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Sample records for drugs aspirin nimesulide

  1. Effect of different non-steroidal anti-inflammatory drugs, aspirin, nimesulide and celecoxib on the disaccharide hydrolases and histoarchitecture of the rat intestinal brush border membrane.

    PubMed

    Sood, N; Kaushal, N; Sanyal, S N

    2008-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause gastrointestinal damage. New anti-inflammatory drugs have been developed in an attempt to improve their gastrointestinal side effect profile which however failed to do so. Therefore, the objective of the present study was to compare the effect of three different NSAIDs, aspirin, nimesulide and celecoxib on the intestinal brush border membrane (BBM) marker enzymes and correlate these alterations to the histoarchitecture of the intestine using electron microscopic study. Female Wistar rats were divided into four different groups viz: Group I (Control), Group II (aspirin treated), Group III (nimesulide treated) and Group IV (celecoxib treated). The Group II, III and IV received the corresponding drugs dissolved in water orally at a dose of 40 mg/kg body weight, while the control received the vehicle only. After 28 days, all the treatment groups demonstrated significant alterations in the activities of intestinal disaccharide hydrolases and alkaline phosphatase in both the crude homogenates and BBM preparations as well. The histopathological observations also showed considerable changes in the intestinal mucosa. It was suggested that NSAIDs like aspirin, nimesulide and celecoxib pose intestinal side effects due to initial changes in the enzymatic composition of the intestinal apical membranes. It was further concluded that newly discovered NSAIDs such as celecoxib has better safety profiles but studies are still required to comment decisively on the suitability of various NSAIDs depending upon their cyclooxygenase enzyme specificity.

  2. Modulations in the intestinal disaccharide hydrolases and membrane dynamics: effect of non-steroidal anti-inflammatory drugs aspirin and nimesulide.

    PubMed

    Kaushal, Naveen; Sanyal, S N

    2007-01-01

    The present study was designed to evaluate the influence of two commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and nimesulide on the biochemical composition and membrane dynamics of rat intestine. Female Wistar rats were divided into three different groups viz: Group I (Control), Group II (aspirin-treated, 50 mg/kg body weight) and Group III (nimesulide-treated, 10 mg/kg body weight). After 28 days, biochemical estimations in both drug treated groups showed an increase in sucrase, lactase, maltase and alkaline phosphatase as compared to the control. Alterations in the intestinal membrane dynamics by fluidity studies and Fourier Transform Infra Red (FTIR) spectroscopy also showed considerable changes. The alterations in the histoarchitecture of the intestine were also seen, which correlated well with the changes in structure and composition of the intestine. The use of NSAIDs like aspirin and nimesulide may cause the gastrointestinal side effects due to initial changes in the enzyme activities and membrane dynamics.

  3. Nimesulide in the treatment of patients intolerant of aspirin and other NSAIDs.

    PubMed

    Senna, G E; Passalacqua, G; Andri, G; Dama, A R; Albano, M; Fregonese, L; Andri, L

    1996-02-01

    Aspirin (acetylsalicylic acid) and other NSAIDs are responsible for many adverse effects. Among them, pseudo-allergic reactions (urticaria/angioedema, asthma, anaphylaxis) affect up to 9% of the population and up to 30% of asthmatic patients. The mechanisms provoking these reactions have not been fully elucidated, but it appears that inhibition of cyclo-oxygenase (COX) plays a central role. The anti-inflammatory action of nimesulide differs from that of other NSAIDs, possibly because of its chemical structure. In particular, nimesulide is selective for COX-2 and displays additional properties in terms of its effects on inflammatory mediator synthesis and release. For these reasons, nimesulide is generally well tolerated by NSAID-intolerant patients and patients with NSAID-induced asthma. The good tolerability of nimesulide as an alternative drug for use in patients with NSAID intolerance has been demonstrated in a large number of clinical studies.

  4. Liposomal Aloe vera trans-emulgel drug delivery of naproxen and nimesulide: A study

    PubMed Central

    Venkataharsha, Panuganti; Maheshwara, Ellutla; Raju, Y Prasanna; Reddy, Vayalpati Ashok; Rayadu, Bandugalla Sanjeev; Karisetty, Basappa

    2015-01-01

    Introduction: The present aim of this study was to formulate naproxen and nimesulide liposomal formulation for incorporation in Aloe vera transemulgel and to carry out in vitro and in vivo evaluation of the formulation. Material and Methods: A. vera gel was prepared and used as a gel base for formulation. Carbopol 934 is used as a gelling agent and Methyl paraben was used as a preservative for the formulation of the gel. Liposomes was formulated by using hydration method. The formulated naproxen and nimesulide liposomal formulation using A. vera trans-emul gel were evaluated for in vitro studies such as drug release, permeation study, and drug content and entrapment efficiency. Paw edema method in Wistar rats induced by carrageenan is used to study in vivo anti-inflammatory action. Result: From the in vitro studies such permeability drug release naproxen 65% (69.6), Nimesulide 65% (61.1), and commercial Nimsulide gel (60.82) at 240 min. In vivo data shows that formulated liposomal transemulgel formulation are superior in their efficacy compared to commercial and A. vera gel. The results are compared with the commercial formulations. Conclusion: From our results, it is concluded that the A. vera trans emul gel using nimesulide and naproxen liposomal formulation is stable and prepared gel base is effective for formulation with high drug release and drug content compared with commercial formulation with significant anti-inflammatory effect. PMID:25599030

  5. A comparative clinical trial evaluating efficacy and safety of fixed dose combination of nimesulide (100 mg) and racemethionine (50 mg) (namsafe) versus reference drug (nimesulide) and other NSAIDs in the treatment of osteoarthritis.

    PubMed

    Prabhu, V V

    2008-06-01

    Sixty consecutive patients of either sex, above the age of 18 years with symptoms of osteo-arthritis participated in this open, randomised, comparative clinical trial carried out over 3 months. Patients were randomised into 5 groups: Group A (paracetamol 500 mg), group B (ibuprofen 400 mg), group C (nimesulide 100 mg), group D (diclofenac 50 mg), and group E [fixed dose combination of nimesulide (100 mg) and racemethionine (50 mg) (namsafe)]. The efficacy parameters were pain intensity, pain on movement, tenderness and swelling. The liver function tests were carried out to estimate the effect of the drugs on the hepatic profile. The Wilcoxon signed rank test and the Kruskal Wallis (one way ANOVA) test were utilised to evaluate the significance of the change from baseline to the final visit. The treatment with combination of nimesulide and racemethionine gave the best relief from tenderness. With respect to pain intensity and pain movement, combination of nimesulide and racemethionine with nimesulide efficacy was comparable. Theliver function test data at the end of 6 months show that combination of nimesulide and racemethionine treated group showed the least rise in the serum asparatate aminotransferase and alanine aminotransferase levels, whereas in the other treatment groups it was very pronounced. Thereby, combination of nimesulide and racemethionine is found to be better for the long-term treatment of osteo-arthritis in patients. The combination of the two agents, namely nimesulide and racemethionine is expected to augment the safety profile of nimesulide, without influencing the effectiveness of the analgesic agent, i.e., nimesulide.

  6. Drug delivery investigations of quaternised poly(propylene imine) dendrimer using nimesulide as a model drug.

    PubMed

    Murugan, E; Geetha Rani, D P; Yogaraj, V

    2014-02-01

    This study describes the demonstration of quaternized poly(propylene imine) dendrimer of generation-3, QPPI (G3) as a drug carrier for poorly soluble drug nimesulide (NMD, an anti-inflammatory drug). QPPI (G3) was prepared by treating the surface amine groups of poly(propylene imine) dendrimer with glycidyltrimethyl ammonium chloride and it was characterized with FTIR, (1)H and (13)C NMR and MALDI-TOF mass spectral techniques. The drug carrying potential of QPPI (G3) was assessed by analyzing drug solubility, in vitro release and cytotoxicity studies. The observed results reveal that the aqueous solubility of NMD has been dramatically increased in the presence of QPPI (G3) and also can sustain the release of NMD. It is further noticed that the complexation of NMD with QPPI (G3) is responsible for increased solubility and sustained release. This complexation was evidenced through NMR ((1)H & 2D) and UV-vis spectral techniques, DSC and DLS studies. Cytotoxicity study through MTT assay on Vero and HBL-100 cell lines reveal that this dendrimer increase the biocompatibility and the tolerance concentration of NMD in drug-dendrimer formulations. The observed results prove that the QPPI (G3) is one of the new promising candidate for effective delivery of NMD.

  7. [Nimesulide: 25 years later].

    PubMed

    Mattia, C; Ciarcia, S; Muhindo, A; Coluzzi, F

    2010-08-01

    The first marketing authorization for nimesulide was approved in Italy in 1985. After one quarter of a century we evaluate its peculiar characteristics compared with other NSAIDs. Nimesulide is the only NSAID related to the arylsulfonamide class and is a "COX-2 preferential NSAIDs", because despite having a prevalent effect on COX-2, has a balanced action on both cyclooxygenase. The gastrointestinal absorption is rapid and complete and explains the short onset of action. Nimesulide is rapidly distributed in the synovial fluid, where it persists longer than in the blood, thus contributing to effectiveness of the drug in pain control. From the standpoint of safety, nimesulide arises NSAIDs with lower risk of upper gastrointestinal bleeding thanks to its preferential activity on COX-2. In relation to the risk of severe hepatic reactions, the benefit/risk profile of nimesulide was considered by european regulatory authorities similar to other NSAIDs. Respecting international guidelines, the use of nimesulide in pain management, as that of other NSAIDs, must be considered as an alternative therapy when paracetamol is ineffective, or where the pain is caused or supported by an inflammatory process.

  8. Hyaluronic acid–nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo

    PubMed Central

    Jian, You-Sin; Chen, Ching-Wen; Lin, Chih-An; Yu, Hsiu-Ping; Lin, Hua-Yang; Liao, Ming-Yuan; Wu, Shu-Huan; Lin, Yan-Fu; Lai, Ping-Shan

    2017-01-01

    Carrier-mediated drug delivery systems are promising therapeutics for targeted delivery and improved efficacy and safety of potent cytotoxic drugs. Nimesulide is a multifactorial cyclooxygenase 2 nonsteroidal anti-inflammatory drug with analgesic, antipyretic and potent anticancer properties; however, the low solubility of nimesulide limits its applications. Drugs conjugated with hyaluronic acid (HA) are innovative carrier-mediated drug delivery systems characterized by CD44-mediated endocytosis of HA and intracellular drug release. In this study, hydrophobic nimesulide was conjugated to HA of two different molecular weights (360 kDa as HA with high molecular weight [HAH] and 43kDa as HA with low molecular weight [HAL]) to improve its tumor-targeting ability and hydrophilicity. Our results showed that hydrogenated nimesulide (N-[4-amino-2-phenoxyphenyl]methanesulfonamide) was successfully conjugated with both HA types by carbodiimide coupling and the degree of substitution of nimesulide was 1%, which was characterized by 1H nuclear magnetic resonance 400 MHz and total correlation spectroscopy. Both Alexa Fluor® 647 labeled HAH and HAL could selectively accumulate in CD44-overexpressing HT-29 colorectal tumor area in vivo, as observed by in vivo imaging system. In the in vitro cytotoxic test, HA–nimesulide conjugate displayed >46% cell killing ability at a nimesulide concentration of 400 µM in HT-29 cells, whereas exiguous cytotoxic effects were observed on HCT-15 cells, indicating that HA–nimesulide causes cell death in CD44-overexpressing HT-29 cells. Regarding in vivo antitumor study, both HAL–nimesulide and HAH–nimesulide caused rapid tumor shrinkage within 3 days and successfully inhibited tumor growth, which reached 82.3% and 76.4% at day 24 through apoptotic mechanism in HT-29 xenografted mice, without noticeable morphologic differences in the liver or kidney, respectively. These results indicated that HA–nimesulide with improved selectivity

  9. Therapeutic effects of nitric oxide-aspirin hybrid drugs.

    PubMed

    Turnbull, Catriona M; Rossi, Adriano G; Megson, Ian L

    2006-12-01

    This review examines the therapeutic potential and mechanisms of action of drugs known as nitric oxide (NO)-aspirins. Drugs of this class have an NO-releasing moiety joined by ester linkage to the aspirin molecule. NO-aspirins have the capability to release NO in addition to retaining the cyclooxygenase-inhibitory action of aspirin. The protective nature of NO led to the development of NO-aspirins in the hope that they might avoid the gastric side effects associated with aspirin. However, it has become apparent that the drug-derived NO instills potential for a wide range of added beneficial effects over the parent compound. In this review, the authors focus on the analgesic, anti-inflammatory, cardiovascular and chemopreventative actions of compounds of this emerging drug class.

  10. Ex vivo Skin Permeation Evaluation of An Innovative Transdermal Vehicle Using Nimesulide and Piroxicam as Model Drugs.

    PubMed

    Pereira, Rafaela de Oliveira; Pelisson E Silva, Taize Carla Costa; de Oliveira Ferreira, Anderson; Brandao, Marcos Antonio Fernandes; Raposo, Nadia Rezende Barbosa; Polonini, Hudson Caetano

    2017-01-01

    The transdermal dosage forms presented a limited usage for a long time, for it was believed that the stratum corneum, the outermost layer of epidermis, made it impracticable the permeation of medications through the skin. Studies exploring this area came up with strategies to overcome this barrier; for example, creating a transdermal vehicle to facilitate the drug absorption. This study aimed to evaluate a new transdermal vehicle through the comparison of its permeation profile and the profile of commercial products, using nimesulide and piroxicam, non steroidal anti-inflammatory drugs. Four different products were evaluated: nimesulide and piroxicam compounded with the new vehicle (emulsion) and commercial nimesulide and piroxicam gels. Ex vivo permeation experiments using Franz-type diffusion cell equipment were conducted, using human skin as membrane. For evaluation of permeated active pharmaceutical ingredients concentrations, we performed quantification from the receptor solution, stratum corneum and viable epidermis + dermis, through high-performance liquid chromatography analyses. The new vehicle promoted increased permeation of active pharmaceutical ingredients through the viable epidermis and dermis, when compared to commercial products, but the stratum corrneum continued to keep the highest retention. The innovative vehicle was capable of enhancing the transdermal absorption of active pharmaceutical ingredients from the compounded formulations, thus, demonstrating the capability thereof to improve the permeability of active pharmaceutical ingredients by transdermal use. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Pressure-temperature phase diagram of the dimorphism of the anti-inflammatory drug nimesulide.

    PubMed

    Barrio, M; Huguet, J; Robert, B; Rietveld, I B; Céolin, R; Tamarit, J Ll

    2017-06-15

    Understanding the phase behavior of active pharmaceutical ingredients is important for formulations of dosage forms and regulatory reasons. Nimesulide is an anti-inflammatory drug that is known to exhibit dimorphism; however up to now its stability behavior was not clear, as few thermodynamic data were available. Therefore, calorimetric melting data have been obtained, which were found to be TI-L=422.4±1.0K, ΔI→LH=117.5±5.2Jg(-1),TII-L=419.8±1.0K and ΔII→LH=108.6±3.3Jg(-1). In addition, vapor-pressure data, high-pressure melting data, and specific volumes have been obtained. It is demonstrated that form II is intrinsically monotropic in relation to form I and the latter would thus be the best polymorph to use for drug formulations. This result has been obtained by experimental means, involving high-pressure measurements. Furthermore, it has been shown that with very limited experimental and statistical data, the same conclusion can be obtained, demonstrating that in first instance topological pressure-temperature phase diagrams can be obtained without necessarily measuring any high-pressure data. It provides a quick method to verify the phase behavior of the known phases of an active pharmaceutical ingredient under different pressure and temperature conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. 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 ...

  13. 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

  14. Genetics of hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs.

    PubMed

    Kim, Seung-Hyun; Sanak, Marek; Park, Hae-Sim

    2013-05-01

    Various hypersensitivity reactions have been reported with aspirin and nonsteroidal anti-inflammatory drugs. Hypersensitivity can occur regardless of a chemical drug structure or its therapeutic potency. Allergic conditions include aspirin-exacerbated respiratory disease (AERD or aspirin-induced asthma), aspirin-induced urticaria/angioedema (AIU), and anaphylaxis. Several genetic studies on aspirin hypersensitivity have been performed to discover the genetic predisposition to aspirin hypersensitivity and to gain insight into the phenotypic diversity. This article updates data on the genetic mechanisms that govern AERD and AIU and summarizes recent findings on the molecular genetic mechanism of aspirin hypersensitivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Drug interactions involving aspirin (acetylsalicylic acid) and salicylic acid.

    PubMed

    Miners, J O

    1989-11-01

    Aspirin (acetylsalicylic acid) is metabolically converted to salicyclic acid by the action of carboxylesterases. Although metabolic drug interactions involving aspirin are theoretically possible, there appear to have been no studies to date which have shown conclusively that aspirin hydrolysis is altered by coadministered drugs. However, a number of treatments are known to affect the rate or extent of aspirin absorption, including activated charcoal, antacids, cholestyramine and metoclopramide. Caffeine and metoprolol have been reported to increase peak salicylic acid concentration following aspirin administration, and coadministration of dipyridamole and aspirin results in higher plasma aspirin concentrations. The mechanism(s) responsible for these latter observations remains unknown. Salicylic acid is extensively bound to plasma albumin, and many of the reported drug interactions involve displacement of the coadministered drug from plasma protein. Protein binding displacement appears to be the basis of salicylic acid interactions with diclofenac, flurbiprofen, ibuprofen, isoxicam, ketoprofen, naproxen, phenytoin and tolmetin. Following displacement of these agents increased clearance of total drug occurs, and consequently the plasma concentration of total drug decreases. Although generally not measured, unbound concentration of the interacting drug should not be markedly altered. Salicylic acid also increases total plasma clearance of fenoprofen but, unlike the interactions with the other propionic acid non-steroidals, plasma protein binding displacement does not appear to be involved. Induction of fenoprofen metabolism is a possibility, although there is no firm evidence from other studies that salicylate is able to induce the metabolism of coadministered drugs. Since salicylic acid is extensively metabolised, it is not surprising that it is able to inhibit the metabolism of certain coadministered drugs and chemicals, an effect which has been reported for

  16. Aspirin

    MedlinePlus

    ... occurs when the heart does not get enough oxygen). Nonprescription aspirin is also used to reduce the ... medications called salicylates. It works by stopping the production of certain natural substances that cause fever, pain, ...

  17. The aspirin story - from willow to wonder drug.

    PubMed

    Desborough, Michael J R; Keeling, David M

    2017-06-01

    The story of the discovery of aspirin stretches back more than 3500 years to when bark from the willow tree was used as a pain reliever and antipyretic. It involves an Oxfordshire clergyman, scientists at a German dye manufacturer, a Nobel Prize-winning discovery and a series of pivotal clinical trials. Aspirin is now the most commonly used drug in the world. Its role in preventing cardiovascular and cerebrovascular disease has been revolutionary and one of the biggest pharmaceutical success stories of the last century. © 2017 John Wiley & Sons Ltd.

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

    PubMed Central

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

    2013-01-01

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

  19. Preparation and characterization of nimesulide containing nanocrystal formulations.

    PubMed

    Gülsün, Tuğba; Budak, Cisem; Vural, Imran; Sahin, Selma; Öner, Levent

    2013-01-01

    The aim of this study was to develop and characterize nanocrystal formulation containing nimesulide. Physical mixture of drug and excipient (nimesulide:pluronic F127, 1:0.5) was also prepared to compare the efficiency of formulations. The physicochemical characteristics of the formulations were determined by means of Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray diffractometry. Particle size, saturation solubilities as a function of pH, and permeability across Caco-2 monolayers were determined for nimesulide in powder, physical mixture, and nanocrystal formulations. In FT-IR analysis, the characteristic peaks that belong to nimesulide were seen in all formulations. X-ray diffractograms displayed that crystalline structure of nimesulide was conserved in the nanocrystal formulation. The interaction between nimesulide and pluronic F127 was demonstrated by DSC analysis. In all conditions, the average particle size of the nanocrystal formulations decreased significantly (p < 0.05) as compared with nimesulide and physical mixture. The solubility of nimesulide in nanocrystal formulation was higher than those of nimesulide in powder and physical mixture. Permeability studies revealed that nimesulide is a highly permeable compound whether in powder form or in physical mixture and nanocrystal formulation. All these results clearly demonstrate that aqueous solubility of poorly water-soluble compounds can be improved by preparing nanocrystal formulations.

  20. Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs.

    PubMed

    Li, Xuanwen; Fries, Susanne; Li, Ruizhi; Lawson, John A; Propert, Kathleen J; Diamond, Scott L; Blair, Ian A; FitzGerald, Garret A; Grosser, Tilo

    2014-11-25

    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.

  1. 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

  2. Nimesulide: patients still exposed to a risk of severe hepatitis.

    PubMed

    2011-05-01

    Nimesulide, a nonsteroidal antiinflammatory drug (NSAID) that has been marketed in France since 1998, is neither more effective nor better tolerated than other NSAIDs. Many reports and reviews published by drug regulatory agencies in Spain, Ireland and Italy have warned of the hepatic adverse effects of nimesulide. In early 2008, 17 cases of nimesulide-induced liver damage requiring transplantation had been reported in Ireland, Italy, Spain, Finland and France. An Italian retrospective study conducted between 1997 and 2001, including about 400 000 patients exposed to NSAIDs, showed that the risk of severe liver damage was twice as high with nimesulide as with other NSAIDs. The European pharmacovigilance database shows that nimesulide is associated with more cases of severe liver damage than other NSAIDs, as well as more cases of liver damage than with cox-2 inhibitors. Young women are particularly at risk. In the vast majority of cases of liver damage, the dose of nimesulide used was that recommended in the summary of product characteristics (SPC). Liver damage occurred within 15 days after taking the first dose of nimesulide in one-third of cases. It is unacceptable that nimesulide still remains on the market in France and other countries: reports of severe liver damage continue to accumulate, and many other therapeutic options are available.

  3. Aspirin and blood pressure: Effects when used alone or in combination with antihypertensive drugs.

    PubMed

    Costa, Ana Catarina; Reina-Couto, Marta; Albino-Teixeira, António; Sousa, Teresa

    Arterial hypertension is a major risk factor for cardiovascular and renal events. Lowering blood pressure is thus an important strategy for reducing morbidity and mortality. Since low-dose aspirin is a cornerstone in the prevention of adverse cardiovascular outcomes, combined treatment with aspirin and antihypertensive drugs is very common. However, the impact of aspirin therapy on blood pressure control remains a subject of intense debate. Recent data suggest that the cardioprotective action of aspirin extends beyond its well-known antithrombotic effect. Aspirin has been shown to trigger the synthesis of specialized pro-resolving lipid mediators from arachidonic acid and omega-3 fatty acids. These novel anti-inflammatory and pro-resolving mediators actively stimulate the resolution of inflammation and tissue regeneration. Additionally, they may contribute to other protective effects on redox status and vascular reactivity that have also been attributed to aspirin. Of note, aspirin has been shown to improve vasodilation through cyclooxygenase-independent mechanisms. On the other hand, higher aspirin doses have been reported to exert a negative impact on blood pressure due to inhibition of cyclooxygenase-2 activity, which reduces renal blood flow, glomerular filtration rate and sodium and water excretion. This review aims to provide an overview of the effects of aspirin on blood pressure and the underlying mechanisms, focusing on the interaction between aspirin and antihypertensive drugs. Studies in both experimental and human hypertension are presented. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Sodium N-(methylsulfonyl)-N-(4-nitro-2-phenoxyphenyl)sulfamate: a water-soluble nimesulide prodrug for parenteral use.

    PubMed

    Rapposelli, Simona; Digiacomo, Maria; Franchi, Silvia; Moretti, Sara; Pinza, Mario; Sacerdote, Paola; Balsamo, Aldo

    2010-10-04

    Several nimesulide preparations (i.e., tablet form, gels) have been marketed, but no parenteral solution has achieved the market because of their low wettability and unsatisfactory chemical-physical properties required for parenteral use. In this paper we describe the synthesis of the nimesulide prodrug 1 and its anti-inflammatory and antihyperalgesic properties. Pharmacological studies, carried out to evaluate the in vivo anti-inflammatory and analgesic activities of compound 1 and nimesulide, showed that sodium sulfamate 1 is an effective nimesulide prodrug that can be administered by parenteral route, undergoing a satisfactory absorption and an extensive transformation into the active nimesulide compound. Moreover, the evaluation of the plasma concentrations of nimesulide after rat treatment with compound 1 showed an increased and dose-dependent release of nimesulide. In contrast, the plasma concentrations of nimesulide, after "native" drug administration, still remain substantially unchanged. These preliminary results prompt further investigations on this prodrug as a possible candidate for parenteral use.

  5. Stress modification of the toxicity of antimotion sickness drugs and Aspirin

    NASA Technical Reports Server (NTRS)

    Shields, D.; Marra, C.; Goodwin, A.; Vernikos-Danellis, J.

    1975-01-01

    The effect of environmental temperature on the toxicity of cyclizine, trimethobenzamide, and Aspirin were studied in mice. LD-50s were compared at 30 C, 22 C, and 15 C. At 30 C the toxicity of all three drugs increased, with that to Aspirin being affected most. Cooling decreased the toxicity of cyclizine and had no significant effect on that of trimethobenzamide or aspirin. These findings indicate that alterations in environmental temperature markedly affect drug toxicity. They emphasize that such alterations, and particularly increases in temperature, do not have to be particularly drastic, but that 'mild' variations in the environment are effective in altering an animal's sensitivity to a drug.

  6. Stress modification of the toxicity of antimotion sickness drugs and Aspirin

    NASA Technical Reports Server (NTRS)

    Shields, D.; Marra, C.; Goodwin, A.; Vernikos-Danellis, J.

    1975-01-01

    The effect of environmental temperature on the toxicity of cyclizine, trimethobenzamide, and Aspirin were studied in mice. LD-50s were compared at 30 C, 22 C, and 15 C. At 30 C the toxicity of all three drugs increased, with that to Aspirin being affected most. Cooling decreased the toxicity of cyclizine and had no significant effect on that of trimethobenzamide or aspirin. These findings indicate that alterations in environmental temperature markedly affect drug toxicity. They emphasize that such alterations, and particularly increases in temperature, do not have to be particularly drastic, but that 'mild' variations in the environment are effective in altering an animal's sensitivity to a drug.

  7. Precipitating factors in asthma. Aspirin, sulfites, and other drugs and chemicals.

    PubMed

    Mathison, D A; Stevenson, D D; Simon, R A

    1985-01-01

    Several types of reactions to drugs and chemicals may precipitate or perpetuate asthmatic relapse. This review focuses on reactions to aspirin and sulfites. Approximately 40 percent of patients with rhinosinusitis, nasal polyps, and asthma and 5 to 10 percent of all asthmatic patients are sensitive to aspirin and aspirin-like nonsteroidal anti-inflammatory drugs at some time in their course. A prudent recommendation to all asthmatics is to substitute acetaminophen for aspirin. When aspirin/aspirin-like drug is essential for treatment of cardiovascular or musculoskeletal disorder, desensitization by cautious oral challenges with graded doses of aspirin can be accomplished. Treatment of the respiratory disorder per se by desensitization followed by daily therapeutic aspirin remains investigational. Sulfur dioxide and sulfites, commonly used as sanitizers and preservatives of foods and pharmaceuticals, may precipitate acute asthma in 5 percent or more of asthmatic patients. When the history suggests sulfite sensitivity, challenges can be used to confirm sensitivity and the patient counseled in avoidance of these chemicals.

  8. Vestibular Schwannoma Growth With Aspirin and Other Nonsteroidal Anti-inflammatory Drugs.

    PubMed

    Hunter, Jacob B; O'Connell, Brendan P; Wanna, George B; Bennett, Marc L; Rivas, Alejandro; Thompson, Reid C; Haynes, David S

    2017-09-01

    To investigate whether the use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) impact the growth of vestibular schwannoma (VS). Retrospective case series. Single academic, tertiary care center. Patients with VS who underwent at least two magnetic resonance imaging (MRI) studies before intervention. Serial MRI studies. VS tumor growth, defined as more than or equal to 2 mm increase in the maximum tumor diameter between consecutive MRI studies, or between the first and last available study. Mean growth rate was also calculated, defined as the change in tumor size divided by length of follow-up. A total of 564 VS patients met inclusion criteria, with 234 (41.2%) taking some type of NSAID. Aspirin use was not associated with VS tumor growth, presenting tumor diameter, or mean VS growth rate. Further, aspirin dosage did not impact growth outcomes or presenting tumor diameter. A total of 96 (17.0%) patients took an NSAID other than aspirin. Neither non-aspirin NSAID use nor degree of cyclooxygenase-2 (COX-2) selectivity, including aspirin, was significantly associated with VS tumor growth, presenting tumor diameter, or mean VS growth rate. While previous studies have suggested a relationship between aspirin usage and VS growth, we found no significant association in our series of 564 observed VS. Furthermore, there was no apparent relationship between aspirin dosage, non-aspirin NSAID use, and COX-2 selectivity with VS growth, presenting tumor diameter at presentation, or mean VS growth rate.

