirect, through other cells present in the peripheral blood. PMID:182720

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

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  19. Determination of effect of aspirin and captopril on cat glomerular ...

    African Journals Online (AJOL)

    Four days later, renovascular hypertension was induced through renal-artery stenosis by clipping half of the left renalarteries. Renal scintigraphy was conducted after four days. After confirming the presence of hypertension, the cats were divided into two groups of 10 animals each (aspirin and captopril groups, respectively).

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

    African Journals Online (AJOL)

    hi-tech

    2006-01-01

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

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

    African Journals Online (AJOL)

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

  2. Transfer of Low Dose Aspirin Into Human Milk.

    Science.gov (United States)

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

    2017-05-01

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

  3. 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.

  4. Determination of effect of aspirin and captopril on cat glomerular ...

    African Journals Online (AJOL)

    of uptake of radioactive agents. Currently, captopril renogram scintigraphy is routinely exploited in detecting renovascular hypertension in humans [1,3]. Our results show that captopril at 5 mg/kg can be used to detect unilateral renovascular hypertension in cats. Comparison of the effects of aspirin scintigraphy with that of ...

  5. Regular aspirin use and stomach cancer risk in China.

    Science.gov (United States)

    Wang, Y; Shen, C; Ge, J; Duan, H

    2015-06-01

    Epidemiological studies on aspirin and stomach cancer have been inconclusive. The purpose of our study was to investigate the association between aspirin and stomach cancer in China. A 1:2 matched case-control study was conducted in four large medical centers. A self-designed questionnaire was used to collect information. Unconditional logistic regression was used to compute crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Our study indicated that risk of stomach cancer was greatly reduced for regular aspirin user (OR = 0.62; 95% CI 0.42-0.80). Specifically, dosage and tablet-years of use were associated with lower risk (OR = 0.54; 95% CI 0.29-0.84 for ≥7 tabs/week; OR = 0.47; 95% CI 0.32-0.81 for ≥10 tablet years, respectively). Furthermore, the finding was strengthened by stratified studies of gender, smoking status, body mass index (BMI) and helicobacter pylori. Our study confirmed that regular aspirin use is a protective factor to stomach cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Low-dose aspirin and risk of intracranial bleeds

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

  9. Effects of preoperative aspirin on cardiocerebral and renal complications in non-emergent cardiac surgery patients: a sub-group and cohort study.

    Directory of Open Access Journals (Sweden)

    Longhui Cao

    Full Text Available BACKGROUND AND OBJECTIVE: Postoperative cardiocerebral and renal complications are a major threat for patients undergoing cardiac surgery. This study was aimed to examine the effect of preoperative aspirin use on patients undergoing cardiac surgery. METHODS: An observational cohort study was performed on consecutive patients (n = 1879 receiving cardiac surgery at this institution. The patients excluded from the study were those with preoperative anticoagulants, unknown aspirin use, or underwent emergent cardiac surgery. Outcome events included were 30-day mortality, renal failure, readmission and a composite outcome--major adverse cardiocerebral events (MACE that include permanent or transient stroke, coma, perioperative myocardial infarction (MI, heart block and cardiac arrest. RESULTS: Of all patients, 1145 patients met the inclusion criteria and were divided into two groups: those taking (n = 858 or not taking (n = 287 aspirin within 5 days preceding surgery. Patients with aspirin presented significantly more with history of hypertension, diabetes, peripheral arterial disease, previous MI, angina and older age. With propensity scores adjusted and multivariate logistic regression, however, this study showed that preoperative aspirin therapy (vs. no aspirin significantly reduced the risk of MACE (8.4% vs. 12.5%, odds ratio [OR] 0.585, 95% CI 0.355-0.964, P = 0.035, postoperative renal failure (2.6% vs. 5.2%, OR 0.438, CI 0.203-0.945, P = 0.035 and dialysis required (0.8% vs. 3.1%, OR 0.230, CI 0.071-0.742, P = 0.014, but did not significantly reduce 30-day mortality (4.1% vs. 5.8%, OR 0.744, CI 0.376-1.472, P = 0.396 nor it increased readmissions in the patients undergoing cardiac surgery. CONCLUSIONS: Preoperative aspirin therapy is associated with a significant decrease in the risk of MACE and renal failure and did not increase readmissions in patients undergoing non-emergent cardiac surgery.

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

    Science.gov (United States)

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

    2011-01-01

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

  11. Intracellular erythrocyte platelet-activating factor acetylhydrolase I inactivates aspirin in blood.

    Science.gov (United States)

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

    2011-10-07

    Aspirin (acetylsalicylic acid) prophylaxis suppresses major adverse cardiovascular events, but its rapid turnover limits inhibition of platelet cyclooxygenase activity and thrombosis. Despite its importance, the identity of the enzyme(s) that hydrolyzes the acetyl residue of circulating aspirin, which must be an existing enzyme, remains unknown. We find that circulating aspirin was extensively hydrolyzed within erythrocytes, and chromatography indicated these cells contained a single hydrolytic activity. Purification by over 1400-fold and sequencing identified the PAFAH1B2 and PAFAH1B3 subunits of type I platelet-activating factor (PAF) acetylhydrolase, a phospholipase A(2) with selectivity for acetyl residues of PAF, as a candidate for aspirin acetylhydrolase. Western blotting showed that catalytic PAFAH1B2 and PAFAH1B3 subunits of the type I enzyme co-migrated with purified erythrocyte aspirin hydrolytic activity. Recombinant PAFAH1B2, but not its family member plasma PAF acetylhydrolase, hydrolyzed aspirin, and PAF competitively inhibited aspirin hydrolysis by purified or recombinant erythrocyte enzymes. Aspirin was hydrolyzed by HEK cells transfected with PAFAH1B2 or PAFAH1B3, and the competitive type I PAF acetylhydrolase inhibitor NaF reduced erythrocyte hydrolysis of aspirin. Exposing aspirin to erythrocytes blocked its ability to inhibit thromboxane A(2) synthesis and platelet aggregation. Not all individuals or populations are equally protected by aspirin prophylaxis, the phenomenon of aspirin resistance, and erythrocyte hydrolysis of aspirin varied 3-fold among individuals, which correlated with PAFAH1B2 and not PAFAH1B3. We conclude that intracellular type I PAF acetylhydrolase is the major aspirin hydrolase of human blood.

  12. 15-epi-lipoxin A4-mediated induction of nitric oxide explains how aspirin inhibits acute inflammation.

    OpenAIRE

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Time Trends of Aspirin and Warfarin Use on Stroke and Bleeding Events in Chinese Patients With New-Onset Atrial Fibrillation.

    Science.gov (United States)

    Guo, Yutao; Wang, Hao; Tian, Yingchun; Wang, Yutang; Lip, Gregory Y H

    2015-07-01

    Much of the clinical epidemiology and treatment patterns for patients with atrial fibrillation (AF) are derived from Western populations. Limited data are available on antithrombotic therapy use over time and its impact on the stroke or bleeding events in newly diagnosed Chinese patients with AF. The present study investigates time trends in warfarin and aspirin use in China in relation to stroke and bleeding events in a Chinese population. We used a medical insurance database involving > 10 million individuals for the years 2001 to 2012 in Yunnan, a southwestern province of China, and performed time-trend analysis on those with newly diagnosed AF. Cox proportional hazards time-varying exposures were used to determine the risk of stroke or bleeding events associated with antithrombotic therapy among patients with AF. Among the randomly sampled 471,446 participants, there were 1,237 patients with AF, including 921 newly diagnosed with AF, thus providing 4,859 person-years of experience (62% men; mean attained age, 70 years). The overall rate of antithrombotic therapy was 37.7% (347 of 921 patients), with 4.1% (38 of 921) on warfarin and 32.3% (298 of 921) on aspirin. Antithrombotic therapy was not related to stroke/bleeding risk scores (CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke (doubled)] score, P = .522; CHA2DS2-VASc [congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, stroke or transient ischemic attack (doubled), vascular disease, age 65 to 74 years, and female sex] score, P = .957; HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 years), drugs/alcohol concomitantly] score, P = .095). The use of antithrombotic drugs (mainly aspirin) increased in both women and men over time, with the rate of aspirin increasing from 4.0% in 2007 to 46.1% in 2012 in the former, and from 7.7% in 2007 to 61

  16. Aspirin desensitization for patients with aspirin-exacerbated respiratory disease: A randomized double-blind placebo-controlled trial.

    Science.gov (United States)

    Esmaeilzadeh, Hossein; Nabavi, Mohammad; Aryan, Zahra; Arshi, Saba; Bemanian, Mohammad Hassan; Fallahpour, Morteza; Mortazavi, Negar

    2015-10-01

    The effect of aspirin desensitization (AD) on immunologic profile of patients with AERD has been poorly understood. This study is aimed at investigating the effect of AD on clinical and immunological markers of patients with AERD. This randomized double-blind placebo-controlled trial comprised 34 adult patients (67.6% female) with chronic rhinosinusitis, nasal polyps, and aspirin-intolerant asthma. The active group underwent AD over a 2-day period with increasing doses of aspirin (60, 125, 325, and 625 mg), followed by receiving aspirin 625 mg twice daily for 6 months. Symptom scores and medication needs of patients with AERD who have undergone AD were significantly lower compared to the placebo group after 6 months (7.5 ± 3.5 vs. 10.6 ± 3.8 and 9.3 ± 2.0 vs. 11.0 ± 3.1, respectively, all p < 0.05). However, no significant difference was observed in serum concentration of IL-10, IFN-γ, and TGF-β between two groups neither at baseline nor at the end of study. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Aspirin for Evidence-Based Preeclampsia Prevention trial: influence of compliance on beneficial effect of aspirin in prevention of preterm preeclampsia.

    Science.gov (United States)

    Wright, David; Poon, Liona C; Rolnik, Daniel L; Syngelaki, Argyro; Delgado, Juan Luis; Vojtassakova, Denisa; de Alvarado, Mercedes; Kapeti, Evgenia; Rehal, Anoop; Pazos, Andrea; Carbone, Ilma Floriana; Dutemeyer, Vivien; Plasencia, Walter; Papantoniou, Nikos; Nicolaides, Kypros H

    2017-12-01

    The Aspirin for Evidence-Based Preeclampsia Prevention trial was a multicenter study in women with singleton pregnancies. Screening was carried out at 11-13 weeks' gestation with an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor). Those with an estimated risk for preterm preeclampsia of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/d) vs placebo from 11-14 until 36 weeks' gestation. Preterm preeclampsia with delivery at aspirin group, as compared with 4.3% (35/822) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74). We sought to examine the influence of compliance on the beneficial effect of aspirin in prevention of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial. This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of aspirin group with compliance ≥90%, in 8/243 (3.3%) of participants in the aspirin group with compliance aspirin group for preterm preeclampsia was 0.24 (95% confidence interval, 0.09-0.65) for compliance ≥90% and 0.59 (95% confidence interval, 0.23-1.53) for compliance aspirin in the prevention of preterm preeclampsia appears to depend on compliance. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Diabetes mellitus and insulin in an aspirin sensitive asthmatic.

