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

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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.

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.

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.

Science.gov (United States)

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

2011-10-07

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

Comparative Proteomic Analysis Provides insight into the Key Proteins as Possible Targets Involved in Aspirin Inhibiting Biofilm Formation of Staphylococcus xylosus

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Chang-Geng Xu

2017-08-01

Full Text Available Staphylococcus xylosus is an opportunistic pathogen that causes infection in humans and cow mastitis. And S. xylosus possesses a strong ability to form biofilms in vitro. As biofilm formation facilitates resistance to antimicrobial agents, the discovery of new medicinal properties for classic drugs is highly desired. Aspirin, which is the most common active component of non-steroidal anti-inflammatory compounds, affects the biofilm-forming capacity of various bacterial species. We have found that aspirin effectively inhibits biofilm formation of S. xylosus by Crystal violet (CV staining and scanning electron microscopy analyses. The present study sought to elucidate possible targets of aspirin in suppressing S. xylosus biofilm formation. Based on an isobaric tag for relative and absolute quantitation (iTRAQ fold-change of >1.2 or <0.8 (P-value < 0.05, 178 differentially expressed proteins, 111 down-regulated and 67 up-regulated, were identified after application of aspirin to cells at a 1/2 minimal inhibitory concentration. Gene ontology analysis indicated enrichment in metabolic processes for the majority of the differentially expressed proteins. We then used the Kyoto Encyclopedia of Genes and Genomes (KEGG pathway database to analyze a large number of differentially expressed proteins and identified genes involved in biosynthesis of amino acids pathway, carbon metabolism (pentose phosphate and glycolytic pathways, tricarboxylic acid cycle and nitrogen metabolism (histidine metabolism. These novel proteins represent candidate targets in aspirin-mediated inhibition of S. xylosus biofilm formation at sub-MIC levels. The findings lay the foundation for further studies to identify potential aspirin targets.

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.

NO-donating aspirin inhibits the growth of leukemic Jurkat cells and modulates β-catenin expression

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Nath, Niharika; Labaze, Georges; Rigas, Basil; Kashfi, Khosrow

2004-01-01

β-Catenin has been implicated in leukemic cell proliferation. We compared the effects of aspirin (ASA) and the ortho, meta, and para positional isomers of NO-donating aspirin (NO-ASA) on cell growth and β-catenin expression in human Jurkat T leukemic cells. Cell growth inhibition was strong: IC 50 for p-, o-, and m- were 20 ± 1.6 (mean ± SEM), 15 ± 1.5, and 200 ± 12 μM, respectively, in contrast to that of ASA (3200 ± 375 μM). The para isomer of NO-ASA degraded β-catenin in a dose- and time-dependent manner coinciding with increasing expression of activated caspase-3. The caspase inhibitor ZVAD blocked β-catenin cleavage by p-NO-ASA and partially reversed cell growth inhibition by p-NO-ASA but not that by ASA. A denitrated analog of p-NO-ASA did not degrade β-catenin indicating the importance of the NO-donating moiety. Our findings suggest that NO-ASA merits further study as an agent against leukemia

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...

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.

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 ...

By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma.

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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.

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.

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.

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

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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-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.

Antiplatelet therapy: aspirin resistance and all that jazz!

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

2013-01-01

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

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

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.

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.

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.

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

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

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.

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

Science.gov (United States)

Tatham, Michael H.; Cole, Christian; Scullion, Paul; Wilkie, Ross; Westwood, Nicholas J.; Stark, Lesley A.; Hay, Ronald T.

2017-01-01

Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-d3, in combination with acetylated lysine purification and LC-MS/MS, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies endogenous acetylation signals at the majority of detectable endogenous sites, cells tolerate aspirin mediated acetylation very well unless cellular deacetylases are inhibited. Although most endogenous acetylations are amplified by orders of magnitude, lysine acetylation site occupancies remain very low even after high doses of aspirin. This work shows that while aspirin has enormous potential to alter protein function, in the majority of cases aspirin-mediated acetylations do not accumulate to levels likely to elicit biological effects. These findings are consistent with an emerging model for cellular acetylation whereby stoichiometry correlates with biological relevance, and deacetylases act to minimize the biological consequences of nonspecific chemical acetylations. PMID:27913581

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.

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.

Interleukin-1 inhibits the synthesis of collagen by fibroblasts.

Science.gov (United States)

Bhatnagar, R; Penfornis, H; Mauviel, A; Loyau, G; Saklatvala, J; Pujol, J P

1986-10-01

Human dermal fibroblasts, exposed to human or porcine Interleukin-1, responded by an inhibition of collagen synthesis in a dose dependent manner. Incubation with Il-1 for more than 8 h was required to see an appreciable effect. The phenomenon was not dependent on the presence of serum in the culture medium. Since a stimulation of prostaglandin E2 secretion was also observed in presence of Il-1, we investigated the eventual role of arachidonic acid metabolites in the phenomenon. Inhibitors interfering with arachidonate metabolism, namely indomethacin, acetyl salicylic acid, BW 755 C and NDGA had no influence on the inhibition of collagen synthesis caused by Il-1. These data suggest that both cyclooxygenase and lipoxygenase derived metabolites of arachidonic acid are unlikely to play a role in the mechanism.

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

Directory of Open Access Journals (Sweden)

Isabella Massimi

2015-01-01

Full Text Available Overexpression of efflux transporters, in human cells, is a mechanism of resistance to drug and also to chemotherapy. We found that multidrug resistance protein-4 (MRP4 overexpression has a role in reducing aspirin action in patients after bypass surgery and, very recently, we found that aspirin enhances platelet MRP4 levels through peroxisome proliferator activated receptor-α (PPARα. In the present paper, we verified whether exposure of human embryonic kidney-293 cells (Hek-293 to aspirin modifies MRP4 gene expression and its correlation with drug elimination and cell toxicity. We first investigated the effect of high-dose aspirin in Hek-293 and we showed that aspirin is able to increase cell toxicity dose-dependently. Furthermore, aspirin effects, induced at low dose, already enhance MRP4 gene expression. Based on these findings, we compared cell viability in Hek-293, after high-dose aspirin treatment, in MRP4 overexpressing cells, either after aspirin pretreatment or in MRP4 transfected cells; in both cases, a decrease of selective aspirin cell growth inhibition was observed, in comparison with the control cultures. Altogether, these data suggest that exposing cells to low nontoxic aspirin dosages can induce gene expression alterations that may lead to the efflux transporter protein overexpression, thus increasing cellular detoxification of aspirin.

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

Science.gov (United States)

Landolfi, R; Patrono, C

1996-09-01

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

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

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 attenuates spontaneous recurrent seizures in the chronically epileptic mice.

Science.gov (United States)

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

2017-08-01

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

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

Science.gov (United States)

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.

Aspirin Desensitization

Science.gov (United States)

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

The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population.

Science.gov (United States)

Falfán-Valencia, Ramcés; Pavón-Romero, Gandhi F; Camarena, Angel; García, María de la Luz; Galicia-Negrete, Gustavo; Negrete-García, María Cristina; Teran, Luis Manuel

2012-01-01

Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17-7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.

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

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.

Aspirin overdose

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/002542.htm Aspirin overdose To use the sharing features on this page, please enable JavaScript. An overdose of aspirin means you have too much aspirin in your ...

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

Energy Technology Data Exchange (ETDEWEB)

Li, Xiaofei; Zhu, Yanshuang [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); He, Huabin [Department of Orthopedics, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Lou, Lianqing; Ye, Weiwei; Chen, Yongxin [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Wang, Jinghe, E-mail: Xiaofeili2000@163.com [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China)

2013-06-28

Highlights: •Novel combination therapy using aspirin and valproic acid (VPA). •Combination of aspirin and VPA elicits synergistic cytotoxic effects. •Combination of aspirin and VPA significantly reduces the drug dosage required alone. •Combination of aspirin and VPA significantly inhibit tumor growth. •Lower dose of aspirin in combination therapy will minimize side effects of aspirin. -- Abstract: Aspirin and valproic acid (VPA) have been extensively studied for inducing various malignancies growth inhibition respectively, despite their severe side effects. Here, we developed a novel combination by aspirin and VPA on hepatocellular cancer cells (HCCs). The viability of HCC lines were analyzed by MTT assay, apoptotic analysis of HepG2 and SMMC-7721 cell was performed. Real time-PCR and Western blotting were performed to determine the expression of apoptosis related genes and proteins such as Survivin, Bcl-2/Bax, Cyclin D1 and p15. Moreover, orthotopic xenograft tumors were challenged in nude mice to establish murine model, and then therapeutic effect was analyzed after drug combination therapy. The viability of HCC lines’ significantly decreased after drug combination treatment, and cancer cell apoptosis in combination group increasingly induced compared with single drug use. Therapeutic effect was significantly enhanced by combination therapy in tumor volume and tumor weight decrease. From the data shown here, aspirin and VPA combination have a synergistic killing effect on hepatocellular cancers cells proliferation and apoptosis.

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

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

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

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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

Could Aspirin and Diets High in Fiber Act Synergistically to Reduce the Risk of Colon Cancer in Humans?

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Pan Pan

2018-01-01

Full Text Available Early inhibition of inflammation suppresses the carcinogenic process. Aspirin is the most commonly used non-steroid anti-inflammatory drugs (NSAIDs, and it irreversibly inhibits cyclooxygenase-1 and -2 (COX1, COX2. Multiple randomized clinical trials have demonstrated that aspirin offers substantial protection from colon cancer mortality. The lower aspirin doses causing only minimal gastrointestinal disturbance, ideal for long-term use, can achieve only partial and transitory inhibition of COX2. Aspirin’s principal metabolite, salicylic acid, is also found in fruits and vegetables that inhibit COX2. Other phytochemicals such as curcumin, resveratrol, and anthocyanins also inhibit COX2. Such dietary components are good candidates for combination with aspirin because they have little or no toxicity. However, obstacles to using phytochemicals for chemoprevention, including bioavailability and translational potential, must be resolved. The bell/U-shaped dose–response curves seen with vitamin D and resveratrol might apply to other phytochemicals, shedding doubt on ‘more is better’. Solutions include: (1 using special delivery systems (e.g., nanoparticles to retain phytochemicals; (2 developing robust pharmacodynamic biomarkers to determine efficacy in humans; and (3 selecting pharmacokinetic doses relevant to humans when performing preclinical experiments. The combination of aspirin and phytochemicals is an attractive low-cost and low-toxicity approach to colon cancer prevention that warrants testing, particularly in high-risk individuals.

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

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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

TRANSCRIPTIONAL INHIBITION OF INTERLEUKIN-12 PROMOTER ACTIVITY IN LEISHMANIA SPP.-INFECTED MACROPHAGES

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Jayakumar, Asha; Widenmaier, Robyn; Ma, Xiaojing; McDowell, Mary Ann

2009-01-01

To establish and persist within a host, Leishmania spp. parasites delay the onset of cell-mediated immunity by suppressing interleukin-12 (IL-12) production from host macrophages. Although it is established that Leishmania spp.-infected macrophages have impaired IL-12 production, the mechanisms that account for this suppression remain to be completely elucidated. Using a luciferase reporter assay assessing IL-12 transcription, we report here that Leishmania major, Leishmania donovani, and Leishmania chagasi inhibit IL-12 transcription in response to interferon-gamma, lipopolysaccharide, and CD40 ligand and that Leishmania spp. lipophosphoglycan, phosphoglycans, and major surface protein are not necessary for inhibition. In addition, all the Leishmania spp. strains and life-cycle stages tested inhibited IL-12 promoter activity. Our data further reveal that autocrine-acting host factors play no role in the inhibitory response and that phagocytosis signaling is necessary for inhibition of IL-12. PMID:18372625

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.

Regulatory T-Cell Augmentation or Interleukin-17 Inhibition Prevents Calcineurin Inhibitor-Induced Hypertension in Mice.

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Chiasson, Valorie L; Pakanati, Abhinandan R; Hernandez, Marcos; Young, Kristina J; Bounds, Kelsey R; Mitchell, Brett M

2017-07-01

The immunosuppressive calcineurin inhibitors cyclosporine A and tacrolimus alter T-cell subsets and can cause hypertension, vascular dysfunction, and renal toxicity. We and others have reported that cyclosporine A and tacrolimus decrease anti-inflammatory regulatory T cells and increase proinflammatory interleukin-17-producing T cells; therefore, we hypothesized that inhibition of these effects using noncellular therapies would prevent the hypertension, endothelial dysfunction, and renal glomerular injury induced by calcineurin inhibitor therapy. Daily treatment of mice with cyclosporine A or tacrolimus for 1 week significantly decreased CD4 + /FoxP3 + regulatory T cells in the spleen and lymph nodes, as well as induced hypertension, vascular injury and dysfunction, and glomerular mesangial expansion in mice. Daily cotreatment with all-trans retinoic acid reported to increase regulatory T cells and decrease interleukin-17-producing T cells, prevented all of the detrimental effects of cyclosporine A and tacrolimus. All-trans retinoic acid also increased regulatory T cells and prevented the hypertension, endothelial dysfunction, and glomerular injury in genetically modified mice that phenocopy calcineurin inhibitor-treated mice (FKBP12-Tie2 knockout). Treatment with an interleukin-17-neutralizing antibody also increased regulatory T-cell levels and prevented the hypertension, endothelial dysfunction, and glomerular injury in cyclosporine A-treated and tacrolimus-treated mice and FKBP12-Tie2 knockout mice, whereas an isotype control had no effect. Augmenting regulatory T cells and inhibiting interleukin-17 signaling using noncellular therapies prevents the cardiovascular and renal toxicity of calcineurin inhibitors in mice. © 2017 American Heart Association, Inc.

Medications Containing Aspirin (Acetylsalicylate) and Aspirin-Like Products

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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 ...

Aspirin Induces Apoptosis through Release of Cytochrome c from Mitochondria

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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.

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 in polycythaemia vera: a pilot study. Gruppo Italiano Studio Policitemia (GISP).

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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.

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.

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

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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...

Novel Synthetic Monothiourea Aspirin Derivatives Bearing Alkylated Amines as Potential Antimicrobial Agents

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Norsyafikah Asyilla Nordin

2017-01-01

Full Text Available A new series of aspirin bearing alkylated amines moieties 1–12 were synthesised by reacting isothiocyanate with a series of aniline derivatives in overall yield of 16–56%. The proposed structures of all the synthesised compounds were confirmed using elemental analysis, FTIR, and 1H and  13C NMR spectroscopy. All compounds were evaluated for antibacterial activities against E. coli and S. aureus via turbidimetric kinetic and Kirby Bauer disc diffusion method. Compound 5 bearing meta -CH3 substituent showed the highest relative inhibition zone diameter against tested bacteria compared to ortho and para substituent. Furthermore, aspirin derivatives bearing shorter chains exhibited better bacterial inhibition than longer alkyl chains.

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

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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

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

Effect of Aspirin on Spinal Cord Injury: An Experimental Study

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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.

[Aspirin and colorectal cancer].

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

2018-02-01

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

Long-term sinonasal outcomes of aspirin desensitization in aspirin exacerbated respiratory disease.

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Cho, Kyu-Sup; Soudry, Ethan; Psaltis, Alkis J; Nadeau, Kari C; McGhee, Sean A; Nayak, Jayakar V; Hwang, Peter H

2014-10-01

This study aimed to assess sinonasal outcomes in patients with aspirin exacerbated respiratory disease (AERD) undergoing aspirin desensitization following endoscopic sinus surgery (ESS). Case series with chart review. University hospital. A retrospective review of sinonasal outcomes was conducted for 30 AERD patients undergoing aspirin desensitization and maintenance therapy following ESS. Sinonasal outcomes were prospectively assessed by the Sinonasal Outcomes Test-22 (SNOT-22) and endoscopic polyp grading system. Data were collected preoperatively, 1 and 4 weeks postsurgery (before desensitization), and 1, 6, 12, 18, 24, and 30 months after aspirin desensitization. Twenty-eight of 30 patients (93.3%) successfully completed aspirin desensitization, whereas 2 of 30 (6.7%) were unable to complete desensitization due to respiratory intolerance. Of the 21 patients who successfully completed a minimum of 24 weeks of follow-up, 20 (95.2%) patients demonstrated sustained endoscopic and symptomatic improvement for a median follow-up period of 33 months. After surgical treatment but before desensitization, patients experienced significant reductions in SNOT-22 and polyp grade scores. In the first 6 months after aspirin desensitization, patients experienced further significant reductions in SNOT-22 scores, whereas polyp grade remained stable. The improvements in symptom endoscopic scores were preserved throughout the follow-up period after desensitization. No patients required additional sinus surgery. One patient had to discontinue aspirin therapy due to gastrointestinal side effects. No other adverse reactions to aspirin were noted. Aspirin desensitization following ESS appears to be a well-tolerated and effective adjunctive therapy for long-term control of nasal polyposis in patients with AERD. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

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

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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...

Paracetamol (acetaminophen), aspirin (acetylsalicylic acid) and indomethacin are anti-androgenic in the rat foetal testis

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Kristensen, David Møbjerg; Lesné, L.; Fol, V. Le

2012-01-01

on gestational day 14.5 rat testes, we herein show that testosterone production was inhibited by paracetamol, at doses of 0.1??m to 100??m. Similar results were obtained for aspirin (1?100??m) and indomethacin (10??m). The production of the other Leydig cell hormone, Insl3, was not disrupted by exposure...... inhibit testosterone production in rat foetal testes in vitro and that these compounds had no effect on gonocyte survival. Parallel determinations of prostaglandin D2 (PGD2) production indicated that the effects of paracetamol and aspirin on PGD2 and testosterone were not connected, whereas the effects...

Glucocorticoids selectively inhibit the transcription of the interleukin 1β gene and decrease the stability of interleukin 1β mRNA

International Nuclear Information System (INIS)

Lee, S.W.; Tsou, A.P.; Chan, H.; Thomas, J.; Petrie, K.; Eugui, E.M.; Allison, A.C.

1988-01-01

Transcription of the interleukin 1β (IL-1β) gene was studied by mRNA hybridization with a cDNA probe in the human promonocytic cell line U-937. Phorbol ester and lipopolysaccharide increased the steady-state level of Il-1β mRNA. Glucocorticoids markedly decreased IL-1β mRNA levels by two mechanisms. Transcription of the IL-1 gene was inhibited, as shown by in vitro transcription assays with nuclei isolated from glucocorticoid-treated cells. Moreover, kinetic analyses and pulse-labeling of mRNAs showed that glucocorticoids selectively decrease the stability of IL-1β mRNA, without affecting the stability of β-actin and FOS mRNAs. Inhibition of the formation and effects IL-1 is a mechanism by which glucocorticoids can exert antiinflammatory and immunosuppressive effects

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.

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

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.

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

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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.

