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Aspirin AND COX

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https://read.qxmd.com/read/30782576/ligand-based-design-and-synthesis-of-pyrazole-based-derivatives-as-selective-cox-2-inhibitors
#1
Manikanta Murahari, Vivek Mahajan, Sreenivasulu Neeladri, Maushmi S Kumar, Y C Mayur
The design and synthesis of novel pyrazole based derivatives has been carried out using the ligand based approach like pharmacophore and QSAR modelling of reported pyrazoles from the available literature to investigate the chemical features that are essential for the design of selective and potent COX-2 inhibitors. Both pharmacophore and QSAR models with good statistical parameters were selected for the design of the lead molecule. Also by exploiting the chemical structures of selective and marketed COX-2 inhibitors, celecoxib and SC-558 were used in designing the molecules which are used in the treatment of inflammation and related disorders...
February 14, 2019: Bioorganic Chemistry
https://read.qxmd.com/read/30778625/metamizole-inhibits-arachidonic-acid-induced-platelet-aggregation-after-surgery-and-impairs-the-effect-of-aspirin-in-hospitalized-patients
#2
C Pfrepper, S Deters, M Metze, R Siegemund, I Gockel, S Petros
PURPOSE: The inhibitory effect of metamizole on platelet aggregation is known for several years, but most studies were conducted in healthy volunteers with contradictory results. Recent studies have shown an inhibitory effect of metamizole on acetylsalicylic acid (ASA)-induced platelet aggregation. We aimed to investigate the effect of metamizole on platelet aggregation after an elective surgery and the effect of metamizole on ASA-induced platelet aggregation in hospitalized patients...
February 18, 2019: European Journal of Clinical Pharmacology
https://read.qxmd.com/read/30768617/baseline-high-sensitivity-c-reactive-protein-predicts-the-risk-of-incident-ankylosing-spondylitis-results-of-a-community-based-prospective-study
#3
Jinmei Su, Liufu Cui, Wenhao Yang, Huijing Shi, Cheng Jin, Rong Shu, Hongfen Li, Xiaofeng Zeng, Shouling Wu, Xiang Gao
BACKGROUND: A hospitalized-based cohort study suggested that elevated C-reactive protein (CRP) levels are associated with radiographic sacroiliitis progression in ankylosing spondylitis (AS) patients. However, data from community-based populations are limited. OBJECTIVE: We sought to determine the association between elevated CRP levels and AS diagnosis in a prospective community-based study of 129,681 Chinese adults over a follow-up period of 8 years. METHODS: We measured the plasma CRP concentration at baseline and every 2 years thereafter with the high-sensitivity (hs)-CRP test...
2019: PloS One
https://read.qxmd.com/read/30747624/serotonin-modulating-antidepressants-and-risk-of-bleeding-after-trauma
#4
Lindsay B Wilson, Mark R Cox, Matthew V Benns, Christina M Pinkston, Leigh A Scherrer
Serotonin-modulating antidepressants have been associated with increased risk of gastrointestinal bleeding and increased blood loss during elective surgery. This study sought to investigate the effect of preinjury selective-serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) use on transfusion requirements after trauma, and to evaluate whether resumption of SSRI/SNRI after trauma may worsen bleeding risk. This was a retrospective matched-cohort study evaluating patients with solid organ injury...
November 1, 2018: American Surgeon
https://read.qxmd.com/read/30742307/statins-and-the-risk-of-bleeding-in-patients-taking-dabigatran
#5
Bo-Lin Ho, Ya-Ju Lin, Sheng-Feng Lin, Ping-Song Chou, Chien-Fu Chen, Ruey-Tay Lin, Han-Hwa Hu, A-Ching Chao
OBJECTIVES: Dabigatran etexilate is a direct thrombin inhibitor that clinicians increasingly prescribe to prevent stroke in patients with nonvalvular atrial fibrillation (NVAF). Clinicians also commonly prescribe statins for primary and secondary prevention of cardiovascular diseases. Little is known about the bleeding risk in patients taking a statin and dabigatran together. The aim of this study was to evaluate the safety and persistence of dabigatran after co-medication with statins...