    Science.gov (United States)

    Caplin, I

    1976-03-01

    The infrequency of diabetes mellitus and asthma in the same individual is re-examined. The antagonism between epinephrine and insulin, as suggested by Konig in 1935, is indeed accurate. The assays done by the Eli Lilly Research Department revealed no in vitro effect of insulin on the CAMP and GMP level of mast cells as occurs in liver cells. It is felt that this effect is probably an in vivo effect produced via the vagus nerve and alpha-adrenergic receptor system stimulation. This would explain the mechanism of aggravation of asthma by excess insulin. Dr. Petersen's studies, the negative intradermal skin tests to insulin and the absence of change on either beef or pork insulin usage by our patient all point to a nonatopic factor in the aggravation of the asthma of this patient. In the uncommon occurrence of asthma and diabetes in the same patient, insulin dosage should be considered as a factor in all such asthmatics who do not respond well to conventional therapy. Two additional asthmatics who also have diabetes did improve with cessation of nocturnal asthma by a reduction of their evening dose of insulin. A high fat, low carbohydrate diet, as suggested by Abrahamson to avoid dietary hyperinsulinism, is certainly worth considering in patients with nocturnal asthma. If patients cannot be made to follow a diet requiring frequent feedings high in protein and fats and low in carbohydrates, another approach suggests itself. Abrahamson was able to relieve the patients who developed nocturnal asthma with hypoglycemia by having them drink a glass of milk. Assuming other causes have been eliminated and a patient awakens each day at 3:00 a.m., an alarm clock could be set at 2:00 a.m. Milk or a milk substitute in milk sensitive patients could be taken at 2:00 a.m. to raise the blood sugar and hopefully prevent the asthma associated with hypoglycemia. Also to be noted is the ubiquitous use of tartrazine in so many drugs, including those used to relieve asthmatic symptoms

  19. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Anand, Sonia S; Bosch, Jackie; Eikelboom, John W; Connolly, Stuart J; Diaz, Rafael; Widimsky, Peter; Aboyans, Victor; Alings, Marco; Kakkar, Ajay K; Keltai, Katalin; Maggioni, Aldo P; Lewis, Basil S; Störk, Stefan; Zhu, Jun; Lopez-Jaramillo, Patricio; O'Donnell, Martin; Commerford, Patrick J; Vinereanu, Dragos; Pogosova, Nana; Ryden, Lars; Fox, Keith A A; Bhatt, Deepak L; Misselwitz, Frank; Varigos, John D; Vanassche, Thomas; Avezum, Alvaro A; Chen, Edmond; Branch, Kelley; Leong, Darryl P; Bangdiwala, Shrikant I; Hart, Robert G; Yusuf, Salim

    2017-11-10

    [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043). Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding. Bayer AG. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Shiuh-Lin Hwang

    2004-01-01

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

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

    Science.gov (United States)

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

    2015-12-23

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

  2. Therapeutic utility of aspirin in the ApcMin/+ murine model of colon carcinogenesis

    International Nuclear Information System (INIS)

    Reuter, Brian K; Zhang, Xiao-Jing; Miller, Mark JS

    2002-01-01

    In recent years it has become evident that nonsteroidal anti-inflammatory drugs, in particular aspirin represent a potential class of cancer chemotherapeutic agents. Despite the wealth of knowledge gained from epidemiological, clinical and animal studies, the effectiveness of aspirin to treat established gastrointestinal cancer has not been determined. The present study examines the ability of aspirin to treat established polyposis in Min/+ mice. Min/+ mice with established polyposis were treated orally once daily from 12–16 weeks of age with either drug vehicle or aspirin (25 mg/kg). Upon completion of treatment, the number, location and size of intestinal tumours was determined. Additional variables examined were the number of apoptotic cells within tumours and COX activity. Administration of aspirin for 4 weeks to Min/+ mice produce no effect on tumour number compared to vehicle-treated Min/+ mice (65 ± 8 vs. 63 ± 9, respectively). In addition, aspirin had no effect on tumour size or location. However, aspirin treatment produced a greater than 2-fold (p < 0.05) increase in the number of apoptotic positive cells within tumours and significantly decreased hepatic PGE 2 content. Aspirin was found to have no effect on tumour number and size when administered to Min/+ mice with established polyposis. The findings in the present study call in to question the utility of aspirin as a stand-alone treatment for established GI cancer. However, aspirin's ability to significantly promote apoptosis may render it suitable for use in combinatorial chemotherapy

  3. Employment of the porous particles for preparation of the capsules containing aspirin and drug release property

    International Nuclear Information System (INIS)

    Hosoi, Fumio; Makuuchi, Keizo; Saito, Kenji; Koishi, Masumi.

    1985-01-01

    Polymer-coated porous particles containing aspirin as a drug were prepared and the rate of release of aspirin was studied. The impregnation of aspirin was carried out by post-graft polymerization, where methyl methacrylate or methacrylic acid was treated with porous particles, pre-irradiated with γ-ray from 60 Co, in the presence of aspirin. Release of aspirin from modified particles was tested with 50 % methanol solution and/or pH 5.2 buffer solution of acetic acid. The amount of aspirin released from capsules increased with time and reached a constant values after 140 h. The amount of aspirin absorbed in porous particles was increased with graft polymerization. In addition, absorption of aspirin in porous particles was significantly enhanced by treating the particle surface with TiO 2 before irradiation. The amount of aspirin released was linearly to the square root of time. It was concluded that the diffusion of aspirin through the polymer matrix was the rate limiting step. (author)

  4. The Helicobacter Eradication Aspirin Trial (HEAT): A Large Simple Randomised Controlled Trial Using Novel Methodology in Primary Care.

    Science.gov (United States)

    Dumbleton, Jennifer S; Avery, Anthony J; Coupland, Carol; Hobbs, F D Richard; Kendrick, Denise; Moore, Michael V; Morris, Clive; Rubin, Greg P; Smith, Murray D; Stevenson, Diane J; Hawkey, Chris J

    2015-09-01

    Clinical trials measuring the effect of an intervention on clinical outcomes are more influential than those investigating surrogate measures but are costly. We developed methods to reduce costs substantially by using existing data in primary care systems, to ask whether Helicobacter pylori eradication would reduce the incidence of hospitalisation for ulcer bleeding in aspirin users. The Helicobacter Eradication Aspirin Trial (HEAT) is a National Institute of Health Research-funded, double-blind placebo controlled randomised trial of the effects of H. pylori eradication on subsequent ulcer bleeding in infected individuals taking aspirin daily, conducted in practices across the whole of England, Wales and Northern Ireland. A bespoke web-based trial management system developed for the trial (and housed within the secure NHS Data Network) communicates directly with the HEAT Toolkit software downloaded at participating practices, which issues queries searching entry criteria (≥ 60 years, on chronic aspirin ≤ 325 mg daily, not on anti-ulcer therapy or non-steroidal anti-inflammatory drugs) for GP review of eligibility. Trial participation is invited using a highly secure automated online mail management system. Interested patients are seen once for consent and breath testing. Those with a positive test are randomised to eradication treatment (lansoprazole, clarithromycin, metronidazole) or placebo, with drug sent by post. Events are tracked by upload of accumulating information in the GP database, patient contact, review of National Hospital Episode Statistics and Office of National Statistics data. HEAT is the largest Clinical Research Network-supported drug trial, with 115,660 invitation letters sent from 850 practices, 22,922 volunteers, and 3038 H. pylori positive patients randomised to active or placebo treatment after 2.5 years of recruitment. 178 practices have performed their first follow-up data search to identify 21 potential endpoints to date. HEAT

  5. Association Between the P2RY12 Receptor Gene Polymorphism and Aspirin Resistance in Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    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

  6. The Helicobacter Eradication Aspirin Trial (HEAT): A Large Simple Randomised Controlled Trial Using Novel Methodology in Primary Care

    Science.gov (United States)

    Dumbleton, Jennifer S.; Avery, Anthony J.; Coupland, Carol; Hobbs, F.D. Richard; Kendrick, Denise; Moore, Michael V.; Morris, Clive; Rubin, Greg P.; Smith, Murray D.; Stevenson, Diane J.; Hawkey, Chris J.

    2015-01-01

    Background Clinical trials measuring the effect of an intervention on clinical outcomes are more influential than those investigating surrogate measures but are costly. We developed methods to reduce costs substantially by using existing data in primary care systems, to ask whether Helicobacter pylori eradication would reduce the incidence of hospitalisation for ulcer bleeding in aspirin users. Methods The Helicobacter Eradication Aspirin Trial (HEAT) is a National Institute of Health Research-funded, double-blind placebo controlled randomised trial of the effects of H. pylori eradication on subsequent ulcer bleeding in infected individuals taking aspirin daily, conducted in practices across the whole of England, Wales and Northern Ireland. A bespoke web-based trial management system developed for the trial (and housed within the secure NHS Data Network) communicates directly with the HEAT Toolkit software downloaded at participating practices, which issues queries searching entry criteria (≥ 60 years, on chronic aspirin ≤ 325 mg daily, not on anti-ulcer therapy or non-steroidal anti-inflammatory drugs) for GP review of eligibility. Trial participation is invited using a highly secure automated online mail management system. Interested patients are seen once for consent and breath testing. Those with a positive test are randomised to eradication treatment (lansoprazole, clarithromycin, metronidazole) or placebo, with drug sent by post. Events are tracked by upload of accumulating information in the GP database, patient contact, review of National Hospital Episode Statistics and Office of National Statistics data. Results HEAT is the largest Clinical Research Network-supported drug trial, with 115,660 invitation letters sent from 850 practices, 22,922 volunteers, and 3038 H. pylori positive patients randomised to active or placebo treatment after 2.5 years of recruitment. 178 practices have performed their first follow-up data search to identify 21

  7. Dual antiplatelet therapy with prasugrel or ticagrelor versus clopidogrel in interventional cardiology

    DEFF Research Database (Denmark)

    Clemmensen, Peter; Dridi, Nadia Paarup; Holmvang, Lene

    2013-01-01

    For several years, clopidogrel plus aspirin has been the dual antiplatelet therapy (DAPT) of choice for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with stent implantation. More recently, prasugrel and ticagrelor have demonstrated greater effica...