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; Barill?, Francesco; Scarpellini, Maria Gabriella; Bertazzoni, Giuliano; Palange, Paolo; Taliani, Gloria; Venditti, Mario; Violi, Francesco

2015-01-01

Background 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. Methods and Results Consecutive patients admitted to the University?Hospital Policlinico Umberto I (Rome, Italy) with community?onset pneumonia were recruited and prospectiv...

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.

Direct and irreversible inhibition of cyclooxygenase-1 by nitroaspirin (NCX 4016).

Science.gov (United States)

Corazzi, Teresa; Leone, Mario; Maucci, Raffaella; Corazzi, Lanfranco; Gresele, Paolo

2005-12-01

Benzoic acid, 2-(acetyl-oxy)-3-[(nitrooxy)methyl]phenyl ester (NCX 4016), a new drug made by an aspirin molecule linked, through a spacer, to a nitric oxide (NO)-donating moiety, is now under clinical testing for the treatment of atherothrombotic conditions. Aspirin exerts its antithrombotic activity by irreversibly inactivating platelet cyclooxygenase (COX)-1. NCX 4016 in vivo undergoes metabolism into deacetylated and/or denitrated metabolites, and it is not known whether NCX 4016 needs to liberate aspirin to inhibit COX-1, or whether it can block it as a whole molecule. The aim of our study was to evaluate the effects of NCX 4016 and its analog or metabolites on platelet COX-1 and whole blood COX-2 and on purified ovine COX (oCOX)-1 and oCOX-2. In particular, we have compared the mechanism by which NCX 4016 inhibits purified oCOX enzymes with that of aspirin using a spectrophotometric assay. All the NCX 4016 derivatives containing acetylsalicylic acid inhibited the activity of oCOX-1 and oCOX-2, whereas the deacetylated metabolites and the nitric oxide-donating moiety were inactive. Dialysis experiments showed that oCOX-1 inhibition by NCX 4016, similar to aspirin, is irreversible. Reversible COX inhibitors (indomethacin) or salicylic acid incubated with the enzyme before NCX 4016 prevent the irreversible inhibition of oCOX-1 by NCX 4016 as well as by aspirin. In conclusion, our data show that NCX 4016 acts as a direct and irreversible inhibitor of COX-1 and that the presence of a spacer and NO-donating moiety in the molecule slows the kinetics of COX-1 inhibition by NCX 4016, compared with aspirin.

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-02-11

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

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

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

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.

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

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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.

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

Comparative evaluation of antiplatelet effect of lycopene with aspirin and the effect of their combination on platelet aggregation: An in vitro study.

Science.gov (United States)

Sawardekar, Swapna B; Patel, Tejal C; Uchil, Dinesh

2016-01-01

The objective was to compare antiplatelet effect of lycopene with aspirin and to study effect of combination of the two on platelet aggregation in vitro, using platelets from healthy volunteers. Platelets were harvested; platelet count of platelet-rich plasma adjusted to 2.5 Χ 10(5)/μL. Aspirin (140 μmol/L) and lycopene (4, 6, 8, 10, and 12 μmol/L) were studied in vitro against adenosine-5'- diphosphate (ADP) (2.5 μM/L) and collagen. All the concentrations of lycopene (4-12 μmol/L) exhibited reduction in maximum platelet aggregation induced by aggregating agents ADP and collagen (P Lycopene at concentration 10 μmol/L showed maximum platelet inhibition (47.05% ± 19.56%) against ADP, whereas lycopene at concentration 8 μmol/L showed maximum platelet inhibition (54.26% ± 30.71%) against collagen. Four μmol/L of lycopene combined with 140 μmol/L and 70 μmol/L aspirin showed greater inhibition of platelets as compared to aspirin 140 μmol/L alone, against both ADP and collagen. The study favorably compares lycopene and aspirin with respect to their antiplatelet activities against ADP and collagen. Lycopene can be considered as a potential target for modifying the thrombotic and pro-inflammatory events associated with platelet activation.

Taking Aspirin to Protect Your Heart

Science.gov (United States)

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

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

NARCIS (Netherlands)

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

1998-01-01

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

Interleukin-4 but not interleukin-10 inhibits the production of leukemia inhibitory factor by rheumatoid synovium and synoviocytes.

Science.gov (United States)

Dechanet, J; Taupin, J L; Chomarat, P; Rissoan, M C; Moreau, J F; Banchereau, J; Miossec, P

1994-12-01

The expression of the proinflammatory cytokine leukemia inhibitory factor (LIF) has been reported in the cartilage and synovium of rheumatoid arthritis (RA) patients. Here, we show that high levels of LIF were constitutively produced by cultures of synovium pieces. Low levels of LIF were produced spontaneously by isolated synoviocytes, but interleukin (IL)-1 beta caused a fourfold enhancement of this secretion. The anti-inflammatory cytokine IL-4 reduced the production of LIF by synovium pieces by 75%, as observed earlier with IL-6, IL-1 beta and tumor necrosis factor (TNF)-alpha. IL-4 had a direct effect since it inhibited LIF production by unstimulated and IL-1 beta- or TNF-alpha-stimulated synoviocytes. Conversely, IL-4 enhanced the production of IL-6, which shares with LIF biological activities and receptor components. The inhibitory effect of IL-4 was dose dependent and was reversed using a blocking anti-IL-4 receptor antibody. Similar inhibitory action of IL-4 on LIF production was observed on synovium pieces from patients with osteoarthritis and on normal synoviocytes. IL-10, another anti-inflammatory cytokine acting on monocytes, had no effect on LIF production by either synovium pieces or isolated synoviocytes. Thus, the production of LIF by synovium tissue was inhibited by IL-4 through both a direct effect on synoviocytes and an indirect effect by inhibition of the production of LIF-inducing cytokines.

Aspirin for Primary Prevention.

Science.gov (United States)

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.

Comparative effect of clopidogrel plus aspirin and aspirin monotherapy on hematological parameters using propensity score matching

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Hayasaka M

2013-02-01

Full Text Available Masatoshi Hayasaka,1 Yasuo Takahashi,2 Yayoi Nishida,2 Yoshikazu Yoshida,1 Shinji Hidaka,3 Satoshi Asai41Department of Pharmacy, Nihon University Itabashi Hospital, Tokyo, 2Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, 3Laboratory of Pharmaceutical Regulatory Science, Department of Pharmacy, School of Pharmacy, Nihon University, Chiba, 4Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, JapanBackground: Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Dual antiplatelet therapy with clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in real-world clinical settings. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters.Methods: We used data from the Nihon University School of Medicine Clinical Data Warehouse obtained between November 2004 and May 2011 to identify cohorts of new users (n = 130 of clopidogrel (75 mg/day plus aspirin (100 mg/day and a propensity score matched sample of new users (n = 130 of aspirin alone (100 mg/day. We used a multivariate regression model to compare serum levels of creatinine, aspartate aminotransferase, and alanine aminotransferase, as well as hematological parameters including hemoglobin level, hematocrit, and white blood cell, red blood cell, and platelet counts up to 2 months after the start of administration of the study drugs.Results: There were no significant differences for any characteristics and baseline laboratory parameters between users of clopidogrel plus aspirin and users of aspirin alone. Reductions in white blood cell and red blood cell counts, hemoglobin levels, and

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.

Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate.

Science.gov (United States)

Brighenti, Elisa; Giannone, Ferdinando Antonino; Fornari, Francesca; Onofrillo, Carmine; Govoni, Marzia; Montanaro, Lorenzo; Treré, Davide; Derenzini, Massimo

2016-09-27

Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL-6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2-mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2-p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes.

Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate

Science.gov (United States)

Brighenti, Elisa; Giannone, Ferdinando Antonino; Fornari, Francesca; Onofrillo, Carmine; Govoni, Marzia; Montanaro, Lorenzo; Treré, Davide; Derenzini, Massimo

2016-01-01

Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL-6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2-mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2-p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes. PMID:27557515

STAT6 Mediates Interleukin-4 Growth Inhibition in Human Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Jennifer L. Gooch

2002-01-01

Full Text Available In addition to acting as a hematopoietic growth factor, interleukin-4 (IL-4 inhibits growth of some transformed cells in vitro and in vivo. In this study, we show that insulin receptor substrate (IRS-1, IRS-2, and signal transducer and activator of transcription 6 (STAT6 are phosphorylated following IL-4 treatment in MCF-7 breast cancer cells. STAT6 DNA binding is enhanced by IL-4 treatment. STAT6 activation occurs even after IRS-1 depletion, suggesting the two pathways are independent. To examine the role of STAT6 in IL-4-mediated growth inhibition and apoptosis, a fulllength STAT6 cDNA was transfected into MCF-7 cells. Transient overexpression of STAT6 resulted in both cytoplasmic and nuclear expression of the protein, increased DNA binding in response to IL-4, and increased transactivation of an IL-4 responsive promoter. In STAT6-transfected cells, basal proliferation was reduced whereas apoptosis was increased. Finally, stable expression of STAT6 resulted in reduced foci formation compared to vector-transfected cells alone. These results suggest STAT6 is required for IL-4mediated growth inhibition and induction of apoptosis in human breast cancer cells.

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

NARCIS (Netherlands)

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

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

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

Science.gov (United States)

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

NOSH–aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model

International Nuclear Information System (INIS)

Chattopadhyay, Mitali; Kodela, Ravinder; Olson, Kenneth R.; Kashfi, Khosrow

2012-01-01

Highlights: ► NOSH–aspirin is the first dual acting NO and H 2 S releasing hybrid. ► Its IC 50 for cell growth inhibition is in the low nano-molar range. ► Structure–activity studies show that the sum of the parts does not equal the whole. ► NOSH–aspirin reduced tumor growth by 85% in mice bearing a colon cancer xenograft. -- Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical anti-cancer agents. However, their long-term use is associated with adverse gastrointestinal effects. Recognition that endogenous gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H 2 S) can increase mucosal defense mechanisms has led to the development of NO- and H 2 S-releasing NSAIDs with increased safety profiles. Here we report on a new hybrid, NOSH–aspirin, which is an NO- and H 2 S-releasing agent. NOSH–aspirin inhibited HT-29 colon cancer growth with IC 50 s of 45.5 ± 2.5, 19.7 ± 3.3, and 7.7 ± 2.2 nM at 24, 48, and 72 h, respectively. This is the first NSAID based agent with such high degree of potency. NOSH–aspirin inhibited cell proliferation, induced apoptosis, and caused G 0 /G 1 cell cycle block. Reconstitution and structure–activity studies representing a fairly close approximation to the intact molecule showed that NOSH–aspirin was 9000-fold more potent than the sum of its parts towards growth inhibition. NOSH–aspirin inhibited ovine COX-1 more than ovine COX-2. NOSH–ASA treatment of mice bearing a human colon cancer xenograft caused a reduction in volume of 85%. Taken together, these results demonstrate that NOSH–aspirin has strong anti-cancer potential and merits further evaluation.

NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model

Energy Technology Data Exchange (ETDEWEB)

Chattopadhyay, Mitali; Kodela, Ravinder [Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, NY 10031 (United States); Olson, Kenneth R. [Department of Physiology, Indiana University School of Medicine, South Bend, IN 46617 (United States); Kashfi, Khosrow, E-mail: kashfi@med.cuny.edu [Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, NY 10031 (United States)

2012-03-16

Highlights: Black-Right-Pointing-Pointer NOSH-aspirin is the first dual acting NO and H{sub 2}S releasing hybrid. Black-Right-Pointing-Pointer Its IC{sub 50} for cell growth inhibition is in the low nano-molar range. Black-Right-Pointing-Pointer Structure-activity studies show that the sum of the parts does not equal the whole. Black-Right-Pointing-Pointer NOSH-aspirin reduced tumor growth by 85% in mice bearing a colon cancer xenograft. -- Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical anti-cancer agents. However, their long-term use is associated with adverse gastrointestinal effects. Recognition that endogenous gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H{sub 2}S) can increase mucosal defense mechanisms has led to the development of NO- and H{sub 2}S-releasing NSAIDs with increased safety profiles. Here we report on a new hybrid, NOSH-aspirin, which is an NO- and H{sub 2}S-releasing agent. NOSH-aspirin inhibited HT-29 colon cancer growth with IC{sub 50}s of 45.5 {+-} 2.5, 19.7 {+-} 3.3, and 7.7 {+-} 2.2 nM at 24, 48, and 72 h, respectively. This is the first NSAID based agent with such high degree of potency. NOSH-aspirin inhibited cell proliferation, induced apoptosis, and caused G{sub 0}/G{sub 1} cell cycle block. Reconstitution and structure-activity studies representing a fairly close approximation to the intact molecule showed that NOSH-aspirin was 9000-fold more potent than the sum of its parts towards growth inhibition. NOSH-aspirin inhibited ovine COX-1 more than ovine COX-2. NOSH-ASA treatment of mice bearing a human colon cancer xenograft caused a reduction in volume of 85%. Taken together, these results demonstrate that NOSH-aspirin has strong anti-cancer potential and merits further evaluation.

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.

Aspirin and salicylate bind to immunoglobulin heavy chain binding protein (BiP) and inhibit its ATPase activity in human fibroblasts.

Science.gov (United States)

Deng, W G; Ruan, K H; Du, M; Saunders, M A; Wu, K K

2001-11-01

Salicylic acid (SA), an endogenous signaling molecule of plants, possesses anti-inflammatory and anti-neoplastic actions in human. Its derivative, aspirin, is the most commonly used anti-inflammatory and analgesic drug. Aspirin and sodium salicylate (salicylates) have been reported to have multiple pharmacological actions. However, it is unclear whether they bind to a cellular protein. Here, we report for the first time the purification from human fibroblasts of a approximately 78 kDa salicylate binding protein with sequence identity to immunoglobulin heavy chain binding protein (BiP). The Kd values of SA binding to crude extract and to recombinant BiP were 45.2 and 54.6 microM, respectively. BiP is a chaperone protein containing a polypeptide binding site recognizing specific heptapeptide sequence and an ATP binding site. A heptapeptide with the specific sequence displaced SA binding in a concentration-dependent manner whereas a control heptapeptide did not. Salicylates inhibited ATPase activity stimulated by this specific heptapeptide but did not block ATP binding or induce BiP expression. These results indicate that salicylates bind specifically to the polypeptide binding site of BiP in human cells that may interfere with folding and transport of proteins important in inflammation.

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...

[Protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats].

Science.gov (United States)

Mu, F H; Hu, F L; Wei, H; Zhang, Y Y; Yang, G B; Lei, X Y; Yang, Y P; Sun, W N; Cui, M H

2016-02-01

To investigate the protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats and its possible mechanism. Acute gastric mucosal injury model was developed with intraperitoneal injection of aspirin in Wistar rats. The rats were divided into normal control group, injury group, sucralfate protection group, compound bismuth and magnesium granules protection group and its herbal components protection group(each group 12 rats). In the protection groups, drugs as mentioned above were administered by gavage before treated with intraperitoneal injection of aspirin. To evaluate the extent of gastric mucosal injury and the protective effect of drugs, gastric mucosal lesion index, gastric mucosal blood flow, content of gastric mucosal hexosamine, prostaglandins (PG), nitric oxide(NO), tumor necrosis factor (TNF), and interleukin (IL) -1, 2, 8 were measured in each group, and histological changes were observed by gross as well as under microscope and electron microscope. Contents of hexosamine, NO, and PG in all the protection groups were significantly higher than those in the injury group (all Pcompound bismuth and magnesium granules group was significantly higher than that in the sucralfate group ((11.29±0.51) vs(10.80±0.36)nmol/ml, Pcompound bismuth and magnesium granules group were significantly lower than those in the sucralfate group ((328.17±6.56) vs(340.23±8.05)pg/ml, PCompound bismuth and magnesium granules and its herbal components may have significant protective effect on aspirin-induced gastric mucosal injury.

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

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Deepak Voora, MD

2016-09-01

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

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

Science.gov (United States)

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

2016-07-01

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

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

Science.gov (United States)

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.

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.

NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model.

Science.gov (United States)

Chattopadhyay, Mitali; Kodela, Ravinder; Olson, Kenneth R; Kashfi, Khosrow

2012-03-16

Nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical anti-cancer agents. However, their long-term use is associated with adverse gastrointestinal effects. Recognition that endogenous gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H(2)S) can increase mucosal defense mechanisms has led to the development of NO- and H(2)S-releasing NSAIDs with increased safety profiles. Here we report on a new hybrid, NOSH-aspirin, which is an NO- and H(2)S-releasing agent. NOSH-aspirin inhibited HT-29 colon cancer growth with IC(50)s of 45.5 ± 2.5, 19.7 ± 3.3, and 7.7 ± 2.2 nM at 24, 48, and 72 h, respectively. This is the first NSAID based agent with such high degree of potency. NOSH-aspirin inhibited cell proliferation, induced apoptosis, and caused G(0)/G(1) cell cycle block. Reconstitution and structure-activity studies representing a fairly close approximation to the intact molecule showed that NOSH-aspirin was 9000-fold more potent than the sum of its parts towards growth inhibition. NOSH-aspirin inhibited ovine COX-1 more than ovine COX-2. NOSH-ASA treatment of mice bearing a human colon cancer xenograft caused a reduction in volume of 85%. Taken together, these results demonstrate that NOSH-aspirin has strong anti-cancer potential and merits further evaluation. Copyright © 2012 Elsevier Inc. All rights reserved.

Increased level of interleukin-13, but not interleukin-4 and interferon-γ in chronic rhinosinusitis with nasal polyps.

Science.gov (United States)

Nabavi, M; Arshi, S; Bahrami, A; Aryan, Z; Bemanian, M H; Esmaeilzadeh, H; Jalali, F; Pousti, S B; Rezaei, N

2014-01-01

This study was performed to investigate the serum level of interleukin (IL)-13, IL-4, and interferon (IFN)-γ in chronic rhinosinusitis with nasal polyps (CRSwNP) and subsequent inflammation pattern and comorbidities including asthma and aspirin intolerance. A case-control study was conducted on 60 adult patients with CRSwNP with mean age of 37.7±12.7 (ranging from 18 to 70) years, and on 20 healthy controls. Serum levels of IL-13, IL-4, and IFN-γ were assessed, using enzyme-linked immunosorbent assay to be compared between case and control groups. Serum level of total immunoglobulin (Ig) E was also assessed in the patients with CRSwNP. Serum level of IL-13 in the patients with CRSwNP was significantly higher than the controls (0.98±1.56 vs. 0.34±0.16 pg/ml, respectively, p=0.002). IL-4 and IFN-γ did not differ significantly between the two groups. Total IgE level was significantly increased in the patients with CRSwNP, compared to the normal values (301.43±516.54 IU/ml, p=0.033). Among the patients with CRSwNP, 12/60 (20%) had aspirin intolerance and 44/60 (73.3%) had asthma. IgE was also higher in asthmatics than non-asthmatics patients (364.9±586.6 vs. 126.7±135.7, respectively, p=0.015). Patients with aspirin intolerance had higher levels of IFN-γ (4.7±1.4 vs. 4.1±0.6, respectively, p=0.022). IL-13 with high level of total IgE was observed in the patients with CRSwNP, which predisposes them to have concomitant asthma. IFN-γ seems to be down-regulated in the patients with CRSwNP, but could be over-expressed in the presence of aspirin intolerance. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

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 ...

Aspirin, Butalbital, and Caffeine

Science.gov (United States)

The combination of aspirin, butalbital, and caffeine comes as a capsule and tablet to take by mouth. It usually is taken every 4 ... explain any part you do not understand. Take aspirin, butalbital, and caffeine exactly as directed. Do not ...

Effects of Atorvastatin calcium combined with Aspirin on serum levels of Hcy, NSE, UA, hs-CRP and inflammatory factors of patients with cerebral infarction

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Shu-Qin Zhang

2017-03-01

Full Text Available Objective: To study the effects of Atorvastatin calcium combined with Aspirin on serum levels of homocysteine (Hcy, neuron-specific enolase (NSE, uric acid (UA, high sensitity C-reactive protein (hs-CRP and inflammatory factors of patients with cerebral infarction. Methods: 100 cases of patients with cerebral infarction from March 2014 to May 2016 were treated in the Department of Neurology of our hospital and affiliated to Huazhong University of Science and Technology of traditional Chinese medicine and Western Medicine. The subjects were divided into the control group (n=50 and the treatment group (n=50 randomly. The control group was treated with Aspirin, the treatment group were treated with Atorvastatin calcium combined with Aspirin. The two groups were treated for 28 d. The serum levels of Hcy, NSE, UA, hs- CRP, interleukin-6 (IL-6, interleukin-8 (IL-8 and tumor necrosis factor-α (TNF-α of the two groups before and after treatment were compared. Results: There were no significantly differences of the serum levels of the Hcy, NSE, UA and hs-CRP of the two groups before treatment (P>0.05. After treatment, the serum levels of the Hcy, NSE, UA and hs-CRP of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group (P0.05. After treatment, the serum levels of the IL-6, IL-8 and TNF-α of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group (P<0.05. Conclusions: Atorvastatin calcium combined with Aspirin can significantly reduce the serum levels of Hcy, NSE, UA, hs-CRP, IL-6, IL-8 and TNF-α of the patients with cerebral infarction.

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

Science.gov (United States)

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.

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.

Aspirin challenge and desensitization: how, when and why.

Science.gov (United States)

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 In The Prevention Of Pre-Eclampsia: Where Are We Now?

LENUS (Irish Health Repository)

2018-03-01

Pre-eclampsia is a pregnancy specific multi-systemic disorder that causes maternal and perinatal morbidity and mortality worldwide. It is estimated to complicate between three to five percent of pregnancies and contributes to 8 to 10% of all preterm births1,2. Aspirin inhibits cyclooxygenase in platelets and endothelium in a fashion that alters the balance between the vasoconstrictor thromboxane and the vasodilator prostacyclin. This potentiates vasodilatation and reduces platelet aggregation, contributors to the endothelial dysfunction seen in preeclampsia. Over 100 clinical trials have examined whether or not Aspirin, when prescribed from early pregnancy, can prevent pre-eclampsia, and the consensus is that it reduces the incidence by approximately 10 to 24 % in women that are deemed to be at risk3,4.

Daily Aspirin Therapy: Understand the Benefits and Risks

Science.gov (United States)

Daily aspirin therapy: Understand the benefits and risks Daily aspirin therapy can be a lifesaving option, but it's not ... everyone. Get the facts before considering a daily aspirin. By Mayo Clinic Staff Daily aspirin therapy may ...

Lunasin-aspirin combination against NIH/3T3 cells transformation induced by chemical carcinogens.

Science.gov (United States)

Hsieh, Chia-Chien; Hernández-Ledesma, Blanca; de Lumen, Ben O

2011-06-01

Carcinogenesis is a multistage process involving a number of molecular pathways sensitive to intervention. Chemoprevention is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. To achieve greater inhibitory effects on cancer cells, combination of two or more chemopreventive agents is commonly considered as a better preventive and/or therapeutic strategy. Lunasin is a promising cancer preventive peptide identified in soybean and other seeds. Its efficacy has been demonstrated by both in vitro and in vivo models. This peptide has been found to inhibit human breast cancer MDA-MB-231 cells proliferation, suppressing cell cycle progress and inducing cell apoptosis. Moreover, lunasin potentiates the effects on these cells of different synthetic and natural compounds, such as aspirin and anacardic acid. This study explored the role of lunasin, alone and in combination with aspirin and anacardic acid on cell proliferation and foci formation of transformed NIH/3T3 cells induced by chemical carcinogens 7,12-dimethylbenz[a]anthracene or 3-methylcholanthrene. The results revealed that lunasin, acting as a single agent, inhibits cell proliferation and foci formation. When combined with aspirin, these effects were significantly increased, indicating that this combination might be a promising strategy to prevent/treat cancer induced by chemical carcinogens.

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

International Nuclear Information System (INIS)

Wang, Xianwei; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L.

2012-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-03-15

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

Mesenchymal stem cells expressing interleukin-18 inhibit breast cancer in a mouse model.

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Liu, Xiaoyi; Hu, Jianxia; Li, Yueyun; Cao, Weihong; Wang, Yu; Ma, Zhongliang; Li, Funian

2018-05-01

Development of an improved breast cancer therapy has been an elusive goal of cancer gene therapy for a long period of time. Human mesenchymal stem cells derived from umbilical cord (hUMSCs) genetically modified with the interleukin (IL)-18 gene (hUMSCs/IL-18) were previously demonstrated to be able to suppress the proliferation, migration and invasion of breast cancer cells in vitro . In the present study, the effect of hUMSCs/IL-18 on breast cancer in a mouse model was investigated. A total of 128 mice were divided into 2 studies (the early-effect study and the late-effect study), with 4 groups in each, including the PBS-, hUMSC-, hUMSC/vector- and hUMSC/IL-18-treated groups. All treatments were injected along with 200 µl PBS. Following therapy, the tumor size, histological examination, and expression of lymphocytes, Ki-67, cluster of differentiation 31 and cytokines [interleukin (IL)-18, IL-12, interferon (IFN)-γ and TNF-α] in each group were analyzed. Proliferation of cells (assessed by measuring tumor size and Ki-67 expression) and metastasis, (by determining pulmonary and hepatic metastasis) of breast cancer cells in the hUMSC/IL-18 group were significantly decreased compared with all other groups. hUMSCs/IL-18 suppressed tumor cell proliferation by activating immunocytes and immune cytokines, decreasing the proliferation index of proliferation marker protein Ki-67 of tumor cells and inhibiting tumor angiogenesis. Furthermore, hUMSCs/IL-18 were able to induce a more marked and improved therapeutic effect in the tumor sites, particularly in early tumors. The results of the present study indicate that hUMSCs/IL-18 were able to inhibit the proliferation and metastasis of breast cancer cells in vivo , possibly leading to an approach for a novel antitumor therapy in breast cancer.

[Interleukin-37 induces apoptosis and autophagy of SMMC-7721 cells by inhibiting phosphorylation of mTOR].

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Li, Tingting; Zhu, Di; Mou, Tong; Guo, Zhen; Pu, Junliang; Wu, Zhongjun

2017-04-01

Objective To investigate the underlying mechanism by which interleukin-37 (IL-37) induces the apoptosis and autophagy in SMMC-7721 cells. Methods SMMC-7721 cells were incubated in vitro and divided into two groups, IL-37 treated group and control group. The cells were treated with (50, 100, 200) ng/mL of recombinant human interleukin-37 (rhIL-37). CCK-8 assay was used to detect the cell proliferation of SMMC-7721 cells. Cell apoptosis was measured by flow cytometry. Western blot analysis was performed to examine the expressions of apoptosis-related proteins, Bax, Bcl-2, and autophagy related proteins, microtubule-associated proteins 1 light chain 3 (LC3), beclin 1 and mammalian target of rapamycin (mTOR). Transmission electron microscopy (TEM) was used to observe the ultrastructures of autophagosomes. Results The rhIL-37 inhibited the proliferation of hepatocellular carcinoma SMMC-7721 cells. It induced the apoptosis and autophagy in SMMC-7721 cells. In the IL-37 treated group, the levels of Bax, LC3 and beclin 1 increased but Bcl-2 decreased. The phosphorylation of mTOR was inhibited in the IL-37 treated group. Autophagosome was obvious in the IL-37 treated group. Conclusion IL-37 induces the apoptosis and autophagy in SMMC-7721 cells, which may be related to the phosphorylation of mTOR.

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

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

LENUS (Irish Health Repository)

Tobin, William Oliver

2012-02-01

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

The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population

OpenAIRE

Falf?n-Valencia, Ramc?s; Pav?n-Romero, Gandhi F.; Camarena, Angel; Garc?a, Mar?a de la Luz; Galicia-Negrete, Gustavo; Negrete-Garc?a, Mar?a Cristina; Teran, Luis Manuel

2011-01-01

Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to th...

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.

Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy

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Yakabe, Mitsutaka; Ota, Hidetaka; Iijima, Katsuya; Eto, Masato; Ouchi, Yasuyoshi; Akishita, Masahiro

2018-01-01

Background Interleukin-6 (IL-6) is an inflammatory cytokine. Whether systemic IL-6 affects atrogene expression and disuse-induced skeletal muscle atrophy is unclear. Methods Tail-suspended mice were used as a disuse-induced muscle atrophy model. We administered anti-mouse IL-6 receptor antibody, beta-hydroxy-beta-methylbutyrate (HMB) and vitamin D to the mice and examined the effects on atrogene expression and muscle atrophy. Results Serum IL-6 levels were elevated in the mice. Inhibition of IL-6 receptor suppressed muscle RING finger 1 (MuRF1) expression and prevented muscle atrophy. HMB and vitamin D inhibited the serum IL-6 surge, downregulated the expression of MuRF1 and atrogin-1 in the soleus muscle, and ameliorated atrophy in the mice. Conclusion Systemic IL-6 affects MuRF1 expression and disuse-induced muscle atrophy. PMID:29351340

Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy.

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Mitsutaka Yakabe

Full Text Available Interleukin-6 (IL-6 is an inflammatory cytokine. Whether systemic IL-6 affects atrogene expression and disuse-induced skeletal muscle atrophy is unclear.Tail-suspended mice were used as a disuse-induced muscle atrophy model. We administered anti-mouse IL-6 receptor antibody, beta-hydroxy-beta-methylbutyrate (HMB and vitamin D to the mice and examined the effects on atrogene expression and muscle atrophy.Serum IL-6 levels were elevated in the mice. Inhibition of IL-6 receptor suppressed muscle RING finger 1 (MuRF1 expression and prevented muscle atrophy. HMB and vitamin D inhibited the serum IL-6 surge, downregulated the expression of MuRF1 and atrogin-1 in the soleus muscle, and ameliorated atrophy in the mice.Systemic IL-6 affects MuRF1 expression and disuse-induced muscle atrophy.

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

DEFF Research Database (Denmark)

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

2013-01-01

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

Inhibition of human lymphocyte proliferation and cleavage of interleukin-2 by Pseudomonas aeruginosa proteases

DEFF Research Database (Denmark)

Theander, T G; Kharazmi, A; Pedersen, B K

1988-01-01

This study was undertaken to determine the effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (ELA) on human lymphocyte function. AP at 50 micrograms/ml and ELA at 12 micrograms/ml caused a 50% inhibition of phytohemagglutinin-induced proliferation. There was no difference...... in the effect of proteases on CD4- and CD8-positive cells. To determine the effect of proteases on interleukin-2 (IL-2)-induced cell proliferation, the proteases and IL-2 were added to the IL-2-dependent CTLL-2 cell line. AP and ELA inhibited the proliferation of these cells. When IL-2 was added in excess......, the inhibition was partly reversed. ELA at 10 micrograms/ml cleaved IL-2, as judged by size chromatography of a reaction mixture containing 125I-labeled IL-2 and the proteases. The ELA-digested IL-2 exhibited a reduced binding capacity to IL-2 receptors on the lymphocytes. Furthermore, treatment...

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

Science.gov (United States)

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

2016-01-01

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

Aspirin overutilization for the primary prevention of cardiovascular disease

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VanWormer JJ

2014-12-01

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

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Science.gov (United States)

2010-04-01

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

Melatonin antagonizes interleukin-18-mediated inhibition on neural stem cell proliferation and differentiation.

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Li, Zheng; Li, Xingye; Chan, Matthew T V; Wu, William Ka Kei; Tan, DunXian; Shen, Jianxiong

2017-09-01

Neural stem cells (NSCs) are self-renewing, pluripotent and undifferentiated cells which have the potential to differentiate into neurons, oligodendrocytes and astrocytes. NSC therapy for tissue regeneration, thus, gains popularity. However, the low survivals rate of the transplanted cell impedes its utilities. In this study, we tested whether melatonin, a potent antioxidant, could promote the NSC proliferation and neuronal differentiation, especially, in the presence of the pro-inflammatory cytokine interleukin-18 (IL-18). Our results showed that melatonin per se indeed exhibited beneficial effects on NSCs and IL-18 inhibited NSC proliferation, neurosphere formation and their differentiation into neurons. All inhibitory effects of IL-18 on NSCs were significantly reduced by melatonin treatment. Moreover, melatonin application increased the production of both brain-derived and glial cell-derived neurotrophic factors (BDNF, GDNF) in IL-18-stimulated NSCs. It was observed that inhibition of BDNF or GDNF hindered the protective effects of melatonin on NSCs. A potentially protective mechanism of melatonin on the inhibition of NSC's differentiation caused IL-18 may attribute to the up-regulation of these two major neurotrophic factors, BNDF and GNDF. The findings indicate that melatonin may play an important role promoting the survival of NSCs in neuroinflammatory diseases. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

AZD5363 inhibits inflammatory synergy between interleukin-17 and insulin/insulin-like growth factor 1

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Chong eChen

2014-12-01

Full Text Available In the United States, one third of population is affected by obesity and almost 29 million people are suffering from type 2 diabetes. Obese people have elevated serum levels of insulin, insulin-like growth factor 1 (IGF1 and interleukin-17 (IL-17. Insulin and IGF1 are known to enhance IL-17-induced expression of inflammatory cytokines and chemokines, which may contribute to the chronic inflammatory status observed in obese people. We have previously demonstrated that insulin/IGF1 signaling pathway crosstalks with IL-17-activated nuclear factor-kappa B (NF-κB pathway through inhibiting glycogen synthase kinase 3β (GSK3β activity. However, it is unclear whether GSK3α also plays a role and whether this crosstalk can be manipulated by AZD5363, a novel pan-Akt inhibitor that has been shown to increase GSK3 activity through reducing phosphorylation of GSK3α and GSK3β. In this study, we investigated IL-17-induced expression of C-X-C motif ligand 1 (Cxcl1, C-C motif ligand 20 (Ccl20 and interleukin-6 (Il-6 in wild-type, GSK3α-/-, and GSK3β-/- mouse embryonic fibroblast (MEF cells as well as in mouse prostate tissues by real-time quantitative PCR. We examined the proteins involved in the signaling pathways by Western blot analysis. We found that insulin and IGF1 enhanced IL-17- induced expression of Cxcl1, Ccl20 and Il-6, which was associated with increased phosphorylation of GSK3α and GSK3β in the presence of insulin and IGF1. AZD5363 inhibited the synergy between IL-17 and insulin/IGF1 through reducing phosphorylation of GSK3α and GSK3β by inhibiting Akt function. These findings imply that the cooperative crosstalk of IL-17 and insulin/IGF1 in initiating inflammatory responses may be alleviated by AZD5363.

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

Energy Technology Data Exchange (ETDEWEB)

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

2009-02-10

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

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

International Nuclear Information System (INIS)

Oikawa, Shinji; Kobayashi, Hatasu; Tada-Oikawa, Saeko; Isono, Yoshiaki; Kawanishi, Shosuke

2009-01-01

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

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

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Yan Wang

2012-10-01

Full Text Available The purpose of this study was to investigate the hydrolyzation of aspirin during the process of dissolution testing for aspirin delayed-release tablets. Hydrolysis product of salicylic acid can result in adverse effects and affect the determination of dissolution rate assaying. In this study, the technique of differential spectra was employed, which made it possible to monitor the dissolution testing in situ. The results showed that the hydrolyzation of aspirin made the percentage of salicylic acid exceed the limit of free salicylic acid (4.0, and the hydrolyzation may affect the quality detection of aspirin delayed-release tablets. Keywords: Aspirin delayed-release tablets, Drug dissolution test, Fiber-optic dissolution system, UV–vis spectrum

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

Science.gov (United States)

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

2017-07-10

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

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

Science.gov (United States)

Chen, H Y; Chou, P

2018-04-01

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

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

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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 ...

Topical diclofenac does not affect the antiplatelet properties of aspirin as compared to the intermediate effects of oral diclofenac: A prospective, randomized, complete crossover study.

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Rowcliffe, M; Nezami, B; Westphal, E S; Rainka, M; Janda, M; Bates, V; Gengo, F

2016-04-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) adversely interact with aspirin, diminishing its antiplatelet effect and potentially placing patients at an increased risk for recurrent thrombotic events. This crossover study aimed to determine whether the topical NSAID diclofenac epolamine 1.3% patch or oral diclofenac 50 mg interfered with the antiplatelet effects of aspirin 325 mg. Twelve healthy men and women aged 18-50 were included. Participants were randomized into 5 treatment arms: aspirin, diclofenac potassium 50 mg, diclofenac patch, diclofenac potassium plus ASA 325 mg, and diclofenac patch plus aspirin. Platelet responsiveness was determined using whole-blood impedance aggregation (WBA) to collagen 1 μg/mL and arachidonic acid (AA) 0.5 mM and was sampled every 2 hours. No significant difference in platelet function was observed following the diclofenac patch and aspirin vs aspirin alone. Oral diclofenac produced a mixed effect with significant reduction in platelet inhibition at hour 2 and hour 8 following aspirin administration. Topical diclofenac does not significantly interfere with the antiplatelet effects of aspirin and may be a safer alternative to the oral formulation. © 2015, The American College of Clinical Pharmacology.

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.

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 .).

[Nonsteroidal Anti-inflammatory Drug and Aspirin-induced Peptic Ulcer Disease].