February 11, 2019: Acta Neurologica Scandinavica
https://read.qxmd.com/read/30737317/a-seven-step-plan-for-becoming-a-moderately-rich-and-famous-biochemist
#6
William L Smith
Omega-6 polyunsaturated fatty acids were identified as essential nutrients in 1930. Their essentiality is largely due to their function as prostaglandin (PG) precursors. I spent most of my career in biochemistry determining how PG biosynthesis is regulated. PGs are lipid mediators formed in response to certain circulating hormones and cytokines. PGs act near their sites of synthesis to signal neighboring cells to coordinate their responses ( e.g. when platelets interact with blood vessels). The committed step in PG synthesis is the conversion of a 20-carbon omega-6 fatty acid called arachidonic acid to prostaglandin endoperoxide H2 (PGH2 )...
February 8, 2019: Journal of Biological Chemistry
https://read.qxmd.com/read/30736774/comparing-australian-orthopaedic-surgeons-reported-use-of-thromboprophylaxis-following-arthroplasty-in-2012-and-2017
#7
Corinne Mirkazemi, Luke R Bereznicki, Gregory M Peterson
BACKGROUND: It is generally accepted that all arthroplasty patients should receive venous thromboembolism (VTE) and bleeding risk assessments, and that postoperative thromboprophylaxis be routinely prescribed where appropriate. Guideline recommendations regarding what to prescribe, however, have been inconsistent over the years, particularly regarding the appropriateness of aspirin. Our aim was to explore thromboprophylaxis patterns in use following hip and knee arthroplasty in Australia, and to examine associated variables...
February 8, 2019: BMC Musculoskeletal Disorders
https://read.qxmd.com/read/30734682/the-effects-of-trifluoromethylated-derivatives-on-prostaglandin-e2-and-thromboxane-a2-production-in-human-leukemic-u937-macrophages
#8
Ivana Beara, Tatjana Majkić, Stefania Fioravanti, Laura Trulli, Neda Mimica-Dukić, Lucio Pellacani, Luciano Saso
BACKGROUND: Convenient approach to modulation of the inflammation is influence on production of inflammatory mediators - eicosanoids, generated in arachidonic acid (AA) metabolism. Common therapeutic activity of non-steroidal anti-inflammatory drugs (NSAID), such as aspirin, includes inhibition of two crucial enzymes of AA metabolism - cyclooxygenase-1 and -2 (COX-1/2), with certain risk for gastrointestinal and renal intolerance. Ever since enrolment of COX-2, particularly overabundance of its main products prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) in numerous pathological processes was recognized, it became significant therapeutic target...
February 8, 2019: Medicinal Chemistry
https://read.qxmd.com/read/30713340/low-dose-anti-inflammatory-combinatorial-therapy-reduced-cancer-stem-cell-formation-in-patient-derived-preclinical-models-for-tumour-relapse-prevention
#9
Bee Luan Khoo, Gianluca Grenci, Joey Sze Yun Lim, Yan Ping Lim, July Fong, Wei Hseun Yeap, Su Bin Lim, Song Lin Chua, Siew Cheng Wong, Yoon-Sim Yap, Soo Chin Lee, Chwee Teck Lim, Jongyoon Han
BACKGROUND: Emergence of drug-resistant cancer phenotypes is a challenge for anti-cancer therapy. Cancer stem cells are identified as one of the ways by which chemoresistance develops. METHOD: We investigated the anti-inflammatory combinatorial treatment (DA) of doxorubicin and aspirin using a preclinical microfluidic model on cancer cell lines and patient-derived circulating tumour cell clusters. The model had been previously demonstrated to predict patient overall prognosis...