  8. Aspirin for the prevention of cognitive decline in the elderly: rationale and design of a neuro-vascular imaging study (ENVIS-ion

    Directory of Open Access Journals (Sweden)

    Reid Christopher M

    2012-02-01

    Full Text Available Abstract Background This paper describes the rationale and design of the ENVIS-ion Study, which aims to determine whether low-dose aspirin reduces the development of white matter hyper-intense (WMH lesions and silent brain infarction (SBI. Additional aims include determining whether a changes in retinal vascular imaging (RVI parameters parallel changes in brain magnetic resonance imaging (MRI; b changes in RVI parameters are observed with aspirin therapy; c baseline cognitive function correlates with MRI and RVI parameters; d changes in cognitive function correlate with changes in brain MRI and RVI and e whether factors such as age, gender or blood pressure influence the above associations. Methods/Design Double-blind, placebo-controlled trial of three years duration set in two Australian academic medical centre outpatient clinics. This study will enrol 600 adults aged 70 years and over with normal cognitive function and without overt cardiovascular disease. Subjects will undergo cognitive testing, brain MRI and RVI at baseline and after 3 years of study treatment. All subjects will be recruited from a 19,000-patient clinical outcome trial conducted in Australia and the United States that will evaluate the effects of aspirin in maintaining disability-free longevity over 5 years. The intervention will be aspirin 100 mg daily versus matching placebo, randomized on a 1:1 basis. Discussion This study will improve understanding of the mechanisms at the level of brain and vascular structure that underlie the effects of aspirin on cognitive function. Given the limited access and high cost of MRI, RVI may prove useful as a tool for the identification of individuals at high risk for the development of cerebrovascular disease and cognitive decline. Trial Registration clinicaltrials.gov Identifier: NCT01038583

  9. Secondary prevention of cardiogenic arterial thromboembolism in the cat: The double-blind, randomized, positive-controlled feline arterial thromboembolism; clopidogrel vs. aspirin trial (FAT CAT).

    Science.gov (United States)

    Hogan, Daniel F; Fox, Philip R; Jacob, Kristin; Keene, Bruce; Laste, Nancy J; Rosenthal, Steven; Sederquist, Kimberly; Weng, Hsin-Yi

    2015-12-01

    To determine if clopidogrel administration is associated with a reduced likelihood of recurrent cardiogenic arterial thromboembolism (CATE) in cats compared to aspirin administration. Secondary aims were to determine if clopidogrel administration had an effect on the composite endpoint of recurrent CATE and cardiac death and to identify adverse effects of chronic clopidogrel or aspirin therapy. Seventy-five cats that survived a CATE event. Multicenter, double-blind, randomized, positive-controlled study. Cats were assigned to clopidogrel (18.75 mg/cat PO q 24 h) or aspirin (81 mg/cat PO q 72 h). Kaplan-Meier survival curves were created for each endpoint and the log rank test performed to compare treatment groups with respect to time to event and the likelihood of the event occurring. The mean age of all cats was 8.0 ± 3.5 yr and 57/75 (76%) were male (p history of heart disease recorded prior to the CATE event. Clopidogrel administration was associated with significantly reduced likelihood of recurrent CATE compared to aspirin (p = 0.024) and had a longer median time to recurrence [443 (95% CI 185-990) days vs. 192 (95% CI 62-364) days, respectively]. Clopidogrel was also associated with a significantly reduced likelihood of the composite endpoint of recurrent CATE or cardiac death (p = 0.033) with a longer median time to event [346 (95% CI 146-495) days vs. 128 (95% CI 58-243) days]. Clopidogrel administration significantly reduces the likelihood of recurrent CATE compared with aspirin in cats; both drugs were well tolerated. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2012-10-01

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

  11. [Gastrointestinal bleeding, NSAIDs, aspirin and anticoagulants].

    Science.gov (United States)

    Lanas, Ángel

    2014-09-01

    The studies presented at the recent American Congress of Gastroenterology in the field of non-variceal upper gastrointestinal bleeding (associated or not to NSAIDs or ASA use) have not been numerous but interesting. The key findings are: a) rabeprazole, the only PPI that had few studies in this field, is effective in the prevention of gastric ulcers; b) famotidine could also be effective in the prevention of complications by AAS; c) the new competitive inhibitors of the acid potassium pump are effective (as much as PPIs) on the recurrence of peptic ulcers by ASA; d) early endoscop (<8 h) in non-variceal upper gastrointestinal bleeding seems to offer no better results than those made in the first 24 h; e) endoscopic therapy in Forrest 1a ulcers does not obliterate the bleeding artery in 30% of cases and is the cause of bleeding recurrence; f) alternative therapies with glue or clotting products are being increasingly used in endoscopic therapy of gastrointestinal bleeding; g) liberal administration of blood in the GI bleeding is associated with poor prognosis; h) lesions of the small intestine are frequent cause of gastrointestinal bleeding when upper endoscopy shows no positive stigmata; and i) capsule endoscopy studies have high performance in gastrointestinal bleeding of obscure origin, if performed early in the first two days after the beginning of the bleeding episode. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  12. Aspirin induces morphological transformation to the secretory state in isolated rabbit parietal cells.

    Science.gov (United States)

    Murthy, U K; Levine, R A

    1991-08-01

    The morphological response of rabbit parietal cells to aspirin was evaluated by grading several ultra-structural features including the extent of the tubulovesicular system, intracellular secretory canaliculi, and microvilli. After exposure of isolated parietal cells and gastric glands to aspirin or histamine, there was an approximately twofold increase in the ratio of secretory to nonsecretory parietal cells, and depletion of extracellular Ca2+ abolished the aspirin-induced morphological changes. Morphometry in parietal cells showed that aspirin induced a sixfold increase in secretory canalicular membrane elaboration. Aspirin potentiated histamine-induced parietal cell respiration and aminopyrine uptake ratio but did not increase basal respiration or aminopyrine uptake, suggesting an apparent dissociation from aspirin-induced morphological changes.

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

    Science.gov (United States)

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

    2017-06-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    OBJECTIVE: To study the prevalence and importance of aspirin resistance in patients with an evolving acute myocardial infarction (AMI) by use of the Platelet Function Analyzer-100. INTRODUCTION: Previous studies have demonstrated the existence of aspirin resistance, but the clinical relevance...... of the phenomenon remains to be clarified. If aspirin resistant patients comprise a high-risk subgroup, it might be expected that the prevalence of aspirin resistance in patients with AMI would be higher than in patients without AMI. We hypothesized that the prevalence of aspirin resistance in patients with AMI...... 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...

  15. 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.

  16. Aspirin inhibits human telomerase activation in unstable carotid plaques

    OpenAIRE

    LI, FANGMING; GUO, YI; JIANG, XIN; ZHONG, JIANXIN; LI, GUANDONG; SUN, SHENGGANG

    2013-01-01

    The activation of telomerase in unstable plaques is an important factor in atherosclerosis, and may be predictive of the risk of cerebrovascular diseases. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase that is essential for telomerase activation. The aim of the present study was to investigate whether aspirin inhibits the activation of telomerase and hTERT in unstable carotid plaques. Polymorphonuclear neutrophils (PMNs) derived from carotid plaques were isolated fr...

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

    OpenAIRE

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

    2004-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

  19. Determination of trace element impurities in aspirin tablets by neutron activation analysis

    International Nuclear Information System (INIS)

    Iskander, F.Y.; Klein, D.E.; Bauer, T.L.

    1986-01-01

    Twenty-five trace and minor elements in five different Egyptian aspirin brands (Aspo, Askin, Aspocid, Aspeol and Rivo) were determined by instrumental neutron activation analysis. It was concluded that the concentration of As, Ba, Br, Co, Cr, Fe (except in Aspocid), Mg, Mn, Rb, Se, Sr and Zn in the Egyptian brands is below or within the concentration range reported for these elements in 16 American aspirin and aspirin-like brands. (author)

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

    OpenAIRE

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

    2004-01-01

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

  1. Does low-dose aspirin increase blood loss after spinal fusion surgery?

    Science.gov (United States)

    Kang, Suk-Bong; Cho, Kyu-Jung; Moon, Kyung-Ho; Jung, Jae-Hoon; Jung, Se-Jin

    2011-04-01

    Low-dose aspirin for the prevention of cardiovascular disease is recommended to be discontinued at least 7 days before spinal surgery. To determine the effect of stopping low-dose aspirin at least 7 days before surgery on the level of the perioperative blood loss or complications related to hemorrhage. Retrospective case study. Patients who underwent spinal fusion surgery for degenerative lumbar disease. Clinical outcome was measured by the Oswestry Disability Index. The aspirin group included 38 patients who had taken 100 mg aspirin for an average of 40.3 months. They stopped aspirin for at least 7 days before surgery (mean, 9.0 days). The control group included 38 patients who had not taken aspirin. Both groups were matched in terms of age, gender, number of fused segments, and surgical procedures. The diagnosis in all patients was degenerative spinal disease. The mean age in the aspirin and control groups was 68.5 and 69.1 years, respectively. The mean number of levels fused was 2.0 segments in both groups. During surgery, the estimated blood loss was 855.3 cc in the aspirin group and 840.8 cc in the control group with no significant difference (p=.84). However, there was a significant difference in blood drainage after surgery. The hemovac blood drainage after surgery was 864.4 cc in the aspirin group but only 458.4 cc in the control group (pdrainage after surgery was significantly higher in the aspirin group despite stopping aspirin 7 days before surgery. Hence, surgeons should pay careful attention to postoperative blood loss and complications related to hemorrhage in patients who have been taking low-dose aspirin. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. 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.

