Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

NASA Astrophysics Data System (ADS)

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.

Aspirin resistance as cardiovascular risk after kidney transplantation

NASA Astrophysics Data System (ADS)

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 < 0.002). Morbidity analysis demonstrated significantly higher incidence of myocardial infarction, hypertension and diabetes mellitus in the RT group (p < 0.05). The subgroup analysis revealed significantly higher incidence of infarction and stroke in the ASA resistant RT group compared to the RT patients without ASA resistance (p < 0.05). Furthermore, the incidence of myocardial infarction and hypertension was significantly higher in the non-resistant RT group than in the group of PC patients without ASA resistance (p < 0.05). These results may suggest that the elevated rate of aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

Acetylsalicylic acid (aspirin) reduces damage to reconstituted human tissues infected with Candida species by inhibiting extracellular fungal lipases

PubMed Central

Trofa, David; Agovino, Mariangela; Stehr, Frank; Schäfer, Wilhelm; Rykunov, Dmitry; Fiser, András; Hamari, Zsuzsanna; Nosanchuk, Joshua D.; Gácser, Attila

2009-01-01

A reconstituted human tissue model was used to mimic Candida albicans and Candida parapsilosis infection in order to investigate the protective effects of acetylsalicylic acid (aspirin, ASA). We found that therapeutic concentrations of ASA reduced tissue damage in the in vitro infection model. We further evaluated the lipase inhibitory effects of ASA by investigating the growth of C. albicans, C. parapsilosis and C. parapsilosis lipase negative (Δcplip1-2/Δcplip1-2) mutants in a lipid rich minimal medium supplemented with olive oil and found that a therapeutic concentration of ASA inhibited the growth of wild type fungi. The lipase inhibitors quinine and ebelactone B were also shown to reduce growth and protect against tissue damage from Candida species, respectively. A lipolytic activity assay also showed that therapeutic concentrations of ASA inhibited C. antarctica and C. cylindracea purified lipases obtained through a commercial kit. The relationship between ASA and lipase was characterized through a computed structural model of the Lipase-2 protein from C. parapsilosis in complex with ASA. The results suggest that development of inhibitors of fungal lipases could result in broad-spectrum therapeutics, especially since fungal lipases are not homologous to their human analogues. PMID:19703582

Therapeutic potential of choline magnesium trisalicylate as an alternative to aspirin for patients with bleeding tendencies.

PubMed

Danesh, B J; Saniabadi, A R; Russell, R I; Lowe, G D

1987-12-01

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p less than 0.005), AA (p less than 0.01) and spontaneous aggregation (p less than 0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

Pharmacokinetic study of a new oral buffered acetylsalicylic acid (ASA) formulation in comparison with plain ASA in healthy volunteers.

PubMed

Viganò, G; Garagiola, U; Gaspari, F

1991-01-01

A single-blind, randomized, crossover pharmacokinetic study was carried out to investigate the bioavailability of a new oral buffered 325 mg acetylsalicylic acid (ASA) formulation (ASPIRINA 03) in comparison with a 325 mg plain tablet. Twelve healthy volunteers of both sexes, aged between 20 and 37 years, received buffered or plain ASA on two separate occasions with a wash-out interval of at least two weeks. ASA and salicylic acid (SA) plasma levels were determined by a chromatographic method. The results showed no difference between the area under concentration time curve (AUC0-infinity) ASA values of both formulations (p = 0.19), and buffered ASA relative bioavailability was 102.49% (= bioequivalence). A significant difference was found between the AUC0-30 min ASA values: 90.5 micrograms. min/ml with buffered and 67.7 micrograms. min/ml with the plain tablet (p less than 0.05). The buffered ASA time of maximum concentration was shorter (28 +/- 8 min) than the plain one (38 +/- 19 min, p less than 0.05). The plasma concentrations and pharmacokinetic parameters of SA were not significantly different after the administration of the two ASA formulations. The plain ASA tablet had a significantly lower (p less than 0.05) dissolution rate than buffered ASA tablet. Moreover, the buffered ASA tablet significantly (p less than 0.01) increased the pH by 0.5 units. In conclusion, the bioavailability of the new oral buffered ASA was equivalent to that of plain ASA, but the plasma concentration peak was reached in a shorter time.

Microfluidic assay of platelet deposition on collagen by perfusion of whole blood from healthy individuals taking aspirin.

PubMed

Li, Ruizhi; Fries, Susanne; Li, Xuanwen; Grosser, Tilo; Diamond, Scott L

2013-08-01

Microfluidic devices can create hemodynamic conditions for platelet assays. We validated an 8-channel device in a study of interdonor response to acetylsalicylic acid (ASA, aspirin) with whole blood from 28 healthy individuals. Platelet deposition was assessed before treatment or 24 h after ingestion of 325 mg ASA. Whole blood (plus 100 μmol/L H-d-Phe-Pro-Arg-chloromethylketone to inhibit thrombin) was further treated ex vivo with ASA (0-500 μmol/L) and perfused over fibrillar collagen for 300 s at a venous wall shear rate (200 s(-1)). Ex vivo ASA addition to blood drawn before aspirin ingestion caused a reduction in platelet deposition [half-maximal inhibitory concentration (IC50) approximately 10-20 μmol/L], especially between 150 and 300 s of perfusion, when secondary aggregation mediated by thromboxane was expected. Twenty-seven of 28 individuals displayed smaller deposits (45% mean reduction; range 10%-90%; P < 0.001) from blood obtained 24 h after ASA ingestion (no ASA added ex vivo). In replicate tests, an R value to score secondary aggregation [deposition rate from 150 to 300 s normalized by rate from 60 to 150 s] showed R < 1 in only 2 of 28 individuals without ASA ingestion, with R > 1 in only 3 of 28 individuals after 500 μmol/L ASA addition ex vivo. At 24 h after ASA ingestion, 21 of 28 individuals displayed poor secondary aggregation (R < 1) without ex vivo ASA addition, whereas the 7 individuals with residual secondary aggregation (R > 1) displayed insensitivity to ex vivo ASA addition. Platelet deposition was not correlated with platelet count. Ex vivo ASA addition caused similar inhibition at venous and arterial wall shear rates. Microfluidic devices quantified platelet deposition after ingestion or ex vivo addition of aspirin.

Study of Pharmacodynamic and Pharmacokinetic Interaction of Bojungikki-Tang with Aspirin in Healthy Subjects and Ischemic Stroke Patients

PubMed Central

Yoo, Jung-Hwa; Yim, Sung-Vin

2018-01-01

Background Bojungikki-tang (BJIKT) is a widely used traditional herbal formula in China, Japan, and Korea. There have been reports that several herbs among BJIKT have interactions with antiplatelet drugs, such as aspirin. This study aimed to assess whether BJIKT interacts with aspirin in terms of pharmacokinetics (PK) and pharmacodynamics (PD) in healthy subjects and ischemic stroke patients. Methods The phase I interaction trial was a randomized, open-label, crossover study of 10 healthy male subjects, and the phase III interaction trial was a randomized, placebo-controlled, parallel study of 43 ischemic stroke patients. Each participant randomly received aspirin + BJIKT or aspirin + placebo. For PK analysis, plasma acetyl salicylic acid (ASA) and salicylic acid (SA) were evaluated, and, for PD analysis, platelet aggregation and plasma thromboxane B2 (TxB2) were measured. Results In the PK parameters, mean area under curve, maximum concertation, and peak concentration time of ASA and SA were not different between two groups in healthy subjects and ischemic stroke patients. In the PD profiles, TxB2 concentrations and platelet aggregation were not affected by coadministration of BJIKT in healthy subjects and ischemic stroke patients. Conclusions These results suggest that coadministration of BJIKT with aspirin may not result in herb-drug interaction. PMID:29599812

Electrochemical behavior of triflusal, aspirin and their metabolites at glassy carbon and boron doped diamond electrodes.

PubMed

Enache, Teodor Adrian; Fatibello-Filho, Orlando; Oliveira-Brett, Ana Maria

2010-08-01

The electrochemical behavior of triflusal (TRF) and aspirin (ASA), before and after hydrolysis in water and in alkaline medium using two different electrode surfaces, glassy carbon and boron doped diamond, was study by differential pulse voltammetry over a wide pH range. The hydrolysis products are 2-(hydroxyl)-4-(trifluoromethyl)-benzoic acid (HTB) for triflusal and salicylic acid (SA) for aspirin, which in vivo represent their main metabolites. The hydrolysis processes were also followed by spectrophotometry. The UV results showed complete hydrolysis after one hour for TRF and after two hours for ASA in alkaline solution. The glassy carbon electrode enables only indirect determination of TRF and ASA through the electrochemical detection of their hydrolysis products HTB and SA, respectively. The oxidation processes of HTB and SA are pH dependent and involve different numbers of electrons and protons. Moreover, the difference between the oxidation peak potential of SA and HTB was equal to 100 mV in the studied pH range from 1 to 8 due to the CF3 of the aromatic ring of HTB molecule. Due to its wider oxidation potential range, the boron doped diamond electrode was used to study the direct oxidation of TRF and ASA, as well as of their respective metabolites HTB and SA.

Assessment of platelet function in acute ischemic stroke patients previously treated with aspirin.

PubMed

Lago, Aida; Parkhutik, Vera; Tembl, Jose Ignacio; Vallés, Juana; Santos, Maria Teresa; Moscardó, Antonio

2014-01-01

Platelet inhibition measured by platelet function tests could be critical to understand the reasons for early recurrence and to guide therapeutic recommendations. We assess the platelet function during the acute phase of ischemic stroke in patients pretreated with aspirin who continue their treatment with aspirin only, are started on clopidogrel only, or add clopidogrel to aspirin. Sixty-four patients were taking aspirin before the stroke. Depending on the administered antiplatelet, 3 groups were defined: ASA: patients who continued on aspirin orally or intravenous acetylsalicylate of lysine, n = 30; CLO: patients who discontinued aspirin and were started on clopidogrel, n = 16; and ASA + CLO: patients who were prescribed both aspirin and clopidogrel, n = 10. Collagen-induced thromboxane A2 (TXA2) synthesis, ADP (adenosine diphosphate)-induced aggregation, and occlusion time (PF-100) were measured. CLO group only had a marked elevation of TXA2 (17.44 ± 15.62 ng/mL, P = .000) and a shortening of the platelet function analyzer (PFA)-100 closure time (157.13 ± 88 seconds, P = .047) compared with the other 2 groups (ASA: TXA2, .62 ± 1.59 ng/mL; ASA + CLO: TXA2 1.79 ± 4.59 ng/mL). They achieved a small (13%) but significant reduction of ADP-induced aggregation (87.00 ± 23.06 mm, P = .008) compared with the ASA group (102.82 ± 22.38 seconds). Stopping aspirin intake within the first 72 hours of the acute stroke drastically increases TXA2 synthesis. During the same time window, the freshly prescribed clopidogrel manages to reduce the ADP-induced aggregation only slightly (13%). This study offers analytic proof that the common practice of replacing aspirin with clopidogrel does not leave stroke patients fully protected during the first days after an ischemic stroke. Possible solutions could be to preserve aspirin during a few days or to use loading doses of clopidogrel at hospital admission. Copyright © 2014 National Stroke Association. Published by Elsevier Inc

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xianwei, E-mail: XWang2@UAMS.edu; Lu, Jingjun; Khaidakov, Magomed

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 cardiacmore » 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

Salicylate pre-treatment attenuates intensity of bronchial and nasal symptoms precipitated by aspirin in aspirin-intolerant patients.

PubMed

Nizankowska, E; Dworski, R; Soja, J; Szczeklik, A

1990-11-01

Aspirin (ASA) and other non-steroidal anti-inflammatory drugs, which are cyclooxygenase (COX) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients. However, salicylate moiety appears to interfere with aspirin inhibitory action on platelets and vascular COX. Such interaction, if present at the level of respiratory tract, may be of interest to pathogenesis of ASA-induced asthma. We performed a double-blind, placebo-controlled, randomized cross-over study on the effect of choline magnesium trisalicylate (CMT, trilisate) pre-treatment on ASA-induced adverse reactions in nine patients. Pulmonary function tests, nasal symptoms score, PNIF and serum salicylate levels were monitored following challenges with threshold doses of ASA. Trilisate administered at a dose of 3000 mg daily for 3 days, offered a moderate protection against ASA-induced symptoms; it diminished the severity and/or delayed the appearance of FEV1 fall. Maximal decreases in FEV1 as well as reaction intensity indexes were significantly lower (P less than 0.02 and P less than 0.002, respectively) after trilisate pre-treatment as compared to placebo. Trilisate also attenuated nasal symptoms in three out of five patients. Although the precise mechanism of the protective action of trilisate is unknown, our data support the possibility of interaction between salicylate and ASA on cyclo-oxygenase locus in the respiratory tract in ASA-intolerant patients.

Chemometrics-assisted Spectrofluorimetric Determination of Two Co-administered Drugs of Major Interaction, Methotrexate and Aspirin, in Human Urine Following Acid-induced Hydrolysis.

PubMed

Maher, Hadir M; Ragab, Marwa A A; El-Kimary, Eman I

2015-01-01

Methotrexate (MTX) is widely used to treat rheumatoid arthritis (RA), mostly along with non-steroidal anti-inflammatory drugs (NSAIDs), the most common of which is aspirin or acetyl salicylic acid (ASA). Since NSAIDs impair MTX clearance and increase its toxicity, it was necessary to develop a simple and reliable method for the monitoring of MTX levels in urine samples, when coadministered with ASA. The method was based on the spectrofluorimetric measurement of the acid-induced hydrolysis product of MTX, 4-amino-4-deoxy-10-methylpteroic acid (AMP), along with the strongly fluorescent salicylic acid (SA), a product of acid-induced hydrolysis of aspirin and its metabolites in urine. The overlapping emission spectra were resolved using the derivative method (D method). In addition, the corresponding derivative emission spectra were convoluted using discrete Fourier functions, 8-points sin xi polynomials, (D/FF method) for better elimination of interferences. Validation of the developed methods was carried out according to the ICH guidelines. Moreover, the data obtained using derivative and convoluted derivative spectra were treated using the non-parametric Theil's method (NP), compared with the least-squares parametric regression method (LSP). The results treated with Theil's method were more accurate and precise compared with LSP since the former is less affected by the outliers. This work offers the potential of both derivative and convolution using discrete Fourier functions in addition to the effectiveness of using the NP regression analysis of data. The high sensitivity obtained by the proposed methods was promising for measuring low concentration levels of the two drugs in urine samples. These methods were efficiently used to measure the drugs in human urine samples following their co-administration.

Quantitative determination of five metabolites of aspirin by UHPLC-MS/MS coupled with enzymatic reaction and its application to evaluate the effects of aspirin dosage on the metabolic profile.

PubMed

Li, Jian-Ping; Guo, Jian-Ming; Shang, Er-Xin; Zhu, Zhen-Hua; Liu, Yang; Zhao, Bu-Chang; Zhao, Jing; Tang, Zhi-Shu; Duan, Jin-Ao

2017-05-10

Acetylsalicylic acid (Aspirin, ASA) is a famous drug for cardiovascular diseases in recent years. Effects of ASA dosage on the metabolic profile have not been fully understood. The purpose of our study is to establish a rapid and reliable method to quantify ASA metabolites in biological matrices, especially for glucuronide metabolites whose standards are not commercially available. Then we applied this method to evaluate the effects of ASA dosage on the metabolic and excretion profile of ASA metabolites in rat urine. Salicylic acid (SA), gentisic acid (GA) and salicyluric acid (SUA) were determined directly by UHPLC-MS/MS, while salicyl phenolic glucuronide (SAPG) and salicyluric acid phenolic glucuronide (SUAPG) were quantified indirectly by measuring the released SA and SUA from SAPG and SUAPG after β-glucuronidase digestion. SUA and SUAPG were the major metabolites of ASA in rat urine 24h after ASA administration, which accounted for 50% (SUA) and 26% (SUAPG). When ASA dosage was increased, the contributions dropped to 32% and 18%, respectively. The excretion of other three metabolites (GA, SA and SAPG) however showed remarkable increases by 16%, 6% and 4%, respectively. In addition, SUA and SUAPG were mainly excreted in the time period of 12-24h, while GA was excreted in the earlier time periods (0-4h and 4-8h). SA was mainly excreted in the time period of 0-4h and 12-24h. And the excretion of SAPG was equally distributed in the four time periods. We went further to show that the excretion of five metabolites in rat urine was delayed when ASA dosage was increased. In conclusion, we have developed a rapid and sensitive method to determine the five ASA metabolites (SA, GA, SUA, SAPG and SUAPG) in rat urine. We showed that ASA dosage could significantly influence the metabolic and excretion profile of ASA metabolites in rat urine. Copyright © 2016 Elsevier B.V. All rights reserved.

Aspirin Allergy Desensitization in Cerebrovascular Disease

PubMed Central

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

2014-01-01

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

Cytokine expression before and after aspirin desensitization therapy in aspirin-exacerbated respiratory disease.

PubMed

Aktas, Ayse; Kurt, Emel; Gulbas, Zafer

2013-12-01

Aspirin exacerbated respiratory disease (AERD) is induced by acetylsalicylic acid (ASA) and/or nonsteroidal antiinflammatory drugs (NSAIDs). Effects of desensitization on many mediators have been examined previously, but few studies addressed the influence of desensitization on T lymphocytes and T lymphocyte-derived cytokines. This study was performed to examine peripheral blood lymphocyte (PBL) cytokine expression in aspirin-sensitive patients who have asthma before and after aspirin desensitization. In this study, the release of interleukin-2 (IL-2), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) by CD4+ T lymphocytes prior to aspirin desensitization were also measured at intracellular levels, and expression of these cytokines after 1 month aspirin desensitization was evaluated. Twelve patients with AERD were included in the study. Two different control groups were formed, one consisted of 15 healthy people and second 12 aspirin tolerant asthmatic (ATA) patients using aspirin. A blood sample was collected prior to desensitization, and the tests were repeated by taking a second blood sample 1 month after the 4-day desensitization treatment. The proportion of lymphocytes secreting IFN-γ in the study group was 15.61 ± 4.40 % before desensitization and 15.08 ± 5.89 % after desensitization. The rate of IFN-γ secreting CD4+ T lymphocytes was 20.51 ± 4.41 % in the normal control group and 16.07 ± 5.7 % in the ATA group (p = 0.021). The ratio of CD4+ T lymphocyte secreting IFN-γ was reduced in patients with AERD before desensitization compared to normal control group (p = 0.040). The levels of IL-2, IL-4, and the subsets of lymphocyte were not different before and after desensitization compared to control groups.

Amino acid derivatives of 5-ASA as novel prodrugs for intestinal drug delivery.

PubMed

Clerici, C; Gentili, G; Boschetti, E; Santucci, C; Aburbeh, A G; Natalini, B; Pellicciari, R; Morelli, A

1994-12-01

In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5-ASA derivatives, namely, (N-L-glutamyl)-amino-2-salicylic acid (1), (N-L-aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-L-proline-L-leucine (3), and 5-(N-L-glutamyl)-aminosalicyl-L-proline-L-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N = 30) and to animals that had undergone prior colostomy (N = 30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, and N-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (> 65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (< 35%) and higher fecal excretion of 5-ASA and its metabolite. The novel glutamate and aspartate derivatives (1 and 2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-L-Glutamyl)-aminosalicyl-L-proline-L-leucine yielded the highest fecal recovery of 5-ASA and its N-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract.

Salicylic acid plasma levels following multiple doses of Norgesic Forte and aspirin.

PubMed

Harrison, L I; Kehe, C R; Goldlust, M B; Kvam, D C; Bianchine, J R

1983-01-01

Plasma salicyclic acid levels from the recommended multiple dose regimen of Norgesic Forte (orphenadrine citrate, aspirin, and caffeine) were compared to those from an equivalent multiple dose regimen of aspirin alone in 24 volunteers. The drugs were administered double-blind so that side effects could also be compared. No statistically significant differences were found between Norgesic Forte and aspirin in peak or trough levels, time to peak level, area under the curve, or mean steady-state level of salicylic acid. Mean steady-state levels averaged 154 +/- 46 (+/- SD) and 152 +/- 49 micrograms/ml on days 5 and 10 following Norgesic Forte versus 161 +/- 49 and 154 +/- 47 micrograms/ml following aspirin. Thus, the aspirin in Norgesic Forte provides an anti-inflammatory amount of salicylic acid equivalent to that of plain aspirin. There was no evidence that the combination of orphenadrine citrate, caffeine, and aspirin in Norgesic Forte caused increased or unusual side effects compared with aspirin alone.

Impact of a Focused Approach for Discharge Teaching Regarding the Use of Aspirin as Anticoagulant After Joint Replacement Surgery.

PubMed

Wittig-Wells, Deborah; Higgins, Melinda; Davis, Erica; Johnson, Ifeya; Louis, Latalya; Mason, Olga; Samms-McPherson, Jacqueline; Sims, Sandra; Jacob, Ani

2015-01-01

Patient education for the use and administration of aspirin (ASA) as an anticoagulant may be deficient. To pilot a knowledge assessment tool regarding the use of aspirin (ASA) as an anticoagulant and to evaluate the impact of a focused approach for discharge teaching. One-group pretest-posttest pilot study. Convenience sample of patients hospitalized for total knee and total hip arthroplasty. Researcher developed ASA quiz. Focused education on aspirin as an anticoagulant. There was a statistically significant improvement in knowledge (Wilcoxon rank sum test Z = 3.880, p < .001).

Acetylsalicylic acid-triggered 15-HETE generation by peripheral leukocytes for identifying ASA sensitivity.

PubMed

Korosec, Peter; Tisler, Ursa; Bajrovic, Nissera; Silar, Mira; Mrhar, Ales; Kosnik, Mitja

2011-10-01

Exposure to acetylsalicylic acid (ASA) may exacerbate respiratory or skin diseases or induce anaphylactoid reactions in apparently healthy individuals. We wanted to evaluate the clinical and diagnostic utility of measuring ASA-induced 15-hydroxyeicosatetraenoic acid (15-HETE) generation. We performed a prospective single-blind study with 26 subjects undergoing clinical evaluation and/or ASA provocation testing. We also included 12 control subjects. Peripheral blood leukocytes were incubated with 500 μM ASA and 15-HETE release was measured by competitive ELISA. We found that 18 subjects were ASA-tolerant and 8 were ASA-intolerant. The mean increase in 15-HETE in intolerant subjects was 34% and this was comparable to the mean increase of 30% observed in ASA-tolerant subjects. A similar mean increase was also observed in control subjects. The ROC calculation showed that the optimal diagnostic threshold would be an increase of greater than 33%. However, the sensitivity of this increase was only 63% and the specificity was 50%. Our data suggest that further studies are needed before the ASA-induced 15-HETE test can be used in clinical practice. Copyright © 2011 Elsevier Ltd. All rights reserved.

High glucose inhibits the aspirin-induced activation of the nitric oxide/cGMP/cGMP-dependent protein kinase pathway and does not affect the aspirin-induced inhibition of thromboxane synthesis in human platelets.

PubMed

Russo, Isabella; Viretto, Michela; Barale, Cristina; Mattiello, Luigi; Doronzo, Gabriella; Pagliarino, Andrea; Cavalot, Franco; Trovati, Mariella; Anfossi, Giovanni

2012-11-01

Since hyperglycemia is involved in the "aspirin resistance" occurring in diabetes, we aimed at evaluating whether high glucose interferes with the aspirin-induced inhibition of thromboxane synthesis and/or activation of the nitric oxide (NO)/cGMP/cGMP-dependent protein kinase (PKG) pathway in platelets. For this purpose, in platelets from 60 healthy volunteers incubated for 60 min with 5-25 mmol/L d-glucose or iso-osmolar mannitol, we evaluated the influence of a 30-min incubation with lysine acetylsalicylate (L-ASA; 1-300 μmol/L) on 1) platelet function under shear stress; 2) aggregation induced by sodium arachidonate or ADP; 3) agonist-induced thromboxane production; and 4) NO production, cGMP synthesis, and PKG-induced vasodilator-stimulated phosphoprotein phosphorylation. Experiments were repeated in the presence of the antioxidant agent amifostine. We observed that platelet exposure to 25 mmol/L d-glucose, but not to iso-osmolar mannitol, 1) reduced the ability of L-ASA to inhibit platelet responses to agonists; 2) did not modify the L-ASA-induced inhibition of thromboxane synthesis; and 3) prevented the L-ASA-induced activation of the NO/cGMP/PKG pathway. Preincubation with amifostine reversed the high-glucose effects. Thus, high glucose acutely reduces the antiaggregating effect of aspirin, does not modify the aspirin-induced inhibition of thromboxane synthesis, and inhibits the aspirin-induced activation of the NO/cGMP/PKG pathway. These results identify a mechanism by which high glucose interferes with the aspirin action.

NOSH-Aspirin Inhibits Colon Cancer Cell Growth: Effects Of Positional Isomerism.

PubMed

Vannini, Federica; Kodela, Ravinder; Chattopadhyay, Mitali; Kashfi, Khosrow

2015-08-01

NOSH-aspirin, a novel hybrid that releases nitric oxide (NO) and hydrogen sulfide (H 2 S) was designed to overcome the potential side effects of aspirin. We compared the cell growth inhibitory properties of ortho-, meta-, and para-NOSH-aspirins. Effects of electron donating/withdrawing groups on the stability and biological activity of these novel compounds were also evaluated. Cell line: HT-29 (Cyclooxygenase, COX-1 & -2 expressing) and HCT 15 (COX null) human colon adenocarcimoa; Cell growth: MTT; Cell cycle phase distribution: Flow cytometry; Apoptosis: subdiploid (sub-G 0 /G 1 ) peak in DNA content histograms; Proliferation: PCNA; ROS: measured hydrogen peroxide and super oxide by flow cytometry using DCFDA and DHE dyes. The IC 50 s for growth inhibition in µM at 24h were, HT-29: ortho-NOSH-ASA (0.04±0.011), meta-NOSH-ASA (0.24±0.11), para-NOSH-ASA (0.46±0.17); significance between the groups were: o vs m P>0.05, o vs p P<0.05, m vs p P>0.05; HCT 15: ortho-NOSH-ASA (0.062±0.006), meta-NOSH-ASA (0.092±0.004), para-NOSH-ASA (0.37±0.04); significance between the groups were: o vs m P<0.01, o vs p P<0.001, m vs p P<0.001. Electron donating/withdrawing groups significantly affected these IC 50 s. All positional isomers qualitatively had similar effects on proliferation, apoptosis, and caused G 0 /G 1 cell cycle arrest in both colon cancer cell lines. The underlying mechanism for these observations appeared to be mediated through ROS, as pretreatment of the cells with N-acetylcysteine, partially blocked these effects. Positional isomerism affects the potency of NOSH-aspirin. The effects appear to be COX independent. Copyright © 2015. Published by Elsevier B.V.

Effects of clopidogrel and aspirin in combination versus aspirin alone on platelet activation and major receptor expression in patients after recent ischemic stroke: for the Plavix Use for Treatment of Stroke (PLUTO-Stroke) trial.

PubMed

Serebruany, Victor L; Malinin, Alex I; Ziai, Wendy; Pokov, Alex N; Bhatt, Deepak L; Alberts, Mark J; Hanley, Dan F

2005-10-01

Clopidogrel is widely used in patients after recent ischemic stroke; however, its ability to yield additional antiplatelet protection on top of aspirin has never been explored in a controlled study. To determine whether clopidogrel with aspirin (C+ASA) will produce more potent platelet inhibition than aspirin alone (ASA) in patients after ischemic stroke, we conducted the Plavix Use for Treatment of Stroke trial. Seventy patients after ischemic stroke were randomly assigned to C+ASA or ASA groups. Platelet studies included aggregometry; cartridge-based analyzers; expression of PECAM-1, P-selectin, GP IIb/IIIa (antigen and activity), vitronectin receptor, and formation of platelet-leukocyte microparticles by flow cytometry. Platelet tests were performed at baseline and after 30 days after randomization. There were no deaths, hospitalizations, or serious adverse events. There were no differences in the baseline platelet characteristics between C+ASA and ASA groups, or significant changes in platelet parameters in the ASA group, except diminished collagen-induced aggregation (P=0.001). In contrast, therapy with C+ASA resulted in a significant inhibition of platelet activity assessed by ADP- (P=0.00001) and collagen-induced (P=0.02) aggregation; closure time prolongation (P=0.03), and reduction of platelet activation units with Ultegra (P=0.00001); expression of PECAM-1 (P=0.01), and GP IIb/IIIa activity with PAC-1 (P=0.02) when compared with ASA group. Therapy with C+ASA also resulted in the reduced formation of platelet-leukocyte microparticles (P=0.02). Treatment with C+ASA for 1 month provides significantly greater inhibition of platelet activity than ASA alone in patients after recent ischemic stroke in the frame of the small randomized trial.

Safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease.

PubMed

McMullan, Kathryn L; Wedner, H James

2013-01-01

Aspirin (ASA) is the drug of choice in patients with coronary artery disease for primary and secondary prevention. This poses a problem for those patients reporting hypersensitivity to this drug or class of drugs. Desensitization to ASA may be carried out safely and effectively in patients with reported ASA or nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity needing ASA for cardiac indications. Our 7-step protocol is one choice for a rapid desensitization protocol. A retrospective chart review was conducted evaluating ASA desensitization in patients with reported ASA or NSAID hypersensitivity and a cardiac indication for ASA. In 160 evaluations over 15 years, 89 desensitizations were performed in both the inpatient and outpatient setting with only 16 reactions (18%). Eleven of these 16 patients (68.7%) were able to take daily ASA. Twenty-six desensitization procedures were performed with our 7-step rapid desensitization protocol in 10 inpatients and 16 outpatients with 3 reactions (18.75% of reactions). Initial reaction to ASA involving angioedema and reacting to ASA within the past year increased the risk of having a reaction to desensitization. Desensitization may be safely performed in patients with reported ASA or NSAID hypersensitivity and a cardiac indication for ASA. Our 7-step rapid protocol may be used in both the inpatient and outpatient setting to desensitize these patients. Patients who had angioedema with ASA ingestion or a reaction to ASA within the past year are at higher risk for reaction during the desensitization protocol. The authors have no funding, financial relationships, or conflicts of interest to disclose. © 2012 Wiley Periodicals, Inc.

Neuroprotective Effect of a New Synthetic Aspirin-decursinol Adduct in Experimental Animal Models of Ischemic Stroke

PubMed Central

Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

2013-01-01

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants. PMID:24073226

Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental animal models of ischemic stroke.

PubMed

Yan, Bing Chun; Park, Joon Ha; Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

2013-01-01

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.

Aspirin Desensitization in Patients With Coronary Artery Disease: Results of the Multicenter ADAPTED Registry (Aspirin Desensitization in Patients With Coronary Artery Disease).

PubMed

Rossini, Roberta; Iorio, Annamaria; Pozzi, Roberto; Bianco, Matteo; Musumeci, Giuseppe; Leonardi, Sergio; Lettieri, Corrado; Bossi, Irene; Colombo, Paola; Rigattieri, Stefano; Dossena, Cinzia; Anzuini, Angelo; Capodanno, Davide; Senni, Michele; Angiolillo, Dominick J

2017-02-01

There are limited data on aspirin (ASA) desensitization for patients with coronary artery disease. The aim of the present study was to assess the safety and efficacy of a standard rapid desensitization protocol in patients with ASA sensitivity undergoing coronary angiography. This is a prospective, multicenter, observational study including 7 Italian centers including patients with a history of ASA sensitivity undergoing coronary angiography with intent to undergo percutaneous coronary intervention. A total of 330 patients with history of ASA sensitivity with known/suspected stable coronary artery disease or presenting with an acute coronary syndrome, including ST-segment-elevation myocardial infarction were enrolled. Adverse effects to aspirin included urticaria (n=177, 53.6%), angioedema (n=69, 20.9%), asthma (n=65, 19.7%), and anaphylactic reaction (n=19, 5.8%). Among patients with urticaria/angioedema, 13 patients (3.9%) had a history of idiopathic chronic urticaria. All patients underwent a rapid ASA (5.5 hours) desensitization procedure. The desensitization procedure was performed before cardiac catheterization in all patients, except for those (n=78, 23.6%) presenting with ST-segment-elevation myocardial infarction who underwent the desensitization after primary percutaneous coronary intervention. Percutaneous coronary intervention was performed in 235 patients (71%) of the overall study population. The desensitization procedure was successful in 315 patients (95.4%) and in all patients with a history of anaphylactic reaction. Among the 15 patients (4.6%) who did not successfully respond to the desensitization protocol, adverse reactions were minor and responded to treatment with corticosteroids and antihistamines. Among patients with successful in-hospital ASA desensitization, 253 patients (80.3%) continued ASA for at least 12 months. Discontinuation of ASA in the 62 patients (19.7%) who had responded to the desensitization protocol was because of medical

Association of gastric acid and mucus secretion level with low-dose aspirin-induced gastropathy.

PubMed

Iijima, Katsunori; Ara, Nobuyuki; Abe, Yasuhiko; Koike, Tomoyuki; Iwai, Wataru; Iwabuchi, Toshimitsu; Ichikawa, Takafumi; Kamata, Yayoi; Ishihara, Kazuhiko; Shimosegawa, Tooru

2012-02-01

Low-dose aspirin is known to cause upper gastrointestinal complications. The mechanism by which the aspirin disrupts gastric mucosal integrity remains to be clarified. In this study we investigated the temporal association of gastric secretory parameters (acid and mucus) with aspirin-induced gastropathy. In 42 long-term low-dose aspirin-takers and the same number of sex- and age-matched controls, pentagastrin-stimulated gastric juice was collected for 10 min during endoscopic examination. The collected gastric juice was divided and half was submitted to analysis for gastric acid (mEq/10 min) and the other half was analyzed for mucin (mg hexose/10 min) output. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score, and a score of more than 4 was defined as the presence of severe gastropathy. While gastric acid secretion did not differ significantly between aspirin-takers and controls, gastric mucus secretion, in terms of mucin output, was significantly increased in aspirin-takers compared to controls (4.1 (SD 4.8) vs. 2.3 (1.4) mg hexose/10 min, P < 0.05). Consequently, the acid/mucin ratio was significantly decreased in aspirin-takers compared to controls (1.2 (1.0) vs. 1.7 (1.4), P < 0.05). In the subanalysis of 25 aspirin-takers without severe gastropathy, gastric mucus secretion was increased and the acid/mucus ratio was decreased compared with controls, but there was no such association in the remaining 17 aspirin-takers with severe gastropathy. Overall, gastric mucus secretion is increased in aspirin-takers, suggesting a functional adaptive response to long-term administration of the drug. However, it is possible that the adaptive response is impaired in some aspirin takers, who might be susceptible to severe upper gastrointestinal complication.

Replacing the acetyl linkage in aspirin with choline and magnesium moieties reduces the occurrence of gastric mucosal injury.

PubMed

Danesh, B J; Nelson, L M; Russell, R I; Docherty, C

1987-02-01

The acetyl moiety in aspirin (acetyl salicylic acid: ASA) is considered to play a major part in the pathogenesis of ASA-induced mucosal injury. At equivalent salicylate doses and pH values, the induction of acute gastric mucosal haemorrhagic erosions in rats by ASA and choline magnesium trisalicylate (CMT), a new non-acetylated salicylate, with and without the potentiating damaging effect of taurodeoxycholic acid (TDCA) were compared. Test solutions were administered by per oral intubation to five groups of fasting Sprague-Dawley rats (n = 24). Gastric mucosa were examined after 4 hours and mucosal injury assessed by a lesion-scoring system. The incidence and severity (median lesion scores with quartiles) of the lesions were 83% and 13 (7:20) respectively for ASA (128 mg kg-1) compared with 17% and 0 (0:0) for CMT (128 mg kg-1) (P less than 0.001 and P less than 0.001). TDCA increased mucosal damage to 100% and 29 (20:34) for ASA compared with 30% and 0 (0:4) for CMT (P less than 0.001) and P less than 0.001). Serum salicylate levels (median values of 1.4 for ASA and 1.5 mmol litre-1 for CMT) were not significantly different. It is concluded that replacing the acetyl moiety in ASA with choline and magnesium moieties reduces the ASA-induced mucosal injury, without affecting blood salicylate concentrations.

Aspirin resistance in patients with hemodynamic cerebral ischemia undergoing extracranial-intracranial bypass surgery.

PubMed

Jussen, Daniel; Horn, Peter; Vajkoczy, Peter

2013-01-01

Aspirin (acetylsalicylic acid, ASA) is the treatment of choice for prevention of vascular events in symptomatic steno-occlusive cerebrovascular disease (CVD). Cerebral revascularization using standard extracranial-intracranial (EC-IC) bypass surgery may be used to revert hemodynamic compromise. Aspirin is prescribed as standard medication in order to avoid bypass failure. Accumulating evidence of an increased risk of major adverse clinical events led to this study, in which we aimed to assess the prevalence of aspirin resistance and prothrombotic disorders among patients scheduled for EC-IC bypass surgery, and the effectiveness of aspirin dose escalation. We prospectively screened patients with circumscribed high-grade stenosis or occlusion of brain-supplying vessels fulfilling the hemodynamic criteria for EC-IC bypass surgery for aspirin resistance using a platelet function analyzer (PFA-100®) test. We also determined their smoking habits and screened for prothrombotic disorders and comorbidities. The patients were divided into 2 major groups: group A had atherosclerotic steno-occlusive CVD and group B consisted of patients with nonatherosclerotic steno-occlusive CVD (moyamoya disease) and a subgroup of pediatric moyamoya patients (pediatric subgroup). Bypass patency was documented via digital subtraction angiography. Standard initial ASA dose applied was 100 mg/day. In cases of aspirin resistance, doses were increased and the PFA-100 test was repeated. A total of 56 patients were included over a time period of 6 months. In group A (n = 25), we found a ratio of 40% of patients with primary resistance to aspirin 100 mg/day. In contrast, in group B (n = 25), only 20% of the patients were resistant to aspirin 100 mg/day; in the pediatric population (n = 6), there was no primary aspirin resistance. After a dose escalation to 300 mg/day, the ratio of aspirin resistance was reduced to 20% in group A and to 0% in group B. Altogether 5 patients with atherosclerotic steno

Aspirin upregulates αB-Crystallin to protect the myocardium against heat stress in broiler chickens

PubMed Central

Tang, Shu; Yin, Bin; Song, Erbao; Chen, Hongbo; Cheng, Yanfen; Zhang, Xiaohui; Bao, Endong; Hartung, Joerg

2016-01-01

We established in vivo and in vitro models to investigate the role of αB-Crystallin (CryAB) and assess the ability of aspirin (ASA) to protect the myocardium during prolonged heat stress. Thirty-day-old chickens were divided into three groups (n = 90): heat stress (HS, 40±1 °C); ASA(−)HS(+), 1 mg/kg ASA orally 2 h before heat stress; and ASA(+)HS(−), pretreated with aspirin, no heat stress (25 °C). Hearts were excised after 0, 1, 2, 3, 5, 7, 10, 15 and 24 h. Heat stress increased body temperature, though the ASA(−)HS(+) group had significantly higher temperatures than the ASA(+)HS(+) group at all time points. Compared to ASA(+)HS(+), the ASA(−)HS(+) group displayed increased sensitivity to heat stress. Pathological analysis revealed the ASA (+)HS(+) myocardium showed less severe changes (narrowed, chaotic fibers; fewer necrotic cells) than the ASA(−)HS(+) group (bleeding and extensive cell death). In vitro, ASA-pretreatment significantly increased primary chicken myocardial cell survival during heat stress. ELISAs indicated ASA induced CryAB in vivo to protect against heat stress-induced myocardial damage, but ASA did not induce CryAB in primary chicken myocardial cells. The mechanisms by which ASA induces the expression of CryAB in vivo and protects the myocardium during heat stress merit further research. PMID:27857180

Relationship between high on aspirin platelet reactivity and oxidative stress in coronary artery by-pass grafted patients.

PubMed

Kuliczkowski, Wiktor; Golanski, Ryszard; Bijak, Michal; Boryczka, Katarzyna; Kaczmarski, Jacek; Watala, Cezary; Golanski, Jacek

2016-03-01

The aim of the study was to assess the responsiveness of blood platelets to acetylsalicylic acid (ASA) in patients following coronary artery bypass grafting (CABG) surgery with relation to oxidative and antioxidative plasma status. The study included 37 patients treated with the CABG procedure. During the first 24 h after CABG patients were given 300 mg of ASA with the following dose of 150 mg daily. The blood was collected before the procedure and 10 days after. Whole blood platelet aggregation induced with arachidonic acid, collagen and adenosine diphosphate (ADP) was performed together with whole blood generation of thromboxane B2 (TxB2). Oxidative stress was measured before and 10 days after CABG with total oxidative plasma status (TOS) and total antioxidative status of the plasma (TAS). TOS/TAS index was calculated. We observed a significant increase in the TOS and TOS/TAS index and ADP-induced aggregation 10 days after CABG in comparison with its level before operation. There was a significant decrease in the arachidonic acid-induced aggregation and serum TxB2 level. Patients with ADP-induced and collagen-induced aggregation in the upper quartile had significantly higher TOS and TOS/TAS index before (ADP) and after the operation (ADP and collagen). There were 19 patients (51%) with high on aspirin platelet reactivity after CABG who had also higher TOS and TOS/TAS index and lower TAS value in comparison with aspirin responders. Despite ASA use, increased oxidative stress after CABG can overcome its antiplatelet effect and increase platelet activation through other pathways.

Aspirin may promote mitochondrial biogenesis via the production of hydrogen peroxide and the induction of Sirtuin1/PGC-1α genes

PubMed Central

Kamble, Pratibha; Selvarajan, Krithika; Narasimhulu, Chandrakala Aluganti; Nandave, Mukesh; Parthasarathy, Sampath

2013-01-01

Based on the rapid hydrolysis of acetyl salicylic acid (ASA, Aspirin) to salicylic acid (SA), the ability of SA to form dihydroxy benzoic acid (DBA), and the latter’s redox reactions to yield hydrogen peroxide (H2O2), we predicted that ASA may have the potential to induce Sirtuin1 (Sirt1) and its downstream effects. We observed that treatment of cultured liver cells with ASA resulted in the induction of Sirt1, peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α), and NAD(P)H quinone oxidoreductase 1 (Nqo1) genes. Paraoxonase 1 (PON1) and Aryl hydrocarbon receptor (AhR) siRNA transfections inhibited the induction of gene expressions by ASA suggesting the need for the acetyl ester hydrolysis and hydroxylation to DHBA. The latter also induced Sirt1, confirming the proposed pathway. As predicted, ASA and SA treatment resulted in the production of H2O2, a known inducer of Sirt1 and confirmed in the current studies. More importantly, ASA treatment resulted in an increase in mitochondria as seen by tracking dyes. We suggest that DHBA, generated from ASA, via its oxidation/reduction reactions mediated by Nqo1 might be involved in the production of O2-. and H2O2. As Sirt1 and PGC-1α profoundly affect mitochondrial metabolism and energy utilization, ASA may have therapeutic potential beyond its ability to inhibit cyclooxygenases. PMID:23228932

Efficacy and safety of apixaban compared with aspirin in the elderly: a subgroup analysis from the AVERROES trial.

PubMed

Ng, Kuan H; Shestakovska, Olga; Connolly, Stuart J; Eikelboom, John W; Avezum, Alvaro; Diaz, Rafael; Lanas, Fernando; Yusuf, Salim; Hart, Robert G

2016-01-01

increasing age is associated with a higher prevalence of atrial fibrillation (AF), and higher risks of stroke and bleeding. We report the effects of apixaban versus acetylsalicylic acid (ASA) in older patients (≥75 years and ≥85 years) compared with younger patients with AF unsuitable for vitamin K antagonists. AVERROES (Apixaban Versus ASA to Prevent Stroke In AF Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) trial (n = 5,599) included 1,898 patients ≥75 years and 366 patients ≥85 years. We compared the baseline characteristics and effects of apixaban compared with aspirin on clinical outcomes by age. compared with aspirin, apixaban was more efficacious for preventing strokes and systemic embolism in patients ≥85 years (absolute rate [AR] 1%/year on apixaban versus 7.5%/year on aspirin; hazard ratio [HR] 0.14, 95% confidence interval [CI] 0.02-0.48) compared with younger patients (AR 1.7%/year on apixaban versus 3.4%/year on aspirin; HR 0.50, 95% CI 0.35-0.69) (P-value for interaction = 0.05). Major haemorrhage was higher in patients ≥85 years compared with younger patients but similar with apixaban versus aspirin in both young and older individuals (4.9%/year versus 1.0%/year on aspirin and 4.7%/year versus 1.2%/year on apixaban) with no significant treatment-by-age interaction (P-value = 0.65). older patients with AF are at particularly high risk of stroke if given aspirin and have substantially greater relative and absolute benefits from apixaban compared with younger patients with no greater risk of haemorrhage. ClinicalTrials.gov number: NCT00496769. URL: https://clinicaltrials.gov/ct2/show/NCT00496769. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Release of 5-Aminosalicylic Acid (5-ASA) from Mesalamine Formulations at Various pH Levels.

PubMed

Abinusawa, Adeyinka; Tenjarla, Srini

2015-05-01

Oral formulations of 5-aminosalicylic acid (5-ASA) for treatment of ulcerative colitis have been developed to minimize absorption prior to the drug reaching the colon. In this study, we investigate the release of 5-ASA from available oral mesalamine formulations in physiologically relevant pH conditions. Release of 5-ASA from 6 mesalamine formulations (APRISO®, Salix Pharmaceuticals, Inc., USA; ASACOL® MR, Procter & Gamble Pharmaceuticals UK Ltd.; ASACOL® HD, Procter & Gamble Pharmaceuticals, USA; MEZAVANT XL®, Shire US Inc.; PENTASA®, Ferring Pharmaceuticals, Ltd., UK; SALOFALK®, Dr. Falk Pharma UK Ltd.) was evaluated using United States Pharmacopeia apparatus I and II at pH values of 1.0 (2 h), 6.0 (1 h), and 6.8 (8 h). Dissolution profiles were determined for each formulation, respectively. Of the tested formulations, only the PENTASA formulation demonstrated release of 5-ASA at pH 1.0 (48%), with 56% cumulative release after exposure to pH 6.0 and 92% 5-ASA release after 6-8 h at pH 6.8. No other mesalamine formulation showed >1% drug release at pH 1.0. The APRISO formulation revealed 36% 5-ASA release at pH 6.0, with 100% release after 3 h at pH 6.8. The SALOFALK formulation revealed 11% 5-ASA release at pH 6.0, with 100% release after 1 h at pH 6.8. No 5-ASA was released by the ASACOL MR, ASACOL HD, and MEZAVANT XL formulations at pH 6.0. At pH 6.8, the ASACOL MR and ASACOL HD formulations exhibited complete release of 5-ASA after 4 and 2 h, respectively, and the MEZAVANT XL formulation demonstrated complete 5-ASA release over 6-7 h. 5-Aminosalicylic acid release profiles were variable among various commercially available formulations. Shire Development LLC.

Aromatic Hydroxylation of Salicylic Acid and Aspirin by Human Cytochromes P450

PubMed Central

Bojić, Mirza; Sedgeman, Carl A.; Nagy, Leslie D.; Guengerich, F. Peter

2015-01-01

Aspirin (acetylsalicylic acid) is a well-known and widely-used analgesic. It is rapidly deacetylated to salicylic acid, which forms two hippuric acids—salicyluric acid and gentisuric acid—and two glucuronides. The oxidation of aspirin and salicylic acid has been reported with human liver microsomes, but data on individual cytochromes P450 involved in oxidation is lacking. In this study we monitored oxidation of these compounds by human liver microsomes and cytochrome P450 (P450) using UPLC with fluorescence detection. Microsomal oxidation of salicylic acid was much faster than aspirin. The two oxidation products were 2,5-dihydroxybenzoic acid (gentisic acid, documented by its UV and mass spectrum) and 2,3-dihydroxybenzoic acid. Formation of neither product was inhibited by desferrioxamine, suggesting a lack of contribution of oxygen radicals under these conditions. Although more liphophilic, aspirin was oxidized less efficiently, primarily to the 2,5-dihydroxy product. Recombinant human P450s 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 all catalyzed the 5-hydroxylation of salicylic acid. Inhibitor studies with human liver microsomes indicated that all six of the previously mentioned P450s could contribute to both the 5- and 3-hydroxylation of salicylic acid and that P450s 2A6 and 2B6 have contributions to 5-hydroxylation. Inhibitor studies indicated that the major human P450 involved in both 3- and 5-hydroxylation of salicylic acid is P450 2E1. PMID:25840124

Monitoring ASA and P2Y12-specific platelet inhibition--comparison of conventional (single) and multiple electrode aggregometry.

PubMed

Krüger, Jan-Christopher; Meves, Saskia H; Kara, Kaffer; Mügge, Andreas; Neubauer, Horst

2014-10-01

Several platelet function test systems exist for the evaluation of the platelet inhibitory effect in patients on P2Y12 inhibitors and/or acetylsalicylic acid (ASA, aspirin) therapy. Studies comparing different available assays found only a poor correlation. The objective of the present study was to evaluate the correlation and agreement between single electrode (SEA) and multiple electrode (MEA) aggregometry. In whole blood arachidonic acid (AA) and adenosine diphosphate (ADP)-induced platelet aggregation was measured simultaneously using SEA (Chrono-Log) and MEA (Multiplate). We analyzed a total of 226 measurements taken from 58 patients on single ASA therapy or dual antiplatelet therapy with ASA and a thienopyridine. A cut-off value for clopidogrel/prasugrel high on-treatment platelet reactivity (HPR) of > 47 units (U) was chosen for MEA testing using hirudin and > 5 Ohm for SEA with citrate anticoagulated blood samples. The respective cut-off values for ASA HPR were > 30 U for the MEA assay and > 1 Ohm for SEA testing. There was a good correlation of the prevalence of thienopyridine-HPR in both whole blood assays (Spearman rank correlation coefficient r = 0.698) and a good inter-rate accordance (Cohen's Kappa statistic κ = 0.648). For AA-induced aggregation, the correlation of the results obtained was significant (r = 0.536; p < 0.001) and detecting ASA-HPR revealed a moderate (κ = 0.482) correlation between both impedance aggregometry assays. Platelet function testing using SEA and MEA provided both good accordance and correlation and therefore study results obtained by these two assays similarly enabled the detection of HPR of thienopyridine (and ASA) therapy.

Clinical evidence for use of acetyl salicylic acid in control of flushing related to nicotinic acid treatment.