February 4, 2019: British Journal of Cancer
https://read.qxmd.com/read/30710735/impact-of-the-chinese-herbal-medicines-on-dual-antiplatelet-therapy-with-clopidogrel-and-aspirin-pharmacokinetics-and-pharmacodynamics-outcomes-and-related-mechanisms-in-rats
#10
Min Xiao, Chenyu Qian, Xi Luo, Mengbi Yang, Yufeng Zhang, Cheyuen Wu, Chungtong Mok, Puiwai Lee, Zhong Zuo
ETHNOPHARMACOLOGICAL RELEVANCE: Dual antiplatelet therapy (DAPT) with aspirin (ASA) and clopidogrel (CLP) has been consistently shown clinical effectiveness in patients with coronary artery disease. According to the literature, four traditional Chinese medicine (TCM) herbs effective for prevention cardiovascular diseases, namely Radix Salvia Miltiorrhiza (Red sage root, Danshen), Radix Pueraria Lobata (Kudzu root, Gegen), Radix Angelica Sinensis (Angelica root, Danggui), and Rhizoma Ligusticum chuanxiong (Szehuan lovage rhizome, Chuanxiong), are of high potential to be co-administered during DAPT...
January 30, 2019: Journal of Ethnopharmacology
https://read.qxmd.com/read/30701538/aspirin-inhibits-cancer-stem-cells-properties-and-growth-of-glioblastoma-multiforme-through-rb1-pathway-modulation
#11
Giacomo Pozzoli, Hany E Marei, Asma Althani, Alma Boninsegna, Patrizia Casalbore, Lionel N J L Marlier, Giulia Lanzilli, Manuela Zonfrillo, Giovanna Petrucci, Bianca Rocca, Pierluigi Navarra, Alessandro Sgambato, Carlo Cenciarelli
Several clinical studies indicated that the daily use of aspirin or acetylsalicylic acid reduces the cancer risk via cyclooxygenases (Cox-1 and Cox-2) inhibition. In addition, aspirin-induced Cox-dependent and -independent antitumor effects have also been described. Here we report, for the first time, that aspirin treatment of human glioblastoma cancer (GBM) stem cells, a small population responsible for tumor progression and recurrence, is associated with reduced cell proliferation and motility. Aspirin did not interfere with cell viability but induced cell-cycle arrest...
January 30, 2019: Journal of Cellular Physiology
https://read.qxmd.com/read/30656820/risks-of-colorectal-neoplasms-and-cardiovascular-thromboembolic-events-after-the-combined-use-of-selective-cox-2-inhibitors-and-aspirin-with-5-years-follow-up-a-meta-analysis
#12
Peirong He, Chaohao Yang, Guian Ye, Huanqin Xie, Wuzhuang Zhong
AIM: To evaluate the association between selective COX-2 inhibitors (coxibs) and the risk of colorectal neoplasm and vascular events with and without low-dose aspirin. METHOD: We searched for randomized controlled trials and comparative studies in PubMed, EMBASE, and Cochrane Library databases using pertinent key terms. Risk ratios (RRs) were calculated for each study with a fixed- or random-effects model. RESULTS: Eight clinical studies with 44,566 subjects were eligible...
January 18, 2019: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
https://read.qxmd.com/read/30651922/modification-of-gastric-cancer-risk-associated-with-proton-pump-inhibitors-by-aspirin-after-helicobacter-pylori-eradication
#13
Ka Shing Cheung, Wai K Leung
Aim: Although proton pump inhibitors (PPIs) can prevent aspirin-induced upper gastrointestinal bleeding, a clinical dilemma exists as long-term use of PPI may also increase the risk of gastric cancer even after Helicobacter pylori (HP) eradication. We aimed to investigate the potential interaction between aspirin and PPIs on GC risk in patients who have HP eradicated. Results: Of the 63,397 HP eradicated subjects (median follow-up 7.6 years), 153 (0.24%) developed GC...