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

    Science.gov (United States)

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

    2017-12-01

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

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

    OpenAIRE

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

    2017-01-01

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

  5. A Proteomic Approach to Analyze the Aspirin-mediated Lysine Acetylome.

    Science.gov (United States)

    Tatham, Michael H; Cole, Christian; Scullion, Paul; Wilkie, Ross; Westwood, Nicholas J; Stark, Lesley A; Hay, Ronald T

    2017-02-01

    Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-d 3 , in combination with acetylated lysine purification and LC-MS/MS, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies endogenous acetylation signals at the majority of detectable endogenous sites, cells tolerate aspirin mediated acetylation very well unless cellular deacetylases are inhibited. Although most endogenous acetylations are amplified by orders of magnitude, lysine acetylation site occupancies remain very low even after high doses of aspirin. This work shows that while aspirin has enormous potential to alter protein function, in the majority of cases aspirin-mediated acetylations do not accumulate to levels likely to elicit biological effects. These findings are consistent with an emerging model for cellular acetylation whereby stoichiometry correlates with biological relevance, and deacetylases act to minimize the biological consequences of nonspecific chemical acetylations. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. A Proteomic Approach to Analyze the Aspirin-mediated Lysine Acetylome*

    Science.gov (United States)

    Tatham, Michael H.; Cole, Christian; Scullion, Paul; Wilkie, Ross; Westwood, Nicholas J.; Stark, Lesley A.; Hay, Ronald T.

    2017-01-01

    Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-d3, in combination with acetylated lysine purification and LC-MS/MS, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies endogenous acetylation signals at the majority of detectable endogenous sites, cells tolerate aspirin mediated acetylation very well unless cellular deacetylases are inhibited. Although most endogenous acetylations are amplified by orders of magnitude, lysine acetylation site occupancies remain very low even after high doses of aspirin. This work shows that while aspirin has enormous potential to alter protein function, in the majority of cases aspirin-mediated acetylations do not accumulate to levels likely to elicit biological effects. These findings are consistent with an emerging model for cellular acetylation whereby stoichiometry correlates with biological relevance, and deacetylases act to minimize the biological consequences of nonspecific chemical acetylations. PMID:27913581

  7. Mechanism of prevention of aspirin-induced gastric lesions by bile duct legation in the rat.

    Science.gov (United States)

    Guth, P H; Paulsen, G; Lynn, D; Aures, D

    1976-11-01

    Gastric reflux of bile has been reported to be essential for the production of acute gastric mucosal lesions by intragastric aspirin in the rat. The purpose of the present study was to determine whether bile duct legation of pylorus ligation in the rat inhibits asprin-induced gastric lesions, and, if so, what the protective mechanisms are. Operations were performed under ether anesthesia. Asprin, 200 mg per kg, was instilled into the stomach 1/2 hr postsurgery (bile duct ligation or pylorus ligation). Four hours later the rats were killed, the stomachs were examined, and mucosal lesions were scored. Bile duct ligation, but not pylorus ligation, significantly protected against aspirin-induced gastric-lesions. Bile duct ligation, in pylorus-ligated rats, inhibited gastric acid output by 78%. Instilling HCl + aspirin in bile duct-ligated rats restored lesion formation. Shunting bile to the colon (to prevent bile reflux) did not prevent aspirin lesions. Salicylate determination, to ascertain whether bile duct ligation altered asprin absorption, revealed no significant differences between bile duct ligation and aspirin, shunt + aspirin, and sham shunt + aspirin in plasma and gastric tissue salicylate concentrations. (1) Bile duct legation protects against aspirin-induced gastric mucosal lesions by inhibiting gastric HCl secretion. As a corollary, a certain amount of acid in the stomach is necessary for aspirin-induced gastric lesions to form. (2) Bile reflux is not necessary for aspirn-induced gastric lesions in the rat.

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

    Directory of Open Access Journals (Sweden)

    Muhammad A. Hussain

    2017-05-01

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

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

    Science.gov (United States)

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

    2017-05-01

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

  10. Longitudinal assessment of thrombin generation potential in response to alteration of antiplatelet therapy after TIA or ischaemic stroke.

    LENUS (Irish Health Repository)

    Tobin, W O

    2013-02-01

    The impact of changing antiplatelet therapy on thrombin generation potential in patients with ischaemic cerebrovascular disease (CVD) is unclear. We assessed patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Thrombin generation was assessed in platelet poor plasma. Ninety-one patients were recruited. Twenty-four were initially assessed on no antiplatelet therapy, and then after 14d (N = 23) and 90d (N = 8) on aspirin monotherapy; 52 were assessed on aspirin monotherapy, and after 14 and 90 days on aspirin and dipyridamole combination therapy; 21 patients were assessed on aspirin and after 14 days (N = 21) and 90 days (N = 19) on clopidogrel. Peak thrombin generation and endogenous thrombin potential were reduced at 14 and 90 days (p ≤ 0.04) in the overall cohort. We assessed the impact of individual antiplatelet regimens on thrombin generation parameters to investigate the cause of this effect. Lag time and time-to-peak thrombin generation were unchanged at 14 days, but reduced 90 days after commencing aspirin (p ≤ 0.009). Lag time, peak thrombin generation and endogenous thrombin potential were reduced at both 14 and 90 days after adding dipyridamole to aspirin (p ≤ 0.01). Lag time was reduced 14 days after changing from aspirin to clopidogrel (p = 0.045), but this effect was not maintained at 90 days (p = 0.2). This pilot study did not show any consistent effects of commencing aspirin, or of changing from aspirin to clopidogrel on thrombin generation potential during follow-up. The addition of dipyridamole to aspirin led to a persistent reduction in peak and total thrombin generation ex vivo, and illustrates the diverse, potentially beneficial, newly recognised \\'anti-coagulant\\' effects of dipyridamole in ischaemic CVD.

  11. Effect of Clopidogrel and Aspirin vs Aspirin Alone on Migraine Headaches After Transcatheter Atrial Septal Defect Closure: The CANOA Randomized Clinical Trial.

    Science.gov (United States)

    Rodés-Cabau, Josep; Horlick, Eric; Ibrahim, Reda; Cheema, Asim N; Labinaz, Marino; Nadeem, Najaf; Osten, Mark; Côté, Mélanie; Marsal, Josep Ramon; Rivest, Donald; Marrero, Alier; Houde, Christine

    2015-11-24

    The occurrence of new-onset migraine attacks is a complication of transcatheter atrial septal defect (ASD) closure. It has been suggested that clopidogrel may reduce migraine attacks after ASD closure. To assess the efficacy of clopidogrel, used in addition to taking aspirin, for the prevention of migraine attacks following ASD closure. Randomized, double-blind clinical trial performed in 6 university hospitals in Canada. Participants were 171 patients with an indication for ASD closure and no history of migraine. Patients were randomized (1:1) to receive dual antiplatelet therapy (aspirin + clopidogrel [the clopidogrel group], n = 84) vs single antiplatelet therapy (aspirin + placebo [the placebo group], n = 87) for 3 months following transcatheter ASD closure. The first patient was enrolled in December 2008, and the last follow-up was completed in February 2015. The primary efficacy outcome was the monthly number of migraine days within the 3 months following ASD closure in the entire study population. The incidence and severity of new-onset migraine attacks, as evaluated by the Migraine Disability Assessment questionnaire, were prespecified secondary end points. A zero-inflated Poisson regression model was used for data analysis. The mean (SD) age of the participants was 49 (15) years and 62% (106) were women. Patients in the clopidogrel group had a reduced mean (SD) number of monthly migraine days within the 3 months following the procedure (0.4 [95% CI, 0.07 to 0.69] days) vs the placebo group (1.4 [95% CI, 0.54 to 2.26] days; difference, -1.02 days [95% CI, -1.94 to -0.10 days]; incident risk ratio [IRR], 0.61 [95% CI, 0.41 to 0.91]; P = .04) and a lower incidence of migraine attacks following ASD closure (9.5% for the clopidogrel group vs 21.8% for the placebo group; difference, -12.3% [95% CI, -23% to -1.6%]; odds ratio [OR], 0.38 [95% CI, 0.15 to 0.89]; P = .03). Among patients with migraines, those in the clopidogrel group had less

  12. Contemporary management of chronic rhinosinusitis with nasal polyposis in aspirin-exacerbated respiratory disease: an evidence-based review with recommendations.

    Science.gov (United States)

    Levy, Joshua M; Rudmik, Luke; Peters, Anju T; Wise, Sarah K; Rotenberg, Brian W; Smith, Timothy L

    2016-12-01

    Chronic rhinosinusitis (CRS) in aspirin-exacerbated respiratory disease (AERD) represents a recalcitrant form of sinonasal inflammation for which a multidisciplinary consensus on patient management has not been reached. Several medical interventions have been investigated, but a formal comprehensive evaluation of the evidence has never been performed. The purpose of this article is to provide an evidence-based approach for the multidisciplinary management of CRS in AERD. A systematic review of the literature was performed and the guidelines for development of an evidence-based review with recommendations were followed. Study inclusion criteria included: adult population >18 years old; CRS based on published diagnostic criteria, and a presumptive diagnosis of AERD. We focused on reporting higher-quality studies (level 2 or higher) when available, but reported lower-quality studies if the topic contained insufficient evidence. Treatment recommendations were based on American Academy of Otolaryngology (AAO) guidelines, with defined grades of evidence and evaluation of research quality and risk/benefits associated with each treatment. This review identified and evaluated the literature on 3 treatment strategies for CRS in AERD: dietary salicylate avoidance, leukotriene modification, and desensitization with daily aspirin therapy. Based on the available evidence, dietary salicylate avoidance and leukotriene-modifying drugs are options following appropriate treatment with nasal corticosteroids and saline irrigation. Desensitization with daily aspirin therapy is recommended following revision endoscopic sinus surgery (ESS). © 2016 ARS-AAOA, LLC.

  13. State of the art: a systematic review of the surgical management of aspirin exacerbated respiratory disease.

    Science.gov (United States)

    Yip, Jonathan; Yao, Christopher M; Lee, John M

    2014-01-01

    Endoscopic sinus surgery is an important modality to the armamentarium of the otolaryngologist managing chronic rhinosinusitis (CRS). Within the spectrum of CRS, there exists a subset of patients who are recalcitrant to conventional treatment strategies, including those with aspirin-exacerbated respiratory disease (AERD). Although surgery is frequently undertaken in this group, there has been no general consensus on the efficacy or optimal extent of surgery. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of published studies was conducted. Inclusion criteria included original publications of adult patients with AERD undergoing surgery, cohorts of greater than five subjects, a minimum follow-up of 3 months, and measurable clinical outcomes. An electronic search was performed using OVID MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Sixteen studies met the criteria for analysis. For our primary objective, sinus surgery appeared to improve patient-reported quality of life (QoL) and symptom profile in AERD. Overall, most studies reported a decrease in radiographic grading, endoscopy scores, and asthma severity. Compared with aspirin-tolerant asthmatic patients, AERD patients may have worse objective measures of disease severity both pre- and postoperatively; however, patient-reported QoL and symptom improvement may be similar after sinus surgery. Finally, this review showed that patients with AERD required revision surgeries sooner and more frequently compared with other subtypes of CRS. We also discussed the role of maximal surgical techniques and additional benefit of postoperative adjunctive therapies in the management of this disease entity. The state of the art in the management of AERD patients suggests that surgery does play an important role in helping establish symptomatic control. In the future, more rigorous studies evaluating the

  14. 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.