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Shim, Young Kwang; Kim, Nayoung

2016-06-25

Despite decreasing Helicobacter pylori prevalence, the prevalence of peptic ulcer disease is increasing in the aged population, mainly due to increasing use of NSAIDs to manage pain and inflammation. In addition, low dose aspirin is employed as an anti-coagulant for those who have suffered or are at high risk of ischemic stroke and cardiovascular disease. However, NSAIDs and aspirin are injurious to mucosa of stomach and duodenum. NSAID-induced inhibition of mucosal prostaglandin synthesis is thought to be a major mechanism of gastrointestinal mucosal injury. The proportion of elderly has increased rapidly in Korea, with the proportion over 65 years old expected to be 24.3% in 2030. In this higher-risk population, the strategy to reduce the incidence of NSAID-related peptic ulcers and complications such as bleeding, obstruction and perforation is very important. Proton pump inhibitors (PPIs) with cyclooxygenase-2 inhibitor can be used for reducing the risk of NSAID-related ulcers and upper gastrointestinal (GI) complications. However, continuous use of PPI has several problems. In addition, NSAID-related problems in the lower GI tract have increased, in contrast to the decrease of NSAID-related upper GI disease. The aim of this review is to provide an evidence-based knowledge regarding the mechanism, complications of treatment, and prevention strategies for NSAID- or aspirin-related peptic ulcer disease in Korea.

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.

Safety and feasibility of liver resection with continued antiplatelet therapy using aspirin.

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Monden, Kazuteru; Sadamori, Hiroshi; Hioki, Masayoshi; Ohno, Satoshi; Saneto, Hiromi; Ueki, Toru; Yabushita, Kazuhisa; Ono, Kazumi; Sakaguchi, Kousaku; Takakura, Norihisa

2017-07-01

Aspirin is widely used for the secondary prevention of ischemic stroke and cardiovascular disease. Perioperative aspirin may decrease thrombotic morbidity, but may also increase hemorrhagic morbidity. In particular, liver resection carries risks of bleeding, leading to higher risks of hemorrhagic morbidity. Our institution has continued aspirin therapy perioperatively in patients undergoing liver resection. This study examined the safety and feasibility of liver resection while continuing aspirin. We retrospectively evaluated 378 patients who underwent liver resection between January 2010 and January 2016. Patients were grouped according to preoperative aspirin prescription: patients with aspirin therapy (aspirin users, n = 31); and patients without use of aspirin (aspirin non-users, n = 347). Aspirin users were significantly older (P aspirin users than among aspirin non-users, no significant difference was identified. No postoperative hemorrhage was seen among aspirin users. Liver resection can be safely performed while continuing aspirin therapy without increasing hemorrhagic morbidity. Our results suggest that interruption of aspirin therapy is unnecessary for patients undergoing liver resection. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Aloin Inhibits Interleukin (IL)-1β-Stimulated IL-8 Production in KB Cells.

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Na, Hee Sam; Song, Yu Ri; Kim, Seyeon; Heo, Jun-Young; Chung, Hae-Young; Chung, Jin

2016-06-01

Interleukin (IL)-1β, which is elevated in oral diseases including gingivitis, stimulates epithelial cells to produce IL-8 and perpetuate inflammatory responses. This study investigates stimulatory effects of salivary IL-1β in IL-8 production and determines if aloin inhibits IL-1β-stimulated IL-8 production in epithelial cells. Saliva was collected from volunteers to determine IL-1β and IL-8 levels. Samples from volunteers were divided into two groups: those with low and those with high IL-1β levels. KB cells were stimulated with IL-1β or saliva with or without IL-1 receptor agonist or specific mitogen-activated protein kinase (MAPK) inhibitors. IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA). MAPK protein expression involved in IL-1β-induced IL-8 secretion was detected by Western blot. KB cells were pretreated with aloin, and its effect on IL-1β-induced IL-8 production was examined by ELISA and Western blot analysis. Saliva with high IL-1β strongly stimulated IL-8 production in KB cells, and IL-1 receptor agonist significantly inhibited IL-8 production. Low IL-1β-containing saliva did not increase IL-8 production. IL-1β treatment of KB cells induced activation of MAPK signaling molecules as well as nuclear factor-kappa B. IL-1β-induced IL-8 production was decreased by p38 and extracellular signal-regulated kinase (ERK) inhibitor treatment. Aloin pretreatment inhibited IL-1β-induced IL-8 production in a dose-dependent manner and inhibited activation of the p38 and ERK signaling pathway. Finally, aloin pretreatment also inhibited saliva-induced IL-8 production. Results indicated that IL-1β in saliva stimulates epithelial cells to produce IL-8 and that aloin effectively inhibits salivary IL-1β-induced IL-8 production by mitigating the p38 and ERK pathway. Therefore, aloin may be a good candidate for modulating oral inflammatory diseases.

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

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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.

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)

Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling

International Nuclear Information System (INIS)

Forward, Nicholas A.; Conrad, David M.; Power Coombs, Melanie R.; Doucette, Carolyn D.; Furlong, Suzanne J.; Lin, Tong-Jun; Hoskin, David W.

2011-01-01

Highlights: → Curcumin inhibits CD4 + T-lymphocyte proliferation. → Curcumin inhibits interleukin-2 (IL-2) synthesis and CD25 expression by CD4 + T-lymphocytes. → Curcumin interferes with IL-2 receptor signaling by inhibiting JAK3 and STAT5 phosphorylation. → IL-2-dependent regulatory T-lymphocyte function and Foxp3 expression is downregulated by curcumin. -- Abstract: Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4 + T-lymphocytes, as well as interleukin-2 (IL-2) and CD25 (α chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca 2+ release to inhibit IκB phosphorylation, which is required for nuclear translocation of the transcription factor NFκB. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4 + CD25 + regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling.

The cytomegalovirus homolog of interleukin-10 requires phosphatidylinositol 3-kinase activity for inhibition of cytokine synthesis in monocytes.

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Spencer, Juliet V

2007-02-01

Human cytomegalovirus (CMV) has evolved numerous strategies for evading host immune defenses, including piracy of cellular cytokines. A viral homolog of interleukin-10, designated cmvIL-10, binds to the cellular IL-10 receptor and effects potent immune suppression. The signaling pathways employed by cmvIL-10 were investigated, and the classic IL-10R/JAK1/Stat3 pathway was found to be activated in monocytes. However, inhibition of JAK1 had little effect on cmvIL-10-mediated suppression of tumor necrosis factor alpha (TNF-alpha) production. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway had a more significant impact on TNF-alpha levels but did not completely relieve the immune suppression, demonstrating that cmvIL-10 stimulates multiple signaling pathways to modulate cell function.

Lactoferrin release and interleukin-1, interleukin-6, and tumor necrosis factor production by human polymorphonuclear cells stimulated by various lipopolysaccharides: relationship to growth inhibition of Candida albicans.

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Palma, C; Cassone, A; Serbousek, D; Pearson, C A; Djeu, J Y

1992-11-01

Lipopolysaccharides (LPSs) from Escherichia coli, Serratia marcescens, and Salmonella typhimurium, at doses from 1 to 100 ng/ml, strongly enhanced growth inhibition of Candida albicans by human polymorphonuclear leukocytes (PMN) in vitro. Flow cytometry analysis demonstrated that LPS markedly augmented phagocytosis of Candida cells by increasing the number of yeasts ingested per neutrophil as well as the number of neutrophils capable of ingesting fungal cells. LPS activation caused augmented release of lactoferrin, an iron-binding protein which itself could inhibit the growth of C. albicans in vitro. Antibodies against lactoferrin effectively and specifically reduced the anti-C. albicans activity of both LPS-stimulated and unstimulated PMN. Northern (RNA blot) analysis showed enhanced production of mRNAs for interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 and in neutrophils within 1 h of stimulation with LPS. The cytokines were also detected in the supernatant of the activated PMN, and their synthesis was prevented by pretreatment of LPS-stimulated PMN with protein synthesis inhibitors, such as emetine and cycloheximide. These inhibitors, however, did not block either lactoferrin release or the anti-Candida activity of LPS-stimulated PMN. These results demonstrate the ability of various bacterial LPSs to augment neutrophil function against C. albicans and suggest that the release of a candidastatic, iron-binding protein, lactoferrin, may contribute to the antifungal effect of PMN. Moreover, the ability to produce cytokines upon stimulation by ubiquitous microbial products such as the endotoxins points to an extraphagocytic, immunomodulatory role of PMN during infection.

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

Induction of lung lesions in Wistar rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate

International Nuclear Information System (INIS)

Ye, Bo; Zhang, Yu-Xia; Yang, Fei; Chen, Hong-Lei; Xia, Dong; Liu, Ming-Qiu; Lai, Bai-Tang

2007-01-01

The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by suitable laboratory animal models, such as animals treated with the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the current study, we established a novel lung cancer model in Wistar rats treated with NNK. Using this model, we assessed the effects of two chemopreventive agents, aspirin and phenethyl isothiocyanate (PEITC), on tumor progression. First, rats were treated with a single-dose of NNK by intratracheal instillation; control rats received iodized oil. The animals were then sacrificed on the indicated day after drug administration and examined for tumors in the target organs. PCNA, p63 and COX-2 expression were analyzed in the preneoplastic lung lesions. Second, rats were treated with a single-dose of NNK (25 mg/kg body weight) in the absence or presence of aspirin and/or PEITC in the daily diet. The control group received only the vehicle in the regular diet. The animals were sacrificed on day 91 after bronchial instillation of NNK. Lungs were collected and processed for histopathological and immunohistochemical assays. NNK induced preneoplastic lesions in lungs, including 33.3% alveolar hyperplasia and 55.6% alveolar atypical dysplasia. COX-2 expression increased similarly in alveolar hyperplasia and alveolar atypical dysplasia, while PCNA expression increased more significantly in the latter than the former. No p63 expression was detected in the preneoplastic lesions. In the second study, the incidences of alveolar atypical dysplasia were reduced to 10%, 10% and 0%, respectively, in the aspirin, PEITC and aspirin and PEITC groups, compared with 62.5% in the carcinogen-treated control group. COX-2 expression decreased after dietary aspirin or aspirin and PEITC treatment. PCNA expression was significantly reduced in the aspirin and PEITC group. (1) A single dose of 25 mg/kg body weight

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

Science.gov (United States)

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

2013-01-01

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

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

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

International Nuclear Information System (INIS)

Cohen, M.M.; Clark, L.; Armstrong, L.; D'Souza, J.

1985-01-01

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

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 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

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 ...

Aspirin resistance as cardiovascular risk after kidney transplantation

Science.gov (United States)

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

2014-05-01

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

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.

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)

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...

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

Science.gov (United States)

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

2015-10-01

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

Preventive Effect of Aspirin Eugenol Ester on Thrombosis in κ-Carrageenan-Induced Rat Tail Thrombosis Model.

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Ning Ma

Full Text Available Based on the prodrug principle, aspirin eugenol ester (AEE was synthesized, which can reduce the side effects of aspirin and eugenol. As a good candidate for new antithrombotic and anti-inflammatory medicine, it is essential to evaluate its preventive effect on thrombosis. Preventive effect of AEE was investigated in κ-carrageenan-induced rat tail thrombosis model. AEE suspension liquids were prepared in 0.5% sodium carboxymethyl cellulose (CMC-Na. AEE was administrated at the dosage of 18, 36 and 72 mg/kg. Aspirin (20 mg/kg, eugenol (18 mg/kg and 0.5% CMC-Na (30 mg/kg were used as control drug. In order to compare the effects between AEE and its precursor, integration of aspirin and eugenol group (molar ratio 1:1 was also designed in the experiment. After drugs were administrated intragastrically for seven days, each rat was injected intraperitoneally with 20 mg/kg BW κ-carrageen dissolved in physiological saline to induce thrombosis. The length of tail-thrombosis was measured at 24 and 48 hours. The blank group just was given physiological saline for seven days without κ-carrageenan administrated. The results indicated that AEE significantly not only reduced the average length of thrombus, PT values and FIB concentration, but also reduced the red blood cell (RBC, hemoglobin (HGB, hematocrit (HCT and platelet (PLT. The effects of AEE on platelet aggregation and anticoagulant in vitro showed that AEE could inhibit adenosine diphosphate (ADP-induced platelet aggregation as dose-dependence but no notable effect on blood clotting. From these results, it was concluded that AEE possessed positive effect on thrombosis prevention in vivo through the reduction of FIB, PLT, inhibition of platelet aggregation and the change of TT and PT values.

Arthritis is inhibited in Borrelia-primed and infected interleukin-17A-deficient mice after administration of anti-gamma-interferon, anti-tumor necrosis factor alpha and anti-interleukin-6 antibodies.

Science.gov (United States)

Kuo, Joseph; Warner, Thomas F; Schell, Ronald F

2017-08-31

The role that cytokines play in the induction of Lyme arthritis is gradually being delineated. We showed previously that severe arthritis developed in a T-cell-driven murine model, even in mice lacking interleukin-17A (IL-17A) and administered anti-gamma-interferon (IFN-γ) antibody. Increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), two pro-inflammatory cytokines, were detected in cultures of popliteal lymph node cells obtained from these mice. We hypothesized that concomitantly administered anti-IL-6, anti-TNF-α and anti-IFN-γ antibodies would inhibit the development of arthritis in IL-17A-deficient mice. Our results showed that swelling of the hind paws and histopathological changes consistent with arthritis were significantly reduced in IL-17A-deficient mice that administered the three anti-cytokine antibodies. These results suggest that treatment with multiple anti-cytokine antibodies can abrogate the induction of Lyme arthritis in mice. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Aspirin resistance: Prevalence and clinical outcome in Egypt

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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.

NCX 4040, a nitric oxide-donating aspirin derivative, inhibits Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

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Choi, Eun-Young; Choe, So-Hui; Hyeon, Jin-Yi; Park, Hae Ryoun; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

2015-12-05

In this study, the effects and underlying mechanisms of NCX 4040, a nitric oxide (NO)-donating aspirin derivative, on the production of proinflammatory mediators were examined using murine macrophages exposed to lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in the etiology of periodontal disease. NCX 4040 significantly reduced P. intermedia LPS-induced production of inducible NO synthase (iNOS)-derived NO, IL-1β and IL-6 as well as their mRNA expression in RAW264.7 cells. Notably, NCX 4040 was much more effective than the parental compound aspirin in reducing LPS-induced production of inflammatory mediators. NCX 4040 induced the expression of heme oxygenase-1 (HO-1) in cells treated with P. intermedia LPS, and the suppressive effect of NCX 4040 on LPS-induced NO production was significantly reversed by SnPP, a competitive HO-1 inhibitor. NCX 4040 did not influence LPS-induced phosphorylation of JNK and p38. IκB-α degradation as well as nuclear translocation and DNA-binding activities of NF-κB p65 and p50 subunits induced by P. intermedia LPS were significantly reduced by NCX 4040. Besides, LPS-induced phosphorylation of STAT1 and STAT3 was significantly down-regulated by NCX 4040. Further, NCX 4040 elevated the SOCS1 mRNA in cells stimulated with LPS. This study indicates that NCX 4040 inhibits P. intermedia LPS-induced production of NO, IL-1β and IL-6 in murine macrophages through anti-inflammatory HO-1 induction and suppression of NF-κB, STAT1 and STAT3 activation, which is associated with the activation of SOCS1 signaling. NCX 4040 could potentially be a promising tool in the treatment of periodontal disease, although further studies are required to verify this. Copyright © 2015 Elsevier B.V. All rights reserved.

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...

Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling

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Forward, Nicholas A.; Conrad, David M. [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Power Coombs, Melanie R.; Doucette, Carolyn D. [Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Furlong, Suzanne J. [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Lin, Tong-Jun [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia (Canada); Hoskin, David W., E-mail: d.w.hoskin@dal.ca [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Surgery, Dalhousie University, Halifax, Nova Scotia (Canada)

2011-04-22

Highlights: {yields} Curcumin inhibits CD4{sup +} T-lymphocyte proliferation. {yields} Curcumin inhibits interleukin-2 (IL-2) synthesis and CD25 expression by CD4{sup +} T-lymphocytes. {yields} Curcumin interferes with IL-2 receptor signaling by inhibiting JAK3 and STAT5 phosphorylation. {yields} IL-2-dependent regulatory T-lymphocyte function and Foxp3 expression is downregulated by curcumin. -- Abstract: Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4{sup +} T-lymphocytes, as well as interleukin-2 (IL-2) and CD25 ({alpha} chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca{sup 2+} release to inhibit I{kappa}B phosphorylation, which is required for nuclear translocation of the transcription factor NF{kappa}B. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4{sup +}CD25{sup +} regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling.

Duration of increased bleeding tendency after cessation of aspirin therapy.

LENUS (Irish Health Repository)

Cahill, Ronan A

2012-02-03

BACKGROUND: Aspirin has a significant effect on hemostasis, so it is often recommended that patients taking aspirin discontinue treatment before elective surgery. While off aspirin, these patients may be at risk of thrombosis. The optimum period of time that aspirin should be withheld is controversial. The aim of this study was to establish the duration of the antihemostatic effect of prolonged aspirin therapy. STUDY DESIGN: In a prospective study, 51 healthy volunteers were randomly assigned into 3 groups, each receiving an identical tablet for 14 days. One group received a placebo tablet; individuals in the other two groups received either 75 mg or 300 mg of aspirin once a day. Template bleeding times and specific platelet function testing (using the PFA-100; Dade Behring) were carried out on subjects before therapy and again after its completion until they returned to baseline. RESULTS: Thirty-eight volunteers complied sufficiently with the protocol to provide useful results. All bleeding times normalized within 96 hours and all platelet function tests within 144 hours after stopping aspirin. There was no demonstrable hemostatic defect in any volunteer persisting by or beyond the sixth day after treatment cessation. There was no apparent difference in duration of effect between those taking either 75 mg or 300 mg of aspirin. CONCLUSIONS: This study uses sensitive measures of platelet function to demonstrate the duration of increased bleeding tendency after withdrawal of aspirin therapy. It supports discontinuation of aspirin therapy 5 days before elective surgery (with the operation being performed on the sixth day).

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.

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.

The Role of Aspirin in the Prevention of Cardiovascular Disease

Science.gov (United States)

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

2014-01-01

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

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)

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

The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases

Directory of Open Access Journals (Sweden)

Omoigui Sota

2007-03-01

Full Text Available Abstract We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation.

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.

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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

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).

Monitoring aspirin therapy with the Platelet Function Analyzer-100

DEFF Research Database (Denmark)

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

2008-01-01

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

Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes.

Science.gov (United States)

Tsai, Wei-Jern; Chang, Chu-Ting; Wang, Guei-Jane; Lee, Tzong-Huei; Chang, Shwu-Fen; Lu, Shao-Chun; Kuo, Yuh-Chi

2011-03-25

Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

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.

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

Interleukin-24 induces neuroblastoma SH-SY5Y cell differentiation, growth inhibition, and apoptosis by promoting ROS production.

