Aspirin challenge and desensitization: how, when and why.

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Cortellini, Gabriele; Caruso, Cristiano; Romano, Antonino

2017-08-01

To investigate the current approach to aspirin challenge (drug provocation) and/or desensitization in patients with histories of hypersensitivity reactions to it, particularly in those with cardiovascular diseases. The literature indicates that patients with coronary artery disease (CAD), including those with an acute coronary syndrome, may safely undergo low-dose aspirin challenge and/or desensitization. Recently, flowcharts regarding challenge/desensitization procedures with aspirin in patients with CAD and histories of aspirin hypersensitivity reactions have become available. Aspirin desensitization and continuous aspirin therapy constitute an effective option in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory diseases (NERD) who have suboptimally controlled asthma or rhinosinusitis, or require multiple revision polypectomies. The use of aspirin has proven to reduce morbidity and mortality associated with CAD. There is a general consensus on aspirin's effectiveness in secondary prevention of CAD. Therefore, aspirin desensitization is necessary in patients with CAD and histories of hypersensitivity reactions to it. The effectiveness of aspirin desensitization and continuous therapy in patients with NERD has been shown in numerous studies. However, shared selection criteria of candidates for aspirin challenge/desensitization procedures, and simple and homogeneous protocols are necessary. Moreover, preventive safety measures are still needed in order to reduce the potential risks of these procedures.

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

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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

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

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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

Aspirin resistance following pediatric cardiac surgery.

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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.

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

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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.

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

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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.

The Role of Aspirin in the Prevention of Cardiovascular Disease

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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

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.

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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

Aspirin resistance as cardiovascular risk after kidney transplantation

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

2014-05-01

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

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.

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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.

Long-term clinical effects of aspirin-desensitization therapy among patients with poorly controlled asthma and non-steroidal anti-inflammatory drug hypersensitivity: An exploratory study

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U. Förster-Ruhrmann

2015-11-01

Full Text Available Background: According to the Global Initiative for Asthma (GINA, the levels of asthma symptom control can be divided into controlled, partially controlled and uncontrolled asthma. Optional therapy for non-steroidal anti-inflammatory drugs (NSAIDs-hypersensitive asthmatics uses aspirin desensitization, but until now, this therapy is not established in difficult to treat cases. The aim of this study was to evaluate the efficacy of aspirin desensitization in patients with poorly controlled asthma. Methods: Patients with poorly controlled asthma, NDAIDs hypersensitivity and aspirin desensitization were included in the retrospective study. The data were compared to those obtained from patients with controlled asthma and aspirin therapy. Lung function, levels of asthma symptom control, asthma medication, the size of nasal polyps (NP and smell function were evaluated over 18 months. Results: Thirty-two patients were included in the study (uncontrolled/partially controlled asthma n = 12; controlled asthma n = 20. After 18 months of follow-up, the patients with poorly controlled asthma had significantly increased forced expiratory volume in 1 s (FEV1 values, as compared to the baseline (66–82%; p = 0.02, the levels of asthma control improved significantly (p  0.05 and the asthma medication was constant. In relation to nasal parameters the sense of smell improved significantly in both groups, NP-scores did not differ significantly. Conclusions: Patients with a poorly controlled asthma and NSAIDs hypersensitivity profit from an add-on aspirin therapy. Keywords: Asthma, Levels of asthma symptom control, GINA, Uncontrolled asthma, Aspirin-exacerbated respiratory disease (AERD, NSAIDs hypersensitivity, NSAIDs sensitive asthma, Nasal polyps

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

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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.

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.

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

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Rouhl, R P W; Lodder, J

2008-11-01

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

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

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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.

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

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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.

Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

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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.

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

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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.

Role of Aspirin in Breast Cancer Survival.

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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.

Early aspirin use and the development of cardiac allograft vasculopathy.

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Kim, Miae; Bergmark, Brian A; Zelniker, Thomas A; Mehra, Mandeep R; Stewart, Garrick C; Page, Deborah S; Woodcome, Erica L; Smallwood, Jennifer A; Gabardi, Steven; Givertz, Michael M

2017-12-01

Cardiac allograft vasculopathy (CAV) remains a leading cause of morbidity and mortality after orthotopic heart transplantation (OHT). Little is known about the influence of aspirin on clinical expression of CAV. We followed 120 patients with OHT at a single center for a median of 7 years and categorized them by the presence or absence of early aspirin therapy post-transplant (aspirin treatment ≥6 months in the first year). The association between aspirin use and time to the primary end-point of angiographic moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) was investigated. Propensity scores for aspirin treatment were estimated using boosting models and applied by inverse probability of treatment weighting (IPTW). Despite a preponderance of risk factors for CAV among patients receiving aspirin (male sex, ischemic heart disease as the etiology of heart failure, and smoking), aspirin therapy was associated with a lower rate of moderate or severe CAV at 5 years. Event-free survival was 95.9% for patients exposed to aspirin compared with 79.6% for patients without aspirin exposure (log-rank p = 0.005). IPTW-weighted Cox regression revealed a powerful inverse association between aspirin use and moderate to severe CAV (adjusted hazard ratio 0.13; 95% confidence interval 0.03-0.59), which was directionally consistent for CAV of any severity (adjusted hazard ratio 0.50; 95% confidence interval 0.23-1.08). This propensity score-based comparative observational analysis suggests that early aspirin exposure may be associated with a reduced risk of development of moderate to severe CAV. These findings warrant prospective validation in controlled investigations. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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

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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.

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

Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

DEFF Research Database (Denmark)

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

2017-01-01

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

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

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

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

2006-05-20

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

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

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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.

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

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

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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.

Dipyridamole plus aspirin versus aspirin alone in the secondary prevention after TIA or stroke: a meta-analysis by risk

OpenAIRE

Halkes, P.H.A.; Gray, Laura J.; Bath, Philip M.W.; Diener, Hans-Christoph; Guiraud-Chaumeil, B.

2008-01-01

Objectives: Our aim was to study the effect of combination therapy with aspirin and dipyridamole (A+D) over aspirin alone (ASA) in secondary prevention after transient \\ud ischemic attack or minor stroke of presumed arterial origin and to perform subgroup analyses to identify patients that might benefit most from secondary prevention with A+D.\\ud Data sources: The previously published meta-analysis of individual patient data was updated with data from ESPRIT (N=2,739); trials without data on ...

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)

Aspirin Desensitization

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... 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 " ...

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

Aspirin overdose

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... 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 ...

Continuous Aspirin Use Does Not Increase Bleeding Risk of Split-Thickness Skin Transplantation Repair to Chronic Wounds.

Science.gov (United States)

Sun, Yanwei; Wang, Yibing; Li, Liang; Zhang, Zheng; Wang, Ning; Wu, Dan

Discontinuation of aspirin therapy before cutaneous surgery may cause serious complications. The aim of this prospective study was to evaluate the bleeding risk of split-thickness skin transplantation repair to chronic wounds in patients on aspirin therapy. A total of 97 patients who underwent split-thickness skin transplantation surgery of chronic wounds during a 2-year period were enrolled. They were categorized on the basis of aspirin therapies. The primary outcome was postoperative bleeding and bleeding complications. Univariate analysis was performed to examine the association between aspirin and bleeding complications. Among the 26 patients taking aspirin continuously in group A, there were 5 bleeding complications (19.23%). Among the 55 nonusers in group B, there were 10 bleeding complications (18.18%). Among the 16 discontinuous patients in group C, there were 3 bleeding complications (18.75%). No statistical differences were found among the groups ( P = .956). Univariate analysis showed that continuous aspirin use was not significantly associated with bleeding complications (odds ratio, 0.933; 95% confidence interval, 0.283-3.074; P = .910 in the aspirin and control groups) and that discontinuous aspirin use was not significantly associated with bleeding complications (odds ratio, 0.963; 95% confidence interval, 0.230-4.025; P = .959 in the aspirin and control groups; odds ratio, 0.969; 95% confidence interval, 0.198-4.752; P = .969 in the aspirin and discontinuous groups). Continuous aspirin use does not produce an additional bleeding risk in patients who undergo split-thickness skin transplantation repair of chronic wounds.

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)

Aspirin overutilization for the primary prevention of cardiovascular disease

Directory of Open Access Journals (Sweden)

VanWormer JJ

2014-12-01

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

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

DEFF Research Database (Denmark)

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

2014-01-01

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

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...

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

Directory of Open Access Journals (Sweden)

Isnatin Miladiyah

2016-01-01

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

Aspirin in the Management of Patients with Prostate Cancer Undergoing Radiotherapy: Friend or Foe?

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Mascan, Bianca; Marignol, Laure

2018-04-01

Aspirin has cyclooxygenase-2 (COX2)-mediated anti-inflammatory and anti-coagulant properties that may confer a positive effect in preventing and limiting the progression of prostate cancer. Prostate cancer has been shown to have poor treatment outcomes due to therapeutic resistance; therefore, COX2 inhibition caused by aspirin could represent an opportunity to augment current therapies. This is particularly of interest to patients undergoing radiation therapy (RT) where inflammation is a common side-effect. This review discusses the evidence for the potential role of aspirin in the management of patients with prostate cancer undergoing RT. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

An assessment of aspirin use in a Nigerian diabetes outpatient clinic.

Science.gov (United States)

Kolawole, B A; Adebayo, R A; Aloba, O O

2004-01-01

We have conducted this study to assess the use of aspirin among adult diabetic outpatients in our hospital. The records of all patients attending the weekly Diabetes clinic of the Wesley Guild Hospital (WGH), Ilesa, Osun state, Nigeria over one month were reviewed and aspirin use evaluated in light of the American Diabetes Association position statement (2003) on aspirin therapy in diabetes. Eighty-two patients in all were studied. Fourty three (52.4%) were males, 39 (47.6%) were females. Their mean age was 59.1 +/- 10.7 yrs (range 31-81). All were type 2 and had been diabetic for a mean of 5.2 +/- 5.7 yrs (1-26yrs). Concurrent hypertension, another major risk factor for cardiovascular disease was found in 71.9% and 12.2% were obese. Aspirin use was contraindicated in 1.2%. All other patients had at least one indication for the use of aspirin based on the ADA criteria but only 39% were taking aspirin regularly. The results of this present study suggest that aspirin is still grossly under utilised in clinic patients with diabetes despite proven benefits. There is need to stimulate awareness amongst health care providers.

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 ...

Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma.

Science.gov (United States)

Niesvizky, Ruben; Martínez-Baños, Déborah; Jalbrzikowski, Jessica; Christos, Paul; Furst, Jessica; De Sancho, Maria; Mark, Tomer; Pearse, Roger; Mazumdar, Madhu; Zafar, Faiza; Pekle, Karen; Leonard, John; Jayabalan, David; Coleman, Morton

2007-12-01

Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.

Aspirin and Omeprazole

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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 ...

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

International Nuclear Information System (INIS)

Ibrahim, M.F.

2013-01-01

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

Transdermal estrogen gel and oral aspirin combination therapy improves fertility prognosis via the promotion of endometrial receptivity in moderate to severe intrauterine adhesion

Science.gov (United States)

Chi, Yugang; He, Ping; Lei, Li; Lan, Yi; Hu, Jianguo; Meng, Ying; Hu, Lina

2018-01-01

Intrauterine adhesion (IUA) is one of the most common gynecological diseases in women of reproductive age. IUA, particularlyin moderate to severe forms, accounts for a large percentage of infertility cases. Clinically, the first-line treatment strategy for IUA is transcervical resection of adhesion (TCRA), followed by adjuvant postoperative treatment. Estrogen is one of the classic chemotherapies used following TCRA and contributes to preventing re-adhesion following surgery. However, estrogen has limited effects in promoting pregnancy, which is the ultimate goal for IUA management. In the present study, a transdermal estrogen gel and oral aspirin combination therapy was used in patients with IUA following TCRA. Compared with in the control group (transdermal estrogen only therapy), the combination therapy significantly increased endometrial receptivity marker (αvβ٣ and laminin) expression in endometrium tissues. Additionally, ultrasonic examination revealed the pulsatility index and resistant index of the uterine artery were lower in the combination therapy group. Combination therapy promoted angiogenesis and prevented fibrosis following TCRA more effectively than estrogen-only therapy. Collectively, the evaluation indices, including American Fertility Society score, endometrial parameters and pregnancy rate, indicated that patients with combination therapy had better prognoses in endometrial repair and pregnancy. In conclusion, postoperative combination therapy with transdermal estrogen gel and oral aspirin may be more efficacious in enhancing endometrial receptivity by increasing uterine blood and angiogenesis, contributing to improved fertility prognosis. The findings of the present study may provide novel guidance to the clinical treatment of IUA. PMID:29512784

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

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

DEFF Research Database (Denmark)

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

2009-01-01

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

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.

Effect of addition of clopidogrel to aspirin on subdural hematoma: meta-analysis of randomized clinical trials.

Science.gov (United States)

Bakheet, Majid F; Pearce, Lesly A; Hart, Robert G

2015-06-01

Clopidogrel combined with aspirin is routinely prescribed after coronary artery stenting, in patients with acute coronary syndromes, and recently to prevent stroke in patients with acute minor ischemic stroke and TIA. Subdural hematomas are an important complication of antithrombotic treatment, but the risk associated with clopidogrel plus aspirin has not been previously defined. To quantify the risk of subdural hematoma associated with dual antiplatelet therapy with clopidogrel plus aspirin. Randomized clinical trials comparing clopidogrel plus aspirin with aspirin alone were identified by searching the Cochrane Central Register of Controlled Trials from 1990 to 2014, and restricted to those with more than 7 days of treatment. Two reviewers independently extracted data about subdural hematomas. Of 24 randomized trials testing clopidogrel added to aspirin, results for subdural hematoma were available for 11 trials, of which eight did not identify any subdural hematomas. The three trials reporting subdural hematomas were double-blind and included patients with recent lacunar stroke, acute coronary syndromes or atrial fibrillation with a total of 23,136 patients (mean age 66 years) and reported 39 subdural hematomas during a mean follow-up 2.1 years per patient. Clopidogrel plus aspirin was associated with a significantly increased risk of subdural hematoma compared with aspirin alone (risk ratio 2.0, 95% CI 1.0, 3.8; P = 0.04; fixed effects model; I2 for heterogeneity of 0%, P = 0.51). The average absolute incidence of subdural hematoma averaged 1.1 (95% CI 0.7,1.6) per 1000 patient - years among those assigned clopidogrel plus aspirin in 11 randomized trials. The absolute rate of subdural hematoma during dual antiplatelet therapy is low, averaging 1.1 per 1000 patient-years. Chronic treatment with clopidogrel plus aspirin significantly increases the risk of subdural hematoma compared with aspirin alone. © 2014 World Stroke Organization.

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

DEFF Research Database (Denmark)

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

2017-01-01

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

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.

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.

Preoperative Aspirin Does Not Increase Transfusion or Reoperation in Isolated Valve Surgery.

Science.gov (United States)

Goldhammer, Jordan E; Herman, Corey R; Berguson, Mark W; Torjman, Marc C; Epstein, Richard H; Sun, Jian-Zhong

2017-10-01

Preoperative aspirin has been studied in patients undergoing isolated coronary artery bypass graft surgery. However, there is a paucity of clinical data available evaluating perioperative aspirin in other cardiac surgical procedures. This study was designed to investigate the effects of aspirin on bleeding and transfusion in patients undergoing non-emergent, isolated, heart valve repair or replacement. Retrospective, cohort study. Academic medical center. A total of 694 consecutive patients having non-emergent, isolated, valve repair or replacement surgery at an academic medical center were identified. Of the 488 patients who met inclusion criteria, 2 groups were defined based on their preoperative use of aspirin: those taking (n = 282), and those not taking (n = 206) aspirin within 5 days of surgery. Binary logistic regression was used to examine relationships among demographic and clinical variables. No significant difference was found between the aspirin and non-aspirin groups with respect to the percentage receiving red blood cell (RBC) transfusion, mean RBC units transfused in those who required transfusion, massive transfusion of RBC, or amounts of fresh frozen plasma, cryoprecipitate, or platelets. Aspirin was not associated with an increase in the rate of re-exploration for bleeding (5.3% v 6.3%, p = 0.478). Major adverse cardiocerebral events (MACE), 30-day mortality, and 30-day readmission rates were not statistically different between the aspirin-and non-aspirin-treated groups. Preoperative aspirin therapy in elective, isolated, valve surgery did not result in an increase in transfusion or reoperation for bleeding and was not associated with reduced readmission rate, MACE, or 30-day mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

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

[Aspirin and colorectal cancer].

Science.gov (United States)

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

2018-02-01

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

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.

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

Effect of Ticagrelor Plus Aspirin, Ticagrelor Alone, or Aspirin Alone on Saphenous Vein Graft Patency 1 Year After Coronary Artery Bypass Grafting: A Randomized Clinical Trial.

Science.gov (United States)

Zhao, Qiang; Zhu, Yunpeng; Xu, Zhiyun; Cheng, Zhaoyun; Mei, Ju; Chen, Xin; Wang, Xiaowei

2018-04-24

The effect of ticagrelor with or without aspirin on saphenous vein graft patency in patients undergoing coronary artery bypass grafting (CABG) is unknown. To compare the effect of ticagrelor + aspirin or ticagrelor alone vs aspirin alone on saphenous vein graft patency 1 year after CABG. Randomized, multicenter, open-label, clinical trial among 6 tertiary hospitals in China. Eligible patients were aged 18 to 80 years with indications for elective CABG. Patients requiring urgent revascularization, concomitant cardiac surgery, dual antiplatelet or vitamin K antagonist therapy post-CABG, and who were at risk of serious bleeding were excluded. From July 2014 until November 2015, 1256 patients were identified and 500 were enrolled. Follow-up was completed in January 2017. Patients were randomized (1:1:1) to start ticagrelor (90 mg twice daily) + aspirin (100 mg once daily) (n = 168), ticagrelor (90 mg twice daily) (n = 166), or aspirin (100 mg once daily) (n = 166) within 24 hours post-CABG. Neither patients nor treating physicians were blinded to allocation. Primary outcome was saphenous vein graft patency 1 year after CABG (FitzGibbon grade A) adjudicated independently by a committee blinded to allocation. Saphenous vein graft patency was assessed by multislice computed tomographic angiography or coronary angiography. Among 500 randomized patients (mean age, 63.6 years; women, 91 [18.2%]), 461 (92.2%) completed the trial. Saphenous vein graft patency rates 1 year post-CABG were 88.7% (432 of 487 vein grafts) with ticagrelor + aspirin; 82.8% (404 of 488 vein grafts) with ticagrelor alone; and 76.5% (371 of 485 vein grafts) with aspirin alone. The difference between ticagrelor + aspirin vs aspirin alone was statistically significant (12.2% [95% CI, 5.2% to 19.2%]; P aspirin alone was not statistically significant (6.3% [95% CI, -1.1% to 13.7%]; P = .10). Five major bleeding episodes occurred during 1 year of follow-up (3 with

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.

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.

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; Middeldorp, Saskia

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

Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease.

Science.gov (United States)

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

2017-08-05

Increased platelet aggregation during antiplatelet therapy may predict cardiovascular events in patients with coronary artery disease. The majority of these patients receive aspirin monotherapy. We aimed to investigate whether high platelet-aggregation levels predict cardiovascular events in stable coronary artery disease patients treated with aspirin. We included 900 stable coronary artery disease patients with either previous myocardial infarction, type 2 diabetes mellitus, or both. All patients received single antithrombotic therapy with 75 mg aspirin daily. Platelet aggregation was evaluated 1 hour after aspirin intake using the VerifyNow Aspirin Assay (Accriva Diagnostics) and Multiplate Analyzer (Roche; agonists: arachidonic acid and collagen). Adherence to aspirin was confirmed by serum thromboxane B 2 . The primary end point was the composite of nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. At 3-year follow-up, 78 primary end points were registered. The primary end point did not occur more frequently in patients with high platelet-aggregation levels (first versus fourth quartile) assessed by VerifyNow (hazard ratio: 0.5 [95% CI, 0.3-1.1], P =0.08) or Multiplate using arachidonic acid (hazard ratio: 1.0 [95% CI, 0.5-2.1], P =0.92) or collagen (hazard ratio: 1.4 [95% CI, 0.7-2.8], P =0.38). Similar results were found for the composite secondary end point (nonfatal myocardial infarction, ischemic stroke, stent thrombosis, and all-cause death) and the single end points. Thromboxane B 2 levels did not predict any end points. Renal insufficiency was the only clinical risk factor predicting the primary and secondary end points. This study is the largest to investigate platelet aggregation in stable coronary artery disease patients receiving aspirin as single antithrombotic therapy. We found that high platelet-aggregation levels did not predict cardiovascular events. © 2017 The Authors. Published on behalf of the American Heart

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

Effects of preoperative aspirin and clopidogrel therapy on perioperative blood loss and blood transfusion requirements in patients undergoing off-pump coronary artery bypass graft surgery.

Science.gov (United States)

Shim, Jae Kwang; Choi, Yong Seon; Oh, Young Jun; Bang, Sou Ouk; Yoo, Kyung Jong; Kwak, Young Lan

2007-07-01

Preoperative exposure to clopidogrel and aspirin significantly increases postoperative bleeding in patients undergoing on-pump coronary artery bypass graft surgery. Off-pump coronary bypass grafting has been proposed as an alternative technique to attenuate postoperative bleeding associated with clopidogrel. This study aimed to determine the effects of aspirin and clopidogrel therapy on perioperative blood loss and blood transfusion requirements in off-pump coronary artery bypass grafting. One hundred six patients scheduled for off-pump coronary artery bypass grafting were divided into three groups: aspirin and clopidogrel discontinued more than 6 days before surgery (group 1, n = 35), aspirin and clopidogrel continued until 3 to 5 days before surgery (group 2, n = 51), and both medications continued within 2 days of surgery (group 3, n = 20). Thromboelastographic tracings were analyzed before induction of anesthesia. Routine coagulation profiles were measured before and after surgery. A cell salvage device was used during surgery and salvaged blood was reinfused. Chest tube drainage and blood transfusion requirement were recorded postoperatively. Patient characteristics, operative data, and thromboelastographic tracings were similar among the groups. There were significant decreases in hematocrit level and platelet count and prolongation in prothrombin time postoperatively in all groups without any intergroup differences. The amounts of perioperative blood loss and blood transfusion required were all similar among the groups. Preoperative clopidogrel and aspirin exposure even within 2 days of surgery does not increase perioperative blood loss and blood transfusion requirements in patients undergoing elective off-pump coronary artery bypass grafting.

Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

Directory of Open Access Journals (Sweden)

Marcella Goetz MORO

Full Text Available Abstract The consumption of low-dose aspirin (LDA to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib and a non-selective COX-2 inhibitor (ibuprofen nonsteroidal anti-inflammatory drug (NSAID in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p 0.05. These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.

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

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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

Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

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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.

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

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

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

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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.

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

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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.

Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice.

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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

Taking Aspirin to Protect Your Heart

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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 ...

Aspirin increases mitochondrial fatty acid oxidation

International Nuclear Information System (INIS)

Uppala, Radha; Dudiak, Brianne; Beck, Megan E.; Bharathi, Sivakama S.; Zhang, Yuxun; Stolz, Donna B.; Goetzman, Eric S.

2017-01-01

The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse the mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders. - Highlights: • Aspirin increases mitochondrial—but inhibits peroxisomal—fatty acid oxidation. • Aspirin acetylates mitochondrial proteins including fatty acid oxidation enzymes. • SIRT3 does not influence the effect of aspirin on fatty acid oxidation. • Increased fatty acid oxidation is likely due to altered mitochondrial morphology and respiration.

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.

Lower mortality rate in elderly patients with community-onset pneumonia on treatment with aspirin.

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

2015-01-06

Pneumonia is complicated by high rate of mortality and cardiovascular events (CVEs). The potential benefit of aspirin, which lowers platelet aggregation by inhibition of thromboxane A2 production, is still unclear. The aim of the study was to assess the impact of aspirin on mortality in patients with pneumonia. Consecutive patients admitted to the University-Hospital Policlinico Umberto I (Rome, Italy) with community-onset pneumonia were recruited and prospectively followed up until discharge or death. The primary end point was the occurrence of death up to 30 days after admission; the secondary end point was the intrahospital incidence of nonfatal myocardial infarction and ischemic stroke. One thousand and five patients (age, 74.7±15.1 years) were included in the study: 390 were receiving aspirin (100 mg/day) at the time of hospitalization, whereas 615 patients were aspirin free. During the follow-up, 16.2% of patients died; among these, 19 (4.9%) were aspirin users and 144 (23.4%; PFiO(2) ratio <300 negatively influenced survival, whereas aspirin therapy was associated with improved survival. Compared to patients receiving aspirin, the propensity score adjusted analysis confirmed that patients not taking aspirin had a hazard ratio of 2.07 (1.08 to 3.98; P=0.029) for total mortality. This study shows that chronic aspirin use is associated with lower mortality rate within 30 days after hospital admission in a large cohort of patients with pneumonia. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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 ...

Aspirin in patients undergoing noncardiac surgery

DEFF Research Database (Denmark)

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

2014-01-01

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

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

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).

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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

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

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

2014-01-01

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

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...

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

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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.

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 ...

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)

Aspirin, Butalbital, and Caffeine

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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 ...

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

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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.

Long-term efficacy of aspirin desensitization in aspirin-exacerbated respiratory disease. Review of two clinical cases

Directory of Open Access Journals (Sweden)

Julio César Cambray-Gutiérrez

2016-05-01

Clinical cases: two patients diagnosed with respiratory disease exacerbated by aspirin, with poor asthma control and need for multiple polypectomies, despite optimal pharmacological management, carrying out protocol desensitization to aspirin (AAS successful, now after 4 years of having carried out, they have adequate asthma control without need for polypectomies with a maintenance dose of aspirin 150 mg/day.

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

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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.

Comparison and analysis on the serum-binding characteristics of aspirin-zinc complex and aspirin.

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Zhang, Hua-Xin; Zhang, Qun; Wang, Hong-Lin; Li, Li-Wei

2017-09-01

This study was designed to compare the protein-binding characteristics of aspirin-zinc complex (AZN) with those of aspirin itself. AZN was synthesized and interacted with a model transport protein, human serum albumin (HSA). Three-dimensional fluorescence, ultraviolet-visible and circular dichroism (CD) spectra were used to characterize the interaction of AZN with HSA under physiological conditions. The interaction mechanism was explored using a fluorescence quenching method and thermodynamic calculation. The binding site and binding locality of AZN on HSA were demonstrated using a fluorescence probe technique and Förster non-radiation energy transfer theory. Synchronous fluorescence and CD spectra were employed to reveal the effect of AZN on the native conformation of the protein. The HSA-binding results for AZN were compared with those for aspirin under consistent experimental conditions, and indicated that aspirin acts as a guide in AZN when binding to Sudlow's site I, in subdomain IIA of the HSA molecule. Moreover, compared with aspirin, AZN showed greater observed binding constants with, but smaller changes in the α-helicity of, HSA, which proved that AZN might be easier to transport and have less toxicity in vivo. Copyright © 2017 John Wiley & Sons, Ltd.

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

Mechanisms of aspirin-sensitive asthma

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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

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

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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

Aspirin for primary prevention of cardiovascular events: meta-analysis of randomized controlled trials and subgroup analysis by sex and diabetes status.

Directory of Open Access Journals (Sweden)

Manling Xie

Full Text Available To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status.We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12.Fourteen trials (107,686 participants were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85-0.95, myocardial infarction (0.86; 0.75-0.93, ischemic stroke (0.86; 0.75-0.98 and all-cause mortality (0.94; 0.89-0.99. There were also increases in hemorrhagic stroke (1.34; 1.01-1.79 and major bleeding (1.55; 1.35-1.78 with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59-0.85 and ischemic stroke among women (0.77; 0.63-0.93. Aspirin use was associated with a reduction (0.65; 0.51-0.82 in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day were as large as those obtained with higher doses (650 mg/day.The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials.

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

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

2015-09-01

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

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

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

2013-01-01

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

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

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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.

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

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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

Acetaminophen and aspirin inhibit superoxide anion generation and lipid peroxidation, and protect against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats.

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Maharaj, D S; Saravanan, K S; Maharaj, H; Mohanakumar, K P; Daya, S

2004-04-01

We assessed the antioxidant activity of non-narcotic analgesics, acetaminophen and aspirin in rat brain homogenates and neuroprotective effects in vivo in rats intranigrally treated with 1-methyl-4-phenyl pyridinium (MPP+). Both drugs inhibited cyanide-induced superoxide anion generation, as well as lipid peroxidation in rat brain homogenates, the combination of the agents resulting in a potentiation of this effect. Acetaminophen or aspirin when administered alone or in combination, did not alter dopamine (DA) levels in the forebrain or in the striatum. Intranigral infusion of MPP+ in rats caused severe depletion of striatal DA levels in the ipsilateral striatum in rats by the third day. Systemic post-treatment of acetaminophen afforded partial protection, whereas similar treatment of aspirin resulted in complete blockade of MPP+-induced striatal DA depletion. While these findings suggest usefulness of non-narcotic analgesics in neuroprotective therapy in neurodegenerative diseases, aspirin appears to be a potential candidate in prophylactic as well as in adjuvant therapy in Parkinson's disease.

New use of low-dose aspirin and risk of colorectal cancer by stage at diagnosis: a nested case-control study in UK general practice.

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García Rodríguez, Luis A; Soriano-Gabarró, Montse; Bromley, Susan; Lanas, Angel; Cea Soriano, Lucía

2017-09-07

Evidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease. We investigated the risk of CRC among new-users of low-dose aspirin (75-300 mg), including risk by stage at diagnosis. Using The Health Improvement Network, we conducted a cohort study with nested case-control analysis. Two cohorts (N = 170,336 each) aged 40-89 years from 2000 to 2009 and free of cancer were identified: i) new-users of low-dose aspirin, ii) non-users of low-dose aspirin, at start of follow-up, matched by age, sex and previous primary care practitioner visits. Patients were followed for up to 12 years to identify incident CRC. 10,000 frequency-matched controls were selected by incidence density sampling where the odds ratio is an unbiased estimator of the incidence rate ratio (RR). RRs with 95% confidence intervals were calculated. Low-dose aspirin use was classified 'as-treated' independent from baseline exposure status to account for changes in exposure during follow-up. Current users of low-dose aspirin (use on the index date or in the previous 90 days) had a significantly reduced risk of CRC, RR 0.66 (95% CI 0.60-0.74). The reduction in risk was apparent across all age groups, and was unrelated to dose, indication, gender, CRC location or case-fatality status. Reduced risks occurred throughout treatment duration and with all low-dose aspirin doses. RRs by aspirin indication were 0.71 (0·63-0·79) and 0.60 (0.53-0.68) for primary and secondary cardiovascular protection, respectively. Among cases with staging information (n = 1421), RRs for current use of low-dose aspirin were 0.94 (0.66-1.33) for Dukes Stage A CRC, 0.54 (0.42-0.68) for Dukes B, 0.71 (0.56-0.91) for Dukes C, and 0.60 (0.48-0.74) for Dukes D. After 5 years' therapy, the RR for Dukes Stage A CRC was 0.53 (0.24-1.19). Patients starting low-dose aspirin therapy have a reduced

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

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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...

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

Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers.

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Nishino, Masafumi; Sugimoto, Mitsushige; Kodaira, Chise; Yamade, Mihoko; Uotani, Takahiro; Shirai, Naohito; Ikuma, Mutsuhiro; Tanaka, Tatsuo; Sugimura, Haruhiko; Hishida, Akira; Furuta, Takahisa

2011-07-01

The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen. Aspirin induced gastric mucosal injury (median MLS = 3). Lansoprazole significantly decreased MLS to 0, which was significantly lower than that by famotidine (MLS = 1) (P lansoprazole regimen were significantly higher than those with famotidine (P lansoprazole appeared to be more protective than famotidine against low-dose aspirin-induced mucosal injury but a larger well-controlled study is necessary to establish a definitive clinical benefit.

The effect of aspirin nanoemulsion on TNFα and iNOS in gastric tissue in comparison with conventional aspirin

Directory of Open Access Journals (Sweden)

Mahmoud FA

2015-08-01

Full Text Available Fatma Abd Elhalim Mahmoud,1,2 Khalid S Hashem,3 Asmaa Mohammed M Hussein Elkelawy21Medical Pharmacology Department, Faculty of Medicine, Cairo University, Giza, 2Clinical Pharmacology Department, Faculty of Medicine, 3Biochemistry Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, EgyptBackground: No dose of aspirin is free of bleeding risk. Even at a dose as low as 75 mg/day, the risk of upper gastrointestinal bleeding is twice as high as among nonusers. Nanoemulsions (NEs are emulsion systems with droplet size in nanometer scale in which oil or water droplets are finely dispersed in the opposite phase with the help of a suitable surfactant to stabilize the system.Objectives: The objective of this study was to determine the effect of aspirin NE in comparison to conventional aspirin.Materials and methods: A total of 24 male rats were used in the study and arbitrarily assigned to four groups. Group 1 was the control group, and was given saline. Group 2 was given blank NE 1.5 mL/kg orally. Group 3 was given aspirin 30 mg/kg body weight orally. Group 4 was given aspirin NE 30 mg/kg body weight orally. Rats were killed, and gastric tissue was quickly excised after dissection of the animals. The tissues were divided into three pieces. The first one was kept in formalin 10% for pathological investigation. The second piece was kept in liquid nitrogen for molecular investigation. The third piece was homogenized in ten volumes of ice-cold phosphate-buffered saline (pH 7 using a Teflon homogenizer until a uniform suspension was obtained. The homogenate was centrifuged at 4,000 rpm for 30 minutes at 4°C to separate the supernatant from cellular debris. The supernatant was then used for the estimation of biochemical assays.Results: The present study shows that aspirin has a toxic effect on the stomach as a result of inducing marked oxidative damage and the release of reactive oxygen species. This was shown by the significant

Aspirin to Zoloft: Ways Medicines Work

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

Application of a radiotelemetric system to evaluate the performance of enteric coated and plain aspirin tablets.

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Lui, C Y; Oberle, R; Fleisher, D; Amidon, G L

1986-05-01

The bioavailability of enteric coated and plain aspirin tablets was studied in four beagle dogs. Blood sampling for enteric coated tablets was planned with the aid of a radiotelemetric system. The release of aspirin from its dosage form was detected by monitoring the change in intestinal pH. Aspirin and salicylic acid levels in plasma obtained from the enteric coated dosage form exhibited familiar concentration versus time absorption profiles. Variation in the plasma concentrations of these two compounds within each dog studied (four runs each) was relatively small when time zero was adjusted to the commencement of tablet dissolution. The plasma levels obtained from plain aspirin (three runs each), however, show atypical absorption. The estimated absolute bioavailability was 0.432 +/- 0.0213 and 0.527 +/- 0.0260 for enteric coated and plain aspirin, respectively. Other pharmacokinetic parameters for these two dosage forms such as the highest observed plasma concentration (Cmax) (10.9 +/- 0.535 microgram/mL versus 13.6 +/- 1.88 micrograms/mL) and the time to reach Cmax (tmax) (26.6 +/- 1.94 min versus 31.0 +/- 7.04 min) agree well. The mean values for gastric emptying time, in vivo coating dissolution time, and in vivo disintegration/dissolution time of the tablet core for enteric coated aspirin are 48.7 +/- 7.23 min, 44.3 +/- 3.80 min, and 34.7 +/- 2.04 min, respectively.

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

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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

Rivaroxaban with or without aspirin in stable cardiovascular disease

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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

Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.

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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 .).

Aspirin and lipid mediators in the cardiovascular system.

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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.

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)

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

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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.

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

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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.

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.

Up-regulation of Ciliary Neurotrophic Factor in Astrocytes by Aspirin

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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

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

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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.

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

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

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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

Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

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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

Talk with Your Doctor about Taking Aspirin Every Day

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... t sure why this works. Can taking aspirin every day cause any side effects? Taking aspirin isn't ... read these benefits and risks of taking aspirin every day . Next section Talk with Your Doctor Previous section ...

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.

A Proteomic Approach to Analyze the Aspirin-mediated Lysine Acetylome*

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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

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

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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.

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

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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.

A Review on the Relationship between Aspirin and Bone Health

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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.

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

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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).

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...

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

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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

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

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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.

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

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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.

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

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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.

Aspirin is first-line treatment for migraine and episodic tension-type headache regardless of headache intensity.

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Lampl, Christian; Voelker, Michael; Steiner, Timothy J

2012-01-01

(1) To establish whether pre-treatment headache intensity in migraine or episodic tension-type headache (ETTH) predicts success or failure of treatment with aspirin; and (2) to reflect, accordingly, on the place of aspirin in the management of these disorders. Stepped care in migraine management uses symptomatic treatments as first-line, reserving triptans for those in whom this proves ineffective. Stratified care chooses between symptomatic therapy and triptans as first-line on an individual basis according to perceived illness severity. We questioned the 2 assumptions underpinning stratified care in migraine that greater illness severity: (1) reflects greater need; and (2) is a risk factor for failure of symptomatic treatment but not of triptans. With regard to the first assumption, we developed a rhetorical argument that need for treatment is underpinned by expectation of benefit, not by illness severity. To address the second, we reviewed individual patient data from 6 clinical trials of aspirin 1000 mg in migraine (N = 2079; 1165 moderate headache, 914 severe) and one of aspirin 500 and 1000 mg in ETTH (N = 325; 180 moderate, 145 severe), relating outcome to pre-treatment headache intensity. In migraine, for headache relief at 2 hours, a small (4.7%) and non-significant risk difference (RD) in therapeutic gain favored moderate pain; for pain freedom at 2 hours, therapeutic gains were almost identical (RD: -0.2%). In ETTH, for headache relief at 2 hours, RDs for both aspirin 500 mg (-4.2%) and aspirin 1000 mg (-9.7%) favored severe pain, although neither significantly; for pain freedom at 2 hours, RDs (-14.2 and -3.6) again favored severe pain. In neither migraine nor ETTH does pre-treatment headache intensity predict success or failure of aspirin. This is not an arguable basis for stratified care in migraine. In both disorders, aspirin is first-line treatment regardless of headache intensity. © 2011 American Headache Society.

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.

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.

The clinical dilemma of "silent desensitization" in aspirin-exacerbated respiratory disease.

Science.gov (United States)

White, Andrew A; Bosso, John V; Stevenson, Donald D

2013-01-01

Aspirin desensitization is a treatment option for patients with aspirin-exacerbated respiratory disease (AERD). Some patients with an excellent history of aspirin or nonsteroidal anti-inflammatory drug (NSAID) reactions have negative aspirin challenges/desensitization. This study discusses the clinical entity of silent desensitization in AERD and the dilemma that this presents to the practicing allergist/immunologist. We discuss a series of patients with a strong history of NSAID reactions who initially underwent a negative challenge/silent desensitization. These patients were subsequently proven to have AERD after a second positive aspirin challenge. Silent desensitization is an uncommon but important outcome to recognize in AERD. Clinicians performing aspirin desensitization should understand that this can occur and consider a second confirmatory aspirin challenge in some patients.

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.

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...

Technetium-aspirin molecule complexes

International Nuclear Information System (INIS)

El-Shahawy, A.S.; Mahfouz, R.M.; Aly, A.A.M.; El-Zohry, M.

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)

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.

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

Regular Use of Aspirin or Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs Is Not Associated With Risk of Incident Pancreatic Cancer in Two Large Cohort Studies.

Science.gov (United States)

Khalaf, Natalia; Yuan, Chen; Hamada, Tsuyoshi; Cao, Yin; Babic, Ana; Morales-Oyarvide, Vicente; Kraft, Peter; Ng, Kimmie; Giovannucci, Edward; Ogino, Shuji; Stampfer, Meir; Cochrane, Barbara B; Manson, JoAnn E; Clish, Clary B; Chan, Andrew T; Fuchs, Charles S; Wolpin, Brian M

2018-04-01

Use of aspirin and/or non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of several cancers, but it is not clear if use of these drugs is associated with risk of pancreatic cancer. We evaluated aspirin and non-aspirin NSAID use and risk of pancreatic adenocarcinoma in 141,940 participants from the Health Professionals Follow-up Study and Nurses' Health Study using multivariable-adjusted Cox proportional hazards regression. We considered several exposure classifications to model differing lag times between NSAID exposure and cancer development. We also conducted a nested case-control study of participants from 3 prospective cohorts using conditional logistic regression to evaluate pre-diagnosis levels of plasma salicylurate, a major metabolite of aspirin, in 396 pancreatic cancer cases and 784 matched individuals without pancreatic cancer (controls). In the prospective cohort study, 1122 participants developed pancreatic adenocarcinoma over 4.2 million person-years. Use of aspirin or non-aspirin NSAIDs was not associated with pancreatic cancer risk, even after considering several latency exposure classifications. In a pre-planned subgroup analysis, regular aspirin use was associated with reduced pancreatic cancer risk among participants with diabetes (relative risk, 0.71; 95% CI, 0.54-0.94). In the nested case-control study, pre-diagnosis levels of salicylurate were not associated with pancreatic cancer risk (odds ratio, 1.08; 95% CI, 0.72-1.61; P trend 0.81; comparing participants in the highest quintile with those in the lowest quintile of plasma salicylurate). Regular aspirin or non-aspirin NSAID use was not associated with future risk of pancreatic cancer in participants from several large prospective cohort studies. A possible reduction in risk for pancreatic cancer among people with diabetes who regularly use aspirin should be further examined in preclinical and human studies. Copyright © 2018 AGA Institute. Published by Elsevier

Aspirin responsiveness changes in obese patients following bariatric surgery.

Science.gov (United States)

Norgard, Nicholas B; Monte, Scott V; Fernandez, Stanley F; Ma, Qing

2017-08-01

Bariatric surgery has emerged as a promising treatment option for weight loss and to counter the metabolic consequences of obesity. Obesity has been linked to a hyperaggregable state, as well as a blunted response to aspirin. This pilot study assessed the hypothesis that bariatric surgery would lead to an improvement in aspirin-induced platelet inhibition and a reduction in platelet aggregability. Fifteen patients scheduled to undergo bariatric surgery were administered two 7-day courses of aspirin 81 mg: the first course administered before surgery and the second was 3 months following surgery. Platelet aggregation was measured before and after each aspirin course using VerifyNow-Aspirin. The primary endpoint was the change in on-treatment aspirin reactive units (ARU) pre- and postsurgery. Data from bariatric surgery study patients were compared to data of normal weighted subjects gathered in a previous study. Roux-en-Y gastric bypass was performed in 80%, and 20% underwent sleeve gastrectomy. The mean starting body mass index (BMI) was 46.9 kg/m 2 . Patients lost on average 24.5 kg, resulting in a postsurgical BMI of 38.5 kg/m 2 . Postbariatric surgery, off-treatment ARU was significantly reduced from presurgery levels (602±59 vs 531±78; P=.035). On-aspirin platelet reactivity was also significantly reduced following surgery (469±60 vs 432±143, P=.03). There was a significant correlation between the extent of weight loss and the degree of improvement in on-aspirin platelet reactivity (r 2 =.49, P=.024). Presurgery on-aspirin platelet reactivity was significantly higher in obese patients compared to normal weighted subjects (469±60 vs 419±52; P=.016) and reduced to the baseline after the surgery (432±63 vs 419±52; P=.54). Aspirin-induced platelet inhibition may be more potent following bariatric surgery. The mechanisms behind this improvement require further investigation. © 2017 John Wiley & Sons Ltd.

Automated processing of electronic medical records is a reliable method of determining aspirin use in populations at risk for cardiovascular events.

Science.gov (United States)

Pakhomov, Serguei Vs; Shah, Nilay D; Hanson, Penny; Balasubramaniam, Saranya C; Smith, Steven A

2010-01-01

Low-dose aspirin reduces cardiovascular risk; however, monitoring over-the-counter medication use relies on the time-consuming and costly manual review of medical records. Our objective is to validate natural language processing (NLP) of the electronic medical record (EMR) for extracting medication exposure and contraindication information. The text of EMRs for 499 patients with type 2 diabetes was searched using NLP for evidence of aspirin use and its contraindications. The results were compared to a standardised manual records review. Of the 499 patients, 351 (70%) were using aspirin and 148 (30%) were not, according to manual review. NLP correctly identified 346 of the 351 aspirin-positive and 134 of the 148 aspirin-negative patients, indicating a sensitivity of 99% (95% CI 97-100) and specificity of 91% (95% CI 88-97). Of the 148 aspirin-negative patients, 66 (45%) had contraindications and 82 (55%) did not, according to manual review. NLP search for contraindications correctly identified 61 of the 66 patients with contraindications and 58 of the 82 patients without, yielding a sensitivity of 92% (95% CI 84-97) and a specificity of 71% (95% CI 60-80). NLP of the EMR is accurate in ascertaining documented aspirin use and could potentially be used for epidemiological research as a source of cardiovascular risk factor information.

Effect of aspirin on tumour cell colony formation and evolution.

Science.gov (United States)

Wodarz, Dominik; Goel, Ajay; Boland, C Richard; Komarova, Natalia L

2017-09-01

Aspirin is known to reduce the risk of colorectal cancer (CRC) incidence, but the underlying mechanisms are not fully understood. In a previous study, we quantified the in vitro growth kinetics of different CRC tumour cell lines treated with varying doses of aspirin, measuring the rate of cell division and cell death. Here, we use these measured parameters to calculate the chances of successful clonal expansion and to determine the evolutionary potential of the tumour cell lines in the presence and absence of aspirin. The calculations indicate that aspirin increases the probability that a single tumour cell fails to clonally expand. Further, calculations suggest that aspirin increases the evolutionary potential of an expanding tumour cell colony. An aspirin-treated tumour cell population is predicted to result in the accumulation of more mutations (and is thus more virulent and more difficult to treat) than a cell population of the same size that grew without aspirin. This indicates a potential trade-off between delaying the onset of cancer and increasing its evolutionary potential through chemoprevention. Further work needs to investigate to what extent these findings apply to in vivo settings, and to what degree they contribute to the epidemiologically documented aspirin-mediated protection. © 2017 The Author(s).

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...

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

, 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...... 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...

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

Science.gov (United States)

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

2017-12-01

The Aspirin for Evidence-Based Preeclampsia Prevention trial was a multicenter study in women with singleton pregnancies. Screening was carried out at 11-13 weeks' gestation with an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor). Those with an estimated risk for preterm preeclampsia of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/d) vs placebo from 11-14 until 36 weeks' gestation. Preterm preeclampsia with delivery at preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial. This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of preeclampsia at screening and the participating center. The choice of cut-off of 90% was based on an exploratory analysis of the treatment effect. Logistic regression analysis was used to investigate predictors of compliance ≥90% among maternal characteristics and medical history. Preterm preeclampsia occurred in 5/555 (0.9%) participants in the aspirin group with compliance ≥90%, in 8/243 (3.3%) of participants in the aspirin group with compliance preeclampsia was 0.24 (95% confidence interval, 0.09-0.65) for compliance ≥90% and 0.59 (95% confidence interval, 0.23-1.53) for compliance preeclampsia and negatively associated with smoking, maternal age preeclampsia in a previous pregnancy. The beneficial effect of aspirin in the prevention of preterm preeclampsia appears to depend on compliance. Copyright © 2017 Elsevier Inc. All rights reserved.

Contemporary medical therapies of atherosclerotic carotid artery disease.

Science.gov (United States)

Cheng, Suk F; Brown, Martin M

2017-03-01

Contemporary medical therapy consists of identification and treatment of all patient-modifiable vascular risk factors. Specific atherosclerotic disease therapies are designed to reduce the risk of thrombosis, and the disease progression in order to reduce the risk of future cardiovascular events. Contemporary medical management emphasizes the need to support the patient in achieving lifestyle modifications and to adjust medication to achieve individualized target values for specific quantifiable risk factors. Antiplatelet therapy in the form of aspirin or clopidogrel is routinely used for the prevention of ischemic stroke in patients who have had a transient ischemic attack or stroke. There is evidence from a recent trial that the use of combination antiplatelet therapy with aspirin and clopidogrel started within 24 hours of minor stroke or transient ischemic attack reduces the risk of recurrent stroke compared to the use of aspirin alone, and therefore we use aspirin plus clopidogrel in recently symptomatic patients with carotid stenosis pending carotid revascularization. Anticoagulation with heparins or vitamin K antagonist is not recommended except in patients at risk for cardio-embolic events. Lowering blood pressure to target levels has been shown to slow down the progression of carotid artery stenosis and reduces the intima-media thickness of the carotid plaque, while lowering lipid levels with statins has become an essential element in the medical therapy of carotid artery stenosis. Diabetes management should be optimized. Lifestyle choices, including tobacco smoking, physical inactivity, unhealthy diet, obesity, and excessive alcohol intake, are all important modifiable vascular risk factors. The combination of dietary modification, physical exercise, and use of aspirin, a statin, and an antihypertensive agent can be expected to give a cumulative relative stroke risk reduction of 80%. The evidence suggests that intensive medical therapy is so effective that

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...

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.

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

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.

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.

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

Prevalence of Ex Vivo High On-treatment Platelet Reactivity on Antiplatelet Therapy after Transient Ischemic Attack or Ischemic Stroke on the PFA-100(®) and VerifyNow(®).

LENUS (Irish Health Repository)

Kinsella, Justin A

2012-09-12

BACKGROUND: The prevalence of ex vivo high on-treatment platelet reactivity (HTPR) to commonly prescribed antiplatelet regimens after transient ischemic attack (TIA) or ischemic stroke is uncertain. METHODS: Platelet function inhibition was simultaneously assessed with modified light transmission aggregometry (VerifyNow; Accumetrics Inc, San Diego, CA) and with a moderately high shear stress platelet function analyzer (PFA-100; Siemens Medical Solutions USA, Inc, Malvern, PA) in a pilot, cross-sectional study of TIA or ischemic stroke patients. Patients were assessed on aspirin-dipyridamole combination therapy (n = 51) or clopidogrel monotherapy (n = 25). RESULTS: On the VerifyNow, HTPR on aspirin was identified in 4 of 51 patients (8%) on aspirin-dipyridamole combination therapy (≥550 aspirin reaction units on the aspirin cartridge). Eleven of 25 (44%) patients had HTPR on clopidogrel (≥194 P2Y12 reaction units on the P2Y12 cartridge). On the PFA-100, 21 of 51 patients (41%) on aspirin-dipyridamole combination therapy had HTPR on the collagen-epinephrine (C-EPI) cartridge. Twenty-three of 25 patients (92%) on clopidogrel had HTPR on the collagen-adenosine diphosphate (C-ADP) cartridge. The proportion of patients with antiplatelet HTPR was lower on the VerifyNow than PFA-100 in patients on both regimens (P < .001). CONCLUSIONS: The prevalence of ex vivo antiplatelet HTPR after TIA or ischemic stroke is markedly influenced by the method used to assess platelet reactivity. The PFA-100 C-ADP cartridge is not sensitive at detecting the antiplatelet effects of clopidogrel ex vivo. Larger prospective studies with the VerifyNow and with the PFA-100 C-EPI and recently released Innovance PFA P2Y cartridges (Siemens Medical Solutions USA, Inc) in addition to newer tests of platelet function are warranted to assess whether platelet function monitoring predicts clinical outcome in ischemic cerebrovascular disease.

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.

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

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

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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.

Anaesthesia in aspirin-induced asthma.

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Celiker, V; Basgül, E

2003-01-01

The triad of bronchial asthma, nasal polyposis, and intolerance to aspirin and aspirin-like chemicals are designated aspirin-induced asthma (AIA) or Samter's syndrome. The exact mechanism of the disease is unknown but it is thought to be a disorder of arachidonic acid metabolism. These patients are frequently referred to allergy clinics for preoperative evaluation for possible anesthetic agent sensitivity, requiring anesthesia for nasal polypectomy or several other reasons. Anesthetists must be aware of their pulmonary dysfunction, because the anesthetic management of asthma requires a specific approach. Marked cross-sensitivity with NSAIDs, which may also precipitate severe bronchospasm and adverse reactions, is the main problem faced by anesthetists in postoperative pain management. This article discusses the relationship between AIA and anesthesia. We also present our experience with 47 patients diagnosed with AIA between 1991 and 2003 in the department of chest diseases and adult allergy unit who underwent surgery requiring general anesthesia. In conclusion, preoperative evaluation of these patients and collaboration between the allergists and anesthesiologists is essential to prevent preoperative, perioperative and postoperative complications.

Simultaneous silencing of ACSL4 and induction of GADD45B in hepatocellular carcinoma cells amplifies the synergistic therapeutic effect of aspirin and sorafenib

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Xia, Hongping; Lee, Kee Wah; Chen, Jianxiang; Kong, Shik Nie; Sekar, Karthik; Deivasigamani, Amudha; Seshachalam, Veerabrahma Pratap; Goh, Brian Kim Poh; Ooi, London Lucien; Hui, Kam M

2017-01-01

Sorafenib is currently the only US Food and Drug Administration (FDA)-approved molecular inhibitor for the systemic therapy of advanced hepatocellular carcinoma (HCC). Aspirin has been studied extensively as an anti-inflammation, cancer preventive and therapeutic agent. However, the potential synergistic therapeutic effects of sorafenib and aspirin on advanced HCC treatment have not been well studied. Drug combination studies and their synergy quantification were performed using the combination index method of Chou-Talalay. The synergistic therapeutic effects of sorafenib and aspirin were evaluated using an orthotopic mouse model of HCC and comprehensive gene profiling analyses were conducted to identify key factors mediating the synergistic therapeutic effects of sorafenib and aspirin. Sorafenib was determined to act synergistically on HCC cells with aspirin in vitro. Using Hep3B and HuH7 HCC cells, it was demonstrated that sorafenib and aspirin acted synergistically to induce apoptosis. Mechanistic studies demonstrated that combining sorafenib and aspirin yielded significant synergistically anti-tumor effects by simultaneously silencing ACSL4 and the induction of GADD45B expression in HCC cells both in vitro and in the orthotopic HCC xenograft mouse model. Importantly, clinical evidence has independently corroborated that survival of HCC patients expressing ACSL4highGADD45Blow was significantly poorer compared to patients with ACSL4lowGADD45Bhigh, thus demonstrating the potential clinical value of combining aspirin and sorafenib for HCC patients expressing ACSL4highGADD45Blow. In conclusion, sorafenib and aspirin provide synergistic therapeutic effects on HCC cells that are achieved through simultaneous silencing of ACSL4 and induction of GADD45B expression. Targeting HCC with ACSL4highGADD45Blow expression with aspirin and sorafenib could provide potential synergistic therapeutic benefits. PMID:28900541

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

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Chinthalapally V. Rao

2012-09-01

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

Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations.

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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

Regular use of aspirin and pancreatic cancer risk

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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.

Use and Misuse of Aspirin in Primary Cardiovascular Prevention

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Sergio Coccheri

2017-04-01

Full Text Available The use of low-dose aspirin in primary prevention of cardiovascular (CV events in healthy or apparently healthy people is a widely debated topic. Many arguments indicate that “primary prevention” is only a conventional definition and that the transition from primary to secondary prevention represents a continuum of increasing levels of CV risk. Although there are no direct proofs of a different efficacy of aspirin at different CV risk levels, in low-risk populations aspirin will appear to be less efficient. In fact, the lower number of events occurring in patients at low risk yields lower absolute numbers of events prevented. As many as 6 meta-analyses of trials of primary CV prevention with aspirin versus placebo, performed between 2009 and 2016, confirmed the above concepts and showed a concordant, significant reduction in nonfatal myocardial infarction, with no significant effects on stroke, as well as on CV and all-cause mortality. The recent demonstration of a moderate protective effect of aspirin on cancer (especially colorectal confers, however, additional value to the use of aspirin, although unusually long durations of treatment and optimal daily compliance seem to be necessary. Because aspirin increases the bleeding risk, the evaluation of its net clinical benefit is an important point of debate. Thus, it is justified to search for a cutoff level of global CV risk above which the net clinical benefit of aspirin becomes evident. Such a threshold value has been calculated considering the data of 9 primary prevention trials, by the Thrombosis Group of the European Society of Cardiology, and has been indicated as a risk value of 2 or more major CV events per 100 persons per year. Also, in the recent 2016 US Guidelines, the main criterion adopted for the indication of aspirin is the level of global CV risk (suggested cutoff is 1 or more major CV events per 100 persons per year. Beyond the different values selected, it is seems very

Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

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Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

2017-11-01

Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the

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

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

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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.

Effect of Aspirin Supplementation on Hemodynamics in Older Firefighters.

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Lane-Cordova, Abbi D; Ranadive, Sushant M; Yan, Huimin; Kappus, Rebecca M; Sun, Peng; Bunsawat, Kanokwan; Smith, Denise L; Horn, Gavin P; Ploutz-Snyder, Robert; Fernhall, B O

2015-12-01

Cardiovascular events are the leading cause of line-of-duty fatality for firefighters. Aspirin reduces the risk of cardiovascular events in men and may reduce fatalities in older (>40 yr) firefighters. We hypothesized that both chronic and acute aspirin supplementation would improve vascular function after live firefighting but that chronic supplementation would also improve resting hemodynamics. Twenty-four firefighters (40-60 yr) were randomly assigned to acute or chronic aspirin supplementation or placebo in a balanced, crossover design. Arterial stiffness, brachial and central blood pressures, as well as forearm vasodilatory capacity and blood flow were measured at rest and immediately after live firefighting. Total hyperemic blood flow (area under the curve (AUC)) was increased (P 0.05 for interaction). Arterial stiffness/central blood pressure increased (P < 0.04) with no effect of aspirin (from 0.0811 ± 0.001 to 0.0844 ± 0.003 m·s·mm⁻¹ Hg⁻¹ in aspirin condition versus 0.0802 ± 0.002 to 0.0858 ± 0.002 m·s⁻¹·mm Hg⁻¹ in placebo condition), whereas peripheral and central systolic and pulse pressures decreased after firefighting across conditions (P < 0.05). Live firefighting resulted in increased AUC and pressure-controlled arterial stiffness and decreased blood pressure in older firefighters, but aspirin supplementation did not affect macro- or microvascular responsiveness at rest or after firefighting.

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 ...

Systemic aspirin and systemic vitamin E in senile cataracts : cataract V

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Sharma Y

1989-01-01

Full Text Available We undertook a prospective study in senile cataract patients using systemic aspirin and systemic vitamin E. Vitamin E treated eyes did show less progression of PSC opacities extent and less new nuclear opacities during the follow-up, but overall vitamin E treated eyes did no better than the control group eyes. More eyes in systemic aspirin treated group maintained the initial vision and loss of vision in the aspirin group was also less marked. Aspirin also caused a significant less mean increase in cortical opacity extent, nuclear/opacity and density and PSC opacity extent and density as well as in ophthalmoscopically graded opacity extent and density. We suggest that aspirin is a potential drug which should be further evaluated in large double blind photodocumentated studies. The present data does not justify the recommendation that aspirin be prescribed for slowing down cataract progression. This must await large studies and confirmation.

The Cost Differential Between Warfarin Versus Aspirin Treatment After a Fontan Procedure.

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Schilling, Chris; Dalziel, Kim; Iyengar, Ajay J; d'Udekem, Yves

2017-08-01

The use of aspirin versus warfarin for treatment of patients after a Fontan procedure remains contentious. Current preference-based models of treatment across Australia and New Zealand show variation in care that is unlikely to reflect patient differences and/or clinical risk. We combine data from the Australian and New Zealand Fontan Registry and a home INR (International Normalised Ratio) monitoring program (HINRMP) from the Royal Children's Hospital (RCH) Melbourne, to estimate the cost difference for Fontan recipients receiving aspirin versus warfarin for 2015. We adopt a societal perspective to costing which includes cost to the health system (e.g. medical consults, pathology tests) and costs to patients and carers (e.g. travel and time), but excludes costs of adverse events. Costs are presented in Australian 2015 dollars; any costs from previous years have been inflated using appropriate rates from the Australian Bureau of Statistics. We find that warfarin patients face additional costs of $825 per annum, with the majority ($584 or 71%) of those borne by the patient or family. If aspirin is as clinically as effective as warfarin, Fontan recipients could be enjoying far less costly, invasive and time-consuming treatment. While achieving such clinical consensus can be difficult, economics shows us that there are large costs associated with a failure to achieve it. Copyright © 2017. Published by Elsevier B.V.

Metabolome analysis of effect of aspirin on Drosophila lifespan extension.

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Song, Chaochun; Zhu, Chenxing; Wu, Qi; Qi, Jiancheng; Gao, Yue; Zhang, Zhichao; Gaur, Uma; Yang, Deying; Fan, Xiaolan; Yang, Mingyao

2017-09-01

Effective approaches for drug development involve the repurposing of existing drugs which are already approved by the FDA. Aspirin has been shown to have many health benefits since its discovery as a nonsteroidal anti-inflammatory drug (NSAID) to treat pain and inflammation. Recent experiments demonstrated the longevity effects of aspirin in Drosophila, but its mechanism remains to be explored. In order to elucidate the effects of drug on metabolism, we carried out the metabolic analysis of aspirin-treated flies. The results identified 404 active metabolites in addition to the extended lifespan and improved healthspan in fly. There were 28 metabolites having significant changes between aspirin-treated group and the control group, out of which 22 compounds were found to have detailed information. These compounds are reported to have important functions in energy metabolism, amino sugar metabolism, and urea metabolism, indicating that aspirin might be playing positive roles in the fly's lifespan and healthspan improvement. Because of the conservation of major longevity pathways and mechanisms in different species, the health benefits of aspirin administration could be extended to other animals and humans as well. Copyright © 2017 Elsevier Inc. All rights reserved.

Glucose impairs aspirin inhibition in platelets through a NAD(P)H oxidase signaling pathway.

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Kobzar, Gennadi; Mardla, Vilja; Samel, Nigulas

2017-07-01

Hyperglycemia has been suggested to play a role in the increased platelet resistance to antiplatelet therapy in patients with diabetes mellitus. Exposure to high glucose impairs platelet inhibition by aspirin. It has been found that antioxidant agents reduce the effect of glucose, confirming the involvement of reactive oxygen species (ROS) in the effect of glucose. The aim of the study was to examine the mechanism of ROS increase by high glucose in aspirin-treated platelets. Platelet aggregation was measured by the optical method, and the production of ROS was detected using luminol-dependent horseradish peroxidase-enhanced chemiluminescence. We found that glucose did not affect ADP-induced platelet aggregation. However, it reduced the effect of aspirin on platelet aggregation, which was accompanied by an increase in ROS generation. The inhibition of NAD(P)H oxidase (NOX) prevented the glucose effect and ROS generation. The same result was recorded after the inhibition of p38 mitogen-activated protein kinases (p38 MAPK), phospholipase A 2 (PLA 2 ) or 12-lipoxygenase (12-LOX). The inhibition of TxA 2 receptor did not decrease the effect of glucose indicating that the effect was not caused by activation of TxA 2 receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

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)

Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

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Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

1989-07-01

1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reaction. 4. Aspirin increased bleeding from a rate on placebo of 1.2 microliters 10 min-1 geometric mean (95% confidence limits) (0.7-1.8) microliters 10 min-1 to 20.0 (11.6-34.2) microliters 10 min-1, (P less than 0.01). The rate of bleeding after aspirin preceded by ethamsylate [14.1 (8.5-23.4) microliters 10 min-1] was not significantly different from that after aspirin alone. 5. We conclude that ethamsylate does not reduce acute aspirin-induced gastric mucosal bleeding in healthy humans.

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.

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

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...

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

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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.

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.

Aspirin and heart disease

Science.gov (United States)

... medlineplus.gov/ency/patientinstructions/000092.htm Aspirin and heart disease To use the sharing features on this page, ... healthy people who are at low risk for heart disease. You provider will consider your overall medical condition ...

Design of radiopharmaceuticals for monitoring gene transfer therapy

International Nuclear Information System (INIS)

Lambrecht, R.M.; Staehler, P.; Kley, J.; Spiegel, M.; Gross, C.; Graepler, F.T.C.; Gregor, M.; Lauer, U.; Oberdorfer, F.

1998-01-01

The development of radiopharmaceuticals for monitoring gene transfer therapy with emission tomography is expected to lead to improved management of cancer by the year 2010. There are now only a few examples and approaches to the design of radiopharmaceuticals for gene transfer therapy. This paper introduces a novel concept for the monitoring of gene therapy. We present the optimisation of the labelling of recombinant human β-NGF ligands for in vitro studies prior to using 123 I for SPET and 124 I for PET studies. (author)

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...

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

On-line monitoring of heavy-ion therapy using PET

International Nuclear Information System (INIS)

Pavlovic, M.

2004-01-01

In this presentation authors present results of on-line monitoring of heavy-ion therapy using PET. It is concluded that in-beam positron emission tomography is a feasible and valuable method for in-situ and non-invasive monitoring of heavy-ion therapy

Aspirin resistance are associated with long-term recurrent stroke events after ischaemic stroke.

Science.gov (United States)

Zhang, Ning; Wang, Zhenhua; Zhou, Lihong

2017-09-01

To investigate the prevalent of aspirin resistance (AR) in stroke and its association with recurrent stroke in 214 patients with ischemic stroke who were receiving aspirin before the stroke onset. Two hundreds and fourteen acute stroke patients who previously received aspirin therapy (100mg/day for ≥7days) were enrolled. Whole blood samples were collected for platelet aggregation testing. The result is expressed in aspirin reaction units (ARU). A cutoff of 550 ARU was used to determine the presence of AR. A follow-up period of 1year was performed to record stroke recurrence events. In this study, the median age was 68 years (IQR, 60-77 years), and 118 (55.1%) were men. A total of 43 of 214 enrolled patients (20.1%) were AR. ARU levels were significantly higher in patients with recurrence than those without (514[IQR: 466-592] vs. 454[IQR: 411-499]; P <0.001). The stroke recurrence distribution across the ARU quartiles ranged between 7.41% (first quartile) to 40.74% (fourth quartile). In multivariate analyses, the 3th and 4th quartile of ARU was significantly associated with stroke recurrence during the observation period compared to the 1st quartile group, and the adjusted risk increased by 215% (OR=3.15 [95% CI 1.96-4.33], P=0.007) and 322% (4.22[2.56-7.16], P<0.001). In multivariate logistic regression analysis, AR was associated with a higher risk of stroke recurrence, and the adjusted risk increased by 365% (OR=4.65; 95% CI=2.99-8.16; P<0.001). In conclusion, AR is not uncommon in Chinese stroke patients who receive anti-platelet medications. Patients with AR may have a greater risk of suffering stroke recurrence events. Copyright © 2017 Elsevier Inc. All rights reserved.

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; Hashimoto, S.; Maas, M.

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

Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history.

Science.gov (United States)

Poon, Liona C; Wright, David; Rolnik, Daniel L; Syngelaki, Argyro; Delgado, Juan Luis; Tsokaki, Theodora; Leipold, Gergo; Akolekar, Ranjit; Shearing, Siobhan; De Stefani, Luciana; Jani, Jacques C; Plasencia, Walter; Evangelinakis, Nikolaos; Gonzalez-Vanegas, Otilia; Persico, Nicola; Nicolaides, Kypros H

2017-11-01

The Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial demonstrated that in women who were at high risk for preterm preeclampsia with delivery at aspirin administration from 11 to 14 until 36 weeks' gestation was associated with a significant reduction in the incidence of preterm preeclampsia (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). We sought to examine whether there are differences in the effect of aspirin on the incidence of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial in subgroups defined according to maternal characteristics and medical and obstetrical history. This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial. Subgroup analysis was performed to assess evidence of differences in the effect of aspirin on incidence of preterm preeclampsia in subgroups defined by maternal age (aspirin effect in subgroups defined according to maternal characteristics and obstetrical history. In participants with chronic hypertension preterm preeclampsia occurred in 10.2% (5/49) in the aspirin group and 8.2% (5/61) in the placebo group (adjusted odds ratio, 1.29; 95% confidence interval, 0.33-5.12). The respective values in those without chronic hypertension were 1.1% (8/749) in the aspirin group and 3.9% (30/761) in the placebo group (adjusted odds ratio, 0.27; 95% confidence interval, 0.12-0.60). In all participants with adherence of ≥90% the adjusted odds ratio in the aspirin group was 0.24 (95% confidence interval, 0.09-0.65); in the subgroup with chronic hypertension it was 2.06 (95% confidence interval, 0.40-10.71); and in those without chronic hypertension it was 0.05 (95% confidence interval, 0.01-0.41). For the complete data set the test of interaction was not significant at the 5% level (P = .055), but in those with adherence ≥90%, after adjustment for multiple comparisons

The effects of aspirin, flurbiprofen, and NO-donating acetylsalicylic acid (NCX 4016) on mice models of endotoxic and septic shock.

Science.gov (United States)

Ulu, Nadir; Iskit, Alper Bektaş; Sökmensüer, Cenk; Güç, Mustafa Oğuz

2015-01-01

Nitric oxide-donating nonsteroidal antiinflammatory drugs (NO-NSAIDs) are a promising new class of antiinflammatory agents, which are obtained by adding NO-donating moieties to the existing conventional NSAID molecules. The aim of this study was to investigate the effects of aspirin, flurbiprofen, and NO-donating acetylsalicylic acid (NCX 4016) on cecal ligation and puncture (CLP) and endotoxin-induced septic shock (LPS) models in mice. Overall survival and spleen and liver weights were monitored in LPS and CLP models. Histopathological examinations of liver and spleen were performed at the end of the experimental protocols. NCX 4016 was able to reverse the increased spleen weight in CLP-operated animals, whereas aspirin or flurbiprofen did not. Similar to the results of the CLP model, none of the drugs modified the survival rates in the LPS model. Flurbiprofen in particular produced significant histopathological damage in spleens and livers, which was less significant with aspirin. NCX 4016 did not cause any liver damage. NCX 4016 has the potential to be used in septic states, while special attention has to be paid to the effects of aspirin and flurbiprofen on the liver and spleen.

Effects of aspirin and enoxaparin in a rat model of liver fibrosis.

Science.gov (United States)

Li, Chen-Jie; Yang, Zhi-Hui; Shi, Xiao-Liu; Liu, De-Liang

2017-09-21

To examine the effects of aspirin and enoxaparin on liver function, coagulation index and histopathology in a rat model of liver fibrosis. METHODS Forty-five male Sprague-Dawley rats were randomly divided into the control group (n = 5) and model group (n = 40). Thioacetamide (TAA) was used to induce liver fibrosis in the model group. TAA-induced fibrotic rats received TAA continuously (n = 9), TAA + low-dose aspirin (n = 9), TAA + high-dose aspirin (n = 9) or TAA + enoxaparin (n = 9) for 4 wk. All rats were euthanized after 4 wk, and both hematoxylin-eosin and Masson staining were performed to observe pathological changes in liver tissue. Liver fibrosis was assessed according to the METAVIR score. Compared with untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the low-dose aspirin, high-dose aspirin and enoxaparin treated groups, especially in the high-dose aspirin treated group. Alanine aminotransferase and total bilirubin were higher, albumin was lower and both prothrombin time and international normalized ratio were prolonged in the four treatment groups compared to controls. No significant differences among the four groups were observed. Aspirin and enoxaparin can alleviate liver fibrosis in this rat model.

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

Investigation progress of imaging techniques monitoring stem cell therapy

International Nuclear Information System (INIS)

Wu Jun; An Rui

2006-01-01

Recently stem cell therapy has showed potential clinical application in diabetes mellitus, cardiovascular diseases, malignant tumor and trauma. Efficient techniques of non-invasively monitoring stem cell transplants will accelerate the development of stem cell therapies. This paper briefly reviews the clinical practice of stem cell, in addition, makes a review of monitoring methods including magnetic resonance and radionuclide imaging which have been used in stem cell therapy. (authors)

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.

FDG-PET in monitoring therapy of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Biersack, H J; Bender, H; Palmedo, H [Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn (Germany)

2004-06-01

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been used successfully for the staging and re-staging of breast cancer. Another significant indication is the evaluation of therapy response. Only limited data are available on the use of FDG-PET in breast cancer after radiation therapy. The same holds true for chemotherapy. Only the therapy response in locally advanced breast cancer after chemotherapy has been investigated thoroughly. Histopathological response could be predicted with an accuracy of 88-91% after the first and second courses of therapy. A quantitative evaluation is, of course, a prerequisite when FDG-PET is used for therapy monitoring. Only a small number of studies have focussed on hormone therapy. In this context, a flare phenomenon with increasing standardised uptake values after initiation of tamoxifen therapy has been observed. More prospective multicentre trials will be needed to make FDG-PET a powerful tool in monitoring chemotherapy in breast cancer. (orig.)

FDG-PET in monitoring therapy of breast cancer

International Nuclear Information System (INIS)

Biersack, H.J.; Bender, H.; Palmedo, H.

2004-01-01

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been used successfully for the staging and re-staging of breast cancer. Another significant indication is the evaluation of therapy response. Only limited data are available on the use of FDG-PET in breast cancer after radiation therapy. The same holds true for chemotherapy. Only the therapy response in locally advanced breast cancer after chemotherapy has been investigated thoroughly. Histopathological response could be predicted with an accuracy of 88-91% after the first and second courses of therapy. A quantitative evaluation is, of course, a prerequisite when FDG-PET is used for therapy monitoring. Only a small number of studies have focussed on hormone therapy. In this context, a flare phenomenon with increasing standardised uptake values after initiation of tamoxifen therapy has been observed. More prospective multicentre trials will be needed to make FDG-PET a powerful tool in monitoring chemotherapy in breast cancer. (orig.)

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.

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 ...

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.

Laser spectroscopy monitoring of cancer therapy

International Nuclear Information System (INIS)

Jyothi Lakshmi, R.; Ullas, G.; Kartha, V.B.; Alexander, Mohan

2000-01-01

Surgery, radiation therapy and chemotherapy are the major treatment modalities for many forms of cancer at present. Monitoring of the therapy, follow up studies on regression of the disease and detection of recurrence are very essential for successful treatment. Any technique which will be of assistance for these purposes will thus be of great help. This paper presents some of our results of Raman and Pulsed Laser fluorescence spectroscopy studies on tissues, body fluids and bone, in oral cancer subjects after radiation therapy

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.

Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration.

Science.gov (United States)

Simes, John; Becattini, Cecilia; Agnelli, Giancarlo; Eikelboom, John W; Kirby, Adrienne C; Mister, Rebecca; Prandoni, Paolo; Brighton, Timothy A

2014-09-23

In patients with a first unprovoked venous thromboembolism (VTE) the risk of recurrent VTE remains high after anticoagulant treatment is discontinued. The Aspirin for the Prevention of Recurrent Venous Thromboembolism (the Warfarin and Aspirin [WARFASA]) and the Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) trials showed that aspirin reduces this risk, but they were not individually powered to detect treatment effects for particular outcomes or subgroups. An individual patient data analysis of these trials was planned, before their results were known, to assess the effect of aspirin versus placebo on recurrent VTE, major vascular events (recurrent VTE, myocardial infarction, stroke, and cardiovascular disease death) and bleeding, overall and within predefined subgroups. The primary analysis, for VTE, was by intention to treat using time-to-event data. Of 1224 patients, 193 had recurrent VTE over 30.4 months' median follow-up. Aspirin reduced recurrent VTE (7.5%/yr versus 5.1%/yr; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51-0.90; P=0.008), including both deep-vein thrombosis (HR, 0.66; 95% CI, 0.47-0.92; P=0.01) and pulmonary embolism (HR, 0.66; 95% CI, 0.41-1.06; P=0.08). Aspirin reduced major vascular events (8.7%/yr versus 5.7%/yr; HR, 0.66; 95% CI, 0.50-0.86; P=0.002). The major bleeding rate was low (0.4%/yr for placebo and 0.5%/yr for aspirin). After adjustment for treatment adherence, recurrent VTE was reduced by 42% (HR, 0.58; 95% CI, 0.40-0.85; P=0.005). Prespecified subgroup analyses indicate similar relative, but larger absolute, risk reductions in men and older patients. Aspirin after anticoagulant treatment reduces the overall risk of recurrence by more than a third in a broad cross-section of patients with a first unprovoked VTE, without significantly increasing the risk of bleeding. www.anzctr.org.au. Unique identifier: ACTRN12611000684921. © 2014 American Heart Association, Inc.

Stability Indicating RP-HPLC Method for Simultaneous Determination of Aspirin and Clopidrogel in Dosage Form

International Nuclear Information System (INIS)

Mohd Gousuddin; Sengupta, P.; Tripathi, V.D.; Das, A.

2016-01-01

Stability-indicating High Performance Liquid Chromatographic (HPLC) method was developed for simultaneous Aspirin and Clopidogrel, A Phenomenex Gemini C-18, 5 μm column having 250 mm x 4.6 mm i.d. in isocratic mode, with mobile phase containing buffer solution 0.3 % orthophosphoric acid : acetonitrile (65:35, v/v). The flow rate was 1 ml/ min and effluents were monitored at 266 nm. For linearity seven points calibration curve were obtained in a concentration range from 0.030-0.120 mg/ ml for aspirin and 0.015-0.060 mg/ ml for clopidogrel with correlation coefficient 0.9999. In the present study stability indicating HPLC method for the combination was tested by degrading the drugs together under various stress conditions like acid hydrolysis, base hydrolysis, oxidation, thermal and photolytic stress which is recommended by ICH guideline. (author)

Aspirin administered to women at 100 mg every other day produces less platelet inhibition than aspirin administered at 81 mg per day: implications for interpreting the women's health study.

Science.gov (United States)

Swaim, Lisa; Hillman, Robert S

2009-07-01

We aimed to determine the relative level of platelet inhibition achieved with low-dose aspirin (81 mg daily) compared with a very low-dose (100 mg every other day). The Womens Health Study (WHS) found that a dose of 100 mg every other day of aspirin provided protection against stroke as primary prophylaxis, but not myocardial infarction. In the United States, the most commonly prescribed dose of aspirin for primary prophylaxis is 81 mg per day. As a result, it is important to know whether these doses are equivalent before extrapolating the results of the WHS to women in the U.S. To achieve this goal, we have studied the effects of these two dosing regimens on platelet function in healthy women meeting the WHS inclusion criteria using a randomized design. We enrolled 49 healthy female volunteers and used a sequential, crossover design to compare the two regimens. The participants received a 17-day course of each aspirin-dosing regimen separated by a 7-day washout period. The degree of platelet inhibition was measured on days 14-17 of each dosing regimen using a point-of-care platelet function assay utilizing arachidonic acid to activate platelets (VerifyNow-Aspirin). Participants platelet response, expressed as Aspirin Response Unit (ARU) attained a significantly greater level of platelet inhibition on days 14-17 while taking aspirin 81 mg daily compared to aspirin 100 mg every other day (31.3% vs. 12.7%, P or=550 ARU, a value correlated with clinical outcomes in several studies, with the 100 mg every other day regimen (72.0% vs. 6.4% with 81 mg daily, P day regimen also resulted in more day-to-day variability in platelet function (P = 0.0002). We found significantly less inhibition of platelet function with the dose used in the WHS than the usual U.S. dose. We observed that the degree of platelet inhibition was significantly less with aspirin 100 mg every other day compared with aspirin 81 mg daily, suggesting that results of the Women's Health Study may have

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)

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...

Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

Science.gov (United States)

García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

2016-01-01

Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin

Gender differences in the activities of aspirin-esterases in rat tissues

Directory of Open Access Journals (Sweden)

Benedito M.A.C.

1998-01-01

Full Text Available The activities of aspirin (acetylsalicylic acid-esterases were measured in several tissues (liver, kidney, adrenal glands, brain and serum from adult male and female Wistar rats. In males, both aspirin-esterase I (assayed at pH 5.5 and II (assayed at pH 7.4 activities were higher in liver homogenates when compared to females (aspirin-esterase I: males 48.9 ± 4.8 (N = 8 and females 29.3 ± 4.2 (N = 8 nmol of salicylic acid formed min-1 mg protein-1; aspirin-esterase II: males 41.4 ± 4.1 (N = 8 and females 26.1 ± 4.5 (N = 8 nmol of salicylic acid formed min-1 mg protein-1, P<0.001. In serum, enzyme activity was higher in females than in males (aspirin-esterase I: males 0.85 ± 0.06 (N = 6 and females 1.18 ± 0.11 (N = 6 nmol of salicylic acid formed min-1 mg protein-1; aspirin-esterase II: males 1.03 ± 0.13 (N = 6 and females 1.34 ± 0.11 (N = 6 nmol of salicylic acid formed min-1 mg protein-1, P<0.001. In the other tissues assayed, no statistically significant difference between males and females was found. There were no statistically significant differences when the enzymes were assayed in different phases of the estrous cycle in liver and serum. These results show that the differences in aspirin-esterase activity observed between males and females are not due to the estrous cycle. The gender difference obtained in our study may indicate an involvement of gonadal hormones in the control of the hydrolysis of aspirin. This possibility is currently under investigation.

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.

Impact of aspirin on fetal growth in diabetic pregnancies according to White classification.

Science.gov (United States)

Adkins, Katlynn; Allshouse, Amanda A; Metz, Torri D; Heyborne, Kent D

2017-10-01

Current US Preventive Services Task Force and other guidelines recommend low-dose aspirin for all pregnant women with pregestational diabetes mellitus to prevent preeclampsia and small-for-gestational-age birth. The Maternal-Fetal Medicine Units High-Risk Aspirin trial did not show a reduction in either preeclampsia or small-for-gestational-age birth in diabetic women. Our objective was to reassess the impact of aspirin on fetal growth in diabetic pregnancies overall and according to White classification. We hypothesized that aspirin improves fetal growth in pregnancies with vascular complications of diabetes at highest risk for poor fetal growth. We conducted secondary analysis of the cohort of diabetic women enrolled in the Maternal-Fetal Medicine Units High-Risk Aspirin trial. The impact of aspirin prophylaxis on birthweight was assessed in the overall cohort and in 2 groups categorized according to White classification as nonvascular (White class B, C, D) or vascular (White class R, F, RF). Birthweight was converted to Z-score normalized for gestational age at delivery and neonatal sex. Difference in birthweight Z-score between aspirin and placebo was tested with a 2-sample t test. The effect of vascular group, aspirin vs placebo randomization, and the interaction of the 2 on normalized birthweight percentile was estimated with linear regression with a multivariable model including covariates body mass index, tobacco use, race, and parity. The percentage of small and large-for-gestational-age newborns born to aspirin- vs placebo-treated women was compared between groups using Pearson exact χ 2 analysis, and an adjusted model was estimated by logistic regression. All 444 women with pregestational diabetes and complete outcome data were included (53 vascular, 391 nonvascular). Aspirin was significantly associated with a higher birthweight Z-score (0.283; 95% confidence interval, 0.023-0.544) in the overall cohort (P = .03). In the adjusted model, the

Surface enhanced Raman spectroscopic studies on aspirin : An experimental and theoretical approach

International Nuclear Information System (INIS)

Premkumar, R.; Premkumar, S.; Parameswari, A.; Mathavan, T.; Benial, A. Milton Franklin; Rekha, T. N.

2016-01-01

Surface enhanced Raman scattering (SERS) studies on aspirin molecule adsorbed on silver nanoparticles (AgNPs) were investigated by experimental and density functional theory approach. The AgNPs were synthesized by the solution-combustion method and characterized by the X-ray diffraction and high resolution-transmission electron microscopy techniques. The averaged particle size of synthesized AgNPs was calculated as ∼55 nm. The normal Raman spectrum (nRs) and SERS spectrum of the aspirin were recorded. The molecular structure of the aspirin and aspirin adsorbed on silver cluster were optimized by the DFT/ B3PW91 method with LanL2DZ basis set. The vibrational frequencies were calculated and assigned on the basis of potential energy distribution calculation. The calculated nRs and SERS frequencies were correlated well with the observed frequencies. The flat-on orientation was predicted from the nRs and SERS spectra, when the aspirin adsorbed on the AgNPs. Hence, the present studies lead to the understanding of adsorption process of aspirin on the AgNPs, which paves the way for biomedical applications.

Surface enhanced Raman spectroscopic studies on aspirin : An experimental and theoretical approach

Energy Technology Data Exchange (ETDEWEB)

Premkumar, R.; Premkumar, S.; Parameswari, A.; Mathavan, T.; Benial, A. Milton Franklin, E-mail: miltonfranklin@yahoo.com [Department of Physics, N.M.S.S.V.N College, Madurai-625019, Tamilnadu, India. (India); Rekha, T. N. [PG and Research Department of Physics, Lady Doak College, Madurai-625 002, Tamilnadu, India. (India)

2016-05-06

Surface enhanced Raman scattering (SERS) studies on aspirin molecule adsorbed on silver nanoparticles (AgNPs) were investigated by experimental and density functional theory approach. The AgNPs were synthesized by the solution-combustion method and characterized by the X-ray diffraction and high resolution-transmission electron microscopy techniques. The averaged particle size of synthesized AgNPs was calculated as ∼55 nm. The normal Raman spectrum (nRs) and SERS spectrum of the aspirin were recorded. The molecular structure of the aspirin and aspirin adsorbed on silver cluster were optimized by the DFT/ B3PW91 method with LanL2DZ basis set. The vibrational frequencies were calculated and assigned on the basis of potential energy distribution calculation. The calculated nRs and SERS frequencies were correlated well with the observed frequencies. The flat-on orientation was predicted from the nRs and SERS spectra, when the aspirin adsorbed on the AgNPs. Hence, the present studies lead to the understanding of adsorption process of aspirin on the AgNPs, which paves the way for biomedical applications.

A review of antithrombotic therapy and the rationale and design of the randomized edoxaban in patients with peripheral artery disease (ePAD) trial adding edoxaban or clopidogrel to aspirin after femoropopliteal endovascular intervention.

Science.gov (United States)

Tangelder, Marco J D; Nwachuku, Chuke E; Jaff, Michael; Baumgartner, Iris; Duggal, Anil; Adams, George; Ansel, Gary; Grosso, Michael; Mercuri, Michele; Shi, Minggao; Minar, Erich; Moll, Frans L

2015-04-01

Compared with the coronary setting, knowledge about antithrombotic therapies after endovascular treatment (EVT) is inadequate in patients with peripheral artery disease (PAD). Based on a review of trials and guidelines, which is summarized in this article, there is scant evidence that antithrombotic drugs improve outcome after peripheral EVT. To address this knowledge gap, the randomized, open-label, multinational edoxaban in patients with Peripheral Artery Disease (ePAD) study (ClinicalTrials.gov identifier NCT01802775) was designed to explore the safety and efficacy of a combined regimen of antiplatelet therapy with clopidogrel and anticoagulation with edoxaban, a selective and direct factor Xa inhibitor, both combined with aspirin. As of July 2014, 203 patients (144 men; mean age 67 years) from 7 countries have been enrolled. These patients have been allocated to once-daily edoxaban [60 mg for 3 months (or 30 mg in the presence of factors associated with increased exposure)] or clopidogrel (75 mg/d for 3 months). All patients received aspirin (100 mg/d) for the 6-month duration of the study. The primary safety endpoint is major or clinically relevant nonmajor bleeding; the primary efficacy endpoint is restenosis or reocclusion at the treated segment(s) measured at 1, 3, and 6 months using duplex ultrasound scanning. All outcomes will be assessed and adjudicated centrally in a masked fashion. The ePAD study is the first of its kind to investigate a combined regimen of antiplatelet therapy and anticoagulation through factor Xa inhibition with edoxaban. © The Author(s) 2015.

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...

Aspirin augments the expression of Adenomatous Polyposis Coli protein by suppression of IKKβ

International Nuclear Information System (INIS)

Ashida, Noboru; Kishihata, Masako; Tien, Dat Nguyen; Kamei, Kaeko; Kimura, Takeshi; Yokode, Masayuki

2014-01-01

Highlights: • Clinical studies revealed aspirin inhibits cancer, but the mechanism is not known. • Adenomatous Polyposis Coli (APC) is a well-known tumor-suppressing gene. • We found aspirin up-regulates the protein of APC. • Aspirin suppressed the expression of IKKβ, an essential kinase in NFκB activation. • The deletion of IKKβ significantly increases the expression of APC protein. - Abstract: Aspirin has been widely used as analgesic, antipyretic and anti-inflammatory medicine for long. In addition to these traditional effects, clinical studies suggest that aspirin can protect against cancer, but its mechanism has not been explored. To unveil it, we identified the proteins up- or down-regulated after incubation with aspirin by using proteomics analysis with Nano-flow LC/MALDI-TOF system. Interestingly, the analysis identified the protein of Adenomatous Polyposis Coli (APC) as one of the most up-regulated protein. APC regulates cell proliferation or angiogenesis, and is widely known as a tumor-suppressing gene which can cause colorectal cancer when it is mutated. Western blots confirmed this result, and real-time PCR indicated it is transcriptionally regulated. We further tried to elucidate the molecular mechanism with focusing on IKKβ. IKKβ is the essential kinase in activation of nuclear factor-kappa B (NF-κB), major transcriptional factors that regulate genes responsible for inflammation or immune response. Previous reports indicated that aspirin specifically inhibits IKKβ activity, and constitutively active form of IKKβ accelerates APC loss. We found that aspirin suppressed the expression of IKKβ, and the deletion of IKKβ by siRNA increases the expression of APC in HEK294 cells. Finally, we observed similar effects of aspirin in human umbilical vein endothelial cells. Taken together, these results reveal that aspirin up-regulates the expression of APC via the suppression of IKKβ. This can be a mechanism how aspirin prevents cancer at

Aspirin augments the expression of Adenomatous Polyposis Coli protein by suppression of IKKβ

Energy Technology Data Exchange (ETDEWEB)

Ashida, Noboru, E-mail: nashida@kuhp.kyoto-u.ac.jp [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Kishihata, Masako [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Tien, Dat Nguyen [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kamei, Kaeko [Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kimura, Takeshi [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Yokode, Masayuki [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan)

2014-04-04

Highlights: • Clinical studies revealed aspirin inhibits cancer, but the mechanism is not known. • Adenomatous Polyposis Coli (APC) is a well-known tumor-suppressing gene. • We found aspirin up-regulates the protein of APC. • Aspirin suppressed the expression of IKKβ, an essential kinase in NFκB activation. • The deletion of IKKβ significantly increases the expression of APC protein. - Abstract: Aspirin has been widely used as analgesic, antipyretic and anti-inflammatory medicine for long. In addition to these traditional effects, clinical studies suggest that aspirin can protect against cancer, but its mechanism has not been explored. To unveil it, we identified the proteins up- or down-regulated after incubation with aspirin by using proteomics analysis with Nano-flow LC/MALDI-TOF system. Interestingly, the analysis identified the protein of Adenomatous Polyposis Coli (APC) as one of the most up-regulated protein. APC regulates cell proliferation or angiogenesis, and is widely known as a tumor-suppressing gene which can cause colorectal cancer when it is mutated. Western blots confirmed this result, and real-time PCR indicated it is transcriptionally regulated. We further tried to elucidate the molecular mechanism with focusing on IKKβ. IKKβ is the essential kinase in activation of nuclear factor-kappa B (NF-κB), major transcriptional factors that regulate genes responsible for inflammation or immune response. Previous reports indicated that aspirin specifically inhibits IKKβ activity, and constitutively active form of IKKβ accelerates APC loss. We found that aspirin suppressed the expression of IKKβ, and the deletion of IKKβ by siRNA increases the expression of APC in HEK294 cells. Finally, we observed similar effects of aspirin in human umbilical vein endothelial cells. Taken together, these results reveal that aspirin up-regulates the expression of APC via the suppression of IKKβ. This can be a mechanism how aspirin prevents cancer at

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…

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

International Nuclear Information System (INIS)

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

1984-01-01

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

Aspirin Allergy Desensitization in Cerebrovascular Disease

Science.gov (United States)

Zuckerman, Scott L; Seder, David B; Tsujiura, Crystiana; Cushing, Deborah; Gallup, Holly; Mocco, J; Hanel, Richard A; Ecker, Robert D

2014-01-01

Summary Aspirin (ASA) is the mainstay of treatment in cerebrovascular and systemic vascular disease. ASA hypersensitivity can pose a challenge to achieving optimum medical management prior to and after neurointerventional treatment. Desensitization to ASA is well described in the allergy and cardiovascular literature, but there are no similar discussions specific to neurointervention. The purpose of our study was to describe our experience with ASA hypersensitivity management and review the relevant literature. Two cases of patients with symptomatic cerebrovascular disease requiring neurointervention who were successfully desensitized to their ASA hypersensitivity prior to treatment are described. The subsequent literature is reviewed. Several ASA desensitization protocols exist and have been proven to successfully treat ASA hypersensitivity and allow for ASA therapy to be safely initiated. We describe several previously published protocols. ASA desensitization is a safe and simple way to manage ASA hypersensitivity. We provide comprehensive management guidelines for the neurointerventionalist engaging in ASA desensitization. PMID:24556294

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

Edoxaban Plus Aspirin vs Dual Antiplatelet Therapy in Endovascular Treatment of Patients With Peripheral Artery Disease: Results of the ePAD Trial.

Science.gov (United States)

Moll, Frans; Baumgartner, Iris; Jaff, Michael; Nwachuku, Chuke; Tangelder, Marco; Ansel, Gary; Adams, George; Zeller, Thomas; Rundback, John; Grosso, Michael; Lin, Min; Mercur, Michele F; Minar, Erich

2018-04-01

To report a randomized study that investigated the safety (risk of major bleeds) and potential efficacy of edoxaban, an oral anticoagulant that targets the major components of arterial thrombi, to prevent loss of patency following endovascular treatment (EVT). Between February 2012 and June 2014, 203 patients who underwent femoropopliteal EVT were randomized to receive aspirin plus edoxaban or aspirin plus clopidogrel for 3 months in the Edoxaban in Peripheral Arterial Disease (ePAD) study ( ClinicalTrials.gov identifier NCT01802775). Randomization assigned 101 patients (mean age 68.0±10.4 years; 67 men) to the edoxaban group and 102 patients (mean age 66.7±8.6 years; 78 men) to the clopidogrel group. The primary safety endpoint was bleeding as classified by the TIMI (Thrombolysis in Myocardial Infarction) criteria and ISTH (International Society of Thrombosis and Hemostasis) criteria; the efficacy endpoint was the rate of restenosis/reocclusion. There were no major or life-threatening bleeding events in the edoxaban group, while there were 2 major and 2 life-threatening bleeding events in the clopidogrel group by the TIMI criteria. By the ISTH classification, there was 1 major and 1 life-threatening bleeding event vs 5 major and 2 life-threatening bleeding events, respectively [relative risk (RR) 0.20, 95% confidence interval (CI) 0.02 to 1.70]. The bleeding risk was not statistically different with either treatment when assessed by TIMI or ISTH. Following 6 months of observation, there was a lower incidence of restenosis/reocclusion with edoxaban compared with clopidogrel (30.9% vs 34.7%; RR 0.89, 95% CI 0.59 to 1.34, p=0.643). These results suggest that patients who have undergone EVT have similar risks for major and life-threatening bleeding events with edoxaban and aspirin compared with clopidogrel and aspirin. The incidence of restenosis/reocclusion events, while not statistically different, was lower with edoxaban and aspirin, but an adequately sized trial

Aspirin use and early age-related macular degeneration: a meta-analysis.

Science.gov (United States)

Kahawita, Shyalle K; Casson, Robert J

2014-02-01

The aim of this review was to evaluate the evidence for an association between Aspirin use and early age-related macular degeneration (ARMD). A literature search was performed in 5 databases with no restrictions on language or date of publication. Four studies involving 10292 individuals examining the association between aspirin and ARMD met the inclusion criteria. Meta-analysis was carried out by Cochrane Collaboration Review Manager 5.2 software (Cochrane Collaboration, Copenhagen, Denmark). The pooled odd ratios showed that Aspirin use was associated with early ARMD (pooled odds ratio 1.43, 95% CI 1.09-1.88). There is a small but statistically significant association between Aspirin use and early ARMD, which may warrant further investigation. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats

DEFF Research Database (Denmark)

Abelson, Klas S P; Kommalage, Mahinda; Höglund, A Urban

2004-01-01

Aspirin and paracetamol have been shown to suppress non-inflammatory pain conditions like thermal, visceral and mechanical pain in mice and rats. The non-inflammatory antinociception appears to be mediated by central receptor mechanisms, such as the cholinergic system. In this study, we tested...... the hypothesis that the non-inflammatory antinociception of aspirin and paracetamol could be mediated by an increase of intraspinal acetylcholine release. Microdialysis probes were placed intraspinally in anesthetized rats for acetylcholine sampling. Subcutaneously administered aspirin 100 and 300 mg....../kg increased, while paracetamol 300 mg/kg decreased intraspinal acetylcholine release. Intraspinal drug administration did not affect acetylcholine release. Our results suggest that an increased intraspinal acetylcholine release could be involved in part of the non-inflammatory pain suppression by aspirin...

Use of Aspirin postdiagnosis improves survival for colon cancer patients

NARCIS (Netherlands)

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

2012-01-01

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

Aspirin: 120 years of innovation. A report from the 2017 Scientific Conference of the International Aspirin Foundation, 14 September 2017, Charité, Berlin.

Science.gov (United States)

Walker, Jaqui; Hutchison, Pippa; Ge, Junbo; Zhao, Dong; Wang, Yongjun; Rothwell, Peter M; Gaziano, J Michael; Chan, Andrew; Burn, John; Chia, John; Langley, Ruth; O'Donnell, Valerie; Rocca, Bianca; Hawkey, Chris

2018-01-01

Acetylsalicylic acid was first synthesised by Dr FeIix Hoffman on 10th August 1897 and Aspirin was born. It quickly became the best-known pain killer in the world and in the 120 years since this event, aspirin has continued to attract interest, innovation and excitement. Set within the walls of the preserved ruins of Rudolf Virchow's lecture hall at Charité, within Berlin's Museum of Medical History, the International Aspirin Foundation's 28th Scientific Conference served to facilitate international, multi-disease, multidisciplinary discussion about the current understanding of aspirin's mechanisms of action and its utility in modern medicine as well as ideas for future research into its multifaceted applications to enhance global health. In addition to the delegates in Berlin, 300 medical doctors at the 19th Annual Scientific Congress of the Chinese Society of Cardiology were able to join the cardiology sessions from Taiyuan, Shangxi province via a live streaming link to and from China. This led to useful discussion and allowed a truly international perspective to the meeting.

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

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.

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.

Cytomorphological monitoring in multimodality therapy of endometral cancer patients

International Nuclear Information System (INIS)

Galil-Ogly, G.A.; Titova, V.A.; Yarovaya, N.Yu.; Ingberman, Ya.Kh.; Bershchanskaya, A.M.; Pukhlikov, A.V.

1990-01-01

The paper is devoted to analysis of clinicomorphological data on the status of a primary endometrial tumor in 209 endometrial cancer patients, treated by radical and palliative radiation therapy (112 patients) and the combined method (88 patients) including preoperative intensive concentrated intracavitary irradiation and hormonotherapy. Dynamic cytological monitoring was performed during radiation therapy and in a period up to 12 mos. after the discontinuation of antitumor therapy. Dynamic cytomorphological monitoring is an important stage in patients who cannot be operated upon as a result of tumor spreading or somatic contraindications

Aspirin Induces Apoptosis through Release of Cytochrome c from Mitochondria

Directory of Open Access Journals (Sweden)

Katja C. Zimmermann

2000-01-01

Full Text Available Nonsteroidal anti-inflammatory drugs (NSAID reduce the risk for cancer, due to their anti proliferative and apoptosis-inducing effects. A critical pathway for apoptosis involves the release of cytochrome c from mitochondria, which then interacts with Apaf-1 to activate caspase proteases that orchestrate cell death. In this study we found that treatment of a human cancer cell line with aspirin induced caspase activation and the apoptotic cell morphology, which was blocked by the caspase inhibitor zVAD-fmk. Further analysis of the mechanism underlying this apoptotic event showed that aspirin induces translocation of Bax to the mitochondria and triggers release of cytochrome c into the cytosol. The release of cytochrome c from mitochondria was inhibited by overexpression of the antiapoptotic protein Bcl-2 and cells that lack Apaf-1 were resistant to aspirin-induced apoptosis. These data provide evidence that the release of cytochrome c is an important part of the apoptotic mechanism of aspirin.

Reduction of indium-111 platelet deposition on Dacron vascular grafts in humans by aspirin plus dipyridamole

International Nuclear Information System (INIS)

Stratton, J.R.; Ritchie, J.L.

1986-01-01

Aspirin plus dipyridamole reduces platelet accumulation on short-term Dacron vascular grafts in man. To determine whether drug inhibition of platelet deposition is sustained on older grafts, we studied 18 men aged 41 to 87 years who had Dacron aortic bifurcation grafts in place a mean of 43.4 months (range 9.8 to 121.0) before and during short-term therapy with aspirin (325 mg tid) plus dipyridamole (75 mg tid). During both the baseline and drug studies, indium-111 ( 111 In) platelet deposition was quantitated by two techniques, standard planar imaging performed at 24, 48, and 72 hr after injection of platelets and single photon emission computed tomographic imaging performed at 24 and 72 hr after injection. All analyses were performed in a blinded fashion. On both the planar and tomographic images, platelet accumulation on the graft was quantitated by a graft/blood ratio that compared activity in the graft to simultaneously collected whole blood 111 In platelet activity. Aspirin plus dipyridamole reduced the tomographic graft/blood ratio at 24 hr (20.6 +/- 3.5 vs 17.3 +/- 2.5) (+/-SEM) and at 72 hr (29.0 +/- 4.8 vs 25.0 +/- 4.1) after injection of platelets (p = .02). Dacron vascular grafts. Similarly, the planar graft/blood ratio was reduced at 24 hr (2.7 +/- 0.5 vs 2.4 +/- 0.5), 48 hr (3.7 +/- 0.9 vs 3.1 +/- 0.7), and 72 hr (4.0 +/- 0.9 vs 3.6 +/- 0.8) (p = .04). We conclude that aspirin (325 mg tid) plus dipyridamole (75 mg tid) reduces platelet accumulation on long-term Dacron vascular grafts

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

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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.

Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells.

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Gu, Mancang; Nishihara, Reiko; Chen, Yang; Li, Wanwan; Shi, Yan; Masugi, Yohei; Hamada, Tsuyoshi; Kosumi, Keisuke; Liu, Li; da Silva, Annacarolina; Nowak, Jonathan A; Twombly, Tyler; Du, Chunxia; Koh, Hideo; Li, Wenbin; Meyerhardt, Jeffrey A; Wolpin, Brian M; Giannakis, Marios; Aguirre, Andrew J; Bass, Adam J; Drew, David A; Chan, Andrew T; Fuchs, Charles S; Qian, Zhi Rong; Ogino, Shuji

2017-10-20

Evidence suggests that nonsteroidal anti-inflammatory drug aspirin (acetylsalicylic acid) may improve patient survival in PIK3CA -mutant colorectal carcinoma, but not in PIK3CA -wild-type carcinoma. However, whether aspirin directly influences the viability of PIK3CA -mutant colon cancer cells is poorly understood. We conducted in vitro experiments to test our hypothesis that the anti-proliferative activity of aspirin might be stronger for PIK3CA -mutant colon cancer cells than for PIK3CA -wild-type colon cancer cells. We measured the anti-proliferative effect of aspirin at physiologic concentrations in seven PIK3CA -mutant and six PIK3CA -wild-type human colon cancer cell lines. After exposure to aspirin, the apoptotic index and cell cycle phase of colon cancer cells were assessed. In addition, the effect of aspirin was examined in parental SW48 cells and SW48 cell clones with individual knock-in PIK3CA mutations of either c.3140A>G (p.H1047R) or c.1633G>A (p.E545K). Aspirin induced greater dose-dependent loss of cell viability in PIK3CA -mutant cells than in PIK3CA -wild-type cells after treatment for 48 and 72 hours. Aspirin treatment also led to higher proportions of apoptotic cells and G0/G1 phase arrest in PIK3CA -mutant cells than in PIK3CA -wild-type cells. Aspirin treatment of isogenic SW48 cells carrying a PIK3CA mutation, either c.3140A>G (p.H1047R) or c.1633G>A (p. E545K), resulted in a more significant loss of cell viability compared to wild-type controls. Our findings indicate that aspirin causes cell cycle arrest, induces apoptosis, and leads to loss of cell viability more profoundly in PIK3CA -mutated colon cancer cells than in PIK3CA -wild-type colon cancer cells. These findings support the use of aspirin to treat patients with PIK3CA -mutant colon cancer.

Combining aspirin with angiotensin converting enzyme inhibitors in heart failure: how safe is it?

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Mehta, H; Mahajan, A; Bansal, N; Vaidya, S; Pathak, L

1998-11-01

The above discussion on the interaction of aspirin and ACE inhibitors seems to suggest that aspirin in high doses may have adverse interaction with ACE inhibitors in patients with heart failure but the data obtained is not sufficient or conclusive to recommended omission of aspirin in patients with heart failure. This raises a query in the mind of the physician whether to use a combination or not? The role of aspirin in the early period after myocardial infarction is well established so is the role of ACE inhibitors. Hence in patients with myocardial infarction and preserved left ventricular function it would not be wrong to administer combination of ACE inhibitors and aspirin. Albeit at a lower dose. In patients with large myocardial infarction or heart failure, warfarin may be an option but still needs to be documented in large trials. As suggested long term use of aspirin after infarction is still ambiguous and may be harmful in patients with heart failure with its anticedent side effects. But long term benefits of ACE inhibitors in heart failure are well documented. Hence if a choice has to be made whether to discontinue either of the two drugs it would be preferable to stop the aspirin. To answer the issue of use of aspirin in patients with heart failure it would be essential to conduct a double blind randomized trial comparing known anti-thrombotic treatment, aspirin and anti-coagulants on mortality in patients with heart failure, especially caused by coronary artery disease. Such a trial is underway at the present and till the results are available it should be left to clinical judgement of the physician whether to administer aspirin in patients with heart failure after weighing the benefits versus risk.

Aspirin Inhibits Platelet-Derived Sphingosine-1-Phosphate Induced Endothelial Cell Migration.

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Polzin, Amin; Knoop, Betül; Böhm, Andreas; Dannenberg, Lisa; Zurek, Mark; Zeus, Tobias; Kelm, Malte; Levkau, Bodo; Rauch, Bernhard H

2018-01-01

Aspirin plays a crucial role in the prevention of cardiovascular diseases. We previously described that aspirin has effects beyond inhibition of platelet aggregation, as it inhibited thrombin-mediated release of sphingosine-1-phosphate (S1P) from human platelets. S1P is a bioactive lipid with important functions on inflammation and apoptosis. In endothelial cells (EC), S1P is a key regulator of cell migration. In this study, we aimed to analyze the effects of aspirin on platelet-induced EC migration. Human umbilical EC migration was measured by Boyden chamber assay. EC migration was induced by platelet supernatants of thrombin receptor-activating peptide-1 (AP1) stimulated platelets. To investigate the S1P receptor subtype that promotes EC migration, specific inhibitors of S1P receptor subtypes were applied. S1P induced EC migration in a concentration-dependent manner. EC migration induced by AP1-stimulated platelet supernatants was reduced by aspirin. S1P1 receptor inhibition almost completely abolished EC migration induced by activated platelets. The inhibition of S1P2 or S1P3 receptor had no effect. Aspirin inhibits EC migration induced by activated platelets that is in part due to S1P and mediated by the endothelial S1P1 receptor. The clinical significance of this novel mechanism of aspirin action has to be investigated in future studies. © 2017 S. Karger AG, Basel.

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

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.

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)

Aspirin for acute treatment of episodic tension-type headache in adults.

Science.gov (United States)

Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

2017-01-13

Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headache days per month), and chronic TTH (15 headache days per month or more). Aspirin is one of a number of analgesics suggested for acute treatment of episodic TTH. To assess the efficacy and safety of aspirin for acute treatment of episodic tension-type headache (TTH) in adults compared with placebo or any active comparator. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and the Oxford Pain Relief Database from inception to September 2016, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites. We included randomised, double-blind, placebo-controlled studies (parallel-group or cross-over) using oral aspirin for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm. Two review authors independently assessed studies for inclusion and extracted data. For various outcomes (predominantly those recommended by the International Headache Society (IHS)), we calculated the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT), one additional harmful outcome (NNH), or to prevent one event (NNTp) for oral aspirin compared to placebo or an active intervention.We assessed the evidence using GRADE and created a 'Summary of findings' table. We included five studies enrolling adults with frequent episodic TTH; 1812 participants took medication, of which 767 were included in comparisons of aspirin 1000 mg with placebo, and 405 in comparisons of aspirin 500 mg or 650 mg with placebo. Not all of these participants provided data for outcomes of interest in this review

Antiplatelet therapy for recurrent stroke prevention: newer perspectives based on (MATCH), (CHARISMA), and (ESPRIT).

Science.gov (United States)

Gorelick, Philip B

2008-01-01

Antiplatelet therapy is an important component of our armamentarium for recurrent stroke prevention. Aspirin is a safe and effective antiplatelet drug for recurrent stroke prevention, however, it has been challenged recently by the thienopyridine derivative, clopidogrel, and the combination agent, aspirin plus extended release dipyridamole. In this review, we discuss recent studies of thienopyridine derivatives and aspirin plus extended-release dipyridamole in stroke prevention and evidence-based guidelines for the administration of these agents in practice for recurrent stroke prevention.

Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery

DEFF Research Database (Denmark)

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

2018-01-01

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

Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

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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

Advances of reporter gene imaging monitoring stem cell therapy

International Nuclear Information System (INIS)

Pei Zhijun; Zhang Yongxue

2010-01-01

Stem cell transplantation in the treatment of various tissue damage or degenerative diseases are research hotspots both at home and abroad. However, ignorance of the homing, differentiation and functional expression of the stem cell in vivo influence the further development of stem cell therapy. As an important component of molecular imaging technology, reporter gene imaging dynamically monitors the change of stem cell in vivo via monitoring the expression of transfected reporter gene. This paper briefly describes the latest research progress and the future development trend of the monitoring of reporter gene imaging in stem cell therapy in vivo. (authors)

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.

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

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

2016-01-01

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

Reduction of NANOG Mediates the Inhibitory Effect of Aspirin on Tumor Growth and Stemness in Colorectal Cancer

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Hefei Wang

2017-11-01

Full Text Available Background/Aims: Cancer stem cells (CSCs are considered to be responsible for tumor relapse and metastasis, which serve as a potential therapeutic target for cancer. Aspirin has been shown to reduce cancer risk and mortality, particularly in colorectal cancer. However, the CSCs-suppressing effect of aspirin and its relevant mechanisms in colorectal cancer remain unclear. Methods: CCK8 assay was employed to detect the cell viability. Sphere formation assay, colony formation assay, and ALDH1 assay were performed to identify the effects of aspirin on CSC properties. Western blotting was performed to detect the expression of the stemness factors. Xenograft model was employed to identify the anti-cancer effects of aspirin in vivo. Unpaired Student t test, ANOVA test and Kruskal-Wallis test were used for the statistical comparisons. Results: Aspirin attenuated colonosphere formation and decreased the ALDH1 positive cell population of colorectal cancer cells. Aspirin inhibited xenograft tumor growth and reduced tumor cells stemness in nude mice. Consistently, aspirin decreased the protein expression of stemness-related transcription factors, including c-Myc, OCT4 and NANOG. Suppression of NANOG blocked the effect of aspirin on sphere formation. Conversely, ectopic expression of NANOG rescued the aspirin-repressed sphere formation, suggesting that NANOG is a key downstream target. Moreover, we found that aspirin repressed NANOG expression in protein level by decreasing its stability. Conclusion: We have provided new evidence that aspirin attenuates CSC properties through down-regulation of NANOG, suggesting aspirin as a promising therapeutic agent for colorectal cancer treatment.

Aspirin-Mediated Acetylation Protects Against Multiple Neurodegenerative Pathologies by Impeding Protein Aggregation.

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Ayyadevara, Srinivas; Balasubramaniam, Meenakshisundaram; Kakraba, Samuel; Alla, Ramani; Mehta, Jawahar L; Shmookler Reis, Robert J

2017-12-10

Many progressive neurological disorders, including Alzheimer's disease (AD), Huntington's disease, and Parkinson's disease (PD), are characterized by accumulation of insoluble protein aggregates. In prospective trials, the cyclooxygenase inhibitor aspirin (acetylsalicylic acid) reduced the risk of AD and PD, as well as cardiovascular events and many late-onset cancers. Considering the role played by protein hyperphosphorylation in aggregation and neurodegenerative diseases, and aspirin's known ability to donate acetyl groups, we asked whether aspirin might reduce both phosphorylation and aggregation by acetylating protein targets. Aspirin was substantially more effective than salicylate in reducing or delaying aggregation in human neuroblastoma cells grown in vitro, and in Caenorhabditis elegans models of human neurodegenerative diseases in vivo. Aspirin acetylates many proteins, while reducing phosphorylation, suggesting that acetylation may oppose phosphorylation. Surprisingly, acetylated proteins were largely excluded from compact aggregates. Molecular-dynamic simulations indicate that acetylation of amyloid peptide energetically disfavors its association into dimers and octamers, and oligomers that do form are less compact and stable than those comprising unacetylated peptides. Hyperphosphorylation predisposes certain proteins to aggregate (e.g., tau, α-synuclein, and transactive response DNA-binding protein 43 [TDP-43]), and it is a critical pathogenic marker in both cardiovascular and neurodegenerative diseases. We present novel evidence that acetylated proteins are underrepresented in protein aggregates, and that aggregation varies inversely with acetylation propensity after diverse genetic and pharmacologic interventions. These results are consistent with the hypothesis that aspirin inhibits protein aggregation and the ensuing toxicity of aggregates through its acetyl-donating activity. This mechanism may contribute to the neuro-protective, cardio

Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

OpenAIRE

Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

1989-01-01

1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reactio...

Aspirin desensitization in aspirin-sensitive asthma: failure to maintain a desensitized state during prolonged therapy.

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Dankner, R E; Wedner, H J

1983-11-01

A patient with a history of asthma induced by acetylsalicylic acid (ASA) was found to be ASA sensitive when orally challenged with ASA. She was successfully desensitized using incremental doses of ASA given orally and maintained on ASA or other nonsteroidal antiinflammatory (NSAI) agents for the treatment of arthritis. After 6 months of uninterrupted therapy the patient developed asthmatic symptoms that were related to ASA and NSAI drug therapy. Although desensitization may be achieved in patients with ASA-sensitive asthma, sensitivity may recur despite continuous therapy.

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.

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...

Effect of transcervical resection of adhesion combined with low-dose aspirin on uterine artery blood flow and Smad2/3 in endometrial tissue

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Qian-Wen Chen

2016-11-01

Full Text Available Objective: To study the effect of transcervical resection of adhesion combined with lowdose aspirin on uterine artery blood flow and Smad2/3 in endometrial tissue. Methods: A total of 78 patients with severe intrauterine adhesions who received transcervical resection of adhesion in our hospital between June 2012 and October 2014 were prospectively studied and randomly divided into two groups, observation group received postoperative estrogenprogestogen combined with low-dose aspirin therapy, and control group received postoperative estrogen-progestogen therapy. Ultrasound examination was conducted before and after treatment to determine uterine artery and endometrial blood flow parameters, intrauterine adhesion tissue was collected to detect the expression levels of Smad2 and Smad3 as well as downstream molecules, and serum was collected to determine the levels of cytokines. Results: On the ovulation day after 3 cycles of treatment, uterine artery RI and PI of observation group were significantly lower than those of control group, and endometrial VI, FI and VFI were significantly higher than those of control group; uPA expression level in intrauterine adhesion tissue of observation group was significantly higher than that of control group, Smad2, Smad3, PAI-1, ADAM15 and ADAM17 expression levels were significantly lower than those of control group, and serum TGF-β, VEGF, CTGF, IGF-I and TNF-α levels were significantly lower than those of control group. Conclusions: Transcervical resection of adhesion combined with low-dose aspirin therapy can improve the postoperative uterine artery and endometrial blood flow state, inhibit extracellular matrix deposition mediated by Smad2/3 signaling pathway and prevent intrauterine re-adhesion in patients with intrauterine adhesions.

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 ...

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)

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.

Ab initio study of aspirin adsorption on single-walled carbon and carbon nitride nanotubes

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Lee, Yongju; Kwon, Dae-Gyeon; Kim, Gunn; Kwon, Young-Kyun

We use ab intio density functional theory to investigate the adsorption properties of acetylsalicylic acid or aspirin on a (10, 0) carbon nanotube (CNT) and a (8, 0) triazine-based graphitic carbon nitride nanotube (CNNT). It is found that an aspirin molecule binds stronger to the CNNT with its adsorption energy of 0.67 eV than to the CNT with 0.51 eV. The stronger adsorption energy on the CNNT is ascribed to the high reactivity of its N atoms with high electron affinity. The CNNT exhibits local electric dipole moments, which cause strong charge redistribution in the aspirin molecule adsorbed on the CNNT than on the CNT. We also explore the influence of an external electric field on the adsorption properties of aspirin on these nanotubes by examining the modifications in their electronic band structures, partial densities of states, and charge distributions. It is found that an electric field applied along a particular direction induces aspirin molecular states in the in-gap region of the CNNT implying a potential application of aspirin detection.

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

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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.

The risk of venous thromboembolism with aspirin compared to anticoagulants after hip and knee arthroplasty.

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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.

Effect of Prior Aspirin Treatment on Patients With Acute Coronary Syndromes: Insights From the PROSPECT Study.

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Brener, Sorin J; Maehara, Akiko; Mintz, Gary S; Weisz, Giora; de Bruyne, Bernard; Serruys, Patrick W; Stone, Gregg W

2015-12-01

Prior aspirin treatment is considered a risk factor for adverse outcomes in acute coronary syndrome (ACS) patients. The relationships between aspirin pretreatment and findings on quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), as well as clinical outcomes, are not well understood. In the PROSPECT trial, QCA and triple-vessel IVUS imaging were performed after successful percutaneous coronary intervention (PCI) of the culprit lesion(s) in ACS patients. We compared patients receiving aspirin within 7 days of enrollment to those naive to aspirin. Propensity score matching was performed to adjust for differences in baseline characteristics. Aspirin-pretreated patients (n = 236; 35%) were older and more likely to have known coronary disease than those without pretreatment (P≤.01 for all). Pretreated patients had more untreated non-culprit lesions with angiographic and IVUS characteristics predictive of future events (53.1% vs 38.6%; PPROSPECT trial, aspirin pretreatment identifies an older population with more advanced coronary disease. Aspirin pretreatment was not an independent predictor of MACE in ACS patients treated with an early invasive strategy. The extent to which aspirin pretreatment is a risk factor for adverse events after PCI in ACS should be revisited.

Aspirin degradation in surface-charged TEMPO-oxidized mesoporous crystalline nanocellulose.

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Carlsson, Daniel O; Hua, Kai; Forsgren, Johan; Mihranyan, Albert

2014-01-30

TEMPO-mediated surface oxidation of mesoporous highly crystalline Cladophora cellulose was used to introduce negative surface charges onto cellulose nanofibrils without significantly altering other structural characteristics. This enabled the investigation of the influence of mesoporous nanocellulose surface charges on aspirin chemical stability to be conducted. The negative surface charges (carboxylate content 0.44±0.01 mmol/g) introduced on the mesoporous crystalline nanocellulose significantly accelerated aspirin degradation, compared to the starting material which had significantly less surface charge (0.06±0.01 mmol/g). This effect followed from an increased aspirin amorphisation ability in mesopores of the oxidized nanocellulose. These results highlight the importance of surface charges in formulating nanocellulose for drug delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

In vivo quantitation of platelet deposition on human peripheral arterial bypass grafts using indium-111-labeled platelets. Effect of dipyridamole and aspirin

International Nuclear Information System (INIS)

Pumphrey, C.W.; Chesebro, J.H.; Dewanjee, M.K.; Wahner, H.W.; Hollier, L.H.; Pairolero, P.C.; Fuster, V.

1983-01-01

Indium-111-labeled autologous platelets, injected 48 hours after operation, were used to evaluate the thrombogenicity of prosthetic material and the effect of platelet inhibitor therapy in vivo. Dacron double-velour (Microvel) aortofemoral artery bifurcation grafts were placed in 16 patients and unilateral polytetrafluoroethylene femoropopliteal grafts were placed in 10 patients. Half the patients in each group received platelet inhibitors before operation (dipyridamole, 100 mg 4 times a day) and after operation (dipyridamole, 75 mg, and acetylsalicylic acid, 325 mg 3 times a day); the rest of the patients served as control subjects. Five-minute scintigrams of the graft region were taken with a gamma camera interfaced with a computer 48, 72, and 96 hours after injection of the labeled platelets. Platelet deposition was estimated from the radioactivities of the grafts and expressed as counts per 100 pixels per microcurie injected. Dipyridamole and aspirin therapy significantly reduced the number of platelets deposited on Dacron grafts and prevented platelet accumulation over 3 days. With the small amount of platelet deposition on polytetrafluoroethylene femoropopliteal artery grafts even in control patients, platelet inhibitor therapy had no demonstrable effect on platelet deposition on these grafts. It is concluded that (1) platelet deposition on vascular grafts in vivo can be quantitated by noninvasive methods, and (2) dipyridamole and aspirin therapy reduced platelet deposition on Dacron aortofemoral artery grafts

Effects of Ramadan fasting on aspirin resistance in type 2 diabetic patients.

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Bouida, Wahid; Beltaief, Kaouthar; Baccouche, Houda; Sassi, Mouna; Dridi, Zohra; Trabelsi, Imen; Laaouiti, Kamel; Chakroun, Taher; Hellara, Ilhem; Boukef, Riadh; Sakly, Nabil; Hassine, Mohsen; Added, Faouzi; Razgallah, Rabie; Najjar, Fadhel; Nouira, Semir

2018-01-01

Ramadan fasting (RF) may affect aspirin resistance. We conducted this study in patients with cardiovascular risk (CVR) factors to assess the effect of RF on aspirin resistance and explore whether type 2 diabetes mellitus (DM) would influence this effect. A total of 177 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking aspirin. Physical exam and standard biological tests including glycaemia and serum lipids data were performed before Ramadan (Pre-R), at the last week of Ramadan (R) and four weeks after the end of Ramadan (Post-R). In the same visits caloric intake was calculated and platelet reactivity to aspirin was assessed using Verify Now point-of-care assay. In the overall population, there was no significant change in absolute aspirin reaction unit (ARU) values and in metabolic parameters. In DM patients (n = 127), ARU change from Pre-R values was+19.7 (p = 0.01) and +14.4 (p = 0.02) respectively at R and Post-R. During Ramadan, glycaemia, triglycerides, and cholesterol levels increased significantly and returned to Pre-R values thereafter. These changes were not observed in non-DM patients. During RF aspirin resistance increased only in DM patients. This effect persisted one month after Ramadan. Simultaneous alteration of glycemic control and increase of serum lipids levels could potentially be a favorable factor. The protocol was registered at clinicaltrials.gov under: NCT02720133.

Effects of Ramadan fasting on aspirin resistance in type 2 diabetic patients

Science.gov (United States)

Bouida, Wahid; Beltaief, Kaouthar; Baccouche, Houda; Sassi, Mouna; Dridi, Zohra; Trabelsi, Imen; Laaouiti, Kamel; Chakroun, Taher; Hellara, Ilhem; Boukef, Riadh; Sakly, Nabil; Hassine, Mohsen; Added, Faouzi; Razgallah, Rabie; Najjar, Fadhel; Nouira, Semir

2018-01-01

Aims Ramadan fasting (RF) may affect aspirin resistance. We conducted this study in patients with cardiovascular risk (CVR) factors to assess the effect of RF on aspirin resistance and explore whether type 2 diabetes mellitus (DM) would influence this effect. Methods A total of 177 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking aspirin. Physical exam and standard biological tests including glycaemia and serum lipids data were performed before Ramadan (Pre-R), at the last week of Ramadan (R) and four weeks after the end of Ramadan (Post-R). In the same visits caloric intake was calculated and platelet reactivity to aspirin was assessed using Verify Now point-of-care assay. Results In the overall population, there was no significant change in absolute aspirin reaction unit (ARU) values and in metabolic parameters. In DM patients (n = 127), ARU change from Pre-R values was+19.7 (p = 0.01) and +14.4 (p = 0.02) respectively at R and Post-R. During Ramadan, glycaemia, triglycerides, and cholesterol levels increased significantly and returned to Pre-R values thereafter. These changes were not observed in non-DM patients. Conclusions During RF aspirin resistance increased only in DM patients. This effect persisted one month after Ramadan. Simultaneous alteration of glycemic control and increase of serum lipids levels could potentially be a favorable factor. Study registration The protocol was registered at clinicaltrials.gov under: NCT02720133. PMID:29529091

Irradiation-Induced Cardiac Connexin-43 and miR-21 Responses Are Hampered by Treatment with Atorvastatin and Aspirin

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Csilla Viczenczova

2018-04-01

Full Text Available Radiation of the chest during cancer therapy is deleterious to the heart, mostly due to oxidative stress and inflammation related injury. A single sub-lethal dose of irradiation has been shown to result in compensatory up-regulation of the myocardial connexin-43 (Cx43, activation of the protein kinase C (PKC signaling along with the decline of microRNA (miR-1 and an increase of miR-21 levels in the left ventricle (LV. We investigated whether drugs with antioxidant, anti-inflammatory or vasodilating properties, such as aspirin, atorvastatin, and sildenafil, may affect myocardial response in the LV and right ventricle (RV following chest irradiation. Adult, male Wistar rats were subjected to a single sub-lethal dose of chest radiation at 25 Gy and treated with aspirin (3 mg/day, atorvastatin (0.25 mg/day, and sildenafil (0.3 mg/day for six weeks. Cx43, PKCε and PKCδ proteins expression and levels of miR-1 as well as miR-21 were determined in the LV and RV. Results showed that the suppression of miR-1 was associated with an increase of total and phosphorylated forms of Cx43 as well as PKCε expression in the LV while having no effect in the RV post-irradiation as compared to the non-irradiated rats. Treatment with aspirin and atorvastatin prevented an increase in the expression of Cx43 and PKCε without change in the miR-1 levels. Furthermore, treatment with aspirin, atorvastatin, and sildenafil completely prevented an increase of miR-21 in the LV while having partial effect in the RV post irradiation. The increase in pro-apoptotic PKCδ was not affected by any of the used treatment. In conclusion, irradiation and drug-induced changes were less pronounced in the RV as compared to the LV. Treatment with aspirin and atorvastatin interfered with irradiation-induced compensatory changes in myocardial Cx43 protein and miR-21 by preventing their elevation, possibly via amelioration of oxidative stress and inflammation.

Effect of aspirin on chromosome aberration and DNA damage induced by X-rays in mice

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Niikawa, M.; Chuuriki, K.; Shibuya, K.; Seo, M.; Nagase, H.

In order to reveal the anticlastogenic potency of aspirin, we evaluated the suppressive ability of aspirin on chromosome aberrations induced by X-ray. Aspirin at doses of 0.5, 5 and 50 mg/kg was administrated intraperitoneally or orally at 0.5 h after or before the X-ray irradiation. The anticlastogenic activity of aspirin on chromosome aberrations induced by X-ray was determined in the mouse micronucleus test and alkaline single cell gel electrophoresis (SCG) assay in vivo. The frequency by polychromatic erythrocytes with micronuclei (MNPCEs) was decreased by about 19-61% at 0.5 h after and about 23-62% at 0.5 h before the X-ray irradiation. DNA damage by X-ray was significantly decreased by oral administration of aspirin at 0.5 h after or before the X-ray irradiation for the SCG assay. We consider aspirin can be used as preventive agents against exposure of X-ray.

Chemotherapeutic potential of diazeniumdiolate-based aspirin prodrugs in breast cancer.

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Basudhar, Debashree; Cheng, Robert C; Bharadwaj, Gaurav; Ridnour, Lisa A; Wink, David A; Miranda, Katrina M

2015-06-01

Diazeniumdiolate-based aspirin prodrugs have previously been shown to retain the anti-inflammatory properties of aspirin while protecting against the common side effect of stomach ulceration. Initial analysis of two new prodrugs of aspirin that also release either nitroxyl (HNO) or nitric oxide (NO) demonstrated increased cytotoxicity toward human lung carcinoma cells compared to either aspirin or the parent nitrogen oxide donor. In addition, cytotoxicity was significantly lower in endothelial cells, suggesting cancer-specific sensitivity. To assess the chemotherapeutic potential of these new prodrugs in treatment of breast cancer, we studied their effect both in cultured cells and in a nude mouse model. Both prodrugs reduced growth of breast adenocarcinoma cells more effectively than the parent compounds while not being appreciably cytotoxic in a related nontumorigenic cell line (MCF-10A). The HNO donor also was more cytotoxic than the related NO donor. The basis for the observed specificity was investigated in terms of impact on metabolism, DNA damage and repair, apoptosis, angiogenesis and metastasis. The results suggest a significant pharmacological potential for treatment of breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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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.

Reprint of: Aspirin use and early age-related macular degeneration: a meta-analysis.

Science.gov (United States)

Kahawita, Shyalle K; Casson, Robert J

2015-06-01

The aim of this review was to evaluate the evidence for an association between Aspirin use and early age-related macular degeneration (ARMD). A literature search was performed in 5 databases with no restrictions on language or date of publication. Four studies involving 10292 individuals examining the association between aspirin and ARMD met the inclusion criteria. Meta-analysis was carried out by Cochrane Collaboration Review Manager 5.2 software (Cochrane Collaboration, Copenhagen, Denmark). The pooled odd ratios showed that Aspirin use was associated with early ARMD (pooled odds ratio 1.43, 95% CI 1.09-1.88). There is a small but statistically significant association between Aspirin use and early ARMD, which may warrant further investigation. Copyright © 2015. Published by Elsevier Inc.

Low-dose aspirin, non-steroidal anti-inflammatory drugs, selective COX-2 inhibitors and breast cancer recurrence

DEFF Research Database (Denmark)

Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

2016-01-01

BACKGROUND: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors may improve outcomes in breast cancer patients. We investigated the association of aspirin, NSAIDs, and use of selective COX-2 inhibitors with breast cancer recurrence. METHODS: We identified incident...... stage I-III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry, who were diagnosed during 1996-2008. Prescriptions for aspirin (>99% low-dose aspirin), NSAIDs, and selective COX-2 inhibitors were ascertained from the National Prescription Registry. Follow-up began....... RESULTS: We identified 34,188 breast cancer patients with 233,130 person-years of follow-up. Median follow-up was 7.1 years; 5,325 patients developed recurrent disease. Use of aspirin, NSAIDs, or selective COX-2 inhibitors was not associated with the rate of recurrence (HRadjusted aspirin = 1.0, 95% CI...

Ambulatory blood pressure monitoring in patients with hyperthyroidism before the introduction of therapy and on therapy

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Stojanović Miloš

2017-01-01

Full Text Available The increased secretion of thyroid gland hormones affects the cardiovascular system by increasing heart rate and often by increasing systolic and diastolic blood pressure. We examined the influence of elevated thyroid hormone on blood pressure. Blood pressure monitoring was performed prior to the introduction of therapy in people with increased FT4 and on therapy when FT4 was in the normal range. We analyzed 32 people, of which 26 women had normal blood pressure values measured by blood pressure monitoring. Average age 45 and body mass index 27 kg/m2. Blood pressure was measured by monitoring blood pressure for 24 hours. On average, before the introduction of the therapy, it was 133/83 mmHg P 96 / min. The blood pressure on average on therapy with tireosuppressive was 128/82 mmHg P 74 / min. The Wilcoxon-Mann-Whitney paired test shows a significant P <0.05 higher systolic blood pressure and pulse rate during the day and night before the treatment, when FT4 was higher, than the time when medication was taking, when the FT4 was in the normal range. No significant difference was found for diastolic blood pressure before the introduction of therapy and during therapy with tireosuppressives. When values of FT4 are increased, monitoring of blood pressure shows significantly higher values of systolic blood pressure and pulse during day and night compared to systolic blood pressure and pulse values when FT4 is in the normal range.

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

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Edward S Huang

2010-12-01

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

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

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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

Is clopidogrel superior to aspirin in secondary prevention of vascular disease?

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Algra Ale

2000-11-01

Full Text Available Abstract The cornerstone in clinical evidence of the relative efficacy of thienopyridines (clopidogrel, ticlopidine versus aspirin in the secondary prevention of vascular disease is the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events trial. This trial showed a modest benefit in the reduction of vascular events by clopidogrel. The results differed according to qualifying disorder: myocardial infarction, -3.7%; ischaemic stroke, +7.3%; and peripheral arterial disease, +23.8% (P = 0.042. Similar results were found for ticlopidine after brain ischaemia. The safety of clopidogrel appears to be similar to that of aspirin and better than that of ticlopidine. However, the recent report of thrombotic thrombocytopenic purpura in association with clopidogrel causes concern.

Effects of Low-Dose Aspirin and Fish Oil on Platelet Function and NF-kappaB in Adults with Diabetes Mellitus

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Block, Robert C; Abdolahi, Amir; Smith, Brian; Meednu, N; Thevenet-Morrison, Kelly; Cai, Xueya; Cui, Huadong; Mousa, Shaker; Brenna, J. Thomas; Georas, S

2013-01-01

SUMMARY Introduction Many diabetics are insensitive to aspirin’s platelet anti-aggregation effects. The possible modulating effects of coadministration of aspirin and fish oil in subjects with diabetes are poorly characterized. Participants and Methods Thirty adults with type 2 diabetes mellitus were treated with aspirin 81 mg/d for 7 days, then with fish oil 4g/day for 28 days, then the combination of fish oil and aspirin for another 7 days. Results Aspirin alone and in combination with fish oil reduced platelet aggregation in most participants. Five of 7 participants classified as aspirin insensitive 1 week after daily aspirin ingestion were sensitive after the combination. Although some platelet aggregation measures correlated positively after aspirin and fish oil ingestion alone and (in combination) in all individuals, correlation was only observed in those who were aspirin insensitive after ingestion of the combination. Conclusions Co-adminstration of aspirin and fish oil may reduce platelet aggregation more than aspirin alone in adults with diabetes mellitus. PMID:23664596

Physicochemical impact studies of gamma rays on "aspirin" analgesics drug and its metal complexes in solid form: Synthesis, spectroscopic and biological assessment of Ca(II), Mg(II), Sr(II) and Ba(II) aspirinate complexes

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Refat, Moamen S.; Sharshar, T.; Elsabawy, Khaled M.; Heiba, Zein K.

2013-09-01

Metal aspirinate complexes, M2(Asp)4, where M is Mg(II), Ca(II), Sr(II) or Ba(II) are formed by refluxed of aspirin (Asp) with divalent non-transition metal ions of group (II) and characterized by elemental analysis and spectroscopic measurements (infrared, electronic, 1H NMR, Raman, X-ray powder diffraction and scanning electron microscopy). Elemental analysis of the chelates suggests the stoichiometry is 1:2 (metal:ligand). Infrared spectra of the complexes agree with the coordination to the central metal atom through three donation sites of two oxygen atoms of bridge bidentate carboxylate group and oxygen atom of sbnd Cdbnd O of acetyl group. Infrared spectra coupled with the results of elemental analyzes suggested a distorted octahedral structure for the M(II) aspirinate complexes. Gamma irradiation was tested as a method for stabilization of aspirin as well as their complexes. The effect of gamma irradiation, with dose of 80 Gy, on the properties of aspirinate complexes was studied. The aspirinate chelates have been screened for their in vitro antibacterial activity against four bacteria, gram-positive (Bacillus subtilis and Staphylococcus aureus) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) and two strains of fungus (Aspergillus flavus and Candida albicans). The metal chelates were shown to possess more antibacterial activity than the free aspirin chelate.

Comparison of aspirin renogram and captopril renogram in the diagnosis of renovascular hypertension

International Nuclear Information System (INIS)

Dabiri Oskoie, S.; Argani, H.

2002-01-01

Renal artery stenosis is the most common cause of secondary hypertension. Preliminary data indicate that aspirin renography with hippurate may be more sensitive for detection renal artery stenosis. In this study 20 patients with known or suspected renal artery stenosis underwent aspirin renography (20 mg/kg orally 1 hour before injection of radiotracer) and captopril renography (50 mg orally) with 99 Tc-DTPA. Renal angiography was performed in all patients. Of the 20 patients enrolled, 11 had unilateral renal artery stenosis on angiography. Captopril renography was positive in 10 patients (915 sensitivity and 90% specificity). Aspirin renogram showed 9 patients with renal artery stenosis correctly (81.85 sensitivity and 100% specificity). Our data suggest that aspirin renography with 99 Tc-DTPA has comparable sensitivity with captopril in detection of unilateral renal artery stenosis

Aspirin use and head and neck cancer survival: an observational study of 11,623 person-years follow-up.

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Kim, Shin-Ae; Roh, Jong-Lyel; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2018-02-01

Acetylsalicylic acid (aspirin) and non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risks for certain human cancers. However, the effects of aspirin and NSAIDs on head and neck squamous cell carcinoma (HNSCC) remain controversial, and the prognostic effects of these drugs in patients with HNSCC are largely unknown. This study examined the clinical impact of aspirin and NSAIDs on disease recurrence and survival in patients with HNSCC. This study analysed a cohort of 1392 consecutive patients who received definitive treatment for previously untreated HNSCC at our tertiary referral center. Aspirin or NSAID use was considered positive if the patients were receiving aspirin or NSAID medication from HNSCC diagnosis to at least 1 year after treatment initiation. Cox proportional hazard models were utilised to determine the association of aspirin and/or NSAID use with recurrence, survival, and second primary cancer occurrence. Of 1392 patients, 81 (5.8%) and 89 (6.4%) received post-diagnosis treatment with aspirin and NSAIDs, respectively. After controlling for clinical factors, aspirin and NSAIDs were not significantly associated with recurrence, survival, or second cancer occurrence (P > 0.05). The cumulative dose of aspirin or NSAIDs did not alter survival outcomes (P > 0.05). Our data illustrated that the use of aspirin or NSAIDs has no effect on survival or recurrence in patients with HNSCC.

Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets.

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Marimuthu, Srinivasan; Chivukula, Raghavender S V; Alfonso, Lloyd F; Moridani, Majid; Hagen, Fred K; Bhat, G Jayarama

2011-11-01

Epidemiological and clinical observations provide consistent evidence that regular intake of aspirin may effectively inhibit the occurrence of epithelial tumors; however, the molecular mechanisms are not completely understood. In the present study, we determined the ability of aspirin to acetylate and post-translationally modify cellular proteins in HCT-116 human colon cancer cells to understand the potential mechanisms by which it may exerts anti-cancer effects. Using anti-acetyl lysine antibodies, here we demonstrate that aspirin causes the acetylation of multiple proteins whose molecular weight ranged from 20 to 200 kDa. The identity of these proteins was determined, using immuno-affinity purification, mass spectrometry and immuno-blotting. A total of 33 cellular proteins were potential targets of aspirin-mediated acetylation, while 16 were identified as common to both the control and aspirin-treated samples. These include enzymes of glycolytic pathway, cytoskeleton proteins, histones, ribosomal and mitochondrial proteins. The glycolytic enzymes which were identified include aldolase, glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase M2, and lactate dehydrogenase A and B chains. Immunoblotting experiment showed that aspirin also acetylated glucose-6-phosphate dehydrogenase and transketolase, both enzymes of pentose phosphate pathway involved in ribonucleotide biosynthesis. In vitro assays of these enzymes revealed that aspirin did not affect pyruvate kinase and lactate dehydrogenase activity; however, it decreased glucose 6 phosphate dehydrogenase activity. Similar results were also observed in HT-29 human colon cancer cells. Selective inhibition of glucose-6-phosphate dehydrogenase may represent an important mechanism by which aspirin may exert its anti-cancer effects through inhibition of ribonucleotide synthesis.

Beam monitoring in radiotherapy and hadron-therapy

International Nuclear Information System (INIS)

Fontbonne, J.M.

2012-01-01

Radiotherapy techniques have evolved over the past twenty years. For photon beams, the development of tools such as multi leaf collimators, machines such as Cyberknife or tomo-therapy, have improved the conformation of treatments to the tumor volume and lowered maximum dose to healthy tissue. In another register, the use of proton-therapy is expanding in all countries and the development of carbon ions beams for hadron-therapy is also increasing. If techniques improve, the control requirements for the monitoring of the dose administered to patients are always the same. This document presents, first, the ins and outs of the different techniques of external beam radiotherapy: photon treatments, protons and hadrons. Starting from the basis of clinical requirements, it sets the variables to be measured in order to ensure the quality of treatment for the different considered modalities. It then describes some implementations, based on precise and rigorous specifications, for the monitoring and measurement of beams delivered by external beam radiotherapy equipments. Two instrumental techniques are particularly highlighted, plastic scintillators dosimetry for the control of megavoltage photon beams and ionization chamber dosimetry applied to proton-therapy or radiobiology experiments conducted at the GANIL facility. Analyzes and perspectives, based on the recent developments of treatment techniques, are delivered in conclusion and can serve as guide for future instrumental developments. (author)

Aspirin exposure reveals novel genes associated with platelet function and cardiovascular events.

Science.gov (United States)

Voora, Deepak; Cyr, Derek; Lucas, Joseph; Chi, Jen-Tsan; Dungan, Jennifer; McCaffrey, Timothy A; Katz, Richard; Newby, L Kristin; Kraus, William E; Becker, Richard C; Ortel, Thomas L; Ginsburg, Geoffrey S

2013-10-01

The aim of this study was to develop ribonucleic acid (RNA) profiles that could serve as novel biomarkers for the response to aspirin. Aspirin reduces death and myocardial infarction (MI), suggesting that aspirin interacts with biological pathways that may underlie these events. Aspirin was administered, followed by whole-blood RNA microarray profiling, in a discovery cohort of healthy volunteers (HV1) (n = 50) and 2 validation cohorts of healthy volunteers (HV2) (n = 53) and outpatient cardiology patients (OPC) (n = 25). Platelet function was assessed using the platelet function score (PFS) in HV1 and HV2 and the VerifyNow Aspirin Test (Accumetrics, Inc., San Diego, California) in OPC. Bayesian sparse factor analysis identified sets of coexpressed transcripts, which were examined for associations with PFS in HV1 and validated in HV2 and OPC. Proteomic analysis confirmed the association of validated transcripts in platelet proteins. Validated gene sets were tested for association with death or MI in 2 patient cohorts (n = 587 total) from RNA samples collected at cardiac catheterization. A set of 60 coexpressed genes named the "aspirin response signature" (ARS) was associated with PFS in HV1 (r = -0.31, p = 0.03), HV2 (r = -0.34, Bonferroni p = 0.03), and OPC (p = 0.046). Corresponding proteins for the 17 ARS genes were identified in the platelet proteome, of which 6 were associated with PFS. The ARS was associated with death or MI in both patient cohorts (odds ratio: 1.2 [p = 0.01]; hazard ratio: 1.5 [p = 0.001]), independent of cardiovascular risk factors. Compared with traditional risk factors, reclassification (net reclassification index = 31% to 37%, p ≤ 0.0002) was improved by including the ARS or 1 of its genes, ITGA2B. RNA profiles of platelet-specific genes are novel biomarkers for identifying patients who do not respond adequately to aspirin and who are at risk for death or MI. Copyright © 2013 American College of Cardiology Foundation. Published by

Imaging reporter gene for monitoring gene therapy

International Nuclear Information System (INIS)

Beco, V. de; Baillet, G.; Tamgac, F.; Tofighi, M.; Weinmann, P.; Vergote, J.; Moretti, J.L.; Tamgac, G.

2002-01-01

Scintigraphic images can be obtained to document gene function at cellular level. This approach is presented here and the use of a reporter gene to monitor gene therapy is described. Two main ways are presented: either the use of a reporter gene coding for an enzyme the action of which will be monitored by radiolabeled pro-drug, or a cellular receptor gene, the action of which is documented by a radio labeled cognate receptor ligand. (author)

Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling

International Nuclear Information System (INIS)

Yang, Guang; Wang, Yuan; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

2017-01-01

Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. - Highlights: • Aspirin inhibits the levels of liquid droplets, triglyceride and cholesterol in HCC cells. • Aspirin is able to down-regulate ACSL1 in HCC cells. • NF-κB inhibitor PDTC can down-regulate ACSL1 and reduces lipogenesis in HCC cells. • Aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling.

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

International Nuclear Information System (INIS)

Sung, Jin Young; Choi, Hyoung Chul

2011-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-05-06

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

Frequency and severity of reactions to a 325-mg aspirin dose during desensitization.

Science.gov (United States)

Schuler, Charles F; Baldwin, James L; Baptist, Alan P

2017-03-01

The frequency with which patients with aspirin-exacerbated respiratory disease (AERD) react to 325 mg of aspirin during aspirin desensitization, or fail to react at all, is not fully known. To determine the rate and type of reaction at 325 mg of aspirin during desensitization. A retrospective study of 104 patients who underwent aspirin desensitization from 2010 to 2016 was performed. A standard desensitization protocol (starting at 20-40 mg, progressing through 325 mg, and extinguishing reactions by dose repetition) was used. Reactions were defined by upper respiratory tract symptoms, lower respiratory tract symptoms, and/or forced expiratory volume in 1 second decrease of 15% or greater. Patients who did and did not react were compared by logistic regression. Eighty-four patients reacted (81%) and 20 did not (19%). Seventy-seven patients who had a provoking reaction at 162 mg of aspirin or less subsequently extinguished their reactions before they reached a dose of 325 mg and had no problems at that dose; one subsequent 325-mg reaction occurred during a protocol violation. One initial provoking reaction to 325 mg occurred. Both 325-mg reactions were mild, and neither met the forced expiratory volume in 1 second criterion for a clinically meaningful change. The remaining 5 patients could not complete the protocol because of persistent reactions or social reasons. Reactors were more likely to have had asthma for more than 10 years than nonreactors (odds ratio, 3.2; 95% confidence interval, 1.0-10.3; P = .05). During aspirin desensitization for AERD, provoking reactions at the 325-mg dose are rare (1%) and mild. Patients who react at 162 mg or less and extinguish their reactions may be able to administer the 325-mg dose at home. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Marcela-Corina Rosu

2014-06-01

Full Text Available Composite nanomaterials represent a new trend in the biomedical field. Coupling inorganic/organic constituents with non-toxicity/biocompatibility properties leads to develop the new systems having special characteristics that can be used in various bio-applications. This paper describes the preparation and characterization of psyllium-based composites containing TiO2 nanoparticles in order to develop new therapeutic strategies for aspirin drug delivery. The structural characteristics of obtained materials were investigated by FTIR spectroscopy. The UV–vis spectrophotometric analysis was performed to evaluate the aspirin release behavior under different pH conditions at 37 °C. Combining psyllium (as an excellent source of fiber with TiO2 inorganic unit (as vehicle of aspirin it was found that polymeric-TiO2 networks have promising potential for controlled aspirin release as therapeutic agent.

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 ...

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.

The Long-Term Benefits of Increased Aspirin Use by At-Risk Americans Aged 50 and Older.

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David B Agus

Full Text Available The usefulness of aspirin to defend against cardiovascular disease in both primary and secondary settings is well recognized by the medical profession. Multiple studies also have found that daily aspirin significantly reduces cancer incidence and mortality. Despite these proven health benefits, aspirin use remains low among populations targeted by cardiovascular prevention guidelines. This article seeks to determine the long-term economic and population-health impact of broader use of aspirin by older Americans at higher risk for cardiovascular disease.We employ the Future Elderly Model, a dynamic microsimulation that follows Americans aged 50 and older, to project their lifetime health and spending under the status quo and in various scenarios of expanded aspirin use. The model is based primarily on data from the Health and Retirement Study, a large, representative, national survey that has been ongoing for more than two decades. Outcomes are chosen to provide a broad perspective of the individual and societal impacts of the interventions and include: heart disease, stroke, cancer, life expectancy, quality-adjusted life expectancy, disability-free life expectancy, and medical costs. Eligibility for increased aspirin use in simulations is based on the 2011-2012 questionnaire on preventive aspirin use of the National Health and Nutrition Examination Survey. These data reveal a large unmet need for daily aspirin, with over 40% of men and 10% of women aged 50 to 79 presenting high cardiovascular risk but not taking aspirin. We estimate that increased use by high-risk older Americans would improve national life expectancy at age 50 by 0.28 years (95% CI 0.08-0.50 and would add 900,000 people (95% CI 300,000-1,400,000 to the American population by 2036. After valuing the quality-adjusted life-years appropriately, Americans could expect $692 billion (95% CI 345-975 in net health benefits over that period.Expanded use of aspirin by older Americans with

The Long-Term Benefits of Increased Aspirin Use by At-Risk Americans Aged 50 and Older.

Science.gov (United States)

Agus, David B; Gaudette, Étienne; Goldman, Dana P; Messali, Andrew

2016-01-01

The usefulness of aspirin to defend against cardiovascular disease in both primary and secondary settings is well recognized by the medical profession. Multiple studies also have found that daily aspirin significantly reduces cancer incidence and mortality. Despite these proven health benefits, aspirin use remains low among populations targeted by cardiovascular prevention guidelines. This article seeks to determine the long-term economic and population-health impact of broader use of aspirin by older Americans at higher risk for cardiovascular disease. We employ the Future Elderly Model, a dynamic microsimulation that follows Americans aged 50 and older, to project their lifetime health and spending under the status quo and in various scenarios of expanded aspirin use. The model is based primarily on data from the Health and Retirement Study, a large, representative, national survey that has been ongoing for more than two decades. Outcomes are chosen to provide a broad perspective of the individual and societal impacts of the interventions and include: heart disease, stroke, cancer, life expectancy, quality-adjusted life expectancy, disability-free life expectancy, and medical costs. Eligibility for increased aspirin use in simulations is based on the 2011-2012 questionnaire on preventive aspirin use of the National Health and Nutrition Examination Survey. These data reveal a large unmet need for daily aspirin, with over 40% of men and 10% of women aged 50 to 79 presenting high cardiovascular risk but not taking aspirin. We estimate that increased use by high-risk older Americans would improve national life expectancy at age 50 by 0.28 years (95% CI 0.08-0.50) and would add 900,000 people (95% CI 300,000-1,400,000) to the American population by 2036. After valuing the quality-adjusted life-years appropriately, Americans could expect $692 billion (95% CI 345-975) in net health benefits over that period. Expanded use of aspirin by older Americans with elevated risk

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-02-01

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

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

International Nuclear Information System (INIS)

Strecker, Ernst-Peter K.; Boos, Irene B.L.; Goettmann, Dieter; Vetter, Sylvia

2004-01-01

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

Low-Dose Aspirin Use and Cognitive Function in Older Age: A Systematic Review and Meta-analysis.

Science.gov (United States)

Veronese, Nicola; Stubbs, Brendon; Maggi, Stefania; Thompson, Trevor; Schofield, Patricia; Muller, Christoph; Tseng, Ping-Tao; Lin, Pao-Yen; Carvalho, André F; Solmi, Marco

2017-08-01

To investigate whether low-dose aspirin (aspirin was not associated with onset of dementia or cognitive impairment (5 studies, N = 26,159; OR = 0.82, 95% CI = 0.55-1.22, P = .33, I 2 = 67%). In three RCTs (N = 10,037; median follow-up 5 years), the use of low-dose aspirin was not associated with significantly better global cognition (SMD=0.005, 95% CI=-0.04-0.05, P = .84, I 2 = 0%) in individuals without dementia. Adherence was lower in participants taking aspirin than in controls, and the incidence of adverse events was higher. This review found no evidence that low-dose aspirin buffers against cognitive decline or dementia or improves cognitive test scores in RCTs. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

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

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

Directory of Open Access Journals (Sweden)

Deepak Voora, MD

2016-09-01

Full Text Available Aspirin prevents cardiovascular disease and colon cancer; however aspirin's inhibition of platelet COX-1 only partially explains its diverse effects. We previously identified an aspirin response signature (ARS in blood consisting of 62 co-expressed transcripts that correlated with aspirin's effects on platelets and myocardial infarction (MI. Here we report that 60% of ARS transcripts are regulated by RUNX1 – a hematopoietic transcription factor - and 48% of ARS gene promoters contain a RUNX1 binding site. Megakaryocytic cells exposed to aspirin and its metabolite (salicylic acid, a weak COX-1 inhibitor showed up regulation in the RUNX1 P1 isoform and MYL9, which is transcriptionally regulated by RUNX1. In human subjects, RUNX1 P1 expression in blood and RUNX1-regulated platelet proteins, including MYL9, were aspirin-responsive and associated with platelet function. In cardiovascular disease patients RUNX1 P1 expression was associated with death or MI. RUNX1 acts as a tumor suppressor gene in gastrointestinal malignancies. We show that RUNX1 P1 expression is associated with colon cancer free survival suggesting a role for RUNX1 in aspirin's protective effect in colon cancer. Our studies reveal an effect of aspirin on RUNX1 and gene expression that may additionally explain aspirin's effects in cardiovascular disease and cancer.

Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

Science.gov (United States)

Weksler, B B; Tack-Goldman, K; Subramanian, V A; Gay, W A

1985-02-01

The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI2 produced by vascular tissues of control subjects who received no aspirin preoperatively (51 +/- 10 pg 6-keto-PGF1 alpha/mg aortic wet weight [mean +/- SEM] in aspirin-treated subjects vs 130 +/- 16 pg/mg in control subjects, and 71 +/- 8 pg/mg saphenous vein wet weight vs 131 +/- 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 +/- 229 ml in aspirin-treated subjects vs 645 +/- 271 ml in control subjects), hematocrit nadir (31.2 +/- 1.9% vs 31.8 +/- 1.7%), or transfusions (2.2 +/- 1.3 units of red blood cells vs 2.2 +/- 1.7 units).(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling.

Science.gov (United States)

Yang, Guang; Wang, Yuan; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

2017-05-06

Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. Copyright © 2017. Published by Elsevier Inc.

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 ...

Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

Directory of Open Access Journals (Sweden)

Zhou L

2015-08-01

Full Text Available Lin Zhou,1,2,* Xingmei Duan,1,2,* Shi Zeng,1 Ke Men,1 Xueyan Zhang,1 Li Yang,1 Xiang Li1 1State Key Laboratory of Biotherapy, Cancer Center and Department of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Sichuan Food and Drug Safety Monitoring and Review of Certification, Adverse Reaction Monitoring Center, Drug Abuse Monitoring Center, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Natural product curcumin (Cur and H2S-releasing prodrug SH-aspirin (SH-ASA are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol-poly (lactide-coglycolide (mPEG-PLGA nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016 in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer. Keywords: drug delivery, cancer therapy, ovarian cancer, synergistic effect

A long-term risk-benefit analysis of low-dose aspirin in primary prevention.

Science.gov (United States)

Wu, I-Chen; Hsieh, Hui-Min; Yu, Fang-Jung; Wu, Meng-Chieh; Wu, Tzung-Shiun; Wu, Ming-Tsang

2016-02-01

The long-term risk-benefit effect of occasional and regular use of low-dose aspirin (≤ 100 mg per day) in primary prevention of vascular diseases and cancers was calculated. One representative database of 1 000 000 participants from Taiwan's National Health Insurance scheme in 1997-2000 was used. The potential study subjects were those aged 30-95 years, were found not to have been prescribed aspirin before 1 January 2000, but to have first been prescribed low-dose aspirin (≤ 100 mg per day) after that date and were followed up to 31 December 2009. Participants prescribed low-dose aspirin risk. A total of 1720 pairs were analysed. During the study period, haemorrhage and ischaemia occurred in 25 (1·45%) and 67 participants (3·90%) in occasional users and 69 (4·01%) and 100 participants (5·81%) in regular users, whereas cancer occurred in 32 participants (1·86%) in occasional users and 26 participants (1·51%) in regular users. The crude and adjusted net clinical risks of low-dose aspirin use between the two frequency of users (≥ 80% vs. prevention against major vascular diseases and cancer. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

OncoTREAT: a software assistant for cancer therapy monitoring

International Nuclear Information System (INIS)

Bornemann, Lars; Dicken, Volker; Kuhnigk, Jan-Martin; Krass, Stefan; Peitgen, Heinz-Otto; Wormanns, Dag; Shin, Hoen-Oh; Bauknecht, Hans-Christian; Diehl, Volker; Fabel, Michael; Meier, Stefan; Kress, Oliver

2007-01-01

ObjectCancer is one of the leading causes of death worldwide and therapy options are often associated with severe stress for the patient and high costs. Therefore, precise evaluation of therapy success is essential. Material and Methods In the framework of the VICORA research project (Virtual Institute for Computer Assistance in Clinical Radiology), a software application was developed to support the radiologist in evaluating the response to tumor therapy. The application provides follow-up support for oncological therapy monitoring by volumetric quantification of lung, liver and brain metastases as well as enlarged lymph nodes and assists the user by temporal registration of lesion positions. Results With close cooperation between computer scientists and radiologists the application was tested and optimized to achieve a high degree of usability. Several clinical studies were carried out to evaluate the robustness and reproducibility of the volumetry methods. Conclusion Automatic volumetry and segmentation allows reliable detection of tumor growth and has the potential to increase reliability and significance of monitoring tumor growth in follow-up examinations. (orig.)

Study of temperature and irradiation influence on the physicochemical properties of Aspirin

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Al-Maydama, Hussein M.; Abduljabbar, Adlia A.; Al-Maqtari, Maher A.; Naji, Khalid M.

2018-04-01

Pure Aspirin samples were treated with a wide spectrum of light (γ-ray, UV- lamp and sunlight) and 40 °C temperature at various time of exposure. The changes in the thermal degradation parameters, crystalline structure, morphology and purity due to radiation and temperature treatments of Aspirin were pursued by comparing their TGA, XRD, SEM and HPLC results. The non-isothermal thermogravimetric analysis curves (TG, DTG and DSC) at 10 °C min-1 heating rate, under nitrogen flow and overheating range of 25-650 °C showed two degradation steps for the treated and untreated Aspirin samples. Accordingly, their thermal behavior and thermal stability were determined. Aspirin samples treated with 40 °C and UV-12 h were proven to be of the lowest thermal stability as their TDTG values (166.7 and 168.8 °C) were lower than that of the untreated sample (TDTG = 181 °C). The degradation kinetics parameters (i.e. activation energy, pre-exponential factor and order of reaction), life time prediction and thermodynamic parameters (ΔG*, ΔH* and ΔS*) were worked out using the Coats-Redfern (CR) expression and standard equations. The lowest activation energy (104.3 kJ mol-1) associated with the highest degradation rate was observed for the UV-12 h treated Aspirin sample. Crystallinity percentage was estimated from XRD and DSC, whereas, morphology and purity changes due to treatments were detected by scanning electron microscopy (SEM) and HPLC. The significant change in crystallinity from the XRD results of the treated Aspirin samples occurred in the (32.2%-58.7%) range. The photocatalytic degradation of Aspirin samples before and after treatments was carried out using TiO2/sunlight system. The photocatalytic degradation of all samples followed pseudo first order kinetics and the shelf life, rate of reaction and efficiency of degradation were determined and discussed. The highest degradation percentage (∼99%) and the associated lowest shelf life (4.3-5.8 min) were observed in

Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

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Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

2008-03-01

Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

Adjuvant Medications That Improve Survival after Locoregional Therapy.

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Boas, F Edward; Ziv, Etay; Yarmohammadi, Hooman; Brown, Karen T; Erinjeri, Joseph P; Sofocleous, Constantinos T; Harding, James J; Solomon, Stephen B

2017-07-01

To determine if outpatient medications taken at the time of liver tumor embolization or ablation affect survival. A retrospective review was done of 2,032 liver tumor embolization, radioembolization, and ablation procedures performed in 1,092 patients from June 2009 to April 2016. Pathology, hepatocellular carcinoma (HCC) stage (American Joint Committee on Cancer), neuroendocrine tumor (NET) grade, initial locoregional therapy, overall survival after initial locoregional therapy, Child-Pugh score, Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index, and outpatient medications taken at the time of locoregional therapy were analyzed for each patient. Kaplan-Meier survival curves were calculated for patients taking 29 medications or medication classes (including prescription and nonprescription medications) for reasons unrelated to their primary cancer diagnosis. Kaplan-Meier curves were compared using the log-rank test. For patients with HCC initially treated with embolization (n = 304 patients), the following medications were associated with improved survival when taken at the time of embolization: beta-blockers (P = .0007), aspirin (P = .0008) and other nonsteroidal antiinflammatory drugs (P = .009), proton pump inhibitors (P = .004), and antivirals for hepatitis B or C (P = .01). For colorectal liver metastases initially treated with ablation (n = 172 patients), beta-blockers were associated with improved survival when taken at the time of ablation (P = .02). Aspirin and beta-blockers are associated with significantly improved survival when taken at the time of embolization for HCC. Aspirin was not associated with survival differences after locoregional therapy for NET or colorectal liver metastases, suggesting an HCC-specific effect. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Immunological Monitoring to Rationally Guide AAV Gene Therapy

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Cedrik Michael Britten

2013-09-01

Full Text Available Recent successes with adeno-associated virus (AAV-based gene therapies fuel the hope for new treatments for hereditary diseases. Pre-existing as well as therapy-induced immune responses against both AAV and the encoded transgenes have been described and may impact on safety and efficacy of gene-therapy approaches. Consequently, monitoring of vector- and transgene-specific immunity is mandated and may rationally guide clinical development. Next to the humoral immune response, the cellular response is central in our understanding of the host reaction in gene therapy. But in contrast to the monitoring of antibodies, which has matured over many decades, sensitive and robust monitoring of T cells is a relatively new development. To make cellular immune assessments fit for purpose, investigators need to know, control and report the critical assay variables that influence the results. In addition, the quality of immune assays needs to be continuously adjusted to allow for exploratory hypothesis generation in early stages and confirmatory hypothesis validation in later stages of clinical development. The concept of immune assay harmonization which includes use of field-wide benchmarks, harmonization guidelines, and external quality control can support the context-specific evolution of immune assays. Multi-center studies pose particular challenges to sample logistics and quality control of sample specimens. Cooperative groups need to define if immune assessments should be performed in one central facility, in peripheral labs or including a combination of both. Finally, engineered reference samples that contain a defined number of antigen-specific T cells may become broadly applicable tools to control assay performance over time or across institutions.

Chronic use of low-dose aspirin is not associated with lower bone mineral density in the general population.

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Bonten, T N; de Mutsert, R; Rosendaal, F R; Jukema, J W; van der Bom, J G; de Jongh, R T; den Heijer, M

2017-10-01

Low-dose aspirin is the cornerstone of secondary prevention of cardiovascular disease. Previous studies suggested that the use of aspirin is associated with an increased fracture risk. However, there is uncertainty whether this is due to an effect of aspirin on bone mineral density (BMD). Between 2008 and 2012, information on medication use and dual X-ray absorptiometry measured vertebral and femoral BMD of 916 participants was collected in the Netherland Epidemiology of Obesity study. The cross-sectional association between chronic low-dose aspirin use and BMD was estimated using linear regression, controlling for demography, body composition, comorbidity and other medication use which could affect BMD. A subgroup analysis in postmenopausal women (n=329) was conducted. After full adjustment, there was no difference between aspirin users and non-users for vertebral BMD (adjusted mean difference: 0.036 (95% CI -0.027 to 0.100) g/cm 2 ) and femoral BMD (adjusted mean difference: 0.001 (-0.067 to 0.069) g/cm 2 ). Also in the subgroup of postmenopausal women, aspirin use was not associated with lower vertebral (adjusted mean difference: 0.069 (-0.046 to 0.184) g/cm 2 ) or femoral BMD (adjusted mean difference: -0.055 (-0.139;0.029) g/cm 2 ). Chronic use of low-dose aspirin is not associated with lower BMD in the general population. The increased risk of fractures observed in aspirin users in previous studies is therefore more likely to be the result of common causes of aspirin use and fractures, but not of direct effects of aspirin on BMD. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Value of PET and PET-CT for monitoring tumor therapy

International Nuclear Information System (INIS)

Chen Xiang; Zhao Jinhua

2007-01-01

18 F-fluorodeoxyglucose ( 18 F-FDG) PET or PET-CT is an accurate test for differentiating residual viable tumor tissue from therapy-induced changes in tumor. Furthermore, quantitative assessment of therapy-induced changes in tumor 18 F-FDG uptake may allow the prediction of tumor response. Treatment may be adjusted according to tumor response. So it is increasingly used to monitor tumor response in patients undergoing chemotherapy and chemoradiotherapy. Here we focused on practical aspects of 18 F-FDG PET or PET-CT for treatment monitoring and on the existing advantages and challenges. (authors)

Mobile compression devices and aspirin for VTE prophylaxis following simultaneous bilateral total knee arthroplasty.

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Nam, Denis; Nunley, Ryan M; Johnson, Staci R; Keeney, James A; Barrack, Robert L

2015-03-01

Recently, Levy et al questioned the effectiveness of mobile compression devices (MCDs) as the sole method of thromboprophylaxis following simultaneous bilateral total knee arthroplasty (TKA). This study's purpose was to assess if the addition of aspirin to MCDs improves venous thromboembolism (VTE) prevention following simultaneous bilateral TKA. Ninety-six patients (192 TKAs) were retrospectively reviewed: 47 patients received MCDs for 10 days and aspirin for 6 weeks postoperatively based on a risk stratification protocol, while 49 patients received warfarin for 4 weeks postoperatively. One symptomatic VTE was noted in the warfarin cohort, while one patient in the MCD/aspirin cohort and three patients in the warfarin cohort were readmitted within 3 months of surgery. In appropriately selected patients, MCDs with aspirin shows promise in VTE prevention following simultaneous bilateral TKA. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of Dispersion Interactions in the Polymorphism and Entropic Stabilization of the Aspirin Crystal

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Reilly, Anthony M.; Tkatchenko, Alexandre

2014-08-01

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

Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways.

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Li, Xuelian; Wang, GuoYuan; QiLi, MuGe; Liang, HaiHai; Li, TianShi; E, XiaoQiang; Feng, Ying; Zhang, Ying; Liu, Xiao; Qian, Ming; Xu, BoZhi; Shen, ZhiHang; Gitau, Samuel Chege; Zhao, DanDan; Shan, HongLi

2018-01-01

Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload-induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 10 mg·kg-1·day-1 of aspirin for 4 weeks. Masson staining and a collagen content assay were used to detect the effects of aspirin on cardiac fibrosis in vivo and in vitro. Western blot and qRT-PCR were applied to examine the impact of aspirin on extracellular signal-regulated kinases (Erks), p-Akt/β-catenin, SerpinE2, collagen I, and collagen III levels in the mice heart. Aspirin significantly suppressed the expression of α-smooth muscle actin (α-SMA; 1.19±0.19-fold) and collagen I (0.95±0.09-fold) in TAC mice. Aspirin, at doses of 100 and 1000 µM, also significantly suppressed angiotensin II-induced α-SMA and collagen I in cultured CFs. The enhanced phosphorylation of Erk1/2 caused by TAC (p-Erk1, 1.49±0.19-fold; p-Erk2, 1.96±0.68-fold) was suppressed by aspirin (p-Erk1, 1.04±0.15-fold; p-Erk2, 0.87±0.06-fold). SerpinE2 levels were suppressed via the Erk1/2 signalling pathway following treatment with aspirin (1.36±0.12-fold for TAC; 1.06±0.07-fold for aspirin+TAC). The p-Akt and β-catenin levels were also significantly inhibited in vivo and in vitro. Our study reveals a novel mechanism by which aspirin alleviates pressure overload-induced cardiac interstitial fibrosis in TAC mice by suppressing the p-Erk1/2 and p-Akt/β-catenin signalling pathways. © 2018 The Author(s). Published by S. Karger AG, Basel.

The analgesic effect of different antidepressants combined with aspirin on thermally induced pain in Albino mice

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Abdalla S. Elhwuegi

2012-04-01

Full Text Available Background:Combination analgesics provide more effective pain relief for a broader spectrum of pain. This research examines the possible potentiation of the analgesic effect of different classes of antidepressants when combined with aspirin in thermal model of pain using Albino mice.Methods:Different groups of six animals each were injected intraperitoneally by different doses of aspirin (50, 100, or 200 mg/kg, imipramine (2.5, 7.5, 15 or 30 mg/kg, fluoxetine (1.25, 2.5, 5 or 7.5 mg/kg, mirtazapine (1.25, 2.5, or 5 mg/kg and a combination of a fixed dose of aspirin (100 mg/kg with the different doses of the three antidepressants. One hour later the analgesic effect of these treatments were evaluated against thermally induced pain. All data were subjected to statistical analysis using unpaired Student's t-test.Results:Aspirin had no analgesic effect in thermally induced pain. The three selected antidepressants produced dose dependent analgesia. The addition of a fixed dose of aspirin to imipramine significantly increased the reaction time (RT of the lowest dose (by 23% and the highest dose (by 20%. The addition of the fixed dose of aspirin to fluoxetine significantly increased RT by 13% of the dose 2.5 mg/Kg. Finally, the addition of the fixed dose of aspirin significantly potentiated the antinociceptive effect of the different doses of mirtazapine (RT was increased by 24, 54 and 38% respectively.Conclusion:Combination of aspirin with an antidepressant might produce better analgesia, increasing the efficacy of pain management and reduces side effects by using smaller doses of each drug.

Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation.

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Cannon, Christopher P; Bhatt, Deepak L; Oldgren, Jonas; Lip, Gregory Y H; Ellis, Stephen G; Kimura, Takeshi; Maeng, Michael; Merkely, Bela; Zeymer, Uwe; Gropper, Savion; Nordaby, Matias; Kleine, Eva; Harper, Ruth; Manassie, Jenny; Januzzi, James L; Ten Berg, Jurrien M; Steg, P Gabriel; Hohnloser, Stefan H

2017-10-19

Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding. In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y 12 inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months) (triple-therapy group) or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus a P2Y 12 inhibitor (clopidogrel or ticagrelor) and no aspirin (110-mg and 150-mg dual-therapy groups). Outside the United States, elderly patients (≥80 years of age; ≥70 years of age in Japan) were randomly assigned to the 110-mg dual-therapy group or the triple-therapy group. The primary end point was a major or clinically relevant nonmajor bleeding event during follow-up (mean follow-up, 14 months). The trial also tested for the noninferiority of dual therapy with dabigatran (both doses combined) to triple therapy with warfarin with respect to the incidence of a composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization. The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; Pdual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; Pdual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups. Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was

Protective effects of essential oil of Citrus limon against aspirin-induced toxicity in IEC-6 cells.

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Bouzenna, Hafsia; Hfaiedh, Najla; Giroux-Metges, Marie-Agnès; Elfeki, Abdelfattah; Talarmin, Hélène

2017-05-01

Aspirin, one of the widely used nonsteroidal anti-inflammatory drugs, is the most highly consumed pharmaceutical product in the world. However, it has several side effects in cells. This study was designed to investigate the antioxidative activity and cytoprotective effects of essential oil of Citrus limon (EOC) extracted from leaves against aspirin-induced damages in the rat small intestine epithelial cells (IEC-6). Biochemical indicators were used to assess cytotoxicity and oxidative damages caused by aspirin treatment on IEC-6. Our results showed that the chemical characterization of EOC identified 25 compounds representing 98.19% of the total oil. The major compounds from this oil were z-citral (53.21%), neryl acetate (13.06%), geranyl acetate (10.33%), and limonene (4.23%). Aspirin induced a decrease in cell viability as well as an increase in superoxide dismutase (SOD) and catalase (CAT) activities. Contrariwise, the co-exposure of cells to aspirin and EOC alleviated every above syndrome by an increase in cell survival and decrease in SOD and CAT activities. In conclusion, the essential oil of C. limon has a potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

Repurposing of Aspirin and Ibuprofen as Candidate Anti-Cryptococcus Drugs

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Ogundeji, Adepemi O.; Pohl, Carolina H.

2016-01-01

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

PEMBUATAN DAN UJI AKTIVITAS SEDIAAN UNGUENTA SCARLESS WOUND DENGAN EKSTRAK BINAHONG DAN ZAT AKTIF ASPIRIN

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Maria Faustina Sari

2015-11-01

Full Text Available Wound is a defect of skin caused by physical or thermal damage. The inflammatory phase in the wound healing usually causes scars. Aspirin is a nonsteroidal anti-inflammatory drug (NSAID that has the ability to inhibit the activity of cyclooxygenase (COX leading to reduced prostaglandin amount. Binahong (Anredera cordifolia is one of the plants that is used as a wound healer. Binahong contains ascorbic acid which has an important role in collagen formation phase. In this study, binahong leaf extract ointment will be combined with aspirin to produce scarless wound ointment. The method used is a purely experimental method. The test method used is histopathology tests then processed by the method of calculating the area of collagen. The data are analyzed using T-test. The addition of aspirin in the preparation of wound healing ointment can’t reduce scar formation allegedly with an incision method of white mice (Mus musculus Swiss Webster. Statistically, the results showed that binahong ointment (UB produces the least scar than ointment base (B, followed binahong-aspirin ointment (UBA, and aspirin ointment (UA.

Continuous glucose monitoring-enabled insulin-pump therapy in diabetic pregnancy

DEFF Research Database (Denmark)

Secher, Anna L; Schmidt, Signe; Nørgaard, Kirsten

2010-01-01

We describe the feasibility of continuous glucose monitoring (CGM)-enabled insulin-pump therapy during pregnancy in a woman with type 1 diabetes, who was treated with CGM-enabled insulin-pump therapy in her third pregnancy. During her first pregnancy, the woman was treated with multiple daily inj...

Low-Dose Aspirin Reduces Breast Cancer Risk in Women with Diabetes: A Nationwide Retrospective Cohort Study in Taiwan.

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Yang, Yi-Sun; Kornelius, Edy; Chiou, Jeng-Yuan; Lai, Yung-Rung; Lo, Shih-Chang; Peng, Chiung-Huei; Huang, Chien-Ning

2017-12-01

Low-dose aspirin is commonly used for preventing cardiovascular disease in people with diabetes, but its association with cancer remains controversial. This study used a nationwide population-based reimbursement database to investigate the relationship between low-dose aspirin use and breast cancer incidence in women with diabetes. This retrospective cohort study was conducted using data retrieved from the National Health Insurance Research Database in Taiwan from January 1, 1998 to December 31, 2011. Women diagnosed as having diabetes with low-dose aspirin use (75-165 mg daily) were identified as the study population, whereas those without low-dose aspirin use were selected as the comparison group. We analyzed 148,739 patients with diabetes. Their mean age (standard deviation) was 63.3 (12.8) years. A total of 27,378 patients were taking aspirin. Overall, the use of aspirin in patients with diabetes reduced the risk of breast cancer by 18% (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94) after adjustment for potential confounders, namely age and comorbidities. Specifically, a cumulative dose of aspirin exceeding 88,900 mg was observed to reduce the risk of breast cancer by 47% (HR, 0.53, 95% CI, 0.43-0.67); however, low (aspirin did not reduce the risk of breast cancer. Our findings suggest that a cumulative aspirin dosage of more than 88,900 mg daily was associated with a reduced risk of breast cancer in women with diabetes. However, additional studies are necessary to confirm these findings.

Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study.

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Sundström, Johan; Hedberg, Jakob; Thuresson, Marcus; Aarskog, Pernilla; Johannesen, Kasper Munk; Oldgren, Jonas

2017-09-26

There are increasing concerns about risks associated with aspirin discontinuation in the absence of major surgery or bleeding. We investigated whether long-term low-dose aspirin discontinuation and treatment gaps increase the risk of cardiovascular events. We performed a cohort study of 601 527 users of low-dose aspirin for primary or secondary prevention in the Swedish prescription register between 2005 and 2009 who were >40 years of age, were free from previous cancer, and had ≥80% adherence during the first observed year of treatment. Cardiovascular events were identified with the Swedish inpatient and cause-of-death registers. The first 3 months after a major bleeding or surgical procedure were excluded from the time at risk. During a median of 3.0 years of follow-up, 62 690 cardiovascular events occurred. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37; 95% confidence interval, 1.34-1.41), corresponding to an additional cardiovascular event observed per year in 1 of every 74 patients who discontinue aspirin. The risk increased shortly after discontinuation and did not appear to diminish over time. In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding was associated with a >30% increased risk of cardiovascular events. Adherence to low-dose aspirin treatment in the absence of major surgery or bleeding is likely an important treatment goal. © 2017 American Heart Association, Inc.

General practitioner attitudes towards prescribing aspirin to carriers of Lynch Syndrome: findings from a national survey.

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Smith, Samuel G; Foy, Robbie; McGowan, Jennifer; Kobayashi, Lindsay C; Burn, John; Brown, Karen; Side, Lucy; Cuzick, Jack

2017-10-01

A dose non-inferiority study comparing 100 mg, 300 mg and 600 mg of aspirin for cancer prevention among Lynch Syndrome carriers is underway (Colorectal Adenoma/Carcinoma Prevention Programme trial 3, CaPP3). To guide implementation of the findings, we investigated general practitioner (GP) attitudes towards aspirin prescribing for Lynch Syndrome carriers. We surveyed 1007 UK GPs (9.6% response rate). Using a within-subjects design, GPs read a statement on harms and benefits of aspirin and indicated their willingness to prescribe aspirin at three doses (100 mg, 300 mg, 600 mg). Approximately two-thirds (70.8%) of GPs had heard of Lynch Syndrome or its associated names, and among those 46.7% were aware of the cancer preventive effects of aspirin among carriers. Two-thirds (68.1%) of GPs reported feeling comfortable discussing harms and benefits of aspirin with a Lynch Syndrome patient. Willingness to prescribe was 91.3% at 100 mg, and declined to 81.8% at 300 mg and 62.3% at 600 mg (p Lynch Syndrome patient in practice (OR 1.44, 95% CI 1.01-2.05, p = 0.045). GPs report limited awareness of Lynch Syndrome and the preventive effects of aspirin among carriers. To ensure the optimal dose identified in the CaPP3 trial is readily available to patients, prescribing guidance and strategies to educate GPs should be developed.

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

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Ludmila Karazhanova

2014-12-01

Full Text Available Introduction. Platelet activation and aggregation are key elements in the development of coronary atherosclerosis. Recent studies have shown that the two polymorphisms of platelet ADP receptor P2RY12 (haplotypes H2 and 34T are associated with increased platelet aggregation and atherothrombotic risk. It was shown that these polymorphisms promote reduced body response to antiplatelet therapy.Aim. We investigated the association of P2RY12 gene polymorphisms with aspirin resistance in patients with coronary artery disease (CAD.Methods. This case-control study included 100 cases with CAD (mean age 57.6 ± 2.8 years treated in the cardiology department of the city hospital Semey, Kazakhstan, 90 of whom suffered from myocardial infarction. The control group (n = 100 were healthy people without a history of CAD, matched on sex and age. Genotyping of polymorphisms H1/H2 in P2RY12 gene was performed by PCR. Statistical analysis was performed using SPSS v.19.0.Results. The distribution of H1/H2 genotypes P2RY12 was 42%, 34%, and 24%, respectively, in cases and 42%, 58%, and 0%, respectively, in controls. All allele frequencies were consistent with the Hardy Weinberg equilibrium (p = 0.0036 and p = 0.0001 in cases and controls, respectively. Genotype H2 was associated with risk of CAD with aspirin resistance (co-dominant model: OR = 3.75, 95% CI 0.14 - 99.88, p = 0.05 and dominant model: OR = 2.78, 95% CI 0.11 - 70.93, p = 0.05. We found significant differences in the distribution of the mutant genotype H2 between CAD patients with aspirin resistance and healthy controls (χ2 = 30.3, p < 0.05.Conclusion. We found an association of H2 haplotype in P2RY12 gene with aspirin resistance in patients with CAD. However, in order to obtain definitive conclusions about the role of genetic variants with the development of aspirin resistance in patients with CAD, there is a need for further research with a larger sample size as well as the use of selective thromboxane

Effect of Low-Dose Aspirin on Chronic Acid Reflux Esophagitis in Rats.

Science.gov (United States)

Masuda, Takahiro; Yano, Fumiaki; Omura, Nobuo; Tsuboi, Kazuto; Hoshino, Masato; Yamamoto, Se Ryung; Akimoto, Shunsuke; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2018-01-01

Clinical role of low-dose aspirin (LDA) in pathogenesis of gastroesophageal reflux disease is by far controversial. This can be attributed to the paucity of basic research detailing the mechanism of LDA-induced esophageal mucosal injury (EI) on underlying chronic acid reflux esophagitis (RE). The aim of this study was to clarify the effect of LDA on chronic RE in rats. Esophagitis was induced in 8-week-old male Wistar rats by ligating the border between forestomach and glandular portion with a 2-0 silk tie and covering the duodenum with a small piece of 18-Fr Nélaton catheter. Seventy-eight chronic RE rat models were divided into five treatment groups, consisting of orally administered vehicle (controls), and aspirin doses of 2, 5, 50 or 100 mg/kg once daily for 28 days. EI was assessed by gross area of macroscopic mucosal injury, severity grade of esophagitis and microscopic depth of infiltration by inflammatory cells. Area of esophagitis in animals with aspirin dose of 100 mg/kg/day showed a 36.5% increase compared with controls, although it failed to achieve statistical significance (p = 0.812). Additionally, the rate of severe EI was increased in animals with aspirin dose of 100 mg/kg/day as compared with controls (p aspirin (100 mg/kg/day) contributed in exacerbating preexisting EI. LDA (2 and 5 mg/kg/day), on the other hand, did not affect chronic RE in this model. LDA seems to be safe for use in patients with chronic RE.

[Low-dose aspirin in patients with diabete melitus: risks and benefits regarding macro and microvascular complications].

Science.gov (United States)

Camargo, Eduardo G; Gross, Jorge Luiz; Weinert, Letícia S; Lavinsky, Joel; Silveiro, Sandra P

2007-04-01

Aspirin is recommended as cardiovascular disease prevention in patients with diabetes mellitus. Due to the increased risk of bleeding and because of the hypothesis that there could be a worsening of microvascular complications related to aspirin, there has been observed an important underutilization of the drug. However, it is now known that aspirin is not associated with a deleterious effect on diabetic retinopathy and there is evidence indicating that it also does not affect renal function with usual doses (150 mg/d). On the other hand, higher doses may prove necessary, since recent data suggest that diabetic patients present the so called "aspirin resistance". The mechanisms of this resistance are not yet fully understood, being probably related to an abnormal intrinsic platelet activity. The employment of alternative antiplatelet strategies or the administration of higher aspirin doses (150-300 mg/d) should be better evaluated regarding effective cardiovascular disease prevention in diabetes as well as the possible effects on microvascular complications.

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

Aspirin in pregnancy : clinical and biochemical studies

NARCIS (Netherlands)

H.A. Bremer (Henk)

1994-01-01

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

Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty.

Science.gov (United States)

Anderson, David R; Dunbar, Michael; Murnaghan, John; Kahn, Susan R; Gross, Peter; Forsythe, Michael; Pelet, Stephane; Fisher, William; Belzile, Etienne; Dolan, Sean; Crowther, Mark; Bohm, Eric; MacDonald, Steven J; Gofton, Wade; Kim, Paul; Zukor, David; Pleasance, Susan; Andreou, Pantelis; Doucette, Steve; Theriault, Chris; Abianui, Abongnwen; Carrier, Marc; Kovacs, Michael J; Rodger, Marc A; Coyle, Doug; Wells, Philip S; Vendittoli, Pascal-Andre

2018-02-22

Clinical trials and meta-analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep-vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge. We performed a multicenter, double-blind, randomized, controlled trial involving patients who were undergoing total hip or knee arthroplasty. All the patients received once-daily oral rivaroxaban (10 mg) until postoperative day 5 and then were randomly assigned to continue rivaroxaban or switch to aspirin (81 mg daily) for an additional 9 days after total knee arthroplasty or for 30 days after total hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism (the primary effectiveness outcome) and bleeding complications, including major or clinically relevant nonmajor bleeding (the primary safety outcome). A total of 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11 of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], -0.55 to 0.66; Paspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, -0.65 to 0.29; P=0.42). Clinically important bleeding occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage points; 95% CI, -1.07 to 0.47; P=0.43). Among patients who received 5 days of rivaroxaban prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with aspirin was not significantly different from rivaroxaban in the prevention of symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT01720108 .).

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

Science.gov (United States)

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

2015-05-01

Aspirin's prevention of cardiovascular disease (CVD) events in individuals with type 2 diabetes mellitus is controversial. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and aspirin all affect the cyclooxygenase enzyme. The relationship between plasma EPA and DHA and aspirin's effects has not been determined. Thirty adults with type 2 diabetes mellitus ingested aspirin (81 mg/day) for 7 days, then EPA+DHA (2.6g/day) for 28 days, then both for another 7 days. Lysophosphatidic acid (LPA) species and more classic platelet function outcomes were determined. Plasma concentrations of total EPA+DHA were associated with 7-day aspirin reduction effects on these outcomes in a "V"-shaped manner for all 11 LPA species and ADP-induced platelet aggregation. This EPA+DHA concentration was quite consistent for each of the LPA species and ADP. These results support aspirin effects on lysolipid metabolism and platelet aggregation depending on plasma EPA+DHA concentrations in individuals with a disturbed lipid milieu. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

Wu, K.K.; Sanduja, R.; Tsai, A.L.; Ferhanoglu, B.; Loose-Mitchell, D.S.

1991-01-01

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

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

DEFF Research Database (Denmark)

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

2015-01-01

BACKGROUND: A comprehensive body of evidence has shown that aspirin has cancer-preventive effects, particularly against gastrointestinal cancer, but its effects on the risk of ovarian cancer are less well established. This nationwide case-control study examined the association between low......-dose aspirin and the risk of ovarian cancer. PATIENTS AND METHODS: We identified all patients in the Danish Cancer Registry aged 30-84 years old with a histologically verified first diagnosis of epithelial ovarian cancer during 2000-2011. Each patient was sex- and age-matched to 15 population controls using...... risk-set sampling. Prescription use, comorbidity, reproductive history, and demographic characteristics data were obtained from nationwide registries. The use of low-dose (75-150 mg) aspirin was defined according to the dose as well as the duration and consistency of use. Conditional logistic...

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

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Yoshihiro Suzuki

2010-05-01

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

Impairment of aminopyrine clearance in aspirin-damaged canine gastric mucosa

International Nuclear Information System (INIS)

Miller, T.A.; Henagan, J.M.; Loy, T.M.

1983-01-01

Using an in vivo canine chambered stomach preparation, the clearance of [ 14 C]aminopyrine across mucosa when intravenously infused and the back-diffusion of this substance from gastric lumen to mucosa when topically applied to gastric epithelium were evaluated in aspirin-damaged gastric epithelium. In mucosa damaged by either 20 mM or 40 mM aspirin, the recovery of [ 14 C]aminopyrine, when topically mixed with acid (pH . 1.1) perfusate solution, was not significantly different from nondamaged control mucosa. In addition, the degree of ''trapping'' of this substance from back-diffusion was not different in damaged mucosa from that observed in nondamaged epithelium. In contrast, when [ 14 C]aminopyrine was intravenously infused, its clearance was significantly impaired in aspirin-damaged mucosa when compared with control studies, as evidenced by the increased ''trapping'' of this substance in injured epithelium. These findings indicate that movement of aminopyrine from plasma to gastric lumen is impaired in damaged epithelium, making the aminopyrine clearance technique an unreliable method to accurately measure absolute gastric blood flow in this experimental setting

Monitoring of peri-operative fluid administration by individualized goal-directed therapy

DEFF Research Database (Denmark)

Bundgaard-Nielsen, M; Holte, Kathrine; Secher, N H

2007-01-01

(n = 725) found a reduced hospital stay. Post-operative nausea and vomiting (PONV) and ileus were reduced in three studies and complications were reduced in four studies. Of the monitors that may be applied for goal-directed therapy, only oesophageal Doppler has been tested adequately; however......, several other options exist. CONCLUSION: Goal-directed therapy with the maximization of flow-related haemodynamic variables reduces hospital stay, PONV and complications, and facilitates faster gastrointestinal functional recovery. So far, oesophageal Doppler is recommended, but other monitors...

Combined aspirin and cilostazol treatment is associated with reduced platelet aggregation and prevention of exercise-induced platelet activation.

Science.gov (United States)

Cleanthis, M; Bhattacharya, V; Smout, J; Ashour, H; Stansby, G

2009-05-01

Cilostazol has proven efficacy in increasing walking distance in claudicants, but it has not been demonstrated to be more effective than placebo in secondary cardiovascular prevention. The direct effect of exercise on platelet function remains less well defined. We have investigated the effect of combination treatment with aspirin and cilostazol on platelet activity in claudicants subjected to repeated treadmill exercise. Nineteen claudicants completed a double-blind, randomised, controlled, cross-over trial. Each subject received a 2-week course of aspirin (75mg) and placebo and aspirin and cilostazol (100mg twice daily). Following each 2-week treatment period, patients participated in a standardised treadmill test (3.2kmh(-1), 10 degrees incline) walking to maximal claudication distance. The exercise was repeated thrice in total, and blood was sampled before and after exercise. Platelet activation was measured using free platelet counting aggregation, flow cytometry for surface markers of platelet activation and soluble P-selectin assay. Compared to aspirin and placebo, combination treatment with aspirin and cilostazol was associated with reduced arachidonic-acid-induced platelet aggregation (pWilcoxon signed-rank test). Aspirin and placebo treatment were associated with elevated P-selectin expression, platelet-monocyte aggregation and reduced CD42b expression (pWilcoxon signed-rank test) post-exercise. No difference was seen in spontaneous platelet aggregation whilst soluble P-selectin was reduced post-exercise with combination treatment with aspirin and cilostazol (pWilcoxon signed-rank test). Combination treatment with aspirin and cilostazol results in suppression of platelet activation and reduces the effect of exercise on platelets. The benefit seen may be a result of cilostazol enhancing the inhibitory effect of aspirin on the cyclo-oxygenase pathway.

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...... on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.)...

Is anti-platelet therapy needed in continuous flow left ventricular assist device patients? A single-centre experience.

Science.gov (United States)

Litzler, Pierre-Yves; Smail, Hassiba; Barbay, Virginie; Nafeh-Bizet, Catherine; Bouchart, François; Baste, Jean-Marc; Abriou, Caroline; Bessou, Jean-Paul

2014-01-01

We report our 5-year experience of continuous flow left ventricular assist device (LVAD) implantation without the use of anti-platelet therapy. Between February 2006 and September 2011, 27 patients (26 men; 1 woman) were implanted with a continuous flow LVAD (HeartMate II, Thoratec Corporation, Pleasanton, CA, USA). The mean age was 55.7 ± 9.9 years. The mean duration of support was 479 ± 436 (1-1555) days with 35.4 patient-years on support. Twenty-one patients were implanted as a bridge to transplantation and 6 for destination therapy. The anticoagulation regimen was fluindione for all patients, with aspirin for only 4 patients. At the beginning of our experience, aspirin was administered to 4 patients for 6, 15, 60 and 460 days. Due to gastrointestinal (GI) bleeding and epistaxis, aspirin was discontinued, and since August 2006, no patients have received anti-platelet therapy. At 3 years, the survival rate during support was 76%. The most common postoperative adverse event was GI bleeding (19%) and epistaxis (30%) (median time: 26 days) for patients receiving fluindione and aspirin. The mean International Normalized Ratio (INR) was 2.58 ± 0.74 during support. Fifteen patients have been tested for acquired Von Willebrand disease. A diminished ratio of collagen-binding capacity and ristocetin cofactor activity to Von Willebrand factor antigen was observed in 7 patients. In the postoperative period, 2 patients presented with ischaemic stroke at 1 and 8 months. One of these 2 patients had a previous history of carotid stenosis with ischaemic stroke. There were no patients with haemorrhagic stroke, transient ischaemic attack or pump thrombosis. The event rate of stroke (ischaemic and haemorrhagic) per patient-year was 0.059 among the patients without aspirin with fluindione regimen only. A fluindione regimen without aspirin in long-duration LVAD support appears to not increase thromboembolic events and could lead to a diminished risk of haemorrhagic stroke.

Caffeine and Aspirin Protecting Albino Rats A gainst Biochemical and Histological Disorders Induced by Whole Body Gamma Irradiation

International Nuclear Information System (INIS)

Abd El-Rahman, N.A.; Sherif, N.H.

2015-01-01

Caffeine is an alkaloid (purine derivative) that contains flavonoids, where as aspirin, natural component of mammalian tissue ( acetylsalicylic acid) is one of the most commonly used non steroidal anti - inflammatory , and it is a necessary factor in the utilization of long - chain fatty acids to produce energy. Furthermore, it has been shown to protect cells from per oxidative stress. Th e objective of the present study is to evaluate the efficacy of caffeine (1,3,7 - trimethyl xanthine) 80 mg/kg b.wt. a nd aspirin ( acetylsalicylic acid) in the amelioration of the physiological and histological changes in stomach and intestine of rats exposed to gamma irradiation . Male albino rats were divided into 8 groups. 1 - Control group: rats not subject to any treatment, 2 - Caffeine group: rats received caffeine ( 80 ml/Kg body weight )via intraperitoneal injection for 21 days, 3 - Aspirin group: rats received aspirin (150 mg / kg body) via intraperitoneal injection for 21 days , 4 - Caffeine + Aspirin group: rats received caffeine a nd aspirin treatment, 5 - Radiation groups: rats were whole body gamma irradiated at 8 Gy , 6 - Caffeine + Radiation group: rats received caffeine for 21 days before whole body gamma irradiation at 8 Gy, 7 - Aspirin + Radiation group: rats received aspirin during 21 days before w hole body gamma irradiation , 8 - Caffeine + Aspirin + Radiation group: rats received caffeine parallel to aspirin for 21 days before whole body gamma irradiation. Animals were sacrificed 24 hrs post irradiation. The results demonstrated that rats exposed to whole body gamma irradiation showed a significant increase in alanine amino transferase (AL ) , aspartate amino transferase ( AST), and alkaline phosphatase (ALP) activities, and a significant decrease in total protein indicating liver injury. A significant increase in urea, creatinine, Na + ,and K + were recorded indicating kidney damage. Alteration of liver and kidney functions was accompanied by a significant

Underutilization of aspirin in people living with human immunodeficiency virus at increased risk for acute myocardial infarction: Systematic review and meta-analysis

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Stella Pak

2017-01-01

Full Text Available Context: With the increased availability of potent combination antiretroviral therapies, the life expectancy of people living with human immunodeficiency virus (PLHIV has greatly increased. This rapid improvement in lifespan has served as a catalyst for a paradigm shift in human immunodeficiency virus (HIV care. The focus of HIV care models has transitioned from the sole treatment of acute opportunistic infections to comprehensive management of chronic diseases, such as cardiovascular disease (CVD. Multiple studies have demonstrated that PLHIV are 50% more likely to develop acute myocardial infarction (AMI, compared to the general population. Cardiovascular risk prevention is becoming an essential component of the overarching HIV treatment plan. Aims: This meta-analysis aims to compare the rate of aspirin use for AMI prevention in indicated patients between PLHIV and general population. Methods: PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL, and MEDLINE databases were used to identify observational cohort trials. Studies were assessed by two reviewers for inclusion criteria. Two separate random-effects meta-analyses' models were performed using the DerSimonian and Laird method. Heterogeneity was assessed using the I2 value. Meta-regression with study level variables was used to explore potential sources of heterogeneity. The funnel-plot-based trim-and-fill method was applied to detect and adjust for potential publication bias. Statistical tests were two-sided and P< 0.05 was considered statistically significant. Results: A total of 13 studies were included for analysis. In these trials, 30.4% of PLHIV with increased risk for coronary heart disease (CHD used aspirin for AMI prevention, compared to 36.9% of patients at risk of CHD in the general population. Conclusions: The results of this meta-analysis provide evidence that aspirin is underutilized in both PLHIV and the general population across broad geographical zones. Aspirin use

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

Low-Dose Aspirin for the Prevention of Preeclampsia.

Science.gov (United States)

Fantasia, Heidi Collins

2018-02-01

Preeclampsia is a hypertensive disorder specific to pregnancy that remains a significant cause of maternal and neonatal morbidity and mortality. Identification of women who are most at risk for preeclampsia is imprecise. Because of the potential negative health consequences of preeclampsia for women and newborns and the lack of effective screening mechanisms preventing preeclampsia is an important component of prenatal care. Researchers have documented that low-dose aspirin, taken daily after the first trimester, can decrease the development of preeclampsia and reduce the incidence of preterm birth and birth of small-for-gestational-age infants. This column includes an overview of low-dose aspirin in pregnancy and a review of current recommendations from leading national organizations. © 2018 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

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

Science.gov (United States)

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

2007-02-01

Oral anticoagulants are better than aspirin for secondary prevention after myocardial infarction and after cerebral ischaemia in combination with non-rheumatic atrial fibrillation. The European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) aimed to determine whether oral anticoagulation with medium intensity is more effective than aspirin in preventing future vascular events in patients with transient ischaemic attack or minor stroke of presumed arterial origin. In this international, multicentre trial, patients were randomly assigned within 6 months after a transient ischaemic attack or minor stroke of presumed arterial origin either anticoagulants (target INR range 2.0-3.0; n=536) or aspirin (30-325 mg daily; n=532). The primary outcome was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever occurred first. In a post hoc analysis anticoagulants were compared with the combination of aspirin and dipyridamole (200 mg twice daily). Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with ClinicalTrials.gov (NCT00161070). The anticoagulants versus aspirin comparison of ESPRIT was prematurely ended because ESPRIT reported previously that the combination of aspirin and dipyridamole was more effective than aspirin alone. Mean follow-up was 4.6 years (SD 2.2). The mean achieved INR was 2.57 (SD 0.86). A primary outcome event occurred in 99 (19%) patients on anticoagulants and in 98 (18%) patients on aspirin (hazard ratio [HR] 1.02, 95% CI 0.77-1.35). The HR for ischaemic events was 0.73 (0.52-1.01) and for major bleeding complications 2.56 (1.48-4.43). The HR for the primary outcome event comparing anticoagulants with the combination treatment of aspirin and dipyridamole was 1.31 (0.98-1.75). Oral

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

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Sang Koo Lee

2008-01-01

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

Cytostatic action of aspirin and its effect on mitomycin C activity. A study in vitro under irradiation

International Nuclear Information System (INIS)

Kammerer, Cornelia; Getoff, Nikola

2001-01-01

Experiments in vitro using E. coli bacteria (AB 1157) proved that aspirin possesses a cytostatic ability under various experimental condition (pH=7.4) in airfree, aerated as well as in media containing N 2 O (converting e aq - into OH- radicals). In the last case the highest effect of aspirin was observed. The combination of aspirin with the well-known cytostaticum, mitomycin C (MMC) leads in airfree as well as in aerated media to a significant decrease of the MMC activity. However, the mixture of aspirin and MMC in the presence of N 2 O causes a synergistic effect, resulting in an enhancement of the MMC activity by a factor of 1.5. Probable reaction steps are presented and discussed. Using the pulse radiolysis method the rate constants for the reactions of e aq - , H and OH- species with aspirin were also determined

Cytoprotective effects of essential oil of Pinus halepensis L. against aspirin-induced toxicity in IEC-6 cells.

Science.gov (United States)

Bouzenna, Hafsia; Hfaiedh, Najla; Bouaziz, Mouhamed; Giroux-Metges, Marie-Agnès; Elfeki, Abdelfattah; Talarmin, Hélène

2017-12-01

Essential oils from Pinus species have been reported to have various therapeutic properties. This study was undertaken to identify the chemical composition and cytoprotective effects of the essential oil of Pinus halepensis L. against aspirin-induced damage in cells in vitro. The cytoprotection of the oil against toxicity of aspirin on the small intestine epithelial cells IEC-6 was tested. The obtained results have shown that 35 different compounds were identified. Aspirin induced a decrease in cell viability, and exhibited significant damage to their morphology and an increase in superoxide dismutase (SOD) and catalase (CAT) activities. However, the co-treatment of aspirin with the essential oil of Pinus induced a significant increase in cell viability and a decrease in SOD and CAT activities. Overall, these finding suggest that the essential oil of Pinus halepensis L. has potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

Cytostatic action of aspirin and its effect on mitomycin C activity. A study in vitro under irradiation

Energy Technology Data Exchange (ETDEWEB)

Kammerer, Cornelia; Getoff, Nikola E-mail: nikola.getoff@univie.ac.at

2001-04-01

Experiments in vitro using E. coli bacteria (AB 1157) proved that aspirin possesses a cytostatic ability under various experimental condition (pH=7.4) in airfree, aerated as well as in media containing N{sub 2}O (converting e{sub aq}{sup -} into OH- radicals). In the last case the highest effect of aspirin was observed. The combination of aspirin with the well-known cytostaticum, mitomycin C (MMC) leads in airfree as well as in aerated media to a significant decrease of the MMC activity. However, the mixture of aspirin and MMC in the presence of N{sub 2}O causes a synergistic effect, resulting in an enhancement of the MMC activity by a factor of 1.5. Probable reaction steps are presented and discussed. Using the pulse radiolysis method the rate constants for the reactions of e{sub aq}{sup -}, H and OH- species with aspirin were also determined.

Dynamic contrast enhanced ultrasound for therapy monitoring

Energy Technology Data Exchange (ETDEWEB)

Hudson, John M. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Williams, Ross [Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Tremblay-Darveau, Charles; Sheeran, Paul S. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Milot, Laurent [Department of Medical Imaging, University of Toronto, Toronto, ON (Canada); Bjarnason, Georg A. [Department of Medical Oncology, University of Toronto, and Sunnybrook Odette Cancer Centre, Toronto, ON (Canada); Burns, Peter N., E-mail: burns@sri.utoronto.ca [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON (Canada)

2015-09-15

Quantitative imaging is a crucial component of the assessment of therapies that target the vasculature of angiogenic or inflamed tissue. Dynamic contrast-enhanced ultrasound (DCE-US) using microbubble contrast offers the advantages of being sensitive to perfusion, non-invasive, cost effective and well suited to repeated use at the bedside. Uniquely, it employs an agent that is truly intravascular. This papers reviews the principles and methodology of DCE-US, especially as applied to anti-angiogenic cancer therapies. Reproducibility is an important attribute of such a monitoring method: results are discussed. More recent technical advances in parametric and 3D DCE-US imaging are also summarised and illustrated.

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

Directory of Open Access Journals (Sweden)

Ioannis Kariotis

2010-06-01

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

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.

Baseline placental growth factor levels for the prediction of benefit from early aspirin prophylaxis for preeclampsia prevention.

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Moore, Gaea S; Allshouse, Amanda A; Winn, Virginia D; Galan, Henry L; Heyborne, Kent D

2015-10-01

Placental growth factor (PlGF) levels early in pregnancy are lower in women who ultimately develop preeclampsia. Early initiation of low-dose aspirin reduces preeclampsia risk in some high risk women. We hypothesized that low PlGF levels may identify women at increased risk for preeclampsia who would benefit from aspirin. Secondary analysis of the MFMU High-Risk Aspirin study including singleton pregnancies randomized to aspirin 60mg/d (n=102) or placebo (n=72), with PlGF collected at 13w 0d-16w 6d. Within the placebo group, we estimated the probability of preeclampsia by PlGF level using logistic regression analysis, then determined a potential PlGF threshold for preeclampsia prediction using ROC analysis. We performed logistic regression modeling for potential confounders. ROC analysis indicated 87.71pg/ml as the threshold between high and low PlGF for preeclampsia-prediction. Within the placebo group high PlGF weakly predicted preeclampsia (AUC 0.653, sensitivity/specificity 63%/66%). We noted a 2.6-fold reduction in preeclampsia with aspirin in the high-PlGF group (12.15% aspirin vs 32.14% placebo, p=0.057), but no significant differences in preeclampsia in the low PlGF group (21.74% vs 15.91%, p=0.445). Unlike other studies, we found that high rather than low PlGF levels were associated with an increased preeclampsia risk. Low PlGF neither identified women at increased risk of preeclampsia nor women who benefitted from aspirin. Further research is needed to determine whether aspirin is beneficial in women with high PlGF, and whether the paradigm linking low PlGF and preeclampsia needs to be reevaluated. High-risk women with low baseline PlGF, a risk factor for preeclampsia, did not benefit from early initiation of low-dose aspirin. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

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

Effects of low dose aspirin (50 mg/day), low dose aspirin plus dipyridamole, and oral anticoagulant agents after internal mammary artery bypass grafting: patency and clinical outcome at 1 year. CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands. Prevention of Coronary Artery Bypass Graft Occlusion by Aspirin, Dipyridamole and Acenocoumarol/Phenprocoumon Study

NARCIS (Netherlands)

van der Meer, J.; Brutel de la Rivière, A.; van Gilst, W. H.; Hillege, H. L.; Pfisterer, M.; Kootstra, G. J.; Dunselman, P. H.; Mulder, B. J.; Lie, K. I.

1994-01-01

This study was performed to compare the efficacy and safety of aspirin, aspirin plus dipyridamole, and oral anticoagulant agents in the prevention of internal mammary artery graft occlusion. Antithrombotic drugs increase vein graft patency after coronary artery bypass surgery. Their benefit after

[Comparison between Endoscopic Therapy and Medical Therapy in Peptic Ulcer Patients with Adherent Clot: A Multicenter Prospective Observational Cohort Study].

Science.gov (United States)

Kim, Si Hye; Jung, Jin Tae; Kwon, Joong Goo; Kim, Eun Young; Lee, Dong Wook; Jeon, Seong Woo; Park, Kyung Sik; Lee, Si Hyung; Park, Jeong Bae; Ha, Chang Yoon; Park, Youn Sun

2015-08-01

The optimal management of bleeding peptic ulcer with adherent clot remains controversial. The purpose of this study was to compare clinical outcome between endoscopic therapy and medical therapy. We also evaluated the risk factors of rebleeding in Forrest type IIB peptic ulcer. Upper gastrointestinal (UGI) bleeding registry data from 8 hospitals in Korea between February 2011 and December 2013 were reviewed and categorized according to the Forrest classification. Patients with acute UGI bleeding from peptic ulcer with adherent clots were enrolled. Among a total of 1,101 patients diagnosed with peptic ulcer bleeding, 126 bleedings (11.4%) were classified as Forrest type IIB. Of the 126 patients with adherent clots, 84 (66.7%) received endoscopic therapy and 42 (33.3%) were managed with medical therapy alone. The baseline characteristics of patients in two groups were similar except for higher Glasgow Blatchford Score and pre-endoscopic Rockall score in medical therapy group. Bleeding related mortality (1.2% vs.10%; p=0.018) and all cause mortality (3.7% vs. 20.0%; p=0.005) were significantly lower in the endoscopic therapy group. However, there was no difference between endoscopic therapy and medical therapy regarding rebleeding (7.1% vs. 9.5%; p=0.641). In multivariate analysis, independent risk factors of rebleeding were previous medication with aspirin and/or NSAID (OR, 13.1; p=0.025). In patients with Forrest type IIB peptic ulcer bleeding, endoscopic therapy was associated with a significant reduction in bleeding related mortality and all cause mortality compared with medical therapy alone. Important risk factor of rebleeding was use of aspirin and/or NSAID.

Validasi Metode HPLC untuk Penetapan Aspirin dan Asam Salisilat dalam Plasma Kelinci (Lepus curpaeums secara Simultan

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Agus Siswanto

2017-02-01

Full Text Available Aspirin is a nonsteroidal anti-inflammatory drug which also has the effect of antiplatelet for stroke prevention. Aspirin inside human body is very easy to break down into salicylic acid as the main metabolite. The aim of this study is to develop and validate the method for determinating aspirin and salicylic acid concentration in plasma by HPLC. Method validation including system suitability test, linearity test, determination of LOD and LOQ, recovery, accuracy and precision. Concentration of analytes in blood is measured by HPLC using benzoic acid as internal standard, with condition Purospher column Endcapped Star RP-18 (250 x 4.6 mm id, 5 m, acetonitrile : buffer phosphate 20 mM pH 2.5 (30:70 v/v as mobile phase, injection volume 20 mL, flow rate 1.5 mL/minute, and UV-Vis detector λ 230 nm. The results showed that the proposed method meets the requirements of system suitability and good linearity (r > 0,990 with LOQ (aspirin = 0.024 mg/mL, salicylic acid = 0.336 mg/mL and LOD (aspirin = 0.007 mg/mL, salicylic acid = 0.101 mg/mL. The method of analysis provides recovery of 85-115 %, accuracy and precision in accordance with the requirements for bioanalytical with CV < 5 %. Therefore, the proposed method is applicable to determine of aspirin and salicylic acid concentration in plasma.

Aspirin and the risk of cardiovascular events in atherosclerosis patients with and without prior ischemic events.

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Bavry, Anthony A; Elgendy, Islam Y; Elbez, Yedid; Mahmoud, Ahmed N; Sorbets, Emmanuel; Steg, Philippe Gabriel; Bhatt, Deepak L

2017-09-01

The benefit of aspirin among patients with stable atherosclerosis without a prior ischemic event is not well defined. Aspirin would be of benefit in outpatients with atherosclerosis with prior ischemic events, but not in those without ischemic events. Subjects from the Reduction of Atherothrombosis for Continued Health registry were divided according to prior ischemic event (n =21 724) vs stable atherosclerosis, but no prior ischemic event (n = 11 872). Analyses were propensity score matched. Aspirin use was updated at each clinic visit and considered as a time-varying covariate. The primary outcome was the first occurrence of cardiovascular death, myocardial infarction, or stroke. In the group with a prior ischemic event, aspirin use was associated with a marginally lower risk of the primary outcome at a median of 41 months (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.65-1.01, P = 0.06). In the group without a prior ischemic event, aspirin use was not associated with a lower risk of the primary outcome at a median of 36 months (HR: 1.03, 95% CI: 0.73-1.45, P = 0.86). In this observational analysis of outpatients with stable atherosclerosis, aspirin was marginally beneficial among patients with a prior ischemic event; however, there was no apparent benefit among those with no prior ischemic event. © 2017 Wiley Periodicals, Inc.

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

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

2011-01-01

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

Controlled release from aspirin based linear biodegradable poly(anhydride esters) for anti-inflammatory activity.

Science.gov (United States)

Dasgupta, Queeny; Movva, Sahitya; Chatterjee, Kaushik; Madras, Giridhar

2017-08-07

This work reports the synthesis of a novel, aspirin-loaded, linear poly (anhydride ester) and provides mechanistic insights into the release of aspirin from this polymer for anti-inflammatory activity. As compared to conventional drug delivery systems that rely on diffusion based release, incorporation of bioactives in the polymer backbone is challenging and high loading is difficult to achieve. In the present study, we exploit the pentafunctional sugar alcohol (xylitol) to provide sites for drug (aspirin) attachment at its non-terminal OH groups. The terminal OH groups are polymerized with a diacid anhydride. The hydrolysis of the anhydride and ester bonds under physiological conditions release aspirin from the matrix. The resulting poly(anhydride ester) has high drug loading (53%) and displays controlled release kinetics of aspirin. The polymer releases 8.5 % and 20%, of the loaded drug in one and four weeks, respectively and has a release rate constant of 0.0035h -0.61 . The release rate is suitable for its use as an anti-inflammatory agent without being cytotoxic. The polymer exhibits good cytocompatibility and anti-inflammatory properties and may find applications as injectable or as an implantable bioactive material. The physical insights into the release mechanism can provide development of other drug loaded polymers. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of aspirin and ticlopidine on platelet deposition in carotid atherosclerosis: assessment by indium-111 platelet scintigraphy

International Nuclear Information System (INIS)

Isaka, Y.; Kimura, K.; Etani, H.; Uehara, A.; Uyama, O.; Yoneda, S.; Kamada, T.; Kusunoki, M.

1986-01-01

The antiplatelet effects of aspirin and ticlopidine were studied by a dual-tracer method, using indium-111 labeled platelets and technetium-99m human serum albumin, in a group of 12 patients with suspected ischemic cerebrovascular disease. The magnitude of platelet accumulation at the carotid bifurcation was expressed as the ratio of radioactivity of indium-111 platelets deposited on the vascular wall to those circulating in the blood-pool (PAI, platelet accumulation index), 48 hr after injection of labeled platelets. PAI values were measured before (baseline studies) and after the antithrombotic therapies (aspirin studies: 325 mg bid for 22.3 +/- 1.3 days, ticlopidine studies: 100 mg tid for 21.8 +/- 2.1 days). At the baseline, the mean PAI value at 24 carotid bifurcations in the patient group was 15.7 +/- 15.3% (mean +/- S.D.) compared to -4.3 +/- 9.1 at 24 carotid bifurcations in 12 normal subjects (p less than 0.01). We defined the upper limit for a normal PAI (%) value to be +13.9, namely the mean PAI plus 2 SD for the carotid bifurcation in normal subjects and used this value for semiquantitative analysis. At the baseline, significant elevation of PAI (more than 13.9%; positive scintigram) was observed at 12 of 24 vessels, while 12 other regions were negative (less than 13.9%). In the lesions with positive scintigraphic results at the baseline, the mean PAI (%) value from the baseline, aspirin and ticlopidine studies was 29.5 +/- 7.0, 11.2 +/- 8.5 (p less than 0.01 versus baseline) and 21.4 +/- 21.3 (not significant from baseline), respectively

Specific recognition and fluorescent determination of aspirin by using core-shell CdTe quantum dot-imprinted polymers

International Nuclear Information System (INIS)

Wei, Xiao; Zhou, Zhiping; Hao, Tongfan; Lu, Kai; Dai, Jiangdong; Xu, Yeqing; Li, Hongji; Zheng, Xudong; Gao, Lin; Wang, Jixiang; Yan, Yongsheng; Zhu, Yanzhuo

2015-01-01

A molecularly imprinted polymer (MIP) was deposited on the surface of CdTe quantum dots (QDs) to act as a recognition element for aspirin. The MIP was synthesized from 3-aminopropyltriethoxysilane as the functional monomer, aspirin as the template, and tetraethoxysilane as the cross-linker via a sol–gel process that leads to surface imprinting. It is shown that the fraction of QDs and the polymerization process affect size and morphology of the MIP-coated QDs. The optical stability, effects of pH, detection time and selective determination of aspirin were optimized. The fluorescence intensity of the particles (photoexcited at 400 nm and measured at 628 nm) decreases linearly with increasing concentration of aspirin in the 2.0–50 μmol L −1 range. The limit of detection (at an S/N of 3) is 0.25 μmol L −1 . The method was successfully applied to the determination of aspirin in human urine and saliva. (author)

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

DEFF Research Database (Denmark)

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

2009-01-01

The optimal duration and dose of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) in the potential prevention of colorectal cancer (CRC) have not been established. We examined this issue in the Danish Diet, Cancer, and Health Study. Self-reported NSAID use at entry (January...... a protective effect against CRC. Further studies of the effective dose of aspirin and the potential interaction between NSAID use and BMI are warranted....

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

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

Science.gov (United States)

Burn, John; Bishop, D Timothy; Mecklin, Jukka-Pekka; Macrae, Finlay; Möslein, Gabriela; Olschwang, Sylviane; Bisgaard, Marie-Luise; Ramesar, Raj; Eccles, Diana; Maher, Eamonn R; Bertario, Lucio; Jarvinen, Heikki J; Lindblom, Annika; Evans, D Gareth; Lubinski, Jan; Morrison, Patrick J; Ho, Judy W C; Vasen, Hans F A; Side, Lucy; Thomas, Huw J W; Scott, Rodney J; Dunlop, Malcolm; Barker, Gail; Elliott, Faye; Jass, Jeremy R; Fodde, Ricardo; Lynch, Henry T; Mathers, John C

2008-12-11

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. 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. Among 1071 persons in 43 centers, 62 were ineligible to participate in the study, 72 did not enter the study, and 191 withdrew from the study. These three categories were equally distributed across the study groups. Over a mean period of 29 months (range, 7 to 74), colonic adenoma or carcinoma developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) (relative risk, 1.0; 95% confidence interval [CI], 0.7 to 1.4). There were no significant differences between the two groups with respect to the development of advanced neoplasia (7.4% and 9.9%, respectively; P=0.33). Among the 727 participants receiving resistant starch or placebo, neoplasia developed in 67 participants receiving starch (18.7%), as compared with 68 receiving placebo (18.4%) (relative risk, 1.0; 95% CI, 0.7 to 1.4). Advanced adenomas and colorectal cancers were evenly distributed in the two groups. The prevalence of serious adverse events was low, and the events were evenly distributed. The use of aspirin, resistant starch, or both for up to 4 years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.) 2008 Massachusetts Medical Society

Aspirin-exacerbated respiratory disease: Prevalence, diagnosis, treatment, and considerations for the future

Science.gov (United States)

Stoner, Ashley N.; Borish, Larry

2016-01-01

Aspirin-exacerbated respiratory disease (AERD) is a late onset condition characterized by the Samter triad (aspirin sensitivity [as well as sensitivity to any nonselective cyclooxygenase inhibitor], nasal polyps, asthma) and additional features, including eosinophilic chronic rhinosinusitis, hypereosinophilia, anosmia, frequent absence of atopy, and, intolerance to ingestion of red wine and other alcoholic beverages. The diagnosis is rare, and, because of this, it is also often missed by physicians. However, it is highly overexpressed in patients with severe asthma (and severe chronic rhinosinusitis with nasal polyps), which makes its recognition essential. For this review, we considered mechanisms involved in the pathogenesis of this disease and discussed the clinical symptoms of AERD. We also discussed the role of aspirin desensitization in the treatment of AERD. Also, we considered medications (e.g, leukotriene modifiers) and surgical interventions that have a role in the treatment of AERD. PMID:28124651

A novel pleiotropic effect of aspirin: Beneficial regulation of pro- and anti-inflammatory mechanisms in microglial cells.

Science.gov (United States)

Kata, Diana; Földesi, Imre; Feher, Liliana Z; Hackler, Laszlo; Puskas, Laszlo G; Gulya, Karoly

2017-06-01

Aspirin, one of the most widely used non-steroidal anti-inflammatory drugs, has extensively studied effects on the cardiovascular system. To reveal further pleiotropic, beneficial effects of aspirin on a number of pro- and anti-inflammatory microglial mechanisms, we performed morphometric and functional studies relating to phagocytosis, pro- and anti-inflammatory cytokine production (IL-1β, tumor necrosis factor-α (TNF-α) and IL-10, respectively) and analyzed the expression of a number of inflammation-related genes, including those related to the above functions, in pure microglial cells. We examined the effects of aspirin (0.1mM and 1mM) in unchallenged (control) and bacterial lipopolysaccharide (LPS)-challenged secondary microglial cultures. Aspirin affected microglial morphology and functions in a dose-dependent manner as it inhibited LPS-elicited microglial activation by promoting ramification and the inhibition of phagocytosis in both concentrations. Remarkably, aspirin strongly reduced the pro-inflammatory IL-1β and TNF-α production, while it increased the anti-inflammatory IL-10 level in LPS-challenged cells. Moreover, aspirin differentially regulated the expression of a number of inflammation-related genes as it downregulated such pro-inflammatory genes as Nos2, Kng1, IL1β, Ptgs2 or Ccr1, while it upregulated some anti-inflammatory genes such as IL10, Csf2, Cxcl1, Ccl5 or Tgfb1. Thus, the use of aspirin could be beneficial for the prophylaxis of certain neurodegenerative disorders as it effectively ameliorates inflammation in the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Aspirin Does Not Increase Heart Failure Events in Heart Failure Patients: From the WARCEF Trial.

Science.gov (United States)

Teerlink, John R; Qian, Min; Bello, Natalie A; Freudenberger, Ronald S; Levin, Bruce; Di Tullio, Marco R; Graham, Susan; Mann, Douglas L; Sacco, Ralph L; Mohr, J P; Lip, Gregory Y H; Labovitz, Arthur J; Lee, Seitetz C; Ponikowski, Piotr; Lok, Dirk J; Anker, Stefan D; Thompson, John L P; Homma, Shunichi

2017-08-01

The aim of this study was to determine whether aspirin increases heart failure (HF) hospitalization or death in patients with HF with reduced ejection fraction receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Because of its cyclooxygenase inhibiting properties, aspirin has been postulated to increase HF events in patients treated with ACE inhibitors or ARBs. However, no large randomized trial has addressed the clinical relevance of this issue. We compared aspirin and warfarin for HF events (hospitalization, death, or both) in the 2,305 patients enrolled in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial (98.6% on ACE inhibitor or ARB treatment), using conventional Cox models for time to first event (489 events). In addition, to examine multiple HF hospitalizations, we used 2 extended Cox models, a conditional model and a total time marginal model, in time to recurrent event analyses (1,078 events). After adjustment for baseline covariates, aspirin- and warfarin-treated patients did not differ in time to first HF event (adjusted hazard ratio: 0.87; 95% confidence interval: 0.72 to 1.04; p = 0.117) or first hospitalization alone (adjusted hazard ratio: 0.88; 95% confidence interval: 0.73 to 1.06; p = 0.168). The extended Cox models also found no significant differences in all HF events or in HF hospitalizations alone after adjustment for covariates. Among patients with HF with reduced ejection fraction in the WARCEF trial, there was no significant difference in risk of HF events between the aspirin and warfarin-treated patients. (Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction trial [WARCEF]; NCT00041938). Copyright © 2017 American College of Cardiology Foundation. All rights reserved.

The Protective Effect of Field Mint Leaves in Reducing Stomach Ulcer in Rats Induced by Aspirin

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Vanitha Ratha Krisnan

2015-09-01

Full Text Available Background: Stomach mucosal wall erosion is caused by the imbalance of the aggressive factors and mucosal defensive factors due to the common causes such as the side effect of consuming non-steroidal anti-inflammatory drugs. Field mint (Menthaarvensis leaves have been used as an alternative option to cure and prevent the gastric problems. The aim of this study was to analyze the protective effect of Field mint leaves infusion in reducing stomach ulcer in rats induced by Aspirin. Methods: The experimental study was conducted at Histology Laboratory of Faculty of Medicine, Universitas Padjadjaran, Bandung. Sixteen rats were divided into 4 groups randomly: group I (control negative group, group II (control positive group, given 90mg/day Aspirin, group III (the treatment group, given 5cc of Field mint leaves infusion and 90 mg Aspirin and group IV (the treatment group, given 5.6µg of Misoprostol and 90 mg Aspirin. Mucosal wall erosions were determined by using microscope. Data were analyzed using non-parametric Kruskal-Wallis test and Mann-Whitney U-test (CI 95% and p-value<0.05 Results: Group II had high score of mucosal wall erosions after given only aspirin. In group III and IV, the score of mucosal wall erosions were low. However there was no difference in score of mucosal wall erosions between group III-IV (p<0.05 Conclusions: Field mint (Menthaarvensis leaves infusion is able to prevent stomach mucosal wall erosions induced by Aspirin as misoprostol does.

Nullification of aspirin induced gastrotoxicity and hepatotoxicity by prior administration of wheat germ oil in Mus musculus: histopathological, ultrastructural and molecular studies.

Science.gov (United States)

Mohamed, H R H; Hamad, S R

2017-08-30

Aspirin (acetyl salicylic acid) is used worldwide to treat various inflammatory conditions and prevent cardiovascular disease, along with reducing the risk of cancer. However, administration of aspirin causes toxic effects, especially in the stomach and liver. Thus, our study examined the protective effect of wheat germ oil on aspirin-induced toxicity in the stomach and liver tissues of Swiss albino mice. Administration of wheat germ oil before aspirin has restored normal hepatic and gastric tissue architecture and DNA integrity has become better than that of a negative health control group compared with the aspirin only treated group. The elevated gastric nitric oxide content in the aspirin only treated group was significantly decreased by wheat germ oil prior administration as a result of reduced the expression of inducible nitric synthase and increased the expression of endothelial nitric oxide synthase compared to their expression in the aspirin administered group. Wheat germ oil pre-administration significantly reduced the level of malondialdehyde, increased the level of glutathione and catalase and superoxide dismutase activities compared with those in aspirin only treated group. We conclude that wheat germ oil has a potential protective effect against aspirin induced gastro- and hepato-toxicity because of its free radical scavenging ability.

Effect of acetyl salicylic acid (aspirin) and Prostaglandins on thyroid tissue and carbohydrate metabolism in liver of male albino rats

International Nuclear Information System (INIS)

Balasubramanian, A.; Ramakrishnan, S.

1979-01-01

Aspirin, both in chronic and acute doses, led to a considerable decrease in percentage uptake of labelled iodine (Na 131 I) and serum protein-bound iodine by the thyroid gland whereas prostaglandins (PGs) did not exhibit any significant effect on both the parameters. Simultaneous administration of aspirin and PGs caused a significant decrease in the two parameters, and on withdrawal of aspirin from the diet the two parameters were restored to normal levels, thus suggesting that the effect of aspirin on thyroid is direct and reversible. Aspirin, both in acute and chronic doses, effected decrease in glycogen levels, in vivo and in vitro incorporation of [U- 14 C] glucose into glycogen, and glycogen synthetase activity in the liver of both fed, and fasting, rat. Prostaglandins, on the other hand, resulted in a significant increase in the three parameters, thus enhancing the rate of liver glycogenesis. Normal levels were restored when both aspirin and PGs were given together. Withdrawal of aspirin also restored normal hepatic glycogenesis. Significant reduction in the activities of hepatic gluconeogenic enzymes, viz. glucose 6-phosphatase, fructose 1,6-diphosphatase, phosphopyruvate carboxylase, pyruvate carboxylase, aspartate aminotransferase and glutamate dehydrogenase was observed due to chronic and acute administration of aspirin and PGs were devoid of any significant effect on gluconeogenic enzymes, thus ruling out the mediation of PGs. (auth.)

Effect of acetyl salicylic acid (aspirin) and Prostaglandins on thyroid tissue and carbohydrate metabolism in liver of male albino rats

Energy Technology Data Exchange (ETDEWEB)

Balasubramanian, A; Ramakrishnan, S [Jawaharlal Inst. of Postgraduate Medical Education and Research, Pondicherry (India)

1979-04-01

Aspirin, both in chronic and acute doses, led to a considerable decrease in percentage uptake of labelled iodine (Na/sup 131/I) and serum protein-bound iodine by the thyroid gland whereas prostaglandins (PGs) did not exhibit any significant effect on both the parameters. Simultaneous administration of aspirin and PGs caused a significant decrease in the two parameters, and on withdrawal of aspirin from the diet the two parameters were restored to normal levels, thus suggesting that the effect of aspirin on thyroid is direct and reversible. Aspirin, both in acute and chronic doses, effected decrease in glycogen levels, in vivo and in vitro incorporation of (U-/sup 14/C) glucose into glycogen, and glycogen synthetase activity in the liver of both fed, and fasting, rat. Prostaglandins, on the other hand, resulted in a significant increase in the three parameters, thus enhancing the rate of liver glycogenesis. Normal levels were restored when both aspirin and PGs were given together. Withdrawal of aspirin also restored normal hepatic glycogenesis. Significant reduction in the activities of hepatic gluconeogenic enzymes, viz. glucose 6-phosphatase, fructose 1,6-diphosphatase, phosphopyruvate carboxylase, pyruvate carboxylase, aspartate aminotransferase and glutamate dehydrogenase was observed due to chronic and acute administration of aspirin and PGs were devoid of any significant effect on gluconeogenic enzymes, thus ruling out the mediation of PGs.

Decreased proinflammatory cytokine production by peripheral blood mononuclear cells from vitiligo patients following aspirin treatment

International Nuclear Information System (INIS)

Zailaie, Mohammad Z.

2005-01-01

Limited studies have shown that treatment of cells with aspirin modulates their cytokine production. Consequently, the aim of the present study is to investigate the pattern of important proinflammatory cytokines production by stimulated peripheral blood mononuclear cells (PBMC) from patients with active vitiligo following long-term treatment with low-dose oral aspirin. The study was conducted at the Vitiligo Unit, King Abdul-Aziz University Medical Center, Jeddah, Kingdom of Saudi Arabia between March and October 2003. Thirty-two patients (18 females and 14 males) with non-segmental vitiligo were divided into 2 equal groups, one group received a daily single dose of oral aspirin (300 mg) and the other group received placebo for a period of 12 weeks. The concentrations of interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) were determined in the supernatant of isolated cultured PMBC after being stimulated with bacterial lipopolysaccharide (LPS), before the start of aspirin treatment and at end of treatment period. Cytokine levels were measured using the quantitative sandwich enzyme-linked immunosorbent assay (ELISA) technique, utilizing commercially available kits. The proinflammatory cytokine production by the PBMC of patients with active vitiligo was significantly increased compared to normal controls. Thus, the relative percentage increase in the production of IL-1beta, IL-6, IL-8 and TNF-alpha was: 39.4%, 110.5% (p<0.05), 91.5% (p<0.01), and 37% (p<0.05). At the end of treatment, proinflammatory cytokine production in the aspirin-treated group of active vitiligo patients was significantly decreased compared to the placebo group. Thus, the relative percentage decrease in the production of IL-1beta IL-6, IL-8 and TNF-alpha was: 42.5%, 45.2% (p<0.05), 30.8% (p<0.01), and 50.6% (p<0.05). The vitiligo activity was arrested in all aspirin-treated patients, while 2 patients demonstrated significant repigmentation.Chronic administration of

Use of paracetamol, ibuprofen or aspirin in pregnancy and risk of cerebral palsy in the child

DEFF Research Database (Denmark)

Petersen, Tanja Gram; Liew, Zeyan; Nybo Andersen, Anne-Marie

2018-01-01

Background: It has been debated whether mild analgesics, mainly paracetamol, adversely affect aspects of neurodevelopment. We examined whether mother's use of paracetamol, aspirin or ibuprofen in pregnancy is associated with increased risk of cerebral palsy (CP) in the child. Method: We included...... registers. We estimated the average causal effect of analgesics on risk of CP using marginal structural models with stabilized inverse probability weights. Results: Paracetamol use was reported in 49% of all pregnancies, aspirin in 3% and ibuprofen in 4%. Prenatal exposure to paracetamol ever in pregnancy......% CI: 1.0-2.5). Children ever prenatally exposed to aspirin in pregnancy had an elevated risk of bilateral spastic CP (aOR 2.4, 95% CI: 1.1-5.3) compared with unexposed. Conclusion: We observed an increased risk of spastic CP in children prenatally exposed to paracetamol and aspirin. Although we...

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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

Science.gov (United States)

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

2012-02-01

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

Aspirin hydrolysis in plasma is a variable function of butyrylcholinesterase and platelet-activating factor acetylhydrolase 1b2 (PAFAH1b2).

Science.gov (United States)

Zhou, Gang; Marathe, Gopal K; Hartiala, Jaana; Hazen, Stanley L; Allayee, Hooman; Tang, W H Wilson; McIntyre, Thomas M

2013-04-26

Aspirin is rapidly hydrolyzed within erythrocytes by a heterodimer of PAFAH1b2/PAFAH1b3 but also in plasma by an unidentified activity. Hydrolysis in both compartments was variable, with a 12-fold variation in plasma among 2226 Cleveland Clinic GeneBank patients. Platelet inhibition by aspirin was suppressed in plasma that rapidly hydrolyzed aspirin. Plasma aspirin hydrolysis was significantly higher in patients with coronary artery disease compared with control subjects (16.5 ± 4.4 versus 15.1 ± 3.7 nmol/ml/min; p = 3.4 × 10(-8)). A genome-wide association study of 2054 GeneBank subjects identified a single locus immediately adjacent to the BCHE (butyrylcholinesterase) gene associated with plasma aspirin hydrolytic activity (lead SNP, rs6445035; p = 9.1 × 10(-17)). However, its penetrance was low, and plasma from an individual with an inactivating mutation in BCHE still effectively hydrolyzed aspirin. A second aspirin hydrolase was identified in plasma, the purification of which showed it to be homomeric PAFAH1b2. This is distinct from the erythrocyte PAFAH1b2/PAFAH1b3 heterodimer. Inhibitors showed that both butyrylcholinesterase (BChE) and PAFAH1b2 contribute to aspirin hydrolysis in plasma, with variation primarily reflecting non-genetic variation of BChE activity. Therefore, aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. Hydrolytic effectiveness varies widely primarily from non-genetic variation of BChE activity that affects aspirin bioavailability in blood and the ability of aspirin to inhibit platelet aggregation.

Use of Low-dose Aspirin as Secondary Prevention of Atherosclerotic Cardiovascular Disease Among US Adults (From the National Health Interview Survey, 2012)

Science.gov (United States)

Fang, Jing; George, Mary G.; Gindi, Renee M.; Hong, Yuling; Yang, Quanhe; Ayala, Carma; Ward, Brian W.; Loustalot, Fleetwood

2015-01-01

Current guidelines recommend that adults with atherosclerotic cardiovascular disease take low-dose aspirin or other antiplatelet medications as secondary prevention of recurrent cardiovascular events. Yet, no national level assessment of low-dose aspirin use for secondary prevention of cardiovascular disease has been reported among a community-based population. Using data from the 2012 National Health Interview Survey, we assessed low-dose aspirin use among those with atherosclerotic cardiovascular disease. We estimated the prevalence ratios of low-dose aspirin use, adjusting for sociodemographic status, health insurance, and cardiovascular risk factors. Among those with atherosclerotic cardiovascular disease (n=3,068), 76% had been instructed to take aspirin, and 88% of those were following this advice. Of those not advised, 11% took aspirin on this own. Overall, 70% were taking aspirin (including those who followed their health care provider's advice and those who were not advised but took aspirin on their own). Logistic regression models showed that women, non-Hispanic blacks and Hispanics, those aged 40–64 years, with a high school education or with some college, or with fewer cardiovascular disease risk factors were less likely to take aspirin than men, non-Hispanic whites, those aged ≥65 years, with a college education or higher, or with all four selected cardiovascular disease risk factors, respectively. Additional analyses conducted among those with coronary heart disease only (n=2,007) showed similar patterns. In conclusion, use of low-dose aspirin for secondary prevention was 70%, with high reported adherence to health care providers' advice to take low-dose aspirin (88%), and significant variability within subgroups. PMID:25670639

Aspirin Hydrolysis in Plasma Is a Variable Function of Butyrylcholinesterase and Platelet-activating Factor Acetylhydrolase 1b2 (PAFAH1b2)*

Science.gov (United States)

Zhou, Gang; Marathe, Gopal K.; Hartiala, Jaana; Hazen, Stanley L.; Allayee, Hooman; Tang, W. H. Wilson; McIntyre, Thomas M.

2013-01-01

Aspirin is rapidly hydrolyzed within erythrocytes by a heterodimer of PAFAH1b2/PAFAH1b3 but also in plasma by an unidentified activity. Hydrolysis in both compartments was variable, with a 12-fold variation in plasma among 2226 Cleveland Clinic GeneBank patients. Platelet inhibition by aspirin was suppressed in plasma that rapidly hydrolyzed aspirin. Plasma aspirin hydrolysis was significantly higher in patients with coronary artery disease compared with control subjects (16.5 ± 4.4 versus 15.1 ± 3.7 nmol/ml/min; p = 3.4 × 10−8). A genome-wide association study of 2054 GeneBank subjects identified a single locus immediately adjacent to the BCHE (butyrylcholinesterase) gene associated with plasma aspirin hydrolytic activity (lead SNP, rs6445035; p = 9.1 × 10−17). However, its penetrance was low, and plasma from an individual with an inactivating mutation in BCHE still effectively hydrolyzed aspirin. A second aspirin hydrolase was identified in plasma, the purification of which showed it to be homomeric PAFAH1b2. This is distinct from the erythrocyte PAFAH1b2/PAFAH1b3 heterodimer. Inhibitors showed that both butyrylcholinesterase (BChE) and PAFAH1b2 contribute to aspirin hydrolysis in plasma, with variation primarily reflecting non-genetic variation of BChE activity. Therefore, aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. Hydrolytic effectiveness varies widely primarily from non-genetic variation of BChE activity that affects aspirin bioavailability in blood and the ability of aspirin to inhibit platelet aggregation. PMID:23508960

Efficacy And Safety of Dabigatran Etexilate Utilization With Concomitant Dual Antiplatelet Therapy In Atrial Fibrillation.

Science.gov (United States)

Centurión Md PhD Facc, Osmar Antonio

2014-01-01

The necessity to add two antiplatelet agents to an oral anticoagulant (OAC) often arises in patients with atrial fibrillation (AF) in routine clinical practice. The majority of AF patients have an indication for continuous OAC, and coronary artery disease co-exists in 25% of these patients. The increasing use of drug-eluting stents to minimize intrastent restenosis necessitates long-term dual antiplatelet therapy with Aspirin plus Clopidogrel to reduce the risk of early and late stent thrombosis. Combined aspirin-clopidogrel therapy, however, is less effective in preventing stroke compared with OAC alone in AF patients, and OAC alone is insufficient to prevent stent thrombosis. The management of AF patients presenting with an acute coronary syndrome poses similar management complexities. Since AF and coronary artery disease with stent placement are common, it is relatively frequent to treat patients with both these conditions, where triple antithrombotic therapy with Aspirin, Clopidogrel and an OAC would be needed. Dabigatran etexilate, an oral direct thrombin inhibitor, has shown that compared with Warfarin given at a dose of 150 mg twice daily significantly reduces stroke with less intracranial bleeding, and at a dose of 110 mg twice daily has similar efficacy with less bleeding. Although, Dabigatran maintained its overall favorable profile compared with Warfarin in patients on dual antiplatelet therapy, we should always bear in mind for the sake of our AF patients that combining dual antiplatelet therapy with chronic anticoagulation with Dabigatran, as well as with Warfarin, significantly increases bleeding risk. This triple therapy association should be evaluated in the individual patient after carefully balancing bleeding versus thrombotic risk.

Advances of reporter gene monitoring stem cell therapy

International Nuclear Information System (INIS)

Zhou Xiang; Yin Hongyan; Zhang Yifan

2010-01-01

Stem cell therapy research has made great progress, demonstrating a broad application prospects. However, stem cell therapy as a new disease treatment, there are still many problems to be solved. Reporter gene imaging is a rapid development in recent years, a non-invasive, sensitive method of monitoring of stem cells, in particular radionuclide reporter gene imaging has high sensitivity and specificity of the advantages of strong and can carry out imaging of deep tissue and repeat imaging, is a tracer in vivo conditions, the most promising stem cell transplantation technique, showing good prospects for development. (authors)

Effect of aspirin treatment on chondromalacia patellae.

OpenAIRE

Bentley, G; Leslie, I J; Fischer, D

1981-01-01

Twenty-nine patients (21 females and 8 males) with chondromalacia patellae diagnosed by arthroscopy were randomly allocated to receive aspirin or placebo for 3 months. Clinical and arthroscopic examination after 3 months showed no significant change in symptoms, signs, or macroscopic appearances in either group. Surgical treatment was performed in 14 patients for deteriorating symptoms.

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.

Early aspirin desensitization in unstable patients with acute coronary syndrome: Short and long-term efficacy and safety.

Science.gov (United States)

Córdoba-Soriano, Juan Gabriel; Corbí-Pascual, Miguel; López-Neyra, Isabel; Navarro-Cuartero, Javier; Hidalgo-Olivares, Víctor; Barrionuevo-Sánchez, Maria Isabel; Prieto-Mateos, Daniel; Gutiérrez-Díez, Antonio; Gallardo-López, Arsenio; Fuentes-Manso, Raquel; Gómez-Pérez, Alberto; Lafuente-Gormaz, Carlos; Jiménez-Mazuecos, Jesús

2016-11-01

Aspirin hypersensitivity is not a rare condition among patients with acute coronary syndrome. However, despite the publication of several successful desensitization protocols, the procedure is not as widespread as expected. We present a cohort of patients with acute coronary syndrome undergoing aspirin desensitization to evaluate its short- and long-term efficacy and safety and to reinforce data from previous studies. Of 1306 patients admitted to our Coronary Care Unit between February 2011 and February 2013, 24 (1.8%) had a history of aspirin hypersensitivity. All 24 patients underwent an eight-dose aspirin desensitization protocol (0.1, 0.3, 1, 3, 10, 25, 50 and 100 mg of aspirin given by mouth every 15 minutes) after premedication with antihistamines and corticosteroids or antileucotrienes. Previously prescribed β blockers and angiotensin-converting enzyme inhibitors were not discontinued. All patients were desensitized within 72 hours of admission. Those requiring urgent catheterization (five patients with ST segment elevation myocardial infarction) were desensitized within 12 hours of catheterization and the remainder before catheterization. All patients were successfully desensitized and only one presented with an urticarial reaction. The five patients with ST segment elevation myocardial infarction were treated with abciximab until desensitization was complete. All but one patient underwent catheterization and 20 underwent percutaneous coronary intervention, most (66%) with the implantation of a bare metal stent. At follow-up (a minimum of 6-24 months), only two patients had discontinued aspirin, both due to gastrointestinal bleeding, and no hypersensitivy reaction had occurred. Aspirin desensitization is effective and safe in unstable patients with acute coronary syndrome in both the short and long term.

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...... and sigmoid colon (at the end of intervention), and the major secondary endpoint was size of the largest polyp. A total of 206 randomized FAP patients commenced intervention, of whom 133 had at least one follow-up endoscopy and were therefore included in the primary analysis. Neither intervention...... significantly reduced polyp count in the rectum and sigmoid colon: aspirin relative risk = 0.77 (95% CI, 0.54-1.10; versus nonaspirin arms); RS relative risk = 1.05 (95% CI, 0.73-1.49; versus non-RS arms). There was a trend toward a smaller size of largest polyp in patients treated with aspirin versus...

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. |

Exploring clinicians' attitudes about using aspirin for risk reduction in people with Lynch Syndrome with no personal diagnosis of colorectal cancer.

Science.gov (United States)

Chen, Yanni; Peate, Michelle; Kaur, Rajneesh; Meiser, Bettina; Wong, Tim; Kirk, Judy; Ward, Robyn L; Goodwin, Annabel; Macrae, Finlay; Hiller, Janet; Trainer, Alison H; Mitchell, Gillian

2017-01-01

Recent research has shown that aspirin reduces the risk of cancers associated with Lynch Syndrome. However, uncertainty exists around the optimal dosage, treatment duration and whether the benefits of aspirin as a risk-reducing medication (RRM) outweigh adverse medication related side-effects. Little is known about clinicians' attitudes, current practice, and perceived barriers to recommending aspirin as a RRM. To explore the attitudes of clinicians who discuss risk management options with patients with Lynch Syndrome towards using aspirin as a RRM. Clinicians were invited through professional organisations to complete an online survey. Topics included their clinical experience with Lynch Syndrome, views and practice of recommending aspirin as a RRM, and knowledge about clinical risk management guidelines for Lynch Syndrome. Comparison of attitudes was made between three professional groups. 181 respondents were included in the analysis: 59 genetics professionals (genetic counsellors and clinical geneticists, medical oncologists with specialist training in familial cancer), 49 gastroenterologists and 73 colorectal surgeons. Most clinicians (76 %) considered aspirin to be an effective RRM and most (72 %) were confident about discussing it. In all professional categories, those who were confident about discussing aspirin with patients perceived it to be an effective RRM (OR = 2.8 [95 % CI = 1.8-4.2], p Lynch Syndrome patients compared to 69 % of gastroenterologists and 68 % of colorectal surgeons. Those who considered aspirin as an effective RRM or who felt confident in their knowledge of the aspirin literature were more likely (OR = 10 [95 % CI = 1.5-65], p = 0.010, OR = 6 [95 % CI = 2.2-16], p Lynch Syndrome per year were more likely to be confident in their knowledge of the aspirin literature and discussing it with patients (OR = 4.1 [95 % CI = 1.6-10.2], p = 0.003). Explicit recommendations to take aspirin, was reported by 65

Prevention of one-year vein-graft occlusion after aortocoronary-bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants. The CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands

NARCIS (Netherlands)

van der Meer, J.; Hillege, H. L.; Kootstra, G. J.; Ascoop, C. A.; Mulder, B. J.; Pfisterer, M.; van Gilst, W. H.; Lie, K. I.

1993-01-01

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

Effect of aspirin treatment on chondromalacia patellae.

Science.gov (United States)

Bentley, G; Leslie, I J; Fischer, D

1981-01-01

Twenty-nine patients (21 females and 8 males) with chondromalacia patellae diagnosed by arthroscopy were randomly allocated to receive aspirin or placebo for 3 months. Clinical and arthroscopic examination after 3 months showed no significant change in symptoms, signs, or macroscopic appearances in either group. Surgical treatment was performed in 14 patients for deteriorating symptoms. Images PMID:7008711

Safety and Efficacy of Warfarin Therapy in Kawasaki Disease.

Science.gov (United States)

Baker, Annette L; Vanderpluym, Christina; Gauvreau, Kimberly A; Fulton, David R; de Ferranti, Sarah D; Friedman, Kevin G; Murray, Jenna M; Brown, Loren D; Almond, Christopher S; Evans-Langhorst, Margaret; Newburger, Jane W

2017-10-01

To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications. We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin. Copyright © 2017 Elsevier Inc. All rights reserved.

Dual antiplatelet therapy reduces stroke but increases bleeding at the time of carotid endarterectomy.

Science.gov (United States)

Jones, Douglas W; Goodney, Philip P; Conrad, Mark F; Nolan, Brian W; Rzucidlo, Eva M; Powell, Richard J; Cronenwett, Jack L; Stone, David H

2016-05-01

Controversy persists regarding the perioperative management of clopidogrel among patients undergoing carotid endarterectomy (CEA). This study examined the effect of preoperative dual antiplatelet therapy (aspirin and clopidogrel) on in-hospital CEA outcomes. Patients undergoing CEA in the Vascular Quality Initiative were analyzed (2003-2014). Patients on clopidogrel and aspirin (dual therapy) were compared with patients taking aspirin alone preoperatively. Study outcomes included reoperation for bleeding and thrombotic complications defined as transient ischemic attack (TIA), stroke, or myocardial infarction. Secondary outcomes were in-hospital death and composite stroke/death. Univariate and multivariable analyses assessed differences in demographics and operative factors. Propensity score-matched cohorts were derived to control for subgroup heterogeneity. Of 28,683 CEAs, 21,624 patients (75%) were on aspirin and 7059 (25%) were on dual therapy. Patients on dual therapy were more likely to have multiple comorbidities, including coronary artery disease (P < .001), congestive heart failure (P < .001), and diabetes (P < .001). Patients on dual therapy were also more likely to have a drain placed (P < .001) and receive protamine during CEA (P < .001). Multivariable analysis showed that dual therapy was independently associated with increased reoperation for bleeding (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.20-2.42; P = .003) but was protective against TIA or stroke (OR, 0.61; 95% CI, 0.43-0.87; P = .007), stroke (OR, 0.63; 95% CI, 0.41-0.97; P = .03), and stroke/death (OR, 0.66; 95% CI, 0.44-0.98; P = .04). Propensity score matching yielded two groups of 4548 patients and showed that patients on dual therapy were more likely to require reoperation for bleeding (1.3% vs 0.7%; P = .004) but less likely to suffer TIA or stroke (0.9% vs 1.6%; P = .002), stroke (0.6% vs 1.0%; P = .04), or stroke/death (0.7% vs 1.2%; P = .03). Within the

Chronic Use of Aspirin and Total White Matter Lesion Volume: Results from the Women's Health Initiative Memory Study of Magnetic Resonance Imaging Study.

Science.gov (United States)

Holcombe, Andrea; Ammann, Eric; Espeland, Mark A; Kelley, Brendan J; Manson, JoAnn E; Wallace, Robert; Robinson, Jennifer

2017-10-01

To investigate the relationship between aspirin and subclinical cerebrovascular heath, we evaluated the effect of chronic aspirin use on white matter lesions (WML) volume among women. Chronic aspirin use was assessed in 1365 women who participated in the Women's Health Initiative Memory Study of Magnetic Resonance Imaging. Differences in WML volumes between aspirin users and nonusers were assessed with linear mixed models. A number of secondary analyses were performed, including lobe-specific analyses, subgroup analyses based on participants' overall risk of cerebrovascular disease, and a dose-response relationship analysis. The mean age of the women at magnetic resonance imaging examination was 77.6 years. Sixty-one percent of participants were chronic aspirin users. After adjusting for demographic variables and comorbidities, chronic aspirin use was nonsignificantly associated with 4.8% (95% CI: -6.8%, 17.9%) larger WML volumes. These null findings were confirmed in secondary and sensitivity analyses, including an active comparator evaluation where aspirin users were compared to users of nonaspirin nonsteroidal anti-inflammatory drugs or acetaminophen. There was a nonsignificant difference in WML volumes between aspirin users and nonusers. Further, our results suggest that chronic aspirin use may not have a clinically significant effect on WML volumes in women. Published by Elsevier Inc.

Venous thromboembolic prophylaxis after simultaneous bilateral total knee arthroplasty: aspirin versus warfarin.

Science.gov (United States)

Goel, R; Fleischman, A N; Tan, T; Sterbis, E; Huang, R; Higuera, C; Parvizi, J; Rothman, R H

2018-01-01

The aims of this study were to compare the efficacy of two agents, aspirin and warfarin, for the prevention of venous thromboembolism (VTE) after simultaneous bilateral total knee arthroplasty (SBTKA), and to elucidate the risk of VTE conferred by this procedure compared with unilateral TKA (UTKA). A retrospective, multi-institutional study was conducted on 18 951 patients, 3685 who underwent SBTKA and 15 266 who underwent UTKA, using aspirin or warfarin as VTE prophylaxis. Each patient was assigned an individualised baseline VTE risk score based on a system using the Nationwide Inpatient Sample. Symptomatic VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT), were identified in the first 90 days post-operatively. Statistical analyses were performed with logistic regression accounting for baseline VTE risk. The adjusted incidence of PE following SBTKA was 1.0% (95% confidence interval (CI) 0.86 to 1.2) with aspirin and 2.2% (95% CI 2.0 to 2.4) with warfarin. Similarly, the adjusted incidence of VTE following SBTKA was 1.6% (95% CI 1.1 to 2.3) with aspirin and 2.5% (95% CI 1.9 to 3.3) with warfarin. The risk of PE and VTE were reduced by 66% (odds ratio (OR) 0.44, 95% CI 0.25 to 0.78) and 38% (OR 0.62, 95% CI 0.38 to 1.0), respectively, using aspirin. In addition, the risk of PE was 204% higher for patients undergoing SBTKA relative to those undergoing UTKA. For each ten-point increase in baseline VTE risk, the risk of PE increased by 25.5% for patients undergoing SBTKA compared with 10.5% for those undergoing UTKA. Patients with a history of myocardial infarction or peripheral vascular disease had the greatest increase in risk from undergoing SBTKA instead of UTKA. Aspirin is more effective than warfarin for the prevention of VTE following SBTKA, and serves as the more appropriate agent for VTE prophylaxis for patients in all risk categories. Furthermore, patients undergoing SBTKA are at a substantially increased risk of VTE, even more so for

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...

Baseline Characteristics of Participants in the ASPREE (ASPirin in Reducing Events in the Elderly) Study.

Science.gov (United States)

McNeil, John J; Woods, Robyn L; Nelson, Mark R; Murray, Anne M; Reid, Christopher M; Kirpach, Brenda; Storey, Elsdon; Shah, Raj C; Wolfe, Rory S; Tonkin, Andrew M; Newman, Anne B; Williamson, Jeff D; Lockery, Jessica E; Margolis, Karen L; Ernst, Michael E; Abhayaratna, Walter P; Stocks, Nigel; Fitzgerald, Sharyn M; Trevaks, Ruth E; Orchard, Suzanne G; Beilin, Lawrence J; Donnan, Geoffrey A; Gibbs, Peter; Johnston, Colin I; Grimm, Richard H

2017-10-12

There are no primary prevention trials of aspirin with relevant geriatric outcomes in elderly people. ASPirin in Reducing Events in the Elderly (ASPREE) is a placebo-controlled trial of low-dose aspirin that will determine whether 5 years of daily 100-mg enteric-coated aspirin extends disability-free and dementia-free life in a healthy elderly population and whether these benefits outweigh the risks. Set in primary care, this randomized double-blind placebo-controlled trial has a composite primary endpoint of death, incident dementia or persistent physical disability. Participants aged 70+ years (non-minorities) or 65+ years (U.S. minorities) were free of cardiovascular disease, dementia, or physical disability and without a contraindication to, or indication for, aspirin. Baseline data include physical and lifestyle, personal and family medical history, hemoglobin, fasting glucose, creatinine, lipid panel, urinary albumin:creatinine ratio, cognition (3MS, HVLT-R, COWAT, SDMT), mood (CES-D-10), physical function (gait speed, grip strength), Katz activities of daily living and quality of life (SF-12). Recruitment ended in December 2014 with 16,703 Australian and 2,411 U.S. participants, a median age of 74 (range 65-98) years and 56% women. Approximately 55% of the U.S. cohort were from minority groups; 9% of the total cohort. Proportions with hypertension, overweight, and chronic kidney disease were similar to age-matched populations from both countries although lower percentages had diabetes, dyslipidemia, and osteoarthritis. Findings from ASPREE will be generalizable to a healthier older population in both countries and will assess whether the broad benefits of daily low-dose aspirin in prolonging independent life outweigh the risks. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Low-dose aspirin and risk of intracranial bleeds: An observational study in UK general practice.

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Cea Soriano, Lucía; Gaist, David; Soriano-Gabarró, Montse; Bromley, Susan; García Rodríguez, Luis A

2017-11-28

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. 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. There were 1,611 cases of ICB (n = 743 for intracerebral hemorrhage [ICH], n = 483 for subdural hematoma [SDH], and n = 385 for subarachnoid hemorrhage [SAH]). RRs (95% CI) were 0.98 (0.84-1.13) for all ICB, 0.98 (0.80-1.20) for ICH, 1.23 (0.95-1.59) for SDH, and 0.77 (0.58-1.01) for SAH. No duration of use or dose-response association was apparent. RRs (95% CI) for ≥1 year of low-dose aspirin use were 0.90 (0.72-1.13) for ICH, 1.20 (0.91-1.57) for SDH, and 0.69 (0.50-0.94) for SAH. Low-dose aspirin is not associated with an increased risk of any type of ICB and is associated with a significantly decreased risk of SAH when used for ≥1 year. © 2017 American Academy of Neurology.

Guided bone regeneration with asymmetric collagen-chitosan membranes containing aspirin-loaded chitosan nanoparticles

Directory of Open Access Journals (Sweden)

Zhang J

2017-12-01

Full Text Available Jiayu Zhang,1 Shiqing Ma,1 Zihao Liu,1 Hongjuan Geng,1 Xin Lu,1 Xi Zhang,1 Hongjie Li,1 Chenyuan Gao,2 Xu Zhang,1 Ping Gao1 1School of Dentistry, Hospital of Stomatology, Tianjin Medical University, Tianjin, 2Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, People’s Republic of China Introduction: Membranes allowing the sustained release of drugs that can achieve cell adhesion are very promising for guided bone regeneration. Previous studies have suggested that aspirin has the potential to promote bone regeneration. The purpose of this study was to prepare a local drug delivery system with aspirin-loaded chitosan nanoparticles (ACS contained in an asymmetric collagen-chitosan membrane (CCM. Methods: In this study, the ACS were fabricated using different concentrations of aspirin (5 mg, 25 mg, 50 mg, and 75 mg. The drug release behavior of ACS was studied. Transmission electron microscopy (TEM and scanning electron microscopy (SEM were used to examine the micromorphology of ACS and aspirin-loaded chitosan nanoparticles contained in chitosan-collagen membranes (ACS-CCM. In vitro bone mesenchymal stem cells (BMSCs were cultured and critical-sized cranial defects on Sprague-Dawley rats were made to evaluate the effect of the ACS-CCM on bone regeneration.Results: Drug release behavior results of ACS showed that the nanoparticles fabricated in this study could successfully sustain the release of the drug. TEM showed the morphology of the nanoparticles. SEM images indicated that the asymmetric membrane comprised a loose collagen layer and a dense chitosan layer. In vitro studies showed that ACS-CCM could promote the proliferation of BMSCs, and that the degree of differentiated BMSCs seeded on CCMs containing 50 mg of ACS was higher than that of other membranes. Micro-computed tomography showed that 50 mg of ACS-CCM resulted in enhanced bone regeneration compared with the control group.Conclusion: This

A beam monitor using silicon pixel sensors for hadron therapy

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhen, E-mail: zwang@mails.ccnu.edu.cn; Zou, Shuguang; Fan, Yan; Liu, Jun; Sun, Xiangming, E-mail: sphy2007@126.com; Wang, Dong; Kang, Huili; Sun, Daming; Yang, Ping; Pei, Hua; Huang, Guangming; Xu, Nu; Gao, Chaosong; Xiao, Le

2017-03-21

We report the design and test results of a beam monitor developed for online monitoring in hadron therapy. The beam monitor uses eight silicon pixel sensors, Topmetal-II{sup -}, as the anode array. Topmetal-II{sup -} is a charge sensor designed in a CMOS 0.35 µm technology. Each Topmetal-II{sup -} sensor has 72×72 pixels and the pixel size is 83×83 µm{sup 2}. In our design, the beam passes through the beam monitor without hitting the electrodes, making the beam monitor especially suitable for monitoring heavy ion beams. This design also reduces radiation damage to the beam monitor itself. The beam monitor is tested with a carbon ion beam at the Heavy Ion Research Facility in Lanzhou (HIRFL). Results indicate that the beam monitor can measure position, incidence angle and intensity of the beam with a position resolution better than 20 µm, angular resolution about 0.5° and intensity statistical accuracy better than 2%.

[Determination of aspirin and free salicylic acid in lysinipirine injection by high performance liquid chromatography].

Science.gov (United States)

Dong, Yu; Zhao, Yuan-zheng; Zhang, Yi-na

2002-05-01

The contents of aspirin and free salicylic acid in lysinipirine injection were determined by high performance liquid chromatography (HPLC). A Hypersil BDS C18 column was used with the mobile phase of methanol-water-acetic acid (35:65:3, volume ratio) and the detection wavelength of 280 nm. The average recoveries of aspirin and salicylic acid added were 99.27% (RSD = 0.8%) and 99.61%(RSD = 1.3%), respectively. The calibration curves had good linearity in the range of 0.028 g/L -0.141 mg/L and 0.77 mg/L -3.85 mg/L, and the correlation coefficients were 0.9999 and 0.9998 for aspirin and salicylic acid respectively.

Salicylic acid metabolites and derivatives inhibit CDK activity: Novel insights into aspirin's chemopreventive effects against colorectal cancer

Science.gov (United States)

Dachineni, Rakesh; Kumar, D. Ramesh; Callegari, Eduardo; Kesharwani, Siddharth S.; Sankaranarayanan, Ranjini; Seefeldt, Teresa; Tummala, Hemachand; Bhat, G. Jayarama

2017-01-01

Aspirin's potential as a drug continues to be evaluated for the prevention of colorectal cancer (CRC). Although multiple targets for aspirin and its metabolite, salicylic acid, have been identified, no unifying mechanism has been proposed to clearly explain its chemopreventive effects. Our goal here was to investigate the ability of salicylic acid metabolites, known to be generated through cytochrome P450 (CYP450) enzymes, and its derivatives as cyclin dependent kinase (CDK) inhibitors to gain new insights into aspirin's chemopreventive actions. Using in vitro kinase assays, for the first time, we demonstrate that salicylic acid metabolites, 2,3-dihydroxy-benzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA), as well as derivatives 2,4-dihydroxybenzoic acid (2,4-DHBA), 2,6-dihydroxybenzoic acid (2,6-DHBA), inhibited CDK1 enzyme activity. 2,3-DHBA and 2,6-DHBA did not inhibit CDK2 and 4; however, both inhibited CDK-6 activity. Interestingly, another derivative, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) was highly effective in inhibiting CDK1, 2, 4 and 6 activity. Molecular docking studies showed that these compounds potentially interact with CDK1. Immunoblotting experiments showed that aspirin acetylated CDK1, and pre-incubation with salicylic acid and its derivatives prevented aspirin-mediated CDK1 acetylation, which supported the data obtained from molecular docking studies. We suggest that intracellularly generated salicylic acid metabolites through CYP450 enzymes within the colonic epithelial cells, or the salicylic acid metabolites generated by gut microflora may significantly contribute to the preferential chemopreventive effect of aspirin against CRC through inhibition of CDKs. This novel hypothesis and mechanism of action in aspirin's chemopreventive effects opens a new area for future research. In addition, structural modification to salicylic acid derivatives may prove useful in the development of novel CDK inhibitors in cancer prevention and

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

[Optimization of calcium alginate floating microspheres loading aspirin by artificial neural networks and response surface methodology].

Science.gov (United States)

Zhang, An-yang; Fan, Tian-yuan

2010-04-18

To investigate the preparation and optimization of calcium alginate floating microspheres loading aspirin. A model was used to predict the in vitro release of aspirin and optimize the formulation by artificial neural networks (ANNs) and response surface methodology (RSM). The amounts of the material in the formulation were used as inputs, while the release and floating rate of the microspheres were used as outputs. The performances of ANNs and RSM were compared. ANNs were more accurate in prediction. There was no significant difference between ANNs and RSM in optimization. Approximately 90% of the optimized microspheres could float on the artificial gastric juice over 4 hours. 42.12% of aspirin was released in 60 min, 60.97% in 120 min and 78.56% in 240 min. The release of the drug from the microspheres complied with Higuchi equation. The aspirin floating microspheres with satisfying in vitro release were prepared successfully by the methods of ANNs and RSM.

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

Directory of Open Access Journals (Sweden)

Alejandro Macchia

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

Low-dose aspirin and risk of intracranial bleeds

DEFF Research Database (Denmark)

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

2017-01-01

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...

The risk of severe salicylate poisoning following the ingestion of topical medicaments or aspirin.