PubMed

Oberwittler, H; Baccara-Dinet, M

2006-06-01

Nicotinic acid (NA) is highly effective and widely used in the management of dyslipidaemia. For many patients, the side effect of flushing of the face and upper body leads to discontinuation. Flushing with NA is mediated by prostaglandins, and as acetyl salicylic acid (ASA, 'aspirin') is a highly effective inhibitor of prostaglandin synthesis, there is a rationale for its use to prevent or reduce the severity of NA-related flushing. This literature survey identified four studies specifically exploring the utility of ASA in preventing NA-related flushing in healthy volunteers. Twenty-three NA studies, where ASA was mandatory or optional within the protocol, and four studies, where background ASA therapy was reported in most participants, were also identified. Although the incidence of flushing in studies using ASA was often high, discontinuation rates due to flushing were low (mean 7.7%). This figure compares favourably with discontinuation rates with NA commonly reported in the literature (up to approximately 40%). There is good supportive evidence for the use of ASA in reducing the severity of NA-related flushing.

Dual antiplatelet therapy versus aspirin alone in patients undergoing transcatheter aortic valve implantation.

PubMed

Ussia, Gian Paolo; Scarabelli, Marilena; Mulè, Massimiliano; Barbanti, Marco; Sarkar, Kunal; Cammalleri, Valeria; Immè, Sebastiano; Aruta, Patrizia; Pistritto, Anna Maria; Gulino, Simona; Deste, Wanda; Capodanno, Davide; Tamburino, Corrado

2011-12-15

Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely accepted strategy in patients undergoing transcatheter aortic valve implantation (TAVI), but this approach is not evidence based. The goal of the present study was to determine whether DAPT in patients undergoing TAVI is associated with improved outcomes compared to aspirin alone. From May 2009 to August 2010, consecutive patients were randomized to receive a 300-mg loading dose of clopidogrel on the day before TAVI followed by a 3-month maintenance daily dose of 75 mg plus aspirin 100 mg lifelong (DAPT group) or aspirin 100 mg alone (ASA group). The primary end point was the composite of major adverse cardiac and cerebrovascular events, defined as death from any cause, myocardial infarction, major stroke, urgent or emergency conversion to surgery, or life-threatening bleeding. The cumulative incidence of major adverse cardiac and cerebrovascular events at 30 days and 6 months was 14% and 16%, respectively. No significant differences between the DAPT and ASA groups were noted at both 30 days (13% vs 15%, p = 0.71) and 6 months (18% vs 15%; p = 0.85). In conclusion, the strategy of adding clopidogrel to aspirin for 3 months after TAVI was not found to be superior to aspirin alone. These results must be confirmed in a larger randomized trial. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparative gastrointestinal blood loss associated with placebo, aspirin, and nabumetone as assessed by radiochromium (/sup 51/Cr)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lussier, A.; Davis, A.; Lussier, Y.

Nabumetone differs from most other nonsteroidal anti-inflammatory drugs. It is presented to the gut as a nonacidic prodrug, and is metabolized to its active form after absorption. Studies in animals and humans suggest it is less irritating to the gastrointestinal mucosa. This study compared the gastrointestinal microbleeding induced by nabumetone to aspirin (acetylsalicylic acid, ASA), and placebo in a double blind parallel study using chromium /sup 51/Cr labelled red cells to quantitate fecal blood loss (FBL) in healthy volunteers. Thirty subjects were randomized to treatment with nabumetone (2000 mg), ASA (3.6 g) or placebo for 21 days following a 7more » day placebo period. Six subjects served as untreated controls. FBL in nabumetone treated subjects was not significantly different to placebo or untreated subjects. In contrast, ASA-treated subjects exhibited significantly increased FBL than the other 3 groups (P less than .0001).« less

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

PubMed Central

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

2017-01-01

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

In vitro metabolism of nitric oxide-donating aspirin: the effect of positional isomerism.

PubMed

Gao, Jianjun; Kashfi, Khosrow; Rigas, Basil

2005-03-01

NO-donating aspirin (NO-ASA) is a potentially important chemopreventive agent against cancer. Since positional isomerism affects strongly its potency in inhibiting colon cancer cell growth, we studied the metabolic transformations of its ortho-, meta-, and para-isomers in rat liver and colon cytosolic, microsomal, and mitochondrial fractions as well as in intact HT-29 human colon cancer cells. NO-ASA and metabolites were determined by high-performance liquid chromatography and products identified by mass spectroscopy, as required. For all three isomers, the acetyl group on the ASA moiety was hydrolyzed rapidly. This was followed by hydrolysis of the ester bond linking the salicylate anion to the spacer. The ortho- and para-isomers produced salicylic acid and a putative intermediate consisting of the remainder of the molecule, which via a rapid step generated nitrate, (hydroxymethyl)phenol, and a conjugate of spacer with glutathione. The meta-isomer, in contrast, generated salicylic acid and (nitroxymethyl)phenol, the latter leading to (hydroxymethyl)phenol and the glutathione-spacer conjugate. This metabolic pathway takes place in its entirety only in the cytosolic fraction of the tissues tested and in intact human colon cancer cells, perhaps reflecting exposure to the cytosolic glutathione S-transferase, which catalyzes the formation of the spacer-glutathione conjugate. Thus, the three positional isomers of NO-ASA differ in their metabolism and these differences correlate with their differential effects on cancer cell growth, underscoring the importance of positional isomerism in modulating drug effects.

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

PubMed

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

2002-05-01

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

3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets.

PubMed

Goyanes, Alvaro; Buanz, Asma B M; Hatton, Grace B; Gaisford, Simon; Basit, Abdul W

2015-01-01

The aim of this study was to explore the potential of fused-deposition 3-dimensional printing (FDM 3DP) to produce modified-release drug loaded tablets. Two aminosalicylate isomers used in the treatment of inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA, mesalazine) and 4-aminosalicylic acid (4-ASA), were selected as model drugs. Commercially produced polyvinyl alcohol (PVA) filaments were loaded with the drugs in an ethanolic drug solution. A final drug-loading of 0.06% w/w and 0.25% w/w was achieved for the 5-ASA and 4-ASA strands, respectively. 10.5mm diameter tablets of both PVA/4-ASA and PVA/5-ASA were subsequently printed using an FDM 3D printer, and varying the weight and densities of the printed tablets was achieved by selecting the infill percentage in the printer software. The tablets were mechanically strong, and the FDM 3D printing was shown to be an effective process for the manufacture of the drug, 5-ASA. Significant thermal degradation of the active 4-ASA (50%) occurred during printing, however, indicating that the method may not be appropriate for drugs when printing at high temperatures exceeding those of the degradation point. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of the formulated blends confirmed these findings while highlighting the potential of thermal analytical techniques to anticipate drug degradation issues in the 3D printing process. The results of the dissolution tests conducted in modified Hank's bicarbonate buffer showed that release profiles for both drugs were dependent on both the drug itself and on the infill percentage of the tablet. Our work here demonstrates the potential role of FDM 3DP as an efficient and low-cost alternative method of manufacturing individually tailored oral drug dosage, and also for production of modified-release formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

[High doses of aspirin reduce natriuresis in hypertensive patients treated with enalapril].

PubMed

Di Gennaro, Federico P; Cingolani, Oscar H; Abbate, Alejandro F; Toblli, Jorge E; Vilches, Antonio

2004-01-01

Angiotensin converting enzyme inhibitors have been shown to be useful in the treatment of essential hypertension while anti-platelet agents improve the overall cardiovascular risk profile in this population. Our aim was to assess the interaction of two different aspirin (ASA) doses--81 and 325 mg/day--with the antihypertensive effect of enalapril as well as their impact upon the urinary sodium excretion (Na(u)). A total of 22 patients between 35 and 65 years of age were included in a prospective double blind trial with a partial cross-over design. We excluded patients with secondary hypertension and recent use of anti-inflammatory drugs. Patients were placed on enalapril and a low sodium diet--<6 g of NaCl/day--and, sequentially, on two different doses of aspirin separated by a 10 day wash out period. Blood pressure (BP) was measured at weekly visits. Systolic, diastolic and mean BP levels decreased significantly in enalapril-treated patients (p<0.01) and no difference was detected between the two AAS dosages although a non-statistically significant difference towards better BP control was observed when 81 mg of ASA was used. Na(u) was higher at baseline when compared with the two periods under ASA (p<0.01) and Na(u) was higher with 81 mg than with 325 mg. These results suggest that in essential hypertensive individuals treated with enalapril and two ASA doses, low doses of ASA are associated with better blood pressure control and higher natriuresis.

Inhibitory activity of aspirin on von Willebrand factor-induced platelet aggregation.

PubMed

Homoncik, M; Jilma, B; Eichelberger, B; Panzer, S

2000-09-01

The effect of aspirin (ASA) on vWF induced platelet - platelet interaction is unknown. We therefore tested the response of platelets to von Willebrand factor (vWF) coated beads induced platelet aggregation before and after i.v. and oral ASA. 1000 mg ASA was infused to 10 healthy individuals and after a wash-out period 7 volunteers received 100 mg ASA orally over a period of 11 days. Prior to ASA and in regular intervals thereafter we tested the reactivity to vWF-coated beads to assess platelet adhesion/aggregation and the fade-out time of ASA effects on platelets. Considerable interindividual variability in response to vWF-coated beads was observed, both before ASA and after treatment with ASA. The maximal response to vWF-coated beads (Tmax), the time lag, and the slope of the curve were significantly affected by i.v. ASA, whereas 100 mg of ASA had only inconstant effect on Tmax and slope. The absolute reduction of Tmax after ASA depended on the pre-ASA level, while the percentage of the reduction was similar in all individuals. Thus, platelet aggregation induced by vWF-coated beads is impaired by ASA. Furthermore, our data indicate a large interindividual variability of the response to ASA shortly after treatment induction, which becomes more constant after prolonged treatment.

Vorapaxar and optimal aspirin dose: The FDA outlook.

PubMed

Serebruany, Victor L; Fortmann, Seth D; Kim, Moo Hyun

2016-01-15

Vorapaxar, a novel thrombin PAR-1 inhibitor, approved for post-myocardial infarction, and peripheral artery disease indications has been tested in 2 major clinical trials. In the successful TRA2P, antecedent aspirin (ASA) has been used in 94% of patients, and in failed TRACER in over 96% of patients. However, both trial publications were silent on the impact of ASA dose on clinical outcomes after voraparax. We determined which ASA dose range should be used in combination with voraparax based on the TRA2P and TRACER secondary FDA review. The data suggest that for both voraparax trials, younger patients, males, and diabetics received higher ASA doses. The interactions between voraparax efficacy and ASA dose ≥ 300 mg was marginally significant by Cox regressions for TRA2P (CI=1.00-1.61; p=0.048) and strongly trended in TRACER (CI=0.98-1.47; p=0.073). Bleeding rates were overall slightly higher with voraparax than with placebo, and were the highest in patients receiving ASA dosages ≥ 300 mg. However, there were no interactions between ASA dose and GUSTO moderate/severe bleeding. In conclusion, the efficacy of voraparax in TRA2P and TRACER, was slightly worse while bleeding was substantially worse with the higher over 300 mg/day of ASA dosages. Voraparax label should recommend ASA daily use in 75 to 100mg range for concomitant use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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.

Experiments with Aspirin.

ERIC Educational Resources Information Center

Borer, Londa L.; Barry, Edward

2000-01-01

Presents a series of experiments that can be used to demonstrate how aspirin can be synthesized and characterized, how the hydrolysis of aspirin can be used as an introduction to kinetics, and how coordination chemistry (chelation) can be introduced by preparing and characterizing the copper complexes of aspirin and salicylic acid. (Contains over…

Orally administered phosphatidic acids and lysophosphatidic acids ameliorate aspirin-induced stomach mucosal injury in mice.

PubMed

Tanaka, Tamotsu; Morito, Katsuya; Kinoshita, Masafumi; Ohmoto, Mayumi; Urikura, Mai; Satouchi, Kiyoshi; Tokumura, Akira

2013-04-01

Recent investigations revealed that lysophosphatidic acid (LPA), a phospholipid with a growth factor-like activity, plays an important role in the integrity of the gastrointestinal tract epithelium. This paper attempts to clarify the effect of orally administered phosphatidic acid (PA) and LPA on aspirin-induced gastric lesions in mice. Phospholipids, a free fatty acid, a diacylglycerol and a triglyceride at 1 mM (5.7 μmol/kg body weight) or 0.1 mM were orally administered to mice 0.5 h before oral administration of aspirin (1.7 mmol/kg). The total length of lesions formed on the stomach wall was measured as a lesion index. Formation of LPA from PA in the mouse stomach was examined by in vitro (in stomach lavage fluid), ex vivo (in an isolated stomach) and in vivo (in the stomach of a living mouse) examinations of phospholipase activity. Palmitic acid, dioleoyl-glycerol, olive oil and lysophosphatidylcholine did not affect the aspirin-induced lesions. In contrast, phosphatidylcholine (1 mM), LPA (1 mM) and PA (0.1, 1 mM) significantly reduced the lesion index. Evidence for formation of LPA from PA in the stomach by gastric phospholipase A2 was obtained by in vitro, ex vivo and in vivo experiments. An LPA-specific receptor, LPA2, was found to be localized on the gastric surface-lining cells of mice. Pretreatment with PA-rich diets may prevent nonsteroidal anti-inflammatory drug-induced stomach ulcers.

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

NASA Astrophysics Data System (ADS)

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yang; Tyagi, M.; Mamontov, Eugene

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 structuralmore » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xiaofei; Zhu, Yanshuang; He, Huabin

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 MTTmore » 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.« less

Comparison of effects of calcium carbasalate and aspirin on gastroduodenal mucosal damage in human volunteers.

PubMed Central

Murray, F E; Hudson, N; Atherton, J C; Cole, A T; Scheck, F; Hawkey, C J

1996-01-01

Calcium carbasalate is a therapeutically active salicylate which seems to cause less gastroduodenal mucosal damage than aspirin in laboratory animals. This endoscopist-blinded, randomised, cross over trial aimed to compare acute gastric mucosal damage in 20 healthy volunteers treated with acetyl salicylic acid (ASA) (650 mg three times daily) and effervescent calcium carbasalate (ECC) (826.8 mg three times daily) bioequivalent to 650 mg ASA over a five day period. Endoscopy was performed immediately before treatment and on day 5 of each treatment. Serum salicylate, thromboxane B2, and gastric mucosal prostaglandin E2 (PGE2) concentrations were measured after endoscopy. ECC caused fewer gastric mucosal erosions than ASA. The total number of gastric erosions was 23.8 (16.1) in the ASA treated subjects compared with 9.1 (8.7) in ECC treated subjects (p = 0.004). Differences between ASA and ECC were significant for both the gastric antrum and body, and for both haemorrhagic and non-haemorrhagic erosions. The mean gastric body Lanza score for mucosal damage was lower after ECC than ASA (p = 0.003). The visual analogue score for gastric body damage was lower for ECC (16.9 mm (15.9)) than for ASA (32.7 mm (20.8)), p = 0.008. Serum salicylate concentrations were similar after both preparations (ASA: 66 (23) mg/l, versus ECC: 58 (17) mg/l, NS). Serum thromboxane B2 was similarly reduced using both preparations-97.2 (3.5)% inhibition with ASA, 95.2 (5.5)% inhibition with calcium carbasalate (NS). Suppression of gastric mucosal PGE2 synthesis was similar with both preparations (ASA: 83.4 (17.1)%; ECC 84.3 (12.9)%; NS). It is concluded that ECC causes significantly less gastroduodenal mucosal damage than ASA administered at bioequivalent doses as judged by serum salicylate, serum thromboxane, and mucosal PGE2 values. ECC may therefore be a less harmful alternative treatment to plain ASA. PMID:8566836

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke.

PubMed

Sacco, Ralph L; Diener, Hans-Christoph; Yusuf, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; Vandermaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2008-09-18

Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.) 2008 Massachusetts Medical Society

In Vitro Interactions between Aspirin and Amphotericin B against Planktonic Cells and Biofilm Cells of Candida albicans and C. parapsilosis

PubMed Central

Zhou, Yabin; Wang, Ganggang; Li, Yutang; Liu, Yang; Song, Yu; Zheng, Wenshuai; Zhang, Ning; Hu, Xiaoyan; Yan, Shikun

2012-01-01

The increase in drug resistance and invasion caused by biofilm formation brings enormous challenges to the management of Candida infection. Aspirin's antibiofilm activity in vitro was discovered recently. The spectrophotometric method and the XTT {2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide} reduction assay used for data generation make it possible to evaluate fungal biofilm growth accurately. The combined use of the most commonly used methods, the fractional inhibitory concentration index (FICI) and a newly developed method, the ΔE model, which uses the concentration-effect relationship over the whole concentration range instead of using the MIC index alone, makes the interpretation of results more reliable. As an attractive tool for studying the pharmacodynamics of antimicrobial agents, time-kill curves can provide detailed information about antimicrobial efficacy as a function of both time and concentration. In the present study, in vitro interactions between aspirin (acetylsalicylic acid [ASA]) and amphotericin B (AMB) against planktonic cells and biofilm cells of Candida albicans and C. parapsilosis were evaluated by the checkerboard microdilution method and the time-kill test. Synergistic and indifferent effects were found for the combination of ASA and AMB against planktonic cells, while strong synergy was found against biofilm cells analyzed by FICI. The ΔE model gave more consistent results with FICI. The positive interactions in concentration were also confirmed by the time-kill test. Moreover, this approach also revealed the pharmacodynamics changes of ASA and synergistic action on time. Our findings suggest a potential clinical use for combination therapy with ASA and AMB to augment activity against biofilm-associated infections. PMID:22391539

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

PubMed

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

2014-08-01

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. 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. 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. 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. © 2014 The British Pharmacological Society.

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

PubMed Central

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

Pharmacokinetics and metabolic rates of acetyl salicylic acid and its metabolites in an Otomi ethnic group of Mexico.

PubMed

Lares-Asseff, Ismael; Juárez-Olguín, Hugo; Flores-Pérez, Janett; Guillé-Pérez, Adrian; Vargas, Arturo

2004-05-01

The objective of this study was to determine pharmacokinetic differences of acetyl salicylic acid (ASA) and its metabolites: gentisic acid (GA), salicylic acid (SA) and salicyluric acid (SUA) between Otomies and Mesticians healthy subjects. Design. Ten Otomies and 10 Mesticians were included. After a single dose of aspirin given orally (15 mg/kg), blood and urine samples were collected at different times. Results. Pharmacokinetic parameters of salicylates showed significant differences, except distribution volume of SA, and elimination half-life of SUA. Metabolic rates of ASA showed significant differences for all rates between both groups. On the other hand, percentages of dose excreted were more reduced for SA and SUA for the Otomies than for the Mesticians. Conclusion. Results reflect differences in the hydrolysis way i.e. from ASA to SA and aromatic hydroxylation i.e. from SA to GA, which were slower in Otomies subjects, showing a possible pharmacokinetic differences about the capabilities of ASA biotransformation as a consequence of ethnic differences.

Aspirin allergy desensitization in cerebrovascular disease. A report of two cases, literature review and management guide for the neurointerventionalist.

PubMed

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

2014-01-01

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

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

PubMed

Dankner, R E; Wedner, H J

1983-11-01

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

[A pharmaceutical of the century will be 100. A historical vignette on the introduction of acetylsalicylic acid to the market in 1899].

PubMed

Kohl, F

1999-10-15

This article describes the historic roots of acetylsalicylic acid (ASA) from the first experiments at 1800 until the introduction into the pharmaceutical market in 1899. In 1869, Hermann Kolbe enlightened the chemical structure of salicylic acid, which was used at that time as an analgetic and antipyretic drug. Because of the side effects, for example the irritation of the stomach, analytical chemists and pharmacologists searched for chemical modifications. In August 1897 Felix Hoffmann (1868-1946) was successful in acetylizing the salicylic acid to acetylsalicylic acid (ASA). Between 1897 and 1899 Kurt Witthauer (1865-1911) collected clinical data and experiences on the efficiency of ASA as an analgetic and antipyretic drug. In 1899 ASA was introduced into the pharmaceutical market as Aspirin and became soon one of the most successful drugs of its time. The indication exceeds analgesia in the mean time and to prophylaxis of myocardial ischaemia or cerebral stroke, among others.

How important is aspirin adherence when evaluating effectiveness of low-dose aspirin?

PubMed

Navaratnam, Kate; Alfirevic, Zarko; Pirmohamed, Munir; Alfirevic, Ana

2017-12-01

Low-dose aspirin (LDA) is advocated for women at high-risk of pre-eclampsia, providing a modest, 10%, reduction in risk. Cardiology meta-analyses demonstrate 18% reduction in serious vascular events with LDA. Non-responsiveness to aspirin (sometimes termed aspirin resistance) and variable clinical effectiveness are often attributed to suboptimal adherence. The aim of this review was to identify the scope of adherence assessments in RCTs evaluating aspirin effectiveness in cardiology and obstetrics and discuss the quality of information provided by current methods. We searched MEDLINE, EMBASE and the Cochrane Library, limited to humans and English language, for RCTs evaluating aspirin in cardiology; 14/03/13-13/03/16 and pregnancy 1957-13/03/16. Search terms; 'aspirin', 'acetylsalicylic acid' appearing adjacent to 'myocardial infarction' or 'pregnancy', 'pregnant', 'obstetric' were used. 38% (25/68) of obstetric and 32% (20/62) of cardiology RCTs assessed aspirin adherence and 24% (6/25) and 29% (6/21) of obstetric and cardiology RCTs, respectively, defined acceptable adherence. Semi-quantitative methods (pill counts, medication weighing) prevailed in obstetric RCTs (93%), qualitative methods (interviews, questionnaires) were more frequent in obstetrics (67%). Two obstetric RCTs quantified serum thromboxane B 2 and salicylic acid, but no quantitative methods were used in cardiology Aspirin has proven efficacy, but suboptimal adherence is widespread and difficult to accurately quantify. Little is currently known about aspirin adherence in pregnancy. RCTs evaluating aspirin effectiveness show over-reliance on qualitative adherence assessments vulnerable to inherent inaccuracies. Reliable adherence data is important to assess and optimise the clinical effectiveness of LDA. We propose that adherence should be formally assessed in future trials and that development of quantitative assessments may prove valuable for trial protocols. Copyright © 2017 Elsevier B.V. All

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients

PubMed Central

Madariaga-Venegas, Francisco; Fernández-Soto, Roberto; Duarte, Luisa Fernanda; Suarez, Nicole; Delgadillo, Daniela; Jara, José A.; Fernández-Ramires, Ricardo; Urzúa, Blanca; Molina-Berríos, Alfredo

2017-01-01

Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro. Disk diffusion assays showed that while NO-ASA had no antifungal effect, the drug potentiated fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20–30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was evaluated using light microscopy after inducing hyphae formation. For all clinical strains assayed, 125 μM NO-ASA significantly decreased the number of filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical event for biofilm formation, was evaluated in 96-well polystyrene plates using crystal violet assay; 125 μM NO-ASA significantly inhibited adhesion. Biofilms were observed with scanning electron microscopy (SEM) and quantified using XTT reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 μM to 700 μM), consistent with SEM findings of altered biofilm microarchitecture. PGE2 and carboxy-PTIO (an NO scavenger) both blocked the antibiofilm effects of NO-ASA, suggesting that the efficacy of NO-ASA may be associated with both inhibition of PGE2 synthesis and release of NO. NO-ASA is a promising novel antibiofilm agent for treating fluconazole-resistant strains of C. albicans. PMID:28493889

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients.

PubMed

Madariaga-Venegas, Francisco; Fernández-Soto, Roberto; Duarte, Luisa Fernanda; Suarez, Nicole; Delgadillo, Daniela; Jara, José A; Fernández-Ramires, Ricardo; Urzúa, Blanca; Molina-Berríos, Alfredo

2017-01-01

Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro. Disk diffusion assays showed that while NO-ASA had no antifungal effect, the drug potentiated fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20-30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was evaluated using light microscopy after inducing hyphae formation. For all clinical strains assayed, 125 μM NO-ASA significantly decreased the number of filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical event for biofilm formation, was evaluated in 96-well polystyrene plates using crystal violet assay; 125 μM NO-ASA significantly inhibited adhesion. Biofilms were observed with scanning electron microscopy (SEM) and quantified using XTT reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 μM to 700 μM), consistent with SEM findings of altered biofilm microarchitecture. PGE2 and carboxy-PTIO (an NO scavenger) both blocked the antibiofilm effects of NO-ASA, suggesting that the efficacy of NO-ASA may be associated with both inhibition of PGE2 synthesis and release of NO. NO-ASA is a promising novel antibiofilm agent for treating fluconazole-resistant strains of C. albicans.

Safety and efficacy of switching anticoagulation to aspirin three months after successful radiofrequency catheter ablation of atrial fibrillation.

PubMed

Uhm, Jae-Sun; Won, Hoyoun; Joung, Boyoung; Nam, Gi-Byoung; Choi, Kee-Joon; Lee, Moon-Hyoung; Kim, You-Ho; Pak, Hui-Nam

2014-09-01

Although current guidelines recommend continuing the same antithrombotic strategy regardless of rhythm control after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF), anticoagulation has a risk of major bleeding. We evaluated the safety of switching warfarin to aspirin in patients with successful AF ablation. Among 721 patients who underwent RFCA of AF, 608 patients (age, 57.3±10.9 years; 77.0% male, 75.5% paroxysmal AF) who had no evidence of AF recurrence at 3 months post-RFCA were included. We compared the thromboembolic and hemorrhagic events in patients for whom warfarin was switched to aspirin (ASA group; n=296) and patients who were kept on warfarin therapy (W group; n=312). There were no significant differences in CHA₂DS₂-VASc or HAS-BLED scores between the groups. In 30 patients in the ASA group and 37 patients in W group, AF recurred and warfarin was restarted or maintained during the 18.0±12.2 months of follow-up. There were no significant differences in thromboembolic (0.3% vs. 1.0%, p=0.342) and major bleeding incidences (0.7% vs. 0.6%, p=0.958) between ASA and W groups during the follow-up period. In the 259 patients with a CHA₂DS₂-VASc score≥2, there were no significant differences in thromboembolism (0.8% and 2.2%, p=0.380) or major bleeding incidences (0.8% and 1.4%, p=0.640) between ASA and W groups. Switching warfarin to aspirin 3 months after successful RFCA of AF could be as safe and efficacious as long-term anticoagulation even in patients with CHA₂DS₂-VASc score≥2. However, strict rhythm monitoring cannot be overemphasized.

Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation.

PubMed

Barden, Anne; Mas, Emilie; Croft, Kevin D; Phillips, Michael; Mori, Trevor A

2014-11-01

Resolution of inflammation is an active process involving specialized proresolving mediators (SPM) formed from the n-3 fatty acids. This study examined the effect of n-3 fatty acid supplementation and aspirin on plasma SPMs in healthy humans. Healthy volunteers (n = 21) were supplemented with n-3 fatty acids (2.4g/day) for 7 days with random assignment to take aspirin (300 mg/day) or placebo from day 5 to day 7. Blood was collected at baseline (day 0), day 5, and day 7. Plasma 18R/S-HEPE, E-series resolvins, 17R/S-HDHA, D-series resolvins, 14R/S-HDHA, and MaR-1 were measured by LC/MS/MS. At baseline concentrations of E- and D- series resolvins and the upstream precursors 18R/S-HEPE, 17R/S-HDHA ranged from 0.1nM to 0.2nM. 14R/S-HDHA was 3-fold higher than the other SPMs at baseline but MaR-1 was below the limit of detection. Supplementation with n-3 fatty acids significantly increased RvE1, 18R/S-HEPE, 17R/S-HDHA, and 14R/S-HDHA but not other SPMs. The addition of aspirin after 5 days of n-3 fatty acids did not affect concentrations of any SPM. N-3 fatty acid supplementation for 5 days results in concentrations of SPMs that are biologically active in healthy humans. Aspirin administered after n-3 fatty acids did not offer any additional benefit in elevating the levels of SPMs. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Effects of omega-3 polyunsaturated fatty acids and aspirin, alone and combined, on canine platelet function.

PubMed

Westgarth, S; Blois, S L; D Wood, R; Verbrugghe, A; Ma, D W

2018-05-01

To compare haemostatic function in healthy dogs after treatment with low-dose aspirin alone, fish oil alone or a combination of these two therapies. Double-blinded randomised controlled clinical trial on 16 healthy client-owned dogs. Comprehensive haemostatic testing was performed at baseline and after 7 days of therapy with low-dose aspirin in all dogs. Following a 14-day washout, six dogs received fish oil, and nine dogs received combination therapy of aspirin plus fish oil; haemostatic testing was performed before and at 7 and 28 days after treatment initiation. Aspirin was associated with significantly decreased platelet function as measured by a collagen-epinephrine cartridge and inhibited arachidonic acid-induced whole-blood platelet aggregometry. Fish oil alone did not significantly affect any haemostatic tests. The combination of aspirin plus fish oil therapy caused a significantly greater inhibition of adenosine diphosphate and collagen-induced whole blood aggregometry compared to aspirin alone. Fish oil added to aspirin therapy appears to augment inhibition of some measures of platelet function in healthy dogs. © 2017 British Small Animal Veterinary Association.

COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance.

PubMed

Poorani, R; Bhatt, Anant N; Dwarakanath, B S; Das, Undurti N

2016-08-15

Polyunsaturated fatty acids (PUFAs) are vital for normal growth and development and physiological function of various tissues in humans. PUFAs have immunomodulatory actions in addition to their ability to modulate inflammation, vascular reactivity, neurotransmission and stem cell biology. PUFAs and their metabolites possess both pro- and anti-inflammatory properties that underlie their actions and involvement in several diseases. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), possesses both cyclo-oxygenase (COX) and lipoxygenase (LOX) inhibitory action and enhances the production of anti-inflammatory lipoxin A4 {(called as epi-lipoxin A4, aspirin-triggered lipoxins (ATLs))}. In addition, at low doses aspirin may not interfere with the production of prostacyclin (PGI2). Both lipoxin A4 and PGI2 have vasodilator, platelet anti-aggregator and anti-inflammatory actions that may underlie the beneficial actions of aspirin. Paradoxically, other NSAIDs may not have the same actions as that of aspirin on PUFA metabolism. Similar anti-inflammatory compounds are formed from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by the action of aspirin termed as resolvins (from EPA and DHA) and protectins and maresins from DHA. PUFAs: arachidonic acid (AA), EPA and DHA and their various products modulate not only inflammation and immune response but also possess actions on various genes, nuclear factors, cyclic AMP and GMP, G-protein coupled receptors (GPRs), hypothalamic neurotransmitters, hormones, cytokines and enzymes, and interact with nitric oxide, carbon monoxide, and hydrogen sulfide to regulate their formation and action and to form new compounds that have several biological actions. These pleiotropic actions of PUFAs and their metabolites may explain their ability to play a role in several physiological actions and diseases. The big challenge is to harness these actions to prevent and manage clinical conditions. Copyright © 2015 Elsevier B.V. All

[Effect of acetylsalicylic acid on the reproductive performance and on offspring from wistar rats].

PubMed

Damasceno, Débora Cristina; Volpato, Gustavo Tadeu; Person, Osmar Clayton; Yoshida, Alessandra; Rudge, Marilza Vieira Cunha; Calderon, Iracema de Mattos Paranhos

2002-01-01

The aim of this paper was to perform a randomized, controlled and blinded study to investigate if a therapeutic dose of acetylsalicylic acid (ASA), taken by pregnant women, may also cause embryotoxic or congenital abnormalities on experimental animal. Females were confirmed to have mated by observations of sperm in a vaginal smear. The day on which spermatozoa were found in the vaginal smear was considered as day 1 of gestation (GD1). After randomization, mated females were assigned to experimental groups and individually caged, were given 50 mg/kg/day of acetylsalicylic acid, by needle gavage once daily, during two different periods of pregnancy. One group of dams (n=11) received aspirin from day 1 to 4 of pregnancy (before embryonic implantation) for evaluation of the blastocysts, and another group received aspirin from day 6 to 15 of pregnancy (organogenic period) for fetal evaluation. Control groups (n=12) received distilled water in same volume and during same periods as their respective experimental groups. The treatment of the dams with ASA, according to minimal therapeutic dose used for humans, did not cause embryotoxic or major malformations on experimental animal but was responsible for rate increased of fetuses presenting ureteric dilatation. After analysis of the data, it appears that, although direct conclusive evidence of adverse effects in humans is lacking, a potential hazard dose exists and thus the indiscriminate use of acetylsalicylic acid (aspirin) is contraindicated.

Aspirin can elicit the recurrence of gastric ulcer induced with acetic acid in rats.

PubMed

Wang, Guo-Zhong; Huang, Guo-Ping; Yin, Guo-Li; Zhou, Gang; Guo, Chun-Juan; Xie, Chun-Gang; Jia, Bing-Bing; Wang, Jin-Fu

2007-01-01

This study was supported by grants of New Ideas Capability for Backbone Teachers in Universities of Heilongjiang and of Scientific Research foundation in Qiqihar Medical College. Ulcer recurrence and poor healing may be critically important to the development of serious gastrointestinal complications in patients with long-term non-steroid anti-inflammatory drugs (NSAIDs). The present study is to investigate the effects of aspirin on ulcer recurrence and healing quality and to explore the mechanism. Gastric ulcers were induced with acetic acid in rats; aspirin was administrated by gavage from day 25 to day 54 after ulcer induction. The gastric juice volume, pH, gastric mucus, gastric mucosal blood flow (GMBF) and prostaglandin E(2) (PGE(2)) were measured. The mRNA transcription of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were analyzed with RT-PCR and protein expression with Western blot. The gastric juice volume was significantly increased in aspirin group compared with those of fasting or saline control groups (P<0.01); while the pH, mucus, GMBF and PGE(2) were significantly decreased in aspirin treated rats compared with those of other two groups (P<0.01). COX-2, evaluated with mRNA and protein expression, was significantly augmented in aspirin group compared with others. The quality of ulcer healing (QOUH) in Aspirin group was poorer than that of fasting or saline control groups. Aspirin enhance the recurrence of gastric ulcer. The inhibition of cycloxygenase, mucus secretion and mucosal blood flow may be involved. Aspirin also impair the quality of ulcer healing.

Antiplatelet effects of aspirin with phytosterols: comparison with non-enteric coated aspirin alone.

PubMed

Antonino, Mark J; Coppolecchia, Rosa; Mahla, Elisabeth; Bliden, Kevin P; Tantry, Udaya S; Gurbel, Paul A

2010-11-01

The novel combination of aspirin and phytosterols may be a potential strategy to treat patients with cardiovascular disease. We sought to determine if the antiplatelet effects of a combination caplet of 81 mg aspirin with 400 mg phytosterols differed from the antiplatelet effects of non-enteric coated aspirin. The first five days of aspirin therapy alone (T1) produced marked reductions in collagen-induced, ADP-induced, and archidonic acid- induced platelet aggregation, and in serum and urine TxB(2) compared to baseline. Five days after randomization to aspirin alone versus aspirin+phytosterols (T2), there were no differences in any measurement of platelet function within each group compared to T1 or between groups. The present study suggests that the antiplatelet effect of non-enteric coated 81 mg twice-daily aspirin therapy alone is not affected by the addition of phytosterols in a combination product. Copyright © 2009 Elsevier Ltd. All rights reserved.

Bioavailability of aspirin in rats comparing the drug's uptake into gastrointestinal tissue and vascular and lymphatic systems: implications on aspirin's chemopreventive action.

PubMed

Lichtenberger, L M; Phan, T; Fang, D; Edler, S; Philip, J; Li-Geng, T; Dial, E J

2016-10-01

Aspirin is an effective analgesic and antiplatelet drug that in addition to its ability to reduce pain, inflammation and fever, appears to have efficacy in the prevention/treatment of a range of diseases including heart disease, numerous cancers and Alzheimer's. It is important to understand the bioavailability of aspirin and its major metabolite, salicylic acid, since dosage and route of administration can vary for treating differing diseases, and the major side-effects of aspirin, upper gastrointestinal ulceration and bleeding, are dose-dependent. We examined the time course for gastroduodenal uptake of aspirin and the appearance of its major metabolite salicylic acid in blood and lymph after intragastric (to simulate oral) and intraduodenal (to simulate enteric-coating) dosing in rats. Results show that after intragastric dosing, intact aspirin is absorbed primarily by the gastric mucosa and to a lesser extent by the duodenal mucosa. When aspirin is dosed intragastrically or intraduodenally, a much greater concentration of aspirin enters the lymph than the blood. In contrast, the concentration of salicylic acid was higher in blood than in lymph. Lymph levels of both aspirin and salicylic acid were sufficiently high so as to perform a pharmacologic function there, possibly as a chemopreventive agent against colon cancer and potentially the metastatic spread of non-gastrointestinal cancers.

Safety and Efficacy of Switching Anticoagulation to Aspirin Three Months after Successful Radiofrequency Catheter Ablation of Atrial Fibrillation

PubMed Central

Uhm, Jae-Sun; Won, Hoyoun; Joung, Boyoung; Nam, Gi-Byoung; Choi, Kee-Joon; Lee, Moon-Hyoung; Kim, You-Ho

2014-01-01

Purpose Although current guidelines recommend continuing the same antithrombotic strategy regardless of rhythm control after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF), anticoagulation has a risk of major bleeding. We evaluated the safety of switching warfarin to aspirin in patients with successful AF ablation. Materials and Methods Among 721 patients who underwent RFCA of AF, 608 patients (age, 57.3±10.9 years; 77.0% male, 75.5% paroxysmal AF) who had no evidence of AF recurrence at 3 months post-RFCA were included. We compared the thromboembolic and hemorrhagic events in patients for whom warfarin was switched to aspirin (ASA group; n=296) and patients who were kept on warfarin therapy (W group; n=312). Results There were no significant differences in CHA2DS2-VASc or HAS-BLED scores between the groups. In 30 patients in the ASA group and 37 patients in W group, AF recurred and warfarin was restarted or maintained during the 18.0±12.2 months of follow-up. There were no significant differences in thromboembolic (0.3% vs. 1.0%, p=0.342) and major bleeding incidences (0.7% vs. 0.6%, p=0.958) between ASA and W groups during the follow-up period. In the 259 patients with a CHA2DS2-VASc score ≥2, there were no significant differences in thromboembolism (0.8% and 2.2%, p=0.380) or major bleeding incidences (0.8% and 1.4%, p=0.640) between ASA and W groups. Conclusion Switching warfarin to aspirin 3 months after successful RFCA of AF could be as safe and efficacious as long-term anticoagulation even in patients with CHA2DS2-VASc score ≥2. However, strict rhythm monitoring cannot be overemphasized. PMID:25048480

Anagrelide reduces thrombotic risk in essential thrombocythaemia vs. hydroxyurea plus aspirin.

PubMed

Dombi, Péter; Illés, Árpád; Demeter, Judit; Homor, Lajos; Simon, Zsofia; Karadi, Eva; Udvardy, Miklos; Egyed, Miklos

2017-02-01

To evaluate the reduction in thrombotic events (TE) in patients with essential thrombocythaemia (ET) treated with anagrelide versus hydroxyurea + aspirin (HU + ASA). A questionnaire was developed using 2008 WHO diagnostic criteria, and thrombotic risk factors were stratified according to Landolfi criteria. Through questionnaire completion, clinicians at Hungarian haematological centres entered data into the Hungarian MPN Registry on patients with myeloproliferative neoplasms. Based on ET registry data, TEs in anagrelide-treated patients (n = 139) were compared with HU + ASA-treated patients (n = 141). Patients were followed up for (median) 6 yr. TEs were reported in significantly fewer anagrelide-treated patients versus HU + ASA (15.1% versus 49.6%; P < 0.001). Numbers of major arterial and major venous events were similar between the groups, although there were over fivefold more minor arterial and minor venous events in the HU + ASA group (P < 0.001). While median age at diagnosis was older and length of follow-up shorter in the HU + ASA group (P < 0.05), this did not influence TE incidence; medication and TE before diagnosis only influenced TE incidence. Anagrelide significantly decreased the number of patients experiencing minor arterial and minor venous TEs versus HU + ASA over 6 yr. Risk of TE after diagnosis was significantly increased if the patient had TE before diagnosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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-/sup 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 intravenouslymore » 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.« less

Acetylsalicylic acid is compounding to antiplatelet effect of C-reactive protein.

PubMed

Boncler, Magdalena; Luzak, Boguslawa; Rozalski, Marcin; Golanski, Jacek; Rychlik, Blazej; Watala, Cezary

2007-01-01

The contribution of inflammatory process to the modulation of platelet response to acetylsalicylic acid (ASA) remains obscure. In our study, we examined the in vitro effect of C-reactive protein (CRP) on the ASA-mediated inhibition of collagen-stimulated platelet reactivity. Influence of CRP on platelet responsiveness to ASA was analysed using classical turbidimetric aggregation and flow cytometry. When acting alone, both C-reactive protein and ASA inhibited collagen-dependent platelet aggregation and reduced the expressions of two platelet surface membrane activation markers: P-selectin and activated GPIIbIIIa complex. Compared to the effects observed for ASA alone, the simultaneous action of both agents lead to further reductions in platelet aggregation (by 56.7+/-1.0% vs. 14.9+/-0.6%, p<0.0001) and lowered the expressions of platelet surface membrane P-selectin (by 72.1+/-5.3% vs. 65.0+/-6.0%, p<0.01) and activated GPIIbIIIa (by 67.0+/-5.6% vs. 47.7+/-8.3%, p<0.01). In general, our findings showed for the first time the augmenting effect of native C-reactive protein in the antiplatelet action of acetylsalicylic acid. Thus, we conclude that the effectiveness of aspirin therapy may strongly depend upon the presence of native CRP in circulation.

Study design of ASPirin in Reducing Events in the Elderly (ASPREE): a randomized, controlled trial.

PubMed

2013-11-01

Cost-effective strategies to maintain healthy active lifestyle in aging populations are required to address the global burden of age-related diseases. ASPREE will examine whether the potential primary prevention benefits of low dose aspirin outweigh the risks in older healthy individuals. Our primary hypothesis is that daily oral 100 mg enteric-coated aspirin will extend a composite primary endpoint termed 'disability-free life' including onset of dementia, total mortality, or persistent disability in at least one of the Katz Activities of Daily Living in 19,000 healthy participants aged 65 years and above ('US minorities') and 70 years and above (non-'US minorities'). ASPREE is a double-blind, randomized, placebo-controlled trial of oral 100mg enteric-coated acetyl salicylic acid (ASA) or matching placebo being conducted in Australian and US community settings on individuals free of dementia, disability and cardiovascular disease (CVD) events. Secondary endpoints are all-cause and cause specific mortality, fatal and non-fatal cardiovascular events, fatal and non-fatal cancer (excluding non-melanoma skin cancer), dementia, mild cognitive impairment, depression, physical disability, and clinically significant bleeding. To 20 September 2013 14,383 participants have been recruited. Recruitment and study completion are anticipated in July 2014 and December 2018 respectively. In contrast to other aspirin trials that have largely focused on cardiovascular endpoints, ASPREE has a unique composite primary endpoint to better capture the overall risk and benefit of aspirin to extend healthy independent lifespan in older adults in the US and Australia. © 2013. Published by Elsevier Inc. All rights reserved.

Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP)

PubMed Central

Wang, Jigang; Zhang, Chong-Jing; Zhang, Jianbin; He, Yingke; Lee, Yew Mun; Chen, Songbi; Lim, Teck Kwang; Ng, Shukie; Shen, Han-Ming; Lin, Qingsong

2015-01-01

Target-identification and understanding of mechanism-of-action (MOA) are challenging for development of small-molecule probes and their application in biology and drug discovery. For example, although aspirin has been widely used for more than 100 years, its molecular targets have not been fully characterized. To cope with this challenge, we developed a novel technique called quantitative acid-cleavable activity-based protein profiling (QA-ABPP) with combination of the following two parts: (i) activity-based protein profiling (ABPP) and iTRAQ™ quantitative proteomics for identification of target proteins and (ii) acid-cleavable linker-based ABPP for identification of peptides with specific binding sites. It is known that reaction of aspirin with its target proteins leads to acetylation. We thus applied the above technique using aspirin-based probes in human cancer HCT116 cells. We identified 1110 target proteins and 2775 peptides with exact acetylation sites. By correlating these two sets of data, 523 proteins were identified as targets of aspirin. We used various biological assays to validate the effects of aspirin on inhibition of protein synthesis and induction of autophagy which were elicited from the pathway analysis of Aspirin target profile. This technique is widely applicable for target identification in the field of drug discovery and biology, especially for the covalent drugs. PMID:25600173

A spectroscopic study of phenylbutazone and aspirin bound to serum albumin in rheumatoid diseases

NASA Astrophysics Data System (ADS)

Maciążek-Jurczyk, M.; Sułkowska, A.; Bojko, B.; Równicka-Zubik, J.; Sułkowski, W. W.

2011-11-01

Interaction of phenylbutazone (PBZ) and aspirin (ASA), two drugs recommended in rheumatoid diseases (RDs), when binding to human (HSA) and bovine (BSA) serum albumins, has been studied by quenching of fluorescence and proton nuclear magnetic resonance ( 1HNMR) techniques. On the basis of spectrofluorescence measurements high affinity binding sites of PBZ and ASA on albumin as well as their interaction within the binding sites were described. A low affinity binding site has been studied by proton nuclear magnetic resonance spectroscopy. Using fluorescence spectroscopy the location of binding site in serum albumin (SA) for PBZ and ASA was found. Association constants Ka were determined for binary (i.e. PBZ-SA and ASA-SA) and ternary complexes (i.e. PBZ-[ASA]-SA and ASA-[PBZ]-SA). PBZ and ASA change the affinity of each other to the binding site in serum albumin (SA). The presence of ASA causes the increase of association constants KaI of PBZ-SA complex. Similarly, PBZ influences KaI of ASA-SA complex. This phenomenon shows that the strength of binding and the stability of the complexes increase in the presence of the second drug. The decrease of KaII values suggests that the competition between PBZ and ASA in binding to serum albumin in the second class of binding sites occurs. The analysis of 1HNMR spectral parameters i.e. changes of chemical shifts and relaxation times of the drug indicate that the presence of ASA weakens the interaction of PBZ with albumin. Similarly PBZ weakens the interaction of ASA with albumin. This conclusion points to the necessity of using a monitoring therapy owning to the possible increase of uncontrolled toxic effects.

ASA24-2016

Cancer.gov

The user interface for all 2016 versions of ASA24, including ASA24-Canada-2016 and ASA24-Australia-2016, employs a responsive design, meaning that these latest versions of the ASA24 system can be used on sm artphones and tablets, in addition to laptops and desktops.

A metabolomics strategy to explore urinary biomarkers and metabolic pathways for assessment of interaction between Danhong injection and low-dose aspirin during their synergistic treatment.

PubMed

Li, Jianping; Guo, Jianming; Shang, Erxin; Zhu, Zhenhua; Zhu, Kevin Yue; Li, Shujiao; Zhao, Buchang; Jia, Lifu; Zhao, Jing; Tang, Zhishu; Duan, Jinao

2016-07-15

The drug combination of Danhong injection (DHI) and low-dose aspirin (ASA) was frequently applied for the treatment of cardiovascular and cerebrovascular diseases. Due to the drug interactions, a lot of potential benefits and risks might exist side by side in the course of combination therapy. However, there had been no studies of interaction between DHI and ASA. Metabolomics was a powerful tool to explore endogenous biomarkers and metabolic pathways. In present study, metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS) coupled with multivariate statistical analysis was performed to provide insight into understanding the interaction between DHI and low-dose ASA. Eleven potential biomarkers of three types were identified and seven metabolic pathways were constructed. The results showed that the interaction between DHI and low-dose ASA during synergistic treatment indeed affected some key endogenous biomarkers and metabolic pathways, which could not happen when DHI or low-dose ASA was used alone. The quality and quantity of endogenous metabolite were both influenced by interaction between DHI and low-dose ASA. In details, the amount of flavin mononucleotide, L-2, 4-diaminobutyric acid (DABA) and 4-aminohippuric acid were significantly increased. On the contrary, the amount of 3-methyluridine, 4, 6-dihydroxyquinoline, cortolone-3-glucuronide, and serotonin were significantly decreased. Furthermore, O-phosphotyrosine, 3-methyl-2-butenal, indoxyl sulfate and dolichyl diphosphate were disappeared in urine. As to metabolic pathways, riboflavin metabolism, pentose and glucuronate interconversions, and tryptophan metabolism were all significantly influenced. The emerging alterations of biomarkers and metabolic pathways were associated with a lot of drugs and diseases based on literature researches, which might influence the co-administration of other drugs or the treatments of relevant

Proteome-wide prediction of targets for aspirin: new insight into the molecular mechanism of aspirin

PubMed Central

Dai, Shao-Xing; Li, Wen-Xing

2016-01-01

Besides its anti-inflammatory, analgesic and anti-pyretic properties, aspirin is used for the prevention of cardiovascular disease and various types of cancer. The multiple activities of aspirin likely involve several molecular targets and pathways rather than a single target. Therefore, systematic identification of these targets of aspirin can help us understand the underlying mechanisms of the activities. In this study, we identified 23 putative targets of aspirin in the human proteome by using binding pocket similarity detecting tool combination with molecular docking, free energy calculation and pathway analysis. These targets have diverse folds and are derived from different protein family. However, they have similar aspirin-binding pockets. The binding free energy with aspirin for newly identified targets is comparable to that for the primary targets. Pathway analysis revealed that the targets were enriched in several pathways such as vascular endothelial growth factor (VEGF) signaling, Fc epsilon RI signaling and arachidonic acid metabolism, which are strongly involved in inflammation, cardiovascular disease and cancer. Therefore, the predicted target profile of aspirin suggests a new explanation for the disease prevention ability of aspirin. Our findings provide a new insight of aspirin and its efficacy of disease prevention in a systematic and global view. PMID:26989626

Proteome-wide prediction of targets for aspirin: new insight into the molecular mechanism of aspirin.

PubMed

Dai, Shao-Xing; Li, Wen-Xing; Li, Gong-Hua; Huang, Jing-Fei

2016-01-01

Besides its anti-inflammatory, analgesic and anti-pyretic properties, aspirin is used for the prevention of cardiovascular disease and various types of cancer. The multiple activities of aspirin likely involve several molecular targets and pathways rather than a single target. Therefore, systematic identification of these targets of aspirin can help us understand the underlying mechanisms of the activities. In this study, we identified 23 putative targets of aspirin in the human proteome by using binding pocket similarity detecting tool combination with molecular docking, free energy calculation and pathway analysis. These targets have diverse folds and are derived from different protein family. However, they have similar aspirin-binding pockets. The binding free energy with aspirin for newly identified targets is comparable to that for the primary targets. Pathway analysis revealed that the targets were enriched in several pathways such as vascular endothelial growth factor (VEGF) signaling, Fc epsilon RI signaling and arachidonic acid metabolism, which are strongly involved in inflammation, cardiovascular disease and cancer. Therefore, the predicted target profile of aspirin suggests a new explanation for the disease prevention ability of aspirin. Our findings provide a new insight of aspirin and its efficacy of disease prevention in a systematic and global view.