December 11, 2018: Oncotarget
https://read.qxmd.com/read/30637134/antiplatelet-therapy-in-acute-mild-moderate-ischemic-stroke-atamis-a-parallel-randomised-open-label-multicentre-prospective-study
#14
REVIEW
Xiaowen Hou, Xiaoqiu Li, Xinhong Wang, Huisheng Chen
Background: A recent study shows that dual antiplatelet therapy with clopidogrel plus aspirin is superior to aspirin monotherapy for minor stroke, which is defined as a National Institutes of Health Stroke Scale (NIHSS)score of ≤3. However, acute mild-moderate ischaemic stroke (4≤NIHSS≤10) still needs aggressive antiplatelet intervention to prevent deterioration and recurrence of stroke. The efficacy and safety of dual antiplatelet therapy versus aspirin monotherapy in the population are not clear...
December 2018: Stroke and Vascular Neurology
https://read.qxmd.com/read/30629157/prediction-of-individual-life-years-gained-without-cardiovascular-events-from-lipid-blood-pressure-glucose-and-aspirin-treatment-based-on-data-of-more-than-500-000-patients-with-type-2-diabetes-mellitus
#15
Gijs F N Berkelmans, Soffia Gudbjörnsdottir, Frank L J Visseren, Sarah H Wild, Stefan Franzen, John Chalmers, Barry R Davis, Neil R Poulter, Annemieke M Spijkerman, Mark Woodward, Sara L Pressel, Ajay K Gupta, Yvonne T van der Schouw, Ann-Marie Svensson, Yolanda van der Graaf, Stephanie H Read, Bjorn Eliasson, Jannick A N Dorresteijn
Aims: Although group-level effectiveness of lipid, blood pressure, glucose, and aspirin treatment for prevention of cardiovascular disease (CVD) has been proven by trials, important differences in absolute effectiveness exist between individuals. We aim to develop and validate a prediction tool for individualizing lifelong CVD prevention in people with Type 2 diabetes mellitus (T2DM) predicting life-years gained without myocardial infarction or stroke. Methods and results: We developed and validated the Diabetes Lifetime-perspective prediction (DIAL) model, consisting of two complementary competing risk adjusted Cox proportional hazards functions using data from people with T2DM registered in the Swedish National Diabetes Registry (n = 389 366)...
January 9, 2019: European Heart Journal
https://read.qxmd.com/read/30607496/incidence-predictors-and-outcomes-of-dapt-disruption-due-to-non-compliance-vs-bleeding-after-pci-insights-from-the-paris-registry
#16
Kamilia Moalem, Usman Baber, Jaya Chandrasekhar, Bimmer E Claessen, Samantha Sartori, Melissa Aquino, George Dangas, Ioannis Iakovou, Antonio Colombo, Anapoorna Kini, Michael Gibson, Mitchell Krucoff, Alaide Chieffo, David Moliterno, Bernhard Witzenbichler, Stuart Pocock, Roxana Mehran
BACKGROUND: The disruption of dual antiplatelet therapy (DAPT) due to non-compliance or bleeding is known to significantly increase the risk of adverse outcomes after percutaneous coronary intervention (PCI). However, it is currently unknown if there are differences in the predictors and clinical impact of disruption due to non-compliance compared with bleeding. METHODS: The patterns of non-adherence to antiplatelet regimens in stented patients (PARIS) registry was an international, multicenter prospective study of PCI patients discharged on DAPT (aspirin + a P2Y12 receptor)...
January 3, 2019: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://read.qxmd.com/read/30604228/aspirin-attenuates-podocyte-injury-in-diabetic-rats-through-overriding-cyclooxygenase-2-mediated-dysregulation-of-ldl-receptor-pathway
#17
Kun Ling Ma, Liang Liu, Yang Zhang, Gui Hua Wang, Ze Bo Hu, Pei Pei Chen, Jian Lu, Chen Chen Lu, Tie Kai Gong, Yu Xiang Gong, Bi Cheng Liu
AIM: This study aimed to investigate the effects of aspirin on podocyte injury and its underlying mechanisms in diabetic nephropathy (DN). METHODS: Eight-week-old male Sprague-Dawley rats were divided into three groups: non-diabetic rats (Control), streptozotocin-induced diabetic rats (DM), and diabetic rats treated with aspirin (DM + Aspirin) for 12 weeks. Intracellular lipid accumulation was evaluated by Oil Red O staining and quantitative free cholesterol assays...
January 2, 2019: International Urology and Nephrology
https://read.qxmd.com/read/30590258/translational-impact-of-novel-widely-pharmacological-characterized-mofezolac-derived-cox-1-inhibitors-combined-with-bortezomib-on-human-multiple-myeloma-cell-lines-viability
#18
Maria Laura Pati, Paola Vitale, Savina Ferorelli, Mariaclara Iaselli, Morena Miciaccia, Angelina Boccarelli, Giuseppe Davide Di Mauro, Cosimo G Fortuna, Thaisa Francielle Souza Domingos, Luiz Cláudio Rodrigues Pereira da Silva, Marcelo de Pádula, Lucio Mendes Cabral, Plínio Cunha Sathler, Angelo Vacca, Antonio Scilimati, Maria Grazia Perrone
A set of novel diarylisoxazoles has been projected using mofezolac (1) as a lead compound to investigate structure-inhibitory activity relationships of new compounds and the cyclooxygenases (COXs) catalytic activity. Mofezolac was chosen because is the most potent and selective reversible COX-1 inhibitor [COX-1 IC50  = 0.0079 μM and COX-2 IC50  > 50 μM, with a selectivity index (SI) in favor of COX-1 higher than 6300]. Seventeen new compounds were synthesized in fair to good yields and evaluated for their COXs inhibitory activity and selectivity...
December 15, 2018: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/30582894/impact-of-prolonged-anticoagulation-with-rivaroxaban-on-provoked-venous-thromboembolism-recurrence-the-improve-vte-study
#19
Craig I Coleman, Alexander G G Turpie, Thomas J Bunz, Jan Beyer-Westendorf, William L Baker
OBJECTIVE: We sought to evaluate the real-world effectiveness and safety of prolonged anticoagulation with rivaroxaban following a provoked venous thromboembolism. METHODS: Using US MarketScan claims from 11/2012-3/2017, we identified adults with ≥1 primary hospitalization/emergency department diagnosis code for venous thromboembolism, a provoking (major or minor, persistent or transient) risk factor, at least 3-months of continuous rivaroxaban treatment and ≥12-months of continuous insurance benefits prior to their qualifying venous thromboembolism...
December 21, 2018: American Journal of Medicine
https://read.qxmd.com/read/30580722/comparative-effectiveness-of-aspirin-and-clopidogrel-versus-aspirin-in-acute-minor-stroke-or-transient-ischemic-attack
#20
Joon-Tae Kim, Man-Seok Park, Kang-Ho Choi, Ki-Hyun Cho, Beom Joon Kim, Jong-Moo Park, Kyusik Kang, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Hyun-Wook Nah, Tai Hwan Park, Sang-Soon Park, Kyung Bok Lee, Jun Lee, Keun-Sik Hong, Yong-Jin Cho, Hong-Kyun Park, Byung-Chul Lee, Kyung-Ho Yu, Mi Sun Oh, Dong-Eog Kim, Wi-Sun Ryu, Jay Chol Choi, Jee-Hyun Kwon, Wook-Joo Kim, Dong-Ick Shin, Min-Ju Yeo, Sung Il Sohn, Jeong-Ho Hong, Ji Sung Lee, Juneyoung Lee, Jeffrey L Saver, S Claiborne Johnston, Hee-Joon Bae
Background and Purpose- This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel-aspirin to that of aspirin monotherapy in patients with acute minor cerebral ischemia using a prospective, nationwide, multicenter, stroke registry database in South Korea. Methods- CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events)-like patients who met eligibility criteria modeled on the CHANCE trial eligibility criteria, including (1) acute minor ischemic stroke defined as National Institutes of Health Stroke Scale score ≤3 or lesion positive transient ischemic attack within 24 hours of onset and (2) noncardioembolic stroke mechanism...
December 7, 2018: Stroke; a Journal of Cerebral Circulation
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