Science.gov (United States)

Li, Yuan; Zhang, Hongwei; Zhu, Xiaoyu; Feng, Dongchuan; Gong, Jinchao; Han, Tao

2013-11-01

Neuroblastoma is among the most aggressive tumors that occur in childhood and infancy. The clinical prognosis of children with advanced-stage neuroblastoma is still poor. Interleukin-24 (IL-24) is emerging as a new cytokine involved in tumor cellular proliferation, differentiation, and apoptosis and has been widely studied as a tumor inhibitor. However, little is known about this cytokine's role in neuroblastoma. In this study, we investigated the possible effects of IL-24 on inducing neuroblastoma cell differentiation, growth inhibition, and apoptosis in vitro. Our data show that IL-24 promotes neuroblastoma SH-SY5Y cell differentiation, growth inhibition, and apoptosis. Furthermore, we found that the differentiation- and apoptosis-inducing action of IL-24 depends on the accumulation of reactive oxygen species (ROS). These results suggest that IL-24 can induce neuroblastoma cell differentiation and apoptosis and may be a potential therapeutic agent for neuroblastoma.

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

Science.gov (United States)

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

2017-09-01

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

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

Aspirin and clopidogrel resistance: methodological challenges and opportunities

Directory of Open Access Journals (Sweden)

Armen Yuri Gasparyan

2010-03-01

Full Text Available Armen Yuri GasparyanClinical Research Unit, Russell’s Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, West Midlands, UKAbstract: Antiplatelet drug resistance is one of the urgent issues in current cardiovascular medicine. Many platelet function tests have been used to define responsiveness of patients with cardiovascular disease to aspirin and clopidogrel. In most studies, cut-off values of platelet function tests for defining responsiveness to antiplatelets were chosen arbitrarily. Different tests provided wide-ranging figures of the prevalence of aspirin and clopidogrel resistance, suggesting poor correlation between currently available platelet function tests. Measurement of platelet size seems to be a promising approach for monitoring antiplatelet drug therapy. This commentary highlights some limitations of studies on aspirin and clopidogrel resistance in patients undergoing coronary interventions.Keywords: aspirin, clopidogrel, resistance, cardiovascular disease, platelet function tests

Progress of interleukin-24 study

International Nuclear Information System (INIS)

Liu Yongzhe; Jin Shunzi

2007-01-01

Interteukin-24 (11-24)is a member of interleukin-10 family. Besides its character as a cytokine, IL-24 could induce apoptosis of different kinds of tumor cells without any harmful effects to normal cells. IL-24 could both promote bystander anti-tumor effect, inhibit tumor growth and angiogenesis in animal models. It also has effects of radiosensitization and immunoregulation. (authors)

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

Science.gov (United States)

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

2017-09-05

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

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

Validation of aspirin response-related transcripts in patients with coronary artery disease and preliminary investigation on CMTM5 function.

Science.gov (United States)

Zhang, J W; Liu, T F; Chen, X H; Liang, W Y; Feng, X R; Wang, L; Fu, Sidney W; McCaffrey, Timothy A; Liu, M L

2017-08-15

Aspirin is widely used in the prevention of cardiovascular diseases, but the antiplatelet responses vary from one patient to another. To validate aspirin response related transcripts and illustrate their roles in predicting cardiovascular events, we have quantified the relative expression of 14 transcripts previously identified as related to high on-aspirin platelet reactivity (HAPR) in 223 patients with coronary artery disease (CAD) on regular aspirin treatment. All patients were followed up regularly for cardiovascular events (CVE). The mean age of our enrolled population was 75.80±8.57years. HAPR patients showed no significant differences in terms of co-morbidities and combined drugs. Besides, the relative expression of HLA-DQA1 was significantly lower in low on-aspirin platelet reactivity (LAPR) patients, when compared with HAPR and high normal (HN) group (p=0.028). What's more, the number of arteries involved, HAPR status and the relative expression of CLU, CMTM5 and SPARC were independent risk factors for CVE during follow up (p<0.05). In addition, overexpression of CMTM5 attenuated endothelial cells (ECs) migration and proliferation, with significantly decreased phosphorylated-Akt levels, while its inhibition promoted these processes in vitro (p<0.05).Our study provides evidence that circulating transcripts might be potential biomarkers in predicting cardiovascular events. CMTM5 might exert anti-atherosclerotic effects via suppressing migration and proliferation in the vessel wall. Nevertheless, larger-scale and long-term studies are still needed. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

Phan, Kevin; Moore, Justin M; Griessenauer, Christoph J; Ogilvy, Christopher S; Thomas, Ajith J

2017-05-01

Recent studies have suggested that the use of low-dose aspirin may reduce the risk of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to evaluate any association between aspirin use and risk of aSAH based on the literature, and whether this is influenced by duration or frequency of aspirin use. A search of electronic databases was done from inception to September 2016. For each study, data on risk of aSAH in aspirin versus nonaspirin users were used to generate odds ratios and 95% confidence intervals, and combined using inverse variance-weighted averages of logarithmic odds ratios in a random-effects models. From 7 included studies, no significant difference was noted between aspirin use of any duration or frequency and nonaspirin users (odds ratio, 1.00; 95% confidence interval, 0.81-1.24; P =0.99). We found a significant association between short-term use of aspirin (3 years of durations of use. No significant association was found between infrequent aspirin use (≤2× per week) or frequent use (≥3× per week) with risk of aSAH. Current evidence suggests that short-term (aspirin is associated with increased risk of aSAH. Limitations include substantial heterogenity of the included studies. The role of long-term aspirin in reducing risk of aSAH remains unclear and ideally should be addressed by an appropriately designed randomized controlled trial. © 2017 American Heart Association, Inc.

Anaesthesia in aspirin-induced asthma.

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Harsh Sheth

Full Text Available Regular aspirin use is associated with reduced risk of colorectal cancer (CRC. Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs. We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05. Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001. Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively, however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively; stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86 compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively, with the direction of association similar to

Regular use of aspirin and pancreatic cancer risk

Directory of Open Access Journals (Sweden)

Mahoney Martin C

2002-09-01

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

Use and Misuse of Aspirin in Primary Cardiovascular Prevention

Directory of Open Access Journals (Sweden)

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 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.

Science.gov (United States)

Hernández-Díaz, Sonia; García Rodríguez, Luis A

2006-09-20

To balance the cardiovascular benefits from low-dose aspirin against the gastrointestinal harm caused, studies have considered the coronary heart disease risk for each individual but not their gastrointestinal risk profile. We characterized the gastrointestinal risk profile of low-dose aspirin users in real clinical practice, and estimated the excess risk of upper gastrointestinal complications attributable to aspirin among patients with different gastrointestinal risk profiles. To characterize aspirin users in terms of major gastrointestinal risk factors (i.e., advanced age, male sex, prior ulcer history and use of non-steroidal anti-inflammatory drugs), we used The General Practice Research Database in the United Kingdom and the Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria in Spain. To estimate the baseline risk of upper gastrointestinal complications according to major gastrointestinal risk factors and the excess risk attributable to aspirin within levels of these factors, we used previously published meta-analyses on both absolute and relative risks of upper gastrointestinal complications. Over 60% of aspirin users are above 60 years of age, 4 to 6% have a recent history of peptic ulcers and over 13% use other non-steroidal anti-inflammatory drugs. The estimated average excess risk of upper gastrointestinal complications attributable to aspirin is around 5 extra cases per 1,000 aspirin users per year. However, the excess risk varies in parallel to the underlying gastrointestinal risk and might be above 10 extra cases per 1,000 person-years in over 10% of aspirin users. In addition to the cardiovascular risk, the underlying gastrointestinal risk factors have to be considered when balancing harms and benefits of aspirin use for an individual patient. The gastrointestinal harms may offset the cardiovascular benefits in certain groups of patients where the gastrointestinal risk is high and the cardiovascular risk is low.

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

Science.gov (United States)

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.

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.

Weighing the Anti-Ischemic Benefits and Bleeding Risks from Aspirin Therapy: a Rational Approach.

Science.gov (United States)

Dugani, Sagar; Ames, Jeffrey M; Manson, JoAnn E; Mora, Samia

2018-02-21

The role of aspirin in secondary cardiovascular prevention is well understood; however, the role in primary prevention is less clear, and requires careful balancing of potential benefits with risks. Here, we summarize the evidence base on the benefits and risks of aspirin therapy, discuss clinical practice guidelines and decision support tools to assist in initiating aspirin therapy, and highlight ongoing trials that may clarify the role of aspirin in cardiovascular disease prevention. In 2016, the USPSTF released guidelines on the use of aspirin for primary prevention. Based on 11 trials (n = 118,445), aspirin significantly reduced all-cause mortality and nonfatal myocardial infarction, and in 7 trials that evaluated aspirin ≤ 100 mg/day, there was significant reduction in nonfatal stroke. The USPSTF recommends individualized use of aspirin based on factors including age, 10-year atherosclerotic cardiovascular disease risk score, and bleeding risk. Several ongoing trials are evaluating the role of aspirin in primary prevention, secondary prevention, and in combination therapy for atrial fibrillation. Evidence-based approaches to aspirin use should consider the anti-ischemic benefits and bleeding risks from aspirin. In this era of precision medicine, tools that provide the personalized benefit to risk assessment, such as the freely available clinical decision support tool (Aspirin-Guide), can be easily incorporated into the electronic health record and facilitate more informed decisions about initiating aspirin therapy for primary prevention. Aspirin has a complex matrix of benefits and risks, and its use in primary prevention requires individualized decision-making. Results from ongoing trials may guide healthcare providers in identifying appropriate candidates for aspirin therapy.

Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes

Science.gov (United States)

2011-01-01

Background Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Methods Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. Results AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. Conclusion AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT. PMID:21435270

Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes

Directory of Open Access Journals (Sweden)

Chang Shwu-Fen

2011-03-01

Full Text Available Abstract Background Arctium lappa (Niubang, a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC, isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Methods Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. Results AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2 and interferon-γ (IFN-γ production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. Conclusion AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

Affinity-purified human interleukin I is cytotoxic to isolated islets of Langerhans

DEFF Research Database (Denmark)

Mandrup-Poulsen, T; Bendtzen, K; Nerup, J

1986-01-01

Addition of highly purified human Interleukin-1 to the culture medium of isolated rat islets of Langerhans for 6 days led to 88% inhibition of glucose-induced insulin-release, reduction of islet contents of insulin and glucagon to 31% and 8% respectively, and disintegration of the islets. These e......Addition of highly purified human Interleukin-1 to the culture medium of isolated rat islets of Langerhans for 6 days led to 88% inhibition of glucose-induced insulin-release, reduction of islet contents of insulin and glucagon to 31% and 8% respectively, and disintegration of the islets...

Effect of Aspirin Supplementation on Hemodynamics in Older Firefighters.

Science.gov (United States)

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.

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.

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

Directory of Open Access Journals (Sweden)

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.

Metabolome analysis of effect of aspirin on Drosophila lifespan extension.

Science.gov (United States)

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.

DESCRIPTION OF EFFECTIVENESS OF CILOSTAZOL AND ASPIRIN AS ADJUVANT OF DIABETIC FOOT WAGNER GRADE II AND III

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Pandji Winata Nurikhwan

2014-09-01

Full Text Available Abstract: Inflammation in patients with diabetic foot will activate platelets and cause aggregation and lead to stasis of blood flow. This inflammation is caused by infection of the diabetic foot. Management of diabetic foot infections in patients is the use of antibiotics. However, the presence of vascularization disorders causing antibiotic delivery to the site of infection to be disrupted so that the process of eradication of infection would be inhibited. One of inflamation markers on patient with diabetic foot is increasing of Erythrocyte Sedimentation Rate (ESRs.The general objective of this study was to determine the efficacy difference between cilostazol and aspirin as an adjuvant to accelerate tissue healing of diabetic foot care Wagner Grade II – III based on erythrocyte sedimentation rate. This study is a descriptive study using the double-blind and randomized pretest-posttest design. A total of 14 samples is obtained by consecutive sampling. The results showed that four patients given cilostazol showed a 35% reduction in ESR and ten patients were given aspirin showed a 35% reduction in ESR. It can be concluded giving cilostazol and aspirin as adjuvant diabetic foot Wagner II and III showed a decrease in ESR.

Effect of different aspirin doses on arterial thrombosis after canine carotid endarterectomy: a scanning electron microscope and indium-111-labeled platelet study

International Nuclear Information System (INIS)

Ercius, M.S.; Chandler, W.F.; Ford, J.W.; Swanson, D.P.; Burke, J.C.

1984-01-01

Although it is widely accepted that aspirin inhibits platelet aggregation in arterial thrombosis, the appropriate dosage of aspirin remains quite controversial. The purpose of this study was to determine the effect of different doses of aspirin (0.5 mg/kg vs. 10 mg/kg) on mural thrombus formation after carotid endarterectomy. Eighteen hours after oral aspirin administration, 20 endarterectomies were performed on mongrel dogs with the use of the operating microscope. Blood flow was then restored for 3 hours and the vessels were prepared for investigation with the scanning electron microscope. Ten endarterectomies were also performed on unmedicated dogs as controls. Five minutes before vessel unclamping, autologous indium-111-labeled platelets were administered intravenously, and the endarterectomized portions of the vessels were studied with a gamma counter system after harvesting. Group 1, the control group, revealed extensive mural thrombus consisting of platelet aggregates, fibrin, red blood cells, and white blood cells. Six of the 10 vessels in Group 2, premedicated with 0.5 mg of aspirin per kg, demonstrated varying amounts of mural thrombus. Group 3 (10 vessels), premedicated with 10 mg of aspirin per kg, revealed a platelet monolayer completely covering the exposed vessel wall media, with scattered white blood cells and infrequent fine fibrin strands overlying the platelet surface. The mean (+/- SD) radioactivity per group expressed as counts/minute/mm2 was: Group 1--2055.3 +/- 1905.5, log . 7.253 +/- 0.926; Group 2--1235.6 +/- 1234.3, log . 6.785 +/- 0.817; Group 3--526 +/- 433.06, log . 5.989 +/- 0.774

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.

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)

Th2 cytokines and asthma — The role of interleukin-5 in allergic eosinophilic disease

Directory of Open Access Journals (Sweden)

Chapman Richard W

2001-03-01

Full Text Available Abstract Interleukin-5 is produced by a number of cell types, and is responsible for the maturation and release of eosinophils in the bone marrow. In humans, interleukin-5 is a very selective cytokine as a result of the restricted expression of the interleukin-5 receptor on eosinophils and basophils. Eosinophils are a prominent feature in the pulmonary inflammation that is associated with allergic airway diseases, suggesting that inhibition of interleukin-5 is a viable treatment. The present review addresses the data that relate interleukin-5 to pulmonary inflammation and function in animal models, and the use of neutralizing anti-interleukin-5 monoclonal antibodies for the treatment of asthma in humans.

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

Science.gov (United States)

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.

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 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.

The immunosuppressives FK 506 and cyclosporin A inhibit the generation of protein factors binding to the two purine boxes of the interleukin 2 enhancer.

Science.gov (United States)

Brabletz, T; Pietrowski, I; Serfling, E

1991-01-11

Like Cyclosporin A (CsA), the macrolide FK 506 is a potent immunosuppressive that inhibits early steps of T cell activation, including the synthesis of Interleukin 2 (II-2) and numerous other lymphokines. The block of II-2 synthesis occurs at the transcriptional level. At concentrations that block T cell activation, FK 506 and CsA inhibit the proto-enhancer activity of Purine boxes of the II-2 promoter and the generation of lymphocyte-specific factors binding to the Purine boxes. Under the same conditions, the DNA binding of other II-2 enhancer factors remains unaffected by both compounds. These results support the view that FK 506 and CsA, which both inhibit the activity of peptidylprolyl cis/trans isomerases, suppress T cell activation by a similar, if not identical mechanism.

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 ...

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

Effect of omega 3 fatty acids plus low-dose aspirin on both clinical and biochemical profiles of patients with chronic periodontitis and type 2 diabetes: a randomized double blind placebo-controlled study.

Science.gov (United States)

Elwakeel, N M; Hazaa, H H

2015-12-01

The aim of this study was, first, to investigate the effect of omega 3 (ω3) fatty acids plus low-dose aspirin with closed debridement in the treatment of patients with periodontitis and type 2 diabetes mellitus (DM), and second, to estimate the expression of monocyte chemoattractant protein-3 (MCP-3) in response to the supposed modulatory therapy. Forty patients with chronic periodontitis and type 2 DM were equally divided into groups 1 (patients received ω3 plus low-dose aspirin for 6 mo) and 2 (patients received placebo during the same period). Evaluation was done clinically (pocket depth, clinical attachment loss, gingival index and plaque index) and biochemically by estimating levels of interleukin 1β and MCP-3 in gingival crevicular fluid, plus investigating the effect of treatment on glycemic control by levels of glycated hemoglobin A1c in serum. All data were collected at baseline, 3 and 6 mo after treatment. Subjects of group 1 showed a highly significant reduction in pocket depth, clinical attachment loss, gingival index (p ≤ 0.01) after 3 and 6 mo compared to group 2. Glycated hemoglobin A1c levels showed a reduction in both groups at the end of the study period, with a non-significant difference (p > 0.05). Furthermore, the treatment protocol showed a significant reduction in levels of MCP-3 and interleukin 1β at 3 and 6 mo compared to the placebo group. Within the limits of the present study, ω3 plus low-dose aspirin proved effective as an adjunct to closed periodontal therapy in the management of patients with periodontitis and type 2 DM. Moreover, MCP-3 was proven to be effective both in the pathogenesis of the disease and as a biomarker in evaluating the response to periodontal treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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.

Suppression of multiple bioactivities of interleukin-1 and interleukin-2 production by U937 conditioned medium

International Nuclear Information System (INIS)

Wiblin, R.T.; Edmonds, K.; Ellner, J.J.

1986-01-01

The human macrophage-like cell line U937 spontaneously produces a factor which blocks interleukin-1 (IL-1) activity for mouse thymocytes but not mitosis of T-lymphoblastoid cells. The authors examined the effects of U937 conditioned medium (CM) on other IL-1 activities and on interleukin-2 (IL-2) production. U937 was cultured at 5 x 10 6 /ml in RPMI-1640 at 37 0 C for 5 days. The resulting CM inhibited the mitogenic response of C3H/HeJ mouse thymocytes to an IL-1 standard, with an inhibitory of activity of 6.64 U/ml (1 U = reciprocal dilution producing 50% inhibition of maximal response). Similarly, CM inhibited (10.12 U/ml) the fibroblast stimulation promoter activity of IL-1. The effect of CM on IL-2 production was assessed in a direct assay in which IL-2 production by γ-irradiated (12,000 rads) MLA-144 lymphosarcoma cells was assayed as 3 H-thymidine incorporation in CTLL-20 cells. The suppressive activity of CM was 4.95 U/ml; CM did not interfere with the response of CTLL-20 to IL-2. These studies establish that U937 produces factors with multiple, related biological activities; U937 CM blocks IL-2 dependent (thymocyte mitogenesis) and IL-2 independent (fibroblast proliferation) IL-1 activities and interferes with production of, but not response to, IL-2. U937 is an excellent model to study growth inhibitory properties of mononuclear phagocytes

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

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.

The use of preoperative aspirin in cardiac surgery: A systematic review and meta-analysis.

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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

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... 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 ...

COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss.

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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.

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

Directory of Open Access Journals (Sweden)

Ning Ma

Full Text Available OBJECTIVES: To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. METHODS: From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. RESULTS: Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5% with acute thrombosis, 5 patients (1.8% with subacute thrombosis, 17 patients (6.2% with stroke, and 2 death (0.7% in low-dose aspirin group, compared with no patient (0% with acute thrombosis, 2 patient (2.1% with subacute thrombosis, 6 patients (6.2% with stroke, and 2 death (2.1% in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. CONCLUSION: Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

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...

Interleukin-6 inhibits early differentiation of ATDC5 chondrogenic progenitor cells.

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Nakajima, Shoko; Naruto, Takuya; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Nishimaki, Shigeru; Yokota, Shumpei

2009-08-01

Interleukin (IL)-6 is a causative agent of systemic juvenile idiopathic arthritis (sJIA), a chronic inflammatory disease complicated with severe growth impairment. Recent trials of anti-IL-6 receptor monoclonal antibody, tocilizumab, indicated that tocilizumab blocks IL-6/IL-6 receptor-mediated inflammation, and induces catch-up growth in children with sJIA. This study evaluates the effects of IL-6 on chondrogenesis by ATDC5 cells, a clonal murine chondrogenic cell line that provides an excellent model for studying endochondral ossification at growth plate. ATDC5 cells were examined for the expression of IL-6 receptor and gp130 by fluorescence-activated cell sorting analysis. Recombinant murine IL-6 was added to ATDC5 cultures to observe cell differentiation, using a quantitative RT-PCR for the chondrogenic differentiation markers type II collagen, aggrecan, and type X collagen. To block IL-6, the anti-mouse IL-6 receptor monoclonal antibody MR16-1 was added. As a result, the cells expressed IL-6 receptor and gp130. The expression of chondrogenic differentiation marker gene was reduced by IL-6, but this was abrogated by MR16-1. We conclude that IL-6 inhibits early chondrogenesis of ATDC5 cells suggesting that IL-6 may affect committed stem cells at a cellular level during chondrogenic differentiation of growth plate chondrocytes, and that IL-6 may be a cellular-level factor in growth impairment in sJIA.

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.

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 ...

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

Science.gov (United States)

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

2015-01-01

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

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

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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.

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

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.

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...

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

Science.gov (United States)

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

2017-11-01

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

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…

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

Science.gov (United States)

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

2015-01-01

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

Synthesis and Chemical and Biological Comparison of Nitroxyl and Nitric Oxide Releasing Diazeniumdiolate-based Aspirin Derivatives

Science.gov (United States)

Basudhar, Debashree; Bharadwaj, Gaurav; Cheng, Robert Y.; Jain, Sarthak; Shi, Sa; Heinecke, Julie L.; Holland, Ryan J.; Ridnour, Lisa A.; Caceres, Viviane M.; Spadari-Bratfisch, Regina C.; Paolocci, Nazareno; Velázquez-Martínez, Carlos A.; Wink, David A.; Miranda, Katrina M.

2013-01-01

Structural modifications of non-steroidal anti-inflammatory drugs (NSAIDs) have successfully reduced the side effect of gastrointestinal ulceration without affecting anti-inflammatory activity, but may increase risk of myocardial infarction with chronic use. That nitroxyl (HNO) reduces platelet aggregation, preconditions against myocardial infarction and enhances contractility led us to synthesize a diazeniumdiolate-based HNO releasing aspirin and to compare it to an NO-releasing analogue. Here, the decomposition mechanisms are described for these compounds. In addition to protection against stomach ulceration, these prodrugs also exhibited significantly enhanced cytotoxcity compared to either aspirin or the parent diazeniumdiolate toward non-small cell lung carcinoma cells (A549) but were not appreciably toxic toward endothelial cells (HUVECs). The HNO-NSAID prodrug inhibited cylcooxgenase-2 and glyceraldehyde 3-phosphate dehydrogenase activity and triggered significant sarcomere shortening compared to control on murine ventricular myocytes. Together, these anti-inflammatory, anti-neoplasic and contractile properties suggest the potential of HNO-NSAIDs in the treatment of inflammation, cancer or heart failure. PMID:24102516

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

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

Inhibition of interleukin-6 expression by the V protein of parainfluenza virus 5

International Nuclear Information System (INIS)

Lin Yuan; Sun Minghao; Fuentes, Sandra M.; Keim, Celia D.; Rothermel, Terri; He Biao

2007-01-01

The V protein of parainfluenza virus 5 (PIV5) plays an important role in the evasion of host immune responses. The V protein blocks interferon (IFN) signaling in human cells by causing degradation of the STAT1 protein, a key component of IFN signaling, and blocks IFN-β production by preventing nuclear translocation of IRF3, a key transcription factor for activating IFN-β promoter. Interleukin-6 (IL-6), along with tumor necrosis factor (TNF)-α and IL-1β, is a major proinflammatory cytokine that plays important roles in clearing virus infection through inflammatory responses. Many viruses have developed strategies to block IL-6 expression. Wild-type PIV5 infection induces little, if any, expression of cytokines such as IL-6 or TNF-α, whereas infection by a mutant PIV5 lacking the conserved C-terminal cysteine rich domain (rPIV5VΔC) induced high levels of IL-6 expression. Examination of mRNA levels of IL-6 indicated that the transcription activation of IL-6 played an important role in the increased IL-6 expression. Co-infection with wild-type PIV5 prevented the activation of IL-6 transcription by rPIV5VΔC, and a plasmid encoding the full-length PIV5 V protein prevented the activation of IL-6 promoter-driven reporter gene expression by rPIV5VΔC, indicating that the V protein played a role in inhibiting IL-6 transcription. The activation of IL-6 was independent of IFN-β even though rPIV5VΔC-infected cells produced IFN-β. Using reporter gene assays and chromatin immunoprecipitation (ChIP), it was found that NF-κB played an important role in activating expression of IL-6. We have proposed a model of activating and inhibiting IL-6 transcription by PIV5

Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions.

Science.gov (United States)

Zhou, Jing; Jin, Jun-O; Patel, Ekta S; Yu, Qing

2015-12-01

Interleukin (IL)-6 is a multi-functional cytokine that can either promote or suppress tissue inflammation depending on the specific disease context. IL-6 is elevated in the exocrine glands and serum of patients with Sjögren's syndrome (SS), but the specific role of IL-6 in the pathogenesis of this disease has not been defined. In this study, we showed that IL-6 expression levels were increased with age in C56BL/6.NOD-Aec1Aec2 mice, a primary SS model, and higher than the control C57BL/6 mice. To assess the role of IL-6 during the immunological phase of SS development, a neutralizing anti-IL-6 antibody was administered into 16 week-old female C56BL/6.NOD-Aec1Aec2 mice, 3 times weekly for a consecutive 8 weeks. Neutralization of endogenous IL-6 throughout the immunological phase of SS development led to increased apoptosis, caspase-3 activation, leukocytic infiltration, and IFN-γ- and TNF-α production in the salivary gland. To further determine the effect of IL-6 on the apoptosis of exocrine gland cells, recombinant human IL-6 or the neutralizing anti-IL-6 antibody was injected into female C57BL/6 mice that received concurrent injection of anti-CD3 antibody to induce the apoptosis of exocrine gland tissues. Neutralization of IL-6 enhanced, whereas administration of IL-6 inhibited apoptosis and caspase-3 activation in salivary and lacrimal glands in this model. The apoptosis-suppressing effect of IL-6 was associated with up-regulation of Bcl-xL and Mcl-1 in both glands. Moreover, IL-6 treatment induced activation of STAT3 and up-regulated Bcl-xL and Mcl-1 gene expression in a human salivary gland epithelial cell line. In conclusion, IL-6 inhibits the apoptosis of exocrine gland tissues and exerts a tissue-protective effect under inflammatory conditions including SS. These findings suggest the possibility of using this property of IL-6 to preserve exocrine gland tissue integrity and function under autoimmune and inflammatory conditions. Copyright © 2015 Elsevier

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.

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.

Interleukin-4 inhibits RANKL-induced expression of NFATc1 and c-Fos: A possible mechanism for downregulation of osteoclastogenesis

International Nuclear Information System (INIS)

Kamel Mohamed, Saad Gad; Sugiyama, Eiji; Shinoda, Kouichiro; Hounoki, Hiroyuki; Taki, Hirofumi; Maruyama, Muneharu; Miyahara, Tatsuro; Kobayashi, Masashi

2005-01-01

Interleukin-4 (IL-4), an anti-inflammatory cytokine, has been shown to inhibit osteoclast differentiation. Therefore, this cytokine is considered to be a promising therapeutic applicant for bone-resorbing diseases such as rheumatoid arthritis (RA). Recently NFATc1, a transcription factor, has been shown to play critical roles in osteoclastogenesis. The aim of this study was to clarify the role of IL-4 on the intracellular signaling of NFATc1. A RAW264.7 monocyte/macrophage cell line and murine bone marrow precursors were differentiated into osteoclasts in the presence of receptor activator of nuclear factor κB ligand (RANKL) and/or macrophage colony-stimulating factor. Tartrate-resistant acid phosphatase (TRAP) staining and a pit assay using dentine were used for the identification of activated osteoclasts. The protein expression of IL-4 receptor, NFATc1, and c-Fos was determined by Western blot analysis. In addition, the gene expression of NFATc1 and c-Fos was determined by reverse transcription and polymerase chain reaction. The IL-4 receptor was constitutively expressed in RAW264.7 cells. RANKL induced osteoclast generation, as determined by TRAP staining and pit assay. IL-4 inhibited RANKL-induced osteoclastogenesis at low concentrations of 10 ng/ml and more. Interestingly, IL-4 potently inhibited RANKL-induced expression of NFATc1 at mRNA level. Furthermore, IL-4 inhibited c-Fos expression, which is shown to be responsible for NFATc1 expression, in time- and dose-dependent manners. In addition, IL-4 inhibited the RANKL-induced expression of NFATc1 and c-Fos in murine bone marrow cells. Thus, we suggest that IL-4 may downregulate osteoclastogenesis in part through inhibition of the expression of transcription factors, NFATc1 and c-Fos. These findings provide new insight into development of new medication for osteoporosis and RA

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.

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

Science.gov (United States)

Landolfi, R; Marchioli, R

1997-01-01

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

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

Science.gov (United States)

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?

Science.gov (United States)

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.

Brucella abortus Inhibits Major Histocompatibility Complex Class II Expression and Antigen Processing through Interleukin-6 Secretion via Toll-Like Receptor 2▿

Science.gov (United States)

Barrionuevo, Paula; Cassataro, Juliana; Delpino, M. Victoria; Zwerdling, Astrid; Pasquevich, Karina A.; Samartino, Clara García; Wallach, Jorge C.; Fossati, Carlos A.; Giambartolomei, Guillermo H.

2008-01-01

The strategies that allow Brucella abortus to survive inside macrophages for prolonged periods and to avoid the immunological surveillance of major histocompatibility complex class II (MHC-II)-restricted gamma interferon (IFN-γ)-producing CD4+ T lymphocytes are poorly understood. We report here that infection of THP-1 cells with B. abortus inhibited expression of MHC-II molecules and antigen (Ag) processing. Heat-killed B. abortus (HKBA) also induced both these phenomena, indicating the independence of bacterial viability and involvement of a structural component of the bacterium. Accordingly, outer membrane protein 19 (Omp19), a prototypical B. abortus lipoprotein, inhibited both MHC-II expression and Ag processing to the same extent as HKBA. Moreover, a synthetic lipohexapeptide that mimics the structure of the protein lipid moiety also inhibited MHC-II expression, indicating that any Brucella lipoprotein could down-modulate MHC-II expression and Ag processing. Inhibition of MHC-II expression and Ag processing by either HKBA or lipidated Omp19 (L-Omp19) depended on Toll-like receptor 2 and was mediated by interleukin-6. HKBA or L-Omp19 also inhibited MHC-II expression and Ag processing of human monocytes. In addition, exposure to the synthetic lipohexapeptide inhibited Ag-specific T-cell proliferation and IFN-γ production of peripheral blood mononuclear cells from Brucella-infected patients. Together, these results indicate that there is a mechanism by which B. abortus may prevent recognition by T cells to evade host immunity and establish a chronic infection. PMID:17984211

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

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

Science.gov (United States)

Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: A Mendelian randomisation analysis

NARCIS (Netherlands)

C.M. Freitag (Christine); A.S. Butterworth (Adam); J. Willeit (Johann); J.M.M. Howson (Joanna M.M.); S. Burgess (Stephen); S. Kaptoge (Stephen); R. Young (Robin); W.K. Ho (Weang Kee); A.M. Wood (Angela); M. Sweeting (Michael); S. Spackman (Sarah); J.R. Staley (James R.); A. Ramond (Anna); E. Harshfield (Eric); S.F. Nielsen (Sune); P. Grande (Peer); L.A. Lange (Leslie); M.J. Bown (Matthew J.); G.T. Jones (Gregory); R.A. Scott (Robert); S. Bevan (Steve); E. Porcu (Eleonora); G. Thorleifsson (Gudmar); L. Zeng (Lingyao); T. Kessler (Thorsten); M. Nikpay (Majid); R. Do (Ron); W. Zhang (Weihua); J. Hopewell; M.E. Kleber (Marcus); G. Delgado; C.P. Nelson (Christopher P.); A. Goel (Anuj); J.C. Bis (Joshua); A. Dehghan (Abbas); S. Ligthart (Symen); G.D. Smith; L. Qu (Liming); F.N.G. Van 'T Hof (Femke); P.I.W. de Bakker (Paul); A.F. Baas (Annette); A.M. van Rij (Andre); G. Tromp (Gerard); H. Kuivaniemi (Helena); M.D. Ritchie (Marylyn D.); S.S. Verma (Shefali S.); D.C. Crawford (Dana); J. Malinowski (Jennifer); M. de Andrade (Mariza); I. Kullo (Iftikhar); P.L. Peissig (Peggy L.); C.A. McCarty (Catherine A.); E.P. Bottinger (Erwin); R.F. Gottesman (Rebecca); D.R. Crosslin (David); D.S. Carrell (David); L.J. Rasmussen-Torvik (Laura); J.A. Pacheco (Jennifer A.); J. Huang (Jie); N.J. Timpson (Nicholas); J. Kettunen (Johannes); M. Ala-Korpela (Mika); G.F. Mitchell (Gary); A. Parsa (Afshin); I.B. Wilkinson (Ian B.); M. Gorski (Mathias); Y. Li (Yong); N. Franceschini (Nora); M.F. Keller (Margaux); S.K. Ganesh (Santhi); C.D. Langefeld (Carl); L. Bruijn (Lucie); M.A. Brown (Matthew); D.M. Evans (David M.); S. Baltic (Svetlana); M.A. Ferreira (Manuel); H. Baurecht (Hansjörg); S. Weidinger (Stephan); A. Franke (Andre); S.A. Lubitz (Steven); M. Müller-Nurasyid (Martina); J.F. Felix (Janine); N.L. Smith (Nicholas); M. Sudman (Marc); S.D. Thompson (Susan D.); E. Zeggini (Eleftheria); K. Panoutsopoulou (Kalliope); M.A. Nalls (Michael); A. Singleton (Andrew); C. Polychronakos (Constantin); J.P. Bradfield (Jonathan); H. Hakonarson (Hakon); D.F. Easton (Douglas); D. Thompson (Deborah); I.P. Tomlinson (Ian); M. Dunlop (Malcolm); K. Hemminki (Kari); G. Morgan (Gareth); T. Eisen (Timothy); H. Goldschmidt (Hartmut); J.M. Allan (James); M. Henrion (Marc); N. Whiffin (Nicola); Y. Wang (Yufei); D. Chubb (Daniel); M.M. Iles (Mark M.); D.T. Bishop (David Timothy); M.H. Law (Matthew H.); N. Hayward (Nick); Y. Luo (Yang); S. Nejentsev (Sergey); M. Barbalic (maja); D. Crossman (David); S. Sanna (Serena); N. Soranzo (Nicole); H.S. Markus (Hugh); N.J. Wareham (Nick); D.J. Rader (Daniel); M.P. Reilly (Muredach); T.L. Assimes (Themistocles); T.B. Harris (Tamara B.); A. Hofman (Albert); O.H. Franco (Oscar); V. Gudnason (Vilmundur); R.P. Tracy (Russell); B.M. Psaty (Bruce); M. Farrall (Martin); H. Watkins (Hugh); A.S. Hall (Alistair); N.J. Samani (Nilesh); W. März (Winfried); R. Clarke (Robert); F.S. Collins (Francis); J.S. Kooner (Jaspal S.); J.C. Chambers (John C.); S. Kathiresan (Sekar); R. McPherson (Ruth); J. Erdmann (Jeanette); A. Kastrati (Adnan); H. Schunkert (Heribert); J-A. Zwart (John-Anker); U. Thorsteinsdottir (Unnur); J. Walston (Jeremy); A. Tybjaerg-Hansen; D.S. Alam (Dewan S.); A. Al Shafi Majumder (Abdullah); E.D. Angelantonio (Emanuele Di); R. Chowdhury (Rajiv); B.G. Nordestgaard (Børge); D. Saleheen; S.G. Thompson (Simon); J. Danesh (John); R. Houlston (Richard)

2015-01-01

textabstractTo investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods: We created a genetic score combining the effects of alleles of

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist : A Mendelian randomisation analysis

NARCIS (Netherlands)

Freitag, Daniel; Butterworth, Adam S.; Willeit, Peter; Howson, Joanna M M; Burgess, Stephen; Kaptoge, Stephen; Young, Robin; Ho, Weang Kee; Wood, Angela M.; Sweeting, Michael; Spackman, Sarah; Staley, James R.; Ramond, Anna; Harshfield, Eric; Nielsen, Sune F.; Grande, Peer; Lange, Leslie A.; Bown, Matthew J.; Jones, Gregory T.; Scott, Robert A.; Bevan, Steve; Porcu, Eleonora; Thorleifsson, Gudmar; Zeng, Lingyao; Kessler, Thorsten; Nikpay, Majid; Do, Ron; Zhang, Weihua; Hopewell, Jemma C.; Kleber, Marcus; Delgado, Graciela E.; Nelson, Christopher P.; Goel, Anuj; Bis, Joshua C.; Dehghan, Abbas; Ligthart, Symen; Smith, Albert V.; Qu, Liming; van 't Hof, Femke N G; de Bakker, Paul I W; Baas, Annette F.; van Rij, Andre; Tromp, Gerard; Kuivaniemi, Helena; Ritchie, Marylyn D.; Verma, Shefali S.; Crawford, Dana C.; Malinowski, Jennifer; de Andrade, Mariza; Kullo, Iftikhar J.; Peissig, Peggy L.; McCarty, Catherine A.; Böttinger, Erwin P.; Gottesman, Omri; Crosslin, David R.; Carrell, David S.; Rasmussen-Torvik, Laura J.; Pacheco, Jennifer A.; Huang, Jie; Timpson, Nicholas J.; Kettunen, Johannes; Ala-Korpela, Mika; Mitchell, Gary F.; Parsa, Afshin; Wilkinson, Ian B.; Gorski, Mathias; Li, Yong; Franceschini, Nora; Keller, Margaux F.; Ganesh, Santhi K.; Langefeld, Carl D.; Bruijn, Lucie; Brown, Matthew A.; Evans, David M.; Baltic, Svetlana; Ferreira, Manuel A.; Baurecht, Hansjörg; Weidinger, Stephan; Franke, Andre; Lubitz, Steven A.; Müller-Nurasyid, Martina; Felix, Janine F.; Smith, Nicholas L.; Sudman, Marc; Thompson, Susan D.; Zeggini, Eleftheria; Panoutsopoulou, Kalliope; Nalls, Mike A.; Singleton, Andrew; Polychronakos, Constantin; Bradfield, Jonathan P.; Hakonarson, Hakon; Easton, Douglas F.; Thompson, Deborah; Tomlinson, Ian P.; Dunlop, Malcolm; Hemminki, Kari; Morgan, Gareth; Eisen, Timothy; Goldschmidt, Hartmut; Allan, James M.; Henrion, Marc; Whiffin, Nicola; Wang, Yufei; Chubb, Daniel; Iles, Mark M.; Bishop, D. Timothy; Law, Matthew H.; Hayward, Nicholas K.; Luo, Yang; Nejentsev, Sergey; Barbalic, Maja; Crossman, David; Sanna, Serena; Soranzo, Nicole; Markus, Hugh S.; Wareham, Nicholas J.; Rader, Daniel J.; Reilly, Muredach; Assimes, Themistocles; Harris, Tamara B.; Hofman, Albert; Franco, Oscar H.; Gudnason, Vilmundur; Tracy, Russell; Psaty, Bruce M.; Farrall, Martin; Watkins, Hugh; Hall, Alistair S.; Samani, Nilesh J.; März, Winfried; Clarke, Robert; Collins, Rory; Kooner, Jaspal S.; Chambers, John C.; Kathiresan, Sekar; McPherson, Ruth; Erdmann, Jeanette; Kastrati, Adnan; Schunkert, Heribert; Stefánsson, Kári; Thorsteinsdottir, Unnur; Walston, Jeremy D.; Tybjærg-Hansen, Anne; Alam, Dewan S.; Al Shafi Majumder, Abdullah; Angelantonio, Emanuele Di; Chowdhury, Rajiv; Nordestgaard, Børge G.; Saleheen, Danish; Thompson, Simon G.; Danesh, John; Houlston, Richard S.

2015-01-01

To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods: We created a genetic score combining the effects of alleles of two common

Interleukin-1 inhibition facilitates recovery from liver injury and promotes regeneration of hepatocytes in alcoholic hepatitis in mice.

Science.gov (United States)

Iracheta-Vellve, Arvin; Petrasek, Jan; Gyogyosi, Benedek; Bala, Shashi; Csak, Timea; Kodys, Karen; Szabo, Gyongyi

2017-07-01

Inflammation and impaired hepatocyte regeneration contribute to liver failure in alcoholic hepatitis (AH). Interleukin (IL)-1 is a key inflammatory cytokine in the pathobiology of AH. The role of IL-1 in liver regeneration in the recovery phase of alcohol-induced liver injury is unknown. In this study, we tested IL-1 receptor antagonist to block IL-1 signalling in a mouse model of acute-on-chronic liver injury on liver inflammation and hepatocyte regeneration in AH. We observed that inhibition of IL-1 signalling decreased liver inflammation and neutrophil infiltration, and resulted in enhanced regeneration of hepatocytes and increased rate of recovery from liver injury in AH. Our novel findings suggest that IL-1 drives sustained liver inflammation and impaired hepatocyte regeneration even after cessation of ethanol exposure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Directory of Open Access Journals (Sweden)

Altman Raul

2012-01-01

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

Insufficient platelet inhibition is related to silent embolic cerebral infarctions after coronary angiography.

Science.gov (United States)

Kim, Bum Joon; Lee, Seung-Whan; Park, Seong-Wook; Kang, Dong-Wha; Kim, Jong S; Kwon, Sun U

2012-03-01

Considering that insufficient platelet inhibition is related to thrombotic complications after coronary angiography, we hypothesized that the extent of platelet inhibition by antiplatelet agents is related to the occurrence of silent embolic cerebral infarction (SECI) after coronary angiography. Among the patients scheduled for coronary artery bypass surgery, we retrospectively analyzed the location of SECI on diffusion-weighted imaging of 272 patients, which was performed after coronary angiography, as a presurgical evaluation in Phase 1 study. In Phase 2 study, we have prospectively recruited 102 patients to compare the extent of platelet inhibition measured by the VerifyNow system among patients with and without SECI. SECI is observed in 45 patients (16.5%) in Phase 1 and 17 (16.7%) in Phase 2. The lesions were slightly more frequent in the right hemisphere. In the Phase 2 study, aspirin reaction units and P(2)Y(12) reaction units were higher in the patients with SECI than those without (aspirin reaction units: 490±72 versus 446±53, P=0.03; P(2)Y(12) reaction units: 352±65 versus 300±77, P=0.009). The incidence of SECI increased with the number of resistant antiplatelets; resistance to both antiplatelet agent (50%), resistance to 1 antiplatelet agent (22%), and no resistance (4%; P=0.023). From the result of logistic regression, higher aspirin reaction units, white blood cell count, low hemoglobin, and nonresponsiveness to antiplatelet agents were independent risk factors. Insufficient platelet inhibition after administration of antiplatelet agents is related with SECI appearing after coronary angiography.

Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

Science.gov (United States)

Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

2013-12-05

Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth. Published by Elsevier Ireland Ltd.

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...

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

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...

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

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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.

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.

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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.

Kaempferol Alleviates the Interleukin-1β-Induced Inflammation in Rat Osteoarthritis Chondrocytes via Suppression of NF-κB.

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Zhuang, Zhengling; Ye, Guangqun; Huang, Bin

2017-08-14

BACKGROUND This study was designed to examine the anti-inflammatory and anti-osteoarthritis (OA) effects of kaempferol in rat articular chondrocytes stimulated with interleukin-1β. MATERIAL AND METHODS Rat articular chondrocytes cultures were treated with interleukin-1β alone or with kaempferol (25, 50, 100, and 200 μM) and interleukin-1β. The effect of kaempferol on chondrocyte cells viability was measured by MTT assay. The effect on prostaglandin E2 (PGE2) and nitric oxide (NO) level were also assessed using the ELISA and Griess reagent, respectively, for kaempferol activity. Moreover, the expression of iNOS, Cox-2 and activation of NF-κB under influence of kaempferol was also assessed by Western blot. RESULTS Kaempferol treatment (up to 100 μM) in a concentration-dependent way caused reduction in the interleukin-1b-stimulated formations of PGE2 and NO. Kaempferol also upregulated the expression of iNOS and Cox-2 in interleukin-1β-stimulated rat OA chondrocytes. Additionally, kaempferol was found to inhibit the IkBa degradation and NF-κB activation in rat chondrocytes stimulated with interleukin-1β. CONCLUSIONS Kaempferol significantly caused reduction in interleukin-1β-stimulated pro-inflammatory mediators in rat OA chondrocytes by inhibiting the NF-κB pathway. These results suggest that kaempferol had significant anti-inflammatory and anti-arthritis effects. Thus, kaempferol, as a novel therapeutic active agent, may prevent, stop, or retard the progression of OA.

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

Science.gov (United States)

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.

Science.gov (United States)

Ornelas, Argentina; Zacharias-Millward, Niki; Menter, David G; Davis, Jennifer S; Lichtenberger, Lenard; Hawke, David; Hawk, Ernest; Vilar, Eduardo; Bhattacharya, Pratip; Millward, Steven

2017-06-01

After more than a century, aspirin remains one of the most commonly used drugs in western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and analgesic properties, a multitude of clinical studies have provided convincing evidence that regular, low-dose aspirin use dramatically lowers the risk of cancer. These observations coincide with recent studies showing a functional relationship between platelets and tumors, suggesting that aspirin's chemopreventive properties may result, in part, from direct modulation of platelet biology and biochemistry. Here, we present a review of the biochemistry and pharmacology of aspirin with particular emphasis on its cyclooxygenase-dependent and cyclooxygenase-independent effects in platelets. We also correlate the results of proteomic-based studies of aspirin acetylation in eukaryotic cells with recent developments in platelet proteomics to identify non-cyclooxygenase targets of aspirin-mediated acetylation in platelets that may play a role in its chemopreventive mechanism.

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.

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

Science.gov (United States)

Chu, Janet N; Maselli, Judith; Auerbach, Andrew D; Fang, Margaret C

2017-07-01

Recent guidelines include aspirin as an option to prevent venous thromboembolism (VTE) in selected patients undergoing hip or knee replacement surgery. However, the efficacy of aspirin after arthroplasty has not been well-defined, particularly in more contemporary patient populations. We compared rates of post-operative VTE between patients who received aspirin-only versus anticoagulants after hip or knee arthroplasty, using data from a large US-based administrative database. We conducted a retrospective cohort study of 231,780 adults who underwent total knee arthroplasty and 110,621 who underwent total hip arthroplasty in 2009-2012 and who received pharmacologic VTE prophylaxis (aspirin or anticoagulant) within the first 7days after surgery. We compared the risk of post-operative VTE between patients receiving aspirin-only vs. anticoagulants, controlling for clinical and hospital characteristics using multivariable logistic regression with propensity score adjustment. Aspirin-only prophylaxis was administered to 7.5% of patients after knee arthroplasty and 8.0% after hip arthroplasty. Post-operative VTE was diagnosed in 2217 (0.96%) patients after knee arthroplasty and 454 (0.41%) after hip arthroplasty. Compared to anticoagulants, aspirin was not associated with a higher risk for post-operative VTE either after knee arthroplasty (adjusted odds ratio and 95% confidence interval [OR] 0.34 [0.24-0.48]) or hip arthroplasty (OR 0.82 [0.45-1.51]). Aspirin was uncommonly administered as the sole prophylactic agent after hip or knee arthroplasty in this study. However, patients who received aspirin-only had similar rates of post-operative VTE compared to patients who received anticoagulants. Further research should focus on distinguishing which patients benefit more from anticoagulants versus aspirin after arthroplasty. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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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

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.

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

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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.

Role of nuclear factor of activated T-cells and activator protein-1 in the inhibition of interleukin-2 gene transcription by cannabinol in EL4 T-cells.

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Yea, S S; Yang, K H; Kaminski, N E

2000-02-01

We previously reported that immunosuppressive cannabinoids inhibited interleukin (IL)-2 steady-state mRNA expression and secretion by phorbol-12-myristate-13-acetate plus ionomycin-activated mouse splenocytes and EL4 murine T-cells. Here we show that inhibition of IL-2 production by cannabinol, a modest central nervous system-active cannabinoid, is mediated through the inhibition of IL-2 gene transcription. Moreover, electrophoretic mobility shift assays demonstrated that cannabinol markedly inhibited the DNA binding activity of nuclear factor of activated T-cells (NF-AT) and activator protein-1 (AP-1) in a time- and concentration-dependent manner in activated EL4 cells. The inhibitory effects produced by cannabinol on AP-1 DNA binding were quite transient, showing partial recovery by 240 min after cell activation and no effect on the activity of a reporter gene under the control of AP-1. Conversely, cannabinol-mediated inhibition of NF-AT was robust and sustained as demonstrated by an NF-AT-regulated reporter gene. Collectively, these results suggest that decreased IL-2 production by cannabinol in EL4 cells is due to the inhibition of transcriptional activation of the IL-2 gene and is mediated, at least in part, through a transient inhibition of AP-1 and a sustained inhibition of NF-AT.

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

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

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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.

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.

The role of interleukin-1ß and interleukin-33 in atopic dermatitis

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Rania M. Abdel Hay

2013-01-01

Full Text Available Introduction: Interleukin-1 super family is a group of cytokines that play a role in the regulation of immune and inflammatory responses. Interleukin-33 is a member of this family and is known to induce expression of the T helper2 cytokines that are important players in atopic dermatitis. Aim: To evaluate the expression of interleukins-1ß and 33 as T helper2 cytokines inducers in patients with atopic dermatitis. Materials andMethods: This study included 20 atopic patients and 20 apparently healthy individuals serving as controls. Skin biopsies from all participants will be examined for detection of interleukins-1ß and 33 by ELISA technique.Results: Both interleukins were statistically higher (P<0.001 in patients than in controls. A statistically significant (P=0.011 highest levels of interleukin-33 was detected in severe cases of atopics when compared to mild and moderate cases. A significant correlation (r=0.632, P=0.003 between both interleukins was detected in atopics.Conclusions: This is the first study to evaluate both interleukin-1ß and33 together in atopic patients. Both interleukins could play a role in the recruitment of lymphocytes during the inflammatory reaction in atopic dermatitis and could be targeted in the treatment of resistant cases.

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...

Using the Platelet Function Analyzer-100 for monitoring aspirin therapy

DEFF Research Database (Denmark)

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

2007-01-01

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

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

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

2017-08-01

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

Interleukin 1α inhibits prostaglandin E2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

International Nuclear Information System (INIS)

Rettori, V.; McCann, S.M.; Gimeno, M.F.; Karara, A.; Gonzalez, M.C.

1991-01-01

Interleukin 1α (IL-1α), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. The authors injected recombinant human IL-1α into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1α caused an almost immediate reduction of plasma LH concentration. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1α (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E 2 into the medium was measured by RIA in the presence or absence of nonrepinephrine. 1α reduced basal LHRH release and blocked LHRH release induced by nonrepinephrine. In conclusion, IL-1α suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E 2 -mediated release of LHRH

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.

Dissimilar effects of chronic treatment with aspirin, flubiprofen and indomethacin on renal prostaglandins

International Nuclear Information System (INIS)

Quilley, C.P.; McGiff, J.C.; Quilley, J.

1986-01-01

Inhibition of prostaglandin (PG) excretion is not sustained during long-term aspirin administration. The authors compared the effects of 9d treatment of SHR rats with aspirin (A), 200 mg/kg/d s.c., flubiprofen (F), 2.5 mg/kg/12h s.c., and indomethacin (I), 2.5 mg/kg/12 s.c. on excretion of radioimmunoassayable PGE 2 and PGF/sub 2α/. Conversion of 1-[ 14 C] arachidonic acid (AA) by renal papillae was also examined. In vehicle-treated control rats (C) PGF/sub 2α/ excretion varied from 32.2 +/- 6.2 (mean +/- SEM) to 41.6 +.- 7.3 ng/6h, 3-fold higher than that of PGE 2 . Within 6h of administration all 3 drugs reduced excretion of PGF/sub 2α/ and PGE 2 to less than 20% and 35% of C rats. Although urinary concentrations of PGF/sub 2α/ and PGE 2 in A-treated rats remained depressed, a 2-fold increase in urine volume resulted in excretion rates similar to C rats. In contrast, urine volume in I- and F-treated rats was unaffected while PGF/sub 2α/ and PGE 2 excretion rates in I-treated rats were 50''% of C rats and were also lower than control in F-treated rats. Paradoxically, metabolism of AA to PGs by by renal papillae dissected on day 10, 2-4h after the last drug dose, was markedly inhibited by A (PGF/sub 2α/ by 62% and PGE 2 by 82%), but unaffected by I and F. As the effects of cyclooxygenase inhibitors differ on in vivo and indices of PG production, their intended action should be verified by measuring PG levels in biological fluids

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

Directory of Open Access Journals (Sweden)

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

Science.gov (United States)

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

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

Science.gov (United States)

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

2017-09-01

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

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

Science.gov (United States)

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.

Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis.

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Johannes J Kovarik

Full Text Available A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR, is responsible for controlling the balance between pro-inflammatory interleukin (IL-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR-activation and glucose-deprivation or co-treatment with 5'-adenosine monophosphate (AMP-activated protein kinase (AMPK activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation.

Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis

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Kernbauer, Elisabeth; Hölzl, Markus A.; Hofer, Johannes; Gualdoni, Guido A.; Schmetterer, Klaus G.; Miftari, Fitore; Sobanov, Yury; Meshcheryakova, Anastasia; Mechtcheriakova, Diana; Witzeneder, Nadine; Greiner, Georg; Ohradanova-Repic, Anna; Waidhofer-Söllner, Petra; Säemann, Marcus D.; Decker, Thomas

2017-01-01

A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR)-activation and glucose-deprivation or co-treatment with 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG) increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation. PMID:28742108

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

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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.

Interleukin-22 Inhibits Bleomycin-Induced Pulmonary Fibrosis

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Minrui Liang

2013-01-01

Full Text Available Pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Recent insight has suggested that early injury/inflammation of alveolar epithelial cells could lead to dysregulation of tissue repair driven by multiple cytokines. Although dysregulation of interleukin- (IL- 22 is involved in various pulmonary pathophysiological processes, the role of IL-22 in fibrotic lung diseases is still unclear and needs to be further addressed. Here we investigated the effect of IL-22 on alveolar epithelial cells in the bleomycin- (BLM- induced pulmonary fibrosis. BLM-treated mice showed significantly decreased level of IL-22 in the lung. IL-22 produced γδT cells were also decreased significantly both in the tissues of lungs and spleens. Administration of recombinant human IL-22 to alveolar epithelial cell line A549 cells ameliorated epithelial to mesenchymal transition (EMT and partially reversed the impaired cell viability induced by BLM. Furthermore, blockage of IL-22 deteriorated pulmonary fibrosis, with elevated EMT marker (α-smooth muscle actin (α-SMA and overactivated Smad2. Our results indicate that IL-22 may play a protective role in the development of BLM-induced pulmonary fibrosis and may suggest IL-22 as a novel immunotherapy tool in treating pulmonary fibrosis.

Interleukin-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process

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Hong, Huixian [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China); Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Shi, Zhenqi [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Qiao, Ping [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Department of Pharmacology, Norman Bethune Medical College, Jilin University, Changchun, Jilin 130021 (China); Li, Hui [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); McCoy, Erin M. [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Mao, Ping [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China); Xu, Hui [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Feng, Xu [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Wang, Shunqing, E-mail: shqwang_cn@yahoo.com [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China)

2013-11-01

Highlights: •IL-3 treatment of bone marrow cells generates a population of hematopoietic cells. •IL-3-dependent hematopoietic cells are capable of differentiating into osteoclasts. •Osteoclasts derived from IL-3-dependent hematopoietic cells are functional. •IL-3 promotes the development of osteoclast progenitors. •IL-3 inhibits the osteoclastogenic process. -- Abstract: Interleukin (IL)-3, a multilineage hematopoietic growth factor, is implicated in the regulation of osteoclastogenesis. However, the role of IL-3 in osteoclastogenesis remains controversial; whereas early studies showed that IL-3 stimulates osteoclastogenesis, recent investigations demonstrated that IL-3 inhibits osteoclast formation. The objective of this work is to further address the role of IL-3 in osteoclastogenesis. We found that IL-3 treatment of bone marrow cells generated a population of cells capable of differentiating into osteoclasts in tissue culture dishes in response to the stimulation of the monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator of nuclear factor kappa B ligand (RANKL). The IL-3-dependent hematopoietic cells were able to further proliferate and differentiate in response to M-CSF stimulation and the resulting cells were also capable of forming osteoclasts with M-CSF and RANKL treatment. Interestingly, IL-3 inhibits M-CSF-/RANKL-induced differentiation of the IL-3-dependent hematopoietic cells into osteoclasts. The flow cytometry analysis indicates that while IL-3 treatment of bone marrow cells slightly affected the percentage of osteoclast precursors in the surviving populations, it considerably increased the percentage of osteoclast precursors in the populations after subsequent M-CSF treatment. Moreover, osteoclasts derived from IL-3-dependent hematopoietic cells were fully functional. Thus, we conclude that IL-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the

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

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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

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

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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.

Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a levels in human subjects with rheumatoid diseases.

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Olaf Schultz

2010-12-01

Full Text Available Interleukin-6 (IL-6 is a pro-inflammatory cytokine that has been found to be increased in type 2 diabetic subjects. However, it still remains unclear if these elevated IL-6 levels are co-incidental or if this cytokine is causally related to the development of insulin resistance and type 2 diabetes in humans. Therefore, in the present study we examined insulin sensitivity, serum adipokine levels and lipid parameters in human subjects before and after treatment with the IL-6 receptor antibody Tocilizumab.11 non-diabetic patients with rheumatoid disease were included in the study. HOMA-IR was calculated and serum levels for leptin, adiponectin, triglycerides, LDL-cholesterol, HDL-cholesterol and lipoprotein (a (Lp (a were measured before as well as one and three months after Tocilizumab treatment. The HOMA index for insulin resistance decreased significantly. While leptin concentrations were not altered by inhibition of IL-6 signalling, adiponectin concentrations significantly increased. Thus the leptin to adiponectin ratio, a novel marker for insulin resistance, exhibited a significant decrease. Serum triglycerides, LDL-cholesterol and HDL-cholesterol tended to be increased whereas Lp (a levels significantly decreased.Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance. Furthermore, our data indicate that inhibition of IL-6 signalling decreases Lp (a serum levels, which might reduce the cardiovascular risk of human subjects.

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

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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.

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

Indoleamine 2,3-Dioxygenase Fine-Tunes Immune Homeostasis in Atherosclerosis and Colitis through Repression of Interleukin-10 Production

NARCIS (Netherlands)

Metghalchi, Sarvenaz; Ponnuswamy, Padmapriya; Simon, Tabassome; Haddad, Yacine; Laurans, Ludivine; Clement, Marc; Dalloz, Marion; Romain, Melissa; Esposito, Bruno; Koropoulis, Vincent; Lamas, Bruno; Paul, Jean-Louis; Cottin, Yves; Kotti, Salma; Bruneval, Patrick; Callebert, Jacques; den Ruijter, Hester; Launay, Jean-Marie; Danchin, Nicolas; Sokol, Harry; Tedgui, Alain; Taleb, Soraya; Mallat, Ziad

2015-01-01

Indoleamine 2,3-dioxygenase 1 (Ido1) is a rate-limiting enzyme that catalizes the degradation of tryptophan along the kynurenine pathway. Here, we show that Ido1 activity sustains an immunostimulatory potential through inhibition of interleukin (Il)10. In atherosclerosis, Ido1-dependent inhibition

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

Before Using Aspirin to Lower Your Risk of Heart Attack or Stroke, Here Is What You Should Know

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... 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 ...

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.

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.

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.

Polysaccharide Isolated from Zizyphus jujuba (紅棗 Hóng Zǎo Inhibits Interleukin-2 Production in Jurkat T Cells

Directory of Open Access Journals (Sweden)

Bo-Yang Hsu

2014-04-01

Full Text Available Zizyphus jujuba (紅棗 Hóng Zǎo, a traditional Chinese herb widely used in many Asian countries, has been shown to possess vital biological activities such as anti-cancer activity. The objective of this study was to evaluate the immunomodulatory effect of deproteinated polysaccharide (DP isolated from Z. jujuba. The DP isolated from Z. jujuba consisted of two polysaccharide fractions and their molecular weights (MWs were found to be 143,108 and 67,633 Da, respectively. The DP could significantly decrease interleukin (IL-2 production in phytohemagglutinin (PHA-activated Jurkat T cells in a dose-dependent manner after 48 h of incubation, with the inhibition being 47.5%, 61.2%, and 81.7% for DP concentrations of 0.75, 1.75, and 2.5 mg/ml, respectively. Thus, our study showed that DP isolated from Z. jujuba may possess anti-inflammatory activity as it could significantly reduce IL-2 production in activated Jurkat T cells.

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

Science.gov (United States)

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

Science.gov (United States)

Reilly, Anthony M.; Tkatchenko, Alexandre

2014-08-01

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

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

Directory of Open Access Journals (Sweden)

Abdalla S. Elhwuegi

2012-04-01

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

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

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.

Protective Effects of Pinus halepensis L. Essential Oil on Aspirin-induced Acute Liver and Kidney Damage in Female Wistar Albino Rats.

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Bouzenna, Hafsia; Samout, Noura; Amani, Etaya; Mbarki, Sakhria; Tlili, Zied; Rjeibi, Ilhem; Elfeki, Abdelfattah; Talarmin, Hélène; Hfaiedh, Najla

2016-08-01

Aromatic and medicinal plants are sources of natural antioxidants thanks to their secondary metabolites. Administration of Pinus halepensis L. (Pinaceae family) in previous studies was found to alleviate deleterious effects of aspirin-induced damage on liver and kidney. The present study, carried out on female rats, evaluates the effects of P. halepensis L. essential oil (EOP) on aspirin (A)-induced damage to liver and kidney. The animals used in this study were rats (n=28) divided into 4 groups of 7 each: (1) a control group (C); (2) a group given NaCl for 56 days then treated with (A) (600 mg/kg) for 4 days (A); (3) a group fed with (EOP) for 56 days then (A) for 4 days; and a group fed with only (EOP) for 56 days and given NaCl for 4 days. Estimations of biochemical parameters in blood were determined using kit methods (Spinreact). Lipid peroxidation levels (TBARS), superoxide dismutase (SOD) and catalase (CAT), glutathione peroxidase (GPx) activities were determined. Histopathological study was done by immersing pieces of both organs in a fixative solution followed by paraffin embeddeding and hematoxylin-eosin staining. Under our experimental conditions, Aspirin at dose 600 mg/kg body weight induced an increase of serum biochemical parameters as well as an oxidative stress in both organs. An increase occurred in TBARS by 108% and 55%, a decrease in SOD by 78% and 53%, CAT by 53% and 78%, and GPx by 78% and 51% in liver and kidney, respectively, compared to control. Administration of EOP given to rats enabled correction in these parameters. It could be concluded that the treatment with P. halepensis L. essential oil inhibited aspirin-induced liver and kidney damage.

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.

Science.gov (United States)

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.

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.

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...

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

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.)...

A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils.

Science.gov (United States)

Ohira, Taisuke; Bannenberg, Gerard; Arita, Makoto; Takahashi, Minoru; Ge, Qingyuan; Van Dyke, Thomas E; Stahl, Gregory L; Serhan, Charles N; Badwey, John A

2004-08-01

Lipoxins and their aspirin-triggered 15-epimers are endogenous anti-inflammatory agents that block neutrophil chemotaxis in vitro and inhibit neutrophil influx in several models of acute inflammation. In this study, we examined the effects of 15-epi-16-(p-fluoro)-phenoxy-lipoxin A(4) methyl ester, an aspirin-triggered lipoxin A(4)-stable analog (ATLa), on the protein phosphorylation pattern of human neutrophils. Neutrophils stimulated with the chemoattractant fMLP were found to exhibit intense phosphorylation of a 55-kDa protein that was blocked by ATLa (10-50 nM). This 55-kDa protein was identified as leukocyte-specific protein 1, a downstream component of the p38-MAPK cascade in neutrophils, by mass spectrometry, Western blotting, and immunoprecipitation experiments. ATLa (50 nM) also reduced phosphorylation/activation of several components of the p38-MAPK pathway in these cells (MAPK kinase 3/MAPK kinase 6, p38-MAPK, MAPK-activated protein kinase-2). These results indicate that ATLa exerts its anti-inflammatory effects, at least in part, by blocking activation of the p38-MAPK cascade in neutrophils, which is known to promote chemotaxis and other proinflammatory responses by these cells.

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

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.

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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

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.

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

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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.

Science.gov (United States)

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.

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

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

Directory of Open Access Journals (Sweden)

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.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-01-01

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

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.

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....

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

Science.gov (United States)

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.

1α,25-Dihydroxyvitamin D(3) inhibits vascular cellular adhesion molecule-1 expression and interleukin-8 production in human coronary arterial endothelial cells.

Science.gov (United States)

Kudo, Keiko; Hasegawa, Shunji; Suzuki, Yasuo; Hirano, Reiji; Wakiguchi, Hiroyuki; Kittaka, Setsuaki; Ichiyama, Takashi

2012-11-01

Kawasaki disease is an acute febrile vasculitis of childhood that is associated with elevated production of inflammatory cytokines, causing damage to the coronary arteries. The production of proinflammatory cytokines and expression of adhesion molecules in human coronary arterial endothelial cells (HCAECs) is regulated by nuclear transcription factor-κB (NF-κB) activation. We have previously reported that the active form of vitamin D, 1α,25-dihydroxyvitamin D(3) (1α,25-(OH)(2)D(3)), inhibits tumor necrosis factor-α (TNF-α)-induced NF-κB activation. In this study, we examined the anti-inflammatory effects of 1α,25-(OH)(2)D(3) on TNF-α-induced adhesion molecule expression (vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1)) and cytokine production (interleukin-6 (IL-6) and IL-8) in HCAECs. Pretreatment with 1α,25-(OH)(2)D(3) significantly inhibited TNF-α-induced VCAM-1 expression and IL-8 production in HCAECs. Our results suggest that adjunctive 1α,25-(OH)(2)D(3) therapy may modulate the inflammatory response during Kawasaki disease vasculitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2015-01-01

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

The anti-interleukin-1 in type 1 diabetes action trial--background and rationale

DEFF Research Database (Denmark)

Pickersgill, Linda M S; Mandrup-Poulsen, Thomas R

2009-01-01

Type 1 diabetes (T1D) is caused by an inflammatory destruction of pancreatic beta-cells. Pro-inflammatory cytokines, in particular interleukin-1 (IL-1), have been suggested to be effector molecules based on the observations that pro-inflammatory cytokines cause beta-cell apoptosis in vitro...... and aggravate diabetes in vivo, and that inhibition of the action of these cytokines reduce diabetes incidence in animal models of type 1 diabetes and islet graft destruction. This review presents the rationale for and design of a recently launched double-blind, multicenter, randomized clinical trial...... that investigates the effect of interleukin-1 antagonism on beta-cell function in subjects with T1D of recent-onset....

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.

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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

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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

Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation.

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Jang, Ja-Young; Kim, Tae-Su; Cai, Jingmei; Kim, Jihyun; Kim, Youngeun; Shin, Kyungha; Kim, Kwang Sei; Park, Sung Kyeong; Lee, Sung-Pyo; Choi, Ehn-Kyoung; Rhee, Man Hee; Kim, Yun-Bae

2013-12-01

The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-dependent manner. Rats were orally administered with nattokinase for 1 week, and their carotid arteries were exposed. Arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Nattokinase delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 160 mg/kg. In addition, a high dose (500 mg/kg) of nattokinase fully prevented the occlusion, as achieved with aspirin (30 mg/kg). The results indicate that nattokinase extracted from fermented soybean inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is suggested that nattokinase could be a good candidate without adverse effects for the improvement of blood flow.

Interferon β protects against avascular osteonecrosis through interleukin 6 inhibition and silent information regulator transcript-1 upregulation.

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Kim, Kyoung Min; Wagle, Sajeev; Moon, Young Jae; Wang, Sung Il; Park, Byung-Hyun; Jang, Kyu Yun; Kim, Jung Ryul

2018-01-09

Synovitis of the affected joint is a common in avascular osteonecrosis (AVN). Increased levels of pro-inflammatory cytokine interleukin-6 (IL-6) have been reported in AVN, but the mechanism of this increase remains unclear. Silent information regulator transcript-1 (SIRT1), an NAD-dependent deacetylase, inhibits the release of inflammatory cytokines. Interferon β (IFN-β) has clear anti-inflammatory properties. We sought to investigate the effects of IFN-β treatment on AVN and to evaluate the specific signal pathway relating to IL-6 and SIRT1 affected during AVN. Using a dissection microscope, AVN was surgically induced in the distal femurs of mice. Exogenous IFN-β was administered to the model mice. The effects of exogenous IFN-β on AVN model mice were assessed using hematoxylin eosin and safranin-O staining, and bone resorption activity was measured using tartrate-resistant acid phosphatase (TRAP) and CD68 staining. Western blots, real-time RT-PCR, and immunohistochemical staining were performed to evaluate the production of SIRT1 and IL-6 in tissues. The RAW 264.7 cell line and bone marrow derived osteoclasts treated with exogenous IFN-β. Histological findings indicated well preserved trabecular bone and decreased osteoclast bone resorption activity in IFN-β treated mice compared with mice in the AVN group. Treatment with IFN-β increased SIRT1 expression and inhibited secretion of IL-6 in this AVN mouse model. IFN-β decreased IL-6 secretion by activating SIRT1 in the RAW 264.7 cell and bone marrow derived osteoclasts. Our work suggests that IFN-β could be used to treat AVN and that both SIRT1 and IL-6 are useful targets for treating patients with AVN.

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

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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

Role of Interleukin-6 in the Radiation Response of Liver Tumors

International Nuclear Information System (INIS)

Chen, Miao-Fen; Hsieh, Ching-Chuan; Chen, Wen-Cheng; Lai, Chia-Hsuan

2012-01-01

Purpose: To investigate the role of interleukin (IL)-6 in biological sequelae and tumor regrowth after irradiation for hepatic malignancy, which are critical for the clinical radiation response of liver tumors. Methods and Materials: The Hepa 1-6 murine hepatocellular cancer cell line was used to examine the radiation response by clonogenic assays and tumor growth delay in vivo. After irradiation in a single dose of 6 Gy in vitro or 15 Gy in vivo, biological changes including cell death and tumor regrowth were examined by experimental manipulation of IL-6 signaling. The effects of blocking IL-6 were assessed by cells preincubated in the presence of IL-6–neutralizing antibody for 24 hours or stably transfected with IL-6–silencing vectors. The correlations among tumor responses, IL-6 levels, and myeloid-derived suppressor cells (MDSC) recruitment were examined using animal experiments. Results: Interleukin-6 expression was positively linked to irradiation and radiation resistance, as demonstrated by in vitro and in vivo experiments. Interleukin-6–silencing vectors induced more tumor inhibition and DNA damage after irradiation. When subjects were irradiated with a sublethal dose, the regrowth of irradiated tumors significantly correlated with IL-6 levels and MDSC recruitment in vivo. Furthermore, blocking of IL-6 could overcome irradiation-induced MDSC recruitment and tumor regrowth after treatment. Conclusion: These data demonstrate that IL-6 is important in determining the radiation response of liver tumor cells. Irradiation-induced IL-6 and the subsequent recruitment of MDSC could be responsible for tumor regrowth. Therefore, treatment with concurrent IL-6 inhibition could be a potential therapeutic strategy for increasing the radiation response of tumors.

Efecto de diferentes dosis de aspirina sobre el precondicionamiento contra el atontamiento en ovejas Effect of different doses of aspirin on preconditioning against stunning in conscious sheep

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Elena C. Lascano

2004-02-01

Full Text Available Se ha postulado que los antiinflamatorios no esteroides que actuan inhibiendo la ciclooxigenasa (COX podrían tener efectos nocivos sobre el corazón. Recientemente se ha demostrado que los inhibidores de la COX-2 bloquean la protección por precondicionamiento tardío (PT. Se desconoce sin embargo, el efecto que pudiera tener la aspirina, el antiinflamatorio no esteroide más ampliamente utilizado en la clínica, sobre el PT en mamíferos grandes. La aspirina actúa inhibiendo las dos isoenzimas de la ciclooxigenasa (COX-1 y COX-2, siendo empleada en dosis altas como droga antiinflamatoria y en dosis bajas como agente antitrombótico. El propósito de este estudio fue analizar qué efecto tienen distintas dosis de aspirina sobre la protección del PT contra el atontamiento y las arritmias en ovejas conscientes. Se consideraron 5 grupos; control (C: 12 min de isquemia (I y 2 hr de reperfusión (R; PT: 6 períodos de 5 min I-5 min R, 24 hr antes de la I de 12 min, y tres grupos igual que PT, pero con 1.5 (PTA1.5, 8 (PTA8 y 20 (PTA20 mg/kg de aspirina respectivamente, administrados 10 min antes de la primera I de precondicionamiento. Los resultados demostraron que la dosis antiinflamatoria de aspirina (20 mg/kg fue capaz de inhibir el PT contra el atontamiento (C vs PTA20, NS, mientras que las dosis bajas (1.5 mg/kg e intermedia (8 mg/kg no afectaron la protección (C vs PT, PT1.5 y PT8, pNon-steroid antiinflammatory drugs, inhibitors of cyclooxigenase (COX, have been postulated to have deletereous effects on the heart. Recently, COX-2 inhibitors have also been found to block late preconditioning (LP protection. Aspirin is the most widely clinically used non-steroid antiinflammatory drug; yet its effect on LP in big mammals has not been determined. It inhibits the two cyclooxigenase isoenzymes (COX-1 and COX-2, at high doses being used as an antiinflammatory drug and at low doses as an antithrombotic agent. The goal of this study was thus, to

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.

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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.

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

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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

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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.

Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation

OpenAIRE

Jang, Ja-Young; Kim, Tae-Su; Cai, Jingmei; Kim, Jihyun; Kim, Youngeun; Shin, Kyungha; Kim, Kwang Sei; Park, Sung Kyeong; Lee, Sung-Pyo; Choi, Ehn-Kyoung; Rhee, Man Hee; Kim, Yun-Bae

2013-01-01

The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-depende...

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

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

Science.gov (United States)

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

2015-01-01

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

Effect of aspirin treatment on chondromalacia patellae.

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