Transfer of Low Dose Aspirin Into Human Milk.

PubMed

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

2017-05-01

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

Comparison of the effect of aspirin and choline magnesium trisalicylate on thromboxane biosynthesis in human platelets: role of the acetyl moiety.

PubMed

Danesh, B J; McLaren, M; Russell, R I; Lowe, G D; Forbes, C D

1989-01-01

Parameters of platelet thromboxane biosynthesis were measured 24 h after ingestion of equivalent salicylate doses (500 mg) of aspirin (ASA) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate. In random order, 10 healthy volunteers received these drugs on 2 separate days, 2 weeks apart. While ASA significantly prolonged bleeding time, and decreased plasma thromboxane generation and serum thromboxane B2 levels, CMT failed to produce such effects. Thus CMT, which lacks an acetyl moiety in its structure, has no inhibitory effect on platelet thromboxane biosynthesis, and may therefore be considered safer than ASA for therapeutic use, when inhibition of platelet function can be hazardous.

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

PubMed

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 < 0.05). The grade of severity correlated with the depth of inflammation (r s  = 0.492, p < 0.001). Maximal dose 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.

Asiago spectroscopic classification of ASAS-SN18ck, ASAS-SN18cp, ASAS-SN18cq and ASASSN-18cj

NASA Astrophysics Data System (ADS)

Tomasella, L.; Benetti, S.; Cappellaro, E.; Turatto, M.

2018-02-01

The Asiago Transient Classification Program (Tomasella et al. 2014, AN, 335, 841) reports the spectroscopic classification of ASAS-SN18ck, ASAS-SN18cp, ASAS-SN18cq and ASASSN-18cj, discovered during the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014, Atel #11178).

5-ASA in ulcerative colitis: improving treatment compliance.

PubMed

Prantera, Cosimo; Rizzi, Marina

2009-09-21

5-Aminosalicylic acid (5-ASA) compounds are a highly effective treatment for ulcerative colitis (UC). While UC patient compliance in clinical studies is over 90%, only 40% of patients in every day life take their prescribed therapy. Adherence to medication has been emphasized recently by a Cochrane meta-analysis that has suggested that future trials of 5-ASA in UC should look at patient compliance rather than drug efficacy. Better compliance can be obtained by reducing the number of tablets and times of administration. Given that the 5-ASA formulations have different delivery systems that split the active moiety in various regions of the intestine, it is particularly important that an adequate dose of the drug arrives at the inflamed part of the colon. 5-ASA Multi matrix (MMx) is a novel, high strength (1.2 g), oral formulation designed for once-daily dosing. It releases the active moiety throughout the colon. Different studies with this compound have shown that it is as effective as 5-ASA enema in the treatment of mild-to-moderate, left-sided UC, and is comparable to a pH-dependent, delayed release 5-ASA (Asacol), even if given once daily. Recently, the effectiveness in the acute phase of UC has been confirmed also in maintenance. In conclusion, at present, 5-ASA MMx seems theoretically the best agent for maintaining patient compliance, and consequently, treatment effectiveness.

Specialized proresolving lipid mediators in humans with the metabolic syndrome after n-3 fatty acids and aspirin.

PubMed

Barden, Anne E; Mas, Emilie; Croft, Kevin D; Phillips, Michael; Mori, Trevor A

2015-12-01

The metabolic syndrome (MetS) is associated with a chronic low-grade inflammatory state and may be affected by the ability to resolve inflammation, which is an active process that involves specialized proresolving lipid mediators (SPMs) derived from n-3 (ω-3) fatty acids. We compared plasma concentrations of SPMs in men and women with features of the MetS and in healthy matched control subjects in response to intakes of n-3 fatty acids and aspirin. MetS volunteers (n = 22) and healthy, matched controls (n = 21) were studied in parallel for 4 wk. Both groups took n-3 fatty acids (2.4 g/d) for 4 wk with the addition of aspirin (300 mg/d) during the last 7 d. Blood was collected at baseline and at 3 and 4 wk. Plasma SPMs were measured with the use of liquid chromatography-tandem mass spectrometry and included 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins, 17-hydroxydocosahexaenoic acid (17-HDHA), D-series resolvins, 14-hydroxydocosahexaenoic acid (14-HDHA), and maresin-1. Baseline SPMs did not differ between groups. There was an increase in the SPM precursors 18-HEPE, 17-HDHA, and 14-HDHA after n-3 fatty acid supplementation that was significantly attenuated in the MetS (P < 0.05). However, the E-series resolvins increased to a similar extent in the groups after n-3 fatty acid supplementation, and the D-series resolvins were not different from those at baseline. The addition of aspirin to n-3 fatty acids did not alter any SPMs in either group. Volunteers with MetS had reduced plasma concentrations of the precursors of the E- and D- series resolvins as well as of 14-HDHA in response to n-3 fatty acid supplementation. However, plasma E-series resolvins were increased to a similar extent after n-3 fatty acid supplementation in both groups, and the addition of aspirin to n-3 fatty acid supplementation did not alter any of the plasma SPMs in MetS and control subjects. Additional studies in the MetS are required to determine whether SPMs affect the ability

Network reconstruction of platelet metabolism identifies metabolic signature for aspirin resistance

NASA Astrophysics Data System (ADS)

Thomas, Alex; Rahmanian, Sorena; Bordbar, Aarash; Palsson, Bernhard Ø.; Jamshidi, Neema

2014-01-01

Recently there has not been a systematic, objective assessment of the metabolic capabilities of the human platelet. A manually curated, functionally tested, and validated biochemical reaction network of platelet metabolism, iAT-PLT-636, was reconstructed using 33 proteomic datasets and 354 literature references. The network contains enzymes mapping to 403 diseases and 231 FDA approved drugs, alluding to an expansive scope of biochemical transformations that may affect or be affected by disease processes in multiple organ systems. The effect of aspirin (ASA) resistance on platelet metabolism was evaluated using constraint-based modeling, which revealed a redirection of glycolytic, fatty acid, and nucleotide metabolism reaction fluxes in order to accommodate eicosanoid synthesis and reactive oxygen species stress. These results were confirmed with independent proteomic data. The construction and availability of iAT-PLT-636 should stimulate further data-driven, systems analysis of platelet metabolism towards the understanding of pathophysiological conditions including, but not strictly limited to, coagulopathies.

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

PubMed

Zhou, Lin; Duan, Xingmei; Zeng, Shi; Men, Ke; Zhang, Xueyan; Yang, Li; Li, Xiang

2015-01-01

Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer.

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

PubMed Central

Zhou, Lin; Duan, Xingmei; Zeng, Shi; Men, Ke; Zhang, Xueyan; Yang, Li; Li, Xiang

2015-01-01

Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer. PMID:26316750

Underutilization of aspirin for primary prevention of cardiovascular disease among HIV-infected patients.

PubMed

Burkholder, Greer A; Tamhane, Ashutosh R; Salinas, Jorge L; Mugavero, Michael J; Raper, James L; Westfall, Andrew O; Saag, Michael S; Willig, James H

2012-12-01

Individuals infected with human immunodeficiency virus (HIV) are at increased risk for cardiovascular disease (CVD) events compared with uninfected persons. However, little is known about HIV provider practices regarding aspirin (ASA) for primary prevention of CVD. A cross-sectional study was conducted among patients attending the University of Alabama at Birmingham 1917 HIV Clinic during 2010 to determine the proportion receiving ASA for primary prevention of CVD and identify factors associated with ASA prescription. Ten-year risk for CVD events was calculated for men aged 45-79 and women aged 55-79. The 2009 US Preventive Services Task Force (USPSTF) guidelines were used to determine those qualifying for primary CVD prevention. Among 397 patients who qualified to receive ASA (mean age, 52.2 years, 94% male, 36% African American), only 66 (17%) were prescribed ASA. In multivariable logistic regression analysis, diabetes mellitus (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.28-5.27), hyperlipidemia (OR, 3.42; 95% CI, 1.55-7.56), and current smoking (OR, 1.87; 95% CI, 1.03-3.41) were significantly associated with ASA prescription. Odds of ASA prescription more than doubled for each additional CVD-related comorbidity present among hypertension, diabetes, hyperlipidemia, and smoking (OR, 2.13, 95% CI, 1.51-2.99). In this HIV-infected cohort, fewer than 1 in 5 patients in need received ASA for primary CVD prevention. Escalating likelihood of ASA prescription with increasing CVD-related comorbidity count suggests that providers may be influenced more by co-occurrence of these diagnoses than by USPSTF guidelines. In the absence of HIV-specific guidelines, interventions to improve HIV provider awareness of and adherence to existing general population guidelines on CVD risk reduction are needed.

Underutilization of Aspirin for Primary Prevention of Cardiovascular Disease Among HIV-Infected Patients

PubMed Central

Burkholder, Greer A.; Tamhane, Ashutosh R.; Salinas, Jorge L.; Mugavero, Michael J.; Raper, James L.; Westfall, Andrew O.; Saag, Michael S.; Willig, James H.

2012-01-01

Background. Individuals infected with human immunodeficiency virus (HIV) are at increased risk for cardiovascular disease (CVD) events compared with uninfected persons. However, little is known about HIV provider practices regarding aspirin (ASA) for primary prevention of CVD. Methods. A cross-sectional study was conducted among patients attending the University of Alabama at Birmingham 1917 HIV Clinic during 2010 to determine the proportion receiving ASA for primary prevention of CVD and identify factors associated with ASA prescription. Ten-year risk for CVD events was calculated for men aged 45–79 and women aged 55–79. The 2009 US Preventive Services Task Force (USPSTF) guidelines were used to determine those qualifying for primary CVD prevention. Results. Among 397 patients who qualified to receive ASA (mean age, 52.2 years, 94% male, 36% African American), only 66 (17%) were prescribed ASA. In multivariable logistic regression analysis, diabetes mellitus (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.28–5.27), hyperlipidemia (OR, 3.42; 95% CI, 1.55–7.56), and current smoking (OR, 1.87; 95% CI, 1.03–3.41) were significantly associated with ASA prescription. Odds of ASA prescription more than doubled for each additional CVD-related comorbidity present among hypertension, diabetes, hyperlipidemia, and smoking (OR, 2.13, 95% CI, 1.51–2.99). Conclusions. In this HIV-infected cohort, fewer than 1 in 5 patients in need received ASA for primary CVD prevention. Escalating likelihood of ASA prescription with increasing CVD-related comorbidity count suggests that providers may be influenced more by co-occurrence of these diagnoses than by USPSTF guidelines. In the absence of HIV-specific guidelines, interventions to improve HIV provider awareness of and adherence to existing general population guidelines on CVD risk reduction are needed. PMID:22942209

Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic acid: a Potential Role in Cancer Prevention

PubMed Central

Dachineni, Rakesh; Ai, Guoqiang; Kumar, D. Ramesh; Sadhu, Satya S.; Tummala, Hemachand; Bhat, G. Jayarama

2015-01-01

Data emerging from the past 10 years have consolidated the rationale for investigating the use of aspirin as a chemopreventive agent; however, the mechanisms leading to its anti-cancer effects are still being elucidated. We hypothesized that aspirin’s chemopreventive actions may involve cell cycle regulation through modulation of the levels or activity of cyclin A2/cyclin dependent kinase-2 (CDK2). In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. The down regulatory effect of either drugs on cyclin A2 levels was prevented by pretreatment with lactacystin, an inhibitor of proteasomes, suggesting the involvement of 26S proteasomes. In-vitro kinase assays showed that lysates from cells treated with salicylic acid had lower levels of CDK2 activity. Importantly, three independent experiments revealed that salicylic acid directly binds to CDK2. Firstly, inclusion of salicylic acid in naïve cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Secondly, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, pre-incubation of CDK2 with salicylic acid, dose-dependently quenched the fluorescence due to ANS. Thirdly, computational analysis using molecular docking studies identified Asp145 and Lys33 as the potential sites of salicylic acid interactions with CDK2. These results demonstrate that aspirin and salicylic acid down-regulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention. Implications Biochemical and structural studies indicate that the anti-proliferative actions of aspirin are mediated through cyclin A2/CDK2. PMID:26685215

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

PubMed Central

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

Subchorionic hematomas are increased in early pregnancy in women taking low-dose aspirin.

PubMed

Truong, Ashley; Sayago, M Mercedes; Kutteh, William H; Ke, Raymond W

2016-05-01

To determine the frequency of subchorionic hematomas (SCH) in first-trimester ultrasound examinations of patients with infertility and recurrent pregnancy loss (RPL) and in patients from a general obstetric population. To determine if the method of assisted reproduction utilized or the use of anticoagulants, such as heparin and aspirin (ASA), influenced frequency of SCH. Prospective, cohort study. Fertility clinic and general obstetrics clinic. Five hundred and thirty-three women who were pregnant in the first-trimester. Not applicable. Frequencies of subchorionic hematomas in women based on diagnosis, use of anticoagulants, and fertility treatment. SCH were identified in 129/321 (40.2%) in the study group compared to 23/212 (10.9%) in the control group. Fertility diagnosis and the use of heparin did not appear to affect the frequency of SCH in the first trimester; however, SCH occurred at an almost four-fold increase in patients taking ASA compared to those not taking ASA, regardless of fertility diagnosis or method of fertility treatment. The use of ASA may be associated with an increased risk of developing a SCH during the first trimester. The increased frequencies of SCH in pregnancies of patients attending a fertility clinic compared to women from a general obstetrical practice was highly correlated with the use of ASA. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Interaction between the LMWH reviparin and aspirin in healthy volunteers

PubMed Central

Klinkhardt, Ute; Breddin, Hans Klaus; Esslinger, Heinz Ulrich; Haas, Silvia; Kalatzis, Andreas; Harder, Sebastian

2000-01-01

Aims To investigate potential interactions between reviparin and acetylsalicylic acid (ASA 300 mg o.d. from day 1–5). Methods In an open, randomized, three-way-cross over study nine healthy volunteers received reviparin (s.c. injection of 6300 anti-Xa units) or placebo from days 3 to 5 and acetylsalicylic acid (ASA 300 mg) or placebo from days 1 to 5. Assessments included bleeding time (BT), collagen (1 µg ml−1) induced platelet aggregation (CAG), heptest, plasma antifactor Xa-activity and activated partial thromboplastin time (aPTT). Results Median bleeding time at day 5 was 5.5 min after reverparin alone and after ASA alone and was 9.6 min after the combination of reviparin and ASA. ASA treatment reduced CAG from 84% to 40 to 50% of Amax; values after combined treatment of reviparin with ASA were not different from those after ASA alone. aPTT was prolonged to 32 s after reviparin; this effect was not modified if subjects received ASA. Combined treatment with ASA and reviparin had no effect on plasma anti-Xa-activity and heptest compared with reviparin alone. Conclusions We could not entirely exclude a small interaction between reviparin and ASA on bleeding time, but the effect is probably without clinical significance. PMID:10759689

The Antineoplastic Effect of Nitric Oxide-Donating Acetylsalicylic Acid (NO-ASA) in Chronic Lymphocytic Leukemia (CLL) Cells is Highly Dependent on its Positional Isomerism.

PubMed

Gehrke, Iris; Razavi, Regina; Poll-Wolbeck, Simon Jonas; Berkessel, Albrecht; Hallek, Michael; Kreuzer, Karl-Anton

2011-10-01

Chronic Lymphocytic Leukemia (CLL) is not curable in patients that are not eligible for allogeneic stem cell transplantation. Therefore, new treatment options are highly desirable. Chemically modified nonsteroidal anti-inflammatory drugs (NSAIDs), such as nitric-oxide-donating acetylsalicylic acid (NO-ASA), have been described to possess antineoplastic capacity. Recently, we could demonstrate a potent apoptosis induction in primary CLL cells in vitro and tumor growth inhibition by para-NO-ASA in a xenograft mouse model. However, little is known about the impact of positional isomerism of NO-ASA on its antineoplastic capacity in CLL. Primary CLL cells were treated with the meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter-Glo luminescence cell viability assay. Caspase and PARP cleavage as well as involvement of β-catenin/Lef-1 signaling was determined by immunoblotting. For caspase inhibition, BD™ ApoBlock was used. Nude mice were xenografted with JVM3 cells and treated with meta-NO-ASA, para-NO-ASA or vehicle control. The meta-isomer was entirely ineffective in inducing CLL cell apoptosis in concentrations up to 100 μM, while para-NO-ASA acted in the low micromolar range. meta-NO-ASA, in contrast to para-NO-ASA, did not alter caspase activity. While para-NO-ASA action involved inhibition of β-catenin/Lef-1 signaling, meta-NO-ASA did not show any impact on this signaling pathway. Further, meta-NO-ASA did not significantly reduce tumor growth in a CLL xenograft mouse model, while para-NO-ASA was highly potent. We conclude that positional isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be suggested that the para-isomer, but not the meta-isomer, generates a chemical structure which is essential for the neoplastic effect of NO-ASA.

The Antineoplastic Effect of Nitric Oxide-Donating Acetylsalicylic Acid (NO-ASA) in Chronic Lymphocytic Leukemia (CLL) Cells is Highly Dependent on its Positional Isomerism

PubMed Central

Gehrke, Iris; Razavi, Regina; Poll-Wolbeck, Simon Jonas; Berkessel, Albrecht; Hallek, Michael; Kreuzer, Karl-Anton

2011-01-01

Background: Chronic Lymphocytic Leukemia (CLL) is not curable in patients that are not eligible for allogeneic stem cell transplantation. Therefore, new treatment options are highly desirable. Chemically modified nonsteroidal anti-inflammatory drugs (NSAIDs), such as nitric-oxide-donating acetylsalicylic acid (NO-ASA), have been described to possess antineoplastic capacity. Recently, we could demonstrate a potent apoptosis induction in primary CLL cells in vitro and tumor growth inhibition by para-NO-ASA in a xenograft mouse model. However, little is known about the impact of positional isomerism of NO-ASA on its antineoplastic capacity in CLL. Methods: Primary CLL cells were treated with the meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter-Glo luminescence cell viability assay. Caspase and PARP cleavage as well as involvement of β-catenin/Lef-1 signaling was determined by immunoblotting. For caspase inhibition, BD™ ApoBlock was used. Nude mice were xenografted with JVM3 cells and treated with meta-NO-ASA, para-NO-ASA or vehicle control. Results: The meta-isomer was entirely ineffective in inducing CLL cell apoptosis in concentrations up to 100 μM, while para-NO-ASA acted in the low micromolar range. meta-NO-ASA, in contrast to para-NO-ASA, did not alter caspase activity. While para-NO-ASA action involved inhibition of β-catenin/Lef-1 signaling, meta-NO-ASA did not show any impact on this signaling pathway. Further, meta-NO-ASA did not significantly reduce tumor growth in a CLL xenograft mouse model, while para-NO-ASA was highly potent. Conclusion: We conclude that positional isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be suggested that the para-isomer, but not the meta-isomer, generates a chemical structure which is essential for the neoplastic effect of NO-ASA. PMID:23556096

Clopidogrel plus indobufen in acute coronary syndrome patients with hypersensitivity to aspirin undergoing percutaneous coronary intervention.

PubMed

Barillà, Francesco; Pulcinelli, Fabio Maria; Mangieri, Enrico; Torromeo, Concetta; Tanzilli, Gaetano; Dominici, Tania; Pellicano, Mariano; Paravati, Vincenzo; Acconcia, Maria Cristina; Gaudio, Carlo

2013-01-01

The prescription of aspirin (acetylsalicylic acid (ASA)) to patients with a history of hypersensitivity to this drug could prove harmful. The aim of the study was to assess the antiplatelet activity and safety of a combined antiplatelet treatment with indobufen and clopidogrel in acute coronary syndrome (ACS) patients with hypersensitivity to aspirin, undergoing coronary stenting. Forty-two consecutive ACS patients treated with stent implantation were randomly assigned to receive clopidogrel 75 mg daily (loading dose 300 mg) plus indobufen 100 mg twice a day (group A), or clopidogrel 75 mg daily, after 300 mg of loading dose (group B). Platelet activity and safety were monitored in both groups at 1, 3, 6, 12, and 18 months with laboratory and clinical evaluation. A lower value of max % platelet aggregation to arachidonic acid and collagen was found in group A compared to group B (31.79 ± 27.33 vs. 73.67 ± 19.92; p < 0.0001 and 28.53 ± 21.32 vs. 73.58 ± 17.71; p < 0.0001, respectively). There was no difference in max % of platelet inhibition to adenosine diphosphate between the two groups (14.23 ± 18.92 vs. 10.30 ± 18.97; p = 0.23). In the population that was under indobufen treatment, the serum thromboxane B2 (TXB2) production at 1 week and 1 month was very low (2.6 ± 1.6 ng/ml and 3.0 ± 2.7 ng/ml, respectively; p = 0.82). The combined treatment was well tolerated in group A patients. This study suggests that the combined antiplatelet treatment with clopidogrel and indobufen could be a good option in ACS patients with hypersensitivity to aspirin undergoing coronary stenting.

[Pharmacokinetics after oral and intravenous administration of d,l-monolysine acetylsalicylate and an oral dose of acetylsalicylic acid in healthy volunteers].

PubMed

Raschka, C; Koch, H J

2001-01-01

We studied the ASA pharmacokinetics of single doses of 500 mg and 1000 mg of D,L-lysine-monoacetylsalicylate (Lys-ASA) administered both orally (Delgesic) and 500 mg parenterally (Aspisol) as well as 500 mg acetylsalicylate (ASA, Aspirin) in 13 healthy volunteers. Blood samples were taken before and at defined times up to 48 h after application of Lys-ASA and ASA. Analysis for ASA and its metabolite salicylic acid were performed by HPLC. All concentration versus time data were presented descriptively. As far as ASA was concerned, differences were assessed by means of ANOVA according to Friedman including post hoc Wilcoxon tests for each time point. Pharmacokinetic parameters were calculated based on a one-compartment model. The concentration vs. time curves after oral intake of 500 mg of ASA and Lys-ASA differed significantly (p < 0.001). Peak serum ASA concentrations (Cmax) were 6.8 mg/l for oral Lys-ASA and 2.7 mg/l for ASA per os. The corresponding tmax-values were 14.2 and 38.0 min. Absolute bioavailabilities for 500 mg doses were 75.4 and 63.4 pour cent, respectively. After intake of 100 mg and 1000 mg oral doses of Lys-ASA Cmax was 2.7 mg/l and 15.9 mg/l, tmax being 14.2 min for the 1000 mg dose. The shortest half-life was found after i.v. injection with 7.5 min. Metabolism was fast with maximum rise of salicylic acid concentration after injection of Lys-ASS. We conclude that concerning time dimension oral administration of Lys-ASA is almost equivalent to i.v. Lys-ASA and may be an alternative for i.v. administration in cases of acute heart attacks.

The Third Ambient Aspirin Polymorph

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shtukenberg, Alexander G.; Hu, Chunhua T.; Zhu, Qiang

Polymorphism in aspirin (acetylsalicylic acid), one of the most widely consumed medications, was equivocal until the structure of a second polymorph II, similar in structure to the original form I, was reported in 2005. Here, the third ambient polymorph of aspirin is described. Lastly, it was crystallized from the melt and its structure was determined using a combination of X-ray powder diffraction analysis and crystal structure prediction algorithms.

The Third Ambient Aspirin Polymorph

DOE PAGES

Shtukenberg, Alexander G.; Hu, Chunhua T.; Zhu, Qiang; ...

2017-05-17

Polymorphism in aspirin (acetylsalicylic acid), one of the most widely consumed medications, was equivocal until the structure of a second polymorph II, similar in structure to the original form I, was reported in 2005. Here, the third ambient polymorph of aspirin is described. Lastly, it was crystallized from the melt and its structure was determined using a combination of X-ray powder diffraction analysis and crystal structure prediction algorithms.

Warfarin and Aspirin Use for Stroke Prevention Among Patients With Atrial Fibrillation: The US National Health and Wellness Survey.

PubMed

Goren, Amir; Liu, Xianchen; Gupta, Shaloo; Simon, Teresa A; Phatak, Hemant

2015-01-01

Vitamin K antagonist (VKA) and aspirin (ASA) are recommended for stroke prevention in patients with atrial fibrillation (AF). This study examined VKA and ASA use and their clinical correlates, including CHADS2 stroke risk scores, among adult patients with AF in the general population. Participants included 1290 (1.72%) adults reporting diagnosis with AF (mean age, 64.9 years; 65% men) from the 2009 US National Health and Wellness Survey, an online, self-administered, nationwide, stratified random sample survey of 75,000 adults. Antithrombotic use patterns, including VKA, ASA, VKA+ASA, and non-VKA/ASA, and their correlates were examined using logistic regressions. Respondents with AF were treated with VKA (26.6%), ASA (34.5%), VKA+ASA (15.4%), or neither (23.5%). Among those with CHADS2 ≥1, 19.3% did not report use of VKA or ASA. Among those with CHADS2 ≥2, 35.7% were treated only with ASA. Adjusting for covariates in logistic regressions, CHADS2 ≥1 was associated with VKA and/or ASA (vs. non-VKA/ASA) use (P ≤ 0.02), but CHADS2 score did not differentiate VKA versus ASA use (P > 0.4). Comorbidities were associated with ASA versus VKA use (P ≤ 0.01). Older age, male gender, married status, and obesity were each associated with use of at least one of the treatments investigated (all P < 0.05). One-in-five AF patients with CHADS2 ≥1 were untreated and more than one-third with CHADS2 ≥2 treated with only ASA for stroke prevention. Our findings suggest that although patient characteristics including CHADS2 score were associated with either VKA or ASA use, CHADS2 score was unrelated to VKA versus ASA treatment.

Upper Gastrointestinal Complications and Cardiovascular/Gastrointestinal Risk Calculator in Patients with Myocardial Infarction Treated with Aspirin.

PubMed

Wen, Lei

2017-08-20

Aspirin is widely used for the prevention of cardiovascular and cerebrovascular diseases for the past few years. However, much attention has been paid to the adverse effects associated with aspirin such as gastrointestinal bleeding. How to weigh the benefits and hazards? The current study aimed to assess the feasibility of a cardiovascular/gastrointestinal risk calculator, AsaRiskCalculator, in predicting gastrointestinal events in Chinese patients with myocardial infarction (MI), determining unique risk factor(s) for gastrointestinal events to be considered in the calculator. The MI patients who visited Shapingba District People's Hospital between January 2012 and January 2016 were retrospectively reviewed. Based on gastroscopic data, the patients were divided into two groups: gastrointestinal and nongastrointestinal groups. Demographic and clinical data of the patients were then retrieved for statistical analysis. Univariate and multiple logistic regression analyses were used to identify independent risk factors for gastrointestinal events. The receiver operating characteristic (ROC) curves were used to assess the predictive value of AsaRiskCalculator for gastrointestinal events. A total of 400 MI patients meeting the eligibility criteria were analyzed, including 94 and 306 in the gastrointestinal and nongastrointestinal groups, respectively. The data showed that age, male gender, predicted gastrointestinal events, and Helicobacter pylori (HP) infection were positively correlated with gastrointestinal events. In multiple logistic regression analysis, predicted gastrointestinal events and HP infection were identified as risk factors for actual gastrointestinal events. HP infection was highly predictive in Chinese patients; the ROC curve indicated an area under the curve of 0.822 (95% confidence interval: 0.774-0.870). The best diagnostic cutoff point of predicted gastrointestinal events was 68.0‰, yielding sensitivity and specificity of 60.6% and 93

Aspirin attenuation of alcohol-induced flushing and intoxication in Oriental and Occidental subjects.

PubMed

Truitt, E B; Gaynor, C R; Mehl, D L

1987-01-01

Aspirin (ASA) was tested in a group of 8 Oriental and 3 Occidental subjects who were shown in a previous study to respond to small doses of ethanol (0.06-0.25 g/kg) with facial flushing. They were compared to a similar group of 11 non-flushing Occidental subjects following a larger ethanol dose (0.37 g/kg) to determine if similar effects could be produced in less sensitive individuals. Control tests of blood ethanol and acetaldehyde (AcH) levels (calculated from breath), facial and neck skin temperatures, body sway (Romberg test), blood pressure, heart rate and 10 Subjective High Assessment Scales (SHAS-Judd, 1977) were conducted before and at 15, 30, 60 and 90 minutes after drinking ethanol as vodka in orange juice. The tests were repeated one week later one hour after receiving 0.64 gm of ASA orally. ASA produced slight changes in the early absorption of ethanol and small decreases in AcH levels in the flushing and non-flushing groups. Facial flushing was markedly reduced in the flushing group, but was slightly increased in the non-flushing Occidentals. Body sway was reduced by ASA in both groups. An alcohol-induced increase in heart rate in the flushing group was reduced with no change in blood pressure. SHAS subjective parameters were widely variable, but indicated that ASA produced reduced sleepiness and earlier relaxation in the flushing group. It is concluded that ASA can block alcohol-induced facial flushing in sensitive subjects and also reduces body sway in the Romberg test and alters some subjective feelings of alcohol intoxication.

Fisher Discrimination of Metabolic Changes in Rats Treated with Aspirin and Ibuprofen.

PubMed

Zhang, Jing; Song, Huanchun; Jiang, Shuying; Chen, Zhibin; Tong, Shuhua; Lin, Feiyan; Wen, Congcong; Zhang, Xiuhua; Hu, Lufeng

2017-01-01

Aspirin and ibuprofen are the most frequently prescribed non-steroidal anti-inflammatory drugs in the world. However, both are associated with a variety of toxicities. We applied serum metabonomics and Fisher discrimination for the early diagnosis of its toxic reaction in order to help diagnose these toxicities. A total of 45 rats were randomly divided into Control group, Aspirin group, and Ibuprofen groups. The experiment groups were given intragastric aspirin (15 mg/kg) or ibuprofen (15 mg/kg) for 3 weeks. Liver function tests were performed and blood metabonomics were analyzed by gas chromatography-mass spectrometry. The most important compounds altered were trihydroxybutyric acid and l-alanine in the aspirin group, and acetoacetic acid, l-alanine, and trihydroxybutyric acid in the ibuprofen group. With respect to metabolic profiles, all 3 groups were completely distinct from one another. Fisher discrimination showed that 91.1% of the original grouped cases were correctly classified by the third week. However, only 55.6% of liver function tests were able to classify grouped cases correctly. Trihydroxybutyric acid, l-alanine, and acetoacetic acid were the most significant indicators of altered serum metabolites following intragastric administration of aspirin and ibuprofen in rates. These metabolomic data may be used for classification of aspirin and ibuprofen toxicity. © 2017 S. Karger AG, Basel.

Aspirin resistance in systemic lupus erythematosus. A pilot study.

PubMed

Akdogan, A; Kilic, L; Akman, U; Dogan, I; Karadag, O; Bilgen, S A; Buyukasik, Y; Kiraz, S; Ertenli, I

2013-07-01

Systemic lupus erythematosus (SLE) patients are at increased risk of thrombosis and cardiovascular diseases. Aspirin is an effective treatment option for these patients. The aim of this study was to investigate the presence of aspirin resistance in SLE patients. We studied aspirin resistance in 33 SLE patients and nine healthy controls by using a Multiplate® impedance aggregometer (Dynabyte GmbH, Munich, Germany). Twenty-six SLE patients were on regular aspirin treatment. Aspirin resistance was found in five (19.2%) out of 26 patients who were on aspirin treatment. When the tests were repeated by adding acetylsalicylic acid in the medium, all of these patients became responsive to the aspirin. SLE disease activity, body mass index, smoking status, and the presence of anticardiolipin antibodies or positive lupus anticoagulant test results were no different in patients with or without aspirin resistance. (p>0.05 for all). Our results suggest that there may be a considerable number of SLE patients with aspirin resistance.

Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor

PubMed Central

Perretti, Mauro; Chiang, Nan; La, Mylinh; Fierro, Iolanda M.; Marullo, Stefano; Getting, Stephen J; Solito, Egle; Serhan, Charles N.

2009-01-01

Aspirin (ASA) and dexamethasone (DEX) are widely used anti-inflammatory agents yet their mechanism(s) for blocking polymorphonuclear neutrophil (PMN) accumulation at sites of inflammation remains unclear. Here, we report that inhibition of PMN infiltration by ASA and DEX is a property shared by aspirin-triggered lipoxins (ATL) and the glucocorticoid-induced annexin 1 (ANXA1)-derived peptides that are both generated in vivo and act at the lipoxin A4 receptor (ALXR/FPRL1) to halt PMN diapedesis. These structurally diverse ligands specifically interact directly with recombinant human ALXR demonstrated by specific radioligand binding and function as well as immunoprecipitation of PMN receptors. In addition, the combination of both ATL and ANXA1-derived peptides limited PMN infiltration and reduced production of inflammatory mediators (that is, prostaglandins and chemokines) in vivo. Together, these results indicate functional redundancies in endogenous lipid and peptide anti-inflammatory circuits that are spatially and temporally separate, where both ATL and specific ANXA1-derived peptides act in concert at ALXR to downregulate PMN recruitment to inflammatory loci. PMID:12368905

Aspirin

MedlinePlus

... of the American Heart Association Cardiology Patient Page Aspirin Jeremy S. Paikin , John W. Eikelboom Download PDF https:// ... treatment of heart attack and stroke. How Does Aspirin Work? Aspirin reduces the risk of heart attacks ...

NO-donating aspirin inhibits angiogenesis by suppressing VEGF expression in HT-29 human colon cancer mouse xenografts

PubMed Central

Ouyang, Nengtai; Williams, Jennie L.; Rigas, Basil

2008-01-01

The inhibitory effect of NO-donating aspirin (NO-ASA) on colon cancer has been demonstrated in vivo and in vitro but its mechanism is still obscure. We investigated the effect of NO-ASA on angiogenesis. Four groups of athymic mice (N = 12) bearing subcutaneous xenotransplants of HT-29 human colon cancer cells were injected intratumorally twice a week for 3 weeks with vehicle or m-NO-ASA or p-NO-ASA; the fourth group received no injections. The necrotic area of tumors, expressed as percentage of total area, was similar in the non-injected and vehicle-injected groups (51.8 ± 2.8 versus 52.2 ± 4.1, P > 0.05; mean ± SEM for these and subsequent values). Compared with the vehicle group, the necrotic area of tumors was higher in the m-NO-ASA-treated (61.0 ± 2.7, P < 0.02) and p-NO-ASA (65.8 ± 2.4, P < 0.001)-treated groups. NO-ASA decreased microvessel density: vehicle = 11.7 ± 0.8; m-NO-ASA = 7.8 ± 0.6 (P = 0.0003 versus vehicle) and p-NO-ASA 6.2 ± 0.7 (P = 0.0001 versus vehicle). The expression of vascular endothelial growth factor (VEGF) was significantly reduced in response to NO-ASA, with the p- isomer being more potent than the m-. NO-ASA altered the spatial distribution of VGEF expression, with 16.7% of the vehicle-treated xenografts displaying diminished VEGF in the inner region of the area between necrosis and the outer perimeter of the tumor, compared with those treated with m- (58.3%) or p-NO-ASA (75%, P < 0.01 for both versus control). Our findings indicate that NO-ASA suppresses the expression of VEGF, which leads to suppressed angiogenesis. The antiangiogenic activity of NO-ASA may be part of its antineoplastic effect. PMID:18544566

Acetylsalicylic acid (aspirin) and salicylic acid interaction with the human erythrocyte membrane bilayer induce in vitro changes in the morphology of erythrocytes.

PubMed

Suwalsky, Mario; Belmar, Jessica; Villena, Fernando; Gallardo, María José; Jemiola-Rzeminska, Malgorzata; Strzalka, Kazimierz

2013-11-01

Despite the well-documented information, there are insufficient reports concerning the effects of salicylate compounds on the structure and functions of cell membranes, particularly those of human erythrocytes. With the aim to better understand the molecular mechanisms of the interaction of acetylsalicylic acid (ASA) and salicylic acid (SA) with cell membranes, human erythrocyte membranes and molecular models were utilized. These consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. The capacity of ASA and SA to perturb the multibilayer structures of DMPC and DMPE was evaluated by X-ray diffraction while DMPC unilamellar vesicles (LUV) were studied by fluorescence spectroscopy. Moreover, we took advantage of the capability of differential scanning calorimetry (DSC) to detect the changes in the thermotropic phase behavior of lipid bilayers resulting from ASA and SA interaction with PC and PE molecules. In an attempt to further elucidate their effects on cell membranes, the present work also examined their influence on the morphology of intact human erythrocytes by means of defocusing and scanning electron microscopy, while isolated unsealed human erythrocyte membranes (IUM) were studied by fluorescence spectroscopy. Results indicated that both salicylates interact with human erythrocytes and their molecular models in a concentration-dependent manner perturbing their bilayer structures. Copyright © 2013 Elsevier Inc. All rights reserved.

Protein nitration and nitrosylation by NO-donating aspirin in colon cancer cells: Relevance to its mechanism of action

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Jennie L.; Ji, Ping; Ouyang, Nengtai

Nitric oxide-donating aspirin (NO-ASA) is a promising agent for cancer prevention. Although studied extensively, its molecular targets and mechanism of action are still unclear. S-nitrosylation of signaling proteins is emerging as an important regulatory mechanism by NO. Here, we examined whether S-nitrosylation of the NF-{kappa}B, p53, and Wnt signaling proteins by NO-ASA might explain, in part, its mechanism of action in colon cancer. NO-ASA releases significant amounts of NO detected intracellularly in HCT116 and HT-29 colon cells. Using a modified biotin switch assay we demonstrated that NO-ASA S-nitrosylates the signaling proteins p53, {beta}-catenin, and NF-{kappa}B, in colon cancer cells inmore » a time- and concentration-dependent manner. NO-ASA suppresses NF-{kappa}B binding to its cognate DNA oligonucleotide, which occurs without changes in the nuclear levels of the NF-{kappa}B subunits p65 and p50 and is reversed by dithiothreitol that reduces -S-NO to -SH. In addition to S-nitrosylation, we documented both in vitro and in vivo widespread nitration of tyrosine residues of cellular proteins in response to NO-ASA. Our results suggest that the increased intracellular NO levels following treatment with NO-ASA modulate cell signaling by chemically modifying key protein members of signaling cascades. We speculate that S-nitrosylation and tyrosine nitration are responsible, at least in part, for the inhibitory growth effect of NO-ASA on cancer cell growth and that this may represent a general mechanism of action of NO-releasing agents.« less

Randomized controlled trial comparing impact on platelet reactivity of twice-daily with once-daily aspirin in people with Type 2 diabetes.

PubMed

Bethel, M A; Harrison, P; Sourij, H; Sun, Y; Tucker, L; Kennedy, I; White, S; Hill, L; Oulhaj, A; Coleman, R L; Holman, R R

2016-02-01

Reduced aspirin efficacy has been demonstrated in people with Type 2 diabetes. Because increased platelet reactivity and/or turnover are postulated mechanisms, we examined whether higher and/or more frequent aspirin dosing might reduce platelet reactivity more effectively. Participants with Type 2 diabetes (n = 24) but without known cardiovascular disease were randomized in a three-way crossover design to 2-week treatment periods with aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily. The primary outcome was platelet reactivity, assessed using the VerifyNow(™) ASA method. Relationships between platelet reactivity and aspirin dosing were examined using generalized linear mixed models with random subject effects. Platelet reactivity decreased from baseline with all doses of aspirin. Modelled platelet reactivity was more effectively reduced with aspirin 100 mg twice daily vs. 100 mg once daily, but not vs. 200 mg once daily. Aspirin 200 mg once daily did not differ from 100 mg once daily. Aspirin 100 mg twice daily was also more effective than once daily as measured by collagen/epinephrine-stimulated platelet aggregation and urinary thromboxane levels, with a similar trend measured by serum thromboxane levels. No episodes of bleeding occurred. In Type 2 diabetes, aspirin 100 mg twice daily reduced platelet reactivity more effectively than 100 mg once daily, and numerically more than 200 mg once daily. Clinical outcome trials evaluating primary cardiovascular disease prevention with aspirin in Type 2 diabetes may need to consider using a more frequent dosing schedule. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Preventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study.

PubMed

Irish, Ashley; Dogra, Gursharan; Mori, Trevor; Beller, Elaine; Heritier, Stephane; Hawley, Carmel; Kerr, Peter; Robertson, Amanda; Rosman, Johan; Paul-Brent, Peta-Anne; Starfield, Melissa; Polkinghorne, Kevan; Cass, Alan

2009-01-21

Haemodialysis (HD) is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF). The Primary failure rate of an AVF ranges between 20-54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s) for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF. The study population is adult patients with stage IV or V chronic kidney disease (CKD) currently on HD or where HD is planned to start within 6 months in whom a planned upper or lower arm AVF is to be the primary HD access. Using a factorial-design trial, patients will be randomised to aspirin or matching placebo, and also to omega-3 fatty acids or matching placebo, resulting in four treatment groups (aspirin placebo/omega-3 fatty acid placebo, aspirin/omega-3 fatty acid placebo, aspirin placebo/omega-3 fatty acid, aspirin/omega-3 fatty acid). Randomisation will be achieved using a dynamic balancing method over the two stratification factors of study site and upper versus lower arm AVF. The medication will be commenced pre-operatively and continued for 3 months post surgery. The primary outcome is patency of the AVF at three months after randomisation. Secondary outcome measures will include functional patency at six and twelve months, primary patency time, secondary (assisted) patency time, and adverse events, particularly bleeding. This multicentre Australian and New Zealand study has been designed to determine whether the outcome of surgery to create de novo AVF can be improved by the use of aspirin and/or omega-3 fatty acids. Recently a placebo-controlled trial has shown that

Cost-Effectiveness of Proton Pump Inhibitor Co-Therapy in Patients Taking Aspirin for Secondary Prevention of Ischemic Stroke.

PubMed

Takabayashi, Nobuyoshi; Murata, Kyoko; Tanaka, Shiro; Kawakami, Koji

2015-10-01

Low-dose aspirin (ASA) is effective for secondary prevention of ischemic stroke but can increase the risks of hemorrhagic stroke, upper gastrointestinal bleeding (UGIB), and dyspepsia. Prophylactic administration of proton pump inhibitors (PPIs) reduces the risks of these digestive symptoms. We investigated the cost effectiveness of adding a PPI to ASA therapy for ischemic stroke patients in Japan. A Markov state-transition model was developed to compare the cost effectiveness of ASA monotherapy with ASA plus PPI co-therapy in patients with histories of upper gastrointestinal ulcers and ischemic stroke. The model takes into account ASA adherence rate and adverse effects due to ASA, including hemorrhagic stroke and UGIB. The analysis was performed from the perspective of healthcare payers in 2013. In the base case, total life-years by PPI co-therapy and monotherapy were 16.005 and 15.932, respectively. The difference in duration of no therapy (no ASA or PPI) between the therapies was 558.5 days, which would prevent 30.3 recurrences of ischemic stroke per 1000 person-years. The incremental cost-effectiveness ratio of PPI co-therapy relative to monotherapy was ¥1,191,665 (US$11,458) per life-year gained. In a one-way sensitivity analysis, PPI co-therapy was consistently cost effective at a willingness to pay of ¥5,000,000 (US$48,077) per life-year gained. In a probabilistic sensitivity analysis, the probability that PPI co-therapy was cost effective was 89.74% at the willingness to pay. Co-therapy with ASA plus PPI appears to be cost-effective compared with ASA monotherapy. The addition of PPI also appeared to prolong the duration of ASA therapy, thereby reducing the risk of ischemic stroke.

Coadministration of the Human Umbilical Cord Matrix-Derived Mesenchymal Cells and Aspirin Alters Postischemic Brain Injury in Rats.

PubMed

Shams ara, Ali; Sheibani, Vahid; Esmaeilpour, Khadije; Eslaminejad, Touba; Nematollahi-Mahani, Seyed N

2015-09-01

Ischemic stroke is an acute brain insult that induces dramatic changes in the neurons. Treatment of brain stroke is one of the main therapeutic targets of neuroprotective therapies. The aim of this study was to evaluate the protective potential of implanted human umbilical cord mesenchymal stem (hUCMs) cells with/without aspirin (ASA) against focal cerebral ischemia. We assessed the migration and distribution of PKH26-labeled cells after transplantation. After day 10 of transient occlusion, we evaluated the effect of ASA and hUCMs on the recovery of learning and memory in rats by Morris water maze. Afterward, animals were sacrificed, and the infarct area in the brain was evaluated using 2, 3, 5-triphenyltetrazolium chloride staining and also by hematoxylin and eosin. The recovery of learning and memory in ischemic animals that received ASA and hUCM cells improved significantly compared with the untreated ischemic animals. Coadministration of ASA and hUCM cells did not improve the outcome at a comparable rate with ASA and hUCM cells alone. PKH26-labeled cells were detectable in the ischemic area of the brain tissue sections. 2,3,5-Triphenyltetrazolium chloride staining and histologic examinations showed that treatment with ASA and hUCM cells could significantly alter the ischemic area. The results of the present study suggest that ASA and hUCM cells can withstand degenerative changes induced by artificial stroke in the rat. Also the learning and memory disturbance in the ASA and cell-treated animals is less pronounced than ischemic animals. Coadministration of ASA and hUCM cells did not raise the outcome higher than administration of ASA and hUCM cells alone. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Impact of acetylsalicylic Acid on the clinicopathological characteristics and prognosis of patients with invasive breast cancer.

PubMed

Sendur, Mehmet A N; Aksoy, Sercan; Ozdemir, Nuriye Y; Zengin, Nurullah; Altundag, Kadri

2014-04-01

The impact of acetylsalicylic acid (ASA) on the clinicopathological characteristics of breast cancer has not yet been elucidated in detail; we therefore aimed to investigate the effects of ASA on the clinicopathological characteristics of patients with breast cancer. Patients diagnosed with breast cancer were retrospectively analyzed. Breast cancer patients who were taking ASA at the time of breast cancer diagnosis were enrolled as ASA users (n = 84); matching patients with the same age who were not taking ASA were included as control group (n = 890). The median age was 56 (range 34-82) years in both groups. ASA users had a significantly lower incidence of grade II-III tumors compared to non-users (P = 0.02). The other clinicopathological characteristics and treatment histories were similar in both groups. In patients using ASA, the disease-free survival (DFS) rate was 97.3%, 89.4%, and 79.9% and in non-users it was 94.1%, 81.8%, and 70.9% in the 1rst, 3rd, and 5th year, respectively (P = 0.01). In aspirin users, the overall survival rate was 95.0%, 90.6%, and 87.6% and in non-users it was 98.1%, 91.2%, and 85.5% in the 1rst, 3rd, and 5th year, respectively (P = 0.50). Using ASA at the time of breast cancer diagnosis was associated with significantly improved DFS in breast cancer patients.

The use of prophylactic gastroprotective therapy in patients with nonsteroidal anti-inflammatory drug- and aspirin-associated ulcer bleeding: a cross-sectional study.

PubMed

Ho, C W; Tse, Y K; Wu, B; Mulder, C J J; Chan, F K L

2013-04-01

Poor adherence to gastroprotective agents (GPAs) is common among users of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (ASA). There are little data on the utilization of GPAs among NSAID and ASA users complicated by ulcer bleeding. To study the utilization of GPA among NSAID and ASA ulcers before the onset of ulcer bleeding. We conducted a cross-sectional study to determine the exposure to NSAIDs, ASA, and GPAs within 4 weeks before endoscopically confirmed ulcer bleeding. Sensitivity analysis was performed to study how improving adherence to GPA use would reduce the risk of ulcer bleeding in high-risk users. Between 2000 and 2009, 1093 and 2277 patients had NSAID- and ASA-associated ulcer bleeding respectively. The incidence of NSAID-associated ulcer bleeding declined by 40%, whereas that of ASA-associated ulcer bleeding increased by 46%. Thirty-nine per cent of NSAID users and 75% of ASA users belonged to high ulcer risk category. Although GPA prescription rate has increased over time, only 41.6% and 30.6% of high-risk NSAID and ASA users received GPAs before ulcer bleeding respectively. Sensitivity analysis showed that if GPAs could reduce bleeding risk by 50%, improving adherence would prevent up to 35% of ulcer bleeding in high-risk users. A substantial proportion of high-risk NSAID and ASA users had not received prophylaxis with gastroprotective agents before ulcer bleeding. These bleeding episodes may be preventable with better adherence to gastroprotective agent use. © 2013 Blackwell Publishing Ltd.

Challenging the FDA black box warning for high aspirin dose with ticagrelor in patients with diabetes.

PubMed

DiNicolantonio, James J; Serebruany, Victor L

2013-03-01

Ticagrelor, a novel reversible antiplatelet agent, has a Food and Drug Administration (FDA) black box warning to avoid maintenance doses of aspirin (ASA) >100 mg/daily. This restriction is based on the hypothesis that ASA doses >100 mg somehow decreased ticagrelor's benefit in the Platelet Inhibition and Patient Outcomes (PLATO) U.S. cohort. However, these data are highly postrandomized, come from a very small subgroup in PLATO (57% of patients in the U.S. site), and make no biological sense. Moreover, the ticagrelor-ASA interaction was not significant by any multivariate Cox regression analyses. The Complete Response Review for ticagrelor indicates that for U.S. PLATO patients, an ASA dose >300 mg was not a significant interaction for vascular outcomes. In the ticagrelor-ASA >300 mg cohort, all-cause and vascular mortality were not significantly increased (hazard ratio [HR] 1.27 [95% CI 0.84-1.93], P = 0.262 and 1.39 [0.87-2.2], P = 0.170), respectively. Furthermore, for major adverse cardiovascular events (MACEs), 30-day all-cause mortality, and 30-day vascular mortality, the strongest interaction is the diabetes-ASA interaction. That is, patients who had diabetes had significantly fewer MACEs through study end (0.49 [0.34-0.63], P < 0.0001), significantly less 30-day all-cause mortality (0.33 [0.20-0.56], P < 0.0001), and significantly less 30-day vascular mortality (0.35 [0.22-0.55], P < 0.0001), respectively, when given high-dose (300-325 mg) ASA, regardless of treatment (clopidogrel or ticagrelor) assignment. The black box warning for the use of maintenance ASA doses >100 mg with ticagrelor is inappropriate for patients with diabetes and not evidence based.

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

PubMed

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.

Does non-acetylated salicylate inhibit thromboxane biosynthesis in human platelets?

PubMed

Danesh, B J; McLaren, M; Russell, R I; Lowe, G D; Forbes, C D

1988-08-01

Ingestion of aspirin (acetyl salicylic acid: ASA) may promote bleeding complications due to inhibition of thromboxane biosynthesis, which results in the prolongation of bleeding time. The effect is believed to be achieved by the irreversible acetylation of the enzyme cyclooxygenase by aspirin. This alteration in platelet function by aspirin prohibits its use in patients with bleeding disorders such as haemophiliacs. Choline magnesium trisalicylate (CMT; Napp Laboratories Ltd) is a non-acetylated salicylate with analgesic and anti-inflammatory effects similar to that of aspirin. However, despite a comparable salicylate absorption from the two drugs, CMT is found to have no inhibitory action in platelet aggregation and to cause less gastric mucosal damage and gastrointestinal blood loss than aspirin. To investigate the role of the acetyl moiety in the inhibition of platelet thromboxane biosynthesis, we studied the effect of CMT and ASA on bleeding time, serum thromboxane B2 (TxB2) and thromboxane (Tx) generation in healthy volunteers.

Dipyrone comedication in aspirin treated stroke patients impairs outcome.

PubMed

Dannenberg, Lisa; Erschoff, Vladimir; Bönner, Florian; Gliem, Michael; Jander, Sebastian; Levkau, Bodo; Kelm, Malte; Hohlfeld, Thomas; Zeus, Tobias; Polzin, Amin

2016-12-01

>50% of stroke patients rely on analgesic medication to control pain. Aspirin is the mainstay of medical treatment of stroke patients; however analgesic medication with dipyrone impairs aspirin antiplatelet effects ex-vivo. The clinical impact of this impairment is unknown. Therefore, we aimed to determine aspirin antiplatelet effects and neurological outcome in stroke patients with aspirin and dipyrone comedication. We conducted a prospective cohort study in 41 patients with stroke. Primary outcome was pharmacodynamic response to aspirin in dipyrone treated stroke patients. Secondary outcome was neurological recovery after stroke. Pharmacodynamic response to aspirin was measured using arachidonic acid induced aggregation in light-transmission aggregometry. Neurological outcome was determined three months after stroke onset by telephone interview. Patient's characteristics were similar in the aspirin-alone group and the aspirin+dipyrone group. Impaired pharmacodynamic response to aspirin occurred in 62% (14/21) of patients with aspirin and dipyrone co-medication. Only 10% (2/20) of aspirin treated patients without analgesic comedication displayed residual platelet reactivity (P=0.001; odds ratio [OR], 18 [95% CI, 3.2-100]). Excellent neurological recovery (measured by three months follow-up modified Rankin Scale<2) was observed in 80% (16/20) of patients in the aspirin-alone group and 48% (10/21) of patients in the aspirin+dipyrone group (P=0.037; OR, 4.4 [95% CI, 1.1-17.7]). Dipyrone comedication in patients with stroke impairs pharmacodynamic response to aspirin. This is associated with worse clinical outcome. Therefore dipyrone should be used with caution in aspirin treated stroke patients. https://clinicaltrials.gov/show/NCT02148939; Identifier: NCT02148939. Copyright © 2016 Elsevier Inc. All rights reserved.

ASAS 095221-4329.8 und ASAS 123034-7703.9 - zwei R-CrB-Stern-Kandidaten aus der ASAS-Datenbank

NASA Astrophysics Data System (ADS)

Huemmerich, Stefan

2011-04-01

During an examination of ASAS Misc-type objects, the stars ASAS 095221-4329.8 GSC 07706-00560, 09:52:21.38 -43:29:40.5) and ASAS 123034-7703.9 (GSC 09416-00380, 12:30:34.22 -77:03:52.7) - both of which show semi-regular variability - were found to exhibit significant obscuration events in their V-band lightcurves. Both stars are likely to be red giants undergoing fading events, possibly of DY Per-type. However, spectroscopy of both stars is needed for a conclusive classification. The corresponding entries in the International Variable Star Index (VSX) have been revised accordingly; variability type was set to "RCB:".

Performing Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease.

PubMed

Waldram, Jeremy D; Simon, Ronald A

2016-11-01

Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic rhinosinusitis with nasal polyps, asthma, and reactions to cyclooxygenase-1-inhibiting drugs. This condition is often refractory to standard medical treatments and results in aggressive nasal polyposis that often requires multiple sinus surgeries. Aspirin desensitization followed by daily aspirin therapy is an important treatment option, and its efficacy has been validated in multiple research studies. Aspirin desensitization is not without risk, but specific protocols and recommendations exist to mitigate the risk. Most patients with AERD can undergo aspirin desensitization in an outpatient setting under the supervision of an allergist. Copyright © 2016 Elsevier Inc. All rights reserved.

Aspirin Desensitization

MedlinePlus

... 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 " ...

Differential induction of peroxisomal beta-oxidation enzymes by clofibric acid and aspirin in piglet tissues.

PubMed

Yu, X X; Odle, J; Drackley, J K

2001-11-01

Peroxisomal beta-oxidation (POX) of fatty acids is important in lipid catabolism and thermogenesis. To investigate the effects of peroxisome proliferators on peroxisomal and mitochondrial beta-oxidation in piglet tissues, newborn pigs (1-2 days old) were allowed ad libitum access to milk replacer supplemented with 0.5% clofibric acid (CA) or 1% aspirin for 14 days. CA increased ratios of liver weight to body weight (P < 0.07), kidney weight to body weight (P < 0.05), and heart weight to body weight (P < 0.001). Aspirin decreased daily food intake and final body weight but increased the ratio of heart weight to body weight (P < 0.01). In liver, activities of POX, fatty acyl-CoA oxidase (FAO), total carnitine palmitoyltransferase (CPT), and catalase were 2.7-, 2.2-, 1.5-fold, and 33% greater, respectively, for pigs given CA than for control pigs. In heart, these variables were 2.2-, 4.1-, 1.9-, and 1.8-fold greater, respectively, for pigs given CA than for control pigs. CA did not change these variables in either kidney or muscle, except that CPT activity was increased approximately 110% (P < 0.01) in kidney. Aspirin increased only hepatic FAO and CPT activities. Northern blot analysis revealed that CA increased the abundance of catalase mRNA in heart by approximately 2.2-fold. We conclude that 1) POX and CPT in newborn pigs can be induced by peroxisomal proliferators with tissue specificity and 2) the relatively smaller induction of POX in piglets (compared with that in young or adult rodents) may be related to either age or species differences.

Stopping versus continuing acetylsalicylic acid before coronary artery bypass surgery: A systematic review and meta-analysis of 14 randomized controlled trials with 4499 patients.

PubMed

Sá, Michel Pompeu Barros Oliveira; Soares, Artur Freire; Miranda, Rodrigo Gusmão Albuquerque; Araújo, Mayara Lopes; Menezes, Alexandre Motta; Silva, Frederico Pires Vasconcelos; Lima, Ricardo Carvalho

2017-11-01

This study aimed to evaluate the efficacy and safety of continuing versus stopping aspirin [acetylsalicylic acid (ASA)] preoperatively in patients undergoing coronary artery bypass graft surgery. MEDLINE, EMBASE, CENTRAL/Cochrane Controlled Trials Register (CCTR), ClinicalTrials.gov, Scientific Electronic Library Online (SciELO), Literatura Latino Americana em Ciências da Saúde (LILACS), Google Scholar and reference lists of relevant articles were searched for randomized controlled trials that reported efficacy outcomes of myocardial infarction and mortality, and safety outcomes of blood loss, packed red blood cell transfusion and surgical re-exploration were compared between groups. Fourteen studies fulfilled our eligibility criteria and included a total of 4499 patients (2329 for 'continuing ASA' and 2170 for 'stopping ASA'). In the pooled analysis, continuing aspirin therapy did not reduce the risk of myocardial infarction [risk ratio 0.834, 95% confidence interval (CI) 0.688-1.010; P = 0.063] or operative mortality (risk ratio 1.384, 95% CI 0.727-2.636; P = 0.323). Preoperative ASA increased postoperative chest tube drainage (mean difference 143 ml, 95% CI 39-248 ml; P = 0.007) and packed red blood cell transfusion (mean difference 142 ml, 95% CI 55-228; P = 0.001) but did not increase the risk of surgical re-exploration (risk ratio 1.316, 95% CI 0.910-1.905; P = 0.145). This meta-analysis found no statistically significant difference regarding the risk of operative mortality and myocardial infarction between the 'continuing ASA' and 'stopping ASA' strategies. On the other hand, the mean volume of blood loss and packed red blood cell transfusion was higher in the 'continuing ASA' group, but this finding did not translate into higher risk of reoperation for bleeding. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Aspirin overdose

MedlinePlus

... 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 ...

Aspirin and lipid mediators in the cardiovascular system.

PubMed

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.

The effect of aspirin dosing on platelet function in diabetic and nondiabetic patients: an analysis from the aspirin-induced platelet effect (ASPECT) study.

PubMed

DiChiara, Joseph; Bliden, Kevin P; Tantry, Udaya S; Hamed, Miruais S; Antonino, Mark J; Suarez, Thomas A; Bailon, Oscar; Singla, Anand; Gurbel, Paul A

2007-12-01

Diabetic patients may have a higher prevalence of platelet aspirin resistance than nondiabetic patients. Our goal was to analyze platelet aspirin responsiveness to various aspirin doses in diabetic and nondiabetic patients. We examined the effect of aspirin (81, 162, and 325 mg/day for 4 weeks each) on platelet aspirin responsiveness in 120 stable outpatients (30 diabetic patients and 90 nondiabetic patients) with coronary artery disease (CAD) using light transmittance aggregometry (LTA), VerifyNow, platelet function analyzer (PFA)-100, and levels of urinary 11-dehydro-thromboxane B(2) (11-dh-TxB(2)). In the total group, a low prevalence (0-2%) of aspirin resistance was observed with all aspirin doses as determined by arachidonic acid-induced LTA. Aspirin resistance was higher at the 81-mg dose in diabetic versus nondiabetic patients using collagen-induced LTA (27 vs. 4%, P = 0.001), VerifyNow (13 vs. 3%, P = 0.05), and urinary 11-dh-TxB(2) (37 vs. 17%, P = 0.03). Diabetic patients treated with 81 mg exhibited higher platelet function measured by VerifyNow, collagen- and ADP-induced LTA, and 11-dh-TxB(2) levels (P aspirin doses significantly inhibited platelet function and decreased aspirin resistance in diabetic patients (P < 0.05). Diabetic patients with CAD treated with 81 mg aspirin exhibit a higher prevalence of aspirin resistance and have significantly higher ADP- and collagen-induced platelet aggregation, 11-dh-TxB(2) levels, and aspirin reaction units measured by VerifyNow than nondiabetic patients. Increased aspirin dosing resulted in similar rates of resistance and platelet function levels between groups. These findings indicate that diabetic patients exhibit a global high platelet reactivity phenotype that may be partially overcome by higher aspirin doses.

Effects of clopidogrel and aspirin combination versus aspirin alone on platelet aggregation and major receptor expression in patients with heart failure: the Plavix Use for Treatment Of Congestive Heart Failure (PLUTO-CHF) trial.

PubMed

Serebruany, Victor L; Malinin, Alex I; Jerome, Scott D; Lowry, David R; Morgan, Athol W; Sane, David C; Tanguay, Jean-François; Steinhubl, Steven R; O'connor, Christopher M

2003-10-01

Persistent platelet activation may contribute to thrombotic events in patients with congestive heart failure (CHF). Chronic use of mild platelet inhibitors could therefore represent an independent avenue to improve morbidity, mortality, and quality of life in this expanding population. Although clopidogrel is widely used in patients with acute coronary syndromes and ischemic stroke, the ability of this novel ADP-receptor antagonist to inhibit platelet function in patients with CHF is unknown. We assessed antiplatelet properties of clopidogrel with aspirin (C+A) versus aspirin alone (A) in patients with CHF with heightened platelet activity. Patients with left ventricular ejection fraction <40%, or CHF symptoms in the setting of preserved systolic function and New York Heart Association class II-IV were screened. Patients were considered to have platelet activation when 4 of the following 5 parameters were met: ADP-induced platelet aggregation >60%; collagen-induced aggregation >70%; whole blood aggregation >18 ohms; expression of GP IIb/IIIa >220 log MFI; and P-selectin cell positivity >8%. All patients were treated with 325 mg of acetylsalycilic acid (ASA) for at least 1 month. Patients receiving an antithrombotic agent other than ASA were excluded. Patients meeting clinical and laboratory criteria were randomly assigned to C+A (n=25), A (n=25) groups, or represent screen failures (n=38). Platelet studies (conventional and whole blood aggregometry, shear-induced activation, expression of 10 major receptors and formation of platelet-leukocyte microparticles) were performed at baseline and after 30 days of therapy. There were no deaths, hospitalizations, or serious adverse events. There were no changes in platelet parameters in the A group. In contrast, therapy with C+A resulted in a significant inhibition of platelet activity assessed by ADP-induced (P =.00001), and epinephrine-induced (P =.0016) aggregation, closure time (P =.04), expression of PECAM-1 (P =.009

Up-regulation of Ciliary Neurotrophic Factor in Astrocytes by Aspirin

PubMed Central

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

Reducing AsA leads to leaf lesion and defence response in knock-down of the AsA biosynthetic enzyme GDP-D-mannose pyrophosphorylase gene in tomato plant.

PubMed

Zhang, Chanjuan; Ouyang, Bo; Yang, Changxian; Zhang, Xiaohui; Liu, Hui; Zhang, Yuyang; Zhang, Junhong; Li, Hanxia; Ye, Zhibiao

2013-01-01

As a vital antioxidant, L-ascorbic acid (AsA) affects diverse biological processes in higher plants. Lack of AsA in cell impairs plant development. In the present study, we manipulated a gene of GDP-mannose pyrophosphorylase which catalyzes the conversion of D-mannose-1-P to GDP-D-mannose in AsA biosynthetic pathway and found out the phenotype alteration of tomato. In the tomato genome, there are four members of GMP gene family and they constitutively expressed in various tissues in distinct expression patterns. As expected, over-expression of SlGMP3 increased total AsA contents and enhanced the tolerance to oxidative stress in tomato. On the contrary, knock-down of SlGMP3 significantly decreased AsA contents below the threshold level and altered the phenotype of tomato plants with lesions and further senescence. Further analysis indicated the causes for this symptom could result from failing to instantly deplete the reactive oxygen species (ROS) as decline of free radical scavenging activity. More ROS accumulated in the leaves and then triggered expressions of defence-related genes and mimic symptom occurred on the leaves similar to hypersensitive responses against pathogens. Consequently, the photosynthesis of leaves was dramatically fallen. These results suggested the vital roles of AsA as an antioxidant in leaf function and defence response of tomato.

Aspirin use and endometrial cancer risk and survival.

PubMed

Takiuchi, Tsuyoshi; Blake, Erin A; Matsuo, Koji; Sood, Anil K; Brasky, Theodore M

2018-01-01

The role of acetylsalicylic acid (aspirin) as a chemo-preventive and adjuvant therapeutic agent for cancers is generating attention. Mounting evidence indicates that aspirin reduces the incidence and mortality of certain obesity-related cancers, particularly colorectal cancer. In endometrial cancer, previous studies examining the effect of aspirin remain inconsistent as to the reduction in the risk of endometrial cancer. While some evidence indicates protective effects in obese women, other studies have showed a potential deleterious effect of these medications on endometrial cancer outcomes. However, exposure measurement across studies has been inconsistent in recording dose, duration, and frequency of use; thus making comparisons difficult. In this article, we review the evidence for the association between endometrial cancer and obesity, the pharmacological differences between regular- and low-dose aspirin, as well as the potential anti-tumor mechanism of aspirin, supporting a possible therapeutic effect on endometrial cancer. A proposed mechanism behind decreased cancer mortality in endometrial cancer may be a result of inhibition of metastasis via platelet inactivation and possible prostaglandin E 2 suppression by aspirin. Additionally, aspirin use in particular may have a secondary benefit for obesity-related comorbidities including cardiovascular disease in women with endometrial cancer. Although aspirin-related bleeding needs to be considered as a possible adverse effect, the benefits of aspirin therapy may exceed the potential risk in women with endometrial cancer. The current evidence reviewed herein has resulted in conflicting findings regarding the potential effect on endometrial cancer outcomes, thus indicating that future studies in this area are needed to resolve the effects of aspirin on endometrial cancer survival, particularly to identify specific populations that might benefit from aspirin use. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative effects of the anti-platelet drugs, clopidogrel, ticlopidine, and cilostazol on aspirin-induced gastric bleeding and damage in rats.

PubMed

Takeuchi, Koji; Takayama, Shinichi; Izuhara, Chitose

2014-08-21

The present study compared the effects of frequently used anti-platelet drugs, such as clopidogrel, ticlopidine, and cilostazol, on the gastric bleeding and ulcerogenic responses induced by intraluminal perfusion with 25 mM aspirin acidified with 25 mM HCl (acidified ASA) in rats. The stomach was perfused with acidified ASA at a rate of 0.4 ml/min for 60 min under urethane anesthesia, and gastric bleeding was measured as the concentration of hemoglobin in the luminal perfusate, which was collected every 15 min. Clopidogrel (10-100mg/kg), ticlopidine (10-300 mg/kg), or cilostazol (3-30 mg/kg) was given p.o. 24h or 90 min before the perfusion of acidified ASA, respectively. Perfusion of the stomach with acidified ASA alone led to slight bleeding and lesions in the stomach. The pretreatment with clopidogrel, even though it did not cause bleeding or damage by itself, dose-dependently increased the gastric bleeding and ulcerogenic responses induced by acidified ASA. Ticlopidine also aggravated the severity of damage by increasing gastric bleeding, and the effects of ticlopidine at 300 mg/kg were equivalent to those of clopidogrel at 100mg/kg. In contrast, cilostazol dose-dependently decreased gastric bleeding and damage in response to acidified ASA. These results demonstrated that clopidogrel and ticlopidine, P2Y12 receptor inhibitors, increased gastric bleeding and ulcerogenic responses to acidified ASA, to the same extent, while cilostazol, a phosphodiesterase III inhibitor, suppressed these responses. Therefore, cilostazol may be safely used in dual anti-platelet therapy combined with ASA, without increasing the risk of gastric bleeding. Copyright © 2014 Elsevier Inc. All rights reserved.

ASA24-Kids (no longer available)

Cancer.gov

ASA24-Kids-2014 was released in February 2014 and until March 2017, researchers can register new studies in this version of the ASA24® system. Funding is not currently available for a mobile accessible version for kids, such as ASA24-2016.

Impact of aspirin on presentation and hospital outcomes in patients with acute coronary syndromes (The Global Registry of Acute Coronary Events [GRACE]).

PubMed

Spencer, Frederick A; Santopinto, Jose J; Gore, Joel M; Goldberg, Robert J; Fox, Keith A A; Moscucci, Mauro; White, Kami; Gurfinkel, Enrique P

2002-11-15

The long-term use of aspirin (ASA) reduces the risk of subsequent acute coronary syndromes in patients with coronary artery disease (CAD). It is less clear whether ASA therapy benefits patients who develop an acute coronary syndrome despite its use. Baseline characteristics, type of acute coronary syndrome, and in-hospital events were compared on the basis of previous use of ASA in 11,388 patients with and without a history of CAD presenting to 94 multinational hospitals. A total of 73.0% of patients with a history of CAD (n = 4,974) were previously on long-term ASA therapy compared with 19.4% of patients without a history of CAD (n = 6,414). After multivariate regression analysis controlling for various potentially confounding factors, patients with a history of CAD who were previously taking ASA were significantly less likely to present with ST-segment elevation myocardial infarction (MI) (adjusted odds ratio [OR] 0.52, 95% confidence intervals [CI] 0.44 to 0.61) or die during hospitalization (OR 0.69, 95% CI 0.50 to 0.95) in comparison to patients who were not taking ASA. Patients without a history of CAD and who were previously taking ASA also had a lower risk of developing ST-segment elevation MI (OR 0.35, 95% CI 0.30 to 0.40) and a trend toward a decreased hospital death rate (OR 0.77, 95% CI 0.55 to 1.07). These results demonstrate that patients with a history of CAD who present with an acute coronary syndrome despite prior ASA use have less severe clinical presentation, fewer hospital complications, and lower in-hospital death rates than patients not previously taking ASA.

Stopping vs. Continuing Aspirin before Coronary Artery Surgery.

PubMed

Myles, Paul S; Smith, Julian A; Forbes, Andrew; Silbert, Brendan; Jayarajah, Mohandas; Painter, Thomas; Cooper, D James; Marasco, Silvana; McNeil, John; Bussières, Jean S; Wallace, Sophie

2016-02-25

Most patients with coronary artery disease receive aspirin for primary or secondary prevention of myocardial infarction, stroke, and death. Aspirin poses a risk of bleeding in patients undergoing surgery, but it is unclear whether aspirin should be stopped before coronary artery surgery. We used a 2-by-2 factorial trial design to randomly assign patients who were scheduled to undergo coronary artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin trial are reported here. Patients were randomly assigned to receive 100 mg of aspirin or matched placebo preoperatively. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. Among 5784 eligible patients, 2100 were enrolled; 1047 were randomly assigned to receive aspirin and 1053 to receive placebo. A primary outcome event occurred in 202 patients in the aspirin group (19.3%) and in 215 patients in the placebo group (20.4%) (relative risk, 0.94; 95% confidence interval, 0.80 to 1.12; P=0.55). Major hemorrhage leading to reoperation occurred in 1.8% of patients in the aspirin group and in 2.1% of patients in the placebo group (P=0.75), and cardiac tamponade occurred at rates of 1.1% and 0.4%, respectively (P=0.08). Among patients undergoing coronary artery surgery, the administration of preoperative aspirin resulted in neither a lower risk of death or thrombotic complications nor a higher risk of bleeding than that with placebo. (Funded by the Australian National Health and Medical Research Council and others; Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.).

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

PubMed

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

2015-01-01

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

Aspirin decreases platelet uptake on Dacron vascular grafts in baboons

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 carotidmore » 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.« less

Urinalysis of MMX-mesalazine as a tool to monitor 5-ASA adherence in daily IBD practice.

PubMed

Römkens, Tessa E H; Te Morsche, Rene; Peters, Wilbert; Burger, David M; Hoentjen, Frank; Drenth, Joost P H

2018-03-01

Adherence is pivotal but challenging in ulcerative colitis (UC) treatment. Many methods to assess adherence are subjective or have limitations. (Nac-)5-aminosalicylic acid (5-ASA) urinalysis by high-performance liquid chromatography (HPLC) seems feasible and reproducible in healthy volunteers. We performed a prospective study in adult quiescent UC patients to evaluate the feasibility of spot (Nac-)5-ASA urinalysis by HPLC to assess adherence in daily inflammatory bowel disease (IBD) care. Twenty-nine patients (51.7% male, mean age 52 ± 11 years) were included (median FU 9 months) and weekly spot urine samples were collected. We found large variation in spot (Nac-)5-ASA urinary excretion that was unrelated to brand, dosing schedule or dosage of 5-ASA. In conclusion, spot (Nac-)5-ASA urinalysis is not applicable to assess 5-ASA adherence in daily IBD care. © 2017 The British Pharmacological Society.

In vitro interference by acetaminophen, aspirin, and metamizole in serum measurements of glucose, urea, and creatinine.

PubMed

Luna-Záizar, Hilda; Virgen-Montelongo, María; Cortez-Álvarez, Cesar R; Ruiz-Quezada, Sandra L; Escutia-Gutiérrez, Raymundo; García-Lemus, Cuauhtémoc R; Mendizabal-Ruiz, Adriana P

2015-05-01

Here we aimed to investigate the in vitro effects of three analgesic-antipyretic drugs frequently used in clinical practice in Mexico - acetaminophen (AAP), aspirin (ASA) and metamizole (MMZ) - on serum measurements of glucose, urea, and creatinine. Each analyte was measured in a base-serum pool spiked with the drugs at subtherapeutic, therapeutic, and toxic doses. Serum glucose and urea were measured using the hexokinase/G-6PDH and urease/GLDH kinetic assays, respectively. Serum creatinine (SCr) was measured with a Jaffe procedure based on the alkaline-picrate reaction and with an enzymatic dry-chemistry system. Measurements were carried out in IL-Monarch and Vitros DT60-II analyzers, respectively. Data were analyzed by the difference-paired interference test and by ANOVA. By the kinetic Jaffe/Monarch procedure, we found positive interference by the drugs on the SCr measurements and by only ASA for urea measurement. For creatinine measurements, the total errors (TEs) were 22-51%, 18-105%, and 15-26% for AAP, ASA, and MMZ respectively, while for urea measurement the TE was 16-21% for ASA. A negative interference by MMZ on SCr (TE=-47%), but no-interference for AAP or ASA, were found via the enzymatic/DT60-II system. In vitro positive interference induced by AAP, ASA, and MMZ (via the alkaline-picrate reaction), or negative interference by MMZ (via a dry-chemistry system), on the SCr measurements highlights the importance of investigating all possible sources of variation that may alter the accuracy of the laboratory tests, in order to provide useful results for making medical decisions for optimal patient care. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

ASA education outreach

NASA Astrophysics Data System (ADS)

Hansen, Uwe J.; Everbach, E. Carr

2003-04-01

A number of very successful Hands-on demo sessions for high school students have been a part of regular ASA meetings for some time. In addition, the Education Committee has organized a series of teacher workshops. These workshops are designed to give high school teachers relatively sophisticated tools to enhance their laboratory content. Workshops for teachers in the elementary grades prepare teachers to use music as a vehicle to introduce additional science concepts. Content and methods associated with both workshops will be discussed. Cyberspace outreach by the ASA was accelerated by the establishment of a Home Page Committee, and more recently by the On-Line Education committee, which is creating an educational website. The website provides a fun way for users to access information including acoustics information, history, demos, and links to the Technical Committee's webpages. The ASA has joined other AIP member societies in developing additional mechanisms, including road shows and nightly news spots.

Clinical and biochemical aspirin resistance in patients with recurrent cerebral ischemia.

PubMed

El-Mitwalli, Ashraf; Azzam, Hanan; Abu-Hegazy, Mohammad; Gomaa, Mohamed; Wasel, Yasser

2013-07-01

Stroke recurrence is an important public health concern. One half of survivors remain disabled, and one seventh requires institutional care. Aspirin remains the cornerstone of primary and secondary stroke prevention; meanwhile, aspirin resistance is one of the possible causes of stroke recurrence. We aimed to evaluate the clinical and biochemical aspirin resistance in patients with recurrent ischemic stroke. We studied demographic characteristics, vascular risk factors, stroke subtypes, radiologic findings and biochemical aspirin resistance tests using both arachidonic acid (AA) and adenosine diphosphate (ADP)-induced light transmittance aggregometry (LTA) on admission and 24 h after observed aspirin ingestion. Of the 82 patients with recurrent cerebral ischemia included in this study, 37 (45%) patients were poor compliant with aspirin. There were no statistically significant differences between the two groups regarding the demographic characteristics, stroke severity, laboratory tests, radiological findings or vascular risk factors. On admission, 19.6% and 4.8% of patients showed aspirin resistance, while 24 h after supervised 300 mg single aspirin dose ingestion, it was 9.8% and 2.4% using ADP and AA-induced LTA respectively. Of the eight aspirin resistant patients, two only showed resistance using both AA and ADP. Aspirin resistance was statistically significantly higher in the male gender, older age, hyperlipidemia, smokers and in all lacunar strokes using AA. Biochemical aspirin resistance in one's series was rather rare (2.4%) and was more prevalent in patients with lacunar strokes. Clinical aspirin failure may often be contributed to poor compliance with aspirin intake. Copyright © 2012 Elsevier B.V. All rights reserved.

Laboratory signs of aspirin response in haemodialysis patients.

PubMed

Kilickesmez, Kadriye O; Kocas, Cuneyt; Okcun, Baris; Abaci, Okay; Kaya, Aysem; Arat, Alev; Gorcin, Bilal; Gurmen, Tevfik

2011-09-01

Aspirin is effective in the secondary prevention and high-risk primary prevention of cardiovascular events. However, clinical and laboratory evidence demonstrates diminished or no response to aspirin in some patients. This study was designed to assess aspirin response in haemodialysis patients. We prospectively enrolled 78 haemodialysis patients (28 female; 58.4 ± 12.6 years old) and 79 patients (29 female; 58.4 ± 10.6 years old) with normal renal function (glomerular filtration rate (GFR) >60 mL/min/1.73 m(2)). All subjects in both the haemodialysis patient group and the control group were taking aspirin (80-300 mg) for at least 30 days and were not taking other antiplatelet agents. Platelet function was assessed by arachidonic acid-induced aggregometry with a Multiplate analyser (Dynabyte Medical, Munich, Germany). Multiplate electrode aggregometry values below 300 AU were applied as a cut-off for response to aspirin. Aspirin non-response was two-fold more prevalent in haemodialysis patients (42.3%) than in patients with normal renal function (21.5%), and this difference was statistically significant (p = 0.005). The two groups were similar in terms of sex, age, tobacco use, the presence of diabetes mellitus, and platelet count. The frequency of aspirin non-response as defined in this study was higher in haemodialysis patients than in patients with normal renal function. However, larger subsets of patients are needed to confirm the present study.

Aspirin

MedlinePlus

... aches. Nonprescription aspirin is also used to prevent heart attacks in people who have had a heart attack in the past or who have angina (chest ... are experiencing or who have recently experienced a heart attack. Nonprescription aspirin is also used to prevent ischemic ...

Mechanisms of colitis-accelerated colon carcinogenesis and its prevention with the combination of aspirin and curcumin: Transcriptomic analysis using RNA-seq.

PubMed

Guo, Yue; Su, Zheng-Yuan; Zhang, Chengyue; Gaspar, John M; Wang, Rui; Hart, Ronald P; Verzi, Michael P; Kong, Ah-Ng Tony

2017-07-01

Colorectal cancer (CRC) remains the leading cause of cancer-related death in the world. Aspirin (ASA) and curcumin (CUR) are widely investigated chemopreventive candidates for CRC. However, the precise mechanisms of their action and their combinatorial effects have not been evaluated. The purpose of the present study was to determine the effect of ASA, CUR, and their combination in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-accelerated colorectal cancer (CAC). We also aimed to characterize the differential gene expression profiles in AOM/DSS-induced tumors as well as in tumors modulated by ASA and CUR using RNA-seq. Diets supplemented with 0.02% ASA, 2% CUR or 0.01% ASA+1% CUR were given to mice from 1week prior to the AOM injection until the experiment was terminated 22weeks after AOM initiation. Our results showed that CUR had a superior inhibitory effect in colon tumorigenesis compared to that of ASA. The combination of ASA and CUR at a lower dose exhibited similar efficacy to that of a higher dose of CUR at 2%. RNA isolated from colonic tissue from the control group and from tumor samples from the experimental groups was subjected to RNA-seq. Transcriptomic analysis suggested that the low-dose combination of ASA and CUR modulated larger gene sets than the single treatment. These differentially expressed genes were situated in several canonical pathways important in the inflammatory network and liver metastasis in CAC. We identified a small subset of genes as potential molecular targets involved in the preventive action of the combination of ASA and CUR. Taken together, the current results provide the first evidence in support of the chemopreventive effect of a low-dose combination of ASA and CUR in CAC. Moreover, the transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from normal colonic tissue to tumor development as well as the cancer inhibitory effects

Medications Containing Aspirin (Acetylsalicylate) and Aspirin-Like Products

MedlinePlus

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 ...

Anaesthesia in aspirin-induced asthma.

PubMed

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.

Aspirin for in vitro fertilisation.

PubMed

Siristatidis, Charalambos S; Dodd, Susanna R; Drakeley, Andrew J

2011-08-10

Aspirin is used to improve the outcome in women undergoing in vitro fertilisation despite inconsistent evidence of its efficacy. The most appropriate time to commence aspirin therapy and the length of treatment required are also still to be determined. This is an update of the review first published in 2007. To determine the effectiveness and safety of aspirin for improving the outcome of in vitro fertilisation and intracytoplasmic sperm injection treatment cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library January 2011), MEDLINE (1966 to January 2011) and EMBASE (1980 to January 2011) databases. We used the research terms: "(aspirin OR acetylsalicylic acid) AND (in-vitro fertilisation OR intracytoplasmic sperm injection)", combined with the Cochrane Menstrual Disorders and Subfertility Group's search strategy, in order to identify randomised controlled trials on aspirin for women undergoing in vitro fertilisation. Randomised controlled trials. Two authors independently selected studies to include in the review, extracted data and assessed trial quality. The searches identified 13 trials which were eligible for inclusion in the review, including a total of 2653 participants. No significant differences were found between the treatment and control groups for any of the outcomes assessed. No significant differences were found in the meta-analysis of studies investigating the effect of aspirin compared with control on live birth rate (RR 0.91, 95% CI 0.72 to 1.15; three studies and 1053 participants), clinical pregnancy rate (RR 1.03, 95% CI 0.91 to 1.17; 10 studies and 2142 participants), ectopic and miscarriage rates (RR 1.86, 95% CI 0.75 to 4.63; RR 1.10, 95% CI 0.68 to 1.77) respectively (three and five studies involving 1135 and 1497 participants). Use of aspirin for women undergoing in vitro fertilisation cannot be recommended due to lack of

Inhibition of cyclooxygenase-independent platelet aggregation by sodium salicylate.

PubMed

Violi, F; Alessandri, C; Praticò, D; Guzzo, A; Ghiselli, A; Balsano, F

1989-06-15

The effect of acetylsalicylic acid (ASA) on platelet aggregation (PA) and thromboxane A2 (TxA2) formation was investigated in vitro and ex vivo after 1 g or 300 mg ASA administration to healthy subjects. 50-100 microM ASA inhibited PA by single aggregating agent such as platelet aggregating factor (PAF) or epinephrine and reduced to less than or equal to 5% of control platelet TxB2 formation, but did not influence PA by epinephrine plus PAF. The latter was inhibited by increasing ASA concentration. In samples incubated with 100 microM ASA and stimulated with epinephrine plus PAF, PA could be inhibited by the addition of 100-300 microM sodium salicylate. After 300 mg-1 g ASA administration to healthy subjects, the inhibition of PA by epinephrine plus PAF was more marked by highest doses of ASA. This study suggests that aspirin inhibits PA with a cyclooxygenase-independent mechanism; this effect is mediated, at least in vitro, by salicylic acid.

Bleeding after tooth extraction in patients taking aspirin and clopidogrel (Plavix®) compared with healthy controls.

PubMed

Sadeghi-Ghahrody, Mohsen; Yousefi-Malekshah, Seyed Hamid; Karimi-Sari, Hamidreza; Yazdanpanah, Hamid; Rezaee-Zavareh, Mohammad Saeid; Yavarahmadi, Mohammadhosein

2016-06-01

The risk of perioperative bleeding is high in patients who take aspirin and clopidogrel after a percutaneous coronary intervention, and whether to stop the drugs is a matter of concern for dentists. The aim of this study was to answer the specific question: should aspirin and clopidogrel bisulphate (Plavix®) be discontinued during a conventional forceps extraction? We studied 64 patients during the first year after percutaneous insertion of coronary stents who were taking aspirin (ASA) 80mg and clopidogrel (Plavix(®)) 75mg, and 50 healthy patients who were to have a conventional forceps extraction at this polyclinic in 2013-2014 and acted as controls. Clinical details (underlying diseases; number of roots; type of tooth; type of haemostasis; and bleeding immediately, 30minutes, and 48hours after intervention) were compared. We evaluated 114 patients with the mean (range) age of 56 (43-76) years, and there were no significant differences in demographic data, underlying diseases, type of tooth, number of roots, and dose of anaesthetic between the groups. There were also no significant differences in the number of bleeds immediately and 30minutes after intervention (P=0.310 and 0.205). The time that the last dose of aspirin had been taken correlated with 30-minute haemostasis (20 compared with 12hours, p=0.037). During the 48hours after the intervention, there were no uncontrolled bleeds or emergency referrals. We conclude that using aspirin and Plavix® simultaneously has no considerable effect on the risk of bleeding in patients having conventional forceps extraction of a single tooth. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Aspirin and Omeprazole

MedlinePlus

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 ...

Evaluation of nitrate-substituted pseudocholine esters of aspirin as potential nitro-aspirins.

PubMed

Gilmer, John F; Moriarty, Louise M; Clancy, John M

2007-06-01

Herein we explore some designs for nitro-aspirins, compounds potentially capable of releasing both aspirin and nitric oxide in vivo. A series of nitrate-bearing alkyl esters of aspirin were prepared based on the choline ester template preferred by human plasma butyrylcholinesterase. The degradation kinetics of the compounds were followed in human plasma solution. All compounds underwent hydrolysis rapidly (t(1/2) approximately 1min) but generating exclusively the corresponding nitro-salicylate. The one exception, an N-propyl, N-nitroxyethyl aminoethanol ester produced 9.2% aspirin in molar terms indicating that the nitro-aspirin objective is probably achievable if due cognisance can be paid to the demands of the activating enzyme. Even at this low level of aspirin release, this compound is the most successful nitro-aspirin reported to date in the key human plasma model.

A Prevention of Pre-eclampsia with the Use of Acetylsalicylic Acid and Low-molecular Weight Heparin - Molecular Mechanisms.

PubMed

Darmochwal-Kolarz, Dorota; Kolarz, Bogdan; Korzeniewski, Michal; Kimber-Trojnar, Zaneta; Patro-Malysza, Jolanta; Mierzynski, Radzisław; Przegalinska-Kałamucka, Monika; Oleszczuk, Jan

Pre-eclampsia appears to be the main cause for the maternal and fetal morbidity and mortality. Pregnant women with pre-eclampsia are more likely to be threatened with conditions which potentially may be lethal, such as: disseminated intravascular coagulation, cerebral hemorrhage, liver and renal failure. Pregnancy complicated with pre-eclampsia is also associated with a greater risk for iatrogenic prematurity, intrauterine growth retardation, premature abruption of placenta, and even intrauterine fetal death. In the majority of cases the reasons for arterial hypertension among pregnant women remain obscure. For the past decades, there were many abortive attempts in the use of some microelements, vitamins or specific diets, such as polyunsaturated fatty acids, for the prophylaxis of pre-eclampsia. Recently, it has been shown that a prevention of pre-eclampsia with the use of a lowmolecular- weight heparins (LMWHs) and acetylsalicylic acid (ASA) could considerably reduce the frequency of preeclampsia. In this review, we present the studies concerning the applications of LMWHs and aspirin in the prophylaxis of pre-eclampsia and some important data about the mechanisms of anti-inflammatory actions of LMWHs and ASA.

Effect of HER-2/Neu Signaling on Sensitivity to TRAIL in Prostate Cancer

DTIC Science & Technology

2007-06-01

acetyl salicylic acid (ASA: aspirin), amiloride, and quercetin inhibit the PI(3)K-Akt signal transduction pathway and promote TRAIL-induced...SUBJECT TERMS HER-2/neu; TRAIL; Amiloride; Aspirin; Quercetin ; PI(3)K; Akt; NF-κB; Survivin 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...by quercetin through Akt dephosphorylation. J Cell Biochem., 100:998-1009. 5. Yoo J, Kim HR, Lee YJ. (2006) Hyperthermia enhances tumour necrosis

"Aspirin resistance" in ischemic stroke: insights using short thrombelastography.

PubMed

Sambu, Nalyaka; Radhakrishnan, Ashwin; Englyst, Nicola; Weir, Nicolas; Curzen, Nick

2013-11-01

Aspirin achieves its antithrombotic effect through inactivation of cyclo-oxygenase (COX)-1, thereby preventing generation of thromboxane (TX)A2 from arachidonic acid (AA). The reported prevalence of aspirin "resistance" varies significantly and is usually based on platelet function tests (PFTs) that use AA-induced platelet reactivity as a surrogate measure of the effect of aspirin, rather than specific assessment of its effect on its therapeutic target (ie, COX-1 inhibition). The reported rates are not only assay specific but also condition specific, with particularly high rates (up to 70%) previously reported in the stroke population. We investigated whether pharmacological responses to aspirin can be reliably determined from a functional test of AA-induced whole-blood clotting. A prospective study included 35 patients admitted with ischemic stroke and commenced on 300 mg aspirin. AA-induced whole-blood clotting was measured using short thrombelastography, a previously extensively validated near-patient PFT. Serum TXB2 and inflammatory biomarkers were also measured. The prevalence of apparent aspirin resistance measured using AA was high (range from 49% to 67%). However, serum [TXB2] was consistently low, thereby confirming adequate inhibition of COX-1 by aspirin. Mean inflammatory biomarker levels were elevated throughout. This study demonstrates that although COX-1 activity is adequately and consistently suppressed by aspirin in stroke patients, this effect is not reliably indicated by whole-blood clotting in response to AA. These data help to explain why the reported prevalence of aspirin resistance in stroke from studies employing AA-induced platelet reactivity is high and cast doubt on the veracity of such reports. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

OH-initiated transformation and hydrolysis of aspirin in AOPs system: DFT and experimental studies.

PubMed

He, Lin; Sun, Xiaomin; Zhu, Fanping; Ren, Shaojie; Wang, Shuguang

2017-08-15

Advanced oxidation processes (AOPs) are widely used in wastewater treatment of pharmaceutical and personal care products (PPCPs). In this work, the OH-initiated transformation as well as the hydrolysis of a typical PPCPs, aspirin, was investigated using density functional theory (DFT) calculations and laboratory experiments. For DFT calculations, the frontier electron densities and bond dissociation energies were analyzed. Profiles of the potential energy surface were constructed, and all the possible pathways were discussed. Additionally, rate constants for each pathway were calculated with transition state theory (TST) method. UV/H 2 O 2 experiments of aspirin were performed and degradation intermediates were identified by UPLC-MS-MS analysis. Different findings from previous experimental works were reported that the H-abstraction pathways at methyl position were dominated and OH-addition pathways on benzene ring were also favored. Meantime, hydroxyl ASA was confirmed as the main stable intermediate. Moreover, it was the first time to use DFT method to investigate the hydrolysis mechanisms of organic ester compound. Copyright © 2017 Elsevier B.V. All rights reserved.

Ibudilast, a phosphodiesterase inhibitor, in combination with low-dose aspirin potently inhibits guinea pig carotid artery thrombosis without extending bleeding time and causing gastric mucosal injury.

PubMed

Matsuzawa, S; Hoshina, K; Sueyoshi, S; Miyata, Y; Manita, S; Ooie, T; Yasue, T; Sasahara, T

2012-12-01

A combination of low-dose aspirin (ASA) and a phosphodiesterase inhibitor has been clinically tried for the secondary prevention of atherothrombotic diseases. The in vivo antithrombotic property of ibudilast (CAS 50847-11-5), a phosphodiesterase 4 (PDE4) inhibitor, was evaluated in a photochemically-induced guinea pig carotid artery thrombosis model in combination with low-dose ASA. The time required to decrease the carotid artery blood flow to the reading "zero" was defined as the time to occlusion (TTO) of the artery through thrombogenesis. Each independent use of ASA (300 mg/kg, p.o.) and ibudilast (3 and 10 mg/kg, p.o.) significantly prolonged the TTO, and ASA (300 mg/kg) significantly increased bleeding time (BT) and gastric mucosal injury. A selective PDE4 inhibitor rolipram (1 and 5 mg/kg, p.o.) tended to prolong the TTO without extending BT. ASA (100 mg/kg) plus ibudilast (3 mg/kg) and ASA (100 mg/kg) plus rolipram (5 mg/kg) markedly prolonged the TTO compared with each agent alone. Interestingly, ASA (100 mg/kg) plus ibudilast (3 mg/kg) caused a longer TTO than ASA (300 mg/kg) alone, without significant extension of BT and gastric mucosal injury as observed in ASA (300 mg/kg). These results indicate that the combination of low-dose ASA and ibudilast has a more potent antithrombotic effect than ASA alone without increasing bleeding tendency and gastric mucosal injury. The potent in vivo antithrombotic effect of this combination may be brought about by an action that is associated with PDE4 inhibition of ibudilast. © Georg Thieme Verlag KG Stuttgart · New York.

Standards 101: The ASA Standards program

NASA Astrophysics Data System (ADS)

Schomer, Paul

2004-05-01

ASA serves as a standards developer under the auspices of the American National Standards Institute (ANSI). The Standards Program is organized through four technical committees (S1, S2, S3, and S12) and one administrative committee (ASACOS). S1 deals with physical acoustics, S2 deals with shock and vibration, S3 deals with physiological and psychological acoustics and S12 deals with noise. ASACOS is the ASA Committee on Standards. The program has three primary tasks: (1) development of national standards (ANSI Standards), (2) national adoption of international standards (ANSI NAIS Standards), (3) providing the USA input to the development of international standards (ISO and IEC Standards). At every level the main work is accomplished in Working Groups (WG) that are staffed by hundreds of volunteers, mainly ASA members from its various technical committees such as Noise, Physical Acoustics, Architectural Acoustics, Physiological and Psychological Acoustics, etc. Overall, the Standards Program involves more ASA members than does any other single function of the society except meetings. It is the biggest outreach function of ASA affecting the health, welfare, and economic well-being of large sectors of society. It is a main way the ASA diffuses the knowledge of acoustics and its practical application, perhaps the main way.

Lack of inhibitory effect of acetylsalicylic acid and meloxicam on whole blood platelet aggregation in cats.

PubMed

Cathcart, Curtis J; Brainard, Benjamin M; Reynolds, Lisa R; Al-Nadaf, Sami; Budsberg, Steven C

2012-02-01

To determine the effects of acetylsalicylic acid (ASA) and meloxicam on feline platelet aggregation and associated platelet thromboxane production and serotonin release. Prospective interventional study. University research facility. Eight healthy male castrated domestic short hair cats from a research colony. Oral medications were administered to 8 cats for 14 days in a randomized, placebo-controlled, crossover design. Treatment groups included: aspirin (ASA) (5 mg/kg q 48 h), meloxicam (0.05 mg/kg q 24 h), and placebo (0.5 mL of water q 24 h). Thromboxane assays (TXB(2) ) and whole blood (impedance) aggregometry (WBA) were performed on samples collected before drug administration, and on days 7, 15, and 17, using adenosine diphosphate (ADP; 10 μM) and collagen (5 μg/mL) as agonists for WBA. Serotonin release was assayed on postaggregation plasma. Oral mucosal bleeding time (OMBT) and complete blood cell counts were measured on days 0 and 15. Neither medication affected WBA at any time point. OMBT decreased in the ASA group relative to baseline. No differences were detected in WBA and OMBT baseline between any groups. No difference was detected in serotonin secretion at any time point. TXB(2) was significantly decreased in the ASA group at all times after initiation of treatment but no change was noted in the meloxicam or placebo groups. At the doses studied, neither meloxicam nor ASA had an inhibitory effect on WBA or OMBT in cats. Thromboxane concentrations were significantly decreased with ASA treatment. © Veterinary Emergency and Critical Care Society 2011.

Evaluation of Aspirin and Clopidogrel resistance in patients with Acute Coronary Syndrome by using Adenosine Diposphate Test and Aspirin Test

PubMed Central

O, Ibrahim; M, Oteh; A, A Syukur; HH, Che Hassan; W, S Fadilah; Rahman, MM

2013-01-01

Objectives: To evaluate Aspirin and Clopidogrel resistance/non-responders in patients with acute coronary syndrome (ACS) by using adenosine diposphate and aspirin tests. Methodology: In the study patients with ACS loaded with 300 mg of clopidogrel and 300 mg aspirin and patients on stable daily dose of 75 mg of clopidogrel (more than 3 days) underwent PCI. Response to clopidogrel and Aspirin was assessed by Adenosine Diphosphate (ADP) Test (20 µmol/L) and Aspirin Test (Acetyl Acid) (ASP) 20 µmol/L, respectively, using the Multiplate Platelet Function Analyzer (Dynabyte Medical, Munich, Germany). Results: Sixty four patients were included in this study out of which 57 were with ACS and 7 scheduled for percutaneous coronary intervention (PCI) electively. The proportion of Aspirin good responders and adequate responders were 76.56% and 18.75%, respectively while adequate response and good response to Clopidogrel accounted for 29.7 and 48.4%, respectively Hyperlipidaemia was only co-morbidity associated with higher AUC ADP value (p: 0.046). Hypertriglyceridaemia and serum calcium were weakly correlated with higher AUC ADP serum calcium r=0.08, triglyceride r=0.12. Patients admitted for scheduled PCI and on stable dose of 75mg clopidogrel exhibited lower AUC ADP value as compared to those admitted with acute coronary syndrome given loading dose of 300mg of Clopidogrel. Post loading dose measurement of anti-platelet therapy among ACS patients using the Multiplate Platelet Function Analyzer showed comparable results with other methods. Conclusions : As determined by Multiplate Platelet Function Analyzer, Aspirin resistance/non-responders in this study in acute coronary syndrome patients accounted for 4.69% while Non-responders in Clopidogrel was 21.9%. PMID:24353516

Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: Old question new insights

PubMed Central

Sostres, Carlos; Gargallo, Carla Jerusalen; Lanas, Angel

2014-01-01

Previous reports clearly demonstrated that Helicobacter pylori (H. pylori) infection, nonsteroidal anti-inflammatory drugs (NSAID) or low dose aspirin (ASA) use significantly and independently increased the risk for the development of peptic ulcer disease. Today, the presence of H. pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications. Whether NSAID intake in the presence of H. pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate. Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years. In addition, the interaction between H. pylori infection and low-dose ASA remains even more controversial. In real clinical practice, we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors. These huge variety of possible combinations greatly hinder the decision making process of physicians. PMID:25071338

Utility of low-dose oral aspirin challenges for diagnosis of aspirin-exacerbated respiratory disease.

PubMed

Jerschow, Elina; Ren, Zhen; Hudes, Golda; Sanak, Marek; Morales, Esperanza; Schuster, Victor; Spivack, Simon D; Rosenstreich, David

2016-04-01

Aspirin-exacerbated respiratory disease (AERD) is diagnosed through graded aspirin challenges that induce hypersensitivity reactions and eicosanoid level changes. It is not known whether diagnostically useful changes also occur after low-dose aspirin challenges that do not induce hypersensitivity reactions. To investigate the utility of low-dose oral aspirin challenges for diagnosing AERD by measuring different clinical parameters and eicosanoid changes. Sixteen patients with AERD and 13 patients with aspirin-tolerant asthma underwent oral challenges with low-dose (20 or 40 mg) aspirin and diagnostic oral graded aspirin challenges (up to 325 mg of aspirin). Forced expiratory volume in 1 second, nasal peak flow, the fraction of exhaled nitric oxide (FeNO), and eicosanoid levels in plasma and urine were analyzed. In patients with AERD but not in those with aspirin-tolerant asthma, 40-mg aspirin challenges induced a significant mean (SEM) decrease from baseline in FeNO (19% [5.1%]; P = .001) without causing any hypersensitivity reaction. The FeNO decrease also occurred after higher-dose aspirin challenges (27.8% [4.9%]; P < .001). The sensitivity and specificity of 40-mg aspirin-induced FeNO changes for identifying AERD were 90% and 100% with an area under the curve of 0.98 (95% CI, 0.92-1.00). The low-dose challenge also induced a significant leukotriene E4 urine increase in patients with AERD (from 6.32 [0.08] to 6.91 [0.15] log-pg/mg creatinine; P < .001), but the sensitivity and specificity of these changes were less than for the FeNO changes. The low-dose aspirin-induced decrease in FeNO in patients with AERD may be useful for the diagnosis of aspirin allergy without inducing a hypersensitivity reaction. clinicaltrials.gov Identifier: NCT01320072. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Kinetics of browning and correlations between browning degree and pyrazine compounds in l-ascorbic acid/acidic amino acid model systems.

PubMed

Yu, Ai-Nong; Zhou, Yong-Yan; Yang, Yi-Ni

2017-04-15

The kinetics of browning and the correlation between browning products (BPs) and pyrazine compounds were investigated by heating equimolar l-ascorbic acid (ASA)/acidic amino acids under weak alkaline conditions at 120-150°C for 10-120min. The formations of BPs and pyrazine compounds from the reaction were monitored by UV-vis and SPME-GC-FID, respectively. The formation of BPs in both ASA/l-glutamic acid and ASA/l-aspartic acid model reaction systems followed zero order reaction kinetics with activation energies (E a ) of 90.13 and 93.38kJ/mol, respectively. ASA/l-aspartic acid browned at a slightly higher rate than ASA/l-glutamic acid. The total concentration of pyrazine compounds was highly and positively correlated with that of BPs. Based on the observed kinetic data, the formation mechanisms of BPs and pyrazine compounds were proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dual antiplatelet therapy with clopidogrel and aspirin increases mortality in 4T1 metastatic breast cancer-bearing mice by inducing vascular mimicry in primary tumour

PubMed Central

Smeda, Marta; Kieronska, Anna; Proniewski, Bartosz; Jasztal, Agnieszka; Selmi, Anna; Wandzel, Krystyna; Zakrzewska, Agnieszka; Wojcik, Tomasz; Przyborowski, Kamil; Derszniak, Katarzyna; Stojak, Marta; Kaczor, Dawid; Buczek, Elzbieta; Watala, Cezary; Wietrzyk, Joanna; Chlopicki, Stefan

2018-01-01

Platelet inhibition has been considered an effective strategy for combating cancer metastasis and compromising disease malignancy although recent clinical data provided evidence that long-term platelet inhibition might increase incidence of cancer deaths in initially cancer-free patients. In the present study we demonstrated that dual anti-platelet therapy based on aspirin and clopidogrel (ASA+Cl), a routine regiment in cardiovascular patients, when given to cancer-bearing mice injected orthotopically with 4T1 breast cancer cells, promoted progression of the disease and reduced mice survival in association with induction of vascular mimicry (VM) in primary tumour. In contrast, treatment with ASA+Cl or platelet depletion did reduce pulmonary metastasis in mice, if 4T1 cells were injected intravenously. In conclusion, distinct platelet-dependent mechanisms inhibited by ASA+Cl treatment promoted cancer malignancy and VM in the presence of primary tumour and afforded protection against pulmonary metastasis in the absence of primary tumour. In view of our data, long-term inhibition of platelet function by dual anti-platelet therapy (ASA+Cl) might pose a hazard when applied to a patient with undiagnosed and untreated malignant cancer prone to undergo VM. PMID:29707148

Clinical Trials of Aspirin Treatment After Desensitization in Aspirin-Exacerbated Respiratory Disease.

PubMed

Kowalski, Marek L; Wardzyńska, Aleksandra; Makowska, Joanna S

2016-11-01

The clinical efficacy of aspirin treatment after desensitization in patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs has been documented in observational studies and in double-blind placebo-controlled trials. There is no general agreement with regard to the optimal maintenance dose or duration of treatment with acetylsalicylic acid after desensitization, thus further studies are necessary to offer clear guidelines to clinicians. This article summarizes data from noncontrolled, active-control, and placebo-controlled trials assessing clinical effectiveness and reporting on safety of treatment with acetylsalicylic acid in desensitized patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2018-02-20

Aspirin is a commonly used medicine for primary and secondary prevention of cardiovascular diseases. It is an acidic medicine associated with gastric irritation and acid reflux, which in turn can lead to low oral pH levels. Therefore, it is important to understand the association between aspirin and oral pH levels in order to achieve an optimum oral health condition among patients who take aspirin on prescription. Out of 373 patients, 162 (44%) were males and 245 (66%) were on aspirin. 71% of aspirin taking patients and 29% of non-aspirin taking patients had oral pH less than 6.5 (P < 0.01). Aspirin showed a significant association with low oral pH levels (odds ratio = 1.91, 95% CI 1.23-2.99, P < 0.01). 78 patients were given antacids and followed up for 4 weeks, 63 of them (81%) showed an improvement in oral pH and the improvement was marked in the group who had oral pH between 5.5-6.0 compared to the group who had oral pH between 6.0-6.5 (P = 0.03). The results show that aspirin therapy is associated with low oral pH and administration of an antacid with aspirin helps to increase the oral pH level.

Papillary Necrosis in Rats Caused by Aspirin and Aspirin-containing Mixtures

PubMed Central

Nanra, Ranjit S.; Kincaid-Smith, Priscilla

1970-01-01

Nearly half the rats gavage-fed with aspirin and aspirin-containing mixtures developed papillary necrosis in 20 weeks. This incidence is similar to that found in rats on A.P.C. mixtures with high and low concentrations of p-chloracetanilide, an impurity of phenacetin. Aspirin alone produced necrosis in 7 out of 19 rats (36·8%) whereas phenacetin in the same dose had failed to cause any renal damage over six to nine months. If these results also apply to man they suggest that aspirin and not phenacetin may be the major factor in analgesic nephropathy in patients taking A.P.C. mixtures. An augmented clearance of aspirin appeared to afford some protection to the medulla, and it is suggested that this observation may have important clinical and epidemiological applications. Imagesp560-a PMID:5454357

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

PubMed Central

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

2016-01-01

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

Antiplatelet effects of aspirin in chronic kidney disease patients.

PubMed

Polzin, A; Dannenberg, L; Sansone, R; Levkau, B; Kelm, M; Hohlfeld, T; Zeus, T

2016-02-01

ESSENTIALS: Chronic kidney disease (CKD) patients have a high risk of cardiovascular events. A pharmacodynamic evaluation of the effects of aspirin in 116 patients was carried out. The antiplatelet effects of aspirin are associated with impaired renal function. The optimal antithrombotic regimen in CKD patients must be investigated on a larger scale. The pharmacodynamic response to aspirin varies significantly between individuals. Insufficient antiplatelet effects of aspirin are associated with increased risk of ischemic events. Chronic kidney disease (CKD) is suggested to affect the pharmacodynamic response to antiplatelet medication. High on-treatment platelet reactivity (HTPR) to clopidogrel has been reported to partially account for the enhanced risk of death and cardiovascular events in CKD patients. Objective To investigate the antiplatelet effects of aspirin in patients with CKD. We conducted a cross-sectional study in 116 patients on permanent aspirin medication. The pharmacodynamic response to aspirin was determined by arachidonic acid-induced thromboxane formation. HTPR to aspirin was more frequent in patients with impaired renal function (47% vs. 22%; odds ratio, 3.16; 95% confidence interval [CI], 1.34-7.41; P = 0.008). The pharmacodynamic response to aspirin was impaired in patients with moderate/severe CKD (92; interquartile range [IQR], 282 ng mL(-1) ) as compared to patients with normal/mildly reduced renal function (36; IQR, 100 ng mL(-1) ; difference in medians, 57; CI, 5-110 ng mL(-1) ; P = 0.013). Bivariate Pearson analysis showed residual thromboxane formation to be correlated with glomerular filtration rate (R = -0.303; R(2) = 0.092; P = 0.001). Patients with CKD were older and more frequently female. Multivariate linear regression analysis revealed that the correlation was independent of age (R = -0.314; R(2) = 0.082; P = 0.002) and gender (R = -0.305; R(2) = 0.077; P = 0.006). Renal function is correlated with pharmacodynamic response to

The effect of low-dose aspirin on the decreased risk of development of dyspepsia and gastrointestinal ulcers associated to cyclooxygenase-2 selective inhibitors.

PubMed

Benito-Garcia, Elizabeth; Michaud, Kaleb; Wolfe, Frederick

2007-08-01

To evaluate the risk of gastrointestinal (GI) symptoms and ulcers associated to the use of low-dose aspirin (ASA) among patients with rheumatoid arthritis (RA) and osteoarthritis (OA) treated with cyclooxygenase-2 (COX-2) drugs, to clarify the controversy in the literature. Using a longitudinal databank, a prospective study using Cox proportional hazards models was performed in patients receiving COX-2 therapy for RA or OA to examine the effect of ASA on GI events. In 4 separate analyses patients reported dyspeptic symptoms and GI ulcers at semiannual intervals for up to 3 years. Ulcers were validated by review of medical records. Among 4240 patients taking COX-2-specific inhibitors, with no ulcer at study start, the age- and sex-adjusted hazard ratios for the effect of ASA on the development of epigastric pain, heartburn, nausea, and ulcers, without these previous events, were 1.11 (95% CI 0.97-1.29), 1.00 (95% CI 0.88-1.15), 1.32 (95% CI 1.13-1.54), and 1.27 (95% CI 0.78-2.05). The use of a propensity score to account for the risk of ASA prescription showed an even lower effect of ASA among all GI variables. This risk occurs within the setting of no prior GI symptoms or GI events, and independently of the use of proton pump inhibitors, other GI drugs, other nonsteroidal antiinflammatory drugs, prednisone, or methotrexate. In actual practice, the use of low-dose ASA has a small effect on the risk of developing dyspeptic symptoms in a group of patients with rheumatic disease.

[Aspirin and colorectal cancer].

PubMed

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.

PubMed

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.

The Effects of EPA, DHA, and Aspirin Ingestion on Plasma Lysophospholipids and Autotaxin

PubMed Central

Block, RC; Duff, R; Lawrence, P; Kakinami, L; Brenna, JT; Shearer, GC; Meednu, N; Mousa, S; Friedman, A; Harris, WS; Larson, Mark; Georas, S

2010-01-01

SUMMARY Lysophophatidylcholine (LPC) and lysophosphatidic acid (LPA) are potent lysolipid mediators increasingly linked with atherosclerosis and inflammation. A current model proposing that plasma LPA is produced when LPC is hydrolyzed by the enzyme autotaxin has not been rigorously investigated in human subjects. We conducted a clinical trial of eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) and aspirin ingestion in normal volunteers. Fasting blood samples were drawn at baseline and after 4-week supplementation with EPA/DHA (3.4 g/d) with and without aspirin (650 mg). Plasma LPC and LPA species and autotaxin activity were measured. EPA-LPC and DHA-LPC concentrations increased significantly with EPA/DHA supplementation whereas EPA- and DHA-LPA did not. Autotaxin activity was unaffected by any treatment, and aspirin had no effect on any endpoint. Taken together, our data demonstrate that plasma LPC, but not LPA, species can be dynamically regulated by dietary supplementation, and argue against a simple model of LPA generation via LPC hydrolysis. PMID:20106646

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

PubMed

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

2014-01-01

Abstract The optimal dose of aspirin for patients presenting with acute myocardial infarction (AMI) while receiving chronic aspirin therapy has not been clearly established. We evaluated whether continued treatment with 100 mg of aspirin or a loading dose (200-500 mg) influences thromboxane A2 (TX) suppression or platelet reactivity. Sixty-four consecutive patients with AMI and 98 healthy subjects (82 aspirin-free and 16 receiving 100 mg daily for a week) were evaluated. Treatment was at the discretion of the attending physician. Collagen (1 µg/ml)-induced TX synthesis, (14)C-serotonin-release, platelet aggregation, and the PFA-100 assay were evaluated. The platelet TX synthesis of patients receiving a loading dose of aspirin was sixfold lower than that of patients receiving 100 mg of aspirin (p<0.005). This was associated with marked reductions in (14)C-serotonin-release and arachidonic-acid-induced aggregation and an increase in the PFA-100 closure time (p<0.01). Categorization of patients according to their TX synthesis (<95% or ≥ 95% inhibition vs. healthy aspirin-free subjects) revealed that 8% of the patients treated with loading doses had a poor response (<95% inhibition) vs. 53% of those treated with 100 mg (p<0.001). Patients with lower TX inhibition had higher serum NT-Pro-BNP (p<0.005), a marker of poor left ventricular systolic function. Administration of a loading dose of aspirin to patients with AMI during existing chronic aspirin treatment induced greater reductions in platelet TX synthesis and TX-dependent platelet reactivity than the continued treatment alone.

Pharmacokinetic and pharmacodynamic interactions of aspirin with warfarin in beagle dogs.

PubMed

Shen, Chenlin; Huang, Xiaohui; Li, Jun; Zhang, Ping; Li, Lin; Zhang, Wei; Hu, Tingting; Pappoe, Faustina; Huang, Jihan; Tang, Haiqin

2016-01-01

1. Warfarin and aspirin are widely used in a wide spectrum of thromboembolic and atherothrombotic diseases. Despite the potential efficacy of warfarin-aspirin therapy, the safety and side effect of combined therapy remains unclear. 2. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and aspirin in beagles after single and multiple doses. 3. Coadministration of aspirin had no significant effects on the area under the plasma concentration time curve (AUC(0-t)) and maximum plasma concentration (Cmax) of R- and S-warfarin after a single dose of warfarin, but significantly increase the AUC(0-t) and Cmax and dramatically decrease the clearance (CL) of R- and S-warfarin after multiple dose of warfarin. Accordingly, there was a slight increase in the AUEC(0-t) and Emax of activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) after multiple dose of warfarin. 4. Coadministration of warfarin had no markedly effects on the AUC(0-t) and Cmax of aspirin and its metabolite salicylic acid after single or multiple dose of aspirin. Meanwhile, the AUEC(0-t) and Emax of inhibition of platelet aggregation (IPA) were not significantly affected by warfarin. 5. Our animal study indicated that coadministration of aspirin with warfarin can cause significant pharmacokinetic and pharmacodynamic drug-drug interactions in beagles. However, more studies are urgently needed to assess related information of warfarin-aspirin drug interactions in healthy volunteers or patients.

Comparison of increased aspirin dose versus combined aspirin plus clopidogrel therapy in patients with diabetes mellitus and coronary heart disease and impaired antiplatelet response to low-dose aspirin.

PubMed

Duzenli, Mehmet Akif; Ozdemir, Kurtulus; Aygul, Nazif; Soylu, Ahmet; Tokac, Mehmet

2008-08-15

The effects of therapy with aspirin 300 mg/day and with combined aspirin 100 mg/day plus clopidogrel 75 mg/day on platelet function were compared in patients with diabetes mellitus and coronary artery disease and impaired antiplatelet responses to aspirin 100 mg/day. The study population consisted of 151 outpatients with type II diabetes mellitus and coronary artery disease who were taking aspirin 100 mg/day. Of the 151 patients, a subgroup of subjects with impaired aspirin response were selected on the basis of the results of platelet aggregometry. Nonresponsiveness to aspirin was defined as mean aggregation > or =69% with 3 micromol/L adenosine diphosphate and mean aggregation > or =70% with 2 micromol/L collagen. Aspirin semiresponders were defined as meeting 1 but not both of these criteria. Nonresponders and semiresponders were randomized equally to aspirin 300 mg/day and aspirin 100 mg/day plus clopidogrel 75 mg/day, and aggregation tests were repeated after 2 weeks. Sixty of the 151 patients with diabetes (40%) were found to respond to aspirin inadequately. Platelet aggregation induced by adenosine diphosphate and collagen decreased significantly after aspirin 300 mg/day or combined therapy. Combined treatment was found to have a stronger inhibitory effect on platelet aggregation induced by adenosine diphosphate than aspirin 300 mg/day (p = 0.002). Impaired aspirin response was resolved by increasing the aspirin dose or adding clopidogrel to aspirin (p <0.0001 for each). However, desired platelet inhibition was achieved in significantly more patients by combined treatment than by aspirin 300 mg/day (p <0.05). In conclusion, aspirin 100 mg/day does not inhibit platelet function adequately in a significant number of patients with diabetes mellitus and coronary artery disease. Increasing the aspirin dose to 300 mg/day or adding clopidogrel to aspirin can provide adequate platelet inhibition in a significant number of those patients with impaired responses to

Aspirin and the Kidney

PubMed Central

1974-01-01

A survey of 763 patients with rheumatoid arthritis and 145 with osteoarthritis in six clinics in New Zealand showed no association between aspirin intake and a score designed to detect analgesic nephropathy. Analgesic nephropathy was diagnosed clinically in three patients taking APC (aspirin, phenacetin, and caffeine or codeine or both) and in one who took aspirin and phenylbutazone and was suspected in one who took aspirin and paracetamol. Isolated aspirin was not implicated. The study showed that most people can take large quantities of salicylates without renal injury. The findings are, however, consistent with the view that there is a risk from APC compounds taken in large quantity, but the numbers at risk in this study were small. Aspirin may have an additive effect with other analgesics in causing renal damage. An increased frequency of urinary tract symptoms in those taking analgesics requires further investigation. PMID:4821007

Standards 101; the ASA standards program

NASA Astrophysics Data System (ADS)

Schomer, Paul D.

2002-11-01

ASA supports the development of standards by serving as the secretariat for standards committees of the American National Standards Institute (ANSI). The program is organized through four ANSI technical committees (S1, S2, S3, and S12) and one administrative committee (ASACOS). S1 deals with physical acoustics, S2 deals with shock and vibration, S3 deals with physiological and psychological acoustics, and S12 deals with noise. ASACOS is the ASA Committee on Standards. The program has three primary tasks: (1) the development of National Standards (ANSI Standards), (2) the national adoption of an international standard (ANSI NAIS Standards), (3) providing the USA input to the development of International Standards (ISO and IEC Standards). At every level the main work is accomplished in Working Groups (WG) that are ''staffed'' by hundreds of volunteers--mainly ASA members from its various technical committees such as Noise, Physical Acoustics, Architectural Acoustics, Psychological and Physiological Acoustics, etc. Overall, the Standards Program involves more ASA members than does any other single function of the Society except meetings and it is the biggest outreach function of ASA affecting the health, welfare, and economic well-being of large segments of the population, the business and industrial community, and government at all levels.

Recurrent Ischemic Lesions After Acute Atherothrombotic Stroke: Clopidogrel Plus Aspirin Versus Aspirin Alone.

PubMed

Hong, Keun-Sik; Lee, Seung-Hoon; Kim, Eung Gyu; Cho, Ki-Hyun; Chang, Dae Il; Rha, Joung-Ho; Bae, Hee-Joon; Lee, Kyung Bok; Kim, Dong Eog; Park, Jong-Moo; Kim, Hahn-Young; Cha, Jae-Kwan; Yu, Kyung-Ho; Lee, Yong-Seok; Lee, Soo Joo; Choi, Jay Chol; Cho, Yong-Jin; Kwon, Sun U; Kim, Gyeong-Moon; Sohn, Sung-Il; Park, Kwang-Yeol; Kang, Dong-Wha; Sohn, Chul-Ho; Lee, Jun; Yoon, Byung-Woo

2016-09-01

In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence. In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding. Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group. Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00814268. © 2016 American Heart Association, Inc.

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

PubMed

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.

Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events.

PubMed

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

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.

PubMed

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.

Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus.

PubMed

Fasano, Serena; Pierro, Luciana; Pantano, Ilenia; Iudici, Michele; Valentini, Gabriele

2017-07-01

Systemic lupus erythematosus (SLE) is associated with an increased risk of cardiovascular disease (CVD). Thromboprophylaxis with low-dose aspirin (ASA) and hydroxychloroquine (HCQ) seems promising in SLE. We investigated the effects of HCQ cumulative dosages (c-HCQ) and the possible synergistic efficacy of ASA and HCQ in preventing a first CV event (CVE) in patients with SLE. Patients consecutively admitted to our center who, at admission, satisfied the 1997 American College of Rheumatology and/or 2012 Systemic Lupus Collaborating Clinics classification criteria for SLE, and had not experienced any CVE, were enrolled. The occurrence of a thrombotic event, use of ASA, and c-HCQ were recorded. Kaplan-Meier analysis was performed to determine the c-HCQ associated with a lower incidence of CVE. Cox regression analysis served to identify factors associated with a first CVE. For the study, 189 patients with SLE were enrolled and monitored for 13 years (median). Ten CVE occurred during followup. At Kaplan-Meier analysis, the CVE-free rate was higher in ASA-treated patients administered a c-HCQ > 600 g (standard HCQ dose for at least 5 yrs) than in patients receiving ASA alone, or with a c-HCQ dose < 600 g (log-rank test chi-square = 4.01, p = 0.04). Multivariate analysis showed that antimalarials plus ASA protected against thrombosis (HR 0.041 and HR 0.047, respectively), while antiphospholipid antibodies (HR 17.965) and hypertension (HR 18.054) increased the risk of a first CVE. Our results suggest that prolonged use of HCQ plus ASA is thromboprotective in SLE and provides additional evidence for its continued use in patients with SLE.

Ticagrelor with aspirin or alone in high-risk patients after coronary intervention: Rationale and design of the TWILIGHT study.

PubMed

Baber, Usman; Dangas, George; Cohen, David J; Gibson, C Michael; Mehta, Shamir R; Angiolillo, Dominick J; Pocock, Stuart J; Krucoff, Mitchell W; Kastrati, Adnan; Ohman, E Magnus; Steg, Philippe Gabriel; Badimon, Juan; Zafar, M Urooj; Chandrasekhar, Jaya; Sartori, Samantha; Aquino, Melissa; Mehran, Roxana

2016-12-01

Dual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Antiplatelet monotherapy with a potent P2Y 12 receptor antagonist may reduce bleeding while maintaining anti thrombotic efficacy compared with conventional DAPT. TWILIGHT is a randomized, double-blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES. Upon enrollment after successful PCI, all patients will be treated with open label low-dose aspirin (81-100 mg daily) plus ticagrelor (90 mg twice daily) for 3 months. Event-free patients will then be randomized in a double-blind fashion to low-dose aspirin versus matching placebo with continuation of open-label ticagrelor for an additional 12 months. The primary hypothesis is that a strategy of ticagrelor monotherapy will be superior with respect to the primary endpoint of bleeding academic research consortium type 2, 3 or 5, while maintaining non-inferiority for ischemic events compared with ticagrelor plus ASA. TWILIGHT is the largest study to date that is specifically designed and powered to demonstrate reductions in bleeding with ticagrelor monotherapy versus ticagrelor plus ASA beyond 3 months post-procedure in a high-risk PCI population treated with DES. The trial will provide novel insights with respect to the potential role of ticagrelor monotherapy as an alternative for long-term platelet inhibition in a broad population of patients undergoing PCI with DES. Copyright © 2016 Elsevier Inc. All rights reserved.

[Preoperative risk assessment with the ASA classification. A prospective study of morbidity and mortality in various ASA classes in 2,937 patients in general surgery].

PubMed

Menke, H; John, K D; Klein, A; Lorenz, W; Junginger, T

1992-12-01

The value of ASA classification in assessment of perioperative risk, i.e. especially postoperative morbidity, was analyzed prospectively using the data of 2937 patients. The analysis took into account the criteria validity, reliability, and sensitivity. The incidence of post-operative morbidity after elective surgery rose from 3.9% in ASA class I to 36% in ASA class IV. Mortality was 0.6% in ASA class II, whereas 9.3% died in ASA class IV. Morbidity, mortality respectively, after emergency surgery was 10.2% in ASA class II compared to 69% in class IV, mortality 1.4% compared to 21.5%. Differences between the ASA classes were confirmed (p-value < 0.05) considering separate kinds of complications and different periods. Furthermore, ASA classification was a valuable reference to length of stay and severity of necessary therapy at the ICU.

Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats.

PubMed

El-Shinnawy, Nashwa A; Abd-Elmageid, Samira A; Alshailabi, Eda M A

2014-05-01

The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients.

PubMed

De Monte, Ariella; Brunetti, Davide; Cattin, Luigi; Lavanda, Francesca; Naibo, Erica; Malagoli, Maria; Stanta, Giorgio; Bonin, Serena

2018-03-01

Metformin, the drug of choice in the treatment of type 2 diabetes mellitus (DM2), in addition to aspirin (ASA), the drug prescribed for cardioprotection of diabetic and non-diabetic patients, have an inhibitory effect on cancer cell survival. The present population-based study conducted in the province of Trieste (Italy), aimed to investigate the prevalence of DM2 in patients with colorectal adenocarcinoma (CRC) and survival for CRC in diabetic and nondiabetic patients. All permanent residents diagnosed with a CRC between 2004 and 2007 were ascertained through the regional health information system. CRC-specific and relative survival probabilities were computed for each group of patients defined by CRC stage, presence or absence of DM2 treated with metformin, and presence or absence of daily ASA therapy. A total of 515 CRC patients without DM2 and 156 with DM2 treated with metformin were enrolled in the study. At the time of CRC diagnosis, 71 (14%) nondiabetic and 39 (25%) diabetic patients were taking ASA daily. The five-year relative survival for stage III CRC was 101% [95% confidence interval (CI)=76-126] in the 18 patients with DM2 treated with metformin and ASA, 55% (95% CI=31-78) in the 23 without DM2 treated with ASA, 55% (95% CI=45-65) in the 150 without DM2 not taking ASA, and 29% (95% CI=13-45) in the 43 with DM2 treated with metformin, however not with ASA. The findings support the hypothesis of a possible inhibitory effect of metformin and ASA on CRC cells. Randomized controlled trials are required to verify this hypothesis.

ASA24-Canada

Cancer.gov

A Canadian adaptation of the Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24-Canada), developed by the Food Directorate at Health Canada in collaboration with NCI, has been freely available since April 2014.

A rapid method for the simultaneous determination of L-ascorbic acid and acetylsalicylic acid in aspirin C effervescent tablet by ultra performance liquid chromatography-tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Wabaidur, Saikh Mohammad; Alothman, Zeid Abdullah; Khan, Mohammad Rizwan

2013-05-01

In present study, a rapid and sensitive method using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of L-ascorbic acid and acetylsalicylic acid in aspirin C effervescent tablet. The optimum chromatographic separation was carried out on a reversed phase Waters® Acquity UPLC BEH C18 column (1.7 μm particle size, 100 mm × 2.1 mm ID) with an isocratic elution profile and mobile phase consisting of 0.1% formic acid in water and acetonitrile (75:25, v/v, pH 3.5) at flow rate of 0.5 mL min-1. The influences of mobile phase composition, flow rate and pH on chromatographic resolution were investigated. The total chromatographic analysis time was as short as 2 min with excellent resolution. Detection and quantification of the target compounds were carried out with a triple quadrupole mass spectrometer using negative electrospray ionization (ESI) and multiple reaction monitoring (MRM) modes. The performance of the method was evaluated and very low limits of detection less than 0.09 μg g-1, excellent coefficient correlation (r2 > 0.999) with liner range over a concentration range of 0.1-1.0 μg g-1 for both L-ascorbic acid and acetylsalicylic acid, and good intraday and interday precisions (relative standard deviations (R.S.D.) <3%), were obtained. Comparison of system performance with traditional liquid chromatography-photo diode array detector (HPLC-PDA) was made with respect to analysis time, sensitivity, linearity and precisions. The proposed UPLC-MS/MS method was found to be reproducible and appropriate for quantitative analysis of L-ascorbic acid and acetylsalicylic acid in aspirin C effervescent tablet.

Prostacyclin production in rabbit arteries in situ: inhibition by arachidonic acid-induced endothelial cell damage or by low-dose aspirin.

PubMed

Ingerman-Wojenski, C; Silver, M J; Smith, J B; Nissenbaum, M; Sedar, A W

1981-04-01

The central artery of the rabbit ear was perfused in situ and effluent fractions from the artery were assayed for 6-keto-prostaglandin F1 alpha (6-K-PGF1 alpha) and thromboxane B2 (TxB2), the stable metabolites of prostacyclin (PGI2) and TxA2, using specific radioimmunoassays. These metabolites of arachidonic acid (AA) were not detected in the effluent during infusion of Tyrode's solution but both metabolites were detected when small amounts of AA were infused into the artery. Examination of the arteries by scanning electron microscopy revealed that high concentrations of AA which caused a short burst of 6-K-PGF1 alpha and TxB2 production damaged the endothelial cells while lower concentrations which stimulated continuous production did not cause damage. When a non-damaging concentration of AA was infused into an artery that had previously received a damaging concentration, PG production was greatly reduced. Pretreatment of the rabbits with 4 mg/kg acetyl-salicylic acid (ASA) inhibited 6-K-PGF1 alpha production by the rabbit ear artery in response to AA and 70% inhibition was still evident 18 hours after ASA.

Aspirin increases metabolism through germline signalling to extend the lifespan of Caenorhabditis elegans

PubMed Central

Huang, Xiao-Bing; Mu, Xiao-Hui; Wan, Qin-Li; He, Xiao-Ming; Wu, Gui-Sheng

2017-01-01

Aspirin is a prototypic cyclooxygenase inhibitor with a variety of beneficial effects on human health. It prevents age-related diseases and delays the aging process. Previous research has shown that aspirin might act through a dietary restriction-like mechanism to extend lifespan. To explore the mechanism of action of aspirin on aging, we determined the whole-genome expression profile of Caenorhabditis elegans treated with aspirin. Transcriptome analysis revealed the RNA levels of genes involved in metabolism were primarily increased. Reproduction has been reported to be associated with metabolism. We found that aspirin did not extend the lifespan or improve the heat stress resistance of germline mutants of glp-1. Furthermore, Oil Red O staining showed that aspirin treatment decreased lipid deposition and increased expression of lipid hydrolysis and fatty acid β-oxidation-related genes. The effect of germline ablation on lifespan was mainly mediated by DAF-12 and DAF-16. Next, we performed genetic analysis with a series of worm mutants and found that aspirin did not further extend the lifespans of daf-12 and daf-16 single mutants, glp-1;daf-12 and glp-1;daf-16 double mutants, or glp-1;daf-12;daf-16 triple mutants. The results suggest that aspirin increase metabolism and regulate germline signalling to activate downstream DAF-12 and DAF-16 to extend lifespan. PMID:28910305

Effect of nabumetone and aspirin on colonic mucosal bleeding time.

PubMed

Basson, M D; Panzini, L; Palmer, R H

2001-04-01

The management of patients taking aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) who require colonoscopy remains controversial because of concerns over bleeding after biopsy or polypectomy. To determine whether patients using the NSAID nabumetone, a non-acidic prodrug with mixed activity against cyclooxygenase-1 (COX-1) and COX-2, exhibited prolonged mucosal bleeding times and how this might compare with mucosal bleeding times in patients using aspirin. We assessed triplicate mucosal bleeding times in patients undergoing screening flexible sigmoidoscopy. We compared 90 patients who had taken no aspirin or NSAIDs within the previous 2 weeks, to 60 patients who had received nabumetone 1 g b.d. by mouth for the previous 2 weeks, and 30 patients who had taken 325 mg aspirin daily for the previous 2 weeks. In each case, the investigator performing the study was blinded to the patient's medication. Mucosal bleeding times did not differ significantly among control or nabumetone-using patients. However, the patients receiving aspirin exhibited significant prolongation. Mucosal bleeding time correlated statistically significantly, but weakly, with skin bleeding time. Nabumetone does not appear to prolong mucosal bleeding time after mucosal pinch biopsy, and skin bleeding time does not reliably screen for prolonged mucosal bleeding time.

Taking Aspirin to Protect Your Heart

MedlinePlus

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

Aspirin Enhances Osteogenic Potential of Periodontal Ligament Stem Cells (PDLSCs) and Modulates the Expression Profile of Growth Factor-Associated Genes in PDLSCs.

PubMed

Abd Rahman, Fazliny; Mohd Ali, Johari; Abdullah, Mariam; Abu Kasim, Noor Hayaty; Musa, Sabri

2016-07-01

This study investigates the effects of aspirin (ASA) on the proliferative capacity, osteogenic potential, and expression of growth factor-associated genes in periodontal ligament stem cells (PDLSCs). Mesenchymal stem cells (MSCs) from PDL tissue were isolated from human premolars (n = 3). The MSCs' identity was confirmed by immunophenotyping and trilineage differentiation assays. Cell proliferation activity was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Polymerase chain reaction array was used to profile the expression of 84 growth factor-associated genes. Pathway analysis was used to identify the biologic functions and canonic pathways activated by ASA treatment. The osteogenic potential was evaluated through mineralization assay. ASA at 1,000 μM enhances osteogenic potential of PDLSCs. Using a fold change (FC) of 2.0 as a threshold value, the gene expression analyses indicated that 19 genes were differentially expressed, which includes 12 upregulated and seven downregulated genes. Fibroblast growth factor 9 (FGF9), vascular endothelial growth factor A (VEGFA), interleukin-2, bone morphogenetic protein-10, VEGFC, and 2 (FGF2) were markedly upregulated (FC range, 6 to 15), whereas pleotropin, FGF5, brain-derived neurotrophic factor, and Dickkopf WNT signaling pathway inhibitor 1 were markedly downregulated (FC 32). Of the 84 growth factor-associated genes screened, 35 showed high cycle threshold values (≥35). ASA modulates the expression of growth factor-associated genes and enhances osteogenic potential in PDLSCs. ASA upregulated the expression of genes that could activate biologic functions and canonic pathways related to cell proliferation, human embryonic stem cell pluripotency, tissue regeneration, and differentiation. These findings suggest that ASA enhances PDLSC function and may be useful in regenerative dentistry applications, particularly in the areas of periodontal health and regeneration.

Aspirin for Primary Prevention.

PubMed

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.

[Dose-response of aspirin on platelet function in very elderly patients].

PubMed

Feng, X R; Liu, M L; Liu, F; Fan, Y; Tian, Q P

2016-10-18

To assess the consequences of switching aspirin dosage from 100 mg/d to 40 mg/d on cardiovascular benefit, bleeding risk and platelet aggregation in very elderly patients. Arachidonic acid induced platelet aggregation(AA-Ag) was measured in 537 patients aged 80 or older treated with aspirin (100 mg/d). In the study, 100 patients with low on-treatment platelet aggregation and at high risk of bleeding and low risk of cardiovascular events, were switched to aspirin (40 mg/d) and their platelet aggregation was measured again 7 days later.Their bleeding and upper gastrointestinal symptoms were also recorded in following 3 months. The study observed a heterogeneous distributed aspirin 100 mg/d AA-Ag (range: 0.42% to 28.78%)in the 537 very elderly patients.Aspirin 100 mg/d AA-Ag before the switch in aspirin 40 mg/d group was 5.00%±2.32% and the rate of the patients with low on-treatment platelet aggregation was 71.00%. The rates of melena or occult blood positive, other minimal bleeding,upper gastrointestinal symptoms and a history of gastrointestinal bleeding in 40 mg/d group were higher than those in 100 mg/d group. On a regimen of aspirin 40 mg/d, AA-Ag increased to 11.21%±4.95%(range: 2.12% to 28.84%) with 95.00%of the patients with AA-Ag<20% and the rate of the patients with low on-treatment platelet aggregation was 15.00%. Multiple variable analysis revealed that aspirin 40 mg/d AA-Ag was significantly influenced by aspirin 100 mg/d AA-Ag, BMI and platelet counts. The rate of gastrointestinal bleeding decreased from 12.00% to 5.00%,and upper gastrointestinal symptoms decreased from 59.00% to 21.00% after the switch in 40 mg/d group. Switching aspirin dosage from 100 mg/d to 40 mg/d reduces the bleeding events and improves upper gastrointestinal symptoms, thus inhibiting platelet aggregation effectively in very elderly patients.

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

NASA Astrophysics Data System (ADS)

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.

Enoxaparin and Aspirin Compared With Aspirin Alone to Prevent Placenta-Mediated Pregnancy Complications: A Randomized Controlled Trial.

PubMed

Haddad, Bassam; Winer, Norbert; Chitrit, Yvon; Houfflin-Debarge, Véronique; Chauleur, Céline; Bages, Karine; Tsatsaris, Vassilis; Benachi, Alexandra; Bretelle, Florence; Gris, Jean-Christophe; Bastuji-Garin, Sylvie

2016-11-01

To evaluate whether daily enoxaparin, added to low-dose aspirin, started before 14 weeks of gestation reduces placenta-mediated complications in pregnant women with previous severe preeclampsia diagnosed before 34 weeks of gestation. In this open-label multicenter randomized trial, we enrolled consenting pregnant women with previous severe preeclampsia diagnosed before 34 weeks of gestation, gestational age at randomization of 7-13 weeks, singleton pregnancy, and no plan for anticoagulation. Eligible patients were randomly assigned to a one-to-one ratio to receive daily either 4,000 international units enoxaparin plus 100 mg aspirin or 100 mg aspirin alone. Randomization was done by a web-based randomization system. The primary composite outcome comprised maternal death, perinatal death, preeclampsia, small for gestational age (less than the 10th percentile), and placental abruption. A sample size of 232 women equally divided into two groups was needed to detect a significant reduction in primary outcome from 55% in the aspirin group to 36.7% in the enoxaparin-aspirin group (α: 0.05, β: 0.8, two-sided). Between November 14, 2009, and February 21, 2015, 257 participants were enrolled. Baseline demographic and clinical factors were similar between groups. Eight women were excluded after randomization (six in the enoxaparin-aspirin group and two in the aspirin group), leaving 124 participants assigned to enoxaparin-aspirin and 125 to aspirin. Five participants were lost to follow-up (two in the enoxaparin-aspirin group and three in the aspirin group). There was no significant difference between the groups in the primary outcome: enoxaparin-aspirin 42 of 122 (34.4%) compared with aspirin alone 50 of 122 (41%) (relative risk 0.84, 95% confidence interval 0.61-1.16, P=.29). The occurrence of complications did not differ between the two groups. Antepartum prophylactic enoxaparin does not significantly reduce placenta-mediated complications in women receiving low

ASA24-2014, 2012, and 2011, all versions (no longer available)

Cancer.gov

Researchers can no longer register new studies to use ASA24-2014, ASA24-Canada-2014 and ASA24-2011; however, all of these versions of the ASA24® system are available for data collection until March 2017.

Aspirin, Non-Aspirin Nonsteroidal Anti-inflammatory Drugs, or Acetaminophen and risk of ovarian cancer

PubMed Central

Lo-Ciganic, Wei-Hsuan; Zgibor, Janice C.; Bunker, Clareann H; Moysich, Kirsten B.; Edwards, Robert P.; Ness, Roberta B.

2012-01-01

Background Aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NA-NSAIDs) and acetaminophen all have biologic effects that might reduce the risk of ovarian cancer. However, epidemiologic data on this question are mixed. Methods A population-based, case-control study in western Pennsylvania, eastern Ohio, and western New York State included 902 women with incident epithelial ovarian cancer who were diagnosed between February 2003 to November 2008 and 1,802 matched controls. Regular use (at least 2 tablets per week for 6 months or more) of aspirin, NA-NSAIDs, and acetaminophen before the reference date (9 months before interview date) was assessed by in-person interview. We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results The OR for aspirin use was 0.81 (95% CI= 0.63–1.03). Decreased risks were found among women who used aspirin continuously (0.71 [0.54–0.94]) or at a low-standardized daily dose (0.72 [0.53–0.97]), who used aspirin for the prevention of cardiovascular disease (0.72 [0.57–0.97]), who used aspirin more recently, or who used selective COX-2 inhibitors (0.60 [0.39–0.94]). No associations were observed among women using non-selective NA-NSAIDs or acetaminophen. Conclusions Risk reductions of ovarian cancer were observed with use of aspirin or selective COX-2 inhibitors. However, the results should be interpreted with caution due to the inherent study limitations and biases. PMID:22252409

Long-term treatment with aspirin desensitization: a prospective clinical trial comparing 100 and 300 mg aspirin daily.

PubMed

Rozsasi, A; Polzehl, D; Deutschle, T; Smith, E; Wiesmiller, K; Riechelmann, H; Keck, T

2008-09-01

The daily dose of aspirin in desensitization in aspirin-sensitive asthmatics with nasal polyps is still a matter of debate. To compare two doses of aspirin during the first year of desensitization and to evaluate long-term effects on nasal/pulmonary symptoms. Patients with positive aspirin provocation test were treated with either 100 or 300 mg aspirin daily. In all patients taking 100 mg aspirin (n = 7) recurrent nasal polyps were observed. No patient experienced reduction of asthma medication or improvement of pulmonary function. In the 300 mg group no recurrent nasal polyps were seen. Asthma medication could be reduced in three patients, pulmonary function was improved in five patients. Thirty-nine consecutively desensitized patients, taking 300 mg aspirin, showed significant improvement of olfaction and polyp-free nasal passages during the first year of therapy. After a median follow-up of 27 months no sinus revision surgery was necessary. Aspirin desensitization followed by 300 mg aspirin daily is efficacious and results in polyp-free nasal airways, improvement of sense of smell, and reduction of the need for sinus revision surgery for recurrent nasal polyps. Aspirin in a dose of 100 mg daily is not sufficient to effectively reduce nasal and bronchial or pulmonary symptoms and to prevent recurrent nasal polyps by at least the first 12 months of treatment.

Choline magnesium trisalicylate in patients with aspirin-induced asthma.

PubMed

Szczeklik, A; Nizankowska, E; Dworski, R

1990-05-01

Treatment of inflammatory diseases of asthmatics can be a serious problem since some patients show intolerance to aspirin and other non-steroidal, anti-inflammatory drugs that are cyclooxygenase inhibitors. Salicylates were believed to be well tolerated, but recent reports have demonstrated that diflunisal and salicylsalicylic acid can precipitate asthma attacks in aspirin-intolerant patients. This study was designed to determine the tolerance of choline magnesium trisalicylate (CMT), a nonacetylated salicylate with potent analgesic and anti-inflammatory activity, in 23 asthmatics with aspirin hypersensitivity confirmed by oral challenge. The study consisted of three phases: 1) patients received increasing doses (50-1,500 mg) of CMT under a single-blind protocol; 2) patients received either a placebo or CMT challenge in a double-blind, randomized, cross-over design; 3) patients received CMT at daily 3,000 mg doses for 1 week. Throughout the study, pulmonary function tests, peak nasal inspiratory flow, and serum salicylate and thromboxane B2 (TXB2) levels were monitored. Results showed no airway obstruction, nasal congestion or rhinorrhea after CMT. There was no significant decrease in serum TXB2 levels, indicating the absence of cyclooxygenase inhibition with CMT. We conclude that choline magnesium trisalicylate is a safe drug for treatment of different anti-inflammatory disorders in asthmatics with aspirin hypersensitivity.

Enzymatic Production of Ascorbic Acid-2-phosphate by Recombinant Acid Phosphatase.

PubMed

Zheng, Kai; Song, Wei; Sun, Anran; Chen, Xiulai; Liu, Jia; Luo, Qiuling; Wu, Jing

2017-05-24

In this study, an environmentally friendly and efficient enzymatic method for the synthesis of l-ascorbic acid-2-phosphate (AsA-2P) from l-ascorbic acid (AsA) was developed. The Pseudomonas aeruginosa acid phosphatase (PaAPase) was expressed in Escherichia coli BL21. The optimal temperature, optimal pH, K m , k cat , and catalytic efficiency of recombinant PaAPase were 50 °C, 5.0, 93 mM, 4.2 s -1 , and 2.7 mM -1 min -1 , respectively. The maximal dry cell weight and PaAPase phosphorylating activity reached 8.5 g/L and 1127.7 U/L, respectively. The highest AsA-2P concentration (50.0 g/L) and the maximal conversion (39.2%) were obtained by incubating 75 g/L intact cells with 88 g/L AsA and 160 g/L sodium pyrophosphate under optimal conditions (0.1 mM Ca 2+ , pH 4.0, 30 °C) for 10 h; the average AsA-2P production rate was 5.0 g/L/h, and the AsA-2P production system was successfully scaled up to a 7.5 L fermenter. Therefore, the enzymatic process showed great potential for production of AsA-2P in industry.

Baseline characteristics of the omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study.

PubMed

Viecelli, Andrea K; Pascoe, Elaine M; Polkinghorne, Kevan R; Hawley, Carmel M; Paul-Brent, Peta-Anne; Badve, Sunil V; Cass, Alan; Johnson, David W; Kerr, Peter G; Mori, Trevor A; Scaria, Anish; Hooi, Seong L; Ong, Meng L; Irish, Ashley B

2016-03-01

The Fish oils and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) trial investigated whether 3 months of omega-3 polyunsaturated fatty acids, either alone or in combination with aspirin, will effectively reduce primary access failure of de novo arteriovenous fistulae. This report presents the baseline characteristics of all study participants, examines whether study protocol amendments successfully increased recruitment of a broader and more representative haemodialysis cohort, including patients already receiving aspirin, and contrasts Malaysian participants with those from Australia, New Zealand and the United Kingdom (UK). This international, randomized, double-blind, placebo-controlled trial included patients older than 19 years with stage 4 or 5 chronic kidney disease currently receiving, or planned within 12 months to receive haemodialysis. Participants (n = 568) were overweight (28.6 ± 7.3 kg/m(2) ), relatively young (54.8 ± 14.3 years), and predominantly male (63%) with a high prevalence of diabetes mellitus (46%) but low rate of ischaemic heart disease (8%). Sixty one percent were planned for lower arm arteriovenous fistula creation. Malaysian participants (n = 156) were younger (51.8 ± 13.6 years vs 57.1 ± 14.2 years, P < 0.001) with a higher prevalence of diabetes mellitus (65% vs 43%, P < 0.001), but less ischaemic heart disease (5% vs 14%, P < 0.01) compared with the combined Australian, New Zealand and UK cohort (n = 228). Protocol modifications allowing for inclusion of patients receiving aspirin increased the prevalence of co-morbidities compared with the original cohort. The FAVOURED study participants, while mostly similar to patients in contemporary national registry reports and comparable recent clinical trials, were on average younger and had less ischaemic heart disease. These differences were reduced as a consequence of including patients already receiving aspirin. © 2015 Asian

Overview of the ASA24® Researcher Website

Cancer.gov

The ASA24 Researcher Website allows researchers, clinicians, and teachers to register to use the ASA24 system for research, clinical practice, or teaching; to manage logistics of data collection; and to obtain analytic output files.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 developmentmore » 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.« less

Localized periorbital edema induced by aspirin.

PubMed

Katz, Y; Goldberg, N; Kivity, S

1993-07-01

We documented localized periorbital edema in two patients with aspirin sensitivity without underlying chronic urticaria. The reaction developed 30 min after ingestion of 62.5 and 125 mg of aspirin, respectively. No systemic symptoms were observed. Other NSAIDs did not induce symptoms. These patients were able to tolerate doses of aspirin after pretreatment with terfenadine. These observations suggest that histamine plays a central role in aspirin-induced skin reaction. Despite the fact that terfenadine blocks the drug-induced reaction, this protocol should be used with caution and only where there is no feasible alternative to aspirin.

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

PubMed

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.

Cost‐Effectiveness of Clopidogrel‐Aspirin Versus Aspirin Alone for Acute Transient Ischemic Attack and Minor Stroke

PubMed Central

Pan, Yuesong; Wang, Anxin; Liu, Gaifen; Zhao, Xingquan; Meng, Xia; Zhao, Kun; Liu, Liping; Wang, Chunxue; Johnston, S. Claiborne; Wang, Yilong; Wang, Yongjun

2014-01-01

Background Treatment with the combination of clopidogrel and aspirin taken soon after a transient ischemic attack (TIA) or minor stroke was shown to reduce the 90‐day risk of stroke in a large trial in China, but the cost‐effectiveness is unknown. This study sought to estimate the cost‐effectiveness of the clopidogrel‐aspirin regimen for acute TIA or minor stroke. Methods and Results A Markov model was created to determine the cost‐effectiveness of treatment of acute TIA or minor stroke patients with clopidogrel‐aspirin compared with aspirin alone. Inputs for the model were obtained from clinical trial data, claims databases, and the published literature. The main outcome measure was cost per quality‐adjusted life‐years (QALYs) gained. One‐way and multivariable probabilistic sensitivity analyses were performed to test the robustness of the findings. Compared with aspirin alone, clopidogrel‐aspirin resulted in a lifetime gain of 0.037 QALYs at an additional cost of CNY 1250 (US$ 192), yielding an incremental cost‐effectiveness ratio of CNY 33 800 (US$ 5200) per QALY gained. Probabilistic sensitivity analysis showed that clopidogrel‐aspirin therapy was more cost‐effective in 95.7% of the simulations at a willingness‐to‐pay threshold recommended by the World Health Organization of CNY 105 000 (US$ 16 200) per QALY. Conclusions Early 90‐day clopidogrel‐aspirin regimen for acute TIA or minor stroke is highly cost‐effective in China. Although clopidogrel is generic, Plavix is brand in China. If Plavix were generic, treatment with clopidogrel‐aspirin would have been cost saving. PMID:24904018

Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus.

PubMed

Bhatt, Deepak L; Grosser, Tilo; Dong, Jing-Fei; Logan, Douglas; Jeske, Walter; Angiolillo, Dominick J; Frelinger, Andrew L; Lei, Lanyu; Liang, Juan; Moore, Jason E; Cryer, Byron; Marathi, Upendra

2017-02-14

A limitation of aspirin is that some patients, particularly those with diabetes, may not have an optimal antiplatelet effect. The goal of this study was to determine if oral bioavailability mediates nonresponsiveness. The rate and extent of serum thromboxane generation and aspirin pharmacokinetics were measured in 40 patients with diabetes in a randomized, single-blind, triple-crossover study. Patients were exposed to three 325-mg aspirin formulations: plain aspirin, PL2200 (a modified-release lipid-based aspirin), and a delayed-release enteric-coated (EC) aspirin. Onset of antiplatelet activity was determined by the rate and extent of inhibition of serum thromboxane B 2 (TXB 2 ) generation. Aspirin nonresponsiveness was defined as a level of residual serum TXB 2 associated with elevated thrombotic risk (<99.0% inhibition or TXB 2 >3.1 ng/ml) within 72 h after 3 daily aspirin doses. The rate of aspirin nonresponsiveness was 15.8%, 8.1%, and 52.8% for plain aspirin, PL2200, and EC aspirin, respectively (p < 0.001 for both comparisons vs. EC aspirin; p = 0.30 for comparison between plain aspirin and PL2200). Similarly, 56% of EC aspirin-treated subjects had serum TXB 2 levels >3.1 ng/ml, compared with 18% and 11% of subjects after administration of plain aspirin and PL2200 (p < 0.0001). Compared with findings for plain aspirin and PL2200, this high rate of nonresponsiveness with EC aspirin was associated with lower exposure to acetylsalicylic acid (63% and 70% lower geometric mean maximum plasma concentration [C max ] and 77% and 82% lower AUC 0-t [area under the curve from time 0 to the last time measured]) and 66% and 72% lower maximum decrease of TXB 2 , with marked interindividual variability. A high proportion of patients treated with EC aspirin failed to achieve complete inhibition of TXB 2 generation due to incomplete absorption. Reduced bioavailability may contribute to "aspirin resistance" in patients with diabetes. (Pharmacodynamic Evaluation of PL2200

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

PubMed Central

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

2014-01-01

The 2013 Aspirin Foundation Conference covered a range of topics from clinical and medical history, epidemiology, health economics, and the current uses of aspirin in general practice and in the treatment and prevention of cancer. The use of aspirin as primary prevention in people at risk of atherosclerotic events is now well known, but its use as a preventative agent in some cancer types is still under discussion, and data on colorectal and lung cancer were presented at this meeting. The potential use of aspirin in preventing vascular disease in HIV patients was also discussed. The cost effectiveness of aspirin as a primary prevention strategy was discussed for the first time in this series of meetings. PMID:24678343

Comparative plasma salicylate and urine salicylurate levels following administration of aspirin, magnesium salicylate, and choline magnesium trisalicylate.

PubMed

Mason, W D

1980-11-01

Eighteen healthy volunteers were administered single doses of commercially available solid dosage forms of aspirin, magnesium salicylate (I), and choline magnesium trisalicylate (II), equivalent to approximately 500 mg of salicylic acid, in a randomized, complete crossover design. Plasma salicylate and urine salicylurate levels were measured by high-pressure liquid chromatography at frequent intervals following dosing; the resultant profiles, areas under the curve (AUC), and percentages of dose excreted as salicylurate were statistically analyzed by an analysis of variance. The plasma salicylate levels following the two dosage forms containing I and II were virtually identical when corrected for small differences in the dose. The plasma salicylic acid level following aspirin was approximately 10% lower during the 1.5--3.0-hr interval due to a portion of unhydrolyzed aspirin, but the dose-corrected AUC for the products tested did not differ significantly (p < 0.05). During the 24 hr following dosing, 66.5 +/- 12.1 68.4 +/- 7.1, and 60.9 +/- 14.1% of the salicylic acid were excreted as urine salicylurate for aspirin, I, and II, respectively, with no significant difference (p < 0.05). Based on this study, there are no significant differences in the rate and extent of absorption of salicylate following the three dosage forms tested, and the elimination kinetics of salicylic acid are not altered by these dosage forms.

Effect of aspirin on the contractility of aortic smooth muscle and the course of blood pressure development in male spontaneously hypertensive rats.

PubMed

Rahmani, M A; David, V; Huang, M; DeGray, G

1998-01-01

The effects of acetylsalicylic acid (ASA) on aortic smooth muscle contractility were studied in aortic rings of male SHR and WKY rats. The rats were administered two intraperitoneal injections of 10 mg/kg of ASA per week for ten weeks. Blood pressure of each rat was monitored twice weekly prior to the i.p. injections. Twenty four hours after the last injection the aortic smooth muscles were evaluated for generation of active tension in response to KCl, Phenylephrine (PE), Clonidine and Norepinephrine (NE). In another set of experiments calcium conductance was evaluated in the presence or absence of endothelium both in ASA treated and non treated animals. We report that aortic rings from ASA-treated SHR animals were more responsive to contractile agents than rings from non-treated SHR male rats. Also, the Ca2+ conductance in vitro was enhanced appreciably in SHR aortic rings denuded of their monolayer of endothelium in response to ASA treatment. No decrease in systolic blood pressure was observed in response to ASA treatment in SHR male rats. These results suggest that acetylsalicylic acid not only may modulate aortic smooth muscle contractility through the metabolites of arachidonic acid but may repair to a great extent the hypertension associated plasma membrane permeability defect of vascular myocytes.

Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to Aspirin.

PubMed

Mohring, Annemarie; Piayda, Kerstin; Dannenberg, Lisa; Zako, Saif; Schneider, Theresa; Bartkowski, Kirsten; Levkau, Bodo; Zeus, Tobias; Kelm, Malte; Hohlfeld, Thomas; Polzin, Amin

2017-01-01

Platelet inhibition by aspirin is indispensable in the secondary prevention of cardiovascular events. Nevertheless, impaired aspirin antiplatelet effects (high on-treatment platelet reactivity [HTPR]) are frequent. This is associated with an enhanced risk of cardiovascular events. The current gold standard to evaluate platelet hyper-reactivity despite aspirin intake is the light-transmittance aggregometry (LTA). However, pharmacologically, the most specific test is the measurement of arachidonic acid (AA)-induced thromboxane (TX) B2 formation. Currently, the optimal cut-off to define HTPR to aspirin by inhibition of TX formation is not known. Therefore, in this pilot study, we aimed to calculate a TX formation cut-off value to detect HTPR defined by the current gold standard LTA. We measured platelet function in 2,507 samples. AA-induced TX formation by ELISA and AA-induced LTA were used to measure aspirin antiplatelet effects. TX formation correlated nonlinearly with the maximum of aggregation in the AA-induced LTA (Spearman's rho R = 0.7396; 95% CI 0.7208-0.7573, p < 0.0001). Receiver operating characteristic analysis and Youden's J statistics revealed 209.8 ng/mL as the optimal cut-off value to detect HTPR to aspirin with the TX ELISA (area under the curve: 0.92, p < 0.0001, sensitivity of 82.7%, specificity of 90.3%). In summary, TX formation ELISA is reliable in detecting HTPR to aspirin. The calculated cut-off level needs to be tested in trials with clinical end points. © 2017 S. Karger AG, Basel.

Orally given gastroprotective capsaicin does not modify aspirin-induced platelet aggregation in healthy male volunteers (human phase I examination).

PubMed

Sandor, B; Papp, J; Mozsik, Gy; Szolcsanyi, J; Keszthelyi, Zs; Juricskay, I; Toth, K; Habon, Tamas

2014-12-01

Capsaicin is a well-known component of red pepper. Recent studies have shown that capsaicin could prevent gastric ulcer provoked by various NSAID-s like acetylsalicylic acid (ASA). Primary objective of this human clinical phase I trial was to investigate whether two different doses of capsaicin co-administered with ASA could alter the inhibitory effect of ASA on platelet aggregation. 15 healthy male subjects were involved in the study and treated orally with 400 μg capsaicin, 800 μg capsaicin, 500 mg ASA, 400 μg capsaicin+500 mg ASA and 800 μg capsaicin+500 mg ASA. Blood was drawn before and 1, 2, 6 and 24 hours after the drug administration. After that epinephrine induced platelet aggregation was measured by optical aggregometry. Between treatments, volunteers had a 6-day wash-out period. Our results showed that capsaicin had no effect on platelet aggregation, while as expected, ASA monotherapy resulted in a significant and clinically effective platelet aggregation inhibition (p ≤ 0.001). The combined ASA-capsaicin therapies reached equivalent effectiveness in platelet aggregation inhibition as ASA monotherapy. Our investigation proved that capsaicin did not influence the inhibitory effect of ASA on platelet aggregation, thus the capsaicin-ASA treatment would combine the antiplatelet effect of ASA with the possible gastroprotection of capsaicin.

Cost-effectiveness of clopidogrel-aspirin versus aspirin alone for acute transient ischemic attack and minor stroke.

PubMed

Pan, Yuesong; Wang, Anxin; Liu, Gaifen; Zhao, Xingquan; Meng, Xia; Zhao, Kun; Liu, Liping; Wang, Chunxue; Johnston, S Claiborne; Wang, Yilong; Wang, Yongjun

2014-06-05

Treatment with the combination of clopidogrel and aspirin taken soon after a transient ischemic attack (TIA) or minor stroke was shown to reduce the 90-day risk of stroke in a large trial in China, but the cost-effectiveness is unknown. This study sought to estimate the cost-effectiveness of the clopidogrel-aspirin regimen for acute TIA or minor stroke. A Markov model was created to determine the cost-effectiveness of treatment of acute TIA or minor stroke patients with clopidogrel-aspirin compared with aspirin alone. Inputs for the model were obtained from clinical trial data, claims databases, and the published literature. The main outcome measure was cost per quality-adjusted life-years (QALYs) gained. One-way and multivariable probabilistic sensitivity analyses were performed to test the robustness of the findings. Compared with aspirin alone, clopidogrel-aspirin resulted in a lifetime gain of 0.037 QALYs at an additional cost of CNY 1250 (US$ 192), yielding an incremental cost-effectiveness ratio of CNY 33 800 (US$ 5200) per QALY gained. Probabilistic sensitivity analysis showed that clopidogrel-aspirin therapy was more cost-effective in 95.7% of the simulations at a willingness-to-pay threshold recommended by the World Health Organization of CNY 105 000 (US$ 16 200) per QALY. Early 90-day clopidogrel-aspirin regimen for acute TIA or minor stroke is highly cost-effective in China. Although clopidogrel is generic, Plavix is brand in China. If Plavix were generic, treatment with clopidogrel-aspirin would have been cost saving. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Complexity in estimation of esomeprazole and its related impurities' stability in various stress conditions in low-dose aspirin and esomeprazole magnesium capsules.

PubMed

Reddy, Palavai Sripal; Hotha, Kishore Kumar; Sait, Shakil

2013-01-01

A complex, sensitive, and precise high-performance liquid chromatographic method for the profiling of impurities of esomeprazole in low-dose aspirin and esomeprazole capsules has been developed, validated, and used for the determination of impurities in pharmaceutical products. Esomeprazole and its related impurities' development in the presence of aspirin was traditionally difficult due to aspirin's sensitivity to basic conditions and esomeprazole's sensitivity to acidic conditions. When aspirin is under basic, humid, and extreme temperature conditions, it produces salicylic acid and acetic acid moieties. These two byproducts create an acidic environment for the esomeprazole. Due to the volatility and migration phenomenon of the produced acetic acid and salicylic acid from aspirin in the capsule dosage form, esomeprazole's purity, stability, and quantification are affected. The objective of the present research work was to develop a gradient reversed-phase liquid chromatographic method to separate all the degradation products and process-related impurities from the main peak. The impurities were well-separated on a RP8 column (150 mm × 4.6mm, X-terra, RP8, 3.5μm) by the gradient program using a glycine buffer (0.08 M, pH adjusted to 9.0 with 50% NaOH), acetonitrile, and methanol at a flow rate of 1.0 mL min(-1) with detection wavelength at 305 nm and column temperature at 30°C. The developed method was found to be specific, precise, linear, accurate, rugged, and robust. LOQ values for all of the known impurities were below reporting thresholds. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis, and thermal degradation in the presence of aspirin. The developed RP-HPLC method was validated according to the present ICH guidelines for specificity, linearity, accuracy, precision, limit of detection, limit of quantification, ruggedness, and robustness.

Aspirin, Butalbital, and Caffeine

MedlinePlus

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 ...

Localized unilateral periorbital edema induced by aspirin.

PubMed

Price, K S; Thomson, D M

1997-11-01

Aspirin intolerance manifested as bronchospasm or urticaria/angioedema has been observed since the beginning of this century. To report a novel case of intolerance to aspirin ingestion. Case report; routine skin testing; pulmonary function testing; aspirin challenge. A 30-year-old man with a history of left ocular trauma at the age of 10 noted a 3-year history of left periorbital angioedema after aspirin but not other nonsteroidal anti-inflammatory drugs. Incremental oral aspirin challenge resulted in this unilateral symptomatology at a dose of 673 mg. To the best of our knowledge, this is the first reported case of unilateral periorbital edema following aspirin ingestion.

[A short history of anti-rheumatic therapy. II. Aspirin].

PubMed

Pasero, G; Marson, P

2010-01-01

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

Aspirin alone and combined with a statin suppresses eicosanoid formation in human colon tissue.

PubMed

Gottschall, Heike; Schmöcker, Christoph; Hartmann, Dirk; Rohwer, Nadine; Rund, Katharina; Kutzner, Laura; Nolte, Fabian; Ostermann, Annika I; Schebb, Nils Helge; Weylandt, Karsten H

2018-05-01

Eicosanoids, including prostaglandins (PGs) and thromboxanes, are broadly bioactive lipid mediators and increase colon tumorigenesis possibly through chronic inflammatory mechanisms. Epidemiological and experimental data suggest that acetylsalicylic acid (ASA) helps prevent colorectal cancer (CRC), possibly through cyclooxygenase (COX)-mediated suppression of eicosanoid, particularly PGE 2 , formation. Recent studies suggest that statins prevent CRC and improve survival after diagnosis. We identified patients on ASA and/or statin treatment undergoing routine colonoscopy and measured eicosanoid levels in colonic mucosa with targeted metabolomics technology (LC-MS/MS). ASA-treated individuals (n = 27) had significantly lower tissue eicosanoid levels of most COX-derived metabolites than untreated individuals (n = 31). In contrast, COX-derived lipid metabolites tended to be higher in patients with statin treatment (n = 7) as compared with those not receiving statins (n = 24). This effect was not discernible in subjects treated with ASA and statins (n = 11): Individuals treated with both drugs showed a pronounced suppression of COX-derived eicosanoids in colon tissue, even compared with subjects treated with ASA alone. Our data from a routine clinical setting support the hypothesis that ASA and statins could inhibit CRC development via lipid mediator modification. Further studies should directly investigate the effect of dual ASA and statin treatment on colon tumorigenesis in humans. Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.

Asiago spectroscopic classification of ASAS-SN18ao

NASA Astrophysics Data System (ADS)

Tomasella, L.; Benetti, S.; Cappellaro, E.; Turatto, M.

2018-01-01

The Asiago Transient Classification Program (Tomasella et al. 2014, AN, 335, 841) reports the spectroscopic classification of ASAS-SN18ao (aka AT2018gm, Atel #11178) discovered during the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014).

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

PubMed

Swaim, Lisa; Hillman, Robert S

2009-07-01

We aimed to determine the relative level of platelet inhibition achieved with low-dose aspirin (81 mg daily) compared with a very low-dose (100 mg every other day). The Womens Health Study (WHS) found that a dose of 100 mg every other day of aspirin provided protection against stroke as primary prophylaxis, but not myocardial infarction. In the United States, the most commonly prescribed dose of aspirin for primary prophylaxis is 81 mg per day. As a result, it is important to know whether these doses are equivalent before extrapolating the results of the WHS to women in the U.S. To achieve this goal, we have studied the effects of these two dosing regimens on platelet function in healthy women meeting the WHS inclusion criteria using a randomized design. We enrolled 49 healthy female volunteers and used a sequential, crossover design to compare the two regimens. The participants received a 17-day course of each aspirin-dosing regimen separated by a 7-day washout period. The degree of platelet inhibition was measured on days 14-17 of each dosing regimen using a point-of-care platelet function assay utilizing arachidonic acid to activate platelets (VerifyNow-Aspirin). Participants platelet response, expressed as Aspirin Response Unit (ARU) attained a significantly greater level of platelet inhibition on days 14-17 while taking aspirin 81 mg daily compared to aspirin 100 mg every other day (31.3% vs. 12.7%, P < 0.0001) with mean +/- SD ARU values of 445 +/- 50 and 570 +/- 68, P < 0.0001. Significantly more daily readings in participants were >or=550 ARU, a value correlated with clinical outcomes in several studies, with the 100 mg every other day regimen (72.0% vs. 6.4% with 81 mg daily, P < 0.0001), and this alternate-day regimen also resulted in more day-to-day variability in platelet function (P = 0.0002). We found significantly less inhibition of platelet function with the dose used in the WHS than the usual U.S. dose. We observed that the degree of platelet

5-ASA affects cell cycle progression in colorectal cells by reversibly activating a replication checkpoint.

PubMed

Luciani, M Gloria; Campregher, Christoph; Fortune, John M; Kunkel, Thomas A; Gasche, Christoph

2007-01-01

Individuals with inflammatory bowel disease are at risk of developing colorectal cancer (CRC). Epidemiologic, animal, and laboratory studies suggest that 5-amino-salicylic acid (5-ASA) protects from the development of CRC by altering cell cycle progression and by inducing apoptosis. Our previous results indicate that 5-ASA improves replication fidelity in colorectal cells, an effect that is active in reducing mutations. In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. CRC cells with different genetic backgrounds such as HT29, HCT116, HCT116(p53-/-), HCT116+chr3, and LoVo were treated with 5-ASA for 2-96 hours. Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. We found that 5-ASA at concentrations between 10 and 40 mmol/L affects cell cycle progression by inducing cells to accumulate in the S phase. This effect was independent of the hMLH1, hMSH2, and p53 status because it was observed to a similar extent in all cell lines under investigation. Moreover, wash-out experiments demonstrated reversibility within 48 hours. Although p53 did not have a causative role, p53 Ser15 was strongly phosphorylated. Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance of genomic stability and counteracts carcinogenesis.

5-ASA Affects Cell Cycle Progression in Colorectal Cells by Reversibly Activating a Replication Checkpoint

PubMed Central

LUCIANI, M. GLORIA; CAMPREGHER, CHRISTOPH; FORTUNE, JOHN M.; KUNKEL, THOMAS A.; GASCHE, CHRISTOPH

2007-01-01

Background & Aims Individuals with inflammatory bowel disease are at risk of developing colorectal cancer (CRC). Epidemiologic, animal, and laboratory studies suggest that 5-amino-salicylic acid (5-ASA) protects from the development of CRC by altering cell cycle progression and by inducing apoptosis. Our previous results indicate that 5-ASA improves replication fidelity in colorectal cells, an effect that is active in reducing mutations. In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. Methods CRC cells with different genetic backgrounds such as HT29, HCT116, HCT116p53−/−, HCT116+chr3, and LoVo were treated with 5-ASA for 2–96 hours. Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. Results We found that 5-ASA at concentrations between 10 and 40 mmol/L affects cell cycle progression by inducing cells to accumulate in the S phase. This effect was independent of the hMLH1, hMSH2, and p53 status because it was observed to a similar extent in all cell lines under investigation. Moreover, wash-out experiments demonstrated reversibility within 48 hours. Although p53 did not have a causative role, p53 Ser15 was strongly phosphorylated. Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. Conclusions Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance of genomic stability and counteracts carcinogenesis. PMID:17241873

Spectroscopic studies of the interaction of aspirin and its important metabolite, salicylate ion, with DNA, A·T and G·C rich sequences

NASA Astrophysics Data System (ADS)

Bathaie, S. Z.; Nikfarjam, L.; Rahmanpour, R.; Moosavi-Movahedi, A. A.

2010-12-01

Among different biological effects of acetylsalicylic acid (ASA), its anticancer property is controversial. Since ASA hydrolyzes rapidly to salicylic acid (SA), especially in the blood, interaction of both ASA and SA (as the small molecules) with ctDNA, oligo(dA·dT) 15 and oligo(dG·dC) 15, as a possible mechanism of their action, is investigated here. The results show that the rate of ASA hydrolysis in the absence and presence of ctDNA is similar. The spectrophotometric results indicate that both ASA and SA cooperatively bind to ctDNA. The binding constants ( K) are (1.7 ± 0.7) × 10 3 M -1 and (6.7 ± 0.2) × 10 3 M -1 for ASA and SA, respectively. Both ligands quench the fluorescence emission of ethidium bromide (Et)-ctDNA complex. The Scatchard plots indicate the non-displacement based quenching (non-intercalative binding). The circular dichroism (CD) spectra of ASA- or SA-ctDsNA complexes show the minor distortion of ctDNA structure, with no characteristic peaks for intercalation of ligands. Tm of ctDNA is decreased up to 3 °C upon ASA binding. The CD results also indicate more distortions on oligo(dG·dC) 15 structure due to the binding of both ASA and SA in comparison with oligo(dA·dT) 15. All data indicate the more affinity for SA binding with DNA minor groove in comparison with ASA which has more hydrophobic character.

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

PubMed

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

Effect of aspirin on the pharmacokinetics and absorption of panax notoginseng saponins.

PubMed

Tian, Zhihao; Pang, Huanhuan; Zhang, Qiang; Du, Shouying; Lu, Yang; Zhang, Lin; Bai, Jie; Li, Pengyue; Li, Danqi; Zhao, Mengdi; Chen, Xiaonan

2018-02-01

Panax notoginseng saponins, a traditional Chinese medicine extraction, and aspirin are both widely used to treat cerebral infarction in China. Good results in clinical practice have been achieved, when Panax notoginseng saponins was taken together with aspirin. To investigate the interaction of the two drugs in vivo, the concentration of notoginsenoside R 1 , ginsenoside Rg 1 , Rb 1 , Re and Rd. in blood were simultaneously measured by UPLC/MS/MS. Sample preparation was carried out by the protein precipitation technique with an internal standard saikosaponin A standard. The separation of six components was achieved by using an ACQUITY UPLC ®BEH C18 column (1.7μm 2.1×100mm) by gradient elution using water (containing 0.2% formic acid) and acetonitrile (containing 0.2% formic acid) as the mobile phase at a flow rate of 0.2mL/min. The pharmacokinetic parameters were determined using non-compartmental analysis. The transport of notoginsenoside R 1 , ginsenoside Rg 1 , Rb 1 , Re and Rd. in MDCK -MDR1 cell monolayer was also used to verify the conclusion of pharmacokinetic drug-drug interaction and study the mechanism of drug interaction. The concentrations of the five components increased in a certain extent when the two drugs administered together in rats. The values of apparent permeability coefficients were significantly increased when the two drugs were used together. Aspirin and salicylic acid could destroy the tight junction protein and open the intercellular space to increase the absorption of Panax notoginseng saponins. Pharmacokinetic drug-drug interaction in vivo existed between Panax notoginseng saponins and aspirin. The drug-drug interaction mainly occurred in the process of absorption. Copyright © 2018 Elsevier B.V. All rights reserved.

Immediate Reactions to More Than 1 NSAID Must Not Be Considered Cross-Hypersensitivity Unless Tolerance to ASA Is Verified.

PubMed

Pérez-Alzate, D; Cornejo-García, J A; Pérez-Sánchez, N; Andreu, I; García-Moral, A; Agúndez, J A; Bartra, J; Doña, I; Torres, M J; Blanca, M; Blanca-López, N; Canto, G

Individuals who develop drug hypersensitivity reactions (DHRs) to chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs) are considered cross-hypersensitive. The hallmark for this classification is that the patient presents a reaction after intake of or challenge with acetylsalicylic acid (ASA). Whether patients react to 2 or more NSAIDs while tolerating ASA remains to be studied (selective reactions, SRs). Objective: To identify patients with SRs to 2 or more NSAIDs including strong COX-1 inhibitors. Patients who attended the Allergy Service of Hospital Infanta Leonor, Madrid, Spain with DHRs to NSAIDs between January 2011 and December 2014 were evaluated. Those with 2 or more immediate reactions occurring in less than 1 hour after intake were included. After confirming tolerance to ASA, the selectivity of the response to 2 or more NSAIDs was demonstrated by in vivo and/or in vitro testing or by controlled administration. From a total of 203 patients with immediate DHRs to NSAIDs, 16 (7.9%) met the inclusion criteria. The patients presented a total of 68 anaphylactic or cutaneous reactions (mean [SD], 4.2 [2.1]). Most reactions were to ibuprofen and other arylpropionic acid derivatives and to metamizole. Two different NSAIDs were involved in 11 patients and 3 in 5 patients. Patients with NSAID-induced anaphylaxis or urticaria/angioedema should not be considered cross-hypersensitive unless tolerance to ASA is verified.

Combination antiplatelet therapy with aspirin and clopidogrel: the role of antecedent and concomitant doses of aspirin. An analysis of 711 patients.

PubMed

Serebruany, Victor L; Malinin, Alex I; Atar, Dan

2007-01-01

Numerous randomized studies have shown that the combination of clopidogrel with aspirin yields better clinical outcomes than monotherapy in patients with acute vascular events. However, the impact of the aspirin dose on the antiplatelet potency of clopidogrel is unclear. We sought to compare the antiplatelet profile of aspirin 81 mg (n = 252) versus aspirin 325 mg (n = 459) before and during conventional clopidogrel loading (300 mg), and/or clopidogrel maintenance (75 mg/daily) therapy. Secondary post hoc analysis of an existing dataset consisting of 711 patients after coronary stenting (n = 601) and ischemic stroke (n = 110) treated previously with aspirin for at least 1 month, and then with aspirin + clopidogrel for at least 7 days was performed. Platelet assessments include conventional and whole blood aggregometry, rapid cartridge-based analyzers, and expression of platelet/endothelial cell adhesion molecule-1, P-selectin, and GPIIb/IIIa activity by flow cytometry measured before and after addition of clopidogrel. There was a small but consistent yet non-significant trend towards more potent platelet inhibition with aspirin 325 mg compared to aspirin 81 mg for every platelet activation parameter before addition of clopidogrel. However, after loading and/or 1 week of chronic treatment with clopidogrel + aspirin, measured platelet parameters became very similar between the groups, and identical for collagen-induced aggregation and PFA-100 analyzer readings. Before addition of clopidogrel, aspirin 325 mg has a tendency to provide stronger platelet inhibition than aspirin 81 mg. However, when clopidogrel and aspirin are used in combination, the higher aspirin dose does not translate into superior antiplatelet action. Given that the existing body of evidence supports the comparable efficacy and, particularly, superior safety of lower versus higher doses of aspirin, aspirin 81 mg should be the dose used in combination with clopidogrel. 2007 S. Karger AG, Basel

Platelet Inhibition by 81 and 325 mg Aspirin Daily in Men vs. Women without Clinically Apparent Cardiovascular Disease

PubMed Central

Qayyum, Rehan; Becker, Diane M.; Yanek, Lisa R.; Moy, Taryn F.; Becker, Lewis C.; Faraday, Nauder; Vaidya, Dhananjay

2011-01-01

Compared to men, women have greater platelet aggregation before and after low-dose aspirin. It is not known whether high-dose aspirin therapy brings residual platelet aggregation in women closer to men. Our objective was to compare the inhibition of platelet aggregation in women and men after low and high-dose aspirin. We enrolled healthy subjects (N=106) in a trial of 14 days of aspirin 81 mg/day followed by 14 days of 325 mg/day. Platelet function was measured at baseline and following both aspirin doses. Women had greater baseline platelet activation measures. After both aspirin doses, both sexes had near complete suppression of platelet aggregation to arachidonic acid in whole blood and in platelet-rich plasma (PRP), the direct cyclooxygenase-1 (COX-1) pathway affected by aspirin. For indirect pathways, women had significantly greater residual platelet activation to collagen and adenosine diphosphate (ADP) in whole blood after both aspirin doses and in response to collagen and ADP in PRP after aspirin 325 mg/day only. After aspirin 325 mg/day, women continued to have greater residual platelet aggregation compared to men after aspirin 81 mg/day in response to collagen (p=0.016 in whole blood and p=0.037 in PRP), ADP (p<0.001 in whole blood and p=0.012 in PRP), and epinephrine (p=0.03 in PRP). Excretion of urinary thromboxane metabolite (urinary 11-dehydro thromboxane B2) decreased after aspirin to a similar extent in both sexes. In conclusion, women continue to have greater residual platelet activity after high-dose aspirin even when compared to men treated with a lower dose of aspirin. PMID:18435972

Aspirin challenge and desensitization: how, when and why.

PubMed

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.

Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy

PubMed Central

Iwamoto, Junichi; Saito, Yoshifumi; Honda, Akira; Matsuzaki, Yasushi

2013-01-01

Low-dose aspirin (LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society. On the other hand, a very low dose of aspirin (10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage. The incidence of LDA-induced gastrointestinal mucosal injury and bleeding has increased. It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug (NSAID)-induced lesions. The pathogenesis related to inhibition of cyclooxygenase (COX)-1 includes reduced mucosal flow, reduced mucus and bicarbonate secretion, and impaired platelet aggregation. The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence. The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation. The factors associated with an increased risk of upper gastrointestinal (GI) complications in subjects taking LDA are aspirin dose, history of ulcer or upper GI bleeding, age > 70 years, concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs, and Helicobacter pylori (H. pylori) infection. Moreover, no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea, acid regurgitation, heartburn, and bloating. It has been shown that the ratios of ulcers located in the body, fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA. Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers. In contrast to NSAID-induced gastrointestinal ulcers, a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers. The eradication of H. pylori is equivalent to treatment with

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

PubMed

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.

The ASA Regional Chapters program

NASA Astrophysics Data System (ADS)

McLaughlin, Elizabeth; Arvelo, Juan

2005-04-01

Are you involved in a Regional Chapter? The Regional Chapters Program certainly embraces the intent of our Society. ``The ASA was founded... to increase and diffuse the knowledge of acoustics and promote its practical applications. Any person... interested in acoustics is eligible for membership.'' The history and the activities of each Chapter are unique. There are currently twenty active chapters uniquely positioned to promote acoustics through outreach and involvement with the public. There have been several new developments in the Regional Chapters Program, the most exciting being the incorporation of Student Chapters! Our first, the Nebraska Student Chapter, was approved at the 75th Meeting of the ASA in NYC. Several more are on their way! Existing Chapters are revitalizing! The Washington DC Chapter has recently found new enthusiasm, re-establishing a robust program. A new student scholarship has been organized thanks to the generosity of Larry and Julia Royster. Another recent enhancement is the expansion of the Regional Chapters Website. There one can find useful materials including an updated Chapter Start-up Kit. Involvement in a chapter is a great way to give back to the ASA, to learn, promote acoustics, to socialize, and to involve new persons in our exciting field!

Double-blind, placebo-controlled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using /sup 99m/Tc-labeled 5-ASA suppositories

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, C.N.; Haber, G.; Aquino, J.A.

1987-12-01

Patients with active distal proctitis received either 5-aminosalicylic (5-ASA) acid or identical placebo suppositories, 500 mg t.i.d. for 6 weeks. Activity at 3 and 6 wks was assessed using a Disease Activity Index (DAI), derived from four categories: number of daily evacuations more than usual, evacuations containing blood, sigmoidoscopy appearance, and physician's overall assessment. Each category was graded 0-3. There was thus 0-12 points scored ranging from complete remission to severe disease. A minimum score of 3 from two categories was necessary for study entry. Of 27 patients randomized, 14 received active medication and 13 placebo. Of the 14 patients,more » with initial mean DAI 7.1 +/- 1.8, 11 were in complete remission at 6 wks (78.6%). Whereas, there was no significant change in the placebo group, with initial mean DAI 7.1 +/- 1.8. An additional 6 patients with inflammatory bowel disease and 6 healthy volunteers were given /sup 99m/Tc-labelled 5-aminosalicylic acid suppositories. The extent of spread was limited to the rectum, and the suppositories were retained for 3 hours. There was no absorbed radioactivity. 5-ASA suppositories are safe, well-tolerated, and effective treatment for active distal proctitis.« less

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

PubMed

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robbins, D.C.; Schwartz, R.S.; Kutny, K.

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 atmore » 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.« less

Aspirin for Primary Prevention of Cardiovascular Events

PubMed Central

Augustovski, Federico A.; Cantor, Scott B.; Thach, Chau T.; Spann, Stephen J.

1998-01-01

OBJECTIVE The use of aspirin for primary prevention of cardiovascular events in the general population is controversial. The purpose of this study was to create a versatile model to evaluate the effects of aspirin in the primary prevention of cardiovascular events in patients with different risk profiles. DESIGN A Markov decision-analytic model evaluated the expected length and quality of life for the cohort's next 10 years as measured by quality-adjusted survival for the options of taking or not taking aspirin. SETTING Hypothetical model of patients in a primary care setting. PATIENTS Several cohorts of patients with a range of risk profiles typically seen in a primary care setting were considered. Risk factors considered included gender, age, cholesterol levels, systolic blood pressure, smoking status, diabetes, and presence of left ventricular hypertrophy. The cohorts were followed for 10 years. Outcomes were myocardial infarction, stroke, gastrointestinal bleed, ulcer, and death. MAIN RESULTS For the cases considered, the effects of aspirin varied according to the cohort's risk profile. By taking aspirin, the lowest-risk cohort would be the most harmed with a loss of 1.8 quality-adjusted life days by taking aspirin; the highest risk cohort would achieve the most benefit with a gain of 11.3 quality-adjusted life days. Results without quality adjustment favored taking aspirin in all the cohorts, with a gain of 0.73 to 8.04 days. The decision was extremely sensitive to variations in the utility of taking aspirin and to aspirin's effects on cardiovascular mortality. The model was robust to other probability and utility changes within reasonable parameters. CONCLUSIONS The decision of whether to take aspirin as primary prevention for cardiovascular events depends on patient risk. It is a harmful intervention for patients with no risk factors, and it is beneficial in moderate and high-risk patients. The benefits of aspirin in this population are comparable to those

Pharmacokinetics and relative bioavailability of fixed-dose combination of clopidogrel and aspirin versus coadministration of individual formulations in healthy Korean men.

PubMed

Choi, Hyang-Ki; Ghim, Jong-Lyul; Shon, Jihong; Choi, Young-Kyung; Jung, Jin Ah

2016-01-01

Simultaneous prescription of clopidogrel and low-dose aspirin is recommended for the treatment of acute coronary syndrome because of improvements in efficacy and patient compliance. In this study, the pharmacokinetics of a fixed-dose combination (FDC) of clopidogrel and aspirin was compared with coadministration of individual formulations to clarify the equivalence of the FDC. This was a randomized, open-label, two-period, two-treatment, crossover study in healthy Korean men aged 20-55 years. Subjects received two FDC capsules of clopidogrel/aspirin 75/100 mg (test) or two tablets of clopidogrel 75 mg and two capsules of aspirin 100 mg (reference) with a 14-day washout period. Plasma concentrations of clopidogrel, aspirin, and salicylic acid were measured using validated ultraperformance liquid chromatography-tandem mass spectrometry. Bioequivalence was assessed by analysis of variance and calculation of the 90% confidence intervals (CIs) of the ratios of the geometric means (GMRs) for AUC last and C max for clopidogrel and aspirin. Sixty healthy subjects were enrolled, and 53 completed the study. Clopidogrel, aspirin, and salicylic acid showed similar absorption profiles and no significant differences in C max , AUC last , and T max between FDC administration and coadministration of individual formulations. The GMRs (90% CI) for the C max and AUC last of clopidogrel were 1.08 (0.95, 1.23) and 0.93 (0.84, 1.03), respectively. The GMRs (90% CI) for the C max and AUC last of aspirin were 0.98 (0.84, 1.13) and 0.98 (0.93, 1.04), respectively. Both treatments were well tolerated in the study subjects. The FDC of clopidogrel and aspirin was bioequivalent to coadministration of each individual formulation. The FDC capsule exhibited similar safety and tolerability profiles to the individual formulations. Therefore, clopidogrel/aspirin 75 mg/100 mg FDC capsules can be prescribed to improve patient compliance.

Platelet function in whole-blood donors is impaired: the effects of painkillers.

PubMed

Curvers, Joyce; Dielis, Arne W J H; Heeremans, Judith; van Wersch, Jan W J

2007-01-01

Aspirin (ASA) or non-aspirin-like nonsteroidal anti-inflammatory drugs (NSAIDs) influence platelet (PLT) function by inhibiting cyclooxygenase enzymes. In this study, the aim was to address the use of ASA or NSAIDs before donation and the effect on PLT function. Donors were asked questions about recent use of ASA or NSAIDs. Furthermore, PLT function was evaluated by measurement of the closure time (CT) in a PLT function analyzer (PFA-100, Dade Behring) and by aggregometry (response to ADP or arachidonic acid [AA]). Of 100 questioned donors, 22 percent had used ASA (n = 4), NSAIDs (n = 6), or paracetamol (n = 12) before donation. Upon assessment of the PLT function in the PFA-100, 27 donors showed values of greater than 180 seconds, indicative of impaired PLT function. Of these, only 7 had used pain killers before donation. Furthermore, 15 of 22 users had normal CTs. Aggregation after stimulation with AA was absent in 33 PLT-rich samples. Again only 8 had reported use of ASA (3), NSAIDs (1), or paracetamol (4). Of the 22 users, 14 had normal AA aggregation responses. All donor samples showed ADP-induced aggregation, indicating PLT integrity. There was no difference between the group of donors who reported the intake of ASA or NSAIDs and the group of donors who did not with respect to the tested PLT function assays. It is concluded that there is a considerable group of donors that use PLT-influencing medication before donation. A relation between the reported use and impaired PLT function in blood donors could not be established, however. Impaired PLT function as tested may have other causes than intake of ASA or NSAIDs.

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

PubMed

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

2017-08-05

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

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

PubMed

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.

Minor oral surgery without stopping daily low-dose aspirin therapy: a study of 51 patients.

PubMed

Madan, Gautam A; Madan, Sonal G; Madan, Gauri; Madan, A D

2005-09-01

The risk of excessive bleeding prompts physicians to stop low-dose long-term aspirin regimens before surgery, which puts the patient at risk from adverse thrombotic events. We hypothesize that most minor oral surgical procedures can be carried out safely without stopping low-dose aspirin. All minor oral surgery patients at our hospital (Madan Dental Hospital, Ahmedabad, India) from May 2002 to May 2003, who were also on long-term low-dose aspirin therapy regimens (acetylsalicylic acid 75 mg to 100 mg/day), were included. Investigation of bleeding time and platelet count was performed. If within normal limits, aspirin was not stopped before surgery. Patients were operated under local anesthesia on an outpatient basis. All wounds were sutured and followed up at 24, 48, and 72 hours, 1 week, and 2 weeks after the procedure. The study included 51 patients (32 males, 19 females), ranging in age from 45 to 70 years. Preoperative values were within normal limits for all patients. Aspirin was not stopped for a single patient. There was no excessive intraoperative bleeding in all cases except 1; there was no postoperative bleeding in all cases. We conclude that most minor oral surgery procedures can be carried out safely without stopping long-term low-dose aspirin regimen.

A calix[4]arene derivative and its selective interaction with drugs (clofibric acid, diclofenac and aspirin).

PubMed

Danil de Namor, Angela F; Al Nuaim, Maan; Villanueva Salas, Jose A; Bryant, Sophie; Howlin, Brendan

2017-03-30

The synthesis and characterisation of a partially substituted calix[4]arene, namely, 5,11,17,23-tetra-tert-butyl,25,27-bis[aminoethoxy] 26,28-dihydroxycalix[4]arene are reported. Its interaction with commonly used pharmaceuticals (clofibric acid, diclofenac and aspirin) was investigated by spectroscopic ( 1 H NMR and UV), electrochemical (conductance measurements) and thermal (titration calorimetry) techniques. It is concluded on the basis of the experimental work and molecular simulation studies that the receptor interacts selectively with these drugs. Preliminary studies on the selective extraction of these pharmaceuticals from water by the calix receptor are reported and the potential for a carrier mediated sensor based on this ligand for 'on site' monitoring of pharmaceuticals is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

The ASAS-SN bright supernova catalogue – I. 2013–2014

DOE PAGES

Holoien, T. W. -S.; Stanek, K. Z.; Kochanek, C. S.; ...

2016-09-12

We present basic statistics for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) during its first year-and-a-half of operations, spanning 2013 and 2014. We also present the same information for all other bright (m V ≤ 17), spectroscopically confirmed supernovae discovered from 2014 May 1 through the end of 2014, providing a comparison to the ASAS-SN sample starting from the point where ASAS-SN became operational in both hemispheres. In addition, we present collected redshifts and near-UV through IR magnitudes, where available, for all host galaxies of the bright supernovae in both samples. This work represents a comprehensivemore » catalogue of bright supernovae and their hosts from multiple professional and amateur sources, allowing for population studies that were not previously possible because the all-sky emphasis of ASAS-SN redresses many previously existing biases. In particular, ASAS-SN systematically finds bright supernovae closer to the centres of host galaxies than either other professional surveys or amateurs, a remarkable result given ASAS-SN's poorer angular resolution. In conclusion, this is the first of a series of yearly papers on bright supernovae and their hosts that will be released by the ASAS-SN team.« less

Aspirin 300 mg/day is effective for treating aspirin-exacerbated respiratory disease.

PubMed

Comert, S; Celebioglu, E; Yucel, T; Erdogan, T; Karakaya, G; Onerci, M; Kalyoncu, A F

2013-11-01

Aspirin desensitization (AD) treatment at doses of up to 1300 mg/day improves outcomes in aspirin-exacerbated respiratory disease (AERD). The aim of this study was to investigate the efficacy of aspirin 300 mg/day in the treatment of patients with AERD. The study included 40 patients diagnosed in our clinic as AERD that were desensitized and treated with aspirin 300 mg/day between December 2005 and December 2012. Changes from the baseline status were analyzed at 1 year and at 3 years of follow-up. Of the 40 patients included, 24 (60%) were female and median (interquartile range [IQR]) age was 45 (40-51) years. Median (IQR) duration of AD was 31.5 (10.5-48.5) months. In total, 29 patients continued treatment for at least 1 year and 18 patients for at least 3 years. The annual rate of use of systemic corticosteroid regimens, episodes of sinusitis, and surgery was significantly lower both at 1 year (P = 0.002, P = 0.01, and P < 0.001, respectively) and at 3 years (P = 0.001, P = 0.03, and P = 0.002, respectively). Significant improvement was observed in the nasal congestion score (P = 0.01) and sense of smell score (P = 0.05) at 1 year and in the postnasal drainage score (P = 0.01) at 3 years. Daily treatment with aspirin 300 mg had beneficial effects in patients with AERD, especially for the control of upper airway disease. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sung, Jin Young; Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr

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 effectsmore » 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.« less

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

PubMed

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.

Does Early Resumption of Low-Dose Aspirin After Evacuation of Chronic Subdural Hematoma With Burr-Hole Drainage Lead to Higher Recurrence Rates?

PubMed

Kamenova, Maria; Lutz, Katharina; Schaedelin, Sabine; Fandino, Javier; Mariani, Luigi; Soleman, Jehuda

2016-11-01

Antiplatelet therapy in patients with chronic subdural hematoma (cSDH) presents significant neurosurgical challenges. Given the lack of guidelines regarding perioperative management with antiplatelet therapy, it is difficult to balance the patient's increased cardiovascular risk and prevalence of cSDH. To better understand the risk and recurrence rates related to resuming low-dose acetylsalicylic acid (ASA) by evaluating our patients' resumption of low-dose ASA at various times after burr-hole drainage of the hematoma. In our retrospective study, 140 consecutive patients taking low-dose ASA undergoing surgical evacuation of cSDH were included. Data included baseline characteristics and rates of recurrence, morbidity, and mortality. A multivariate logistic regression model analyzed the association between ASA resumption time and recurrence rates. No statistically significant association was observed between early postoperative resumption of low-dose ASA and recurrence of cSDH (odds ratio, 1.01; 95% confidence interval, 1.001-1.022; P = .06). Corresponding odds ratios and risk differences for restarting ASA treatment on postoperative days 1, 7, 14, 21, 28, 35, or 42 were estimated at 1.53 and 5.9%, 1.42 and 5.1%, 1.33 and 4.1%, 1.23 and 3.2%, 1.15 and 2.2%, 1.07 and 1.1%, and 1.01 and 0.2%, respectively (P > .05). Cardiovascular event rates, surgical morbidity, and mortality did not significantly differ between patients with or without ASA therapy. Given the few published studies regarding ASA use in cranial neurosurgery, our findings elucidate one issue, showing comparable recurrence rates with early or late resumption of low-dose ASA after burr-hole evacuation of cSDH. ASA, acetylsalicylic acidCAD, coronary artery diseaseCI, confidence intervalcSDH, chronic subdural hematomaGCS, Glasgow Coma ScalemRS, modified Rankin ScaleOR, odds ratioRD, risk difference.

A cost-effectiveness analysis of combination antiplatelet therapy for high-risk acute coronary syndromes: clopidogrel plus aspirin versus aspirin alone.

PubMed

Schleinitz, Mark D; Heidenreich, Paul A

2005-02-15

Although clopidogrel plus aspirin is more effective than aspirin alone in preventing subsequent vascular events in patients with unstable angina, the cost-effectiveness of this combination has yet to be examined in this high-risk population. To determine the cost-effectiveness of clopidogrel plus aspirin compared with aspirin alone. Cost-utility analysis. Published literature. Patients with unstable angina and electrocardiographic changes or non-Q-wave myocardial infarction. time horizon: Lifetime. Societal. Combination therapy with clopidogrel, 75 mg/d, plus aspirin, 325 mg/d, for 1 year, followed by aspirin monotherapy, was compared with lifelong aspirin therapy, 325 mg/d. Lifetime costs, life expectancy in quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio. Patients treated with aspirin alone lived 9.51 QALYs after their initial event and incurred expenses of 127,700 dollars; the addition of clopidogrel increased life expectancy to 9.61 QALYs and costs to 129,300 dollars. The incremental cost-effectiveness ratio for clopidogrel plus aspirin compared with aspirin alone was 15,400 dollars per QALY. The analysis of 1 year of therapy was robust to all sensitivity analyses. In the probabilistic sensitivity analysis, fewer than 3% of simulations resulted in cost-effectiveness ratios over 50,000 dollars per QALY. The cost-effectiveness of longer combination therapy depends critically on the balance of thrombotic event rates, durable efficacy, and the increased bleeding rate in patients taking clopidogrel. This analysis may not apply to patients with severe heart failure, those undergoing long-term anticoagulant therapy, those recently managed with revascularization, or those undergoing short-term treatment with glycoprotein IIb/IIIa inhibitors. In patients with high-risk acute coronary syndromes, 1 year of therapy with clopidogrel plus aspirin results in greater life expectancy than aspirin alone, at a cost within the traditional limits

ASA24® Researcher Instructions

Cancer.gov

Step-by-step instructions, including screen shots, for setting-up a study to collect 24-hour recalls or food records are available for download to help researchers, clinicians, and educators use the ASA24 system.

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

PubMed

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

2015-01-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, M.M.; Clark, L.; Armstrong, L.

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 /sup 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 0.75more » 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.« less

ASAS definition for sacroiliitis on MRI in SpA: applicable to children?

PubMed

Herregods, Nele; Dehoorne, Joke; Van den Bosch, Filip; Jaremko, Jacob Lester; Van Vlaenderen, Joke; Joos, Rik; Baraliakos, Xenofon; Varkas, Gaëlle; Verstraete, Koenraad; Elewaut, Dirk; Jans, Lennart

2017-04-11

The Assessment of Spondyloarthritis International Society (ASAS) definition for a 'positive' Magnetic Resonance Imaging (MRI) for sacroiliitis is well studied and validated in adults, but studies about the value of this definition in children are lacking. The aim of this study is to evaluate whether the adult ASAS definition of a positive MRI of the sacroiliac joints can be applied to children with a clinical suspicion of Juvenile Spondyloarthritis (JSpA). Two pediatric musculoskeletal radiologists blinded to clinical data independently retrospectively reviewed sacroiliac (SI) joint MRI in 109 children suspected of sacroiliitis. They recorded global impression (sacroiliitis yes/no) and whether the adult ASAS definition for sacroiliitis was met at each joint. This was compared to gold-standard clinical diagnosis of JSpA. Additionally, MRI were scored according to'adapted' ASAS definitions including other features of sacroiliitis on MRI. JSpA was diagnosed clinically in 47/109 (43%) patients. On MRI, sacroiliitis was diagnosed by global assessment in 30/109 patients, of whom 14 also fulfilled ASAS criteria. No patients with negative global assessment for sacroiliitis fulfilled ASAS criteria. Sensitivity (SN) for JSpA was higher for global assessment (SN = 49%) than for ASAS definition (SN = 26%), but the ASAS definition was more specific (SP = 97% vs. 89%). Modifying adult ASAS criteria to allow bone marrow edema (BME) lesions seen on only one slice, synovitis or capsulitis, increased SN to 36%, 32% and 32% respectively, only slightly lowering SP. Including structural lesions increased SN to 28%, but lowered specificity to 95%. The adult ASAS definition for sacroiliitis has low sensitivity in children. A pediatric-specific definition of MRI-positive sacroiliitis including BME lesions visible on one slice only, synovitis and/or capsulitis may improve diagnostic utility, and increase relevance of MRI in pediatric rheumatology practice.

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 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...

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 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...

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Code of Federal Regulations, 2010 CFR

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...

Ueber den Nachweis von Exoplaneten in der ASAS-3 Datenbank

NASA Astrophysics Data System (ADS)

Huemmerich, Stefan; Bernhard, Klaus

2015-02-01

Under favourable circumstances, transits of known exoplanets with large amplitudes like WASP-18 b can be observed in the ASAS-3 database. An attempt to search for exoplanets using ASAS-3 data is discussed.

In vitro and in vivo assessment of platelet function in healthy dogs during administration of a low-dose aspirin regimen.

PubMed

Haines, Jillian M; Thomason, John M; Seage, Eileen C; Wills, Robert W; Bulla, Camilo; Lunsford, Kari V; Mackin, Andrew J

2016-02-01

To assess the in vitro and in vivo platelet function of healthy dogs during administration of a low-dose aspirin regimen. 16 dogs. Dogs received aspirin (1 mg/kg, PO, q 24 h) for 7 days. Blood and urine samples were collected before (day 1; baseline) and on days 3 and 7 of the low-dose aspirin regimen. Platelet function was evaluated by use of turbidimetric and conventional impedance aggregometry, multiple-electrode impedance aggregometry, a platelet function analyzer (PFA), and determination of urine 11-dehydro-thromboxane B2 concentration. Turbidimetric aggregometry results were compared with the results obtained by the other 4 methods. Fourteen days after cessation of aspirin, platelet-rich plasma was incubated with acetylsalicylic acid and platelet function was assessed by turbidimetric aggregometry to determine whether this technique could accurately identify dogs that responded to the low-dose aspirin regimen. Of the 16 dogs, 13 had turbidimetric and conventional impedance aggregometry results that were decreased by > 25% from baseline on days 3 and 7, and 4 and 7 dogs had PFA closure times > 300 seconds on days 3 and 7, respectively. The median urine 11-dehydro-thromboxane B2 concentration-to-creatinine concentration ratio decreased by 49% between days 1 and 7. Turbidimetric aggregometry results were correlated with conventional impedance aggregometry results. There was poor agreement between the turbidimetric aggregometry and PFA results. The multiple-electrode impedance aggregometry protocol failed to reliably detect aspirin-induced platelet dysfunction. In vitro incubation of platelet-rich plasma with acetylsalicylic acid followed by turbidimetric aggregometry did not predict whether dogs responded to the low-dose aspirin regimen. Results indicated that the response to a low-dose aspirin regimen varied among healthy dogs.

Patient-independent variables affecting the assessment of aspirin responsiveness by serum thromboxane measurement.

PubMed

Petrucci, Giovanna; Rizzi, Alessandro; Cavalca, Viviana; Habib, Aida; Pitocco, Dario; Veglia, Fabrizio; Ranalli, Paola; Zaccardi, Francesco; Pagliaccia, Francesca; Tremoli, Elena; Patrono, Carlo; Rocca, Bianca

2016-10-28

The serum TXB 2 (sTXB 2 ) assay reflects the pharmacodynamics of platelet inhibition by low-dose aspirin. However, different studies reported variable sTXB 2 values. sTXB 2 assay requires whole blood incubation at 37 °C as a condition for optimal thrombin generation, arachidonic acid release and its metabolism by platelet cyclooxygenase-1 to form TXA 2 . Access to 37 °C incubation may be variably delayed, and different methods to quantitate sTXB 2 may contribute to variable results between different Centers. We investigated whether delaying 37 °C incubation and/or analytical issues affect sTXB 2 concentrations, biasing the assessment of aspirin responsiveness. Sixty-eight samples from 54 volunteers, on- and off-aspirin, were incubated at 37 °C immediately after sampling (reference sample) or after 5, 10, 15, 20, 30 or 60 minutes at room temperature (RT); 8 samples remained at RT 60 minutes, without subsequent incubation; 314 sera were measured by enzyme immunoassay (EIA) and liquid chromatography-tandem mass-spectrometry (LC/MS-MS) methods. sTXB 2 concentrations decreased exponentially as a function of the delay before 37 °C incubation, ranging from 94 ± 11 % at 5 minutes to 23 ± 22 % of the reference sample after 60 minutes at RT. There was high agreement between EIA and LC/MS-MS. Moreover, we simulated the influence of a 15- or 30-minute delayed incubation on 300 sTXB2 measurements from previously-studied, aspirin-treated patients. Delayed incubation reduced the percentage of aspirin 'non-responders' by 22 % to 52 %, depending on the response threshold. In conclusion, a variable delay in the 37 °C incubation of blood samples may affect the assessment of platelet cyclooxygenase-1 inhibition by aspirin and confound the characterization of the determinants of aspirin responsiveness.

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

PubMed

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 < .001). At the 5-year follow-up, multivariate logistic regression analysis results showed a strong association between aspirin 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.

Time-dependent changes in non-COX-1-dependent platelet function with daily aspirin therapy

PubMed Central

Voora, Deepak; Ortel, Thomas L.; Lucas, Joseph E.; Chi, Jen-Tsan; Becker, Richard C.; Ginsburg, Geoffrey S.

2012-01-01

Objectives To develop an integrated metric of non COX-1 dependent platelet function (NCDPF) to measure the temporal response to aspirin in healthy volunteers and diabetics. Background NCDPF on aspirin demonstrates wide variability, despite suppression of COX-1. Although a variety of NCDPF assays are available, no standard exists and their reproducibility is not established. Methods We administered 325mg/day aspirin to two cohorts of volunteers (HV1, n = 52, and HV2, n = 96) and diabetics (DM, n = 74) and measured NCDPF using epinephrine, collagen, and ADP aggregometry and PFA100 (collagen/epi) before (Pre), after one dose (Post), and after several weeks (Final). COX-1 activity was assessed with arachidonic acid aggregometry (AAA). The primary outcome of the study, the platelet function score (PFS), was derived from a principal components analysis of NCDPF measures. Results The PFS strongly correlated with each measure of NCDPF in each cohort. After two or four weeks of daily aspirin the Final PFS strongly correlated (r > 0.7, p<0.0001) and was higher (p < 0.01) than the Post PFS. The magnitude and direction of the change in PFS (Final - Post) in an individual subject was moderately inversely proportional to the Post PFS in HV1 (r = −0.45), HV2 (r = −0.54), DM (r = −0.68), p<0.0001 for all. AAA remained suppressed during aspirin therapy. Conclusions The PFS summarizes multiple measures of NCDPF. Despite suppression of COX-1 activity, NCDPF during aspirin therapy is predictably dynamic: those with heightened NCDPF continue to decline whereas those with low/normal NCDPF return to pre-aspirin levels over time. PMID:22294277

Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.

PubMed

van der Sluis, Rencia; Erasmus, Elardus

2016-10-01

Activation of fatty acids by the acyl-CoA synthetases (ACSs) is the vital first step in fatty acid metabolism. The enzymatic and physiological characterization of the human xenobiotic/medium chain fatty acid: CoA ligases (ACSMs) has been severely neglected even though xenobiotics, such as benzoate and salicylate, are detoxified through this pathway. This review will focus on the nomenclature and substrate specificity of the human ACSM ligases; the biochemical and enzymatic characterization of ACSM1 and ACSM2B; the high sequence homology of the ACSM2 genes (ACSM2A and ACSM2B) as well as what is currently known regarding disease association studies. Several discrepancies exist in the current literature that should be taken note of. For example, the single nucleotide polymorphisms (SNPs) reported to be associated with aspirin metabolism and multiple risk factors of metabolic syndrome are incorrect. Kinetic data on the substrate specificity of the human ACSM ligases are non-existent and currently no data exist on the influence of SNPs on the enzyme activity of these ligases. One of the biggest obstacles currently in the field is that glycine conjugation is continuously studied as a one-step process, which means that key regulatory factors of the two individual steps remain unknown.

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

PubMed

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.

Impairment of aminopyrine clearance in aspirin-damaged canine gastric mucosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

Using an in vivo canine chambered stomach preparation, the clearance of (/sup 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 (/sup 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,more » when (/sup 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.« less

Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.

PubMed

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; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin 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 Clinical

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

PubMed

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

The ASAS-SN catalogue of variable stars I: The Serendipitous Survey

NASA Astrophysics Data System (ADS)

Jayasinghe, T.; Kochanek, C. S.; Stanek, K. Z.; Shappee, B. J.; Holoien, T. W.-S.; Thompson, Toda A.; Prieto, J. L.; Dong, Subo; Pawlak, M.; Shields, J. V.; Pojmanski, G.; Otero, S.; Britt, C. A.; Will, D.

2018-07-01

The All-Sky Automated Survey for Supernovae (ASAS-SN) is the first optical survey to routinely monitor the whole sky with a cadence of ˜2-3 d down to V ≲ 17 mag. ASAS-SN has monitored the whole sky since 2014, collecting ˜100-500 epochs of observations per field. The V-band light curves for candidate variables identified during the search for supernovae are classified using a random forest classifier and visually verified. We present a catalogue of 66 179 bright, new variable stars discovered during our search for supernovae, including 27 479 periodic variables and 38 700 irregular variables. V-band light curves for the ASAS-SN variables are available through the ASAS-SN variable stars data base (https://asas-sn.osu.edu/variables). The data base will begin to include the light curves of known variable stars in the near future along with the results for a systematic, all-sky variability survey.

The ASAS-SN Catalog of Variable Stars I: The Serendipitous Survey

NASA Astrophysics Data System (ADS)

Jayasinghe, T.; Kochanek, C. S.; Stanek, K. Z.; Shappee, B. J.; Holoien, T. W.-S.; Thompson, Todd A.; Prieto, J. L.; Dong, Subo; Pawlak, M.; Shields, J. V.; Pojmanski, G.; Otero, S.; Britt, C. A.; Will, D.

2018-04-01

The All-Sky Automated Survey for Supernovae (ASAS-SN) is the first optical survey to routinely monitor the whole sky with a cadence of ˜2 - 3 days down to V≲ 17 mag. ASAS-SN has monitored the whole sky since 2014, collecting ˜100 - 500 epochs of observations per field. The V-band light curves for candidate variables identified during the search for supernovae are classified using a random forest classifier and visually verified. We present a catalog of 66,533 bright, new variable stars discovered during our search for supernovae, including 27,753 periodic variables and 38,780 irregular variables. V-band light curves for the ASAS-SN variables are available through the ASAS-SN variable stars database (https://asas-sn.osu.edu/variables). The database will begin to include the light curves of known variable stars in the near future along with the results for a systematic, all-sky variability survey.

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.

PubMed

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

Citing ASA24® Dietary Assessment Tool in Publications & Presentations

Cancer.gov

In order to show and maintain support for ASA24, documenting its use in through publications is extremely useful to the National Cancer Institute (NCI). Please cite ASA24 as follows, depending on the version used in your study.

Pharmacokinetics in Wistar Rats of 5-[(4-Carboxybutanoyl)Amino]-2-Hydroxybenzoic Acid: A Novel Synthetic Derivative of 5-Aminosalicylic Acid (5-ASA) with Possible Anti-Inflammatory Activity

PubMed Central

Correa-Basurto, José; Rosales Hernández, Martha Cecilia; Padilla Martínez, Itzia Irene; Mendieta-Wejebe, Jessica Elena

2016-01-01

5-[(4-carboxybutanoyl)amino]-2-hydroxybenzoic acid (C2) is a novel synthetic derivative of 5-aminosalicylic acid (5-ASA), which is currently being evaluated ex vivo as an anti-inflammatory agent and has shown satisfactory results. This study aimed to obtain the pharmacokinetic profiles, tissue distribution and plasma protein binding of C2 in Wistar Rats. Additionally, an HPLC method was developed and validated to quantify C2 in rat plasma. The pharmacokinetic profiles of intragastric, intravenous and intraperitoneal administration routes at singles doses of 100, 50, and 100 mg/kg, respectively, were studied in Wistar rats. The elimination half-life of intravenously administered C2 was approximately 33 min. The maximum plasma level of C2 was reached approximately 24 min after intragastric administration, with a Cmax value of 2.5 g/mL and an AUCtot value of 157 μg min-1/mL; the oral bioavailability was approximately 13%. Following a single intragastric or oral dose (100 mg/kg), C2 was distributed and detected in all examined tissues (including the brain and colon). The results showed that C2 accumulates over time. The plasma protein binding results indicated that the unbound fraction of C2 at concentrations of 1 to 20 μg/mL ranged from 89.8% to 92.5%, meaning that this fraction of C2 is available to cross tissues. Finally, the blood-plasma partitioning (BP ratio) of C2 in rat plasma was 0.71 and 0.6 at concentrations of 5 and 10 μg/mL, respectively, which indicates that C2 is free in the plasmatic phase and not inside blood cells. The results of this study suggest that a fraction of the administered C2 dose is absorbed in the stomach, and the fraction that is not absorbed reaches the small intestine and colon. This distribution constitutes the main advantage of C2 compared with 5-ASA for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). PMID:27454774

Chinese Herbal Medicine for Aspirin Resistance: A Systematic Review and Meta-Analysis

PubMed Central

Chen, Jiandong; Zhang, Haowen; Chen, Xiaohu

2016-01-01

Objectives To assess the effectiveness and safety of Chinese herbal medicine (CHM) for the treatment of aspirin resistance (AR). Methods A comprehensive research of seven electronic databases was performed for comparative studies evaluating CHM for AR. Two authors independently extracted data and assessed the methodological quality of the included trials using the Cochrane risk of bias tool. Data wasere synthesized by using RevMan 5.3 software. (PROSPERO Registration #CRD42015020182) Results 18 randomized controlled trials (RCTs) involving 1,460 patients were included. 15 RCTs reported significant difference in the reduction of platelet aggregation rate (PAR) induced by adenosine diphosphate (ADP) (P<0.05), and 11 reported significant effect of CHM plus aspirin to reduce PAR induced by arachidonic acid (AA) (P<0.05) compared with aspirin 100mg/d treatment. The pooling data of 3 RCTs showed the thromboxane B2 (TXB2) in patients with CHM plus aspirin versus aspirin were significantly reduced (Random Effect model (RE), Standard Deviation (SD) = -95.93, 95% Confidential Interval (CI)[-118.25,-73.61], P<0.00001). Subgroup analysis showed that TXB2 (Fixed Effect model (FE), SD = -89.23, 95%CI[-121.96,-56.49], P<0.00001) had significant difference in Tongxinluo capsule plus aspirin versus aspirin. 2 RCTs reported the clinical effective rate, and the meta-analysis result showed a significant difference in intervention and control group (FE, Relative Risk (RR) = 1.67, 95%CI[1.15, 2.42], P = 0.007<0.05). In 4 trials, CHM plus aspirin had better effects of reducing the reoccurrence of cerebral infarction than aspirin (FE, RR = 0.24, 95%CI [0.11, 0.49], P<0.0001). And one trial showed that CHM plus aspirin could decrease the National Institutes of Health Stroke Scale (NHISS) score (P<0.05) and increase the Barthel Index (BI) score (P<0.05). 4 trials stated that there were no adverse effects occurred in intervention group, and analysis showed significant difference of CHM or

Does aspirin use prevent acute coronary syndrome in patients with pneumonia: multicenter prospective randomized trial.

PubMed

Oz, Fahrettin; Gul, Sule; Kaya, Mehmet G; Yazici, Mehmet; Bulut, Ismet; Elitok, Ali; Ersin, Gunay; Abakay, Ozlem; Akkoyun, Cayan D; Oncul, Aytac; Cetinkaya, Erdogan; Gibson, Michael C; Oflaz, Huseyin

2013-05-01

The aim of this study was to test the hypothesis that aspirin would reduce the risk for acute coronary syndromes (ACSs) in patients with pneumonia. Pooled data suggest that pneumonia may trigger an ACS as a result of inflammatory reactions and the prothrombotic changes in patients with pneumonia. Hypothetically considering its antiaggregating and anti-inflammatory effects, aspirin might also be beneficial for the primary prevention of ACS in patients with pneumonia. One hundred and eighty-five patients with pneumonia who had more than one risk factor for cardiovascular disease were randomized to an aspirin group (n=91) or a control group (n=94). The patients in the aspirin group received 300 mg of aspirin daily for 1 month. ECGs were recorded on admission and 48 h and 30 days after admission to assess silent ischemia. The level of high-sensitivity cardiac troponin T was measured on admission and 48 h after admission. The primary endpoint was the development of ACS within 1 month. The secondary endpoints included cardiovascular death and death from any cause within 1 month. The χ-test showed that the rates of ACS at 1 month were 1.1% (n=1) in the aspirin group and 10.6% (n=10) in the control group (relative risk, 0.103; 95% confidence interval 0.005-0.746; P=0.015). Aspirin therapy was associated with a 9% absolute reduction in the risk for ACS. There was no significant decrease in the risk of death from any cause (P=0.151), but the aspirin group had a decreased risk of cardiovascular death (risk reduction: 0.04, P=0.044). This randomized open-label study shows that acetyl salicylic acid is beneficial in the reduction of ACS and cardiovascular mortality among patients with pneumonia.

Gastro-protective effect of methanol extract of Vernonia amygdalina (del.) leaf on aspirin-induced gastric ulcer in Wistar rats.

PubMed

Adefisayo, Modinat A; Akomolafe, Rufus O; Akinsomisoye, Stephen O; Alabi, Quadri K; Ogundipe, Olaofe L; Omole, Joseph G; Olamilosoye, Kehinde P

2017-01-01

This study investigated the protective effects of methanol extract of Vernonia amygdalina leaf (MEVA) on aspirin induced gastric ulcer in rats. Thirty Wistar rats, 150-200 g were divided into six groups as follows: Group 1 (control) rats received 2 mL/kg of propylene glycol for 28 consecutive days. Group 2 (Ulcer Control) received 150 mg/kg/day of aspirin suspended in 3 mL of 1% carboxymethylcellulose in water orally for 3 consecutive days during which the rats were fasted for the induction of ulcer. Group 3 received cimetidine at 100 mg/kg/day orally for 28 consecutive days and thereafter treated as group 2. Groups 4, 5 and 6 received MEVA orally at 200, 300 and 400 mg/kg/day respectively for 28 consecutive days and thereafter were treated with aspirin as group 2. All the animals were sacrifice at the end of the study to determine the gastric pH, gastric acidity, gastric ulcer score, haematological indices, superoxide dismutase (SOD) activity, reduced glutathione (GSH) and Lipid peroxidation (LPO) levels. The result showed that aspirin significantly (p < 0.05) increased gastric ulcer score and index, decreased gastric pH, gastric acidity, SOD activity, GSH level as well as increased LPO level. It induced significant necrosis of the stomach tissue. Administration of MEVA significantly (p < 0.05) increased gastric pH, but decreased gastric acid secretion and reversed alteration of haematological parameters. It also significantly (p < 0.05) increased SOD activity, GSH level and decreased LPO level. The results suggest that Vernonia amygdalina possesses gastro-protective properties against aspirin-induced gastric ulcer.

Edoxaban versus placebo, aspirin, or aspirin plus clopidogrel for stroke prevention in atrial fibrillation. An indirect comparison analysis.

PubMed

Blann, A D; Skjøth, F; Rasmussen, L H; Larsen, T B; Lip, G Y H

2015-08-01

As non-valvular atrial fibrillation (AF) brings a risk of stroke, oral anticoagulants (OAC) are recommended. In 'real world' clinical practice, many patients (who may be, or perceived to be, intolerant of OACs) are either untreated or are treated with anti-platelet agents. We hypothesised that edoxaban has a better net clinical benefit (NCB, balancing the reduction in stroke risk vs increased risk of haemorrhage) than no treatment or anti-platelet agents. We performed a network meta-analysis of published data from 24 studies of 203,394 AF patients to indirectly compare edoxaban with aspirin alone, aspirin plus clopidogrel, and placebo. Edoxaban 30 mg once daily significantly reduced the risk of all stroke, ischaemic stroke and mortality compared to placebo and aspirin. Compared to aspirin plus clopidogrel, there was a lower risk of intra-cranial haemorrhage (ICH). Edoxaban 60 mg once-daily had a reduced risk of any stroke and systemic embolism compared to placebo, aspirin, and aspirin plus clopidogrel. Mortality rates for both edoxaban doses were estimated to be lower compared to any anti-platelet, and significantly lower compared to placebo. With overall reduced risk of ischemic stroke and ICH, both edoxaban doses bring a NCB of mean (SD) 1.68 (0.15) saved events per 100 patients per year compared to anti-platelet drugs in a clinical trial population. The NCB was demonstrated to be lower, at 0.77 (0.12) events saved (p< 0.01) when modeled to data from a 'real world' cohort of AF patients. In conclusion, edoxaban is likely to provide even better protection from stroke and ICH than placebo, aspirin alone, or aspirin plus clopidogrel in both clinical trial populations and unselected community populations. Both edoxaban doses would also bring a positive NCB compared to anti-platelet drugs or placebo/non-treatment based on 'real world' data.

Salix alba attenuated oxidative stress in the heart and kidney of hypercholesterolemic rabbits.

PubMed

Amel Zabihi, Narges; Mahmoudabady, Maryam; Soukhtanloo, Mohammad; Hayatdavoudi, Parichehr; Beheshti, Farimah; Niazmand, Saeed

2018-01-01

Oxidative stress plays a critical role in the development of hypercholesterolemia-induced complications. This study evaluated the effects of aspirin and Salix alba hydroethanolic extract on oxidative stress in the heart and kidney of hypercholesterolemic rabbits. The antioxidant activity, as well as total phenolic and salicin content of S. alba (Sa) extract were assessed by DPPH radical scavenging activity, Folin-Ciocalteu and HPLC methods, respectively. Animals were divided into two groups of control (fed with normal chow), and HD (fed with high cholesterol diet for 6 weeks). Then, hypercholesterolemic animals allocated to the following treatment groups: CHO (received HD), Sa extract (HD plus extract 60 and 120 mg/kg), and aspirin (HD plus aspirin 120 mg/kg) and received the treatments on a daily basis for 6 weeks. MDA, GSH, and nitrite concentrations as well as the activities of SOD and CAT were evaluated in cardiac and kidney tissues. The scavenging activity, total phenolic content and salicin were 19.1 µg/ml (IC50), 153.75 ± 3.6 mg of gallic acid/g, and 18.03 µg/mg, respectively. In comparison to CHO group, MDA levels were diminished in Sa and ASA groups but GSH levels were improved. NO metabolites increased in the heart of Sa 120 mg/kg group and in the kidney of all Sa and ASA treated groups. SOD activity increased only in the heart of Sa groups and in the kidney of Sa and ASA groups. CAT activity increased in the heart and kidney tissues of all Sa and ASA treated groups. The results showed S. alba extract improved redox homeostasis in heart and kidney tissues of hypercholesterolemic rabbits. The extract antioxidant property may be related to its phenolic content.

Salix alba attenuated oxidative stress in the heart and kidney of hypercholesterolemic rabbits

PubMed Central

Amel Zabihi, Narges; Mahmoudabady, Maryam; Soukhtanloo, Mohammad; Hayatdavoudi, Parichehr; Beheshti, Farimah; Niazmand, Saeed

2018-01-01

Objective: Oxidative stress plays a critical role in the development of hypercholesterolemia-induced complications. This study evaluated the effects of aspirin and Salix alba hydroethanolic extract on oxidative stress in the heart and kidney of hypercholesterolemic rabbits. Materials and Methods: The antioxidant activity, as well as total phenolic and salicin content of S. alba (Sa) extract were assessed by DPPH radical scavenging activity, Folin-Ciocalteu and HPLC methods, respectively. Animals were divided into two groups of control (fed with normal chow), and HD (fed with high cholesterol diet for 6 weeks). Then, hypercholesterolemic animals allocated to the following treatment groups: CHO (received HD), Sa extract (HD plus extract 60 and 120 mg/kg), and aspirin (HD plus aspirin 120 mg/kg) and received the treatments on a daily basis for 6 weeks. MDA, GSH, and nitrite concentrations as well as the activities of SOD and CAT were evaluated in cardiac and kidney tissues. Results: The scavenging activity, total phenolic content and salicin were 19.1 µg/ml (IC50), 153.75 ± 3.6 mg of gallic acid/g, and 18.03 µg/mg, respectively. In comparison to CHO group, MDA levels were diminished in Sa and ASA groups but GSH levels were improved. NO metabolites increased in the heart of Sa 120 mg/kg group and in the kidney of all Sa and ASA treated groups. SOD activity increased only in the heart of Sa groups and in the kidney of Sa and ASA groups. CAT activity increased in the heart and kidney tissues of all Sa and ASA treated groups. Conclusion: The results showed S. alba extract improved redox homeostasis in heart and kidney tissues of hypercholesterolemic rabbits. The extract antioxidant property may be related to its phenolic content. PMID:29379769

Antiplatelet therapy: aspirin resistance and all that jazz!

PubMed

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.

Regular aspirin use and lung cancer risk.

PubMed

Moysich, Kirsten B; Menezes, Ravi J; Ronsani, Adrienne; Swede, Helen; Reid, Mary E; Cummings, K Michael; Falkner, Karen L; Loewen, Gregory M; Bepler, Gerold

2002-11-26

Although a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk. We conducted a hospital-based case-control study to evaluate the role of regular aspirin use in lung cancer etiology. Study participants included 868 cases with primary, incident lung cancer and 935 hospital controls with non-neoplastic conditions who completed a comprehensive epidemiological questionnaire. Participants were classified as regular aspirin users if they had taken the drug at least once a week for at least one year. Results indicated that lung cancer risk was significantly lower for aspirin users compared to non-users (adjusted OR = 0.57; 95% CI 0.41-0.78). Although there was no clear evidence of a dose-response relationship, we observed risk reductions associated with greater frequency of use. Similarly, prolonged duration of use and increasing tablet years (tablets per day x years of use) was associated with reduced lung cancer risk. Risk reductions were observed in both sexes, but significant dose response relationships were only seen among male participants. When the analyses were restricted to former and current smokers, participants with the lowest cigarette exposure tended to benefit most from the potential chemopreventive effect of aspirin. After stratification by histology, regular aspirin use was significantly associated with reduced risk of small cell lung cancer and non-small cell lung cancer. Overall, results from this hospital-based case-control study suggest that regular aspirin use may be associated with reduced risk of lung cancer.

Regular aspirin use and lung cancer risk

PubMed Central

Moysich, Kirsten B; Menezes, Ravi J; Ronsani, Adrienne; Swede, Helen; Reid, Mary E; Cummings, K Michael; Falkner, Karen L; Loewen, Gregory M; Bepler, Gerold

2002-01-01

Background Although a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk. Methods We conducted a hospital-based case-control study to evaluate the role of regular aspirin use in lung cancer etiology. Study participants included 868 cases with primary, incident lung cancer and 935 hospital controls with non-neoplastic conditions who completed a comprehensive epidemiological questionnaire. Participants were classified as regular aspirin users if they had taken the drug at least once a week for at least one year. Results Results indicated that lung cancer risk was significantly lower for aspirin users compared to non-users (adjusted OR = 0.57; 95% CI 0.41–0.78). Although there was no clear evidence of a dose-response relationship, we observed risk reductions associated with greater frequency of use. Similarly, prolonged duration of use and increasing tablet years (tablets per day × years of use) was associated with reduced lung cancer risk. Risk reductions were observed in both sexes, but significant dose response relationships were only seen among male participants. When the analyses were restricted to former and current smokers, participants with the lowest cigarette exposure tended to benefit most from the potential chemopreventive effect of aspirin. After stratification by histology, regular aspirin use was significantly associated with reduced risk of small cell lung cancer and non-small cell lung cancer. Conclusions Overall, results from this hospital-based case-control study suggest that regular aspirin use may be associated with reduced risk of lung cancer. PMID:12453317

Aspirin for the prevention of colorectal cancer

PubMed Central

Garcia-Albeniz, X.; Chan, A.T.

2011-01-01

Over 600,000 people worldwide die of colorectal cancer (CRC) annually, highlighting the importance of developing effective prevention strategies. Among proposed chemopreventive interventions, aspirin is perhaps the agent with the strongest body of evidence that supports wider spread use to significantly reduce the population burden of CRC. Several epidemiological studies, four randomized controlled trials (RCTs) of colorectal polyp recurrence, and RCTs in patients with hereditary colorectal cancer syndromes, have shown that aspirin reduces incidence of colorectal neoplasia. Recently, in a pooled analysis of five cardiovascular-prevention RCTs linked to cancer outcomes, daily aspirin use at any dose reduced the risk of CRC by 24% and of CRC-associated mortality by 35% after a delay of 8–10 years. In an expanded meta-analysis of 8 cardiovascular-prevention RCTs, daily aspirin use at any dose was associated with a 21% lower risk of all cancer death, including CRC, with benefit only apparent after 5 years. In this review, we will summarize human studies of aspirin in CRC prevention as well as discuss the safety profile and mechanism of aspirin in CRC prevention. PMID:22122763

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

PubMed

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

2013-07-29

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

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

PubMed

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.

Role of Aspirin in Breast Cancer Survival.

PubMed

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.

Caffeic acid phenethyl ester protects kidneys against acetylsalicylic acid toxicity in rats.

PubMed

Bozkurt, Yasar; Bozkurt, Mehtap; Turkçu, Gul; Sancaktutar, Ahmet Ali; Soylemez, Haluk; Penbegul, Necmettin; Atar, Murat; Bodakcı, Mehmet Nuri; Hatipoglu, Namık Kemal; Yuksel, Hatice; Kıbrıslı, Erkan; Yavuz, Celal

2012-01-01

The aim of this study was to investigate the protective effect of caffeic acid phenethyl ester (CAPE) on acetylsalicylic acid (ASA)-induced renal damage in rats. A total of 40 rats were randomly divided into five groups, with eight rats in each group-group 1: control, not receiving any medication; group 2: ASA (50 mg/kg/day); group 3: ASA (50 mg/kg/day) + CAPE (20 μg/kg/day); group 4: ASA (100 mg/kg/day); and group 5: ASA (100 mg/kg/day) + CAPE (20 μg/kg/day). ASA and CAPE were given via orogastric gavage for 5 days. The total oxidant status (TOS), total antioxidant capacity (TAC), and paraoxonase-1 (PON-1) activity of the blood samples and kidney tissues were determined. Histopathological examinations of the kidneys were performed using light microscopic methods. The TOS level in the serum of rats and kidney tissues given ASA (groups 2 and 4) significantly increased, but the levels of TAC and PON-1 in these tissues significantly decreased in group 4 when compared with the control rats (p < 0.05). The levels of TAC and PON-1 in the kidney tissues increased and the levels of TOS decreased in the CAPE treatment groups (groups 3 and 5) when compared with the rats in the no CAPE treatment groups (groups 2 and 4). The PON-1, TAC, and TOS values reverted to normal levels in group 5 when compared to group 4 (p < 0.05). These results were supported by histopathological observation. Oxidative stress plays an important role in ASA-induced nephrotoxicity, and CAPE may protect against ASA-induced nephrotoxicity in rats.

Temporal Aspects of the Action of ASA404 (Vadimezan; DMXAA)

PubMed Central

Baguley, Bruce C; Siemann, Dietmar W

2013-01-01

ASA404, a flavonoid tumor-vascular disrupting agent (Tumor-VDA), is in clinical trial for the treatment of non-small cell lung cancer. Its action differs from both that of the tubulin binding class of Tumor-VDAs and antiangiogenic agents. In mice, ASA404 induces a sequence of changes in tumor tissue, starting within one hour with increased vascular permeability, increased endothelial apoptosis and decreased blood flow. Later effects include the release of serotonin, induction of tumor necrosis factor and other cytokines and chemokines, as well as induction of nitric oxide. This cascade of events induces sustained effects on blood flow, tumor hypoxia, vascular failure, inflammatory responses and, in some tumors, complete regression. One feature of the action of ASA404 against murine tumors is its ability to potentiate the effects of radiation and a variety of chemotherapeutic agents. The flavonoid class appears to be unique because of its dual action on vascular endothelial function and innate immunity. The translation of preclinical to clinical results demands an understanding of both the mechanisms underlying the dual effects and the species differences in ASA404 activity. Clinical trials indicate that the future of ASA404 as an effective agent relies on a deep appreciation of its cellular action. PMID:20964495

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

PubMed

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.

Variation of ascorbic acid concentration in fruits of cultivated and wild apples.

PubMed

Fang, Ting; Zhen, Qiaoling; Liao, Liao; Owiti, Albert; Zhao, Li; Korban, Schuyler S; Han, Yuepeng

2017-06-15

Ascorbic acid (AsA) content in mature fruits of 457 apple accessions were measured, and a great variation in AsA concentration was detected. Wild fruits showed significantly higher level of AsA than cultivated fruits. Fruit AsA content was positively correlated with malic acid content, but negatively correlated with fruit weight and soluble solid content. Thus, the difference in AsA content between the wild and cultivated fruits could be attributed to an indirect consequence of human selection for larger fruit size, less acidity, and increased sweetness during apple domestication. Additionally, AsA concentration was extremely high in fruit at the juvenile stage, but dramatically decreased at the expanding and mature stages. The expression levels of three genes controlling AsA accumulation, MdGGP1, MdDHAR3-3, and MdNAT7-2, were significantly negatively correlated with AsA contents in fruits, suggesting a feedback regulation mechanism in AsA-related gene expression. Our results could be helpful for future apple breeding. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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.

A novel water-soluble vitamin E derivative protects against aspirin-induced gastric mucosal injury in rats.

PubMed

Isozaki, Yutaka; Yoshida, Norimasa; Ichikawa, Hiroshi; Kuroda, Masaaki; Kokura, Satoshi; Naito, Yuji; Okanoue, Takeshi; Yoshikawa, Toshikazu

2005-12-01

Oxygen radical-mediated lipid peroxidation and neutrophil activation may be involved in the development of gastric mucosal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). Vitamin E is one of the lipid-soluble antioxidants and is generally considered to protect against lipid peroxidation of the cell membrane and to scavenge singlet oxygen and superoxide anion radicals. Our object was to investigate the antioxidative effects of water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetra-methylchroman-6-ol (TMG), on aspirin-induced gastric mucosal injury in rats. Gastric injury was induced by intragastric administration of aspirin and 0.15 N HCl in male Sprague-Dawley rats. TMG dissolved in physiological saline was injected intraperitoneally 0.5 h before the aspirin administration. The intragastric administration of acidified aspirin induced hyperemia and hemorragic erosions in rat stomach. The increase in total area of gastric erosions was reduced by pretreatment with TMG in a dose-dependent manner. The increases of thiobarbituric acid-reactive substances (TBA-RS) and myeloperoxidase (MPO) activity 3 h after aspirin administration were significantly inhibited by pretreatment with TMG. The gastric concentration of cytokine-induced neutrophil chemoattractants-1 (CINC-1) increased after aspirin administration, and the increase was also inhibited by pretreatment with TMG. These results suggest that TMG is effective for the treatment of aspirin-induced gastric injury. This anti-inflammatory effect of TMG seems to be related to impairment of lipid peroxidation, neutrophil function and cytokine production in gastric mucosa.

Repurposing of Aspirin and Ibuprofen as Candidate Anti-Cryptococcus Drugs.

PubMed

Ogundeji, Adepemi O; Pohl, Carolina H; Sebolai, Olihile M

2016-08-01

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. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

PubMed

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.

BOREAS RSS-2 Extracted Reflectance Factors Derived from ASAS Imagery

NASA Technical Reports Server (NTRS)

Russell, C.; Hall, Forrest G. (Editor); Nickerson, Jaime (Editor); Dabney, P.; Kovalick, W.; Graham, D.; Bur, Michael; Irons, James R.; Tierney, M.

2000-01-01

The BOREAS RSS-2 team derived atmospherically corrected bidirectional reflectance factor means from multispectral, multiangle ASAS imagery for small homogeneous areas near several BOREAS sites. The ASAS imagery was acquired from the C-130 aircraft platform in 1994 and 1996. The data are stored in tabular ASCII files.

Effects of aspirin in combination with EPA and DHA on HDL-C cholesterol and ApoA1 exchange in individuals with type 2 diabetes mellitus.

PubMed

Block, Robert C; Holub, Ashley; Abdolahi, Amir; Tu, Xin M; Mousa, Shaker A; Oda, Michael N

2017-11-01

Low-dose aspirin is an effective drug for the prevention of cardiovascular disease (CVD) events but individuals with diabetes mellitus can be subject to 'aspirin resistance'. Thus, aspirin's effect in these individuals is controversial. Higher blood levels of seafood-derived omega-3 polyunsaturated fatty acids (ω3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also have beneficial effects in reducing risk of CVD events but few studies have examined the interaction of plasma EPA and DHA with aspirin ingestion. Our study examined the combinatory effects of EPA, DHA, and aspirin ingestion on HDL-cholesterol (HDL-C) and apoA-I exchange (shown to be associated with CVD event risk). 30 adults with Type 2 diabetes mellitus ingested aspirin (81mg/day) for 7 consecutive days, EPA+DHA (2.6g/day) for 28 days, then both for 7 days. Plasma was collected at baseline and at 5 subsequent visits including 4h after each aspirin ingestion. Mixed model methods were used to determine HDL-C-concentrations and apoA-I exchange compared to the baseline visit values. LOWESS curves were used for non-linear analyses of outcomes to help discern change patterns, which was followed by piecewise linear functions for formal testing of curvilinear relationships. Significant changes (p < 0.05) compared to baseline in both HDL-C-concentrations and apoA-I exchange were present at different times. After 7 days of aspirin-only ingestion, apoA-I exchange was significantly modified by increasing levels of DHA concentration, with increased apoA-I exchange observed up until log(DHA) of 4.6 and decreased exchange thereafter (p = 0.03). These LOWESS curve effects were not observed for EPA or HDL-C (p > 0.05). Aspirin's effects on apoA-I exchange were the greatest when EPA or DHA concentrations were moderate compared to high or low. Comparison of EPA, DHA, and EPA+DHA LOWESS curves, demonstrated that the majority of the effect is due to DHA. Our results strongly suggest that plasma concentrations

Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

PubMed Central

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

Does aspirin or non-aspirin non-steroidal anti-inflammatory drug use prevent colorectal cancer in inflammatory bowel disease?

PubMed Central

Burr, Nick E; Hull, Mark A; Subramanian, Venkataraman

2016-01-01

AIM: To determine whether aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) prevent colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD). METHODS: We performed a systematic review and meta-analysis. We searched for articles reporting the risk of CRC in patients with IBD related to aspirin or NA-NSAID use. Pooled odds ratios (OR) and 95%CIs were determined using a random-effects model. Publication bias was assessed using Funnel plots and Egger’s test. Heterogeneity was assessed using Cochran’s Q and the I2 statistic. RESULTS: Eight studies involving 14917 patients and 3 studies involving 1282 patients provided data on the risk of CRC in patients with IBD taking NA-NSAIDs and aspirin respectively. The pooled OR of developing CRC after exposure to NA-NSAIDs in patients with IBD was 0.80 (95%CI: 0.39-1.21) and after exposure to aspirin it was 0.66 (95%CI: 0.06-1.39). There was significant heterogeneity (I2 > 50%) between the studies. There was no change in the effect estimates on subgroup analyses of the population studied or whether adjustment or matching was performed. CONCLUSION: There is a lack of high quality evidence on this important clinical topic. From the available evidence NA-NSAID or aspirin use does not appear to be chemopreventative for CRC in patients with IBD. PMID:27053860

Clinical and Immunological Efficacy of Aspirin Desensitization in Nasal Polyp Patients with Aspirin-Exacerbated Respiratory Disease

PubMed Central

Mortazavi, Negar; Esmaeilzadeh, Hossein; Abbasinazari, Mohammad; Babaie, Delara; Alyasin, Soheila; Nabavizadeh, Hesamodin; Esmailzadeh, Elmira

2017-01-01

This study aimed to investigate the efficacy and the underlining mechanism of aspirin desensitization among patients with Aspirin Exacerbated Respiratory Disease (AERD). Thirty-eight patients, who had undergone an aspirin challenge test and were diagnosed as having AERD, were engaged in a double-blind randomized clinical trial. They were divided into two groups—an active group of patients who went through aspirin desensitization, and the control group, receiving placebo. Clinical symptoms and the quality of life of the patients—in addition to the levels of interleukin 4 and 5 (IL4), (IL5)—were documented at the beginning of the study and again after six months of aspirin desensitization. The quality of life of the patients was significantly higher in the active group after six months (P = 0.001). Medication requirements and symptom score were manifested to be significantly lower in the active group after six months than at the beginning of the study (P = 0.005, 0.017 respectively). Forced expiratory volume in the second one (FEV1) was, also, significantly higher in the active group after six months of the study (P = 0.032). IL5 was found to be significantly lower in the active group after six months (P = 0.019). However, no significant difference was observed in the levels of IL4 between the two groups (P = 0.152). The study revealed that aspirin desensitization can improve the quality of life of patients with AERD, lessen their symptoms and medication requirements, lower their levels of IL5, and improve some pulmonary function tests such as FEV1. PMID:29552073

EV-077 in vitro inhibits platelet aggregation in type-2 diabetics on aspirin.

PubMed

Sakariassen, Kjell S; Femia, Eti A; Daray, Federico M; Podda, Gian M; Razzari, Cristina; Pugliano, Mariateresa; Errasti, Andrea E; Armesto, Arnaldo R; Nowak, Wanda; Alberts, Pēteris; Meyer, Jean-Philippe; Sorensen, Alexandra S; Cattaneo, Marco; Rothlin, Rodolfo P

2012-11-01

This study aimed to characterize the in vitro effect of EV-077, a compound that antagonises the binding of prostanoids and isoprostanes to the thromboxane receptor (TP) and inhibits the thromboxane synthase (TS), on platelet aggregation of patients with type-2 diabetes and coronary artery disease (CAD) on chronic aspirin treatment. The effect of EV-077 on 8-iso-PGE(2)-mediated TP receptor contraction of human arteries was also investigated. Fifty-two type-2 diabetics with CAD on chronic aspirin (100 mg) treatment were studied. Arachidonic acid-induced platelet aggregation was measured by impedance aggregometry in platelet-rich plasma (PRP) and whole blood anticoagulated with hirudin, and by light transmission aggregometry in citrate-anticoagulated PRP following 10-min in vitro exposure to EV-077 (100 nmol/l) or control. The effect of EV-077 was measured on isometric contraction of 24 human umbilical arteries induced by isoprostane 8-iso-PGE(2). Arachidonic acid (1 mmol/l) induced substantial aggregation in hirudin-anticoagulated whole blood (63 ± 4 AU), which was significantly reduced by in vitro exposure to EV-077 (38 ± 3 AU, P<0.001). Virtually no arachidonic acid-induced aggregation in citrate-anticoagulated or hirudin-anticoagulated PRP was observed. EV-077 potently, competitively and reversibly inhibited TP mediated contraction of umbilical arteries by 8-iso-PGE(2) (P<0.01). Aspirin did not completely inhibit arachidonic acid-induced platelet aggregation in whole blood from type-2 diabetics with CAD. This aggregation is likely induced by prostanoids and/or isoprostanes produced by leukocytes, because it was significantly reduced by EV-077. The TP receptor-mediated contraction of human arteries induced by isoprostane 8-iso-PGE(2) was effectively inhibited by EV-077. Copyright © 2012 Elsevier Ltd. All rights reserved.

Phospho-Aspirin (MDC-22) Prevents Pancreatic Carcinogenesis in Mice.

PubMed

Mattheolabakis, George; Papayannis, Ioannis; Yang, Jennifer; Vaeth, Brandon M; Wang, Ruixue; Bandovic, Jela; Ouyang, Nengtai; Rigas, Basil; Mackenzie, Gerardo G

2016-07-01

Pancreatic cancer is a deadly disease with a dismal 5-year survival rate of <6%. The currently limited treatment options for pancreatic cancer underscore the need for novel chemopreventive and therapeutic agents. Accumulating evidence indicates that aspirin use is associated with a decreased risk of pancreatic cancer. However, the anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we developed phospho-aspirin (MDC-22), a novel derivative of aspirin, and evaluated its chemopreventive efficacy in preclinical models of pancreatic cancer. Phospho-aspirin inhibited the growth of human pancreatic cancer cell lines 8- to 12-fold more potently than aspirin; based on the 24-hour IC50 values. In a Panc-1 xenograft model, phospho-aspirin, at a dose of 100 mg/kg/d 5 times per week for 30 days, reduced tumor growth by 78% (P < 0.01 vs. vehicle control). Furthermore, phospho-aspirin prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. In p48-Cre;Kras(G12D) mice, cerulein treatment (6 hourly injections two times per week for 3 weeks) led to a significant increase in ductal metaplasia, replacing the majority of the exocrine compartment. Administration of phospho-aspirin 100 mg/kg/day five times per week for 21 days (starting on the first day of cerulein injection) inhibited the acinar-to-ductal metaplasia, reducing it by 87% (P < 0.01, vs. cerulein-treated control). Phospho-aspirin appeared to be safe, with the animals showing no signs of toxicity during treatment. Mechanistically, phospho-aspirin inhibited EGFR activation in pancreatic cancer, an effect consistently observed in pancreatic cancer cells, primary acinar explants and in vivo In conclusion, our findings indicate that phospho-aspirin has strong anticancer efficacy in preclinical models of pancreatic cancer, warranting its further evaluation. Cancer Prev Res; 9(7); 624-34. ©2016 AACR. ©2016 American Association

The ASAS-SN Bright Supernova Catalog – II. 2015

DOE PAGES

Holoien, T. W. -S.; Brown, J. S.; Stanek, K. Z.; ...

2017-01-16

Here, this paper presents information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) during 2015, its second full year of operations. The same information is presented for bright (mV ≤ 17), spectroscopically confirmed supernovae discovered by other sources in 2015. As with the first ASAS-SN bright supernova catalogue, we also present redshifts and near-ultraviolet through infrared magnitudes for all supernova host galaxies in both samples. Combined with our previous catalogue, this work comprises a complete catalogue of 455 supernovae from multiple professional and amateur sources, allowing for population studies that were previously impossible. This is themore » second of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.« less

The ASAS-SN Bright Supernova Catalog – II. 2015

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holoien, T. W. -S.; Brown, J. S.; Stanek, K. Z.

Here, this paper presents information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) during 2015, its second full year of operations. The same information is presented for bright (mV ≤ 17), spectroscopically confirmed supernovae discovered by other sources in 2015. As with the first ASAS-SN bright supernova catalogue, we also present redshifts and near-ultraviolet through infrared magnitudes for all supernova host galaxies in both samples. Combined with our previous catalogue, this work comprises a complete catalogue of 455 supernovae from multiple professional and amateur sources, allowing for population studies that were previously impossible. This is themore » second of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.« less

Peroxisome proliferation activation receptor alpha modulation of Ca2+-regulated exocytosis via arachidonic acid in guinea-pig antral mucous cells.

PubMed

Sawabe, Yukinori; Shimamoto, Chikao; Sakai, Akiko; Kuwabara, Hiroko; Saad, Adel H; Nakano, Takashi; Takitani, Kimitaka; Tamai, Hiroshi; Mori, Hiroshi; Marunaka, Yoshinori; Nakahari, Takashi

2010-08-01

Indomethacin (IDM, 10 microm), not aspirin (ASA; 10 microm), enhanced the Ca(2+)-regulated exocytosis stimulated by 1 microm acetylcholine (ACh) in guinea-pig antral mucous cells. Indomethacin inhibits prostaglandin G/H (PGG/H) and 15R-hydroperoxy-eicosatetraenoic acid (15R-HPETE) production from arachidonic acid (AA), while ASA inhibits PGG/H production but accelerates 15R-HPETE production. This suggests that IDM accumulates AA. Arachidonic acid (2 microm) enhanced Ca(2+)-regulated exocytosis in antral mucous cells to a similar extent to IDM. Moreover, a stable analogue of AA, arachidonyltrifluoromethyl ketone (AACOCF(3)), also enhanced Ca(2+)-regulated exocytosis, indicating that AA, not products from AA, enhances Ca(2+)-regulated exocytosis. We hypothesized that AA activates peroxisome proliferation activation receptor alpha (PPARalpha), because AA is a natural ligand for PPARalpha. A PPARalpha agonist (WY14643; 1 microm) enhanced Ca(2+)-regulated exocytosis, and a PPARalpha blocker (MK886; 50 microm) abolished the enhancement of Ca(2+)-regulated exocytosis induced by AA, IDM, AACOCF(3) and WY14643. Western blotting and immunohistochemical examinations demonstrated that PPARalpha exists in antral mucous cells. Moreover, MK886 decreased the frequency of Ca(2+)-regulated exocytosis activated by 1 microm ACh or 2 microm thapsigargin alone by 25-30%. Thus, ACh stimulates AA accumulation via an [Ca(2+)](i) increase, which activates PPARalpha, leading to enhancement of Ca(2+)-regulated exocytosis in antral mucous cells. A novel autocrine mechanism mediated via PPARalpha enhances Ca(2+)-regulated exocytosis in guinea-pig antral mucous cells.

The effect of simvastatin, aspirin, and their combination in reduction of atheroma plaque

NASA Astrophysics Data System (ADS)

Kurniati, Neng Fisheri; Permatasari, Anita

2015-09-01

Atherosclerosis is one of the risk factors of cardiovascular disease. Atherosclerosis is a chronic inflammatory disease caused by high level of cholesterol especially low density lipoprotein (LDL) and accumulation of neutrophil and macrophage in the artery wall. Thickness of aortic wall is an early stage of atherosclerosis plaque formation. Identification of atherosclerosis plaque formation was done by measuring level of total cholesterol, triglycerides, HDL, LDL, interleukin-18 (IL-18), myeloperoxidase (MPO) and measuring the thickness of aortic wall. Atherosclerosis's model induced by high fat diet and CCT (cholesterol, cholic acid, and propyltiouracil) oral administration. Rats induced cholesterol divided into positive control, simvastatin 25 mg/kg bw, aspirin 20 mg/kg bw, and combination simvastatin 25 mg/kg and aspirin 20 mg/kg bw group for 3 weeks. In the third week, therapy was given to atherosclerosis's model. Then, in the fourth and fifth week, therapy was given but induction of high cholesterol was stopped due to the massive loss of body weight. Total cholesterol, triglycerides, HDL, LDL, MPO, and IL-18 measured by uv-vis spectrophotometry and ELISA. In the end of therapy, aorta's rats was isolated to identify the thickness of aorta wall. In the fourth week, after 1 week of treatment, only combination group showed significantly higher total cholesterol, LDL and MPO compared to positive control group. Level of triglycerides and HDL in all groups did not significantly differ compared to positive control group. After 2 weeks continuing drug treatment, the level of total cholesterol, MPO, and IL-18 were decreased in all groups, and aspirin group showed the lowest level. The level of triglycerides was decreased in simvastatin and aspirin group, and aspirin group showed the lowest. Only combination group showed the lowest level of LDL. Based on histopathology result, the thickness of aortic wall was reduced in all groups and aspirin group showed the lowest.

Variability of non-response to aspirin in patients with peripheral arterial occlusive disease during long-term follow-up.

PubMed

Linnemann, Birgit; Prochnow, Stephanie; Mani, Helen; Schwonberg, Jan; Lindhoff-Last, Edelgard

2009-10-01

Non-responsiveness to aspirin as detected by laboratory tests may identify patients at high risk for future vascular events. The aim of this prospective study was to evaluate whether non-responsiveness to aspirin is stable over time. Ninety-eight patients with stable peripheral arterial occlusive disease (PAOD) treated with 100 mg/d aspirin were followed over a median timeframe of 17 months. Platelet function tests were performed initially and at follow-up using arachidonic acid-induced light transmittance aggregometry (LTA) in native platelet-rich plasma with the Behring Coagulation Timer and by measuring the collagen-epinephrine closure time (CT) on a Platelet Function Analyzer (PFA-100). When determining platelet function using LTA, four patients (4.1%) had residual platelet function (i.e., MaxAggr > or =78%) despite aspirin treatment, whereas, according to the PFA-100 results, 12 patients (12.2%) were identified as non-responders (i.e., CT <192 s). Fifty-seven patients who were still under treatment with 100 mg/d aspirin at the time of follow-up provided a second blood sample. Further platelet function tests with the PFA-100 system identified a persistent non-responsiveness to aspirin over time in three patients (5.3%) whereas four (7.0%) and 15 (26.3%) patients had changes in response status when platelet function was assessed by LTA and on the PFA-100(R), respectively. We conclude that true non-responsiveness to aspirin is a rare phenomenon in stable PAOD patients. Furthermore, we conclude that in a number of patients, aspirin non-responsiveness is not stable over time.

Discovery of 11 ASAS-SN Supernovae

NASA Astrophysics Data System (ADS)

Brimacombe, J.; Cacella, P.; Stone, G.; Fernandez, J. M.; Vallely, P.; Stanek, K. Z.; Kochanek, C. S.; Brown, J. S.; Shields, J.; Thompson, T. A.; Shappee, B. J.; Holoien, T. W.-S.; Prieto, J. L.; Bersier, D.; Dong, Subo; Bose, S.; Chen, Ping; Stritzinger, M.; Holmbo, S.; Nicholls, B.; Post, R. S.

2018-05-01

During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014), using data from 14-cm telescopes in Hawaii, Texas, South Africa, and Chile, we discovered several new transient sources.

Talk with Your Doctor about Taking Aspirin Every Day

MedlinePlus

... En español Talk with Your Doctor about Taking Aspirin to Prevent Disease Browse Sections The Basics Overview ... and Risks What are the benefits of taking aspirin regularly? Low-dose aspirin can reduce your risk ...

The assessment of the antibacterial and antifungal activities of aspirin, EDTA and aspirin-EDTA combination and their effectiveness as antibiofilm agents.

PubMed

Al-Bakri, A G; Othman, G; Bustanji, Y

2009-07-01

To evaluate the antimicrobial activities of aspirin, EDTA and an aspirin-EDTA (A-EDTA) combination against Pseudomonas aeruginosa, Escherichia coli and Candida albicans in planktonic and biofilm cultures. Minimal inhibitory concentrations (MIC) and minimal biocidal concentrations (MBC) were determined using twofold broth microdilution and viable counting methods, respectively. Aspirin's recorded MIC values ranged from 1.2 to 2.7 mg ml(-1). Checkerboard assay demonstrated a synergism in antimicrobial activity upon combination. Aspirin's minimal biofilm eradication concentration values (MBEC) against the established biofilms ranged between 1.35 and 3.83 mg ml(-1). A complete eradication of bacterial biofilms was achieved after a 4-h treatment with the A-EDTA combination. Both aspirin and EDTA possess broad-spectrum antimicrobial activity for both planktonic and biofilm cultures. Aspirin used at the MBEC for 24 h was successful in eradicating P. aeruginosa, E. coli and C. albicans biofilms established on abiotic surfaces. Moreover, the exposure to the A-EDTA combination (4 h) effected complete bacterial biofilm eradication. There is a continuous need for the discovery of new antimicrobial agents. Aspirin and EDTA are 'nonantibiotic drugs', the combination of which can be used successfully to treat and eradicate biofilms established on abiotic surfaces.

Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer: Summary of epidemiologic evidence of cancer risk and prognosis.

PubMed

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.

Ascorbic acid metabolism during sweet cherry (Prunus avium) fruit development

PubMed Central

Ni, Zhiyou; Lin, Lijin; Tang, Yi; Wang, Zhihui; Wang, Xun; Wang, Jin; Lv, Xiulan; Xia, Hui

2017-01-01

To elucidate metabolism of ascorbic acid (AsA) in sweet cherry fruit (Prunus avium ‘Hongdeng’), we quantified AsA concentration, cloned sequences involved in AsA metabolism and investigated their mRNA expression levels, and determined the activity levels of selected enzymes during fruit development and maturation. We found that AsA concentration was highest at the petal-fall period (0 days after anthesis) and decreased progressively during ripening, but with a slight increase at maturity. AsA did nevertheless continue to accumulate over time because of the increase in fruit fresh weight. Full-length cDNAs of 10 genes involved in the L-galactose pathway of AsA biosynthesis and 10 involved in recycling were obtained. Gene expression patterns of GDP-L-galactose phosphorylase (GGP2), L-galactono-1, 4-lactone dehydrogenase (GalLDH), ascorbate peroxidase (APX3), ascorbate oxidase (AO2), glutathione reductase (GR1), and dehydroascorbate reductase (DHAR1) were in accordance with the AsA concentration pattern during fruit development, indicating that genes involved in ascorbic acid biosynthesis, degradation, and recycling worked in concert to regulate ascorbic acid accumulation in sweet cherry fruit. PMID:28245268

Pulsating Stars in the ASAS-3 Database. I. beta Cephei Stars

NASA Astrophysics Data System (ADS)

Pigulski, A.

2005-06-01

We present results of an analysis of the ASAS-3 data for short-period variables from the recently published catalog of over 38000 stars. Using the data available in the literature we verify the results of the automatic classification related to \\beta Cep pulsators. In particular, we find that 14 stars in the catalog can be classified unambiguously as new beta Cep stars. By means of periodogram analysis we derive the frequencies and amplitudes of the excited modes. The main modes in the new beta Cep stars have large semi-amplitudes, between 35 and 80 mmag. Up to four modes were found in some stars. Two (maybe three) new beta Cep stars are members of southern young open clusters: ASAS 164409-4719.1 belongs to NGC 6200, ASAS 164630-4701.2 is a member of Hogg 22, and ASAS 164939-4431.7 could be a member of NGC 6216. We also analyze the photometry of four known beta Cep stars in the ASAS-3 catalog, namely IL Vel, NSV 24078, V1449 Aql and SY Equ. Finally, we discuss the distribution of beta Cep stars in the Galaxy.

Platelet function analysis with two different doses of aspirin.

PubMed

Aydinalp, Alp; Atar, Ilyas; Altin, Cihan; Gülmez, Oykü; Atar, Asli; Açikel, Sadik; Bozbaş, Hüseyin; Yildirir, Aylin; Müderrisoğlu, Haldun

2010-06-01

We aimed to compare the level of platelet inhibition using the platelet function analyzer (PFA)-100 in patients receiving low and medium doses of aspirin. On a prospective basis, 159 cardiology outpatients (83 men, 76 women; mean age 60.9 ± 9.9 years) taking 100 mg/day or 300 mg/day aspirin at least for the previous 15 days were included. Of these, 79 patients (50%) were on 100 mg and 80 patients (50.3%) were on 300 mg aspirin treatment. Blood samples were collected between 09:30 and 11:00 hours in the morning. Platelet reactivity was measured with the PFA-100 system. Incomplete platelet inhibition was defined as a normal collagen/epinephrine closure time (< 165 sec) despite aspirin treatment. Baseline clinical and laboratory characteristics of the patient groups taking 100 mg or 300 mg aspirin were similar. The overall prevalence of incomplete platelet inhibition was 22% (35 patients). The prevalence of incomplete platelet inhibition was significantly higher in patients treated with 100 mg of aspirin (n = 24/79, 30.4%) compared with those treated with 300 mg of aspirin (n = 11/80, 13.8%) (p = 0.013). In univariate analysis, female sex (p = 0.002) and aspirin dose (p = 0.013) were significantly correlated with incomplete platelet inhibition. In multivariate analysis, female sex (OR: 0.99; 95% CI 0.9913-0.9994; p = 0.025) and aspirin dose (OR: 3.38; 95% CI 1.4774-7.7469; p = 0.003) were found as independent factors predictive of incomplete platelet inhibition. Our findings suggest that treatment with higher doses of aspirin can reduce incomplete platelet inhibition especially in female patients.

Native Platelet Aggregation and Response to Aspirin in Persons With the Metabolic Syndrome and Its Components

PubMed Central

Yanek, Lisa R.; Faraday, Nauder; Moy, Taryn F.; Becker, Lewis C.; Becker, Diane M.

2009-01-01

Abstract Background Aspirin chemoprophylaxis for coronary artery disease (CAD) is recommended for persons with the metabolic syndrome. We determined the extent to which persons with increased risk for CAD with and without the metabolic syndrome accrued antiplatelet benefits from aspirin therapy. Methods We examined 2088 apparently healthy persons with a family history of CAD for the components that comprise metabolic syndrome and classified them according to national guidelines as having the metabolic syndrome or not. We assayed whole blood for ex vivo agonist-induced platelet aggregation (collagen, adenosine diphosphate, and arachidonic acid) and assessed a measure of in vivo platelet activation using urinary 11-dehydrothromboxane B2 (TxM), at baseline and after 2 weeks of treatment with 81 mg/day aspirin. Results At baseline, in multivariable analyses adjusted for race, age, sex, and risk factors, persons with metabolic syndrome had more aggregable platelets in response to all three agonists and higher levels of TxM (P < 0.005 for all) compared to those without metabolic syndrome. Postaspirin, although all individuals had lower platelet activation measures, subjects with metabolic syndrome retained higher platelet aggregation to adenosine diphosphate (P = 0.002) and higher TxM (P < 0.001), while aggregation to arachidonic acid (P = 0.12) and collagen (P = 0.08) were marginally different between those with and without the metabolic syndrome. Conclusions Among persons with an increased risk for CAD, metabolic syndrome was independently associated with overall greater platelet aggregation and activation at baseline and lesser, though significant, effect following aspirin, suggesting that low-dose aspirin therapy alone may not be sufficient to provide optimal anti-platelet protection in persons with metabolic syndrome. PMID:19351291

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

PubMed

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 < 0.001), with a higher proportion of males (P < 0.001) and higher frequencies of hypertension (P  = 0.004) and diabetes mellitus (P < 0.001). No significant differences were observed in intraoperative parameters. Although the frequency of major morbidity tended to be higher among 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.

Complex roles of the old drug aspirin in cancer chemoprevention and therapy.

PubMed

Hua, Hui; Zhang, Hongying; Kong, Qingbin; Wang, Jiao; Jiang, Yangfu

2018-06-01

The nonsteroidal anti-inflammatory agent aspirin is widely used for preventing and treating cardiovascular and cerebrovascular diseases. In addition, epidemiologic evidences reveal that aspirin may prevent a variety of human cancers, while data on the association between aspirin and some kinds of cancer are conflicting. Preclinical studies and clinical trials also reveal the therapeutic effect of aspirin on cancer. Although cyclooxygenase is a well-known target of aspirin, recent studies uncover other targets of aspirin and its metabolites, such as AMP-activated protein kinase, cyclin-dependent kinase, heparanase, and histone. Accumulating evidence demonstrate that aspirin may act in different cell types, such as epithelial cell, tumor cell, endothelial cell, platelet, and immune cell. Therefore, aspirin acts on diverse hallmarks of cancer, such as sustained tumor growth, metastasis, angiogenesis, inflammation, and immune evasion. In this review, we focus on recent progress in the use of aspirin for cancer chemoprevention and therapy, and integratively analyze the mechanisms underlying the anticancer effects of aspirin and its metabolites. We also discuss mechanisms of aspirin resistance and describe some derivatives of aspirin, which aim to overcome the adverse effects of aspirin. © 2018 Wiley Periodicals, Inc.

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

PubMed

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 (p<0.01, Wilcoxon signed-rank test). Aspirin and placebo treatment were associated with elevated P-selectin expression, platelet-monocyte aggregation and reduced CD42b expression (p<0.05, Wilcoxon 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 (p<0.05, Wilcoxon 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.

Platelet response to increased aspirin dose in patients with persistent platelet aggregation while treated with aspirin 81 mg.

PubMed

Gengo, Fran; Westphal, Erica S; Rainka, Michelle M; Janda, Maria; Robson, Matthew J; Hourihane, J Maurice; Bates, Vernice

2016-04-01

This study demonstrates that patients who are taking 81 mg of aspirin and are nonresponsive benefit from a dose of 162 mg or greater vs a different antiplatelet therapy. We identified 100 patients who were nonresponsive to aspirin 81 mg via whole blood aggregometry and observed how many patients became responsive at a dose of 162 mg or greater. Platelet nonresponsiveness was defined as >10 Ω of resistance to collagen 1 µg/mL and/or an ohms ratio of collagen 1 µg/mL to collagen 5 µg/mL >0.5 and/or >6 Ω to arachidonate. Borderline response was defined as an improvement in 1 but not both of the above criteria. Of the initial 100 patients who were nonresponsive to an aspirin dose of 81 mg, 79% became responsive at a dose of 162 mg or >162 mg. Only 6% did not respond to any increase in dose. We believe that patients treated with low-dose aspirin who have significant risk for secondary vascular events should be individually assessed to determine their antiplatelet response. Those found to have persistent platelet aggregation despite treatment with 81 mg of aspirin have a higher likelihood of obtaining an adequate antiplatelet response at a higher aspirin dose. © 2015, The American College of Clinical Pharmacology.

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

PubMed

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 <37 weeks' gestation, which was the primary outcome, occurred in 1.6% (13/798) participants in the aspirin group, as compared with 4.3% (35/822) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74). We sought to examine the influence of compliance on the beneficial effect of aspirin in prevention of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial. This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of <90% and ≥90%, after adjustment for the estimated risk of preterm 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 <90%, in 22/588 (3.7%) of participants in the placebo group with compliance ≥90%, and in 13/234 (5.6%) of participants in the placebo group

Prevention or treatment of ARDS with aspirin: a review of preclinical models and meta- analysis of clinical studies

PubMed Central

Panka, Bernardo Amisa; de Grooth, Harm-Jan; Spoelstra–de Man, Angeliquè; Looney, Mark; Tuinman, Pieter-Roel

2016-01-01

Background The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions directed at lung injury itself, have proven effective in improving outcome of patients with ARDS. Platelet activation was identified as a key component in ARDS pathophysiology and may provide an opportunity for preventive and therapeutic strategies. We hypothesize that use of acetyl salicylic acid (ASA) may prevent and/or attenuate lung injury. Methods We conducted a systematic review of preclinical studies and meta-analysis of clinical studies investigating the efficacy of ASA in the setting of lung injury. MEDLINE, EMBASE AND COCHRANE databases were searched. Results The literature search yielded 1314 unique articles. Fifteen pre-clinical studies and eight clinical studies fulfilled the in- and exclusion criteria. In the animal studies, the overall effect of ASA was positive, e.g. ASA improved survival and attenuated inflammation and pulmonary edema. Mechanisms of actions involved, among others, are interference with the neutrophil-platelets interaction, reduction of leukotrienes, neutrophil extracellular traps and prostaglandins. High dose ASA may be the drug of choice. A meta-analysis of 3 clinical studies showed an association between ASA use and a reduced incidence of ARDS (OR 0.59, 95% CI 0.36–0.98), albeit with substantial between-study heterogeneity. All studies had their own shortcomings in methodological quality. Conclusion This systematic review of preclinical studies and meta-analysis of clinical studies suggests a beneficial role for ASA in ARDS prevention and treatment. However, the currently available data is insufficient to justify an indication for ASA in ARDS. The body of literature does support further studies in humans. We suggest clinical trials in which the mechanisms of action of ASA in lung injury models is being evaluated to guide optimal timing and dose

Low-dose aspirin for preventing recurrent venous thromboembolism.

PubMed

Brighton, Timothy A; Eikelboom, John W; Mann, Kristy; Mister, Rebecca; Gallus, Alexander; Ockelford, Paul; Gibbs, Harry; Hague, Wendy; Xavier, Denis; Diaz, Rafael; Kirby, Adrienne; Simes, John

2012-11-22

Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued. Aspirin may be effective in preventing a recurrence of venous thromboembolism. We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin, at a dose of 100 mg daily, or placebo for up to 4 years. The primary outcome was a recurrence of venous thromboembolism. During a median follow-up period of 37.2 months, venous thromboembolism recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to aspirin (a rate of 6.5% per year vs. 4.8% per year; hazard ratio with aspirin, 0.74; 95% confidence interval [CI], 0.52 to 1.05; P=0.09). Aspirin reduced the rate of the two prespecified secondary composite outcomes: the rate of venous thromboembolism, myocardial infarction, stroke, or cardiovascular death was reduced by 34% (a rate of 8.0% per year with placebo vs. 5.2% per year with aspirin; hazard ratio with aspirin, 0.66; 95% CI, 0.48 to 0.92; P=0.01), and the rate of venous thromboembolism, myocardial infarction, stroke, major bleeding, or death from any cause was reduced by 33% (hazard ratio, 0.67; 95% CI, 0.49 to 0.91; P=0.01). There was no significant between-group difference in the rates of major or clinically relevant nonmajor bleeding episodes (rate of 0.6% per year with placebo vs. 1.1% per year with aspirin, P=0.22) or serious adverse events. In this study, aspirin, as compared with placebo, did not significantly reduce the rate of recurrence of venous thromboembolism but resulted in a significant reduction in the rate of major vascular events, with improved net clinical benefit. These results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy for a first episode of unprovoked venous thromboembolism. (Funded by National Health

A data base of ASAS digital imagery. [Advanced Solid-state Array Spectroradiometer

NASA Technical Reports Server (NTRS)

Irons, James R.; Meeson, Blanche W.; Dabney, Philip W.; Kovalick, William M.; Graham, David W.; Hahn, Daniel S.

1992-01-01

The Advanced Solid-State Array Spectroradiometer (ASAS) is an airborne, off-nadir tilting, imaging spectroradiometer that acquires digital image data for 29 spectral bands in the visible and near-infrared. The sensor is used principally for studies of the bidirectional distribution of solar radiation scattered by terrestial surfaces. ASAS has acquired data for a number of terrestial ecosystem field experiments and investigators have received over 170 radiometrically corrected, multiangle, digital image data sets. A database of ASAS digital imagery has been established in the Pilot Land Data System (PLDS) at the NASA/Goddard Space Flight Center to provide access to these data by the scientific community. ASAS, its processed data, and the PLDS are described, together with recent improvements to the sensor system.

Aspirin treatment increases the risk of cerebral microbleeds.

PubMed

Ge, Lihong; Niu, Guangming; Han, Xiaodong; Gao, Yang; Wu, Qiong; Wu, Hui; Zhang, Ying; Guo, Dongling

2011-11-01

The objective of the study was to determine the frequency of cerebral microbleeds (CMBs) by using phasesensitive imaging in patients with previous transient ischemic attack (TIA) or stroke who were receiving aspirin treatment. We retrospectively analyzed 300 outpatients with ischemic cerebrovascular disease: 150 had been receiving aspirin treatment for >1 year (patients), and 150 controls had not previously received aspirin. Cerebral microbleeds were defined by a trained observer (blinded to clinical details) according to results of T2-weighted, T1-weighted, diffusion-weighted, and phase-sensitive magnetic resonance imaging (MRI). Numerous vascular risk factors including white matter hyperintensity (WMH), duration of aspirin treatment, age, hypertension or diabetes mellitus were investigated for a possible association with the presence of CMBs in the two groups. The frequency of CMBs (60/150 (40%) vs 18/150 (12%); odds ratio 4.899, p <0.0001) and intracerebral hemorrhage (ICH)(42/150 (28%) vs 2/150 (1%); odds ratio 28.778, p <0.0001) were significantly higher in the patients than in the controls. Among patients, those using aspirin for >5 years(42/68 (62%) showed a higher frequency of CMBs than those receiving aspirin for ≤ 5 years(18/82 (22%); odds ratio 5.744, p<0.0001). WMH (p=0.020/0.030, 0.007/0.000) age (p=0.007/0.000) and hypertension (p=0.000/0.033), in patients and controls respectively, were each associated with CMBs. There was a clear impact of aspirin treatment on CMBs associated with intracerebral hemorrhage in Chinese patients. The frequency of CMBs and hemorrhagic complications was higher in patients treated with long-term aspirin.

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

PubMed Central

2013-01-01

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

Baseline Oral 5-ASA Use and Efficacy and Safety of Budesonide Foam in Patients with Ulcerative Proctitis and Ulcerative Proctosigmoiditis: Analysis of 2 Phase 3 Studies.

PubMed

Bosworth, Brian P; Sandborn, William J; Rubin, David T; Harper, Joseph R

2016-08-01

Rectal budesonide foam is a second-generation corticosteroid efficacious for active mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. This subgroup analysis examined the impact of baseline oral 5-aminosalicylic acid (5-ASA) on the efficacy and safety of budesonide foam in patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis. Patients received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo, with or without continued stable dosing of baseline oral 5-ASAs, for remission induction at week 6 (primary endpoint) in 2 identically designed, randomized, double-blind, phase 3 studies. Of the 267 and 279 patients randomized to treatment with budesonide foam or placebo (pooled population), 55.1% and 55.2%, respectively, reported baseline 5-ASA use. A significantly greater percentage of patients achieved remission with budesonide foam versus placebo, either with (42.2% versus 31.8%, respectively; P = 0.03) or without (40.0% versus 14.4%; P < 0.0001) baseline 5-ASA use at week 6. A significantly greater percentage of patients achieved a Modified Mayo Disease Activity Index rectal bleeding subscale score of 0 at week 6, regardless of baseline 5-ASA use (5-ASA, 50.3% versus 35.7%; P = 0.003: no 5-ASA, 45.8% versus 19.2%; P < 0.0001). The frequency of adverse events was comparable between groups, regardless of baseline 5-ASA use. Budesonide foam was efficacious and safe for induction of remission of mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis in patients receiving oral 5-ASA at baseline and those who were not (Clinicaltrials.gov: NCT01008410 and NCT01008423).

Prevalence of Aspirin Resistance in Diabetic Patients and its Associated Factors

PubMed Central

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

2015-01-01

Background: Aspirin resistance has posed a major dilemma in the prevention of cardiovascular disease and stroke. There have been many factors that have been associated with aspirin resistance. Among these factors, the inflammatory processes of diabetes and glycaemic control have been significantly associated with aspirin resistance. Our study evaluated the prevalence of aspirin resistance and its associated factors. Methods: This was a cross-sectional, interventional study, which was implemented from October to November 2012 at the Hospital Universiti Sains Malaysia (HUSM). Sixty-nine patients with diabetes who were taking aspirin were enrolled. The glycosylated haemoglobin (HbA1c) and C-reactive protein (CRP) levels were measured in these patients. The thromboelastography (TEG) level was measured using a TEG machine by a trained technician employing standard methods. The variables obtained were analysed for prevalence of aspirin resistance, HbA1c, CRP, and TEG level. The Chi-square test (and Fisher exact test where applicable) were used to evaluate the associations between aspirin resistance with glycaemic control (HbA1c) and inflammatory markers (CRP). Results: The prevalence of aspirin resistance was 17.4% (95%; CI 9.3, 28.4). Glycaemic control (HbA1c) and inflammatory markers (CRP) were not associated with aspirin resistance. Aspirin resistance was prevalent in our study population and was comparable to other studies. The mean HbA1c in the aspirin-resistant group was 8.9%, whereas the mean HbA1c in the aspirin-sensitive group was 8.6%. Conclusion: There was no significant difference in HbA1c between the two groups. There was no significant association between CRP levels and aspirin resistance. PMID:25892950

Does ASA classification impact success rates of endovascular aneurysm repairs?

PubMed

Conners, Michael S; Tonnessen, Britt H; Sternbergh, W Charles; Carter, Glen; Yoselevitz, Moises; Money, Samuel R

2002-09-01

The purpose of this study was to evaluate the technical success, clinical success, postoperative complication rate, need for a secondary procedure, and mortality rate with endovascular aneurysm repair (EAR), based on the physical status classification scheme advocated by the American Society of Anesthesiologists (ASA). At a single institution 167 patients underwent attempted EAR. Query of a prospectively maintained database supplemented with a retrospective review of medical records was used to gather statistics pertaining to patient demographics and outcome. In patients selected for EAR on the basis of acceptable anatomy, technical and clinical success rates were not significantly different among the different ASA classifications. Importantly, postoperative complication and 30-day mortality rates do not appear to significantly differ among the different ASA classifications in this patient population.

Biosynthesis of l-Ascorbic Acid and Conversion of Carbons 1 and 2 of l-Ascorbic Acid to Oxalic Acid Occurs within Individual Calcium Oxalate Crystal Idioblasts1

PubMed Central

Kostman, Todd A.; Tarlyn, Nathan M.; Loewus, Frank A.; Franceschi, Vincent R.

2001-01-01

l-Ascorbic acid (AsA) and its metabolic precursors give rise to oxalic acid (OxA) found in calcium oxalate crystals in specialized crystal idioblast cells in plants; however, it is not known if AsA and OxA are synthesized within the crystal idioblast cell or transported in from surrounding mesophyll cells. Isolated developing crystal idioblasts from Pistia stratiotes were used to study the pathway of OxA biosynthesis and to determine if idioblasts contain the entire path and are essentially independent in OxA synthesis. Idioblasts were supplied with various 14C-labeled compounds and examined by micro-autoradiography for incorporation of 14C into calcium oxalate crystals. [14C]OxA gave heavy labeling of crystals, indicating the isolated idioblasts are functional in crystal formation. Incubation with [1-14C]AsA also gave heavy labeling of crystals, whereas [6-14C]AsA gave no labeling. Labeled precursors of AsA (l-[1-14C]galactose; d-[1-14C]mannose) also resulted in crystal labeling, as did the ascorbic acid analog, d-[1-14C]erythorbic acid. Intensity of labeling of isolated idioblasts followed the pattern OxA > AsA (erythorbic acid) > l-galactose > d-mannose. Our results demonstrate that P. stratiotes crystal idioblasts synthesize the OxA used for crystal formation, the OxA is derived from the number 1 and 2 carbons of AsA, and the proposed pathway of ascorbic acid synthesis via d-mannose and l-galactose is operational in individual P. stratiotes crystal idioblasts. These results are discussed with respect to fine control of calcium oxalate precipitation and the concept of crystal idioblasts as independent physiological compartments. PMID:11161021

Inappropriate combination of warfarin and aspirin.

PubMed

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

2016-03-01

A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (p<0.05 for all). The use of combination therapy was similar between different CHADS-VASc scores. In patients with MHV, higher combination therapy was observed in males (41% vs. 26.7% in females; p=0.070), concomitant vascular disease (47.8% vs. 29.8%; p=0.091), and AF (56.3% vs. 29.8%; p=0.033). Independent predictors of warfarin-aspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (p<0.001). The combination of warfarin and aspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV.

Study of oxidative and inflammatory parameters in LDLr-KO mice treated with a hypercholesterolemic diet: Comparison between the use of Campomanesia xanthocarpa and acetylsalicylic acid.

PubMed

Klafke, Jonatas Zeni; Pereira, Roberta Lelis Dias; Hirsch, Gabriela Elisa; Parisi, Mariana Migliorini; Porto, Fernando Garcez; de Almeida, Amanda Spring; Rubin, Fabiane Horbach; Schmidt, Aline; Beutler, Henrique; Nascimento, Sabrina; Trevisan, Gabriela; Brusco, Indiara; de Oliveira, Sara Marchesan; Duarte, Marta Maria Medeiros Frescura; Duarte, Thiago; Viecili, Paulo Ricardo Nazário

2016-10-15

Atherosclerosis is an inflammatory disease that affects the arterial wall leading to myocardial, cerebral, and peripheral ischemic syndromes. The use of low doses of aspirin inhibits platelet aggregation and inflammation and prevents cardiovascular mortality. However, ASA may produce hemorrhagic events. Thus, several studies have sought new natural compounds to suppress platelet aggregation without causing serious adverse effects. In this sense, this study aims to compare the effects of Campomanesia xanthocarpa plant extract with those of acetylsalicylic acid (ASA) on inflammatory parameters observed in homozygous mice knockout for the low-density lipoprotein receptor (LDLr-KO) treated with a hypercholesterolemic diet. In this study, 28 male LDLr-KO mice were divided into three groups and fed a hypercholesterolemic diet for 4 weeks. Thereafter, the animals that received the hypercholesterolemic diet were treated for 5 days with (1) distilled water, (2) C. xanthocarpa extract, or (3) acetylsalicylic acid. The levels of inflammatory markers were assessed in the blood samples. The gastric tolerability of the animals after oral administration of the treatments was assessed through quantification of the lesions in the gastric mucosa. The levels of proinflammatory cytokines IL-1, IL-6, TNF-α, and INF-γ were reduced to 19.2 ± 3%, 20.4 + 1.3%, 24.7 ± 1.2%, and 20.8 ± 1.7%, respectively, in the group treated with C. xanthocarpa, when compared to control group. Furthermore, treatment with plant extract significantly increased the levels of the anti-inflammatory cytokine IL-10 by 27.3 ± 5.9%, but ASA showed no significant effect on the same cytokines when compared to the control group, with the exception of IL-10, which presented an increase of 8.6 ± 3.5%. Treatments with C. xanthocarpa and ASA also caused significant reductions of 26.4 ± 3% and 38.4± 6% in the serum levels of oxLDL, respectively. However, only treatment with C. xanthocarpa reduced the

Lyophilized aspirin with trehalose may decrease the incidence of gastric injuries in healthy dogs.

PubMed

Lin, Lee-Shuan; Kayasuga, Yuko; Shimohata, Nobuyuki; Kamata, Hiroyuki; Suzuki, Shigeki; Echigo, Ryosuke; Mochizuki, Manabu; Chung, Ung-Il; Sasaki, Nobuo

2012-11-01

Trehalose has several novel anti-inflammatory and cell-protective functions. We hypothesized that lyophilized aspirin/trehalose could decrease the severity of aspirin-induced gastropathy. Thirteen dogs were assigned into aspirin, lyophilized aspirin/trehalose, and control groups, and the gastric lesions were assessed on gastroscopy with the modified Lanza scale. Another 6 dogs were used to measure the plasma aspirin concentration by high-performance liquid chromatography after aspirin or lyophilized aspirin/trehalose administration. The results indicated that lyophilized aspirin/trehalose induced less gastric ulceration than aspirin despite maintaining therapeutic concentrations of plasma aspirin in both the groups. Lyophilized aspirin/trehalose might be a solution to decrease aspirin-induced gastropathy.

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

PubMed

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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.

Perioperative aspirin management after POISE-2: some answers, but questions remain.

PubMed

Gerstein, Neal Stuart; Carey, Michael Christopher; Cigarroa, Joaquin E; Schulman, Peter M

2015-03-01

Aspirin constitutes important uninterrupted lifelong therapy for many patients with cardiovascular (CV) disease or significant (CV) risk factors. However, whether aspirin should be continued or withheld in patients undergoing noncardiac surgery is a common clinical conundrum that balances the potential of aspirin for decreasing thrombotic risk with its possibility for increasing perioperative blood loss. In this focused review, we describe the role of aspirin in treating and preventing cardiovascular disease, summarize the most important literature on the perioperative use of aspirin (including the recently published PeriOperative ISchemic Evaluation [POISE]-2 trial), and offer current recommendations for managing aspirin during the perioperative period. POISE-2 suggests that aspirin administration during the perioperative period does not change the risk of a cardiovascular event and may result in increased bleeding. However, these findings are tempered by a number of methodological issues related to the study. On the basis of currently available literature, including POISE-2, aspirin should not be administered to patients undergoing surgery unless there is a definitive guideline-based primary or secondary prevention indication. Aside from closed-space procedures, intramedullary spine surgery, or possibly prostate surgery, moderate-risk patients taking lifelong aspirin for a guideline-based primary or secondary indication may warrant continuation of their aspirin throughout the perioperative period.

Early aspirin use and the development of cardiac allograft vasculopathy.

PubMed

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.

Synthesis and anti-cancer potential of the positional isomers of NOSH-aspirin (NBS-1120) a dual nitric oxide and hydrogen sulfide releasing hybrid.

PubMed

Vannini, Federica; MacKessack-Leitch, Andrew C; Eschbach, Erin K; Chattopadhyay, Mitali; Kodela, Ravinder; Kashfi, Khosrow

2015-10-15

We recently reported the synthesis of NOSH-aspirin, a novel hybrid compound capable of releasing both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e., ortho-NOSH-aspirin. Here we report on the synthesis of meta- and para-NOSH-aspirins. We also made a head-to-head evaluation of the effects of these three positional isomers of NOSH-aspirin on colon cancer cell kinetics and induction of reactive oxygen species, which in recent years has emerged as a key event in causing cancer cell regression. Electron donating/withdrawing groups incorporated about the benzoate moiety significantly affected the potency of these compounds with respect to colon cancer cell growth inhibition. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Role of Aspirin in the Prevention of Cardiovascular Disease

PubMed Central

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

2014-01-01

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

Aspirin (single dose) for perineal pain in the early postpartum period.

PubMed

Molakatalla, Sujana; Shepherd, Emily; Grivell, Rosalie M

2017-02-09

Perineal trauma (due to spontaneous tears, surgical incision (episiotomy) or in association with operative vaginal birth) is common after vaginal birth, and is often associated with postpartum perineal pain. Birth over an intact perineum may also lead to perineal pain. There are adverse health consequences associated with perineal pain for the women and their babies in the short- and long-term, and the pain may interfere with newborn care and the establishment of breastfeeding. Aspirin has been used in the management of postpartum perineal pain and its effectiveness and safety should be assessed. To determine the efficacy of a single dose of aspirin (acetylsalicylic acid), including at different doses, in the relief of acute postpartum perineal pain. We searched Cochrane Pregnancy and Childbirth's Trials Register (30 August 2016), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (31 May 2016) and reference lists of retrieved studies. Randomised controlled trials (RCTs) assessing single dose aspirin compared with placebo, no treatment, a different dose of aspirin, or single dose paracetamol/acetaminophen for women with perineal pain in the early postpartum period. We planned to include cluster-RCTs but none were identified. Quasi-RCTs and cross-over studies were not eligible for inclusion in this review. Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included RCTs. Data were checked for accuracy. The quality of the evidence for the main comparison (aspirin versus placebo) was assessed using the GRADE approach. We included 17 RCTs, with 16 involving 1132 women randomised to aspirin or placebo (one RCT did not report numbers of women). Two RCTs (of 16) did not contribute data to review meta-analyses. All women had perineal pain post-episiotomy, and were not breastfeeding. Studies were published between 1967 and 1997, and the risk of bias was often unclear due to poor

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2018-04-01

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

Aspirin responsiveness changes in obese patients following bariatric surgery.

PubMed

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.

Short-term prevention of thromboembolic complications in patients with atrial fibrillation with aspirin plus clopidogrel: the Clopidogrel-Aspirin Atrial Fibrillation (CLAAF) pilot study.

PubMed

Lorenzoni, Roberto; Lazzerini, Guido; Cocci, Franca; De Caterina, Raffaele

2004-07-01

We evaluated the short-term safety and efficacy of aspirin-plus-clopidogrel as antithrombotic therapy in nonvalvular atrial fibrillation (AF). Thirty patients (11 women, 45 to 75 years of age) with non-high-risk permanent (n = 12) or persistent AF awaiting cardioversion (n = 18) underwent transesophageal echocardiography to exclude left heart thrombi and were then randomly assigned to receive warfarin (international normalized ratio, 2 to 3 for 3 weeks) or aspirin (100 mg/d alone for 1 week)-plus-clopidogrel (75 mg/d added to aspirin for 3 weeks). Bleeding time and serum thromboxane B2 were measured at entry and at 3 weeks. Bleeding time, not affected by warfarin, was prolonged by 71% by aspirin (P <.05) and further, by 144%, by adding clopidogrel (P <.01 vs aspirin alone; +319%, P <.01, vs baseline). Thromboxane B2, not affected by warfarin, was reduced by aspirin (-98%, P <.01) but not further by clopidogrel. No thrombi or dense spontaneous echo-contrast were found at the 3-week transesophageal echocardiography. Seven of 9 patients receiving warfarin and 7 of 9 patients receiving aspirin-plus-clopidogrel, undergoing electrical cardioversion, achieved sinus rhythm. No thromboembolic or hemorrhagic events occurred in both arms throughout the 3-week treatment and a further 3-month follow-up. Aspirin-plus-clopidogrel and warfarin were equally safe and effective in preventing thromboembolism in this small group of patients with non-high-risk AF.

Assessment methods for aspirin-mediated platelet antiaggregation in type 2 diabetic patients: degree of correlation between 2 point-of-care methods.

PubMed

Cubero Gómez, Jose M; Navarro Puerto, María A; Acosta Martínez, Juan; De Mier Barragán, María I; Pérez Santigosa, Pastor L; Sánchez Burguillos, Francisco; Molano Casimiro, Francisco; Pastor Torres, Luis

2014-07-01

Impaired response to antiplatelet therapy in diabetic patients results in a higher incidence of drug-eluting stent thrombosis. This study determined the prevalence of high on-aspirin (AS) platelet reactivity in type 2 diabetic patients treated with percutaneous coronary intervention (PCI) using the VerifyNow Aspirin Assay (VN) and platelet function analyzer PFA-100 (PFA-100) and analyzed the correlation between both methods. Type 2 diabetic patients (100) with non-ST-elevation acute coronary syndrome who underwent PCI and Xience V drug-eluting stent implantation were included in this study. After PCI, platelet antiaggregation mediated by acetylsalicylic acid was assessed by VN and PFA-100. The degree of correlation and concordance was then determined. When assayed with VN, 7% of the patients were nonresponders to aspirin (aspirin reaction units >550), and when assayed with PFA-10, 41% were nonresponders (closure time <193 seconds). Of the patients, 4% were nonresponders to aspirin according to VN but were sensitive to aspirin according to PFA-100, and 38% were sensitive to aspirin according to VN and nonresponders according to PFA-100. Overall, 55% of the patients were aspirin-sensitive in both methods. The Spearman's coefficient between VN and PFA-100 results was r = 0.09 (P = 0.35). The kappa index value was 0.0062 (P = 0.91). There is no concordance or correlation between the VN and PFA-100 results. Therefore, the use of these analyses should be restricted to clinical research, which limits its application in clinical practice.

Biological properties of citral and its potential protective effects against cytotoxicity caused by aspirin in the IEC-6 cells.

PubMed

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

2017-03-01

Citral, 3,7-dimethyl-2,6-octadienal, is a key component of several essential oils extracted from lemon-scented herbal plants. The present study was designed to investigate the antioxidant activities of citral and assess its possible protective effects against aspirin-induced toxicity in vitro. We used IEC-6 cells (rat small intestine epithelial cells). The antioxidant activities were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH), β-carotene/linoleic acid and Ferric reducing antioxidant power (FRAP). Cytotoxicity was evaluated by cell viability, anti-oxidant enzyme activities, malondialdehyde (MDA) production and by the expression of MAPKs (Mitogen-Activated Protein Kinases) pathways. According to results, citral showed an important antioxidant activity. It inhibited the oxidation of linoleic acid, a moderate DPPH was found and it showed a Ferric reducing antioxidant potential with an EC 50 value of 125±28.86μg/mL. Then, the co-treatment of aspirin with citral significantly decreased the aspirin-induced cell death, and the MDA level. It modulated the superoxide dismutase (SOD) and glutathione (GSH) activities. Also, the activation of MAPKs was attenuated by citral. These findings suggest that citral can protect IEC-6 cells against aspirin-induced oxidative stress that may help to discover new chemicals out of natural antioxidant substances. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Is there an ideal way to initiate antiplatelet therapy with aspirin? A crossover study on healthy volunteers evaluating different dosing schemes with whole blood aggregometry

PubMed Central

2011-01-01

Background Guidelines recommend an early initiation of aspirin treatment in patients with acute cerebral ischemia. Comparative studies on the best starting dose for initiating aspirin therapy to achieve a rapid antiplatelet effect do not exist. This study evaluated the platelet inhibitory effect in healthy volunteers by using three different aspirin loading doses to gain a model for initiating antiplatelet treatment in acute strokes patients. Methods Using whole blood aggregometry, this study with a prospective, uncontrolled, open, crossover design examined 12 healthy volunteers treated with three different aspirin loading doses: intravenous 500 mg aspirin, oral 500 mg aspirin, and a course of 200 mg aspirin on two subsequent days followed by a five-day course of 100 mg aspirin. Aspirin low response was defined as change of impedance exceeding 0 Ω after stimulation with arachidonic acid. Results Sufficient antiplatelet effectiveness was gained within 30 seconds when intravenous 500 mg aspirin was used. The mean time until antiplatelet effect was 74 minutes for 500 mg aspirin taken orally and 662 minutes (11.2 hours) for the dose scheme with 200 mg aspirin with a high inter- and intraindividual variability in those two regimes. Platelet aggregation returned to the baseline range during the wash-out phase within 4 days. Conclusion Our study reveals that the antiplatelet effect differs significantly between the three different aspirin starting dosages with a high inter- and intraindividual variability of antiplatelet response in our healthy volunteers. To ensure an early platelet inhibitory effect in acute stroke patients, it could be advantageous to initiate the therapy with an intravenous loading dose of 500 mg aspirin. However, clinical outcome studies must still define the best way to initiate antiplatelet treatment with aspirin. PMID:21466682

Effect of aspirin on tumour cell colony formation and evolution.

PubMed

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).

Anti-tumor and Anti-angiogenic Effects of Aspirin-PC in Ovarian Cancer

PubMed Central

Huang, Yan; Lichtenberger, Lenard M.; Taylor, Morgan; Bottsford-Miller, Justin N.; Haemmerle, Monika; Wagner, Michael J.; Lyons, Yasmin; Pradeep, Sunila; Hu, Wei; Previs, Rebecca A.; Hansen, Jean M.; Fang, Dexing; Dorniak, Piotr L.; Filant, Justyna; Dial, Elizabeth J.; Shen, Fangrong; Hatakeyama, Hiroto; Sood, Anil K.

2016-01-01

To determine the efficacy of a novel and safer (for gastrointestinal tract) aspirin (aspirin-PC) in preclinical models of ovarian cancer, in vitro dose-response studies were performed to compare the growth-inhibitory effect of aspirin-PC vs. aspirin on 3 human (A2780, SKOV3ip1, HeyA8), and a mouse (ID8) ovarian cancer cell line over an 8-day culture period. In the in vivo studies, the aspirin test drugs were studied alone and in the presence of a VEGF-A inhibitor (bevacizumab or B20), due to an emerging role for platelets in tumor growth following anti-angiogenic therapy, and we examined their underlying mechanisms. Aspirin-PC was more potent (vs. aspirin) in blocking the growth of both human and mouse ovarian cancer cells in monolayer culture. Using in vivo model systems of ovarian cancer, we found that aspirin-PC significantly reduced ovarian cancer growth by 50–90% (depending on the ovarian cell line/density). The efficacy was further enhanced in combination with Bevacizumab or B20. The growth-inhibitory effect on ovarian tumor mass and number of tumor nodules was evident, but less pronounced for aspirin and the VEGF inhibitors alone. There was no detectable gastrointestinal toxicity. Both aspirin and aspirin-PC also inhibited cell proliferation, angiogenesis and increased apoptosis of ovarian cancer cells. In conclusion, PC-associated aspirin markedly inhibits the growth of ovarian cancer cells, which exceeds that of the parent drug, in both cell culture and in mouse model systems. We also found that both aspirin-PC and aspirin have robust anti-neoplastic action in the presence of VEGF blocking drugs. PMID:27638860

Baseline Oral 5-ASA Use and Efficacy and Safety of Budesonide Foam in Patients with Ulcerative Proctitis and Ulcerative Proctosigmoiditis: Analysis of 2 Phase 3 Studies

PubMed Central

Sandborn, William J.; Rubin, David T.; Harper, Joseph R.

2016-01-01

Background: Rectal budesonide foam is a second-generation corticosteroid efficacious for active mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. This subgroup analysis examined the impact of baseline oral 5-aminosalicylic acid (5-ASA) on the efficacy and safety of budesonide foam in patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis. Methods: Patients received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo, with or without continued stable dosing of baseline oral 5-ASAs, for remission induction at week 6 (primary endpoint) in 2 identically designed, randomized, double-blind, phase 3 studies. Results: Of the 267 and 279 patients randomized to treatment with budesonide foam or placebo (pooled population), 55.1% and 55.2%, respectively, reported baseline 5-ASA use. A significantly greater percentage of patients achieved remission with budesonide foam versus placebo, either with (42.2% versus 31.8%, respectively; P = 0.03) or without (40.0% versus 14.4%; P < 0.0001) baseline 5-ASA use at week 6. A significantly greater percentage of patients achieved a Modified Mayo Disease Activity Index rectal bleeding subscale score of 0 at week 6, regardless of baseline 5-ASA use (5-ASA, 50.3% versus 35.7%; P = 0.003: no 5-ASA, 45.8% versus 19.2%; P < 0.0001). The frequency of adverse events was comparable between groups, regardless of baseline 5-ASA use. Conclusions: Budesonide foam was efficacious and safe for induction of remission of mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis in patients receiving oral 5-ASA at baseline and those who were not (Clinicaltrials.gov: NCT01008410 and NCT01008423). PMID:27416045

ASCORBIC ACID RETENTION AND COLOR OF STRAWBERRIES AS RELATED TO LOW-LEVEL IRRADIATION AND STORAGE TIME

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wells, C.E.; Tichenor, D.A.; Martin, D.C.

1963-01-01

Freshly picked strawberries were irradiated in a gamma source and ascorbic acid (ASA) and its oxidative breakdown products were measured at intervals during 3 to 6 months' storage. Reduced ASA, dehydroascorbic acid (DHA), diketogulonic acid (DKA), and total ASA were determined in unirradiated strawberries and in strawberries receiving 0.3 and 0.8 Mrad. Irradiation caused a significant loss of total ASA. Storage at 35 un. Concent 85% F for 180 days resulted in further losses, most of which occurred during the first 95 days. Addition of a glucose oxidase packet to atmospheric packs did not affect retention of total ASA. Amore » significant amount of reduced ASA was destroyed by irradiation, the loss being greater at the higher level used. Relatively large amounts er irradiation in the presence of almost complete retention of total ASA indicated that the degradation followed the usual pattern: reduced ASA to DHA to DKA. After 180 days storage, practically all of the reduced ASA was destroyed in air-packed irradiated samples, but comparable glucose-oxidase-packed samples retained 33 to 47% of their original reduced ASA. Measurement of the Gardner a color value revealed a significant able color variability among samples. Color losses were higher at higher doses. (H.R.D.)« less

Aspirin and the prevention of venous thromboembolism following total joint arthroplasty

PubMed Central

Azboy, I.; Barrack, R.; Thomas, A. M.; Haddad, F. S.; Parvizi, J.

2017-01-01

The number of arthroplasties being performed increases each year. Patients undergoing an arthroplasty are at risk of venous thromboembolism (VTE) and appropriate prophylaxis has been recommended. However, the optimal protocol and the best agent to minimise VTE under these circumstances are not known. Although many agents may be used, there is a difference in their efficacy and the risk of bleeding. Thus, the selection of a particular agent relies on the balance between the desire to minimise VTE and the attempt to reduce the risk of bleeding, with its undesirable, and occasionally fatal, consequences. Acetylsalicylic acid (aspirin) is an agent for VTE prophylaxis following arthroplasty. Many studies have shown its efficacy in minimising VTE under these circumstances. It is inexpensive and well-tolerated, and its use does not require routine blood tests. It is also a ‘milder’ agent and unlikely to result in haematoma formation, which may increase both the risk of infection and the need for further surgery. Aspirin is also unlikely to result in persistent wound drainage, which has been shown to be associated with the use of agents such as low-molecular-weight heparin (LMWH) and other more aggressive agents. The main objective of this review was to summarise the current evidence relating to the efficacy of aspirin as a VTE prophylaxis following arthroplasty, and to address some of the common questions about its use. There is convincing evidence that, taking all factors into account, aspirin is an effective, inexpensive, and safe form of VTE following arthroplasty in patients without a major risk factor for VTE, such as previous VTE. Cite this article: Bone Joint J 2017;99-B:1420–30. PMID:29092979

Theoretical modeling of infrared spectra of aspirin and its deuterated derivative

NASA Astrophysics Data System (ADS)

Boczar, Marek; Wójcik, Marek J.; Szczeponek, Krzysztof; Jamróz, Dorota; Zi e̡ba, Adam; Kawałek, Bożena

2003-01-01

Theoretical simulation of the νs stretching band is presented for aspirin (acetylsalicylic acid) and its OD derivative at 300 and 77 K. The simulation takes into account an adiabatic coupling between the high-frequency O-H(D) stretching and the low-frequency intermolecular O⋯O stretching modes, linear and quadratic distortions of the potential energy for the low-frequency vibrations in the excited state of the O-H(D) stretching vibration, resonance interaction between two hydrogen bonds in the dimer, and Fermi resonance between the O-H(D) stretching and the overtone of the O-H(D) bending vibrations. The effect of deuteration and the temperature has been successfully reproduced by our model calculations. Infrared, far-infrared, Raman and low-frequency Raman spectra of the polycrystalline aspirin have been measured. The geometry and experimental frequencies are compared with the results of our B3LYP/6-31++G** calculations.

78 FR 32477 - ASA Gold and Precious Metals Limited; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-30

... strategy consistent with its current fundamental investment policy and to achieve its desired portfolio... approval of its shareholders, ASA replaced its fundamental investment policies that, among other things... SECURITIES AND EXCHANGE COMMISSION [Investment Company Act Release No. 30539; 812-13877] ASA Gold...

Nutrient and Food Group Analysis in the 2016 ASA24® System

Cancer.gov

Researchers, clinicians, and educators can use the ASA24 system to analyze 65 nutrients and 37 food groups (U.S. and Canadian versions) from food recall or record data. Analyses for ASA24-Australia-2016 provide 41 nutrients and no food groups.

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.

PubMed

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 < .001), whereas the difference between ticagrelor alone vs aspirin alone was not statistically significant (6.3% [95% CI, -1.1% to 13.7%]; P = .10). Five major bleeding

Aspirin inhibits surface glycoprotein IIb/IIIa, P-selectin, CD63, and CD107a receptor expression on human platelets.

PubMed

McKenzie, Marcus E; Malinin, Alex I; Bell, Christopher R; Dzhanashvili, Alex; Horowitz, Eric D; Oshrine, Benjamin R; Atar, Dan; Serebruany, Victor L

2003-04-01

Platelet inhibition after aspirin therapy reduces the risk for the development of acute coronary syndromes. However, the mechanism by which aspirin affect platelets other than by prostaglandin blockade is unclear. We sought to determine the in vitro effects of aspirin on the surface expression of nine platelet receptors using whole blood flow cytometry. Blood from 24 healthy volunteers was incubated for 30 min with 1.8 and 7.2 mg/l phosphate-buffered saline-diluted acetylsalicylic acid in the presence or absence of apyrase. Platelet serotonin release, and the surface expression of platelet receptors with or without apyrase were determined using the following monoclonal antibodies: anit-CD41 [glycoprotein (GP)IIb/IIIa], CD42b (GPIb), CD62p (P-selectin), CD51/CD61 (vitronectin receptor), CD31 [platelet/endothelial cellular adhesion molecule-1 (PECAM-1)], CD107a [lysosomal associated membrane protein (LAMP)-1], CD107b (LAMP-2), CD63 (LIMP or LAMP-3), and CD151 (PETA-3). Samples were then immediately fixed with 2% paraformaldehyde, and run on the flow cytometer within 48 h. Aspirin does not affect serotonin release from human platelets. Dose-dependent inhibition of GPIIb/IIIa, P-selectin, CD63, and CD107a receptor expression was observed in the aspirin-treated whole-blood samples. Apyrase potentiates the effects of aspirin, and independently inhibits PECAM-1. In addition to the known effect of irreversibly inhibiting platelet cyclooxygenase-1, thereby blocking thromboxane A(2) synthesis, it appears that aspirin exhibits direct effects on selective major platelet receptors.