  9. Somatic Drugs for Psychiatric Diseases: Aspirin or Simvastatin for Depression?

    PubMed Central

    Rahola, Juan Gibert

    2012-01-01

    The evolution in the understanding of the neurobiology of most prevalent mental disorders such as major depressive disorder (MDD), bipolar disorder or schizophrenia has not gone hand in hand with the synthesis and clinical use of new drugs that would represent a therapeutic revolution such as that brought about by selective serotonin reuptake inhibitors (SSRIs) or atypical antipsychotics. Although scientists are still a long way from understanding its true aetiology, the neurobiological concept of depression has evolved from receptor regulation disorder, to a neurodegenerative disorder with a hippocampal volume decrease with the controversial reduction in neurotrophins such as BDNF, to current hypotheses that consider depression to be an inflammatory and neuroprogressive process. As regards antidepressants, although researchers are still far from knowing their true mechanism of action, they have gone from monoaminergic hypotheses, in which serotonin was the main protagonist, to emphasising the anti-inflammatory action of some of these drugs, or the participation of p11 protein in their mechanism of action. In the same way, according to the inflammatory hypothesis of depression, it has been proposed that some NSAIDS such as aspirin or drugs like simvastatin that have an anti-inflammatory action could be useful in some depressive patients. Despite the fact that there may be some data to support their clinical use, common sense and the evidence advise us to use already tested protocols and wait for the future to undertake new therapeutic strategies. PMID:23204984

  10. Ab initio study of pristine and Si-doped capped carbon nanotubes interacting with nimesulide molecules

    NASA Astrophysics Data System (ADS)

    Zanella, Ivana; Fagan, Solange B.; Mota, R.; Fazzio, A.

    2007-05-01

    The interaction of the nimesulide molecule with pristine and Si-doped capped carbon nanotubes is studied by first-principle calculations. The nimesulide molecules, which are basic components of an anti-inflammatory drug, combined with carbon nanostructures, could result in novel drug delivery systems. In this Letter, the nimesulide interaction with pristine capped nanotubes is shown as occuring in a physisorption regime and it is demonstrated that this interaction can be much more intense when the capped nanotube is substitutionaly doped with an Si atom. Then, the Si-doped capped nanotube can constitute a feasible novel nimesulide molecule delivery system.

  11. Mechanistic insights into a classic wonder drug--aspirin.

    PubMed

    Lei, Jinping; Zhou, Yanzi; Xie, Daiqian; Zhang, Yingkai

    2015-01-14

    Aspirin, one of the oldest and most common anti-inflammatory agents, has recently been shown to reduce cancer risks. The principal pharmacological effects of aspirin are known to arise from its covalent modification of cyclooxygenase-2 (COX-2) through acetylation of Ser530, but the detailed mechanism of its biochemical action and specificity remains to be elucidated. In this work, we have filled this gap by employing a state-of-the-art computational approach, Born-Oppenheimer molecular dynamics simulations with ab initio quantum mechanical/molecular mechanical potential and umbrella sampling. Our studies have characterized a substrate-assisted inhibition mechanism for aspirin acetylating COX: it proceeds in two successive stages with a metastable tetrahedral intermediate, in which the carboxyl group of aspirin serves as the general base. The computational results confirmed that aspirin would be 10-100 times more potent against COX-1 than against COX-2, and revealed that this inhibition specificity between the two COX isoforms can be attributed mainly to the difference in kinetics rate of the covalent inhibition reaction, not the aspirin-binding step. The structural origin of this differential inhibition of the COX enzymes by aspirin has also been elucidated.

  12. Genotoxicity of nimesulide in Wistar rats.

    PubMed

    Borkotoky, Debojyoti; Panda, Sushen K; Sahoo, Gyana R; Parija, Subas C

    2014-04-01

    It is mandatory for all new drugs to be tested for their potential genotoxicity in addition to general toxicity testing. Some old drugs have not been tested adequately for their genotoxic effects because these were in use before the local regulations were enforced. According to the material safety database, the toxicological effect of nimesulide is not yet fully understood. The present study therefore aimed to explore the genotoxic potential of nimesulide in Wistar albino rats. Nimesulide at the dose level of 50 (Gr-50), 100 (Gr-100) and 200 (Gr-200) mg/kg body weight (b.w.) was given orally. Each rat in treated groups (Gr-50 to Gr-200; n = 10) and negative control group (Gr-NC; n = 10) were administered orally (p.o.) with nimesulide and normal saline, respectively, for 14 days. Similarly, rats of positive control (Gr-PC; n = 10) were administered with cyclophosphamide (CPA; 20 mg/kg b.w.) intraperitoneally. CPA served as positive control, whereas normal saline served as as negative control. Approximately 1-2 mL of blood was collected from retro-orbital sinus for comet assay and subsequently rats were sacrificed to aspirate the femoral bone marrow for the micronucleus test. Structural chromosomal aberration, micronucleated polychromatic erythrocytes (MnPCEs), polychromatic erythrocytes (PCEs) and comet tail length were calculated using micronucleus assay and comet assay, respectively, which served as markers of genotoxicity. In the present study, it was observed that a significant increase in (1) different classified structural chromosomal aberrations with increase in nimesulide dose, such as gaps (50 mg/kg), gaps, breaks and pulverizations (100 mg/kg) and gaps, breaks, fragments, rings and pulverizations (200 mg/kg) and (2) % MnPCE and comet tail length was observed in animals treated with CPA (p < 0.001) or 200 mg of nimesulide (p < 0.05), as compared to negative control. In conclusion, nimesulide (200 mg/kg b.w.) produced a

  13. Photochemical stability of nimesulide.

    PubMed

    Kovaríková, Petra; Mokrý, Milan; Klimes, Jirí

    2003-03-26

    HPLC and TLC methods for monitoring of the photochemical stability of nimesulide are presented. Solution of nimesulide sodium salt was exposed to the light of wavelengths 254 nm. The presence of degradation products (2-phenoxy4-nitroaniline and methanesulfonic acid) was observed. In the exposed sample, 2-phenoxy4-nitroaniline was detected by HPLC analysis and sulfonic acid was detected by TLC analysis. An isocratic HPLC chromatographic condition was described for determination of nimesulide in a presence of its degradation product. The sample was analysed on Separon SGX, C(18), 250 x 4.6 i.d. 7 microm analytical column. The mobile phase was consisted of a mixture of acetonitrile and ammonium phosphate (pH 7.9; 0.02 M) (35:65 v/v). UV detector was performed at 245 nm. Propylparaben was employed as an internal standard. Standard area response was linear respect to concentration of nimesulide over range 150-500 microg/ml. As a validation of the method, the accuracy and between-day precision were done. The detection limit of 2-phenoxy4-nitroaniline was 0.12 microg/ml. The solvent system for TLC analysis was consisted of ethylacetate and cyclohexane (45:55), the samples were plotted on silica gel UV-254 nm. UV lamp (254 nm) and the chemical detection were used.

  14. A pharmacokinetic/pharmacodynamic approach vs. a dose titration for the determination of a dosage regimen: the case of nimesulide, a Cox-2 selective nonsteroidal anti-inflammatory drug in the dog.

    PubMed

    Toutain, P L; Cester, C C; Haak, T; Laroute, V

    2001-02-01

    The present experiment was designed to determine a dosage regimen (dose, interval of administration) in the dog for nimesulide, a nonsteroidal anti-inflammatory drug with in vitro selectivity for the inhibition of cyclo-oxygenase 2 (Cox-2), using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The PK/PD results were compared with those obtained using a classical dose titration study. In the PK/PD experiment, 11 dogs were subjected to Freund's adjuvant arthritis characterized by permanent hyperthermia. Nimesulide (5 mg/kg, oral route) was tested during the secondary phase of the inflammatory response. In the dose titration study, nimesulide (0, 3, 6 and 9 mg/kg, oral route) was tested in eight other dogs using a reversible urate crystal arthritis in a 4-period crossover design. Different PD endpoints (including lameness assessed by force plate and hyperthermia) were regularly measured during the PK/PD experiment, and plasma samples were obtained to determine the plasma nimesulide concentration. The data were modeled using an indirect effect model. The IC50 of nimesulide for lameness was 6.26 +/- 3.01 microg/mL, which was significantly higher than the EC50 value obtained for antipyretic effect (2.72 +/- 1.29 microg/mL). The ED50 estimated from the classical dose titration study were 1.34 mg/kg (lameness) and 3.0 mg/kg (skin temperature). The PK/PD parameters were used to simulate different dosage regimens (dose, interval of administration). The antipyretic and anti-inflammatory effects were calculated from the model for the recommended dosage regimen (5 mg/kg/24 h). It was apparent from this approach, that this dosage regimen enabled 76% of the theoretical maximal drug efficacy to be obtained for pyresis and 43% for lameness. It was concluded from the comparison of in vivo and in vitro IC50, that nimesulide is a potent NSAID for which some Cox-1 inhibition is required to obtain clinically relevant efficacy.

  15. Study of nimesulide release from solid pharmaceutical formulations in tween 80 solutions.

    PubMed

    Purcaru, Stefana-Oana; Ionescu, Mihaela; Raneti, Cristina; Anuta, Valentina; Mircioiu, I; Belu, Ionela

    2010-01-01

    Nimesulide is a weakly acidic non-steroidal anti-inflammatory drug (NSAIDs). Like many non-steroidal anti-inflammatory drugs, Nimesulide is very sparingly soluble in water (≈ 0.01 mg/mL).The poor aqueous solubility and wettability of Nimesulide gives rise to difficulties in pharmaceutical formulations for oral or parenteral delivery, which may lead to variable bioavailability. Based on the Biopharmaceutical Classification System (BCS), Nimesulide is considered a BCS 2 drug (poorly soluble and highly permeable). Solubilization in surfactant solutions above critical micelle concentration (CMC) offers one approach to the formulation of poorly soluble drugs. Weakly acidic and basic drugs may be brought into solution by the solubilizing action of surfactants. In this study, different concentrations of Tween 80 was used in combination with buffer (pH 7.4) to increase the solubility of Nimesulide. The results show that the dependence of the released amount on the Tween concentration is not linear, very low Tween concentration showing a decrease of "solubility", probably connected to a critical micelle concentration at the interface Nimesulide solution. An "analytical" artefact connected to a decreasing ultraviolet absorption of Nimesulide because of Nimesulide precipitation, the formation of a colloidal solution is possible, and the phenomenon remains to be searched further. It is hard to explain that for an almost complete solubilization a significant Tween quantity is necessary and this should be more than that of other slightly soluble drugs.

  16. 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.

  17. Aspirin as a COX Inhibitor and Anti-inflammatory Drug in Human Skeletal Muscle.

    PubMed

    Ratchford, Steve M; Lavin, Kaleen M; Perkins, Ryan K; Jemiolo, Bozena; Trappe, Scott W; Trappe, Todd A

    2017-07-13

    Although aspirin is one of the most common anti-inflammatory drugs in the world, the effect of aspirin on human skeletal muscle inflammation is almost completely unknown. This study examined the potential effects and related time course of an orally consumed aspirin dose on the inflammatory PGE2/COX pathway in human skeletal muscle. Skeletal muscle biopsies were taken from the vastus lateralis of 10 healthy adults (5M/5F, 25±2y) before and 2, 4, and 24h after consuming a standard dose of aspirin (975mg) and partitioned for analysis of 1) in vivo PGE2 levels in resting skeletal muscle and 2) ex vivo skeletal muscle PGE2 production when stimulated with the COX substrate arachidonic acid (5μM). PGE2 levels in vivo and PGE2 production ex vivo were generally unchanged at each time point after aspirin consumption. However, most individuals clearly showed suppression of PGE2, but at varying time points after aspirin consumption. When the maximum suppression after aspirin consumption was examined for each individual, independent of time, both PGE2 levels in vivo (Pre: 184±17, Post: 104±23pg/g wet wt) and PGE2 production ex vivo (Pre: 2.74±0.17, Post: 2.09±0.11pg/mg wet wt/min) were reduced (P<0.05) by 44% and 24%, respectively. These results provide evidence that orally consumed aspirin can inhibit the COX pathway and reduce the inflammatory mediator PGE2 in human skeletal muscle. Findings from this study highlight the need to expand our knowledge regarding the potential role for aspirin regulation of the deleterious influence of inflammation on skeletal muscle health in aging and exercising individuals. Copyright © 2016, Journal of Applied Physiology.

  18. Comparison of small-bowel mucosal injury between low-dose aspirin and non-aspirin non-steroidal anti-inflammatory drugs: a capsule endoscopy study.

    PubMed

    Watari, Ikue; Oka, Shiro; Tanaka, Shinji; Igawa, Atsushi; Nakano, Makoto; Aoyama, Taiki; Yoshida, Shigeto; Chayama, Kazuaki

    2014-01-01

    The differences in the severity of small-bowel toxicity induced by aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) remain unclear. This study aimed at clarifying these differences in small-bowel mucosal injury by using capsule endoscopy (CE). We retrospectively compared the records of 78 and 40 obscure gastrointestinal bleeding patients receiving low-dose aspirin (LDA) and non-aspirin NSAIDs, respectively. All patients were found to have small-bowel mucosal injuries on CE. The two groups were compared for the number of small-bowel mucosal injuries and CE scores on the basis of the findings of CE. The mean numbers of reddened lesions in the LDA group and non-aspirin NSAID group were 2.49 ± 3.15 and 1.65 ± 3.04; the mean numbers of erosions/ulcers 1.56 ± 3.75 and 6.08 ± 10.4, and the mean CE scores 154 ± 294 and 520 ± 758, respectively. The mean number of reddened lesions was significantly higher and the mean number of erosions/ulcers and CE scores significantly lower in the LDA group than in the other non-aspirin NSAID group. Small-bowel mucosal injuries were significantly milder in the LDA group than in the non-aspirin NSAID group, though reddened lesions were more frequent in the LDA group.

  19. 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.

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

    PubMed Central

    Ogundeji, Adepemi O.; Pohl, Carolina H.

    2016-01-01

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

  1. Nimesulide aggravates redox imbalance and calcium dependent mitochondrial permeability transition leading to dysfunction in vitro.

    PubMed

    Singh, Brijesh Kumar; Tripathi, Madhulika; Pandey, Pramod Kumar; Kakkar, Poonam

    2010-09-10

    Nimesulide (selective cyclooxygenase-2 inhibitor) is a nonsteroidal anti-inflammatory drug for the symptomatic treatment of painful conditions like osteoarthritis, spondilitis and primary dysmenorrhoea. Nimesulide induced liver damage is a serious side effect of this otherwise popular drug. The mechanism involved in nimesulide induced hepatotoxicity is still not fully elucidated. However, both mitochondrial dysfunction and oxidative stress have been implicated in contributing to liver injury in susceptible patients. Mitochondria besides being the primary source of energy, act as a hub of signals responsible for initiating cell death, irrespective of the pathway, i.e. apoptosis or necrosis. The present study was aimed to explore the role of compounding stress, i.e. Ca(2+) overload and GSH depletion in nimesulide induced mitochondrial toxicity and dysfunction. Our study showed that, nimesulide (100 microM) treatment resulted into rapid depletion of GSH (60%) in isolated rat liver mitochondria and significant Ca(2+) dependent MPT changed. Enhanced ROS generation (DCF fluorescence) was also observed in mitochondria treated with nimesulide. An important finding was that the concentration at which nimesulide oxidized reduced pyridine nucleotides (autofluorescence of NAD(P)H), it affected mitochondrial electron flow (MTT activity decreased by 75%) and enhanced mitochondrial depolarization significantly as assessed by Rhodamine 123 fluorescent probe. Therefore, nimesulide was found to aggravate redox imbalance and affect Ca(2+) dependent mitochondrial membrane permeability transition leading to dysfunction and ultimately cell death.

  2. Phase transformation in conformational polymorphs of nimesulide.

    PubMed

    Sanphui, Palash; Sarma, Bipul; Nangia, Ashwini

    2011-06-01

    Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) and a COX-2 inhibitor. The native crystal structure of nimesulide (or Form I) has been characterized in the literature by X-ray powder diffraction (XRPD) lines, whereas full three-dimensional coordinates are known for a second polymorph (Form II). A detailed structural characterization and phase stability of nimesulide polymorphs were carried out. Rod-like crystals of Form I (space group Pca2(1); number of symmetry-independent molecules, Z' = 2) were crystallized from EtOH concomitantly with Form II (C2/c, Z' = 1). These conformational polymorphs have different torsion angles at the phenoxy and sulfonamide groups. The crystal structures are stabilized by N-H · · · O hydrogen bonds and C-H · · · O, C-H · · · π interactions. Phase transition from the metastable Form (II) to the stable modification (I) was studied using differential scanning calorimetry, hot-stage microscopy, solid-state grinding, solvent-drop grinding, and slurry crystallization. The phase transition was monitored by infrared, Raman, and ss-nuclear magnetic resonance spectroscopy; and XRPD and single-crystal X-ray diffraction. The stable polymorph I was obtained in excess during solution crystallization, grinding, and slurry methods. Intrinsic dissolution and equilibrium solubility experiments showed that the metastable Form II dissolves much faster than the stable Form I. Copyright © 2011 Wiley-Liss, Inc.

  3. 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

  4. Nimesulide as a promising neuroprotectant in brain ischemia: new experimental evidences.

    PubMed

    Candelario-Jalil, Eduardo

    2008-04-01

    Nimesulide is a preferential inhibitor of cyclooxygenase-2 (COX-2) and it is one of the most prescribed non-steroidal anti-inflammatory drugs (NSAID) worldwide. Nimesulide was recently shown to have neuroprotective properties in animal models of acute neurologic injury. In particular, nimesulide is highly effective in reducing ischemic brain injury. This neuroprotective efficacy has been demonstrated in animal models of transient and permanent focal cerebral ischemia, global brain ischemia, embolic stroke, and chronic cerebral hypoperfusion. Nimesulide has been shown to reduce infarction, improve neurological function, attenuate blood-brain barrier disruption and edema, and reduce leukocyte infiltration into the ischemic brain. These beneficial effects have been observed even when the first treatment is given several hours after the onset of ischemia, demonstrating the wide therapeutic time window for nimesulide's neuroprotection. This is of great relevance since most stroke patients reach the emergency room several hours after the onset of symptoms, a time at which most medical interventions are not effective. In addition, nimesulide produces a long-lasting neuroprotection. This is of importance since some 'neuroprotective' compounds only produce a delay in cell death, and not a permanent protection. Its several mechanisms of action in neuroprotection make nimesulide a desirable and promising candidate as therapy for acute brain ischemia. This article reviews recent knowledge on the effects of nimesulide against brain injury, with particular emphasis in cerebral ischemia, and makes a critical appraisal of its therapeutic potential in the management of patients with brain ischemia.

  5. Benefit of low-dose aspirin and non-steroidal anti-inflammatory drugs in septic patients

    PubMed Central

    2013-01-01

    Analyzing medical records of 979 patients with severe sepsis or septic shock provided some evidence that the use of low-dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) was associated with decreased hospital mortality. However, the benefit was abolished when aspirin and NSAIDs were given together. PMID:23294562

  6. Dissolution Profile of Nimesulide from Pharmaceutical Preparations for Oral Use.

    PubMed

    Tubić, Biljana; Uzunović, Alija; Pilipović, Saša; Gagić, Žarko

    2016-01-01

    Nimesulide belongs to the group of semi-selective COX-2 inhibitors, widely used in solid oral formulations. In the present work the influence of surfactants among other drug excipients, as well as particle size of the active substance and the effects of medium pH on the dissolution rate of nimesulide from solid pharmaceutical forms. For that purpose, four different preparations containing 100 mg nimesulide per tablet and available in the market of Bosnia and Herzegovina (labeled here as A, B, C and D) were studied. The test for the assessment of dissolution profiles of the formulations was performed in surfactant-free dissolution medium pH 7.5. The dissolution profiles were compared by calculating difference (f1), and similarity (f2) factors. The increasing dissolution medium pH value from 7.5 to 7.75 resulted in a significant increase of nimesulide dissolution rate from the examined formulations. Also, the results showed that particle size affects to a great extent the dissolution rate and the best results were achieved with micronized nimesulide. The presence of the surfactants among the other excipients expressed a negligible effect on the dissolution profile.

  7. Experimental and Mathematical Studies on the Drug Release Properties of Aspirin Loaded Chitosan Nanoparticles

    PubMed Central

    Wan, Ajun; Shi, Yifei; Zhang, Yueyue; Chen, Yupeng

    2014-01-01

    The study of drug release dynamic is aiming at understanding the process that drugs release in human body and its dynamic characteristics. It is of great significance since these characteristics are closely related to the dose, dosage form, and effect of the drugs. The Noyes-Whitney function is used to represent how the solid material is dissolved into solution, and it is well used in study of drug dynamic. In this research, aspirin (acetylsalicylic acid (ASA)) has been encapsulated with different grades of chitosan (CS) varying in molecular weight (Mw) for the purpose of controlled release. The encapsulation was accomplished by ionic gelation technology based on assembly of positively charged chitosan and negatively charged sodium tripolyphosphate (TPP). The encapsulation efficiency, loading capacity, and drug release behavior of aspirin loaded chitosan nanoparticles (CS-NPs) were studied. It was found that the concentration of TPP and Aspirin, molecular weights of chitosan have important effect on the drug release patterns from chitosan nanoparticles. The results for simulation studies show that the Noyes-Whitney equation can be successfully used to interpret the drug release characteristics reflected by our experimental data. PMID:24987696

  8. In-vitro assessment and pharmacodynamics of nimesulide incorporated Aloe vera transemulgel.

    PubMed

    Vandana, K R; Yalavarthi, Prasanna R; Sundaresan, C R; Sriramaneni, Raghava N; Vadlamudi, Harini C

    2014-06-01

    The aim of the investigation was to prepare nimesulide emulsion for incorporation in Aloe vera gel base to formulate 'nimesulide - Aloe vera transemulgel' (NAE) and to carryout in-vitro assessment and in-vivo anti-inflammatory studies of the product. Although the use of nimesulide is banned for oral administration, due to its potential for inducing hepatotoxicity and thrombocytopenia, the use of nimesulide for topical delivery is prominent in the treatment of many inflammatory conditions including rheumatoid arthritis. The drug loading capacity of transdermal gels is low for hydrophobic drugs such as nimesulide. Nimesulide can be effectively incorporated into emulgels (a combination of emulsion and gel). Aloe vera has a mild anti-inflammatory effect and in the present study Aloe vera gel was formulated and used as a gel base to prepare NAE. The emulgels thus prepared were evaluated for viscosity, pH, in-vitro permeation, stability and skin irritation test. In-vivo anti-inflammatory studies were performed using carrageenan induced hind paw edema method in Wistar rats. The results were compared with that of commercial nimesulide gel (CNG). From the in-vitro studies, effective permeation of nimesulide from NAE (53.04 %) was observed compared to CNG (44.72 %) at 30 min indicating better drug release from NAE. Topical application of the emulgel found no skin irritation. Stability studies proved the integrity of the formulation. The percentage of inhibition of edema was highest for the prepared NAE (67.4 % inhibition after 240 min) compared to CNG (59.6 %). From our results, it was concluded that the Aloe vera gel acts as an effective gel base to prepare nimesulide emulgel with high drug loading capacity (86.4 % drug content) compared to CNG (70.5 % drug content) with significant anti-inflammatory effect.

  9. An Overview Of The Physiology And Pharmacology Of Aspirin And Nonsteroidal Anti-inflammatory Drugs

    PubMed Central

    Koester, Michael C.

    1993-01-01

    In this article, I present an overview of the actions and effects of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Although athletic trainers cannot prescribe or dispense prescription medications, they should be as aware of their effects as they are of other methods of injury treatment. To set the discussion in proper perspective, the inflammatory process and its mediators are reviewed briefly. The eicosanoids are a family of very active chemicals, which include: the prostaglandins, thromboxane, and the leukotrienes. They affect inflammation as well as numerous other body processes. Ingesting aspirin and NSAIDs blocks the production of prostaglandins and thromboxane, resulting in desired and undesired effects. The NSAIDs were developed to have the same action as aspirin, but with fewer adverse side effects. Many NSAIDs are currently available, and the decision as to which agent to use depends upon various factors. Surprisingly, recent studies suggest that some NSAIDs may hinder the healing process. Although not a NSAID, acetaminophen has many important clinical uses. Armed with an understanding of how these drugs act, and their potentially harmful aspects, the athletic trainer can assist the team physician in designing an aspirin- or NSAID-therapy regimen. PMID:16558240

  10. Aspirin, nonsteroidal anti-inflammatory drugs, acetaminophen, and pancreatic cancer risk: a clinic-based case-control study.

    PubMed

    Tan, Xiang-Lin; Reid Lombardo, Kaye M; Bamlet, William R; Oberg, Ann L; Robinson, Dennis P; Anderson, Kristin E; Petersen, Gloria M

    2011-11-01

    Aspirin and other nonsteroidal anti-inflammatory drugs (NSAID) show indisputable promise as cancer chemoprevention agents. However, studies have been inconsistent as to whether aspirin has a protective effect in development of pancreatic cancer. To further evaluate the association between aspirin, NSAID, and acetaminophen use with pancreatic cancer risk, we used a clinic-based case-control study of 904 rapidly ascertained histologically or clinically documented pancreatic ductal adenocarcinoma cases, and 1,224 age- and sex-matched healthy controls evaluated at Mayo Clinic from April 2004 to September 2010. Overall, there is no relationship between non-aspirin NSAID or acetaminophen use and risk of pancreatic cancer. Aspirin use for 1 d/mo or greater was associated with a significantly decreased risk of pancreatic cancer (OR = 0.74, 95% CI: 0.60-0.91, P = 0.005) compared with never or less than 1 d/mo. Analysis by frequency and frequency-dosage of use categories showed reduced risk (P = 0.007 and 0.022, respectively). This inverse association was also found for those who took low-dose aspirin for heart disease prevention (OR = 0.67, 95% CI: 0.49-0.92, P = 0.013). In subgroup analyses, the association between aspirin use and pancreatic cancer was not significantly affected by pancreatic cancer stage, smoking status, or body mass index. Our data suggest that aspirin use, but not non-aspirin NSAID use, is associated with lowered risk of developing pancreatic cancer.

  11. Aspirin, nonaspirin nonsteroidal anti-inflammatory drugs, acetaminophen and ovarian cancer survival.

    PubMed

    Nagle, Christina M; Ibiebele, Torukiri I; DeFazio, Anna; Protani, Melinda M; Webb, Penelope M

    2015-04-01

    Aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to decrease tumor progression in pre-clinical models of ovarian cancer, however the influence of these drugs on survival in women following a diagnosis of ovarian cancer is unknown. We included 1305 Australian women diagnosed with incident invasive epithelial ovarian cancer, recruited into a population-based case-control study. Use of aspirin, nonaspirin NSAIDs and acetaminophen in the 5 years preceding ovarian cancer diagnosis was assessed from self-reports. Deaths were ascertained up to October 2011 via linkage with the Australian National Death Index. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CI). During a mean follow-up time of 4.9 years (SD 2.8 years), there were 834 deaths, of which 779 (93% of deaths) were from ovarian cancer. We found uniformly inverse, but non-significant, HRs for ever use in the last five years of aspirin, nonaspirin NSAIDs and acetaminophen compared with no use (adjusted HRs 0.92 [95% CI 0.81-1.06], 0.91 [95% CI 0.80-1.05] and 0.91 [95% CI 0.69-1.20], respectively). There was no evidence of any dose response trends. The results remained unchanged when we limited the outcome to ovarian cancer mortality. Associations did not differ by histologic subtype, age at diagnosis or stage. Given current interest in the role of aspirin and nonaspirin NSAIDs in cancer survival these results are noteworthy given they are the first to investigate these associations in women with ovarian cancer. Our results provide no strong evidence that pre-diagnostic use of aspirin or nonaspirin NSAIDs are associated with improved survival in women with ovarian cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo‐oxygenase‐2 inhibitors, traditional non‐aspirin non‐steroidal anti‐inflammatory drugs, aspirin and combinations

    PubMed Central

    Lanas, A; García‐Rodríguez, L A; Arroyo, M T; Gomollón, F; Feu, F; González‐Pérez, A; Zapata, E; Bástida, G; Rodrigo, L; Santolaria, S; Güell, M; de Argila, C M; Quintero, E; Borda, F; Piqué, J M

    2006-01-01

    Background The risks and benefits of coxibs, non‐steroidal anti‐inflammatory drugs (NSAIDs), and aspirin treatment are under intense debate. Objective To determine the risk of peptic ulcer upper gastrointestinal bleeding (UGIB) associated with the use of coxibs, traditional NSAIDs, aspirin or combinations of these drugs in clinical practice. Methods A hospital‐based, case–control study in the general community of patients from the National Health System in Spain. The study included 2777 consecutive patients with endoscopy‐proved major UGIB because of the peptic lesions and 5532 controls matched by age, hospital and month of admission. Adjusted relative risk (adj RR) of UGIB determined by conditional logistic regression analysis is provided. Results Use of non‐aspirin‐NSAIDs increased the risk of UGIB (adj RR 5.3; 95% confidence interval (CI) 4.5 to 6.2). Among non‐aspirin‐NSAIDs, aceclofenac (adj RR 3.1; 95% CI 2.3 to 4.2) had the lowest RR, whereas ketorolac (adj RR 14.4; 95% CI 5.2 to 39.9) had the highest. Rofecoxib treatment increased the risk of UGIB (adj RR 2.1; 95% CI 1.1 to 4.0), whereas celecoxib, paracetamol or concomitant use of a proton pump inhibitor with an NSAID presented no increased risk. Non‐aspirin antiplatelet treatment (clopidogrel/ticlopidine) had a similar risk of UGIB (adj RR 2.8; 95% CI 1.9 to 4.2) to cardioprotective aspirin at a dose of 100 mg/day (adj RR 2.7; 95% CI 2.0 to 3.6) or anticoagulants (adj RR 2.8; 95% CI 2.1 to 3.7). An apparent interaction was found between low‐dose aspirin and use of non‐aspirin‐NSAIDs, coxibs or thienopyridines, which increased further the risk of UGIB in a similar way. Conclusions Coxib use presents a lower RR of UGIB than non‐selective NSAIDs. However, when combined with low‐dose aspirin, the differences between non‐selective NSAIDs and coxibs tend to disappear. Treatment with either non‐aspirin antiplatelet or cardioprotective aspirin has a similar risk of UGIB. PMID

  13. Aspirin allergy.

    PubMed

    Speer, F; Denison, T R; Baptist, J E

    1981-03-01

    This paper represents a 17-year prospective study of the clinical characteristics of patients with a history of having had allergic reactions to aspirin. The following points are especially important. (1) The most common manifestation is urticarica/angioedema; the second most common, asthma. (2) Women of child-bearing age are especially prone to develop aspirin sensitivity, otherwise the age of onset is approximately equal in the two sexes, varying from one year to 60 years. (3) Although an immunologic basis of aspirin sensitivity has not been demonstrated, 90% of its victims are also sensitive to inhalants (76%), foods (74%) or drugs (43%). (4) The authors could not confirm the widely held view that aspirin cross-reacts with tartrazine. (5) They were also unable to confirm another widely held view that asthmatic patients who are sensitive to aspirin have a strong tendency to develop nasal polyps. (6) The prognosis of asthma in patients sensitive to aspirin does not differ from that of patients who are not. These findings underline the importance of giving every aspirin-sensitive patient the benefit of a complete allergic work-up.

  14. Nimesulide inhibits pathogenic fungi: PGE2-dependent mechanisms.

    PubMed

    de Matos, Rafaelle Fonseca; Mendonça, Lúcia Carla Vasconcelos; da Silva Souza, Kaira Geiliane; Fonseca, Adriana Aparecida Durães; Costa, Elaine Mirla Souza; de Lima, Marcus Vinicius Dias; Vieira, José Maria Dos Santos; de Brito, Mioni Thielli Figueiredo Magalhães; Monteiro, Marta Chagas

    2017-03-01

    Certain non-steroidal anti-inflammatory drugs can inhibit fungal growth, fungal prostaglandin E2 production, and enzyme activation. This study aims to investigate the antifungal effect of nimesulide against pathogenic filamentous fungi and yeast. The experiments detailed below were also designed to investigate whether the action is dependent on E2 fungal prostaglandins. Our data showed that nimesulide exhibited potent antifungal activity, mainly against Trichophyton mentagrophytes (ATCC 9533) and Cryptococcus neoformans with MIC values of 2 and 62 μg/mL, respectively. This drug was also able to inhibit the growth of clinic isolates of filamentous fungi, such as Aspergillus fumigatus, and dermatophytes, such as T. rubrum, T. mentagrophytes, Epidermophyton floccosum, Microsporum canis, and M. gypseum, with MIC values ranging from 112 to 770 μg/mL. Our data also showed that the inhibition of fungal growth by nimesulide was mediated by a mechanism dependent on PGE2, which led to the inhibition of essential fungal enzymes. Thus, we concluded that nimesulide exerts a fungicidal effect against pathogenic filamentous fungi and yeast, involving the inhibition of fungal prostaglandins and fungal enzymes important to the fungal growth and colonization.

  15. Open access gastroscopy findings are unrelated to the use of aspirin and non-steroidal anti-inflammatory drugs.

    PubMed Central

    Mansfield, J C; Greenaway, J R; Contractor, B R; Idle, N; Bramble, M G

    1997-01-01

    This study aims to determine whether priority should be given to patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin when selecting which dyspeptic patients to refer for open access gastroscopy. A total of 8156 patients underwent gastroscopy, all of whom had upper gastrointestinal symptoms. Patients taking NSAIDs or aspirin showed no significant differences in the frequency of ulcer disease when age-matched groups were compared. Although NSAIDs and aspirin are frequently implicated in gastrointestinal bleeding in the elderly, patients referred for investigation of dyspepsia show no increase in major endoscopic pathology. PMID:9463986

  16. Involvement of mitochondria mediated pathways in hepatoprotection conferred by Fumaria parviflora Lam. extract against nimesulide induced apoptosis in vitro.

    PubMed

    Tripathi, Madhulika; Singh, Brijesh Kumar; Mishra, Chetna; Raisuddin, Sheikh; Kakkar, Poonam

    2010-03-01

    Nimesulide, a popular nonsteroidal anti-inflammatory drug, has been associated with serious hepatotoxicity. Reactive oxygen species (ROS) and mitochondrial perturbations have been implicated in drug induced hepatotoxicity, although their role in the pathway needs exploration. Study was undertaken to elucidate the effect of Fumaria parviflora Lam. (Fp) on nimesulide induced cell death in primary rat hepatocyte cultures. Fp extract treated cells showed increased viability as compared to nimesulide stressed cells as assessed by MTT assay. LDH leakage increased significantly at 500microM nimesulide, and the data suggested that apoptosis was the predominant mechanism responsible for cell death. Nimesulide induced apoptosis was further confirmed by DNA fragmentation and chromatin condensation. Nimesulide exposure increased intracellular ROS, translocation of Bax and Bcl2 followed by mitochondrial depolarization and cytochrome c (Cyt c) release along with caspase-9/-3 activity confirming involvement of mitochondria in nimesulide induced apoptosis. Events like membrane depolarization of mitochondria, expression of Bax, Bcl2, externalization of phosphatidyl serine are substantially reversed by the pre-treatment of Fp extract. Thus, the study indicates that Fp extract modulates critical events regulating pro and anti-apoptotic proteins in mitochondria dependent apoptosis induced by nimesulide.

  17. Guaifenesin enhances the analgesic potency of ibuprofen, nimesulide and celecoxib in mice.

    PubMed

    Sliva, Jiri; Dolezal, Tomas; Sykora, David; Vosmanska, Magda; Krsiak, Miloslav

    2009-01-01

    Previously, we found that guaifenesin enhances analgesia induced by paracetamol. The aim of the present study was to determine whether guaifenesin is able to also increase analgesic activity in the non-steroid anti-inflammatory drugs ibuprofen, nimesulide and celecoxib. In addition we investigated the influence of guaifenesin on plasma levels of nimesulide. A model of visceral pain consisting of intraperitoneal injection of acetic acid (writhing test) was used. Levels of nimesulide in plasma were measured by HPLC. All drugs were given orally and tested in mice. Guaifenesin alone did not produce any antinociceptive effect. Simultaneous administration of guaifenesin (200 mg/kg) and subanalgesic doses of ibuprofen (10 and 30 mg/kg), nimesulide (10 and 20 mg/kg) or celecoxib (1 and 5 mg/kg) resulted in a significant antinociceptive effects. The plasma levels of nimesulide were significantly higher in combination with guaifenesin at 30, 60 and 90 min after oral administration in comparison to nimesulide monotherapy. The present results suggest that guaifenesin might enhance the analgesic activity of various non-steroidal anti-inflammatory drugs.

  18. Effects of nimesulide and its reduced metabolite on mitochondria

    PubMed Central

    Mingatto, Fábio Erminio; dos Santos, Antonio Cardozo; Rodrigues, Tiago; Pigoso, Acácio Antonio; Uyemura, Sérgio Akira; Curti, Carlos

    2000-01-01

    We investigated the effects of nimesulide, a recently developed non-steroidal anti-inflammatory drug, and of a metabolite resulting from reduction of the nitro group to an amine derivative, on succinate-energized isolated rat liver mitochondria incubated in the absence or presence of 20 μM Ca2+, 1 μM cyclosporin A (CsA) or 5 μM ruthenium red.Nimesulide uncoupled mitochondria through a protonophoretic mechanism and oxidized mitochondrial NAD(P)H, both effects presenting an EC50 of approximately 5 μM.Within the same concentration range nimesulide induced mitochondrial Ca2+ efflux in a partly ruthenium red-sensitive manner, and induced mitochondrial permeability transition (MPT) when ruthenium red was added after Ca2+ uptake by mitochondria. Nimesulide induced MPT even in de-energized mitochondria incubated with 0.5 mM Ca2+.Both Ca2+ efflux and MPT were prevented to a similar extent by CsA, Mg2+, ADP, ATP and butylhydroxytoluene, whereas dithiothreitol and N-ethylmaleimide, which markedly prevented MPT, had only a partial or no effect on Ca2+ efflux, respectively.The reduction of the nitro group of nimesulide to an amine derivative completely suppressed the above mitochondrial responses, indicating that the nitro group determines both the protonophoretic and NAD(P)H oxidant properties of the drug.The nimesulide reduction product demonstrated a partial protective effect against accumulation of reactive oxygen species derived from mitochondria under conditions of oxidative stress like those resulting from the presence of t-butyl hydroperoxide.The main conclusion is that nimesulide, on account of its nitro group, acts as a potent protonophoretic uncoupler and NAD(P)H oxidant on isolated rat liver mitochondria, inducing Ca2+ efflux or MPT within a concentration range which can be reached in vivo, thus presenting the potential ability to interfere with the energy and Ca2+ homeostasis in the liver cell. PMID:11082123

  19. Aspirin and other nonsteroidal anti-inflammatory drugs and risk of non-hodgkin lymphoma.

    PubMed

    Teras, Lauren R; Gapstur, Susan M; Patel, Alpa V; Thun, Michael J; Diver, W Ryan; Zhai, Yusheng; Jacobs, Eric J

    2013-03-01

    Few large prospective studies have examined associations between nonsteroidal anti-inflammatory drug (NSAID) use and non-Hodgkin lymphoma (NHL). We examined the association between NSAID use and NHL incidence among 149,570 participants in the Cancer Prevention Study-II Nutrition cohort. Aspirin and nonaspirin NSAID use were reported at enrollment in 1992 and updated on periodic follow-up questionnaires. During follow-up through 2007, 1,709 incident NHLs were identified. Time-dependent hazard ratios were calculated using extended Cox regression. Compared to no use, current use of 60+ NSAID pills/month (aspirin and nonaspirin NSAIDs combined) was associated with slightly higher NHL incidence (hazard ratio [HR] = 1.26, 95% confidence interval [CI], 1.04-1.53), but no association with frequency of use was observed when NSAID exposure was lagged by approximately 2 years (HR = 1.08, 95% CI, 0.88-1.32). Long duration regular use (current use of 30+ pills/month for ≥5 years) was not associated with NHL incidence (HR = 1.09, 95% CI, 0.91-1.33). In subtype analyses, current use of 60+ NSAID pills/month was associated with follicular lymphoma incidence (HR = 1.87, 95% CI, 1.08-3.24). This association persisted when NSAID exposure was lagged (HR = 1.76, 95% CI, 1.04-2.98) and was similar for aspirin and nonaspirin NSAIDs. The association of current, but not lagged, NSAID use with risk of all NHL could be attributable to use of NSAIDs to relieve symptoms of undiagnosed NHL. However, the association with follicular lymphoma persisted in analyses where NSAID use was lagged and should be investigated further. These findings are particularly important for aspirin as the risks and benefits of prophylactic daily use are weighed.

  20. Aspirin in dermatology: Revisited

    PubMed Central

    Bubna, Aditya Kumar

    2015-01-01

    Aspirin has been one of the oldest drugs in the field of medicine, with a wide range of applications. In dermatology, aspirin has shown benefit in a variety of disorders. Recently, reduction of melanoma risk with aspirin has been demonstrated. Although an analgesic to begin with, aspirin has come a long way; after cardiology, it is now found to be useful even in dermatology. PMID:26753146

  1. Nondestructive prediction of the drug content of an aspirin suppository by near-infrared spectroscopy.

    PubMed

    Otsuka, Eri; Abe, Hiroyuki; Aburada, Masaki; Otsuka, Makoto

    2010-07-01

    A suppository dosage form has a rapid effect on therapeutics, because it dissolves in the rectum, is absorbed in the bloodstream, and passes the hepatic metabolism. However, the dosage form is unstable, because a suppository is made in a semisolid form, and so it is not easy to mix the bulk drug powder in the base. This article describes a nondestructive method of determining the drug content of suppositories using near-infrared spectrometry (NIR) combined with chemometrics. Suppositories (aspirin content: 1.8, 2.7, 4.5, 7.3, and 9.1%, w/w) were produced by mixing an aspirin bulk powder with hard fat at 50 degrees C and pouring the melt mixture into a plastic mold (2.25 mL). NIR spectra of 12 calibration and 12 validation sample sets were recorded 5 times. A total of 60 spectral data were used as a calibration set to establish a calibration model to predict drug content with a partial least-squares (PLS) regression analysis. NIR data of the suppository samples were divided into two wave number ranges, 4000-12500 cm(-1) (LR), and 5900-6300 cm(-1) (SR). Calibration models for the aspirin content of the suppositories were calculated based on LR and SR ranges of second-derivative NIR spectra using PLS. The models for LR and SR consisted of five and one principal components (PC), respectively. The plots of predicted values against actual values gave a straight line with regression coefficient constants of 0.9531 and 0.9749, respectively. The mean bias and mean accuracy of the calibration models were calculated based on the SR of variation data sets, and were lower than those of LR, respectively. Limiting the wave number of spectral data sets is useful to help understand the calibration model because of noise cancellation and to measure objective functions.

  2. Combined dipyridamole and aspirin pellet formulation for improved oral drug delivery. Part 1: Development pharmaceutics.

    PubMed

    Deasy, P B; Murtagh, P W

    1996-01-01

    The dissolution profile of various weight fractions of dipyridamole: hydropropylmethylcellulose acetate succinate (HPMC-AS) and dipyridamole: hydroxypropylmethylcellulose phthalate co-precipitates lead to the choice of 1:2 dipyridamole: HPMC-AS as the controlled-release component. It was deposited to form two-third of the total dose as an inner layer on inert sucrose cores by air suspension coating for release mainly in the small intestine. Further examination of this material by IR spectroscopy, differential scanning calorimetry and X-ray diffraction indicated some free drug, preferentially soluble under gastric pH conditions. One-third of the total dose was applied by pan coating as an outer layer of micronized dipyridamole around the inner enteric co-precipitate layer. Aspirin-loaded cores were prepared also by pan coating for use in the final product, which contained both anti-platelet drugs.

  3. Photoacoustic study of the penetration kinetics of nimesulid into human skin

    NASA Astrophysics Data System (ADS)

    Barja, P. R.; Veloso, D. J. D. V.

    2010-03-01

    The photoacoustic (PA) effect is observed when modulated (or pulsed) light is absorbed by a sample inside a closed chamber and converted in heat, generating acoustic waves; PA measurements have been employed to evaluate transdermal penetration of topically applied drugs. Phonophoresis is the utilization of ultrasonic (US) energy to enhance absorption of drugs across the epidermal barrier, and its usefulness has been shown by PA measurements. The aim of the present work was to determine the characteristic absorption times of the anti-inflammatory Nimesulid (gel) in human skin, with and without help of therapeutic phonophoresis. After local cleaning, measurements were performed in the forearm of each volunteer before Nimesulid application and for different times after application through massage with the US equipment head; the protocol was repeated for the opposite forearm, but without US emission. Curves of the PA signal level as a function of time were adjusted by a Boltzmann equation, leading to the determination of the characteristic absorption time (about 12 minutes). No significant gain was observed in Nimesulid absorption with the utilization of US radiation, indicating that topic application of Nimesulid does not require the use of phonophoresis, due to the natural fast penetration of the Nimesulid gel.

  4. Nimesulide-induced electrophile stress activates Nrf2 in human hepatocytes and mice but is not sufficient to induce hepatotoxicity in Nrf2-deficient mice.

    PubMed

    Kale, Vijay M; Hsiao, Chin-ju J; Boelsterli, Urs A

    2010-05-17

    Nimesulide is a widely prescribed nitroaromatic sulfoanilide-type nonsteroidal anti-inflammatory drug that, despite its favorable safety profile, has been associated with rare cases of idiosyncratic drug-induced liver injury (DILI). Because reactive metabolites have been implicated in DILI, we aimed at investigating whether hepatic bioactivation of nimesulide produces a protein-reactive intermediate in hepatocytes. Also, we explored whether nimesulide can activate the transcription factor Nrf2 that would protect from drug-induced hepatocyte injury. We found that [(14)C]-nimesulide covalently bound to human liver microsomes (<50 pmol/mg under standard conditions) or immortalized human hepatocytes in a sulfaphenazole-sensitive, rifampicin-inducible manner; yet the overall extent of binding was modest. Although exposure of hepatocytes to nimesulide was not associated with increased net levels of superoxide anion, nimesulide (100 microM, 24 h) caused nuclear translocation of Nrf2 in a sulfaphenazole-sensitive manner, indicating a role of electrophilic metabolites. However, knockdown of Nrf2 with siRNA did not make the cells more sensitive to nimesulide-induced cell injury. Similarly, exposure of wild-type C57BL/6x129 Sv mice to nimesulide (100 mg/kg/day, po, for 5 days) was associated with nuclear translocation of immunoreactive Nrf2 in a small number of hepatocytes and induced >2-fold the expression levels of the Nrf2-target gene Nqo1 in wild-type but not Nrf2-null mice. Nimesulide administered to Nrf2(-/-) knockout mice did not cause increases in serum ALT activity or any apparent histopathological signs of liver injury. In conclusion, these data indicate that nimesulide is bioactivated by CYP2C to a protein-reactive electrophilic intermediate that activates the Nrf2 pathway even at nontoxic exposure levels.

  5. Nimesulide improves the disease modifying anti-rheumatic profile of methotrexate in mice with collagen-induced arthritis.

    PubMed

    Al-Abd, Ahmed M; Inglis, Julia J; Nofal, Salwa M; Khalifa, Amani E; Williams, Richard O; El-Eraky, Wafaa I; Abdel-Naim, Ashraf B

    2010-10-10

    Methotrexate is a disease modifying anti-rheumatic drug that is widely used for the treatment of rheumatoid arthritis. Nimesulide is a non-steroidal anti-inflammatory drug which is frequently used as adjuvant therapy for symptomatic alleviation of rheumatoid arthritis. In this study, we have evaluated the potential influence of nimesulide on the disease modifying anti-rheumatic properties of methotrexate using the collagen-induced arthritis model. Mice were immunized with collagen type II for the induction of arthritis and treated with methotrexate (2.5mg/kg) twice a week, nimesulide (20mg/kg) every other day or a combination of both drugs. Treatment started one week after the onset of arthritis until day 40. An arthritic index was used to compare the severity of arthritis between different treatments. In addition, articular hyperalgesia, joint stiffness, radiological deterioration and intra-articular leucocytic infiltration were evaluated. Methotrexate alone showed modest but significant analgesic and anti-inflammatory effects, and the effects of nimesulide were comparable. On the other hand, nimesulide significantly improved the disease modifying anti-rheumatic profile of methotrexate in terms of arthritic index and joint mobility. Furthermore, although nimesulide failed to show any radiological evidence of articular protection, it significantly improved methotrexate-induced joint protection as judged by X-ray analysis.

  6. 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 " ...

  7. 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 ...

  8. Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity.

    PubMed

    Carbone, Laura D; Tylavsky, Frances A; Cauley, Jane A; Harris, Tamara B; Lang, Thomas F; Bauer, Douglas C; Barrow, Karen D; Kritchevsky, Stephen B

    2003-10-01

    BMD was examined in users of NSAIDs (by COX selectivity) and aspirin in the Health ABC cohort (n = 2853). Significantly higher BMD was found in users of relative COX-2 selective NSAIDs with aspirin (COX-2/ASA) compared with nonusers. This suggests a role for COX-2/ASA in osteoporosis. The purpose of this study was to determine the relationship of nonsteroidal anti-inflammatory drug (NSAID) use, by cyclo-oxygenase selectivity (COX), and aspirin use on bone mineral density (BMD) in participants from the Health, Aging, and Body Composition (Health ABC) population-based cohort. It is known that NSAIDs inhibit the COX enzyme and decrease production of prostaglandins, which are involved in regulation of bone turnover. COX has two isoforms, COX-1 and COX-2. Production of prostaglandins associated with bone loss is primarily mediated through the COX-2 pathway. In addition, aspirin may have effects on bone independent of the prostaglandin pathway. NSAID (by COX selectivity) and aspirin use and BMD were assessed in 2853 adults (49.5% women, 50.5% men: 43.1% black, 56.9% white; mean age: 73.6 years) from the Health ABC cohort. For the purposes of this analysis, relative COX-1 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of > 1 in whole blood, and relative COX-2 selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of < 1 in whole blood. Analysis of covariance was used to compare BMD across each NSAID use and aspirin use category adjusting for age, race, gender, weight, height, study site, calcium and vitamin D supplementation, Womac score, history of rheumatoid arthritis, history of arthritis other than rheumatoid, and smoking status. After adjustment for possible confounders, current use of relative COX-2 selective NSAIDs with aspirin was associated with higher BMD at the whole body (4.2%, 1.2-7.3 CI) and total hip (4.6%, 0.5-8.8 CI) by DXA and at both trabecular (34.1%, 15.4-52.7 CI) and cortical spine (12.8%, 2.3-23.3 CI

  9. Hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs).

    PubMed

    de Weck, A L; Gamboa, P M; Esparza, R; Sanz, M L

    2006-01-01

    Hypersensitivity to aspirin and other non steroidal anti-inflammatory drugs (NSAIDs) manifesting in the airways (rhinosinusitis, polyps, asthma) or in the skin (urticaria, angioedema) is the second most frequent untoward allergic reaction to drugs. Various aspects of this syndrome, such as its clinical features, the cell types and mediators involved, the role of underlying chronic inflammatory processes, the patterns of cross-reactivity between NSAIDs, the major role of sulfidoleukotrienes (LTC4) and of some other mediators such as prostaglandin E2 (PGE2) and C5a are briefly reviewed. It has been assumed for a long time that there were no reliable in vitro tests for that condition and that diagnostic confirmation can only be ascertained by provocation challenge. This appears no longer to be true, since several recent studies using a leukotriene release test (CAST) or a basophil activation test (BAT) on blood basophils, or a combination of both tests, yields positive results (70-75%) in a sizeable number of clinically validated cases, with a high specificity (above 85%). The finding in that syndrome of hyperreactive basophils suggests that the NSAID hypersensitivity syndrome is due to the associated effect of several factors: 1) Localized inflammatory processes causing a non specific cellular hyperreactivity; 2) An abnormal pharmacogenetic reaction to NSAIDs resulting in a hyperproduction of LTC4 and other mediators by activated mast cells, basophils and eosinophils.

  10. In vivo selectivity of nonsteroidal antiinflammatory drugs and gastrointestinal ulcers in rats.

    PubMed

    Laudanno, O M; Cesolari, J A; Esnarriaga, J; San Miguel, P; Bedini, O A

    2000-07-01

    The aim of the present work was to study in vivo COX-2-COX-1 selectivity of 16 nonsteroidal anti-inflammatory drugs (NSAIDs) in equipotent ulcerogenic doses in two in vivo experimental models. Indomethacin, ibuprofen, nimesulide, aceclofenac, aspirin, sodium diclofenac, meloxicam, naproxene, paracetamol, piroxicam, tenoxicam, nabumetone, ketoprofen, mefenamic acid, etodolac, and ketorolac were administered to female Wistar rats (N = 10 each group). In experiment I, solid food plus subcutaneous NSAIDs were given. In experiment II, NSAIDs were given by oral gavage and in bolus. Macroscopic gastric antral ulcer area (30%) and intestinal erosiva area (295 mm2) in experiment I and necrotic gastric fundus area (65%) and erosive intestinal area (182 mm2), "in vivo" the NSAIDs COX-1 was showed. Neutrofilia assessed in gastric intestinal mucosa where also ibuprofen and paracetamol not given neotrophilic infiltration. In conclusion, COX-2-COX-1 selectivity was demonstrated in vivo with the drugs aceclofenac, nabumetone, meloxicam, nimesulide, and paracetamol.

  11. Effects of nimesulide on testicular functions in prepubertal albino rats.

    PubMed

    Ugochukwu, Agbasi Patrick; Ebere, Orisakwe Orish; Okwuoma, Abanobi

    2011-11-23

    Daily consumption of painkillers has almost become a routine in many parts of Africa and Asia due to manual labor, especially in young adults. In view of the wide-scale use of painkillers in many parts of Africa and Asia, it is feared that the use of nimesulide may constitute an appreciable public health risk. The present work is aimed at assessing the long-term testicular toxicity of nimesulide in growing male albino rats. Male albino rats aged 4-5 weeks and weighing between 36 and 42 g were obtained from the Toxicology Unit of the Department of Pharmacology, Faculty of Pharmacy University of Nigeria, Nsukka, Nigeria. The animals were housed singly in a cross-ventilated room at a temperature 22°C±3°C and a 12-h light/12-h dark cycle. They were fed with standard rat pellets (Pfizer Pharmaceuticals, Ikeja, Nigeria) and were given water ad libitum. The rats were divided into three groups of five rats each: the first and second groups orally received 5 and 7.5 mg/kg/day of nimesulide, respectively, whereas the third group did not receive any drug and acted as controls for 56 days. Weekly body weight of each rat was taken. Blood samples were collected on the 56th day by cardiac puncture, and serum samples were frozen until analysis. Rats were sacrificed under ether anesthesia. Epididymal semen number was counted using a Neubauer counting chamber. Sperm motility was assayed microscopically within 5 min at 37°C. Estradiol and testosterone were analyzed with electrochemiluminescence immunoassay using Elecsys autoanalyzer, model 1010 (Roche, Mannheim, Germany). The testes were excised, weighed, and fixed in Bouin fluid and processed for histopathology. Treatment with nimesulide did not significantly affect body weight, absolute and relative testis weights, or epididymal sperm number, but there were significant differences in testosterone and estradiol levels. At the doses studied, there were no significant changes in testicular architecture except for mild degenerative

  12. Effects of non steroidal anti-inflammatory drugs on the antioxidant defense system and the membrane functions in the rat intestine.

    PubMed

    Nair, P; Kanwar, S Singh; Sanyal, S Nath

    2006-01-01

    the treatment groups. These results indicate that celecoxib may be accepted as a safer drug in terms of overall gastro-intestinal toxicity as compared to the aspirin and nimesulide.

  13. Aspirin and other non-steroidal anti-inflammatory drug use and colorectal cancer survival: a cohort study

    PubMed Central

    Walker, A J; Grainge, M J; Card, T R

    2012-01-01

    Background: Aspirin has been widely reported to reduce the incidence of colorectal cancer. Recently, a survival benefit after diagnosis has also been suggested. Data regarding such a benefit are to date contradictory. This study examines the effect of non-steroidal anti-inflammatory drug (NSAID) use on mortality in colorectal cancer in a larger patient cohort than previously to further clarify this effect, especially in terms of exposure timing and dosing. Methods: A study using the General Practice Research Database assessed whether aspirin or NSAID exposure in the year immediately following diagnosis affected all-cause mortality in a cohort of 13 994 colorectal cancer patients. Cox proportional hazards modelling adjusted for age, gender, smoking, body mass index and comorbidity. Results: Overall mortality was slightly lower in patients treated with aspirin, (hazard ratio (HR)=0.91; 95% confidence interval (CI)=0.82–1.00). This effect was observed only in patients treated with prophylaxis-dose aspirin (HR=0.89, CI=0.80–0.98) and only in patients taking aspirin before diagnosis (HR=0.86, CI=0.76–0.98). Differential effects were observed depending on the time after diagnosis. Up to 5 years, a reduction in mortality was observed for aspirin users (HR=0.83, CI=0.75–0.92), whereas after 10 years there was an increase in mortality (HR=1.94, CI=1.26–2.99). For NSAID use, no significant effect was observed on overall mortality (HR=1.07, CI=0.98–1.15). High-dose NSAID use was associated with a slight increase in mortality (HR=1.41, CI=1.26–1.56). Interpretation: These findings provide further indication that aspirin may be beneficial in reducing mortality in colorectal cancer during the first 5 years. The same cannot be said for other NSAIDs, where a small increase in mortality was observed. PMID:23011483

  14. Colonic diverticular hemorrhage associated with the use of nonsteroidal anti-inflammatory drugs, low-dose aspirin, antiplatelet drugs, and dual therapy.

    PubMed

    Nagata, Naoyoshi; Niikura, Ryota; Aoki, Tomonori; Shimbo, Takuro; Kishida, Yoshihiro; Sekine, Katsunori; Tanaka, Shohei; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Akiyama, Junichi; Yanase, Mikio; Mizokami, Masashi; Uemura, Naomi

    2014-10-01

    The effects of various medications on lower gastrointestinal tract remains unknown. Here, we investigated the effects of nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, and antiplatelet drugs associated with diverticular bleeding. This prospective study involved patients with diverticulosis who underwent colonoscopy. Alcohol and smoking, medications, and Charlson comorbidity index and Gastrointestinal Symptom Rating Scale scores were assessed. The medications evaluated were nine kinds of NSAIDs, two kinds of low-dose aspirin, 10 kinds of nonaspirin antiplatelet drugs, three kinds of anticoagulants, acetaminophen, and corticosteroids. Adjusted odds ratios (aOR) were estimated by a logistic regression model. A total of 911 patients with non-bleeding diverticula (n = 758) and bleeding diverticula (n = 153) were enrolled. Independent risk factors were alcohol consumption (light drinker, aOR 3.4; ≥ moderate drinker, aOR 3.3), smoking index (≥ 400, aOR 2.0), NSAIDs (aOR 4.6), low-dose aspirin (aOR 1.9), and nonaspirin antiplatelet drugs (aOR 2.2). The drugs significantly associated with bleeding were loxoprofen (aOR 5.0), diclofenac (aOR 3.1), diclofenac suppository (aOR 8.0), etodolac (aOR 4.9), enteric-coated aspirin (aOR 3.9), buffered aspirin (aOR 9.9), clopidogrel (aOR 2.5), and cilostazol (aOR 7.3). Dual therapy carried a higher risk than monotherapy (single NSAID, aOR 3.6, P < 0.01; dual, aOR 23, P < 0.01; single antiplatelet drug, aOR 2.0, P < 0.01; dual, aOR 4.1, P < 0.01). Besides alcohol and smoking, NSAIDs, low-dose aspirin, and antiplatelet drugs are risk factors for diverticular bleeding. The magnitude of risk may differ between different kinds of NSAIDs and antiplatelet drugs, and dual therapy with NSAIDs or antiplatelet drugs increases the risk of bleeding. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  15. Imidazolium ionic liquids as solvents of pharmaceuticals: influence on HSA binding and partition coefficient of nimesulide.

    PubMed

    Azevedo, Ana M O; Ribeiro, Diogo M G; Pinto, Paula C A G; Lúcio, Marlene; Reis, Salette; Saraiva, M Lúcia M F S

    2013-02-25

    In this work, the influence of imidazolium ionic liquids (ILs) on bio-chemical parameters that influence the in vivo behavior of nimesulide was evaluated. In this context, the binding of nimesulide to human serum albumin (HSA), in IL media, was studied. In parallel, the evaluation of the interaction of drug-IL systems, with micelles of hexadecylphosphocholine (HDPC), enabled the calculation of partition coefficients (K(p)). Both assays were performed in buffered media in the absence and in the presence of emim [BF(4)], emim [Ms] and emim [TfMs] 1%. Even though there was an increase of the dissociation constant (K(d)) in IL media, nimesulide still binds to HSA by means of strong interactions. The thermodynamic analysis indicates that the interaction is spontaneous for all the tested systems. Moreover, the studied systems exhibited properties that are favorable to the interaction of the drug with biological membranes, with K(p) values 2.5-3.5 higher than in aqueous environment. The studied nimesulide-IL systems presented promising characteristics regarding the absorption and distribution of the drug in vivo, so that the studied solvents seem to be good options for drug delivery.

  16. Enteric-coated aspirin versus other antiplatelet drugs in acute non-cardioembolic ischemic stroke: post-marketing study in Japan.

    PubMed

    Takahashi, Shunichi; Mizuno, Osamu; Sakaguchi, Toshiaki; Yamada, Takashi; Inuyama, Lyo

    2014-01-01

    Japanese guidelines recommend aspirin 160-300 mg/day, starting within 48 h, for patients with acute cerebral infarction. However, there are few reports evaluated in Japanese patients. Our objective was to examine the safety and efficacy of enteric-coated aspirin, compared with other oral antiplatelet drugs, in Japanese patients with acute ischemic stroke. We performed a prospective, non-randomized, observational and multicenter study between June 2005 and December 2007. Patients with symptomatic acute ischemic stroke, including transient ischemic attack (TIA), who started enteric-coated aspirin or other antiplatelet drugs within 7 days of hospitalization were registered. Outcome measures evaluated within 3 months were incidence of cerebral and non-cerebral hemorrhagic events, recurrence of ischemic stroke or TIA, non-cerebral ischemic events and death from any cause. Overall, 2,548 and 830 patients treated with enteric-coated aspirin (100-300 mg/day) or other antiplatelet drugs, respectively, were registered; approximately 60% were male, mean age was 70 years, 85% had pre-existing cardiovascular disease or other complications. Enteric-coated aspirin of 100 mg was mainly prescribed, and only approximately half of the patients were started on it within 48 h after onset of ischemic stroke. Safety and efficacy population excluded patients without follow-up data were 2,521 in enteric-coated aspirin and 807 in other antiplatelets. Hemorrhagic events occurred in 46 (1.8%) in the enteric-coated aspirin group and in 13 (1.6%) in the other antiplatelet drugs group, there was not significant. Recurrent ischemic stroke or TIA occurred in 39 (1.5%) of the enteric-coated aspirin and in 18 (2.2%) of other antiplatelet drugs, and there were any-cause death in 16 (0.6%) and 8 (1.0%). Incidences were slightly lower in the enteric-coated aspirin group compared with the other antiplatelet drugs group, but not statistically significant. It seems that these results showed the

  17. Dipolar reorientations in amorphous nimesulide: a TSDC and DSC study.

    PubMed

    Ramos, Joaquim J Moura; Diogo, Hermínio P

    2016-05-10

    The experimental techniques of differential scanning calorimetry (DSC) and thermally stimulated depolarization currents (TSDC) were used to study the thermal behavior of the pharmaceutical drug nimesulide and its slow molecular mobility in the amorphous solid state. The glass forming ability, the glass stability and the tendency for crystallization from the equilibrium melt were investigated by DSC. The general kinetic features of the main relaxation, including the dynamic fragility, were studied by both experimental techniques. The TSDC study of the secondary relaxations did not disclose fast modes. However slow modes were detected, that were ascribed to the Johari - Goldstein relaxation on the basis of an aging study.

  18. 5-aminosalicylic acid in combination with nimesulide inhibits proliferation of colon carcinoma cells in vitro

    PubMed Central

    Fang, Hai-Ming; Mei, Qiao; Xu, Jian-Ming; Ma, Wei-Juan

    2007-01-01

    AIM: To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms. METHODS: Inhibitory effects of drugs (5-ASA, nimesulide and their combination) on HT-29 colon carcinoma cells were investigated by thiazolyl blue tetrazolium bromide (MTT) assay. Cellular apoptosis and proliferation were detected by TUNEL assay and immunocytochemical staining, respectively. RESULTS: Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 μmol/L inhibited proliferation of HT-29 colon carcinoma cells in a dose-dependent manner in vitro (t = 5.122, P < 0.05; t = 3.086, P < 0.05, respectively). The inhibition rate of HT-29 colon carcinoma cell proliferation was also increased when pretreated with 5-ASA (100 μmol/L) or nimesulide (100 μmol/L) for 12-96 h, which showed an obvious time-effect relationship (t = 6.149, P < 0.05; t = 4.159, P < 0.05, respectively). At the concentration of 10-500 μmol/L, the apoptotic rate of HT-29 colon carcinoma cells significantly increased (t = 18.156, P < 0.001; t = 19.983, P < 0.001, respectively), while expression of proliferating cell nuclear antigen (PCNA) was remarkably decreased (t = 6.828, P < 0.05; t = 14.024, P < 0.05, respectively). 5-ASA in combination with nimesulide suppressed the proliferation of HT-29 colon carcinoma cells more than either of these agents in a dose-dependent and time-dependent manner (t = 5.448, P < 0.05; t = 4.428, P < 0.05, respectively). CONCLUSION: 5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential. PMID:17569127

  19. Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats.

    PubMed

    Arslan, Aynur; Ozcicek, Adalet; Suleyman, Bahadir; Coban, Taha Abdulkadir; Cimen, Ferda Keskin; Nalkiran, Hatice Sevim; Kuzucu, Mehmet; Altuner, Durdu; Cetin, Nihal; Suleyman, Halis

    2016-11-01

    Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide.

  20. Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats

    PubMed Central

    Arslan, Aynur; Ozcicek, Adalet; Suleyman, Bahadir; Coban, Taha Abdulkadir; Cimen, Ferda Keskin; Nalkiran, Hatice Sevim; Kuzucu, Mehmet; Altuner, Durdu; Cetin, Nihal; Suleyman, Halis

    2016-01-01

    Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide. PMID:27333839

  1. Effect of nimesulide and indomethacin on contractility and the Ca2+ channel current in myometrial smooth muscle from pregnant women

    PubMed Central

    Sawdy, Robert; Knock, Gregory A; Bennett, Philip R; Poston, Lucilla; Aaronson, Philip I

    1998-01-01

    The non-steroidal anti-inflammatory drug (NSAID) indomethacin inhibits both constitutive and inducible forms of cyclo-oxygenase (COX-1 and COX-2, respectively), while nimesulide is a selective COX-2 inhibitor. Uterine COX-2 is upregulated before and during term and pre-term labour, and prostaglandins play a crucial role in parturition. We therefore evaluated the effects of these drugs on myometrial contractility and the voltage-gated Ca2+ channel current in tissue strips and isolated human myometrial smooth muscle cells (HMSMC) from myometrial biopsies taken with informed consent from women undergoing caesarean section at term (not in labour).Nimesulide and indomethacin caused almost complete inhibition of spontaneous myometrial contractions at concentrations of 100 and 300 μM, respectively. The Ca2+ channel current was inhibited in a concentration-dependent manner by both drugs, with a 40% reduction of the current at 100 μM nimesulide and 300 μM indomethacin. Nimesulide also accelerated the decay of the Ca2+ channel current.The inhibition of the Ca2+ channel current by 100 μM nimesulide and 300 μM indomethacin was unaffected by the presence of either PGF2α or PGE2 (30 μM), and was of similar magnitude whether 10 mM Ba2+ or 1.5 mM Ca2+ was used as the charge carrier.The concentrations of indomethacin and nimesulide required to suppress spontaneous contractility in human pregnant myometrium were much higher than those necessary to inhibit prostaglandin production. The results suggest that both nimesulide and indomethacin inhibit myometrial contractility via mechanisms independent of cyclo-oxygenase inhibition. Blockade of the Ca2+ current may contribute to this effect. PMID:9863649

  2. Natural lipid nanoparticles containing nimesulide: synthesis, characterization and in vivo antiedematogenic and antinociceptive activities.

    PubMed

    Raffin, Renata P; Lima, Amanda; Lorenzoni, Ricardo; Antonow, Michelli B; Turra, Cláudia; Alves, Marta P; Fagan, Solange B

    2012-04-01

    Lipid nanoparticles are drug delivery systems able to increase bioavailability of poorly soluble drugs. They can be prepared with different lipid materials, especially natural lipids. Shea butter is a natural lipid obtained from the Butyrospermum parkii seed and rich in oleic and stearic acids. Nimesulide is a COX 2 selective anti-inflammatory that is poorly soluble in water. The purpose of this study was to develop and characterize shea butter lipid nanoparticles using a new technique and evaluate the in vivo activity of these nanoparticles. Lipid nanoparticles were prepared by melting shea butter and mixing with an aqueous phase using a high shear mixer. The nanoparticles presented pH of 6.9 +/- 0.1, mean particle size of 90 nm and a narrow polydispersity (0.21). Zeta potential was around -20 mV and the encapsulation efficiency was 97.5%. Drug release was evaluated using dialysis bags and presented monoexponential profile with t50% of 4.80 h (free drug t50% was only 2.86 h). Antinociceptive activity was performed by the acetic acid model. Both nimesulide and nimesulide-loaded nanoparticles presented significant activity compared to the control. The in vivo anti-inflammatory activity was evaluated by paw edema and was statistically different for the nanoparticles containing nimesulide compared to free nimesulide, blank nanoparticles and saline. In conclusion, the use of shea butter as encapsulating lipid was very successful and allowed nanoparticles to be prepared with a very simple technique. The nanoparticles presented significant pharmacological effects that were not seen for free drug administration.

  3. Neutrophil- and myeloperoxidase-mediated metabolism of reduced nimesulide: evidence for bioactivation.

    PubMed

    Yang, Min; Chordia, Mahendra D; Li, Fengping; Huang, Tao; Linden, Joel; Macdonald, Timothy L

    2010-11-15

    Nimesulide, a widely used nonsteroidal anti-inflammatory drug (NSAID), has been associated with rare idiosyncratic hepatotoxicity. The chemical mechanisms underlying the liver injury remain unknown. We have undertaken the detailed study of the metabolic pathways of nimesulide in an effort to identify potential reactive metabolites. A previous report from this laboratory has demonstrated that one of the known nimesulide metabolites, termed reduced nimesulide (M1), is further bioactivated by human liver microsomes (HLMs) to form a reactive diiminoquinone species M2. The formation of M2 was confirmed indirectly by trapping with N-acetylcysteine (NAC). The aim of this study was to explore the fate of M1 in an inflammatory environment created by the recruitment of leukocytes. Leukocytes upon activation produce hydrogen peroxide (H(2)O(2)) and other myeloperoxidase (MPO) products, such as hypochlorous acid (HOCl), that are capable of metabolite oxidation. We demonstrate here that the reduced nimesulide, M1, undergoes a facile oxidation with activated neutrophils or with MPO in the presence of H(2)O(2) or HOCl to produce a variety of reactive as well as stable metabolites. One major metabolite, M3, was also produced by HLM as determined by trapping with NAC. Other metabolites, for example, M6, M8, and M9, were unique to the myeloperoxidase, because of their mode of formation from activation of the amino group of reduced nimesulide. The structures of some of these reactive metabolites were proposed on the basis of liquid chromatography-tandem mass spectrometry analyses and established by their comparison with synthetic standards. Metabolite M6 is interesting because it provides clear evidence of amine activation and indicates the potential of the reactive intermediate of M1 to conjugate with protein nucleophiles. In summary, our results demonstrate that a known nimesulide metabolite could be bioactivated by MPO through a pathway distinct from HLM-mediated pathways and that

  4. Determination of the adequate dosage of rebamipide, a gastric mucoprotective drug, to prevent low-dose aspirin-induced gastrointestinal mucosal injury

    PubMed Central

    Ota, Kazuhiro; Takeuchi, Toshihisa; Nouda, Sadaharu; Ozaki, Haruhiko; Kawaguchi, Shinpei; Takahashi, Yoshiaki; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Kuramoto, Takanori; Higuchi, Kazuhide

    2016-01-01

    Small intestinal mucosal injury caused by low-dose aspirin is a common cause of obscure gastrointestinal bleeding. We aimed to investigate the protective effects and optimal dose of rebamipide for low-dose aspirin-induced gastrointestinal mucosal injury. In this prospective randomized trial, 45 healthy volunteers (aged 20–65 years) were included and divided into three groups. The groups received enteric-coated aspirin 100 mg (low-dose aspirin) plus omeprazole 10 mg (Group A: proton pump inhibitor group), low-dose aspirin plus rebamipide 300 mg (Group B: standard-dose group), or low-dose aspirin plus rebamipide 900 mg (Group C: high-dose group). Esophagogastroduodenoscopy and video capsule endoscopy were performed, and the fecal occult blood reaction and fecal calprotectin levels were measured before and two weeks after drug administration. Although the fecal calprotectin levels increased significantly in Group A, they did not increase in Groups B and C. The esophagogastroduodenoscopic and video capsule endoscopic findings and the fecal occult blood test findings did not differ significantly among the three groups. In conclusion, standard-dose rebamipide is sufficient for preventing mucosal injury of the small intestine induced by low-dose aspirin, indicating that high-dose rebamipide is not necessary. PMID:27895392

  5. Determination of the adequate dosage of rebamipide, a gastric mucoprotective drug, to prevent low-dose aspirin-induced gastrointestinal mucosal injury.

    PubMed

    Ota, Kazuhiro; Takeuchi, Toshihisa; Nouda, Sadaharu; Ozaki, Haruhiko; Kawaguchi, Shinpei; Takahashi, Yoshiaki; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Kuramoto, Takanori; Higuchi, Kazuhide

    2016-11-01

    Small intestinal mucosal injury caused by low-dose aspirin is a common cause of obscure gastrointestinal bleeding. We aimed to investigate the protective effects and optimal dose of rebamipide for low-dose aspirin-induced gastrointestinal mucosal injury. In this prospective randomized trial, 45 healthy volunteers (aged 20-65 years) were included and divided into three groups. The groups received enteric-coated aspirin 100 mg (low-dose aspirin) plus omeprazole 10 mg (Group A: proton pump inhibitor group), low-dose aspirin plus rebamipide 300 mg (Group B: standard-dose group), or low-dose aspirin plus rebamipide 900 mg (Group C: high-dose group). Esophagogastroduodenoscopy and video capsule endoscopy were performed, and the fecal occult blood reaction and fecal calprotectin levels were measured before and two weeks after drug administration. Although the fecal calprotectin levels increased significantly in Group A, they did not increase in Groups B and C. The esophagogastroduodenoscopic and video capsule endoscopic findings and the fecal occult blood test findings did not differ significantly among the three groups. In conclusion, standard-dose rebamipide is sufficient for preventing mucosal injury of the small intestine induced by low-dose aspirin, indicating that high-dose rebamipide is not necessary.

  6. Aspirin-Induced Acute Liver Injury

    PubMed Central

    Satoskar, Rohit

    2014-01-01

    Aspirin is thought to be a relatively safe drug in adults. The association of aspirin and Reye syndrome in children is well documented. We report a 41-year-old female with pericarditis who was treated with high-dose aspirin and developed subsequent acute liver injury. After discontinuation of aspirin, liver enzyme elevation and right upper quadrant pain both resolved. We conclude that high-dose aspirin should be considered as a potentially hepatotoxic agent. PMID:26157904

  7. Systematic review: interactions between aspirin, and other nonsteroidal anti-inflammatory drugs, and polymorphisms in relation to colorectal cancer

    PubMed Central

    Andersen, V; Vogel, U

    2014-01-01

    Background Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin (acetylsalicylic acid, ASA). Long-term use of NSAIDs has been associated with lowered risk of colorectal cancer (CRC), but the use is hampered by adverse effects. Also, the anti-carcinogenic effects of NSAIDs are incompletely understood. Understanding biological effects of NSAIDs may help developing new preventive medical strategies. Aim To identify gene–environment interactions between genetic variation and NSAID use in relation to risk of CRC. Methods We performed a PubMed literature search and all studies reporting original data on interactions between NSAIDs and polymorphisms in relation to CRC were evaluated. Results We found indications that aspirin interacted with rs6983267 close to MYC (encoding a transcription factor involved in cell cycle progression, apoptosis and cellular transformation) and NSAIDs interacted with rs3024505 and rs1800872 in or close to IL10 (encoding IL-10) in preventing CRC. Homozygous carriers of the variant allele of rs6983267 (ca. 25% of the population) halved their risk for CRC by aspirin use compared to homozygous wildtype carriers who did not benefit from aspirin intake. No interaction between use of NSAIDs and PTGS-2 (encoding COX-2) in relation to CRC risk was detected. Other findings of interactions between genes in inflammatory and oncogenic pathways and NSAIDs were considered suggestive. Conclusions Knowledge of underlying biological effects of NSAIDs in relation to CRC is scarce and the basis for stratifying the patients for preventive treatment is not yet available. Further studies assessing interactions between long-term NSAID exposure and genetic variation in relation to CRC are warranted in large well-characterised prospective cohorts. PMID:24889212

  8. The Use of Multi-Walled Carbon Nanotubes as Possible Carrier in Drug Delivery System for Aspirin

    NASA Astrophysics Data System (ADS)

    Yusof, Alias Mohd.; Buang, Nor Aziah; Yean, Lee Sze; Ibrahim, Mohd. Lokman

    2009-06-01

    Carbon nanotubes (CNTs) have raised great interest in a number of applications, including field emission, energy storage, molecular electronics, sensors, biochips and drug delivery systems. This is due to their remarkable mechanical properties, chemical stability and biofunctionalizability. This nanomaterial is low in weight, has high strength and a high aspect ratio (long length compared to a small diameter). This paper will present a brief overview of drugs adsorbed onto the surface of carbon nanotubes via sonication method. The surface area of carbon nanotubes was measured by methylene blue method, Carbon nanotubes synthesized by catalytic chemical vapor deposition (CCVD) method were purified and functionalized in a mixture of concentrated acids (H2SO4:HNO3 = 3:1) at room temperature (25° C) via sonication in water bath, yielding carboxylic acid group on the CNTs' surface. CNT was successfully loaded with 48 %(w/w) aspirin molecules by suspending CNTs in a solution of aspirin in alcohol. Analysis of loaded CNTs by Field Emission-Scanning Electron Microscope (FESEM), Fourier Transform Infrared Spectrum (FITR) and UV-visible Spectroscopy confirmed the loading of the drug onto the CNTs. The work presented is a prelude to the direction of using carbon nanotubes as a drug delivery system to desired sites in human body.

  9. Aspirin revealed

    NASA Astrophysics Data System (ADS)

    Lacey, D.; Hu, X. K.; Loboda, A. V.; Mosey, N. J.; Lipson, R. H.

    2007-03-01

    Experiments are described where the experimental conditions have been optimized to detect aspirin by MALDI mass spectrometry. Although protonated aspirin was not observed by MALDI, sodium and potassium aspirin adducts could be found. Significantly better signals could be obtained by using Rb and Cs salts as cationization sources. Quantum calculations were carried out to determine the structure and energetics of the Li, K, Rb, and Cs alkali--aspirin adducts.

  10. Natural terpenes prevent mitochondrial dysfunction, oxidative stress and release of apoptotic proteins during nimesulide-hepatotoxicity in rats.

    PubMed

    Singh, Brijesh Kumar; Tripathi, Madhulika; Chaudhari, Bhushan P; Pandey, Pramod K; Kakkar, Poonam

    2012-01-01

    Nimesulide, an anti-inflammatory and analgesic drug, is reported to cause severe hepatotoxicity. In this study, molecular mechanisms involved in deranged oxidant-antioxidant homeostasis and mitochondrial dysfunction during nimesulide-induced hepatotoxicity and its attenuation by plant derived terpenes, camphene and geraniol has been explored in male Sprague-Dawley rats. Hepatotoxicity due to nimesulide (80 mg/kg BW) was evident from elevated SGPT, SGOT, bilirubin and histo-pathological changes. Antioxidants and key redox enzymes (iNOS, mtNOS, Cu/Zn-SOD, Mn-SOD, GPx and GR) were altered significantly as assessed by their mRNA expression, Immunoblot analysis and enzyme activities. Redox imbalance along with oxidative stress was evident from decreased NAD(P)H and GSH (56% and 74% respectively; P<0.001), increased superoxide and secondary ROS/RNS generation along with oxidative damage to cellular macromolecules. Nimesulide reduced mitochondrial activity, depolarized mitochondria and caused membrane permeability transition (MPT) followed by release of apoptotic proteins (AIF; apoptosis inducing factor, EndoG; endonuclease G, and Cyto c; cytochrome c). It also significantly activated caspase-9 and caspase-3 and increased oxidative DNA damage (level of 8-Oxoguanine glycosylase; P<0.05). A combination of camphene and geraniol (CG; 1:1), when pre-administered in rats (10 mg/kg BW), accorded protection against nimesulide hepatotoxicity in vivo, as evident from normalized serum biomarkers and histopathology. mRNA expression and activity of key antioxidant and redox enzymes along with oxidative stress were also normalized due to CG pre-treatment. Downstream effects like decreased mitochondrial swelling, inhibition in release of apoptotic proteins, prevention of mitochondrial depolarization along with reduction in oxidized NAD(P)H and increased mitochondrial electron flow further supported protective action of selected terpenes against nimesulide toxicity. Therefore CG, a

  11. Association of the variants in AGT gene with modified drug response in Korean aspirin-intolerant asthma patients.

    PubMed

    Pasaje, Charisse Flerida A; Kim, Jeong-Hyun; Park, Byung-Lae; Cheong, Hyun Sub; Park, Tae-Joon; Lee, Jin-Sol; Kim, Yongha; Bae, Joon Seol; Kim, Jin Moo; Park, Jong Sook; Park, Choon-Sik; Shin, Hyoung Doo

    2011-10-01

    The angiotensinogen (AGT) gene enhances the effect of several bronchoconstrictors and produces a peptide that is accumulated in the airways of asthma patients; events that may underpin the pathogenesis of aspirin-intolerant asthma (AIA). To carry out a case-control analysis between AGT and aspirin-induced bronchospasm following treatment with an anti-asthma drug, montelukast (MLK), 38 single nucleotide polymorphisms (SNPs) in AGT were genotyped in 56 AIA cohort. Genotyping was performed with TaqMan assay and haplotypes were inferred using PHASE algorithm ver. 2.0. Statistical analyses of each SNPs and haplotypes were performed using SAS version 9.1. Among 13 variants displaying significant signals, two SNPs (+2401C>G and +2476C>T) in the intronic region of AGT were significantly associated with modification of drug response even after correction for multiple testing (P=0.0009-0.002; P(corr)=0.02-0.03). Furthermore, the two variants also exhibited associations with MLK response rate (P=0.0003-0.0006; P(corr)=0.006-0.01). Although our results are preliminary and further replication in a larger-scale group of subjects should be warranted, these observations provide evidence that AGT variants might be one of genetic factors involved in the response of anti-asthma drugs in AIA patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Assessing the influence of media composition and ionic strength on drug release from commercial immediate-release and enteric-coated aspirin tablets.

    PubMed

    Karkossa, Frank; Klein, Sandra

    2017-10-01

    The objective of this test series was to elucidate the importance of selecting the right media composition for a biopredictive in-vitro dissolution screening of enteric-coated dosage forms. Drug release from immediate-release (IR) and enteric-coated (EC) aspirin formulations was assessed in phosphate-based and bicarbonate-based media with different pH, electrolyte composition and ionic strength. Drug release from aspirin IR tablets was unaffected by media composition. In contrast, drug release from EC aspirin formulations was affected by buffer species and ionic strength. In all media, drug release increased with increasing ionic strength, but in bicarbonate-based buffers was delayed when compared with that in phosphate-based buffers. Interestingly, the cation species in the dissolution medium had also a clear impact on drug release. Drug release profiles obtained in Blank CarbSIF, a new medium simulating pH and average ionic composition of small intestinal fluid, were different from those obtained in all other buffer compositions studied. Results from this study in which the impact of various media parameters on drug release of EC aspirin formulations was systematically screened clearly show that when developing predictive dissolution tests, it is important to simulate the ionic composition of intraluminal fluids as closely as possible. © 2017 Royal Pharmaceutical Society.

  13. Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: a case-control study, systematic review and meta-analysis.

    PubMed

    Neill, Annette S; Nagle, Christina M; Protani, Melinda M; Obermair, Andreas; Spurdle, Amanda B; Webb, Penelope M

    2013-03-01

    Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk of a number of cancer types, however, previous studies of endometrial cancer have yielded inconclusive results. We analyzed data from the Australian National Endometrial Cancer Study (ANECS), a population-based case-control study (1,398 cases, 740 controls). We systematically reviewed all the evidence linking aspirin/NSAIDs use with endometrial cancer and conducted a meta-analysis. For ANECS, unconditional logistic regression was used to estimate odds ratios (OR) adjusting for potential confounders. For the systematic review, we searched Pubmed, Embase, Web of Science and conducted a review of citations from retrieved articles. The meta-analysis risk estimates were pooled using a random-effects model. In our case-control study, women who had ever used aspirin in the last 5 years had a significantly lower risk of endometrial cancer OR = 0.78 [95% confidence interval (CI): 0.63-0.97]. There was a significant inverse dose-response (p-trend <0.001) such that women who reported using ≥2 aspirin/week had almost half the risk OR = 0.54 (0.38-0.78). No significant associations were observed between use of half-aspirin/day, non-aspirin NSAIDs or paracetamol and endometrial cancer risk. The results were similar when examined by cancer subtype. Nine studies were included in the meta-analysis. The overall pooled risk estimate for any versus no use of aspirin was 0.87 (0.79-0.96) with no evidence of heterogeneity. The pooled risk estimate for obese women (BMI ≥ 30 kg/m(2) ) was 0.72 (0.58-0.90) but there was no association for non-obese women. Overall these results suggest that aspirin may reduce the risk of endometrial cancer, particularly among obese women.

  14. Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin?

    PubMed

    Strand, Vibeke

    2007-12-22

    Cyclo-oxygenase-2 selective inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) are associated with increased risk of acute cardiovascular events. Only aspirin offers primary and secondary cardiovascular prophylaxis, but trials have not answered directly whether low-dose aspirin is cardioprotective with COX-2 inhibitors. A large inception cohort study showed that concomitant use of aspirin reduced risk of cardiovascular events when given with rofecoxib, celecoxib, sulindac, meloxicam, and indometacin but not when given with ibuprofen. In large trials assessing gastrointestinal safety, there were fewer gastrointestinal events in patients using both COX-2 inhibitors and aspirin than in those using non-selective NSAIDs and aspirin; significantly fewer uncomplicated upper gastrointestinal events took place in the MEDAL trial. Analysis of VIGOR and two capsule endoscopy studies showed significantly less distal gastrointestinal blood loss with COX-2 inhibitors than with non-selective NSAIDs. Endoscopy trials showed that low-dose aspirin does not diminish the gastrointestinal benefits of COX-2 inibitors over non-selective NSAIDs. In an elderly epidemiological cohort receiving aspirin, both celecoxib and rofecoxib reduced risk of admission for gastrointestinal events. Comparison of the cardiovascular and gastrointestinal risks is difficult: likelihood and severity of cardiovascular events differ between individuals, agents, and exposure. Mortality associated with gastrointestinal events is less frequent than with cardiovascular events, but asymptomatic ulcers can result in severe complications. Data support the conclusion that COX-2 inhibitors are preferable to non-selective NSAIDs in patients with chronic pain and cardiovascular risk needing low-dose aspirin, but relative risks and benefits should be assessed individually for each patient.

  15. Aspirin, Nonaspirin Nonsteroidal Anti-inflammatory Drug, and Acetaminophen Use and Risk of Invasive Epithelial Ovarian Cancer: A Pooled Analysis in the Ovarian Cancer Association Consortium

    PubMed Central

    2014-01-01

    Background Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. Methods We analyzed pooled data from 12 population-based case–control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided. Results Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (≥500mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91). Conclusions Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use. PMID:24503200

  16. Indirect role of alpha2-adrenoreceptors in anti-ulcer effect mechanism of nimesulide in rats.

    PubMed

    Suleyman, Halis; Halici, Zekai; Cadirci, Elif; Hacimuftuoglu, Ahmet; Keles, Sait; Gocer, Fatma

    2007-05-01

    Nimesulide, a non-steroidal, anti-inflammatory drug, produces ulcerogenic effects in adrenalectomized rats but is gastro-protective in intact rats. The objective of this study was to determine whether adrenal gland hormones are involved in the anti-ulcer effects of nimesulide. The results revealed that 100 mg/kg nimesulide produces gastric ulceration in adrenalectomized rats, which is prevented by prednisolone and adrenaline. The anti-ulcer effects of adrenaline and prednisolone in adrenalectomized rats were in turn antagonized by yohimbine, a selective alpha(2)-receptor blocker, but not by doxazosine (alpha(1)-receptor blocker) or propranolol (beta-blocker). Adrenaline prevented the formation of indomethacin-induced ulcers in both adrenalectomized and intact rats, but prednisolone increased the indomethacin-induced ulcerous area in intact rats, whereas it decreased the size of the ulcers in adrenalectomized rats. In addition, prednisolone prevented ulcer formation in intact rats in which the adrenaline concentration had been decreased by metyrosine. These results suggest that glucocorticoids are anti-ulcerogenic in not only adrenalectomized rats but also in intact rats with diminished circulating levels of adrenaline. In the light of these data, the effect of nimesulide on plasma adrenaline concentrations was studied. In comparison to the adrenaline levels found in intact control rats, the administration of nimesulide at doses of 10, 20, 40 and 100 mg/kg decreased adrenaline concentrations by 12.8, 22.6, 30.4, and 58.2%, respectively, without affecting blood corticosterone concentrations. The anti-ulcer effect of nimesulide was observed to be dose-dependent, and the strength of this effect was directly correlated the decreasing concentration of adrenaline. The concentration of adrenaline was decreased by 60.9% in rats treated with 300 mg/kg metyrosine in which prednisolone produced anti-ulcer effects. In summary, we have shown that nimesulide produces its anti

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

    PubMed

    Shim, Young Kwang; Kim, Nayoung

    2016-06-25

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

  18. [Mechanisms of aspirin intolerance].

    PubMed

    Moneret-Vautrin, D A; Wayoff, M; Bonne, C

    1985-01-01

    Aspirin intolerance brings on cutaneous and/or respiratory reactions. The mechanisms are to be elucidated precisely, but are not IgE-mediated. 193 patients with nasal polyps are studied. With systematic aspirin oral challenge, 27% belong to the classical triad: asthma, polyps and aspirin sensitivity. Other drugs or chemicals intolerance are associated in 42%: alcohol, metabisulfites, benzoates, tartrazine, codeine... A link with the non-allergic eosinophilic rhinitis is suggested. A short review of several pathogenic hypothesis is discussed. Among a comparative study, the authors showed that the aspirin-intolerant patients' platelets have a quite normal arachidonic acid metabolism. The clue is probably towards an abnormal instability of cells membranes and excessive receptors sensitivity to leukotrienes.

  19. Magnesium sulfate and nimesulide have synergistic effects on rescuing brain damage after transient focal ischemia.

    PubMed

    Wang, Liang-Chao; Huang, Chih-Yuan; Wang, Hao-Kuang; Wu, Ming-Hsiu; Tsai, Kuen-Jer

    2012-05-01

    Magnesium sulfate and nimesulide are commonly used drugs with reported neuroprotective effects. Their combination as stroke treatment has the potential benefits of decreasing individual drug dosage and fewer adverse effects. This study evaluated their synergistic effects and compared a low-dose combination with individual drug alone and placebo. Sprague-Dawley rats underwent 90 min of focal ischemia with intraluminal suture occlusion of the middle cerebral artery followed by reperfusion. The rats were randomly assigned to receive one of the following treatments: placebo, magnesium sulfate (MgSO₄; 45 mg/kg) intravenously immediately after the induction of middle cerebral artery occlusion, nimesulide (6 mg/kg) intraperitoneally before reperfusion, and combined therapy. Three days after the ischemia-reperfusion insult, therapeutic outcome was assessed by 2,3,5-triphenyltetrazolium chloride staining and a 28-point neurological severity scoring system. Cyclooxygenase-2, prostaglandin E₂, myeloperoxidase, and caspase-3 expression after treatment were evaluated using Western blot analyses and immunohistochemical staining, followed by immunoreactive cell analysis using tissue cytometry. Only the combination treatment group showed a significant decrease in infarction volume (10.93±6.54% versus 26.43±7.08%, p<0.01), and neurological severity score (p<0.05). Low-dose MgSO₄ or nimesulide showed no significant neuroprotection. There was also significant suppression of cyclooxygenase-2, prostaglandin E₂, myeloperoxidase, and caspase-3 expression in the combination treatment group, suggesting that the combination of the two drugs improved the neuroprotective effects of each individual drug. MgSO₄ and nimesulide have synergistic effects on ischemia-reperfusion insults. Their combination helps decrease drug dosage and adverse effects. Combined treatment strategies may help to combat stroke-induced brain damage in the future.

  20. Rapeseed oil-rich diet alters in vitro menadione and nimesulide hepatic mitochondrial toxicity.

    PubMed

    Monteiro, João P; Silva, Ana M; Jurado, Amália S; Oliveira, Paulo J

    2013-10-01

    Diet-induced changes in the lipid composition of mitochondrial membranes have been shown to influence physiological processes. However, the modulation effect of diet on mitochondrially-active drugs has not yet received the deserved attention. Our hypothesis is that modulation of membrane dynamics by diet impacts drug-effects on liver mitochondrial functioning. In a previous work, we have shown that a diet rich in rapeseed oil altered mitochondrial membrane composition and bioenergetics in Wistar rats. In the present work, we investigated the influence of the modified diet on hepatic mitochondrial activity of two drugs, menadione and nimesulide, and FCCP, a classic protonophore, was used for comparison. The results showed that the effects of menadione and nimesulide were less severe on liver mitochondria for rats fed the modified diet than on rats fed the control diet. A specific effect on complex I seemed to be involved in drug-induced mitochondria dysfunction. Liver mitochondria from the modified diet group were more susceptible to nimesulide effects on MPT induction. The present work demonstrates that diet manipulation aimed at modifying mitochondrial membrane properties alters the toxicity of mitochondria active agents. This work highlights that diet may potentiate mitochondrial pharmacologic effects or increase drug-induced liabilities.

  1. Design and content determination of nimesulide injectable formulation.

    PubMed

    Luo, Lei; Tao, Wanfu; Bourkaib, Nadia; Luo, Yonghuang

    2015-07-01

    The aim of the present study was to formulate Nimesulide inject able solution, establish a method for content determination, and accumulate data for registration of a new Nimesulide formulation. The optimal Nimesulide inject able formulation was determined based on the results of single factor test and orthogonal test. Moreover, clarity, stability, pH, content and related substances of Nimesulide were used as the main study indicators. The content of Nimesulide in inject able solution was determined by the high performance liquid chromatography (HPLC) method. The mobile phase consisted of V (methanol): V (potassium dihydrogen phosphate, pH 4.2)=60:40 at a flow rate of 1.0 mL/min. The detection was carried out with UV detector (λ(max) =254 nm) under a column temperature of 25°C and an injection volume of 20μL. The optimal inject able formulation was 4% Nimesulide, 4% ethanolamine, 0.1% L-cysteine, 0.01% EDTA-2Na, a suitable amount of lactic acid and water for injection. Nimesulide detection limits range from 20 to 80 μg/mL with a correlation coefficient of 0.9995 and high average recovery 99.91% (RSD=0.06%). In conclusion, the formulation was suitable for Nimesulide inject able form, and the determination method was simple, sensitive and accurate. Therefore, the Nimesulide inject able formulation can be used for industrial production and effectively controlled.

  2. Effect of pH and water-soluble polymers on the aqueous solubility of nimesulide in the absence and presence of beta-cyclodextrin derivatives.

    PubMed

    Alexanian, Christina; Papademou, Helen; Vertzoni, Maria; Archontaki, Helen; Valsami, Georgia

    2008-11-01

    The aqueous solubility of nimesulide in the absence and presence of beta-cyclodextrin (beta-CD) and its alkyl derivatives hydroxypropyl-beta-CD and methyl-beta-CD was studied. We also investigated the effect of water-soluble polymers, hydroxypropylmethyl-cellulose, sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol on the solubilization efficacy and complexation ability of cyclodextrins with nimesulide. The solubility of nimesulide in the absence and presence of cyclodextrins and polymers was studied using a phase solubility technique combined with a spectrophotometric method. The study was carried out at 25 degrees C and pH values of 6.0 and 7.0. Conditions in terms of polymer concentration and polymer heating with and without sonication were optimized. Values of the solubility enhancement factor of nimesulide in the presence of each cyclodextrin and in the absence and presence of each polymer were determined and the formation constants, K, of the inclusion complexes formed calculated. beta-CDs increased the aqueous solubility of nimesulide in the following order: methyl-beta-CD > beta-CD > hydroxypropyl-beta-CD. Addition of hydroxypropylmethyl-cellulose at a concentration of 0.1% (w/v) had the greatest influence on complexation of all three beta-CDs with nimesulide, while preheating of the polymer at 70 degrees C under sonication resulted in an additional two-fold increase in the aqueous solubility of the drug. Sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol had minor effects on the aqueous solubility of nimesulide. Thus beta-CD, hydroxypropyl-beta-CD and methyl-beta-CD are proposed as good solubilizing agents for nimesulide in the presence and absence of hydroxypropylmethyl-cellulose in order to enhance its oral bioavailability.

  3. Competition between low-dose aspirin and other NSAIDs for COX-1 binding and its clinical consequences for the drugs' antiplatelet effects.

    PubMed

    Stepensky, David; Rimon, Gilad

    2015-01-01

    NSAIDs are frequently used in modern medicine to inhibit the COX enzymes and induce analgesic, antipyretic, anti-inflammatory, and antiplatelet effects. Concomitant treatment with two or more NSAIDs can lead to their competition for binding and inhibition of the COX enzymes and altered time course of the pharmacological effects. The competition between the low-dose aspirin and other NSAIDs for binding to COX-1 is described, including the recent findings on the differences in the interaction of NSAIDs with the individual COX-1 subunits, and the clinical consequences of this drug-drug interaction. The major pharmacokinetic (PK) and pharmacodynamic (PD) factors that govern the interaction of low-dose aspirin with other NSAIDs are explained, along with the approaches for prediction of the magnitude of this interaction using mechanism-based PK-PD modeling. Concomitant administration of other NSAIDs can diminish the antiplatelet effects of low-dose aspirin, increase the risk of thromboembolic effects (heart attacks and strokes), and lead to patient morbidity and mortality. The healthcare providers and the patients are seldom aware to this clinical problem and its consequences. Despite this drug interaction, low-dose aspirin possesses high clinical safety and it is not expected to be replaced by the recently approved drugs.

  4. Thermosensitive and mucoadhesive in situ gel based on poloxamer as new carrier for rectal administration of nimesulide.

    PubMed

    Yuan, Yuan; Cui, Ying; Zhang, Li; Zhu, Hui-Ping; Guo, Yi-Sha; Zhong, Bo; Hu, Xia; Zhang, Ling; Wang, Xiao-Hui; Chen, Li

    2012-07-01

    Poloxamer 407 has excellent thermo-sensitive gelling properties. Nevertheless, these gels possess inadequate poor bioadhesiveness and high permeability to water, which limited its' application as a thermoresponsive matrix. The main aim of the present investigation was to develop thermosensitive and mucoadhesive rectal in situ gel of nimesulide (NM) by using mucoadhesive polymers such as sodium alginate (Alg-Na) and HPMC. These gels were prepared by addition of mucoadhesive polymers (0.5%) to the formulations of thermosensitive gelling solution containing poloxamer 407 (18%) and nimesulide (2.0%). Polyethylene glycol (PEG) was used to modify gelation temperature and drug release properties. The gelation temperature and drug release rate of the prepared in situ gels were evaluated. Gelation temperature was significantly increased with incorporation of nimesulide (2.0%) in the poloxamer solution, while the addition of the mucoadhesive polymers played a reverse role on gelation temperature. The addition of PEG polymers increased the gelation temperature and the drug release rate. Among the formulations examined, the poloxamer 407/nimesulide/sodium alginate/PEG 4000 (18/2.0/0.5/1.2%) exhibited the appropriate gelation temperature, acceptable drug release rate and rectal retention at the administration site. Furthermore, the micrographic results showed that in situ gel, given at the dose of 20mg/kg, was safe for no mucosa irritation. In addition, it resulted in significantly higher initial serum concentrations, C(max) and AUC of NM compared to the solid suppository.

  5. Selective inhibition of COX-2 in humans is associated with less gastrointestinal injury: a comparison of nimesulide and naproxen

    PubMed Central

    Shah, A; Thjodleifsson, B; Murray, F; Kay, E; Barry, M; Sigthorsson, G; Gudjonsson, H; Oddsson, E; Price, A; Fitzgerald, D; Bjarnason, I

    2001-01-01

    BACKGROUND—Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal anti-inflammatory drugs.
AIMS—We compared the biochemical and gastrointestinal effects of nimesulide, a potent and selective COX-2 inhibitor, with naproxen which exhibits no selectivity.
SUBJECTS—Thirty six healthy volunteers were randomised to nimesulide 100 mg or naproxen 500 mg twice daily for two weeks in a double blind, crossover study with a washout between treatments.
METHODS—Gastrointestinal side effects were assessed by endoscopy, and by estimation of small intestinal absorption-permeability and inflammation. Comparisons were made between variables at the end of each treatment phase.
RESULTS—Nimesulide caused significantly less gastric injury using the modified Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039). Nimesulide had lower visual analogue scores (VAS) for haemorrhage and erosive lesions in the stomach (p<0.001) and for mucosal injection in the duodenum (p=0.039). Naproxen increased excretion of calprotectin, a marker of intestinal inflammation (5.5 (1.2) to 12.1 (2.1) mg/l) while nimesulide had no effect (treatment difference p=0.03). Naproxen abolished platelet aggregation to arachidonic acid and suppressed serum thromboxane B2 (TXB2) by 98%, indices of COX-1 activity. In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB2 by 29%. Production of prostaglandin E2 and prostacyclin by gastric biopsies, also COX-1 dependent, was inhibited by naproxen, but not by nimesulide. COX-2 activity, determined as endotoxin induced prostaglandin E2 formation in plasma, was markedly suppressed by both treatments.
INTERPRETATION—Nimesulide has preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses and induces less gastrointestinal damage than that seen with naproxen in the short term

  6. An aspirin a day.

    PubMed

    Majerus, Philip W

    2014-01-01

    The title of this article is also its punch line. The thesis that I will prove is that every adult, with a few exceptions, should take one 325 mg aspirin tablet each day. The drug is extraordinary and is beneficial in myriad ways. In this dosage the toxicity of the treatment is minimal. Since the drug is sold "over the counter", not requiring prescription, it is cheap and its benefits are easily underestimated. I do not use extensive reference citations; but just tell the story of aspirin.

  7. [U.S. Food and Drug Administration (FDA) strengthens warning that non-aspirin non steroidal anti-inflammatory drugs (NSAIDs) can cause myocardial infarctions or strokes: the dentist's perspective].

    PubMed

    Rosen, E; Tsesis, I; Vered, M

    2015-10-01

    This short communication is aimed to update dental practitioners regarding the recently published warning of the U.S. Food and Drug Administration (FDA) regarding the risk for severe cardiovascular complications such as myocardial infarction or stroke following the use of non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs).

  8. Adenosine signalling mediates the anti-inflammatory effects of the COX-2 inhibitor nimesulide.

    PubMed

    Caiazzo, Elisabetta; Maione, Francesco; Morello, Silvana; Lapucci, Andrea; Paccosi, Sara; Steckel, Bodo; Lavecchia, Antonio; Parenti, Astrid; Iuvone, Teresa; Schrader, Jürgen; Ialenti, Armando; Cicala, Carla

    2016-07-15

    Extracellular adenosine formation from ATP is controlled by ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase/CD39) and ecto-5'-nucleotidase (e-5NT/CD73); the latter converts AMP to adenosine and inorganic phosphate, representing the rate limiting step controlling the ratio between extracellular ATP and adenosine. Evidence that cellular expression and activity of CD39 and CD73 may be subject to changes under pathophysiological conditions has identified this pathway as an endogenous modulator in several diseases and was shown to be involved in the molecular mechanism of drugs, such as methotrexate, salicylates , interferon-β. We evaluated whether CD73/adenosine/A2A signalling pathway is involved in nimesulide anti-inflammatory effect, in vivo and in vitro. We found that the adenosine A2A agonist, 4-[2-[[6-amino-9-(N-ethyl-β-d-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid hydrochloride (CGS21680, 2mg/kg ip.), inhibited carrageenan-induced rat paw oedema and the effect was reversed by co-administration of the A2A antagonist -(2-[7-amino-2-[2-furyl][1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol (ZM241385; 3mg/kg i.p.). Nimesulide (5mg/kg i.p.) anti-inflammatory effect was inhibited by pre-treatment with ZM241385 (3mg/kg i.p.) and by local administration of the CD73 inhibitor, adenosine 5'-(α,β-methylene)diphosphate (APCP; 400μg/paw). Furthermore, we found increased activity of 5'-nucleotidase/CD73 in paws and plasma of nimesulide treated rats, 4h following oedema induction. In vitro, the inhibitory effect of nimesulide on nitrite and prostaglandin E2 production by lipopolysaccharide-activated J774 cell line was reversed by ZM241385 and APCP. Furthermore, nimesulide increased CD73 activity in J774 macrophages while it did not inhibit nitrite accumulation by lipopolysaccharide-activated SiRNA CD73 silenced J774 macrophages. Our data demonstrate that the anti-inflammatory effect of nimesulide in part is mediated by CD73

  9. Applying response surface methodology to optimize nimesulide permeation from topical formulation.

    PubMed

    Shahzad, Yasser; Afreen, Urooj; Nisar Hussain Shah, Syed; Hussain, Talib

    2013-01-01

    Nimesulide is a non-steroidal anti-inflammatory drug that acts through selective inhibition of COX-2 enzyme. Poor bioavailability of this drug may leads to local toxicity at the site of aggregation and hinders reaching desired therapeutic effects. This study aimed at formulating and optimizing topically applied lotions of nimesulide using an experimental design approach, namely response surface methodology. The formulated lotions were evaluated for pH, viscosity, spreadability, homogeneity and in vitro permeation studies through rabbit skin using Franz diffusion cells. Data were fitted to linear, quadratic and cubic models and best fit model was selected to investigate the influence of permeation enhancers, namely propylene glycol and polyethylene glycol on percutaneous absorption of nimesulide from lotion formulations. The best fit quadratic model explained that the enhancer combination at equal levels significantly increased the flux and permeability coefficient. The model was validated by comparing the permeation profile of optimized formulations' predicted and experimental response values, thus, endorsing the prognostic ability of response surface methodology.

  10. Potential of prescription registries to capture individual-level use of aspirin and other nonsteroidal anti-inflammatory drugs in Denmark: trends in utilization 1999–2012

    PubMed Central

    Schmidt, Morten; Hallas, Jesper; Friis, Søren

    2014-01-01

    Background Due to over-the-counter availability, no consensus exists on whether adequate information on nonsteroidal anti-inflammatory drug (NSAID) use can be obtained from prescription registries. Objectives To examine utilization of aspirin and nonaspirin NSAIDs in Denmark between 1999 and 2012 and to quantify the proportion of total sales that was sold on prescription. Method Based on nationwide data from the Danish Serum Institute and the Danish National Prescription Registry, we retrieved sales statistics for the Danish primary health care sector to calculate 1-year prevalences of prescription users of aspirin or nonaspirin NSAIDs, and to estimate the corresponding proportions of total sales dispensed on prescription. Results Both low-dose aspirin and nonaspirin NSAIDs were commonly used in the Danish population between 1999 and 2012, particularly among elderly individuals. The 1-year prevalence of prescribed low-dose aspirin increased throughout the study period, notably among men. Nonaspirin NSAID use was frequent in all age groups above 15 years and showed a female preponderance. Overall, the prevalence of prescribed nonaspirin NSAIDs decreased moderately after 2004, but substantial variation according to NSAID subtype was observed; ibuprofen use increased, use of all newer selective cyclooxygenase-2 inhibitors nearly ceased after 2004, diclofenac use decreased by nearly 50% after 2008, and naproxen use remained stable. As of 2012, the prescribed proportion of individual-level NSAID sales was 92% for low-dose aspirin, 66% for ibuprofen, and 100% for all other NSAIDs. Conclusion The potential for identifying NSAID use from prescription registries in Denmark is high. Low-dose aspirin and nonaspirin NSAID use varied substantially between 1999 and 2012. Notably, use of cyclooxygenase-2 inhibitors nearly ceased, use of diclofenac decreased markedly, and naproxen use remained unaltered. PMID:24872722

  11. Quantification of nimesulide in human plasma by high-performance liquid chromatography with ultraviolet detector (HPLC-UV): application to pharmacokinetic studies in 28 healthy Korean subjects.

    PubMed

    Kim, Mi-Sun; Park, Yoo-Sin; Kim, Shin-Hee; Kim, Sang-Yeon; Lee, Min-Ho; Kim, Youn-Hee; Kim, Do-Wan; Yang, Seok-Chul; Kang, Ju-Seop

    2012-05-01

    Nimesulide is a selective COX-2 inhibitor that is as effective as the classical non-acidic nonsteroidal anti-inflammatory drugs in the relief of various pain and inflammatory conditions, but is better tolerated with lower incidences of adverse effects than other drugs. After oral dose of 100 mg nimesulide to western subjects, a mean maximal concentration (C(max)) of 2.86 ∼ 6.5 µg/mL was reached at 1.22 ∼ 2.75 h and mean t(1/2β) of 1.8 ∼ 4.74 h. This study developed a robust method for quantification of nimesulide for the pharmacokinetics and suitability of its dosage in Korea and compared its suitability with other racial populations. Nimesulide and internal standard were extracted from acidified samples with methyl tert-butyl ether and analyzed by high-performance liquid chromatography with ultraviolet detection (HPLC-UV). The 28 healthy volunteers took 2 tablets of 100 mg nimesulide and blood concentrations were analyzed during the 24 h post dose. Several pharmacokinetic parameters were represented: AUC(0-infinity) = 113.0 mg-h/mL, C(max) = 12.06 mg/mL, time for maximal concentrations (T(max)) = 3.19 h and t(1/2β) = 4.51 h. These were different from those of western populations as follows: AUC was 14.5% and C(max) was 28% that of of Korean subjects and T(max) and t(1/2β) were also different. The validated HPLC-UV method was successfully applied for the pharmacokinetic studies of nimesulide in Korean subjects. Because the pharmacokinetics of nimesulide were different from western populations, its dosage regimen needs to be adjusted for Koreans. © The Author [2012]. Published by Oxford University Press. All rights reserved.

  12. Noninvasive quantitation of drug concentration in prostate and seminal vesicles: improvement and validation with desipramine and aspirin.

    PubMed

    Cao, Ying-Jun; Caffo, Brian; Choi, Leena; Radebaugh, Christine L; Fuchs, Edward J; Hendrix, Craig W

    2008-02-01

    The accessory glands of the male genital tract are the sites of several major health problems, including benign prostatic hyperplasia, prostate cancer, and human immunodeficiency virus (HIV) transmission. We aimed to validate and improve our noninvasive method for the quantitation of drug concentrations in these physiological subcompartments. Twenty-seven men were dosed with 100 mg desipramine (a weak base) and 975 mg aspirin (a weak acid) and ejaculated their semen in 1 pass across 5 compartments of a collection device 2.5 hours later. A Bayesian latent-variable model previously developed by our group was further advanced for the estimation of drug concentrations in prostate and seminal vesicles based on drug and biomarker concentrations in the split ejaculate. Under normality assumptions, desipramine concentration (with 95% credible intervals) in prostate and seminal vesicles were 27 (8.3-52) ng/mL and 7.6 (4.0-11) ng/mL, respectively; salicylate concentration in prostate and seminal vesicles were 2.0 (0.093-6.5) microg/mL, and 9.9 (8.2-12) microg/mL, respectively. The prostate-to-seminal vesicles concentration ratio was 0.20 (0.0087-0.75) for salicylate and 3.6 (0.91-9.9) for desipramine. We conclude that our quantitative analysis along with the split ejaculate method is sensitive, reproducible, and applicable for the assessment of pharmacokinetics of the accessory glands of the male genital tract.

  13. Self-Assembled Lipid Cubic Phase and Cubosomes for the Delivery of Aspirin as a Model Drug.

    PubMed

    Kulkarni, Chandrashekhar V; Vishwapathi, Vinod Kumar; Quarshie, Abraham; Moinuddin, Zeinab; Page, James; Kendrekar, Pravin; Mashele, Samson S

    2017-09-05

    Three-dimensionally organized lipid cubic self-assemblies and derived oil-in-water emulsions called "cubosomes" are attractive for various biotechnological applications due to their ability to be loaded with functional molecules and their associated sustained release properties. Here, we employed both of these lipid-based systems for the delivery of a model drug, aspirin, under comparable conditions. Studies were performed by varying drug-to-lipid ratio and the type of release medium, water and phosphate buffer saline (PBS). Release rates were determined using UV-vis spectroscopy, and small-angle X-ray scattering was used to confirm the type of self-assembled nanostructures formed in these lipid systems. The release from the bulk lipid cubic phase was sustained as compared to that of dispersed cubosomes, and the release in PBS was more efficient than in water. The tortuosity of the architecture, length of the diffusion pathway, type of nanostructure, and physicochemical interaction with the release media evidently contribute to these observations. This work is particularly important as it is the first report where both of these nanostructured lipid systems have been studied together under similar conditions. This work provides important insights into understanding and therefore controlling the release behavior of lipid-based drug nanocarriers.

  14. High on treatment platelet reactivity against aspirin by non-steroidal anti-inflammatory drugs--pharmacological mechanisms and clinical relevance.

    PubMed

    Hohlfeld, T; Saxena, A; Schrör, K

    2013-05-01

    Inhibition of platelet function by aspirin results from irreversible inhibition of platelet cyclooxygenase (COX)-1. While sufficient inhibition is obtained at antiplatelet doses (75-325 mg/day) in most (≥95%) treated patients, the antiplatelet effect of aspirin and subsequent cardiovascular risk reduction is much less in clinical settings and disease-dependent. Several reasons for this "high on treatment platelet reactivity" are known. This paper reviews the evidence for an interaction between aspirin and other COX inhibitors, namely non-steroidal anti-inflammatory drugs (NSAIDs). Numerous experimental studies demonstrated a pharmacodynamic interaction between aspirin and NSAIDs. This likely occurs within the hydrophobic substrate channel of platelet COX-1 and might be explained by molecular competition between inhibitor drugs and substrate (arachidonic acid) at overlapping binding sites. This interaction is found with some compounds, notably ibuprofen and dipyrone (metamizole), but not with others, such as diclofenac and acetaminophen (paracetamol). Hence, this interaction is not a class effect of NSAIDs and/or non-steroidal analgesics but rather due to specific structural requirements which still remain to be defined. In vivo studies on healthy subjects and patients tend to confirm this type of interaction as well as large differences between NSAIDs and non-steroidal analgesics, respectively. These interactions may be clinically relevant and may increase the cardiovascular risk in long-term treatment for primary and secondary cardiovascular prevention in patients with chronic inflammation, such as rheumatoid arthritis. These patients have an elevated risk for myocardial infarctions and may require chronic antiplatelet treatment by aspirin in addition to treatment of inflammatory pain.

  15. Nimesulide, a selective COX-2 inhibitor, acts synergistically with ionizing radiation against A549 human lung cancer cells through the activation of caspase-8 and caspase-3.

    PubMed

    Kim, Byeong Mo; Won, Juyoon; Maeng, Kyung Ah; Han, Young Soo; Yun, Yeon-Sook; Hong, Sung Hee

    2009-05-01

    Several lines of evidence suggest that non-steroidal anti-inflammatory drugs (NSAIDs) have a radiosensitizing effect on cancer cells in vitro and in vivo, but little is known about the underlying cellular mechanism. In this study, we found that the treatment with the NSAID nimesulide significantly increased the sensitivity of A549 human non-small cell lung cancer cells to radiotherapy. The combined nimesulide-radiation treatment increased apoptosis, induced the cleavage of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP), activated caspase-8, and induced cleavage of Bid. A pan-caspase inhibitor, z-VAD-fmk, suppressed this increase in apoptosis and also suppressed the cleavage of caspase-8, caspase-3, and PARP, suggesting a caspase-dependent mechanism. In addition, z-IETD-fmk, a selective caspase-8 inhibitor, suppressed the nimesulide- and radiation-induced cleavage activation of caspase-9, caspase-3, caspase-8, and Bid, and suppressed the concomitant apoptosis, indicating that the nimesulide-induced increase in radiosensitivity was initiated by caspase-8. However, the caspase-3 inhibitor z-DEVD-fmk failed to suppress activation of the caspase-8/Bid pathway, indicating that caspase-3 activation occurred downstream of caspase-8 activation in our experiments. Marked antitumor effects, which were evaluated by measuring protracted tumor regression, were observed when nude mice were treated with a combination of nimesulide at a clinically achievable dose (0.5 mg/kg) and radiation therapy. Our results, demonstrating the radiosensitivity-increasing and tumor growth-inhibiting effects of nimesulide, suggest that nimesulide may be suitable as an adjuvant to enhance the efficacy and selectivity of radiotherapy.

  16. Nimesulide-induced severe hemolytic anemia and acute liver failure leading to liver transplantation.

    PubMed

    Rodrigo, L; de Francisco, R; Pérez-Pariente, J M; Cadahia, V; Tojo, R; Rodriguez, M; Lucena, Ma I; Andrade, R J

    2002-11-01

    We present the case of a 63-year-old woman who had undergone 7 months of treatment with Nimesulide (100 mg/b.i.d.) for symptomatic osteoarthritis. The patient was admitted to our unit with a clinical picture of progressive jaundice over 3 weeks. Clinical and analytical studies revealed acute liver failure, this being confirmed by liver biopsy, which showed submassive necrosis. Serological tests for different viral agents causing hepatitis were all negative. In addition, she presented a picture of severe haemolytic anaemia resistant to several treatments and needed multiple transfusions. Twenty-three days after admission, the patient presented hepatic encephalopathy and received an orthotopic liver transplant on day 25. The evolution after transplantation was good and the patient continues in good health with no evidence of haemolysis almost 2 years later. Liver toxicity due to Nimesulide is well known, but to our knowledge the occurrence of haemolytic anaemia has not been related to this drug previously. For these reasons, Nimesulide has been restricted or removed from the market in several countries in recent months.

  17. Comparative analysis of preemptive analgesic effect of tramadol chlorhydrate and nimesulide following third molar surgery.

    PubMed

    da Costa Araújo, Fábio Andrey; de Santana Santos, Thiago; de Morais, Hécio Henrique Araújo; Laureano Filho, José Rodrigues; de Oliveira E Silva, Emanuel Dias; Vasconcellos, Ricardo José Holanda

    2012-12-01

    The aim of this prospective, randomized, controlled, paired trial was to perform a comparative analysis of the preemptive analgesic effect of nimesulide and tramadol chlorhydrate during third molar surgery. The study was carried out between March and November 2009, involving 94 operations in 47 male and female patients with bilateral impacted lower third molars in comparable positions. The sample was divided into two groups. Group A received an oral dose of 100 mg of nimesulide 1 h prior to surgery. Group B received an oral dose of 100 mg of tramadol chlorhydrate 1 h prior to surgery. The following aspects were evaluated in the postoperative period: adverse effects of the drugs; amount of rescue medication used (acetaminophen 750 mg); and pain 5, 6, 24, 36, 48, 60, 72 and 84 h after surgery using a visual analog pain scale. Peak pain occurred 5 h after surgery in both groups, with a mean pain score of 2.3 in Group A and 3.0 in Group B; this difference did not achieve statistical significance (p > 0.141). Based on the sample studied, nimesulide and tramadol chlorhydrate demonstrate similar preemptive analgesic effects when used in lower third molar surgeries.

  18. Use of aspirin, non-steroidal anti-inflammatory drugs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis: a cohort study.

    PubMed

    Wu, Shaowei; Han, Jiali; Qureshi, Abrar A

    2015-02-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to induce or exacerbate psoriasis. We aimed to evaluate the association between several widely used analgesics, including aspirin, non-aspirin NSAIDs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis (PsA) in a large cohort of US women, the Nurses' Health Study II (1991-2005). Information on regular use of aspirin, NSAIDs, and acetaminophen was collected for 95,540 participants during the follow-up. During 1,321,280 person-years of follow-up, we documented 646 incident psoriasis cases and 165 concomitant PsA cases. Compared to women who reported no use, regular acetaminophen and NSAIDs users with more than 10 years of use had multivariate hazard ratios of 3.60 [95% confidence interval (CI): 2.02-6.41] and 2.10 (95% CI: 1.11-3.96) for PsA, respectively. There was no clear association between aspirin and risk of psoriasis or PsA. In conclusion, long-term acetaminophen and NSAIDs use may be associated with an increased risk of PsA. Special attention on psoriasis and PsA screening may be needed for those who are prescribed for acetaminophen and NSAIDs for long-term periods.

  19. Aspirin for Reducing Your Risk of Heart Attack and Stroke: Know the Facts

    MedlinePlus

    ... the-Counter Medicines Safe Daily Use of Aspirin Aspirin for Reducing Your Risk of Heart Attack and ... any pharmacy, grocery or convenience store and buy aspirin without a prescription. The Drug Facts label on ...

  20. Aspirin and allergic diseases: a review.

    PubMed

    Settipane, G A

    1983-06-14

    Aspirin intolerance manifests itself as an acute urticaria-angioedema, bronchospasm, severe rhinitis, or shock occurring within three hours of aspirin ingestion. Aspirin intolerance occurs most commonly in patients with chronic urticaria (23 percent), in whom it is mostly manifested by the urticarial type of aspirin intolerance, and in asthmatic persons (4 to 19 percent), in whom it is mostly manifested by the bronchospastic type. The frequency of aspirin intolerance in patients with nasal polyps is about 23 percent, and consists of the bronchospastic type of intolerance. There is no definite evidence that aspirin intolerance is mediated by an immunologic reaction. In the bronchospastic type, an association between prostaglandins and the slow-reacting substance of anaphylaxis seems likely. The pathogenic mechanism for the urticarial type of aspirin intolerance is unknown. Under carefully controlled conditions, a transient desensitization to aspirin is possible. Various drugs, most of which are prostaglandin inhibitors, cross-react with aspirin in intolerant persons. They are, in decreasing order of frequency, as follows: indomethacin (100 percent), ibuprofen, mefenamic acid, phenylbutazone, sodium benzoate, tartrazine and acetaminophen (5 percent). Aspirin is an efficacious drug with increasing therapeutic use. In order to minimize its risk and increase its safety, physicians should familiarize themselves with those high-risk conditions where aspirin therapy should be avoided, or at least used cautiously.

  1. The effect of guggulipid and nimesulide on MPTP-induced mediators of neuroinflammation in rat astrocytoma cells, C6.

    PubMed

    Niranjan, Rituraj; Rajasekar, N; Nath, Chandishwar; Shukla, Rakesh

    2012-12-05

    Oxidative stress plays an important role in the pathophysiology of Parkinson's disease (PD) but its mechanism is still not properly explored. Cyclooxygenase-2 (COX-2) inhibition has also been known a major neuroprotective strategy in the various 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) induced models of Parkinson's disease (PD) but its role in astrocytes is still not properly understood. The present study demonstrated that, guggulipid and nimesulide (preferentially selective COX-2 inhibitor) treatment of rat astrocytoma cells, C6 for 24 h significantly decreased MPTP (400 μM) induced nitrative and oxidative stress and intracellular calcium ion (Ca(2+)) level. Guggulipid and nimesulide also deactivated MPTP-induced P-p38 MAPK (Phosphorylated p38 mitogen-activated protein kinase) and down regulated expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and CHOP (C/EBP, homologous protein 10). At transcriptional level of inflammatory cytokine genes, guggulipid and nimesulide down regulated MPTP-induced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA expressions with up regulations in interleukin-6 (IL-6) and interleukin-1α (IL-1α) mRNA expressions. In addition to this, guggulipid and nimesulide inhibited translocation of nuclear factor kappa-B (NF-κB) from cytosol to nucleus. In conclusion, our findings elucidated the potential antioxidant and anti-neuroinflammatory effect of guggulipid and nimesulide in rat astrocytoma cells C6, which may suggest the use of these drugs in the management of neuroinflammation associated pathophysiology of PD.

  2. Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis

    PubMed Central

    Schwier, Nicholas; Tran, Nicole

    2016-01-01

    Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of therapy for the treatment of idiopathic pericarditis (IP). A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician’s understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts. ASA, ibuprofen, indometacin, and ketorolac relatively have the most evidence in the treatment of IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is the drug of choice in patients with coronary artery disease (CAD), heart failure (HF), or renal disease, but should be avoided in patients with asthma and nasal polyps, who are naïve to ASA therapy. Ibuprofen is an inexpensive and relatively accessible option in patients who do not have concomitant CAD, HF, or renal disease. Indometacin is not available over-the-counter in the USA, and has a relatively higher incidence of central nervous system (CNS) adverse effects. Ketorolac is an intravenous option; however, clinicians must be mindful of the maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the disease process of IP, they are part of first-line therapy (along with colchicine), for preventing recurrence of IP. ASA/NSAID choice should be dictated by comorbid conditions, tolerability, and adverse effects. Additionally, the clinician should be mindful of considerations such as tapering, high-sensitivity CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy. PMID:27023565

  3. Drug-protein binding of Danhong injection and the potential influence of drug combination with aspirin: Insight by ultrafiltration LC-MS and molecular modeling.

    PubMed

    Zhu, Junfeng; Yi, Xiaojiao; Huang, Peng; Chen, Shuqing; Wu, Yongjiang

    2017-02-05

    Danhong injection (DHI) is a widely used Chinese medicine injection (CMI) for the clinical treatment of cardiovascular and cerebrovascular diseases. In this study, a simple and efficient in vitro method based on ultrafiltration LC-MS and molecular modeling has been developed to study the human serum albumin (HSA) binding of the compounds in DHI. Seven major components including protocatechuic aldehyde, p-coumaric acid, salvianolic acid D, rosmarinic acid, salvianolic acid E, lithospermic acid and salvianolic acid B were identified as HSA ligands and their binding degrees in the proposed non-saturated model were 26.17, 37.69, 99.77, 91.78, 96.91, 99.42 and 98.10%, respectively. Considering the drug-HSA binding property of the compounds in DHI may change during drug combination therapy, competitive binding assay was carried out to evaluate the influence of aspirin on the DHI-HSA binding. Experimental results revealed that the salvianolic acids in DHI had stronger binding ability to HSA than sodium salicylate. To further verify the results above, molecular modeling and probe displacement assay were conducted to investigate the optimum binding site and binding affinity of the ligands on HSA. Our findings suggested that the established method could be a powerful tool to study the drug-HSA binding property of CMIs.

  4. The influence of excipients on the stability of the moisture sensitive drugs aspirin and niacinamide: comparison of tablets containing lactose monohydrate with tablets containing anhydrous lactose.

    PubMed

    Du, J; Hoag, S W

    2001-01-01

    The purpose of this study is to test the hypothesis that in tablet formulations, moisture-sensitive drugs formulated with lactose monohydrate have the same stability as formulations containing anhydrous lactose, and to characterize the kinetics of niacinamide degradation in the solid state. Aspirin and niacinamide decomposition were used as indicators of stability. Aspirin and niacinamide tablets containing either lactose monohydrate or anhydrous lactose were separately investigated at different temperatures and relative humidities; the stability tests were done at 25 degrees C--60% RH, 40 degrees C--80% RH, 60 degrees C--60% RH, 60 degrees C--80% RH, and 80 degrees C--80% RH. Official U.S. Pharmacopeia methods were used for the aspirin and niacinamide assays. Statistical analysis showed that tablets containing lactose monohydrate have the same stability as tablets containing anhydrous lactose, which means that even though water is present in the crystal structure, the bound water does not influence the reaction rate. In addition, niacinamide degradation in the solid-state can be described by a third order rate equation.

  5. Use of Aspirin, Nonsteroidal Anti-inflammatory Drugs, and Acetaminophen (Paracetamol), and Risk of Psoriasis and Psoriatic Arthritis: A Cohort Study

    PubMed Central

    Wu, Shaowei; Han, Jiali; Qureshi, Abrar A.

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to induce or exacerbate psoriasis. We aimed to evaluate the association between several widely used analgesics, including aspirin, nonaspirin NSAIDs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis (PsA) in a large cohort of US women (1991–2005). Information on regular use of aspirin, NSAIDs, and acetaminophen was collected for 95 540 participants during the follow-up. During 1 321 280 person-years of follow-up, we documented 646 incident psoriasis cases and 165 concomitant PsA cases. Compared to women who reported no use, regular acetaminophen and NSAIDs users with more than 10 years of use had multivariate hazard ratios (HRs) of 3.60 [95% confidence interval (CI): 2.02–6.41] and 2.10 (95% CI: 1.11–3.96) respectively for PsA. There was no clear association between aspirin and risk of psoriasis or PsA. In conclusion, long-term acetaminophen and NSAIDs use may be associated with an increased risk of PsA. Special attention on psoriasis and PsA screening may be needed for those who are prescribed for acetaminophen and NSAIDs. PMID:24691893

  6. Clinicians' Reports in Electronic Health Records Versus Patients' Concerns in Social Media: A Pilot Study of Adverse Drug Reactions of Aspirin and Atorvastatin.

    PubMed

    Topaz, Maxim; Lai, Kenneth; Dhopeshwarkar, Neil; Seger, Diane L; Sa'adon, Roee; Goss, Foster; Rozenblum, Ronen; Zhou, Li

    2016-03-01

    Large databases of clinician reported (e.g., allergy repositories) and patient reported (e.g., social media) adverse drug reactions (ADRs) exist; however, whether patients and clinicians report the same concerns is not clear. Our objective was to compare electronic health record data and social media data to better understand differences and similarities between clinician-reported ADRs and patients' concerns regarding aspirin and atorvastatin. This pilot study explored a large repository of electronic health record data and social media data for clinician-reported ADRs and patients concerns for two common medications: aspirin (n = 31,817 ADRs accessible in clinical data; n = 19,186 potential ADRs accessible in social media data) and atorvastatin (n = 15,047 ADRs accessible in clinical data; n = 23,408 potential ADRs accessible in social media data). We found that the most frequently reported ADRs matched the most frequent patients' concerns. However, several less frequently reported reactions were more prevalent on social media (i.e., aspirin-induced hypoglycemia was discussed only on social media). Overall, we found a relatively strong positive and statistically significant correlation between the frequency ranking of reactions and patients' concerns for atorvastatin (Pearson's r = 0.61, p < 0.001) but not for aspirin (Pearson's r = 0.1, p = 0.69). Future studies should develop further natural language methods for a more detailed data analysis (i.e., identifying causality and temporal aspects in the social media data).

  7. Temporal variability in the antiplatelet effects of clopidogrel and aspirin after elective drug-eluting stent implantation. An ADAPT-DES substudy.

    PubMed

    Nührenberg, Thomas G; Stratz, Christian; Leggewie, Stefan; Hochholzer, Willibald; Valina, Christian M; Gick, Michael; Kirtane, Ajay J; Stone, Gregg W; Neumann, Franz-Josef; Trenk, Dietmar

    2015-11-01

    Given conflicting data on temporal variability in pharmacodynamic platelet responses to clopidogrel, we investigated platelet reactivity on clopidogrel and aspirin for up to six months after elective percutaneous coronary intervention (PCI) with drug-eluting stents. Platelet reactivity was determined in 102 patients before loading with clopidogrel and aspirin, and on maintenance therapy after PCI on day 1, at one month and six months by VerifyNow™ P2Y12 and Aspirin assays and by residual platelet aggregation (RPA) on light transmission aggregometry using adenosine diphosphate and arachidonic acid. By VerifyNow testing, median (interquartile range) P2Y12 reaction units (PRU) on clopidogrel were 166 (90-234), 195 (124-257), and 198 (141-252) on day 1, one month and six months after PCI, respectively (p=0.005 day 1 to 1 month, and p=0.86 1 month to 6 months). Using a cut-off of > 208 PRU, 35 % of patients had high platelet reactivity (HPR) to clopidogrel on day 1, 43 % at one month, and 46 % at six months after PCI. Between day 1 and six months after PCI, 38.2 % of patients changed clopidogrel responder status at least once. Other cut-offs and RPA yielded similar results. Platelet inhibition by aspirin was consistent over time with only five patients being characterised as having HPR. Considerable variation in individual on-clopidogrel platelet reactivity was present during both the subacute and the late phases of maintenance therapy after elective PCI. Hence, the utility of contemporary platelet function testing to guide antiplatelet therapy may be limited.

  8. Association of nonsteroidal anti-inflammatory drugs and aspirin use and the risk of head and neck cancers: a meta-analysis of observational studies

    PubMed Central

    Liu, Huai; Jian, Chengzhu; Wang, Hui; Huang, Jin

    2016-01-01

    Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have emerged as the potential chemopreventive agents for a number of cancer types, however, previous studies of head and neck cancers (HNC) have yielded inconclusive results. We performed a meta-analysis of observational studies to quantitatively assess the association between NSAIDs use and the risk for HNC. Methods We searched Pubmed, Embase, Google scholar, and Cochrane library for relevant studies that were published in any language, from January 1980 to April 2016. We pooled the odds ratio (OR) from individual studies and performed subgroup, heterogeneity, and publication bias analyses. Results A total of eleven studies (eight case-control studies and three cohort studies), involving 370,000 participants and 10,673 HNC cases contributed to this meta-analysis. The results of these studies suggested that neither use of overall NSAIDs (OR=0.95; 95% CI, 0.81-1.11), aspirin (OR=0.93; 95% CI, 0.79-1.10), nor nonsteroidal NSAIDs (OR=0.92; 95% CI, 0.76-1.10) were associated with HNC risk. Similar nonsteroidal results were observed when stratified by HNC sites, study design, sample size, and varied adjustment factors. However, we found significant protective effect of ibuprofen (OR=0.85; 95% CI, 0.72-0.99) and long-term aspirin use (≧5years) (OR=0.75; 95% CI, 0.65-0.85) on HNC risk, with low heterogeneity and publication bias. Conclusions Our meta-analysis results do not support the hypothesis that overall use of NSAIDs significant reduces the risk of HNC. Whereas, we cannot rule out a modest reduction in HNC risk associated with ibuprofen and long-term aspirin use. PMID:27533449

  9. Design and synthesis of a biotinylated probe of COX-2 inhibitor nimesulide analog JCC76.

    PubMed

    Zhong, Bo; Lama, Rati; Smith, Kerri M; Xu, Yan; Su, Bin

    2011-09-15

    JCC76 is a derivative of cyclooxygenase-2(COX-2) selective inhibitor nimesulide and exhibits potent anti-breast cancer activity. It selectively induces apoptosis of Her2 positive breast cancer cells. However, the specific molecular targets of JCC76 still remain unclear, which significantly withdraw the further drug development of JCC76. To identify the molecular targets of JCC76, a six carbon linker and biotin conjugated JCC76 probe was designed and synthesized. The anti-proliferation activity of the probe and its analogs was evaluated. Published by Elsevier Ltd.

  10. A review of analytical techniques for determination of oxicams, nimesulide and nabumetone.

    PubMed

    Starek, Małgorzata; Krzek, Jan

    2009-01-15

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the group most often used in human health care, since they are available without prescription for treatment of fever and minor pain. The present review submitted the use of various analytical techniques for the determination of oxicams, nimesulide and nabumetone. This review covers the time period from 1990 to 2008 during which over 200 analytical methods including all types of chromatographic, spectrophotometric and voltammetric techniques were reported. Presented application concerns analysis of chosen NSAIDs from pharmaceutical formulations and biological samples.

  11. [Bleeding gastric ulcers and acute hepatitis: 2 simultaneous adverse reactions due to nimesulide in a case].

    PubMed

    Tejos, S; Torrejón, N; Reyes, H; Meneses, M

    2000-12-01

    A 66 year-old obese woman with arthrosis, self-medicated with oral nimesulide, 200 mg daily. After 6 weeks she developed nausea, jaundice and dark urine. Two weeks later she had recurrent hematemesis and was hospitalized. Besides obesity and anemia her physical examination was unremarkable. An upper GI endoscopy revealed 3 acute gastric ulcers and a 4th one in the pyloric channel. Abdominal ultrasonogram showed a slightly enlarged liver with diffuse reduction in ecogenicity; the gallbladder and biliary tract were normal. Blood tests demonstrated a conjugated hyperbilirubinemia (maximal total value: 18.4 mg/dl), ALAT 960 U/l, ASAT 850 U/l, GGT 420 U/l, alkaline phosphatases mildly elevated, pro-time 49% and albumin 2.7 mg/dl. Serum markers for hepatitis A, B and C viruses were negative. ANA, AMA, anti-SmA, were negative. Ceruloplasmin was normal. A liver biopsy showed bridging necrosis and other signs of acute toxic liver damage. Gastric ulcers healed after conventional treatment and hepatitis subsided after 2 months leaving no signs of chronic liver damage. The diagnosis of toxic hepatitis due to nimesulide was supported by the time-course of drug usage, sex, age, absence of other causes of liver disease, a compatible liver biopsy and the improvement after drug withdrawal. Peptic ulcers or toxic hepatitis have been previously described as independent adverse reactions in patients taking nimesulide or other NSAIDs but their simultaneous occurrence in a single patient is a unique event that deserves to be reported.

  12. Chemical insights in the concept of hybrid drugs: the antitumor effect of nitric oxide-donating aspirin involves a quinone methide but not nitric oxide nor aspirin.

    PubMed

    Hulsman, Niels; Medema, Jan Paul; Bos, Carina; Jongejan, Aldo; Leurs, Rob; Smit, Martine J; de Esch, Iwan J P; Richel, Dick; Wijtmans, Maikel

    2007-05-17

    Hybrid drug 1 (NO-ASA) continues to attract intense research from chemists and biologists alike. It consists of ASA and a -ONO2 group connected through a spacer and is in preclinical development as an antitumor drug. We report that, contrary to current beliefs, neither ASA nor NO contributes to this antitumor effect. Rather, an unsubstituted QM was identified as the sole cytotoxic agent. QM forms from 1 after carboxylic ester hydrolysis and, in accordance with the HSAB theory, selectively reacts with cellular GSH, which in turn triggers cell death. Remarkably, a derivative lacking ASA and the -ONO2 group is 10 times more effective than 1. Thus, our data provide a conclusive molecular mechanism for the antitumor activity of 1. Equally importantly, we show for the first time that a "presumed invisible" linker in a hybrid drug is not so invisible after all and is in fact solely responsible for the biological effect.

  13. The Effects of Etodolac, Nimesulid and Naproxen Sodium on the Frequency of Sister Chromatid Exchange after Enclused Third Molars Surgery

    PubMed Central

    Öztürk, Şükrü; Koçak, Hülya; Palanduz, Şükrü; Çefle, Kıvanç

    2008-01-01

    Purpose Non-steroidal anti-inflammatory drugs (NSAID) are frequently used in oral surgical procedures in dentistry. The evaluation of the frequency of sister chromatid exchange (SCE) is accepted as a reliable cytogenetic method to assess the genotoxic effects of environmental factors. Materials and Methods In this study, the genotoxic effects of various NSAIDs were assessed in 30 patients to who they were administered following encluosed third molar surgery using SCE analysis before and after the operation. The frequency of SCE was evaluated before the operation and after 3 days of etodolac, nimesulid and naproxen use. Results There was no statistically significant difference in the frequency of SCE between the preoperative and postoperative states in patients given etodolac, nimesulid or naproxen sodium. Conclusion Short term use of selective and non-selective NSAIDs was not associated with a significant genotoxic effect that could be detected using the SCE method in peripheric lymphocytes. PMID:18972594

  14. Management of NSAID/aspirin-induced small intestinal damage by GI-sparing NSAIDs, anti-ulcer drugs and food constituents.

    PubMed

    Satoh, H; Takeuchi, K

    2012-01-01

    Recent advances in endoscopic techniques such as capsule endoscopy have revealed that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) often cause mucosal lesions not only in the upper gastrointestinal tract, but also in the small intestine in humans. Gastric and duodenal lesions caused by NSAIDs can be treated with anti-secretory agents such as proton pump inhibitors or histamine H2-receptor antagonists; however, these drugs are ineffective in treating NSAID-induced lesions in the small intestine. Furthermore, there are few effective agents for the treatment of small intestinal lesions. Therefore, identification of effective therapies for the treatment of NSAID/aspirin-induced small intestinal lesions remains an urgent priority. In the present review, we focus on novel pharmacological treatments to prevent or reduce NSAID-induced intestinal lesions, i.e., 1) GI-sparing NSAIDs (NO- or H2S-NSAIDs, NSAIDs mixed with phosphatidylcholine); 2) anti-ulcer drugs such as mucosal protective agents (misoprostol, rebamipide, teprenone, etc.) and anti-secretory agents (lansoprazole, etc.); 3) antibiotics (metronidazole) and probiotics (Lactobacillus sp.); and 4) food constituents (lactoferrin and soluble dietary fibers). We surveyed data from clinical trials evaluating these novel treatments. Also reviewed herein were the pros and cons of the novel protective methods from the standpoint of safety, efficacy, convenience, and cost.

  15. 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)...

  16. 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)...

  17. Different effects of cytoprotective drugs on ethanol- and aspirin-induced gastric mucosal injury in pylorus-ligated rats

    SciTech Connect

    Takeuchi, K.; Nishiwaki, H.; Niida, H.; Okabe, S. )

    1990-02-01

    In anesthetized rats oral administration (2 ml) of both ethanol (50% in 150 mM HCl) and aspirin (80 mM in 150 mM HCl) produced bandlike lesions in the stomach, while more generalized lesions occurred in the pylorus-ligated stomach when the irritant was given intragastrically through the fistula prepared in the rumen and the mucosal folds were removed by stomach distension. The bandlike lesions induced in the intact stomach by both irritants were significantly and dose-dependently prevented by 16,16-dimethyl PGE2 (dmPGE2: 3 and 10 micrograms/kg, subcutaneously), cysteamine (30 and 100 mg/kg, subcutaneously) or timoprazole (10 and 30 mg/kg, per os) at the doses which significantly inhibited gastric motility. In the pylorus-ligated stomach, however, neither of these agents showed any protection against the generalized lesions induced by ethanol, but such lesions caused by aspirin were significantly prevented only by dmPGE2. These agents also showed similar effects against the reduction of transmucosal PD in the pylorus-ligated stomach exposed to ethanol and aspirin. These results suggest that (1) the formation of bandlike lesions caused by ethanol and aspirin depends on the presence of mucosal folds and may be prevented by the agents that inhibit gastric motility, (2) the pathogenesis of the lesions induced by aspirin and ethanol may be different in the pylorus-ligated stomach, and (3) dmPGE2 has a unique protective ability that is not shared by usual cytoprotective agents.

  18. Sodium salicylate sensitivity in an asthmatic patient with aspirin sensitivity.

    PubMed

    Park, H S; Lim, Y S; Suh, J E; Rhu, N S; Cho, D I; Kim, J W

    1991-06-01

    Non-acetylated salicylates have been recommended for use as alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs) in aspirin and/or tartrazine-sensitive patients. We experienced a case of an aspirin-sensitive asthmatic patient who developed a broncho-obstructive reaction after taking 100 mg of sodium salicylate. The result of this study suggests that sodium salicylate may cross-react with aspirin in aspirin-and tartrazine-sensitive patients.

  19. Sodium salicylate sensitivity in an asthmatic patient with aspirin sensitivity.

    PubMed Central

    Park, H. S.; Lim, Y. S.; Suh, J. E.; Rhu, N. S.; Cho, D. I.; Kim, J. W.

    1991-01-01

    Non-acetylated salicylates have been recommended for use as alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs) in aspirin and/or tartrazine-sensitive patients. We experienced a case of an aspirin-sensitive asthmatic patient who developed a broncho-obstructive reaction after taking 100 mg of sodium salicylate. The result of this study suggests that sodium salicylate may cross-react with aspirin in aspirin-and tartrazine-sensitive patients. PMID:1751016

  20. Neuroprotective mechanism of losartan and its interaction with nimesulide against chronic fatigue stress.

    PubMed

    Kumar, Anil; Singh, Barinder; Mishra, Jitendriya; Sah, Sangeeta Pilkhwal; Pottabathini, Raghavender

    2015-12-01

    Potential role of angiotensin-II and cyclooxygenase have been suggested in the pathophysiology of chronic fatigue stress. The present study has been designed to evaluate the neuroprotective effect of losartan and its interaction with nimesulide against chronic fatigue stress and related complications in mice. In the present study, male Laca mice (20-30 g) were subjected to running wheel activity test session (RWATS) for 6 min daily for 21 days. Losartan, nimesulide and their combinations were administered daily for 21 days, 45 min before being subjected to RWATS. Various behavioral and biochemical and neuroinflammatory mediators were assessed subsequently. 21 days RWATS treatment significantly decreased number of wheel rotations/6 min indicating fatigue stress like behaviors as compared to naive group. 21 days treatment with losartan (10 and 20 mg/kg, ip), nimesulide (5 and 10 mg/kg, po) and their combinations significantly improved behavior [increased number of wheel rotations, reversal of post-exercise fatigue, locomotor activity, antianxiety-like behavior (number of entries, latency to enter and time spent in mirror chamber), and memory performance (transfer latency in plus-maze performance task)], biochemical parameters (reduced serum corticosterone, brain lipid peroxidation, nitrite concentration, acetylcholinesterase activity, restored reduced glutathione levels and catalase activity) as compared to RWATS control. Besides, TNF-α, CRP levels were significantly attenuated by these drugs and their combinations as compared to control. The present study highlights the role of cyclooxygenase modulation in the neuroprotective effect of losartan against chronic fatigue stress-induced behavioral, biochemical and cellular alterations in mice.

  1. Nimesulide binding site in the B0AT1 (SLC6A19) amino acid transporter. Mechanism of inhibition revealed by proteoliposome transport assay and molecular modelling.

    PubMed

    Pochini, Lorena; Seidita, Angela; Sensi, Cristina; Scalise, Mariafrancesca; Eberini, Ivano; Indiveri, Cesare

    2014-06-01

    The effect of pharmaceutical compounds on the rat kidney B0AT1 transporter in proteoliposomes has been screened. To this aim, inhibition of the transport activity by the different compounds was measured on Na(+)-[(3)H]glutamine co-transport in the presence of membrane potential positive outside. Most of the tested drugs had no effect on the transport activity. Some compounds exhibited inhibitory effects from 5 to 88% at concentration of 300μM. Among the tested compounds, only the anti-inflammatory drug nimesulide exerted potent inhibition on B0AT1. From dose response analysis, an IC50 value of 23μM was found. Inhibition kinetic analysis was performed: noncompetitive inhibition of the glutamine transport was observed while competitive behaviour was found when the inhibition was analyzed with respect to the Na(+) concentration. Several molecules harbouring functional groups of nimesulide (analogues) were tested as inhibitors. None among the tested molecules has the capacity to inhibit the transport with the exception of the compound NS-398, whose chemical structure is very close to that of whole nimesulide. The IC50 for this compound was 131μM. Inhibition kinetics showed behaviour of NS-398 identical to that of nimesulide, i.e., noncompetitive inhibition respect to glutamine and competitive inhibition respect to Na(+). Molecular docking of nimesulide suggested that this drug is able to bind B0AT1 in an external dedicated binding site and that its binding produces a steric hindrance effect of the protein translocation path abolishing the transporter activity.

  2. Association of aspirin and non-steroidal anti-inflammatory drug use with risk of colorectal cancer according to genetic variants

    PubMed Central

    Nan, Hongmei; Hutter, Carolyn M.; Lin, Yi; Jacobs, Eric J.; Ulrich, Cornelia M.; White, Emily; Baron, John A.; Berndt, Sonja I.; Brenner, Hermann; Butterbach, Katja; Caan, Bette J.; Campbell, Peter T.; Carlson, Christopher S.; Casey, Graham; Chang-Claude, Jenny; Chanock, Stephen J.; Cotterchio, Michelle; Duggan, David; Figueiredo, Jane C.; Fuchs, Charles S.; Giovannucci, Edward L.; Gong, Jian; Haile, Robert W.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jenkins, Mark A.; Jiao, Shuo; Lindor, Noralane M.; Lemire, Mathieu; Le Marchand, Loic; Newcomb, Polly A.; Ogino, Shuji; Pflugeisen, Bethann M.; Potter, John D.; Qu, Conghui; Rosse, Stephanie A.; Rudolph, Anja; Schoen, Robert E.; Schumacher, Fredrick R.; Seminara, Daniela; Slattery, Martha L.; Thibodeau, Stephen N.; Thomas, Fridtjof; Thornquist, Mark; Warnick, Greg S.; Zanke, Brent W.; Gauderman, W. James; Peters, Ulrike; Hsu, Li; Chan, Andrew T.

    2015-01-01

    Importance Use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer. Prior studies examining a potential differential relationship of aspirin and NSAIDs with colorectal cancer risk according to genetic factors have been limited to analyses of candidate genes or pathways. Objective To comprehensively identify common genetic markers that characterize individuals who may obtain differential benefit from aspirin and/or NSAID chemoprevention, we tested gene by environment (G X E) interactions between regular use of aspirin and/or NSAIDs and single nucleotide polymorphisms (SNPs) across the genome in relation to risk of colorectal cancer. Design Case-control study using the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) that enrolled cases of colorectal cancer ascertained between 1976 and 2011 and matched controls. Odds ratios (ORs) of colorectal cancer and 95% confidence intervals (95% CIs) were estimated using conventional logistic regression analysis and case-only interaction analysis, after adjusting for age, sex, center, the first three principal components to account for population structure, and known colorectal cancer risk factors. For all genome-wide analyses, a two-sided p-value<5.0×10-8, which yields a genome-wide significance level of 0.05, was considered statistically significant. Setting 10 observational studies (5 case-control and 5 cohort studies) that were initiated between 1976 and 2003 across the U.S., Canada, Australia and Germany. Participants 8,634 colorectal cancer cases and 8,553 controls of European descent. Exposures Genome-wide SNP data generated from genome-wide association scans and imputation to HapMap II, as well as information on regular use of aspirin and/or NSAIDs and other colorectal cancer risk factors collected using in-person interviews and/or structured questionnaires. Main Outcomes and Measures

  3. [Blood platelets and asthma caused by aspirin].

    PubMed

    Joseph, M; Capron, A; Ameisen, J C; Martinot, J B; Tonnel, A B

    1987-10-01

    Platelets isolated from patients with aspirin-induced asthma (ASA patients) react abnormally in vitro to aspirin and to non-steroid anti-inflammatory drugs (NSAID), by generating cytocidal molecules, that can kill parasitic larvae and to oxygen-dependent free radicles, which may be detected by chemiluminescence, although these drugs do not have a similar effect on platelets from normal donors or allergic asthmatics. The abnormality appears to be associated with the inhibiting properties of NSAID and aspirin on the cyclo-oxygenase pathway, that leads to a defect of the binding of prostaglandin endoperoxide PGH2 to its receptors on the platelet membrane. In addition, another metabolite from the lipoxygenase pathway which is at present poorly defined seems to participate in the anomaly. Sodium salicylate, a naturally produced catabolite of aspirin, that is well-tolerated by ASA patients, inhibits the abnormal response of the platelets and this opens new perspectives in the management of aspirin-sensitive intolerance.

  4. Associations of aspirin, nonsteroidal anti-inflammatory drug and paracetamol use with PSA-detected prostate cancer: findings from a large, population-based, case-control study (the ProtecT study).

    PubMed

    Murad, Ali S; Down, Liz; Davey Smith, George; Donovan, Jenny L; Athene Lane, Janet; Hamdy, Freddie C; Neal, David E; Martin, Richard M

    2011-03-15

    Evidence from laboratory studies suggests that chronic inflammation plays an important role in prostate cancer aetiology. This has resulted in speculation that nonsteroidal anti-inflammatory drugs may protect against prostate cancer development. We analysed data from a cross-sectional case-control study (n(cases) = 1,016; n(controls) = 5,043), nested within a UK-wide population-based study that used prostate specific antigen (PSA) testing for identification of asymptomatic prostate cancers, to investigate the relationship of aspirin, nonsteroidal anti-inflammatory drug (NSAID) and paracetamol use with prostate cancer. In conditional logistic regression models accounting for stratum matching on age (5-year age bands) and recruitment centre, use of non-aspirin NSAIDs [odds ratio (OR) = 1.32; 95% confidence interval (CI): 1.04-1.67] or all NSAIDs (OR = 1.25; 95% CI = 1.07-1.47) were positively associated with prostate cancer. There were weaker, not conventionally statistically significant, positive associations of aspirin (OR = 1.13; 95% CI = 0.94-1.36) and paracetamol (OR = 1.20; 95% CI = 0.90-1.60) with prostate cancer. Mutual adjustment for aspirin, non-aspirin NSAIDs or paracetamol made little difference to these results. There was no evidence of confounding by age, family history of prostate cancer, body mass index or self-reported diabetes. Aspirin, NSAID and paracetamol use were associated with reduced serum PSA concentrations amongst controls. Our findings do not support the hypothesis that NSAIDs reduce the risk of PSA-detected prostate cancer. Our conclusions are unlikely to be influenced by PSA detection bias because the inverse associations of aspirin, NSAID and paracetamol use with serum PSA would have attenuated (not generated) the observed positive associations.

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

    NASA Astrophysics Data System (ADS)

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

    2013-09-01

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

  6. Isomeric iodinated analogs of nimesulide: Synthesis, physicochemical characterization, cyclooxygenase-2 inhibitory activity, and transport across Caco-2 cells.

    PubMed

    Yamamoto, Yumi; Arai, Jun; Hisa, Takuya; Saito, Yohei; Mukai, Takahiro; Ohshima, Takashi; Maeda, Minoru; Yamamoto, Fumihiko

    2016-08-15

    Isomeric iodinated derivatives of nimesulide, with an iodine substituent on the phenoxy ring, were prepared with the aim of identifying potential candidate compounds for the development of imaging agents targeting cyclooxygenase-2 (COX-2) in the brain. Both the experimental logP7.4 and pKa values for these iodinated analogs were in the acceptable range for passive brain penetration. The para-iodo-substituted analog was a more potent and selective COX-2 inhibitor than nimesulide, with a potency that was comparable to the reference drug, celecoxib. Iodination at the ortho- or meta-position of the phenoxy ring was associated with a substantial loss of COX-2 inhibitory activity. Transport studies across Caco-2 cell monolayers in the presence and absence of a P-glycoprotein (P-gp) inhibitor, verapamil, indicated that the para-iodo-substituted analog was not a P-gp transport substrate; this feature is a prerequisite for potential in vivo brain imaging compounds. The para-iodo-substituted analog of nimesulide appears to be an attractive candidate for the development of radioiodine-labeled tracers for in vivo brain imaging of COX-2 levels.

  7. High-intensity Statin Treatments in Clinically Stable Patients on Aspirin Monotherapy 12 Months After Drug-eluting Stent Implantation: A Randomized Study.

    PubMed

    Im, Eui; Cho, Yun-Hyeong; Suh, Yongsung; Cho, Deok-Kyu; Her, Ae-Young; Kim, Yong Hoon; Lee, Kyounghoon; Kang, Woong Chol; Yun, Kyeong Ho; Yoo, Sang-Yong; Cheong, Sang-Sig; Shin, Dong-Ho; Ahn, Chul-Min; Kim, Jung-Sun; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong-Ki

    2017-07-14

    Current guidelines on the treatment of blood cholesterol recommend continuous maintenance of high-intensity statin treatment in drug-eluting stent (DES)-treated patients. However, high-intensity statin treatment is frequently underused in clinical practice after stabilization of DES-treated patients. Currently, the impact of continuous high-intensity statin treatment on the incidence of late adverse events in these patients is unknown. We investigated whether high-intensity statin treatment reduces late adverse events in clinically stable patients on aspirin monotherapy 12 months after DES implantation. Clinically stable patients who underwent DES implantation 12 months previously and received aspirin monotherapy were randomly assigned to receive either high-intensity (40mg atorvastatin, n = 1000) or low-intensity (20mg pravastatin, n = 1000) statin treatment. The primary endpoint was adverse clinical events at 12-month follow-up (a composite of all death, myocardial infarction, revascularization, stent thrombosis, stroke, renal deterioration, intervention for peripheral artery disease, and admission for cardiac events). The primary endpoint at 12-month follow-up occurred in 25 patients (2.5%) receiving high-intensity statin treatment and in 40 patients (4.1%) receiving low-intensity statin treatment (HR, 0.58; 95%CI, 0.36-0.92; P = .018). This difference was mainly driven by a lower rate of cardiac death (0 vs 0.4%, P = .025) and nontarget vessel myocardial infarction (0.1 vs 0.7%, P = .033) in the high-intensity statin treatment group. Among clinically stable DES-treated patients on aspirin monotherapy, high-intensity statin treatment significantly reduced late adverse events compared with low-intensity statin treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01557075. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  8. In vitro study of the antioxidant properties of nimesulide and 4-OH nimesulide: effects on HRP- and luminol-dependent chemiluminescence produced by human chondrocytes.

    PubMed

    Zheng, S X; Mouithys-Mickalad, A; Deby-Dupont, G P; Deby, C M; Maroulis, A P; Labasse, A H; Lamy, M L; Crielaard, J M; Reginster, J Y; Henrotin, Y E

    2000-11-01

    Reactive oxygen species (ROS) are now recognized to play an important role in the pathogenesis of rheumatic diseases and constitute an interesting therapeutic target for drugs. This in vitro study was designed to evaluate the antioxidant properties of nimesulide (NIM), a nonsteroidal antiinflammatory drug of the sulfonanilide class, and its main metabolite 4-OH nimesulide (4-OHNIM). The scavenging effects of NIM and 4-OH NIM on hydroxyl radical ((.)OH) and superoxide anions (O(minusd)(2)) were investigated by electron spin resonance (ESR), using 5, 5-dimethylpyrroline-N-oxide (DMPO) as the spin trap agent. The quenching properties of these drugs on hypochlorite anion was studied by luminol enhanced chemiluminescence. Finally, the effects of NIM and 4-OHNIM on the reactive oxygen species production by human articular chondrocytes were recorded by HRP and luminol-enhanced chemiluminescence. By this method it has been demonstrated that NIM and 4-OHNIM, at concentrations ranging from 10 to 100 microM, are potent scavengers of(.)OH whereas only 4-OHNIM was capable to scavenge O(minusd)(2). Chemiluminescence generated by HOCl was also significantly and dose-dependently inhibited by both NIM and 4-OHNIM. Nevertheless, at each concentration tested, the inhibitory effect of 4-OHNIM was significantly more marked, even at the highest concentration (100 microM). Furthermore, when chondrocytes were pre-incubated for 48-96 h with NIM or 4-OHNIM, the luminol- and HRP-dependent CL produced by the cells was significantly inhibited in a dose-dependent manner. NIM and 4-OHNIM may protect cartilage against oxidative stress, not only by scavenging ROS but also by inhibiting their production by chondrocytes. Copyright 2000 OsteoArthritis Research Society International.

  9. Aspirin and some other nonsteroidal anti-inflammatory drugs inhibit cystic fibrosis transmembrane conductance regulator protein gene expression in T-84 cells.

    PubMed

    Tondelier, D; Brouillard, F; Lipecka, J; Labarthe, R; Bali, M; Costa de Beauregard, M A; Torossi, T; Cougnon, M; Edelman, A; Baudouin-Legros, M

    1999-01-01

    Cystic fibrosis (CF) is caused by mutations in the CF gene, which encodes CF transmembrane conductance regulator protein (CFTR), a transmembrane protein that acts as a cAMP-regulated chloride channel The disease is characterized by inflammation but the relationship between inflammation, abnormal transepithelial ion transport, and the clinical manifestations of CF are uncertain. The present study was undertaken to determine whether three nonsteroidal anti-inflammatory drugs (NSAIDs) (aspirin, ibuprofen, and indomethacin) modulate CFTR gene expression in T-84 cells. Treatment with NSAIDs reduced CFTR transcripts, and decreased cAMP-stimulated anion fluxes, an index of CFTR function. However, the two phenomena occurred at different concentrations of both drugs. The results indicate that NSAIDs can regulate both CFTR gene expression and the function of CFTR-related chloride transport, and suggest that NSAIDs act via multiple transduction pathways.

  10. Aspirin, non-aspirin analgesics and the risk of hypertension in the SUN cohort.

    PubMed

    Beunza, Juan José; Martínez-González, Miguel Angel; Bes-Rastrollo, Maira; Núñez-Córdoba, Jorge María; Toledo, Estefanía; Alonso, Alvaro

    2010-03-01

    The use of aspirin and non-aspirin analgesics has been associated with changes in blood pressure. The aim of this study was to investigate prospectively the association between the regular use of aspirin and non-aspirin analgesics and the incidence of hypertension. The SUN project is an ongoing, continuously expanding, prospective cohort of Spanish university graduates initially free of hypertension, cardiovascular disease, diabetes and cancer; 9986 (mean age 36 years) were recruited during 1999-2005 and followed up for a mean of 51 months. Regular aspirin and non-aspirin analgesic use and the presence of other risk factors for hypertension were assessed by questionnaire at baseline, and the incidence of hypertension was assessed using biennial follow-up questionnaires. In total, 543 new cases of hypertension were identified during follow-up. Regular aspirin use (i.e. 2 or more days/week) was associated with a higher risk of hypertension (hazard ratio=1.45; 95% confidence interval, 1.02-2.04) after adjustment for various confounding factors. Regular use of non-aspirin analgesic drugs was also associated with a higher risk of hypertension (hazard ratio=1.69; 95% confidence interval, 1.28-2.23). The regular use of aspirin and non-aspirin analgesics were both associated with an increased risk of developing hypertension, independently of other risk factors.

  11. Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate cancer incidence and mortality: a systematic review and meta-analysis

    PubMed Central

    2014-01-01

    Background It has been postulated that non-steroidal anti-inflammatory drugs (NSAIDs) use leads to decreased prostate cancer (PCa) risk. In recent years, NSAIDs’ role in PCa development has been extensively studied; however, there is not yet a definitive answer. Moreover, the epidemiological results for NSAIDs’ effect on PCa-specific mortality have been inconsistent. Therefore, we performed a meta-analysis to examine the controversy. Methods We performed a literature database search and included all published studies conducted in the general population exposed to any NSAID, extracting an odds ratio (OR) or a hazard ratio (HR) with 95% confidence intervals (95% CIs) that compared the incidence of PCa or PCa-specific mortality with non-exposure. We derived a pooled OR or HR using random or fixed effects models, as appropriate. Subgroup analyses were also performed. Results Thirty-nine studies (20 case–control and 19 cohort studies) were included in this analysis. Thirty-one studies were available concerning NSAID use and PCa incidence and eight studies on PCa-specific mortality. Compared to non-use, aspirin use was statistically significantly associated with PCa incidence risk, and the association was slightly stronger for advanced PCa than for total PCa (OR = 0.92, 95% CI = 0.87 to 0.97 for total PCa; OR = 0.81, 95% CI = 0.73 to 0.89 for advanced PCa). Aspirin use seems also to be associated with a modest reduction in PCa-specific mortality (HR = 0.86, 95% CI = 0.78 to 0.96 for total PCa; OR = 0.81, 95% CI = 0.71 to 0.92 for advanced PCa). Generally, the pooled effects for any NSAIDs, NA-NSAIDs and cyclooxygenase-2 inhibitors demonstrated no adverse or beneficial effects on PCa development or PCa-specific mortality, but the results were not consistent. The effect estimates did not vary markedly when stratified by study design and study quality but varied by geographic region. Furthermore, long-term aspirin use (≥4 years) was also significantly associated

  12. Timing of Aspirin and Other Nonsteroidal Anti-Inflammatory Drug Use Among Patients With Colorectal Cancer in Relation to Tumor Markers and Survival.

    PubMed

    Hua, Xinwei; Phipps, Amanda I; Burnett-Hartman, Andrea N; Adams, Scott V; Hardikar, Sheetal; Cohen, Stacey A; Kocarnik, Jonathan M; Ahnen, Dennis J; Lindor, Noralane M; Baron, John A; Newcomb, Polly A

    2017-08-20

    Purpose Regular use of aspirin is associated with improved survival for patients with colorectal cancer (CRC). However, the timing of and the subtype of CRC that would benefit the most from using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to survival is unclear. Patients and Methods In all, 2,419 patients age 18 to 74 years with incident invasive CRC who were diagnosed from 1997 to 2008 were identified from population-based cancer registries in the United States, Canada, and Australia. Detailed epidemiologic questionnaires were administered at study enrollment and at 5-year follow-up. Survival outcomes were completed through linkage to national death registries. BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator phenotype were also evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for overall survival (OS) and CRC-specific survival. Results After a median of 10.8 years of follow-up since diagnosis, 381 deaths (100 as a result of CRC) were observed. Compared with nonusers, postdiagnostic aspirin-only users had more favorable OS (HR, 0.75; 95% CI, 0.59 to 0.95) and CRC-specific survival (HR, 0.44; 95% CI, 0.25 to 0.71), especially among those who initiated aspirin use (OS: HR, 0.64; 95% CI, 0.47 to 0.86; CRC-specific survival: HR, 0.40; 95% CI, 0.20 to 0.80). The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status ( Pinteraction = .01). Use of any NSAID after diagnosis was associated with improved OS only among participants with KRAS wild-type tumors (HR, 0.60; 95% CI, 0.46 to 0.80) but not among those with KRAS-mutant tumors (HR, 1.24; 95% CI, 0.78 to 1.96). Conclusion Among long-term CRC survivors, regular use of NSAIDs after CRC diagnosis was significantly associated with improved survival in individuals with KRAS wild-type tumors.

  13. In vitro-in vivo correlation study on nimesulide loaded hydroxypropylmethylcellulose microparticles.

    PubMed

    Khan, Shujaat Ali; Ahmad, Mahmood; Murtaza, Ghulam; Aamir, Muhammad Naeem; Kousar, Rozina; Rasool, Fatima; Shahiq-u-Zaman

    2010-06-01

    This study involves mathematical simulation model such as in vitro-in vivo correlation (IVIVC) development for various extended release formulations of nimesulide loaded hydroxypropylmethylcellulose (HPMC) microparticles (M1, M2 and M3 containing 1, 2, and 3 g HPMC, respectively and 1 g drug in each) having variable release characteristics. In vitro dissolution data of these formulations were correlated to their relevant in vivo absorption profiles followed by predictability worth analysis of these Level A IVIVC. Nimaran was used as control formulation to validate developed formulations and their respective models. The regression coefficients of IVIVC plots for M1, M2, M3 and Nimaran were 0.834 9, 0.831 2, 0.927 2 and 0.898 1, respectively. The internal prediction error for all formulations was within limits, i.e., < 10%. A good IVIVC was found for controlled release nimesulide loaded HPMC floating M3 microparticles. In other words, this mathematical simulation model is best fit for biowaiver studies which involves study parameters as those adopted for M3 because the value of its IVIVC regression coefficient is the closest to 1 as compared to M1 and M2.

  14. Aspirin for the next generation

    PubMed Central

    Henderson, Nick; Smith, Tom

    2013-01-01

    First used as an analgesic and antipyretic, investigations into aspirin’s anti-inflammatory effects led to its establishment in 1974 as a drug that altered the activity of platelets to influence the course and incidence of myocardial infarction and cerebrovascular disease. It became the standard in treatment and prevention of vascular disorders. The 25th International Scientific Meeting on aspirin held at the Royal College of Physicians in London on 24th October 2012 took aspirin into fresh fields, among them cancer, diabetes, dementia and gynaecology. PMID:23589729

  15. 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.

  16. Treatment of de Quervain disease with triamcinolone injection with or without nimesulide. A randomized, double-blind, placebo-controlled trial.

    PubMed

    Jirarattanaphochai, Kitti; Saengnipanthkul, Sukit; Vipulakorn, Kitiwan; Jianmongkol, Surut; Chatuparisute, Piyawan; Jung, Surachai

    2004-12-01

    There is uncertainty as to whether supplemental oral nonsteroidal anti-inflammatory medication improves the effectiveness of steroid injections in the treatment of de Quervain disease. We tested the hypothesis that there are no significant differences in the success rates when this condition is treated with triamcinolone injection with or without supplemental oral nimesulide. In a randomized, double-blind trial, 160 patients with de Quervain disease received an injection of 10 mg of triamcinolone acetonide and either 200 mg of oral nimesulide for seven days (eighty patients) or placebo tablets for seven days (eighty patients). An independent, blinded evaluator assessed the primary outcomes (tenderness, pain, and the result on the Finkelstein test) at three weeks after injection. Adverse reactions were assessed, and probabilities of recurrence for both groups were compared. Factors possibly predictive of disease recurrence were also assessed. The success rate after one injection was 67% in the nimesulide group and 68% in the placebo group. The overall success rates after single or multiple injections with a mean follow-up of 13.6 months were 95% for both groups. No significant differences were noted with respect to the success rates (p = 0.69) or pain scores after treatment (p = 0.11). The most common adverse reactions to triamcinolone injection and nimesulide were pain after injection and dyspepsia, respectively. The symptoms of de Quervain disease recurred in 33% of the patients in the nimesulide group and in 37% of those in the placebo group. The median time of recurrence was at the fifth month in the nimesulide group and at the fourth month in the placebo group. The recurrence of symptoms was significantly (p = 0.01) related to the presence of crepitation (relative risk, 2.13; 95% confidence interval, 1.19 to 3.80). Supplemental oral administration of the nonsteroidal anti-inflammatory drug nimesulide does not improve the effectiveness of a single injection of

  17. 76 FR 53907 - Determination That TALWIN COMPOUND (Aspirin; Pentazocine Hydrochloride) Tablets, 325 Milligrams...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... HUMAN SERVICES Food and Drug Administration Determination That TALWIN COMPOUND (Aspirin; Pentazocine... Food and Drug Administration (FDA) has determined that TALWIN COMPOUND (aspirin; pentazocine... drug applications (ANDAs) for aspirin; pentazocine HCl tablets, 325 mg; EQ 12.5 mg base, if all...

  18. Impact of Aspirin and Clopidogrel Hyporesponsiveness in Patients Treated With Drug-Eluting Stents: 2-Year Results of a Prospective, Multicenter Registry Study.

    PubMed

    Stuckey, Thomas D; Kirtane, Ajay J; Brodie, Bruce R; Witzenbichler, Bernhard; Litherland, Claire; Weisz, Giora; Rinaldi, Michael J; Neumann, Franz-Josef; Metzger, D Christopher; Henry, Timothy D; Cox, David A; Duffy, Peter L; Mazzaferri, Ernest L; Gurbel, Paul A; Mehran, Roxana; Généreux, Philippe; Ben-Yehuda, Ori; Simonton, Charles A; Stone, Gregg W

    2017-08-28

    In this analysis of 2-year outcomes in the ADAPT-DES (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents) study, the authors sought to examine the independent associations between platelet reactivity to both aspirin and clopidogrel and subsequent outcomes. The relationship between platelet reactivity and long-term adverse events following implantation of drug-eluting stents (DES) has been incompletely characterized. The ADAPT-DES study was a multicenter registry of patients undergoing routine platelet function testing following percutaneous coronary intervention with DES. The primary study endpoint was definite or probable stent thrombosis (ST); other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding. A total of 8,582 patients were enrolled between 2008 and 2010; 46.3% of patients were on dual antiplatelet therapy at 2 years without discontinuation. At 2 years, definite or probable ST occurred in 92 patients (1.07%). In patients treated with dual antiplatelet therapy continuously for 2 years, high platelet reactivity on clopidogrel was independently associated with definite or probable ST (adjusted hazard ratio [HR]: 2.16; 95% confidence interval [CI]: 1.27 to 3.67; p = 0.003), myocardial infarction (adjusted HR: 1.35; 95% CI: 1.05 to 1.74; p = 0.02), freedom from clinically relevant bleeding (adjusted HR: 0.74; 95% CI: 0.62 to 0.90; p = 0.002), and all-cause mortality (adjusted HR: 1.36; 95% CI: 1.01 to 1.85; p = 0.04). Between years 1 and 2, high platelet reactivity was not associated with the very late ST and in patients on aspirin monotherapy, aspirin hyporesponsiveness was not associated with adverse outcomes. The present study confirms the strong relationship of high platelet reactivity on clopidogrel to 2-year ischemic and bleeding outcomes after DES. The majority of stent-related events occurred within the first year. Copyright © 2017 American College of Cardiology Foundation. Published by

  19. 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 ...

  20. 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…

  1. 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…

  2. Ibuprofen or aspirin in rheumatoid arthritis therapy.

    PubMed

    Blechman, W J; Schmid, F R; April, P A; Wilson, C H; Brooks, C D

    1975-07-28

    Ibuprofen is a nonsteroidal drug with analgesic, antipyretic, and anti-inflammatory properties that was recently introduced for use in antiarthritis therapy in the United States. In a year-long double-blind multiclinic trial in 885 patients with rheumatoid arthritis, ibuprofen was at least as satisfactory as aspirin, considering both efficacy and tolerance. In the majority of patients, daily doses ranged from 800 to 1,600 mg of ibuprofen and 3 to 6 gm of aspirin. The drugs did not differ greatly in providing relief from arthritis symptoms, but ibuprofen was definitely better tolerated, especially in regard to gastrointestinal complaints. Seven percent of the ibuprofen group dropped out of the study because of adverse reactions, as compared with 16% of the aspirin group; 17% of the ibuprofen group and 31% of the aspirin group had gastrointestinal symptoms.

  3. Point-of-care platelet function assays demonstrate reduced responsiveness to clopidogrel, but not aspirin, in patients with Drug-Eluting Stent Thrombosis whilst on dual antiplatelet therapy

    PubMed Central

    Hobson, Alex R; Petley, Graham; Morton, Geraint; Dawkins, Keith D; Curzen, Nick P

    2008-01-01

    Background To test the hypothesis that point-of-care assays of platelet reactivity would demonstrate reduced response to antiplatelet therapy in patients who experienced Drug Eluting Stent (DES) ST whilst on dual antiplatelet therapy compared to matched DES controls. Whilst the aetiology of stent thrombosis (ST) is multifactorial there is increasing evidence from laboratory-based assays that hyporesponsiveness to antiplatelet therapy is a factor in some cases. Methods From 3004 PCI patients, seven survivors of DES ST whilst on dual antiplatelet therapy were identified and each matched with two patients without ST. Analysis was performed using (a) short Thrombelastogram PlateletMapping™ (TEG) and (b) VerifyNow Aspirin and P2Y12 assays. TEG analysis was performed using the Area Under the Curve at 15 minutes (AUC15) as previously described. Results There were no differences in responses to aspirin. There was significantly greater platelet reactivity on clopidogrel in the ST group using the Accumetrics P2Y12 assay (183 ± 51 vs. 108 ± 31, p = 0.02) and a trend towards greater reactivity using TEG AUC15 (910 ± 328 vs. 618 ± 129, p = 0.07). 57% of the ST group by TEG and 43% of the ST cases by Accumetrics PRU had results > two standard deviations above the expected mean in the control group. Conclusion This study demonstrates reduced platelet response to clopidogrel in some patients with DES ST compared to matched controls. The availability of point-of-care assays that can detect these responses raises the possibility of prospectively identifying DES patients at risk of ST and manipulating their subsequent risk. PMID:18312665

  4. Purine Pathway Implicated in Mechanism of Resistance to Aspirin Therapy: Pharmacometabolomics-Informed-Pharmacogenomics

    PubMed Central

    Yerges-Armstrong, Laura M.; Ellero-Simatos, Sandrine; Georgiades, Anastasia; Zhu, Hongjie; Lewis, Joshua; Horenstein, Richard B.; Beitelshees, Amber L.; Dane, Adrie; Reijmers, Theo; Hankemeier, Thomas; Fiehn, Oliver; Shuldiner, Alan R.; Kaddurah-Daouk, Rima

    2014-01-01

    Though aspirin is a well-established antiplatelet agent, the mechanisms of aspirin resistance remain poorly understood. Metabolomics allows for measurement of hundreds of small molecules in biological samples enabling detailed mapping of pathways involved in drug response. We defined the metabolic signature of aspirin exposure in subjects from the Heredity and Phenotype Intervention (HAPI) Heart Study. Many metabolites, including known aspirin catabolites, changed upon exposure to aspirin and pathway enrichment analysis identified purine metabolism as significantly affected by drug exposure. Further, purines were associated with aspirin response and poor responders had higher post-aspirin adenosine and inosine than good responders (N=76;p<4×10-3 both). Using our established “pharmacometabolomics-informs-pharmacogenomics” approach we identified genetic variants in adenosine kinase (ADK) associated with aspirin response. Combining metabolomics and genomics allowed for more comprehensive interrogation of mechanisms of variation in aspirin response - an important step toward personalized treatment approaches for cardiovascular disease. PMID:23839601

  5. Lack of pharmacist-physician communication associated with nimesulide-induced oligohydramnios during pregnancy.

    PubMed

    Grincevičienė, Švitrigailė; Volochovič, Jelena; Grincevičius, Jonas

    2016-04-01

    The consequences of medication errors can be serious, especially in pregnant women. When decision-making is critical, physician-pharmacist communication has the potential to improve patient safety. In this report, we describe the case of a pregnant woman who developed oligohydramnios after taking nimesulide for neuropathic pain. The drug was improperly prescribed by a family physician and mistakenly dispensed by a community pharmacist. Oligohydramnios was observed during ultrasound examination and an iatrogenic cause was suspected. This case is presented to raise awareness that patient safety is threatened because of a lack of physician-pharmacist communication, especially for pregnant patients. Healthcare professionals are continually at-risk for making errors at work. Effective inter-professional communication should be an organisational tool to prevent adverse events for pregnant women.

  6. Acetylation of prostaglandin synthase by aspirin.

    PubMed Central

    Roth, G J; Stanford, N; Majerus, P W

    1975-01-01

    When microsomes of sheep or bovine seminal vesicles are incubated with [acetyl-3H]aspirin (acetyl salicylic acid), 200 Ci/mol, we observe acetylation of a single protein, as measured by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The protein has a molecular weight of 85,000 and corresponds to a similar acetylated protein found in the particulate fraction of aspirin-treated human platelets. The aspirin-mediated acetylation reaction proceeds with the same time course and at the same concentration as does the inhibition of prostaglandin synthase (cyclo-oxygenase) (EC 1.14.99.1; 8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase) by the drug. At 100 muM aspirin, 50% inhibition of prostaglandin synthase and 50% of maximal acetylation are observed after 15 min at 37 degrees. Furthermore, the substrate for cyclo-oxygenase, arachidonic acid, inhibits protein acetylation by aspirin at concentrations (50% inhibition at 10-30 muM) which correlate with the Michaelis constant of arachidonic acid as a substrate for cyclooxygenase. Arachidonic acid analogues and indomethacin inhibit the acetylation reaction in proportion to their effectiveness as cyclo-oxygenase inhibitors. The results suggest that aspirin acts as an active-site acetylating agent for the enzyme cyclo-oxygenase. This action of aspirin may account for its anti-inflammatory and anti-platelet action. PMID:810797

  7. Effects of nimesulide, acetylsalicylic acid, ibuprofen and nabumetone on cyclooxygenase-1- and cyclooxygenase-2-mediated prostanoid production in healthy volunteers ex vivo.

    PubMed

    Kerola, Markku; Vuolteenaho, Katriina; Kosonen, Outi; Kankaanranta, Hannu; Sarna, Seppo; Moilanen, Eeva

    2009-01-01

    : The beneficial actions of non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with inhibition of cyclooxygenase-2 (COX-2), whereas some of their adverse effects are associated mainly with inhibition of COX-1. Selective COX-2 inhibitors reduce the risk of gastrointestinal adverse events, but increase the risk of thromboembolic events pointing to importance of optimal COX-1/COX-2 inhibition in drug safety. We compared the effects of acetylsalicylic acid, ibuprofen, nabumetone and nimesulide on COX-1 and COX-2 pathways in healthy volunteers in an ex vivo set-up using single oral doses commonly used to treat acute pain. In a randomized, double-blind four-phase cross-over study, 15 healthy volunteers were given orally a single dose of either acetylsalicylic acid 500 mg, ibuprofen 400 mg, nabumetone 1 g or nimesulide 100 mg. Blood samples were drawn before and 1, 3, 6, 24 and 48 hr after the drug for the assessment of COX-1 and COX-2 activity. COX-1 activity was measured as thromboxane(2) production during blood clotting and COX-2 activity as endotoxin-induced prostaglandin E(2) synthesis in blood leucocytes. The data show that after a single oral dose these four NSAIDs have different profiles of action on COX-1 and COX-2. As expected, acetylsalicylic acid appeared to be COX-1-selective and ibuprofen effectively inhibited both COX-1 and COX-2. Nabumetone showed only a slight inhibitory effect on COX-1 and COX-2. Nimesulide caused almost complete suppression of COX-2 activity and a partial reduction of COX-1 activity. This confirms the relative COX-2 selectivity of nimesulide.

  8. Nimesulide/methyl β-cyclodextrin inclusion complexes: physicochemical characterization, solubility, dissolution, and biological studies.

    PubMed

    Auda, Sayed H

    2014-03-01

    Nimesulide (NIM) is an insoluble nonsteroidal anti-inflammatory drug (NSAID). Complexation of drug with methyl β-cyclodextrin was evaluated to improve solubility and dissolution rate of NIM. Complexation was achieved via a coevaporation technique to obtain different drug to polymer molar ratios (1:1, 1:2, and 1:3). The physicochemical characterization of the systems using powder X-ray diffraction and infrared spectroscopy was carried out to understand the influence of this technological process on the physical status of single components and complex systems and to detect possible interactions between drug and carrier. Moreover, quantitative solubility and in vitro dissolution studies of NIM alone and NIM inclusion complexes were studied in the dissolution media of phosphate buffer pH 5.5 and 7.4. The analysis provided existence of a molecular interaction between drug and carrier together in the complex state. The study showed that the inclusion systems enhanced of drug solubility, dissolution rate, and anti-inflammatory activity.

  9. [Study of aspirin and its interaction with DNA by Raman and UV spectroscopies].

    PubMed

    Kang, Qian-qian; Zhou, Guang-ming

    2012-03-01

    Normal Raman spectroscopy and surface-enhanced Raman spectroscopy of aspirin and aspirin tablet were reported, and the vibrational and enhanced peaks were assigned; the interaction of aspirin with DNA was investigated by SERS and UV. The results showed that NRS and SERS of aspirin and aspirin tablet were consistent basically, which indicated that excipient hardly affected the detection of aspirin; in SERS, aspirin was absorbed perpendicularly on silver colloid through the carboxyl group and the benzene ring; The interaction was mainly caused by the inserting-action mode between aspirin and DNA, and the benzene ring and C=O of aspirin were inserted between the base pair of the double helix structure of DNA, which provided important information and useful reference for understanding deeply the mechanism of action of this kind of drug.

  10. Aspirin inhibits formation of cholesterol rafts in fluid lipid membranes.

    PubMed

    Alsop, Richard J; Toppozini, Laura; Marquardt, Drew; Kučerka, Norbert; Harroun, Thad A; Rheinstädter, Maikel C

    2015-03-01

    Aspirin and other non-steroidal anti-inflammatory drugs have a high affinity for phospholipid membranes, altering their structure and biophysical properties. Aspirin has been shown to partition into the lipid head groups, thereby increasing membrane fluidity. Cholesterol is another well known mediator of membrane fluidity, in turn increasing membrane stiffness. As well, cholesterol is believed to distribute unevenly within lipid membranes leading to the formation of lipid rafts or plaques. In many studies, aspirin has increased positive outcomes for patients with high cholesterol. We are interested if these effects may be, at least partially, the result of a non-specific interaction between aspirin and cholesterol in lipid membranes. We have studied the effect of aspirin on the organization of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) membranes containing cholesterol. Through Langmuir-Blodgett experiments we show that aspirin increases the area per lipid and decreases compressibility at 32.5 mol% cholesterol, leading to a significant increase of fluidity of the membranes. Differential scanning calorimetry provides evidence for the formation of meta-stable structures in the presence of aspirin. The molecular organization of lipids, cholesterol and aspirin was studied using neutron diffraction. While the formation of rafts has been reported in binary DPPC/cholesterol membranes, aspirin was found to locally disrupt membrane organization and lead to the frustration of raft formation. Our results suggest that aspirin is able to directly oppose the formation of cholesterol structures through non-specific interactions with lipid membranes.

  11. Nonsteroidal Anti-Inflammatory Drug and Aspirin Use, and Mortality among Critically Ill Pandemic H1N1 Influenza Patients: an Exploratory Analysis.

    PubMed

    Epperly, Holly; Vaughn, Frances L; Mosholder, Andrew D; Maloney, Elizabeth M; Rubinson, Lewis

    2016-05-20

    We explored nonsteroidal anti-inflammatory drug (NSAID) and aspirin (ASA) use and mortality in the U.S. Department of Health and Human Services' registry of 683 adult and 838 pediatric critically ill pandemic 2009 H1N1 influenza (pH1N1) patients. Among adults, 88 (12.9%) and 101 (14.8%) reported pre-admission use of an NSAID and ASA, respectively; mortality was similar (23-24%) regardless of NSAID or ASA use. Mortality among 89 pediatric NSAID users and 749 nonusers did not differ significantly (10.1% and 8.8%, respectively). One of 16 pediatric ASA users died. Among pediatric patients, the adjusted relative risk estimate for NSAID use and 90-day mortality was higher when influenza vaccination was included in the model (risk ratio [RR] = 1.5; 95% confidence interval, 0.7-3.2), although not statistically significant. Among adults, RR estimates did not change appreciably after adjusting for age, sex, health status, or vaccine status. We found no compelling evidence that NSAID or ASA use influenced mortality in severe pH1N1.

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

    PubMed

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

    2014-07-28

    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.

  13. 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.

  14. [From the willow to aspirin].

    PubMed

    Lafont, Olivier

    2007-07-01

    At the beginning was the willow bark, which was considered as a medicine by Hippocrates, Dioscorides and Plinus. During the XVIIIth century, the Reverend Edward Stone re-discovered the willow for the cure of agues. In 1829, the french pharmacist Pierre Joseph Leroux isolated salicin. Raffaelle Piria was the first to synthesize salicylic acid from salicin (salicoside). Hermann Kolbe prepared salicylic acid from sodium phenate and carbon dioxide. And then acetylsalicylic acid was first prepared by Charles Gerhardt in 1853, but he did not succeed in identifying its structure. Felix Hoffmann, Arthur Eichengrun and Heinrich Dresen from Bayer Laboratories were at the origin of the use of Aspirin as a medicine. In 1971, John Vane showed that aspirin-like drugs inhibited prostaglandine synthesis.

  15. 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... placenta, and metritis. (2) Systemic therapy with methylprednisolone is contraindicated in animals with...

  16. 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... placenta, and metritis. (2) Systemic therapy with methylprednisolone is contraindicated in animals with...

  17. 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... placenta, and metritis. (2) Systemic therapy with methylprednisolone is contraindicated in animals with...

  18. Aspirin: History and Applications; Cross-Curricular Instructional Strategies, Ideas, and Applications for Teaching about Aspirin in the Science Classroom

    ERIC Educational Resources Information Center

    Hademenos, George

    2005-01-01

    Of the thousands of drugs and medicines available for the prevention, treatment, and control of human disease and discomfort, the most widely used is aspirin. The primary reason for aspirin's popularity is its capabilities as a pain reliever, fever reducer, and anti-inflammatory agent. This article explores the historical development of aspirin…

  19. Aspirin: History and Applications; Cross-Curricular Instructional Strategies, Ideas, and Applications for Teaching about Aspirin in the Science Classroom

    ERIC Educational Resources Information Center

    Hademenos, George

    2005-01-01

    Of the thousands of drugs and medicines available for the prevention, treatment, and control of human disease and discomfort, the most widely used is aspirin. The primary reason for aspirin's popularity is its capabilities as a pain reliever, fever reducer, and anti-inflammatory agent. This article explores the historical development of aspirin…

  20. Novel 4-acetamide-2-alkylthio-N-acetanilides resembling nimesulide: Synthesis, cell viability evaluation and in silico studies.

    PubMed

    Catarro, Mafalda; Serrano, João; Cavalheiro, Eunice; Ramos, Susana; Santos, Adriana O; Silvestre, Samuel; Almeida, Paulo

    2017-08-15

    Since nimesulide, a nonsteroidal anti-inflammatory drug, is known to be a selective inhibitor of cyclooxygenase-2 and shows activity against cancer cells, there has been much interest in developing related molecules with enhanced anticancer properties. Taking in consideration structural features of nimesulide analogues ten new ortho-(akylthio)-N-alkylacetanilides were synthesized and fully characterized. The antiproliferative effect of these acetanilides was evaluated against human breast (MCF-7) and prostate (LNCaP) cancer cell lines as well as normal human dermal fibroblasts (NHDF). In particular, acetoacetanilides with methylcyclohexyl and/or 2,4-dimethylbenzyl groups linked to amide group and/or to sulfur atom had interesting cytotoxicities against human breast cancer cells. Moreover, these groups caused an increase in the antiproliferative effect against both cancer cells. Docking studies revealed the possibility of these acetoacetanilides to be potential ligands of the androgen receptor, though hormone-independent mechanisms may be involved in antiproliferative effects shown by these acetoacetanilides. In addition, 3D-QSAR studies demonstrated that the cytotoxic activity against the human breast cancer cell line was dependent on both bulkiness and electrostatic nature of the N- and S-alkyl groups of acetoacetanilides. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Impairment of aspirin antiplatelet effects by non-opioid analgesic medication

    PubMed Central

    Polzin, Amin; Hohlfeld, Thomas; Kelm, Malte; Zeus, Tobias

    2015-01-01

    Aspirin is the mainstay in prophylaxis of cardiovascular diseases. Impaired aspirin antiplatelet effects are associated with enhanced incidence of cardiovascular events. Comedication with non-opioid analgesic drugs has been described to interfere with aspirin, resulting in impaired aspirin antiplatelet effects. Additionally, non-opioid analgesic medication has been shown to enhance the risk of cardiovascular events and death. Pain is very frequent and many patients rely on analgesic drugs to control pain. Therefore effective analgesic options without increased risk of cardiovascular events are desirable. This review focuses on commonly used non-opioid analgesics, interactions with aspirin medication and impact on cardiovascular risk. PMID:26225198

  2. Impairment of aspirin antiplatelet effects by non-opioid analgesic medication.

    PubMed

    Polzin, Amin; Hohlfeld, Thomas; Kelm, Malte; Zeus, Tobias

    2015-07-26

    Aspirin is the mainstay in prophylaxis of cardiovascular diseases. Impaired aspirin antiplatelet effects are associated with enhanced incidence of cardiovascular events. Comedication with non-opioid analgesic drugs has been described to interfere with aspirin, resulting in impaired aspirin antiplatelet effects. Additionally, non-opioid analgesic medication has been shown to enhance the risk of cardiovascular events and death. Pain is very frequent and many patients rely on analgesic drugs to control pain. Therefore effective analgesic options without increased risk of cardiovascular events are desirable. This review focuses on commonly used non-opioid analgesics, interactions with aspirin medication and impact on cardiovascular risk.

  3. Dissolution and pharmacokinetics of a novel micronized aspirin formulation.

    PubMed

    Voelker, M; Hammer, M

    2012-08-01

    Aspirin (acetylsalicylic acid, ASA) has been used as an analgesic, antipyretic and antiinflammatory drug for many years. A new 500 mg aspirin tablet formulation containing micronized active ingredient and an effervescent component has been developed for potential improvement in the onset of action for acute pain treatment. This paper describes the dissolution and the pharmacokinetics of the new formulation in comparison with regular aspirin tablets, aspirin granules and aspirin effervescent tablets. Micronized aspirin tablets dissolve significantly faster over a pH range from 1.2 to 6.8 compared to regular 500 mg aspirin tablets. Plasma concentration time curve comparison to regular 500 mg aspirin tablets showed a substantial improvement in the time to maximum plasma concentrations (T(max)) (ASA 17.5 min vs. 45 min) and an increase in maximum plasma concentration (C(max)) (ASA 13.8 μg/ml vs. 4.4 μg/ml) while the overall extent of exposure (AUC) remains almost unchanged. The data suggest a potential improvement for onset of action in treating acute pain with the new micronized aspirin formulation.

  4. NO-aspirin: mechanism of action and gastrointestinal safety.

    PubMed

    Fiorucci, S; Del Soldato, P

    2003-05-01

    Nitric oxide-releasing aspirins are new chemical entities obtained by adding a nitric oxide-releasing moiety to aspirin. NCX-4016 is the prototype of this family of molecules. NCX-4016 consists of the parent molecule (aspirin) linked to a 'spacer' via an ester linkage, which is in turn connected to a nitric oxide-releasing moiety. Both aspirin and nitric oxide moieties of NCX-4016 contribute to its effectiveness, the latter occurring via both cyclic guanosyl monophosphate-dependent and -independent mechanisms. In vitro studies have shown that NCX-4016 inhibits platelet aggregation induced by aspirin-sensitive (arachidonic acid) and aspirin-insensitive (thrombin) agonist. In contrast to aspirin, NCX-4016 exerts a multilevel regulation of inflammatory target, including caspase-1 and NF-kappaB. This broad spectrum of activities translates to an increased potency of this drug in modulating cardiovascular inflammation. Human studies have shown, that while nitric oxide-aspirin maintains its anti-thrombotic activity, it spares the gastrointestinal tract. Indeed, a 7-day course of NCX-4016 results in 90% reduction of gastric damage caused by equimolar doses of aspirin. Further studies are ongoing to define whether this superior anti-inflammatory and anti-thrombotic profile translates in clinical benefits in patients with cardiovascular diseases.

  5. Molecular targets of aspirin and cancer prevention

    PubMed Central

    Alfonso, L; Ai, G; Spitale, R C; Bhat, G J

    2014-01-01

    Salicylates from plant sources have been used for centuries by different cultures to treat a variety of ailments such as inflammation, fever and pain. A chemical derivative of salicylic acid, aspirin, was synthesised and mass produced by the end of the 19th century and is one of the most widely used drugs in the world. Its cardioprotective properties are well established; however, recent evidence shows that it can also act as a chemopreventive agent. Its antithrombotic and anti-inflammatory actions occur through the inhibition of cyclooxygenases. The precise mechanisms leading to its anticancer effects are not clearly established, although multiple mechanisms affecting enzyme activity, transcription factors, cellular signalling and mitochondrial functions have been proposed. This review presents a brief account of the major COX-dependent and independent pathways described in connection with aspirin's anticancer effects. Aspirin's unique ability to acetylate biomolecules besides COX has not been thoroughly investigated nor have all the targets of its primary metabolite, salicylic acid been identified. Recent reports on the ability of aspirin to acetylate multiple cellular proteins warrant a comprehensive study to investigate the role of this posttranslational modification in its anticancer effects. In this review, we also raise the intriguing possibility that aspirin may interact and acetylate cellular molecules such as RNA, and metabolites such as CoA, leading to a change in their function. Research in this area will provide a greater understanding of the mechanisms of action of this drug. PMID:24874482

  6. Prevention of dipyrone (metamizole) induced inhibition of aspirin antiplatelet effects.

    PubMed

    Polzin, Amin; Richter, Stefan; Schrör, Karsten; Rassaf, Tienush; Merx, Marc W; Kelm, Malte; Hohlfeld, Thomas; Zeus, Tobias

    2015-07-01

    We have recently shown that dipyrone (metamizole), a non-opioid analgesic, can nullify aspirin (acetylsalicylic acid; ASA) antiplatelet effects in patients with coronary artery disease (CAD). In this study, we analysed the aspirin and dipyrone drug-drug interaction in order to identify strategies to prevent the dipyrone induced inhibition of asprin antiplatelet effects. Platelet function was measured by arachidonic acid-induced light-transmission aggregometry, thromboxane (TX) B2- formation by immunoassay. Dipyrone metabolite plasma levels were determined by high-performance-liquid-chromatography (HPLC). In seven healthy individuals, in vitro ASA (30 µM/ 100 µM/ 300 µM/ 1,000 µM) and dipyrone (10 µM) coincubation revealed, that the aspirin and dipyrone interaction can be overcome by increasing doses of aspirin. In 36 aspirin and dipyrone comedicated CAD patients, addition of ASA (30 µM/ 100 µM) in vitro inhibited, but did not completely overcome the dipyrone induced reduction of aspirin antiplatelet effects. Notably, the inhibition of thromboxane formation in aspirin and dipyrone comedicated CAD patients coincided with dipyrone plasma levels. In a cross-over designed study in four healthy individuals, we were able to prove that inhibition of aspirin (100 mg/ day) effects by dipyrone (750 mg/ day) was reversible. Furthermore, aspirin (100 mg/ day) medication prior to dipyrone (750 mg/ day) intake prevented the inhibition of antiplatelet effects by dipyrone in 12 healthy individuals. In conclusion, aspirin medication prior to dipyrone intake preserves antiplatelet effects, circumventing the pharmacodynamic drug-drug interaction at the level of cyclooxygenase-1.

  7. Involvement of electron and hydrogen transfers through redox metabolism on activity and toxicity of the nimesulide.

    PubMed

    Borges, Rosivaldo S; Oliveira, Juliana P; Matos, Rafaelle F; Chaves Neto, Antonio M J; Carneiro, Agnaldo S; Monteiro, Marta C

    2015-07-01

    An electronic study of nimesulide was performed by using density functional theory calculations. The activities of the six different derivatives were related with electron donating or accepting capacities. All compounds which had nitro moiety had low electron donating and high electron accepting capacities. However, the reduced derivative of nimesulide have more electron donating capacity than other compounds. The highest spin density contribution in nitro and lowest spin density contribution on phenoxyl moieties can be related with preferential metabolism by reduction when compared with the oxidation. The redox behavior between nitro and amino groups can be related with anti-inflammatory mechanism of nimesulide. These results explain the redox influence of nitro moiety on biological metabolism and mechanism of nimesulide.

  8. Isosorbide-based aspirin prodrugs: integration of nitric oxide releasing groups.

    PubMed

    Jones, Michael; Inkielewicz, Iwona; Medina, Carlos; Santos-Martinez, Maria Jose; Radomski, Anna; Radomski, Marek W; Lally, Maeve N; Moriarty, Louise M; Gaynor, Joanne; Carolan, Ciaran G; Khan, Denise; O'Byrne, Paul; Harmon, Shona; Holland, Valerie; Clancy, John M; Gilmer, John F

    2009-11-12

    Aspirin prodrugs and related nitric oxide releasing compounds hold significant therapeutic promise, but they are hard to design because aspirin esterification renders its acetate group very susceptible to plasma esterase mediated hydrolysis. Isosorbide-2-aspirinate-5-salicylate is a true aspirin prodrug in human blood because it can be effectively hydrolyzed to aspirin upon interaction with plasma BuChE. We show that the identity of the remote 5-ester dictates whether aspirin is among the products of plasma-mediated hydrolysis. By observing the requirements for aspirin release from an initial panel of isosorbide-based esters, we were able to introduce nitroxymethyl groups at the 5-position while maintaining ability to release aspirin. Several of these compounds are potent inhibitors of platelet aggregation. The design of these compounds will allow better exploration of cross-talk between COX inhibition and nitric oxide release and potentially lead to the development of selective COX-1 acetylating drugs without gastric toxicity.

  9. Aspirin for vascular dementia

    PubMed Central

    Rands, Gianetta; Orrell, Martin

    2014-01-01

    Background Aspirin is widely prescribed for patients with a diagnosis of vascular dementia. In a survey of UK geriatricians and psychiatrists 80% of patients with clinical diagnoses of vascular dementia were prescribed aspirin. However, a number of queries remain unanswered. Is there convincing evidence that aspirin benefits patients with vascular dementia? Does aspirin affect cognition and behaviour, or improve prognosis? Does the risk of cerebral or gastric haemorrhage outweigh any benefit? Objectives To assess the randomised trial evidence for efficacy and safety of aspirin in the treatment of vascular dementia. Search methods We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register on 12 March 2012 using the terms: aspirin OR “acetylsalicylic acid”. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources. In addition, relevant websites were searched and some journals were handsearched. Specialists in the field were approached for unpublished material and any publications found were searched for additional references. Selection criteria Randomised controlled trials investigating the effect of aspirin for vascular dementia were eligible for inclusion. Data collection and analysis Retrieved studies were analysed independently by both review authors. Methodology and results were critically appraised and outcomes scanned included cognition, behavioural change, mortality and institutionalisation. Main results No trials were eligible for inclusion in this review. Authors’ conclusions The most recent search for references to relevant research was carried out in March 2012. No trials were found for inclusion in this systematic review. Low-dose aspirin is frequently used as ‘treatment as normal’ in control groups and as a baseline treatment in pharmacological trials. There is still no good evidence that

  10. Aspirin and spinal haematoma after neuraxial anaesthesia: Myth or reality?

    PubMed

    Vela Vásquez, R S; Peláez Romero, R

    2015-11-01

    The safety of aspirin therapy in neuraxial anaesthesia has been historically questioned, and the current recommendations are still heterogeneous. A comprehensive review of clinical evidence and a comparative analysis of European and American guidelines were performed. Low-dose aspirin produces a selective, complete and irreversible cyclooxygenase-1 blockade, and higher doses do not increase the antiplatelet effect. Additional cyclooxygenase-2 blockade by high-dose aspirin might decrease the antithrombotic efficacy by inhibiting endothelial prostacyclin synthesis. Different doses of aspirin have been shown to be safe in a broad population subjected to neuraxial anaesthesia or analgesia. In the few case reports of spinal haematoma involving aspirin therapy, additional complicating factors were present. Considering the available evidence, the majority of national scientific societies agree that the isolated use of aspirin does not increase the risk of spinal haematoma and does not represent a contraindication to neuraxial blocks. The precautions regarding higher doses do not seem to be justified. Although aspirin alone is considered to be safe in neuraxial anaesthesia, the concurrent administration of other antithrombotic drugs significantly increases the risk of spinal haematoma and the recommended safety times for each of these other drugs must be strictly followed. An individualized assessment of the risks and benefits should be performed, before performing a neuraxial technique or catheter removal in a patient receiving aspirin.

  11. Interaction of nimesulide, a cyclooxygenase-2 inhibitor, with cisplatin in normotensive and spontaneously hypertensive rats.

    PubMed

    Al Suleimani, Yousuf M; Abdelrahman, Aly M; AlMahruqi, Ahmed S; Alhseini, Ishaq S; Tageldin, Mohamed H; Mansour, Mohamed E; Ali, Badreldin H

    2010-01-01

    We investigated the effect of administration of nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, on cisplatin (CP)-induced nephrotoxicity in rats. WKY rats and SHRs were divided into four groups, each. The first and second groups received saline and oral nimesulide (20mg/kg/day for 6 days), respectively, whereas the third and fourth groups received a single intraperitoneal (i.p.) injection of CP (5mg/kg) and CP (5mg/kg) and nimesulide (20mg/kg/day for 5 days), respectively. At the end of the experiment, rats were anesthetized and blood pressure and renal blood flow (RBF) were monitored, followed by intravenous (i.v.) injection of norepinephrine (NE). Nephrotoxicity was evaluated histopathologically and biochemically. CP caused a reduction in baseline RBF in both WKY and SHRs. It increased the concentrations of urea and creatinine and kidney relative weight, and decreased body weight in both WKY and SHRs. Histopathologically, CP caused remarkable renal damage in both WKY rats and SHRs. