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Aspirin AND COX

Mojgan Najafzadeh, Charmaine Normington, Badie K Jacob, Mohammad Isreb, Rajendran C Gopalan, Diana Anderson
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzyme activity which affects the inflammatory response. Inflammation is associated with increasing cancer incidence. Pre-clinical and clinical studies have shown that NSAID treatment could cause an anti-tumor effect in cancers. In the present study, blood was taken from healthy individuals (n = 17) and patients with respiratory diseases or lung cancer (n = 36). White blood cells (WBC) were treated with either a micro-suspension, i.e., bulk (B) or nano-suspension (N) of aspirin (ASP) or ibuprofen (IBU) up to 500 μg/ml in the comet assay and up to 125 μg/ml in the micronucleus assay...
2016: Frontiers in Molecular Biosciences
Jennifer Hill, Trever Burnett, Rohit Katial
Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by severe persistent asthma, hyperplastic eosinophilic sinusitis with nasal polyps, and an intolerance to aspirin and other NSAIDs that preferentially inhibit COX-1. For more than 30 years, aspirin desensitization has proven to be of significant long-term benefit in carefully selected patients with AERD. Despite this, the exact mechanisms behind the therapeutic effects of aspirin desensitization remain poorly understood. In this article, we review the current understanding of the mechanisms of aspirin desensitization and discuss future areas of investigation...
November 2016: Immunology and Allergy Clinics of North America
Whitney W Stevens, Robert P Schleimer
Aspirin-Exacerbated Respiratory Disease (AERD) and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) are both characterized by the presence of chronic sinonasal inflammation and nasal polyps. Unlike in CRSwNP, AERD patients develop respiratory reactions following ingestion of COX-1 inhibitors. AERD patients also, on average, have worse upper respiratory disease with increased sinonasal symptoms, mucosal inflammation and requirements for revision sinus surgery when compared to CRSwNP patients. While no single genetic factor has been identified in either CRSwNP or AERD to date, differences in the metabolism of arachidonic acid as well as innate immune cell activation may uniquely contribute to AERD pathogenesis...
November 2016: Immunology and Allergy Clinics of North America
Farah Z Dawood, Suzanne Judd, Virginia J Howard, Nita A Limdi, James F Meschia, Mary Cushman, George Howard, David M Herrington, Elsayed Z Soliman
The relation between inflammation and prothrombotic state in atrial fibrillation (AF) is well recognized. This suggests a potential role for high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, in improving prediction of stroke in participants with AF. Cox proportional hazard analysis was used to examine the risk of stroke in 25,841 participants (40% black and 55% women) with and without AF who were enrolled in the Reasons for Geographic and Racial Differences in Stroke study from 2003 to 2007...
September 14, 2016: American Journal of Cardiology
Isabella Massimi, Lavinia Vittoria Lotti, Flavia Temperilli, Massimo Mancone, Gennaro Sardella, Simone Calcagno, Ombretta Turriziani, Luigi Frati, Fabio M Pulcinelli
Platelet multidrug resistance protein4 (MRP4)-overexpression has a role in reducing aspirin action. Aspirin in vivo treatment enhances platelet MRP4 expression and MRP4 mediated transport inhibition reduces platelet function and delays thrombus formation. The aim of our work was to verify whether MRP4 expression is enhanced in platelets obtained from patients under chronic aspirin treatment and whether it correlates with residual platelet reactivity. We evaluated changes on mRNA and protein-MRP4 expression and platelet aggregation in four populations: healthy volunteers (HV), aspirin-free control population (CTR), patients who started the treatment less than one month ago (ASA<1 month patients) and aspirinated patients who started the treatment more than two months ago (ASA>2 months patients)...
September 29, 2016: Thrombosis and Haemostasis
Qiao Tang, Yajun Liu, Tao Li, Xiang Yang, Guirong Zheng, Hongning Chen, Lee Jia, Jingwei Shao
Metastasis currently remains the predominant cause of breast carcinoma treatment failure. The effective targeting of metastasis-related-pathways in cancer holds promise for a new generation of therapeutics. In this study, we developed an novel Asp-UA conjugate, which was composed of classical "old drug" aspirin and low toxicity natural product ursolic acid for targeting breast cancer metastasis. Our results showed that Asp-UA could attenuate the adhesion, migration and invasion of breast cancer MCF-7 and MDA-MB-231 cells in a more safe and effective manner in vitro...
September 24, 2016: Oncotarget
Lisa E Vaughan, Anna Prizment, Cindy K Blair, William Thomas, Kristin E Anderson
PURPOSE: Few studies have evaluated the chemopreventive effect of aspirin on the cancer risk in elderly women. We examined associations between frequency, dose, and duration of aspirin use with incidence of 719 aspirin-sensitive cancers (cancers of colon, pancreas, breast, and ovaries) in the Iowa Women's Health Study (IWHS), a prospective cohort of women over 70 years old. METHODS: Aspirin frequency, dose, and duration were self-reported in the 2004 IWHS questionnaire...
September 27, 2016: Cancer Causes & Control: CCC
Jacob B Hunter, David O Francis, Brendan P O'Connell, Edmond K Kabagambe, Marc L Bennett, George B Wanna, Alejandro Rivas, Reid C Thompson, David S Haynes
OBJECTIVE: To characterize the risk and predictors of growth during observation of vestibular schwannomas (VS). STUDY DESIGN: Retrospective case series. SETTING: Single academic, tertiary care center. PATIENTS: Five hundred sixty-four consecutive VS patients who underwent at least two magnetic resonance imaging (MRI) studies before intervention. INTERVENTION(S): Serial MRI studies. MAIN OUTCOME MEASURE(S): Tumor growth, defined as a ≥2 mm increase in the maximum tumor diameter between consecutive MRI studies, or between the first and last study...
September 23, 2016: Otology & Neurotology
Swati Singh, Manika Awasthi, Veda P Pandey, Upendra N Dwivedi
In the present study, 300 plant derived secondary metabolites (100 each of alkaloid, flavonoid, and terpenoid), have been screened for their anti-cancerous activity through inhibition of selected key enzymatic targets, namely cyclooxygenases (COXs), topoisomerases (Topos), and aromatase by molecular docking approach. Furthermore, the stability of the complexes of top hits, from each class of secondary metabolites, with their respective enzymatic targets was analyzed using molecular dynamics (MD) simulation analyses and binding free energy calculations...
September 25, 2016: Journal of Biomolecular Structure & Dynamics
Alfi Yasmina, Anthonius de Boer, Vera H M Deneer, Patrick C Souverein, Olaf H Klungel
AIMS: To assess antiplatelet use patterns after a first myocardial infarction (MI) and to evaluate the determinants of antiplatelet non-persistence. METHODS: This study was conducted in 4,690 patients from the Utrecht Cardiovascular Pharmacogenetics cohort with first MI between 1986-2010, who were followed for a maximum of 10 years. Medication use and event diagnosis were obtained from the Dutch PHARMO Record Linkage System. Antiplatelet users were classified as persistent users (gap between prescriptions ≤ 90 days), non-persistent users (>90 days gap and no refills), and restarters (a new prescription after a > 90 days gap)...
September 23, 2016: British Journal of Clinical Pharmacology
T-C Shen, C-L Lin, C H Liao, C-C Wei, F-C Sung, C-H Kao
AIM: To examine the incidence of asthma in adult patients with major depressive disorder (MDD). METHODS: From the National Health Insurance database of Taiwan, we identified 30 169 adult patients who were newly diagnosed with MDD between 2000 and 2010. Individuals without depression were randomly selected four times and frequency matched for sex, age and year of diagnosis. Both cohorts were followed-up for the occurrence of asthma up to the end of 2011. Adjusted hazard ratios (aHRs) of asthma were estimated using the Cox proportional hazards method...
September 19, 2016: Epidemiology and Psychiatric Sciences
Che-Sheng Chu, Po-Han Chou, Ching-Heng Lin, Chin Cheng, Chia-Jui Tsai, Tsuo-Hung Lan, Min-Wei Huang, Gerald Nestadt
BACKGROUND: Previous research has suggested a link between antidepressants use and the development of cerebrovascular events, but there has never been any study investigating the risk of stroke in obsessive-compulsive disorder (OCD) patients treated with a selective serotonin reuptake inhibitor (SSRI). METHODS: A retrospective observational cohort study was conducted using data from the National Health Insurance Database of Taiwan between the year of 2001 and 2009...
2016: PloS One
Jarrett J Failing, Heidi D Finnes, Lisa A Kottschade, Jacob B Allred, Svetomir N Markovic
Ipilimumab can induce long-term survival in 20% of patients with metastatic melanoma. Concurrent chronic medications may impact the patient's immune system, possess antimelanoma properties, and potentially affect clinical outcomes. This retrospective study sought to describe the efficacy and toxicity effects of 12 classes of chronic medications in metastatic melanoma patients treated with ipilimumab. A total of 159 adults who received ipilimumab for metastatic melanoma at Mayo Clinic (Rochester, Minnesota, USA) from 1 March 2011 through 31 December 2014 were included...
September 3, 2016: Melanoma Research
Maryam Alsadat Hashemipour, Hoda Mehrabizadeh Honarmand, Farideh Falsafi, Mehrnaz Tahmasebi Arashlo, Saied Rajabalian, Sayed Amir Hossein Gandjalikhan Nassab
STATEMENT OF THE PROBLEM: Use of cyclooxygenase inhibitors as chemotherapy agents has attracted the attention of a large number of investigators in recent years. Given the importance of cancer therapy, only a limited number of studies have been carried out to investigate the effects of cyclooxygenase inhibitors on specific cell lines. PURPOSE: This research aimed to determine the in vitro cytotoxic effects of cyclooxygenase inhibitors (COX-1 and COX-2 inhibitors) on KB, Saos-2, 1321N, U-87MG, SFBF-PI 39 cell lines...
September 2016: Journal of Dentistry
Khaled R A Abdellatif, Wael A A Fadaly, Amany A Azouz
A new series of 1,3,5-triarylpyrazolines 13a-l was synthesized and all prepared compounds were evaluated for their in vitro COX-1/COX-2 inhibitory activity and in vivo anti-inflammatory activity. All test compounds were more selective for the COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compound 13h was the most COX-2 selective compound (COX-2 selectivity index (SI) = 10.23) and the most potent anti-inflammatory derivative (ED50  = 60.1 µmol/kg) in comparison with celecoxib (COX-2 SI = 9...
October 2016: Archiv der Pharmazie
Amrit Bajrangee, Nicola Ryan, Ciara Vangjeli, Marian Brennan, Dermot Cox, Denis C Shields, Desmond Fitzgerald, Andrew Maree
BACKGROUND: Serotonin (5-HT) induces platelet aggregation by activating its 5-HT2A receptor. Platelet uptake is mediated by the 5-HT transporter (5-HTT). A common 5-HTT promoter (5-HTTLPR) splice variant results in long (L) and short (S) alleles. 5-HTTLPR genotype has been associated with increased platelet activation and risk of MI. Variation within HTR2A gene (C1354T) that encodes the 5-HT2A receptor has also been associated with enhanced platelet aggregation. We hypothesised that 5-HTT and/or HTR2A variation may influence platelet response to aspirin in patients with stable CAD...
October 2016: Thrombosis Research
Lestari Dewi
INTRODUCTION: The enzyme cyclooxygenase (COX) is an enzyme that catalyzes the formation of one of the mediators of inflammation, the prostaglandins. Inhibition of COX allegedly can improve inflammation-induced pathological conditions. AIM: The purpose of the present study was to evaluate the potential of Sargassum sp. components, Fucoidan and alginate, as COX inhibitors. MATERIAL AND METHODS: The study was conducted by means of a computational (in silico) method...
June 2016: Medical Archives
Johannes T H Nielen, Pieter C Dagnelie, Pieter J Emans, Nicole Veldhorst-Janssen, Arief Lalmohamed, Tjeerd-Pieter van Staa, Annelies E R C H Boonen, Bart J F van den Bemt, Frank de Vries
BACKGROUND: There has been much debate recently on the best type of thromboprophylaxis following elective total joint replacement surgery. OBJECTIVE: This study aims to compare rates of venous thromboembolism (VTE), gastro-intestinal (GI) bleeding and mortality events, with use of new oral anticoagulants (NOAC) or low-molecular-weight heparins (LMWHs) compared with aspirin in patients undergoing total joint replacement. METHODS: A population-based retrospective cohort study was performed using the Clinical Practice Research Datalink...
September 4, 2016: Pharmacoepidemiology and Drug Safety
Peter A Soden, Sara L Zettervall, Klaas H J Ultee, Bruce E Landon, A James O'Malley, Philip P Goodney, Randall R DeMartino, Shipra Arya, Marc L Schermerhorn
BACKGROUND: Dual antiplatelet therapy (DAPT) after coronary stenting prolongs survival by preventing both in-stent thrombosis and other cardiovascular atherothrombotic events. Patients with peripheral artery disease (PAD) typically have a heavy burden of unrevascularized coronary artery disease and also stand to benefit from increased atherothrombotic protection with DAPT. The potential benefit of DAPT compared with aspirin alone in patients with PAD is not well described. METHODS: We identified all patients undergoing an initial elective lower extremity revascularization (bypass or endovascular) from 2003 to 2016 in the Vascular Quality Initiative registry discharged on aspirin or aspirin plus a thienopyridine antiplatelet agent (DAPT)...
August 26, 2016: Journal of Vascular Surgery
Deepak Voora, A Koneti Rao, Gauthami S Jalagadugula, Rachel Myers, Emily Harris, Thomas L Ortel, Geoffrey S Ginsburg
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...
September 2016: EBioMedicine
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