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

    Science.gov (United States)

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

    2017-06-01

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

  16. Aspirin As Secondary Prevention in Patients With Colorectal Cancer: An Unselected Population-Based Study.

    Science.gov (United States)

    Bains, Simer J; Mahic, Milada; Myklebust, Tor Åge; Småstuen, Milada Cvancarova; Yaqub, Sheraz; Dørum, Liv Marit; Bjørnbeth, Bjørn Atle; Møller, Bjørn; Brudvik, Kristoffer Watten; Taskén, Kjetil

    2016-07-20

    Regular use of aspirin (acetylsalicylic acid) is associated with reduced incidence and mortality of colorectal cancer (CRC). However, aspirin as primary prevention is debated because of the risk of hemorrhagic adverse effects. Aspirin as secondary prevention may be more justified from a risk-benefit perspective. We have examined the association between aspirin use after the diagnosis of CRC with CRC-specific survival (CSS) and overall survival (OS). An observational, population-based, retrospective cohort study was conducted by linking patients diagnosed with CRC from 2004 through 2011 (Cancer Registry of Norway) with data on their aspirin use (The Norwegian Prescription Database). These registries cover more than 99% of the Norwegian population and include all patients in an unselected and consecutive manner. Exposure to aspirin was defined as receipt of aspirin prescriptions for more than 6 months after the diagnosis of CRC. Multivariable Cox-proportional hazard analyses were used to model survival. The main outcome measures of the study were CSS and OS. A total of 23,162 patients diagnosed with CRC were included, 6,102 of whom were exposed to aspirin after the diagnosis of CRC (26.3%). The median follow-up time was 3.0 years. A total of 2,071 deaths (32.9%, all causes) occurred among aspirin-exposed patients, of which 1,158 (19.0%) were CRC specific. Among unexposed patients (n = 17,060), there were 7,218 deaths (42.3%), of which 5,375 (31.5%) were CRC specific. In multivariable analysis, aspirin exposure after the diagnosis of CRC was independently associated with improved CSS (hazard ratio [HR], 0.85; 95% CI, 0.79 to 0.92) and OS (HR, 0.95; 95% CI, 0.90 to 1.01). Aspirin use after the diagnosis of CRC is independently associated with improved CSS and OS. © 2016 by American Society of Clinical Oncology.

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

    Science.gov (United States)

    Alexander, John H; Lopes, Renato D; Thomas, Laine; Alings, Marco; Atar, Dan; Aylward, Philip; Goto, Shinya; Hanna, Michael; Huber, Kurt; Husted, Steen; Lewis, Basil S; McMurray, John J V; Pais, Prem; Pouleur, Hubert; Steg, Philippe Gabriel; Verheugt, Freek W A; Wojdyla, Daniel M; Granger, Christopher B; Wallentin, Lars

    2014-01-01

    We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was left to the discretion of the treating physician. In this predefined analysis, simple and marginal structured models were used to adjust for baseline and time-dependent confounders associated with aspirin use. Outcome measures included stroke or systemic embolism, ischaemic stroke, myocardial infarction, mortality, major bleeding, haemorrhagic stroke, major or clinically relevant non-major bleeding, and any bleeding. On Day 1, 4434 (24%) patients were taking aspirin. Irrespective of concomitant aspirin use, apixaban reduced stroke or systemic embolism [with aspirin: apixaban 1.12% vs. warfarin 1.91%, hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.39-0.85 vs. without aspirin: apixaban 1.11% vs. warfarin 1.32%, HR 0.84, 95% CI 0.66-1.07; P interaction = 0.10] and caused less major bleeding than warfarin (with aspirin: apixaban 3.10% vs. warfarin 3.92%, HR 0.77, 95% CI 0.60-0.99 vs. without aspirin: apixaban 1.82% vs. warfarin 2.78%, HR without aspirin 0.65, 95% CI 0.55-0.78; P interaction = 0.29). Similar results were seen in the subgroups of patients with and without arterial vascular disease. Apixaban had similar beneficial effects on stroke or systemic embolism and major bleeding compared with warfarin, irrespective of concomitant aspirin use.

  18. 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 ...

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  20. Photocatalytic Performance and Degradation Mechanism of Aspirin by TiO2 through Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    Lezhuo Li

    2018-03-01

    Full Text Available In the present work, the photocatalytic performance of P25TiO2 was investigated by means of the degradation of aspirin, while the reaction system was systematically optimized by central composite design (CCD based on the response surface methodology (RSM. In addition, three variables of initial pH value, initial aspirin concentration and P25 concentration were selected to assess the dependence of degradation efficiencies of aspirin. Meanwhile, a predicted model of degradation efficiency was estimated and checked using analysis of variance (ANOVA. The results indicated that the PC removal of aspirin by P25 was significantly influenced by all these variables in descending order as follows: P25 concentration > initial aspirin concentration > initial pH value. Moreover, the parameters were optimized by the CCD method. Under the conditions of an initial pH value of 5, initial aspirin concentration of 10 mg/L and P25 concentration of 50 mg/L, the degradation efficiency of aspirin was 98.9%with 60 min of Xenon lamp irradiation. Besides, based on the liquid chromatography-mass spectrometry measurements, two main PC degradation pathways of aspirin by TiO2 were deduced and the tentative degradation mechanism was also proposed.

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

    African Journals Online (AJOL)

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

  2. Aspirin for Primary Prevention of Cardiovascular Disease and Cancer. A Benefit and Harm Analysis

    NARCIS (Netherlands)

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

    2015-01-01

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

  3. 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

  4. 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…

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

    NARCIS (Netherlands)

    CHEUNG, PK; VISSER, J; BAKKER, WW

    1994-01-01

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

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

    African Journals Online (AJOL)

    1983-04-30

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

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

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

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

    International Nuclear Information System (INIS)

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

    1972-01-01

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

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

    African Journals Online (AJOL)

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

  11. 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

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

    Directory of Open Access Journals (Sweden)

    Seung-Woo Shin

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

  13. Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies.

    Science.gov (United States)

    Sadou Yayé, Hassane; Rietveld, Ivo B; Barrio, Maria; Secrétan, Philippe-Henri; Faucheron, Antoine; Karoui, Maher; Tilleul, Patrick; Yagoubi, Najet; Do, Bernard

    2017-09-30

    The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA). To improve patient adherence to such treatments, combination therapies (polypill) are envisioned. Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC). The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MS n ) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis. A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited. No cocrystals of TIC and ASA have been found. The appearance of the eutectic liquid was linked with a clear onset of chemical instability of the two pharmaceuticals. The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites. Seven interaction products were observed by LC-HR-MS n linked to corresponding degradation products. The most important degradation pathway is N-dealkylation. In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2017-12-15

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

  16. 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...

  17. Incidence of intracranial bleeds in new users of low-dose aspirin

    DEFF Research Database (Denmark)

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

    2017-01-01

    BACKGROUND: Low-dose aspirin protects against ischemic cardiovascular (CV) events as well as colorectal cancer (CRC). However, low-dose aspirin may be associated with a small increased risk of intracranial bleeds (ICB). OBJECTIVES: To obtain incidence rates of ICB overall and by patient subgroups...... among new users of low-dose aspirin. PATIENTS/METHODS: Using The Health Improvement Network (THIN) UK primary care database (2000-2012), we identified a cohort of new users of low-dose aspirin aged 40-84 years (N=199,079; mean age at start of follow-up, 63.9 years) and followed them, for up to 14 years...... estimates of the absolute risk of ICB for incorporation into risk-benefit assessments of low-dose aspirin use. This article is protected by copyright. All rights reserved....

  18. Antiplatelet therapy: views from the experts

    NARCIS (Netherlands)

    Easton, J. D.; Diener, H. C.; Bornstein, N. M.; Einhäupl, K.; Gent, M.; Kaste, M.; Sacco, R. L.; Tijssen, J. G.; van Gijn, J.

    1999-01-01

    Antiplatelet therapy is recommended for stroke prevention in persons with a history of thromboembolic stroke or transient ischemic attack (TIA) that is not of cardiac origin. Aspirin was the first antiplatelet agent to be used in this context and is still the most frequently prescribed preventive

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

    Science.gov (United States)

    Hernández-Díaz, Sonia; García Rodríguez, Luis A

    2006-09-20

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

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

    Directory of Open Access Journals (Sweden)

    García Rodríguez Luis A

    2006-09-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

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

    2015-01-01

    Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer. The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50-65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit-harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening-eradication before starting aspirin prophylaxis. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

  3. The risk of venous thromboembolism with aspirin compared to anticoagulants after hip and knee arthroplasty.

    Science.gov (United States)

    Chu, Janet N; Maselli, Judith; Auerbach, Andrew D; Fang, Margaret C

    2017-07-01

    Recent guidelines include aspirin as an option to prevent venous thromboembolism (VTE) in selected patients undergoing hip or knee replacement surgery. However, the efficacy of aspirin after arthroplasty has not been well-defined, particularly in more contemporary patient populations. We compared rates of post-operative VTE between patients who received aspirin-only versus anticoagulants after hip or knee arthroplasty, using data from a large US-based administrative database. We conducted a retrospective cohort study of 231,780 adults who underwent total knee arthroplasty and 110,621 who underwent total hip arthroplasty in 2009-2012 and who received pharmacologic VTE prophylaxis (aspirin or anticoagulant) within the first 7days after surgery. We compared the risk of post-operative VTE between patients receiving aspirin-only vs. anticoagulants, controlling for clinical and hospital characteristics using multivariable logistic regression with propensity score adjustment. Aspirin-only prophylaxis was administered to 7.5% of patients after knee arthroplasty and 8.0% after hip arthroplasty. Post-operative VTE was diagnosed in 2217 (0.96%) patients after knee arthroplasty and 454 (0.41%) after hip arthroplasty. Compared to anticoagulants, aspirin was not associated with a higher risk for post-operative VTE either after knee arthroplasty (adjusted odds ratio and 95% confidence interval [OR] 0.34 [0.24-0.48]) or hip arthroplasty (OR 0.82 [0.45-1.51]). Aspirin was uncommonly administered as the sole prophylactic agent after hip or knee arthroplasty in this study. However, patients who received aspirin-only had similar rates of post-operative VTE compared to patients who received anticoagulants. Further research should focus on distinguishing which patients benefit more from anticoagulants versus aspirin after arthroplasty. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells.

    Science.gov (United States)

    Kastrati, Irida; Delgado-Rivera, Loruhama; Georgieva, Gergana; Thatcher, Gregory R J; Frasor, Jonna

    2017-01-18

    Inflammation is a cancer hallmark that underlies cancer incidence and promotion, and eventually progression to metastasis. Therefore, adding an anti-inflammatory drug to standard cancer regiments may improve patient outcome. One such drug, aspirin (acetylsalicylic acid, ASA), has been explored for cancer chemoprevention and anti-tumor activity. Besides inhibiting the cyclooxygenase 2-prostaglandin axis, ASA's anti-cancer activities have also been attributed to nuclear factor ĸB (NFĸB) inhibition. Because prolonged ASA use may cause gastrointestinal toxicity, a prodrug strategy has been implemented successfully. In this prodrug design the carboxylic acid of ASA is masked and additional pharmacophores are incorporated. This protocol describes how we synthesized an aspirin-fumarate prodrug, GTCpFE, and characterized its inhibition of the NFĸB pathway in breast cancer cells and attenuation of the cancer stem-like properties, an important NFĸB-dependent phenotype. GTCpFE effectively inhibits the NFĸB pathway in breast cancer cell lines whereas ASA lacks any inhibitory activity, indicating that adding fumarate to ASA structure significantly contributes to its activity. In addition, GTCpFE shows significant anti-cancer stem cell activity by blocking mammosphere formation and attenuating the cancer stem cell associated CD44 + CD24 - immunophenotype. These results establish a viable strategy to develop improved anti-inflammatory drugs for chemoprevention and cancer therapy.

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

    Science.gov (United States)

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

    2017-05-01

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

  6. The role of antiplatelet therapy in primary prevention. A review

    DEFF Research Database (Denmark)

    Østergaard, Lauge Klement Moltke; Fosbøl, Emil L; Roe, Matthew T

    2017-01-01

    in individuals without established cardiovascular disease who have a relatively low, but linear trajectory of cardiovascular risk. Several large randomized trials have investigated the efficacy and safety of antiplatelet therapy (primarily aspirin) for patients without established cardiovascular disease......The efficacy of antiplatelet therapy for the secondary prevention of cardiovascular disease after an ischemic event is well established. However, the role for antiplatelet therapy for the primary prevention of cardiovascular disease is more complex because of the interplay of efficacy vs safety....... The pharmacological profile of the most commonly used primary prevention antiplatelet agent, aspirin, has been delineated by randomized clinical trials and showcased in practice guidelines for reducing cardiovascular risk. For this indication, aspirin has been consistently shown to reduce the risk of non...

  7. Selenium and aspirin in people living with HIV and AIDS in Nigeria.

    Science.gov (United States)

    Durosinmi, M A; Armistead, H; Akinola, N O; Onayemi, O; Adediran, I A; Olasode, O A; Elujoba, A A; Irinoye, O; Ogun, S A; Odusoga, O L; Falola, O L; Muraina, H A

    2008-12-01

    Aspirin and selenium have been shown in vitro and in vivo to inhibit HIV production through inhibition of the transcription factor, the nuclear factor kappa binding (NF-eB). The aim of this study was to examine the efficacy or otherwise of these drugs in people living with HIV and AIDS (PLWAS) in resource limited countries. Consenting HAART-naive PLWAS with mean CD4 count of 256.8 +/- 67.6 cells/ul were recruited into the study. Pretherapy blood count, serum biochemistry, chest x-ray, urinary glucose and protein and microscopy and culture of both urine and stool were checked in all cases. Each patient was treated for six months and CD4 counts were repeated at the end of the study. Thirty two patients (23 (72%) females and nine (28%) males), aged 22-52 (median = 36) years were recruited. Twenty-three (72%) were randomised into selenium and aspirin (SAM) and nine (28%) into selenium (SM); multivitamin was added to each arm. Eighteen (56.2%) patients completed the study. Sixteen (88.9%) patients are already on HAART since the termination of the study; one absconded and one died of disease progression. Fourteen (43.8%) of the initial 32 patients dropped out (11 (78.6%) were lost to follow-up, two (14.3%) died and one (7.1%) opted for HAART before completing the study). The post-treatment CD4 count was 293.0 +/-102.2 cells/ml, compared to the pre-therapy mean of 256.8 +/- 67.6 cells/ul, an average rise of 36.2 cells/ul, the difference was not statistically significant (p = 0.059). The post-therapy mean weight was significantly higher than the pretherapy weight, 61.6+/-15.2 kg versus 60.0+/-14.3 kg (p = 0.015). The SAM/SM combination regimen improved the quality of life of PLWAS, however, a greater number of patients and a longer period of follow up, are necessary to arrive at a more meaningful conclusion.

  8. Effects of the coadministration of Huatuo Zaizao pills and aspirin on hemorrheology and blood coagulation in rabbits

    OpenAIRE

    QU, SHUJUN; WANG, TIAN; ZHANG, JIANQIAO; SUN, XUE; YU, PENGFEI; KONG, LIANG; CHONG, YATING; QIU, XIAOLEI; FU, FENGHUA

    2013-01-01

    Huatuo Zaizao pills (HT) is a compound used in Chinese medicine for the treatment of cerebrovascular diseases. The present study aimed to investigate the effects of the coadministration of HT and aspirin on hemorrheology and blood coagulation in rabbits. Rabbits were randomly divided into the control, HT, aspirin and HT plus aspirin groups (n=5 animals per group). The rabbits were treated with HT at a dose of 1 g/kg, aspirin at a dose of 5 mg/kg or HT (1 g/kg) plus aspirin (5 mg/kg) administe...

  9. Low-dose aspirin and comorbidities are significantly related to bleeding peptic ulcers in elderly patients compared with nonelderly patients in Japan.

    Science.gov (United States)

    Higuchi, Toru; Iwakiri, Ryuichi; Hara, Megumi; Shimoda, Ryo; Sakata, Yasuhisa; Nakayama, Atsushi; Nio, Kenta; Yamaguchi, Shunsuke; Yamaguchi, Daisuke; Watanabe, Akira; Akutagawa, Takashi; Sakata, Hiroyuki; Fujimoto, Kazuma

    2014-01-01

    The present study was conducted using data accumulated from our earlier study of bleeding peptic ulcers, focusing on elderly patients. A total of 461 patients with bleeding peptic ulcers underwent emergency endoscopy at Saga Medical School Hospital between 1999 and 2011. Risk factors for bleeding peptic ulcers were compared between two groups: an elderly group (≥65 years old) and a nonelderly group (<65 years old). The relationship between drug use and age was examined using multiple logistic regression models. In the elderly group, the factors were compared between Period I (1999-2005) and Period II (2006-2011). The proportion of men and the incidence of Helicobacter pylori infection were lower in the elderly group than in the nonelderly group. The use of low-dose aspirin, antithrombotic drugs and corticosteroids, but not nonsteroidal anti-inflammatory drugs, was higher in the elderly group. A multiple logistic regression analysis of prescribed medications indicated that low-dose aspirin was more frequently used in the elderly group. The rate of comorbidities was higher and the hemoglobin levels were lower in the elderly group. The rates of rebleeding within one week and death within one month did not differ in the elderly group. Compared with that observed in Period I, the incidence of Helicobacter pylori infection was decreased and the rate of comorbidities was increased in Period II. This study indicates that factors related to bleeding peptic ulcers in elderly patients have shifted from Helicobacter pylori infection to comorbidities associated with low-dose aspirin, suggesting a close relationship between low-dose aspirin therapy and comorbidities in elderly patients with peptic ulcers.

  10. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

    Directory of Open Access Journals (Sweden)

    Nami Shrestha Palikhe

    2012-01-01

    Full Text Available Aspirin-exacerbated respiratory disease (AERD refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis.

  11. Aspirin locally disrupts the liquid-ordered phase

    Science.gov (United States)

    Alsop, Richard J.; Himbert, Sebastian; Dhaliwal, Alexander; Schmalzl, Karin; Rheinstädter, Maikel C.

    2018-02-01

    Local structure and dynamics of lipid membranes play an important role in membrane function. The diffusion of small molecules, the curvature of lipids around a protein and the existence of cholesterol-rich lipid domains (rafts) are examples for the membrane to serve as a functional interface. The collective fluctuations of lipid tails, in particular, are relevant for diffusion of membrane constituents and small molecules in and across membranes, and for structure and formation of membrane domains. We studied the effect of aspirin (acetylsalicylic acid, ASA) on local structure and dynamics of membranes composed of dimyristoylphosphocholine (DMPC) and cholesterol. Aspirin is a common analgesic, but is also used in the treatment of cholesterol. Using coherent inelastic neutron scattering experiments and molecular dynamics (MD) simulations, we present evidence that ASA binds to liquid-ordered, raft-like domains and disturbs domain organization and dampens collective fluctuations. By hydrogen-bonding to lipid molecules, ASA forms `superfluid' complexes with lipid molecules that can organize laterally in superlattices and suppress cholesterol's ordering effect.

  12. Oral anti platelet drugs in dermatology | Al Aboud | Sudanese ...

    African Journals Online (AJOL)

    An up-to-date overview of antithrombotic drugs, with their currently reported beneficial cutaneous effects and skin side effect, is presented. Attempts to balance traditional pharmacodynamic concepts with the newly described empiric benefits are made. A concise, current and useful reference for dermatologists with an ...

  13. Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations.

    Directory of Open Access Journals (Sweden)

    Harsh Sheth

    Full Text Available Regular aspirin use is associated with reduced risk of colorectal cancer (CRC. Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs. We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05. Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001. Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively, however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively; stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86 compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively, with the direction of association similar to

  14. Randomised clinical trial: prevention of recurrence of peptic ulcers by rabeprazole in patients taking low-dose aspirin.

    Science.gov (United States)

    Iwakiri, R; Higuchi, K; Kato, M; Fujishiro, M; Kinoshita, Y; Watanabe, T; Takeuchi, T; Yamauchi, M; Sanomura, M; Nakagawa, H; Sugisaki, N; Okada, Y; Ogawa, H; Arakawa, T; Fujimoto, K

    2014-10-01

    Few studies have evaluated the effects of rabeprazole on low-dose aspirin (LDA)-induced gastroduodenal injuries. To conduct a randomised, double-blind, triple-dummy, active-controlled, multicentre trial, named the PLANETARIUM study, to assess the efficacy, dose-response relationship and safety of rabeprazole for peptic ulcer recurrence in Japanese patients on long-term LDA therapy. Eligible patients had a history of endoscopically confirmed peptic ulcers and were receiving long-term LDA (81 or 100 mg/day) therapy for cardiovascular or cerebrovascular protection. Subjects were randomly segregated into three groups receiving rabeprazole 10 mg once daily (standard dose in Japan), rabeprazole 5 mg once daily, or teprenone (geranylgeranylacetone; mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of peptic ulcers over 24 weeks. Among 472 randomised subjects, 452 subjects (n = 151, 150, 151, respectively) constituted the full analysis set. The cumulative recurrence rates of peptic ulcers over 24 weeks in the 10- and 5-mg rabeprazole groups were 1.4% and 2.8%, respectively, both of which were significantly lower than that in the teprenone group (21.7%). The cumulative occurrence rate of bleeding ulcers over 24 weeks in the teprenone group was 4.6%, while bleeding ulcers were not observed in the 10- or 5-mg rabeprazole groups. Rabeprazole was well tolerated at both doses. Rabeprazole prevents the recurrence of peptic ulcers with no evidence of a major dose-response effect in subjects on low-dose aspirin therapy. © 2014 John Wiley & Sons Ltd.

  15. Glucose-lowering therapies in patients with diabetes mellitus and chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Minara Shamkhalovna Shamkhalova

    2013-11-01

    Full Text Available Expansion of diabetic population (predominantly due to type 2 diabetes mellitus with chronic kidney disease (CKD comorbidity constitutes one of the major challenges in modern medicine.Throughout the course of diabetes nephropathy development, from its debut to the terminal stage, survival rate and quality of life are lower than those of other categories of patients. This indicates crucial role of hyperglycemia in accelerated metabolic degradation typical of CKD.Renal disease severely narrows the spectrum of available glucose-lowering agents. Concurrent treatment for hypertension and dyslipidemia, as well as anti-platelet therapy and stimulation of erythropoiesis becomes a complex issue. A creative and patient-oriented approach with clear metabolic and cardiovascular goals should be instrumental in its solution.

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

    Science.gov (United States)

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

    2013-06-21

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

  17. A net clinical benefit analysis of warfarin and aspirin on stroke in patients with atrial fibrillation: a nested case–control study

    Directory of Open Access Journals (Sweden)

    Azoulay Laurent

    2012-06-01

    Full Text Available Abstract Background As the management of patients treated with anticoagulants and antiplatelet drugs entails balancing coagulation levels, we evaluated the net clinical benefit of warfarin and aspirin on stroke in a large cohort of patients with atrial fibrillation (AF. Methods A population-based cohort study of all patients at least 18 years of age with a first-ever diagnosis of chronic AF during the period 1993–2008 was conducted within the United Kingdom General Practice Research Database. A nested case–control analysis was conducted to estimate the risk of ischemic stroke and intracranial hemorrhage associated with the use of warfarin and aspirin. Cases were matched up to 10 controls on age, sex, and date of cohort entry. The adjusted net clinical benefit of warfarin and aspirin (expressed as the number of strokes prevented per 100 persons per year was calculated by subtracting the ischemic stroke rate (prevented by therapy from the intracranial hemorrhage (ICH rate (increased by therapy. Results The cohort included 70,766 patients newly-diagnosed with chronic AF, of whom 5519 experienced an ischemic stroke and 689 an ICH during follow-up. The adjusted net clinical benefit of warfarin was 0.59 (95% CI: 0.45, 0.73. However, the benefit was not seen for patients below (0.08, 95%: -0.38, 0.54 and above (−0.49, 95% CI: -1.13, 0.15 therapeutic range. The net clinical benefit of warfarin, apparent after 3 months of continuous use, increased as a function of CHADS2 score. The net clinical benefit was not significant with aspirin (−0.07, 95% CI: -0.22, 0.08, though it was seen in certain subgroups. Conclusions Warfarin provides a net clinical benefit in patients with atrial fibrillation, which is maintained with longer duration of use, particularly when used within therapeutic range. A similar net effect is not as clear with aspirin.

  18. Inhibitory Influence of Panax notoginseng Saponins on Aspirin Hydrolysis in Human Intestinal Caco-2 Cells.

    Science.gov (United States)

    Sun, Zongxi; Wu, Yali; Yang, Bing; Zhu, Baochen; Hu, Shaonan; Lu, Yang; Zhao, Bo; Du, Shouying

    2018-02-18

    Herb-drug interactions are important safety concerns in clinical practice. The interactions occur firstly in the intestinal absorption for orally administered drugs. Aspirin and Panax notoginseng saponins (PNS)-based drugs are often combined in China to prevent larger-artery atherosclerosis. Here, we aimed to characterize the aspirin transport across Caco-2 cell monolayers, a model of the intestinal absorption, and further to evaluate the influence of PNS on aspirin hydrolysis and the relating mechanisms. Transcellular transport of aspirin and the influence of PNS were explored using Caco-2 cell monolayers. The protein expression of human carboxylesterase 1 (hCE1) and hCE2 in Caco-2 cells after PNS treatment was analyzed by ELISA, and the mRNA level were determined by qRT-PCR. In the study, Caco-2 cells showed high level of hydrolase activity, and most aspirin was hydrolyzed inside the cells during the transport process. Interestingly, PNS were demonstrated to inhibit the esterase activities responsible for aspirin hydrolysis in Caco-2 cells. PNS could also decrease the protein expression of hCE1 and hCE2, whereas exhibited minor effect on the mRNA expression. These results indicated that oral administration of PNS-based drugs might inhibit the hydrolysis of aspirin during intestinal absorption thus promoting its bioavailability.

  19. Effects of aspirin on small-cell lung cancer mortality and metastatic presentation.

    Science.gov (United States)

    Maddison, Paul

    2017-04-01

    Although meta-analysis data have shown that taking regular aspirin may reduce lung cancer mortality, individual trial data results are conflicting, and the data on the effects of aspirin on different histological subtypes of lung tumours, in particular small-cell lung cancer, are sparse. We conducted a prospective observational study of 313 patients with a new diagnosis of small-cell lung cancer and recorded use of aspirin before and after tumour diagnosis. Seventy-one (23%) patients were taking regular daily aspirin for more than 2 years at the time of tumour diagnosis. We found that regular use of aspirin had no effect on survival nor metastatic presentation compared to data from small-cell lung cancer patients not taking aspirin. The lack of survival benefit in patients with small-cell lung cancer taking long-term aspirin may be due to the low expression of cyclooxygenase-2 in small-cell lung cancer tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Rivaroxaban with or without aspirin in patients with stable coronary artery disease

    DEFF Research Database (Denmark)

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

    2018-01-01

    coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100....... The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, palone did not significantly improve the primary outcome when compared with treatment...... with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p

  1. Transrectal ultrasound-guided biopsy of the prostate: aspirin increases the incidence of minor bleeding complications

    International Nuclear Information System (INIS)

    Halliwell, O.T.; Yadegafar, G.; Lane, C.; Dewbury, K.C.

    2008-01-01

    Aim: To assess whether patients taking aspirin were more likely to experience bleeding complications after transrectal ultrasound (TRUS)-guided prostate biopsy. Materials and methods: Three hundred and eighty-seven patients taking aspirin who underwent prostate biopsy over a 3.5 year period and 731 patients not taking aspirin over a 2 year period returned a questionnaire assessing the incidence and severity of bleeding complications. Results: Patients taking aspirin had a significantly higher cumulative incidence of haematuria and rectal bleeding, but not of haemospermia. They also had a longer mean duration of bleeding, but no increase in bleeding severity. Severe bleeding was very uncommon in both groups and no patients required intervention for bleeding complications. Conclusion: Aspirin exacerbates minor bleeding complications in patients undergoing TRUS guided biopsy of the prostate, but in this large group of aspirin-taking patients no dangerous bleeding complications were encountered. It may be that the risks associated with aspirin cessation outweigh the risks of haemorrhagic complications

  2. Low-Dose Aspirin in Heart Failure Not Complicated by Atrial Fibrillation

    DEFF Research Database (Denmark)

    Madelaire, Christian; Gislason, Gunnar; Kristensen, Søren L

    2018-01-01

    OBJECTIVES: This study sought to assess safety and effectiveness of low-dose aspirin in heart failure (HF) not complicated by atrial fibrillation. BACKGROUND: Despite lack of evidence, low-dose aspirin is widely used in patients with HF and sinus rhythm with and without prior ischemic heart disease....... METHODS: The study included 12,277 patients with new-onset HF during 2007 to 2012 who had no history of atrial fibrillation. Of 5,450 patients using low-dose aspirin at baseline, 3,840 were propensity matched to non-aspirin users in a 1:1 ratio. Propensity-matched Cox models were calculated with respect...... to the primary composite outcome of all-cause mortality, myocardial infarction, and stroke and the secondary outcomes of bleeding and HF readmission. RESULTS: The composite outcome occurred in 1,554 (40.5%) patients in the aspirin group and 1,604 (41.8%) patients in the non-aspirin group. Aspirin use...

  3. 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.

  4. COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss.

    Science.gov (United States)

    Crabb, Simon J; Martin, Karen; Abab, Julia; Ratcliffe, Ian; Thornton, Roger; Lineton, Ben; Ellis, Mary; Moody, Ronald; Stanton, Louise; Galanopoulou, Angeliki; Maishman, Tom; Geldart, Thomas; Bayne, Mike; Davies, Joe; Lamb, Carolynn; Popat, Sanjay; Joffe, Johnathan K; Nutting, Chris; Chester, John; Hartley, Andrew; Thomas, Gareth; Ottensmeier, Christian; Huddart, Robert; King, Emma

    2017-12-01

    Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears. Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL. Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. 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.

  6. 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.

  7. Aspirin for Stroke Prevention in Elderly Patients With Vascular Risk Factors: Japanese Primary Prevention Project.

    Science.gov (United States)

    Uchiyama, Shinichiro; Ishizuka, Naoki; Shimada, Kazuyuki; Teramoto, Tamio; Yamazaki, Tsutomu; Oikawa, Shinichi; Sugawara, Masahiro; Ando, Katsuyuki; Murata, Mitsuru; Yokoyama, Kenji; Minematsu, Kazuo; Matsumoto, Masayasu; Ikeda, Yasuo

    2016-06-01

    The effect of aspirin in primary prevention of stroke is controversial among clinical trials conducted in Western countries, and no data are available for Asian populations with a high risk of intracranial hemorrhage. The objective of this study was to evaluate the effect of aspirin on the risk of stroke and intracranial hemorrhage in the Japanese Primary Prevention Project (JPPP). A total of 14 464 patients (age, 60-85 years) with hypertension, dyslipidemia, and diabetes mellitus participated and were randomized into 2 treatment groups: 100 mg of aspirin or no aspirin. The median follow-up period was 5.02 years. The cumulative rate of fatal or nonfatal stroke was similar for the aspirin (2.068%; 95% confidence interval [CI], 1.750-2.443) and no aspirin (2.299%; 95% CI, 1.963-2.692) groups at 5 years; the estimated hazard ratio was 0.927 (95% CI, 0.741-1.160; P=0.509). Aspirin nonsignificantly reduced the risk of ischemic stroke or transient ischemic attack (hazard ratio, 0.783; 95% CI, 0.606-1.012; P=0.061) and nonsignificantly increased the risk of intracranial hemorrhage (hazard ratio, 1.463; 95% CI; 0.956-2.237; P=0.078). A Cox regression adjusted by the risk factors for all stroke, which were age >70 years, smoking, and diabetes mellitus, supported the above result. Aspirin did not show any net benefit for the primary prevention of stroke in elderly Japanese patients with risk factors for stroke, whereas age >70 years, smoking, and diabetes mellitus were risk factors for stroke regardless of aspirin treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00225849. © 2016 American Heart Association, Inc.

  8. Stability Indicating Liquid Chromatographic Method for Simultaneous determination of Aspirin and Omeprazole.

    Science.gov (United States)

    Patel, Vandana B; Patel, Aishwarya D; Shah, Dimal A

    2017-10-23

    Aspirin combination is prescribed for the its thrombolytic activity where gastric ulceration is the major side effects of aspirin which can be prevented by combining it with proton pump inhibitor omeprazole. Present study describes development of analytical method for the estimation of aspirin and omeprazole in combination. Objective of the present study was to develop and validate chromatographic method for simultaneous analysis of aspirin and omeprazole. Isocratic, reversed phase stability indicating liquid chromatographic method was developed for the simultaneous determination of Aspirin and Omeprazole in combination. The separation was achieved on a Thermo Scientific Hypersil ODS (250 x 4.6 mm, 5 µm) column, kept at ambient temperature, using acetonitrile: methanol: 0.05 M phosphate buffer (40:5:55; pH 4 adjusted with 0.1% tri ethyl amine) as a mobile phase at a flow rate of 1 mL/min and UV detection was performed at 225 nm. The retention time was found to be 3.9 min for aspirin and 5.3 min for omeprazole. The method was oberved to be linear in the range of 2 - 80 μg/mL for aspirin and 1 - 40 μg/mL for omeprazole, respectively. The proposed method was validated as per ICH guidelines Q2 (R1). The developed RP- HPLC method was successfully applied for the simultaneous estimation of aspirin and omeprazole in the presence of degradation products of both the drugs. The present study describes liquid chromatographic method for the estimation of aspirin and omeprzole in combination. The method can be used for the analysis of stability samples and routine quality control samples. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    International Nuclear Information System (INIS)

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

    1981-01-01

    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

  10. A Proteomic Approach to Analyze the Aspirin-mediated Lysine Acetylome*

    OpenAIRE

    Tatham, Michael H.; Cole, Christian; Scullion, Paul; Wilkie, Ross; Westwood, Nicholas J.; Stark, Lesley A.; Hay, Ronald T.

    2016-01-01

    This work is supported by Cancer Research UK Grant C434/A13067 (M.H.T & R.T.H) and Wellcome Trust Grant 098391/Z/12/7 (R.T.H.). Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino-acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet...

  11. Global Trends in Aspirin Resistance-Related Research from 1990 to 2015: A Bibliometric Analysis.

    Science.gov (United States)

    Al-Jabi, Samah W

    2017-12-01

    Aspirin resistance can be defined as the inability of the usual dose of aspirin medication to produce its antithrombotic effect. Patients with diabetes or cardiovascular disease are at higher risk of stroke, myocardial infarction or cardiovascular death due to aspirin resistance. The aim of this bibliometric study was to identify and analyse the status and trends of aspirin resistance research production at global level through publications indexed in the Scopus database; this will shed new light on future research trends and help researchers predict dynamic direction of research. Literature search using the Scopus database was conducted to assess publications related to aspirin resistance. The selected publications included the terms related to aspirin resistance in the title, abstract or keywords. The searching was accomplished on 20 March 2016 and can be considered to include all publications up to 31 December 2015. Global cumulative publication output on aspirin resistance consists of 986 papers during 1990-2015. Among the 986 documents, 19 (1.9%) were published before 2000, 567 (57.5%) were published from 2000 to 2009 and 400 (40.6%) were published from 2010 to 2015, with peak of publications on this topic in 2008. The leading country in the field of aspirin resistance was the United States, which had the greatest counts of independent articles (165) and international collaboration articles (44). Turkey was in the second rank with 78 articles, followed by Italy (68), the UK (62) and Poland (60). The total number of citations for all documents was 26,342, and the average citations per document were 26.7. The h-index for all aspirin resistance publications was 82. This study presents the results of the first bibliometric study (including quantitative and qualitative analysis) of scientific publications in the field of aspirin renitence at global level. Aspirin resistance-related researches have notably increased in the last years, especially from 2000 to 2015

  12. 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.

  13. 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.

  14. Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations.

    Science.gov (United States)

    Sheth, Harsh; Northwood, Emma; Ulrich, Cornelia M; Scherer, Dominique; Elliott, Faye; Barrett, Jennifer H; Forman, David; Wolf, C Roland; Smith, Gillian; Jackson, Michael S; Santibanez-Koref, Mauro; Haile, Robert; Casey, Graham; Jenkins, Mark; Win, Aung Ko; Hopper, John L; Marchand, Loic Le; Lindor, Noralane M; Thibodeau, Stephen N; Potter, John D; Burn, John; Bishop, D Timothy

    2018-01-01

    Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All Paspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer

  15. Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations

    Science.gov (United States)

    Ulrich, Cornelia M.; Scherer, Dominique; Elliott, Faye; Barrett, Jennifer H.; Forman, David; Wolf, C. Roland; Smith, Gillian; Jackson, Michael S.; Santibanez-Koref, Mauro; Haile, Robert; Casey, Graham; Jenkins, Mark; Win, Aung Ko; Hopper, John L.; Marchand, Loic Le; Lindor, Noralane M.; Thibodeau, Stephen N.; Potter, John D.; Burn, John; Bishop, D. Timothy

    2018-01-01

    Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin’s chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05). Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001). Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively), however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68–0.86; rs1105879 OR = 0.77 95% CI = 0.69–0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that

  16. Gastrointestinal risk factors and prescribing pattern of antiulcer agents in patients taking low-dose aspirin in Japan.

    Science.gov (United States)

    Iwasawa, Makiko; Wada, Kyoichi; Takada, Mitsutaka

    2017-11-21

    To identify prescribing patterns of antiulcer agents in patients on low-dose aspirin (LDA) and to evaluate the number of gastrointestinal (GI) risk factors of the patients. A retrospective chart review of patients taking LDA was conducted at the National Cerebral and Cardiovascular Center in Japan. The rate of concomitant use of antiulcer agents and the risk of each patient to develop GI complications were evaluated. Of the 314 patients, 64 were not on antiulcer agents and 55 of them had >1 risk factor. More patients not on antiulcer agents had started LDA before hospitalization. The rate of coprescribing antiulcer agents with LDA was high. However, the timing of initiating LDA therapy affected the prescribing pattern of antiulcer agents. © 2017 Royal Pharmaceutical Society.

  17. The role of nitric oxide in aspirin induced thrombolysis in vitro and the purification of aspirin activated nitric oxide synthase from human blood platelets.

    Science.gov (United States)

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

    2007-11-01

    Aspirin, a well-known inhibitor of platelet aggregation, is extensively used for the prevention/treatment of coronary artery disease. The beneficial and antithrombotic effects of the compound are related to the inhibition of platelet cyclooxygenase. It is currently believed that aspirin has no effect on the formed thrombus, which results in coronary artery disease. It was found that the exposure of platelets to 4.0 microM aspirin either in vitro or in vivo resulted in fibrinolysis of the formed "clot" produced by the recalcification of platelet-rich plasma due to the production of NO in these cells by the compound. The lysis of clot in the presence of aspirin was found to be related to the fibrinolysis with simultaneous appearance of fibrin degradation products due to the generation of serine proteinase activity by NO in the assay mixture. The aspirin activated nitric oxide synthase that catalyzed the synthesis of NO in platelets was solubilized by Triton X-100 treatment and purified to homogeneity by chromatography on DEAE cellulose and Sephadex G-50 columns. The enzyme was found to be a single chain polypeptide with M.W. 19 kDa. The treatment of human plasminogen with NO was found to directly activate the zymogen to plasmin with the production of preactivation peptide in the absence of cofactors, or cells without the formation of cyclic GMP in the assay mixture. (c) 2007 Wiley-Liss, Inc.

  18. Aspirin and other NSAIDs as chemoprevention agents in melanoma

    Science.gov (United States)

    Goodman, James R.; Grossman, Douglas

    2014-01-01

    Melanoma incidence is increasing and, despite recent therapeutic advances, the prognosis for patients with metastatic disease remains poor. Thus early detection and chemoprevention are promising strategies for improving patient outcomes. Aspirin (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) have demonstrated chemoprotective activity in several other cancers, and have been proposed as chemopreventive agents for melanoma. Throughout the last decade, however, a number of case-control, prospective, and interventional studies of NSAIDs and melanoma risk have yielded conflicting results. These inconsistent findings have led to uncertainty about the clinical utility of NSAIDs for melanoma chemoprevention. This mini-review highlights current knowledge of NSAID mechanisms of action and rationale for use in melanoma, provides a comparative review of outcomes and limitations of prior studies, and discusses the future challenges in demonstrating that these drugs are effective agents for mitigating melanoma risk. PMID:24694780

  19. Aspirin for the Prevention of Preeclampsia and Intrauterine Grow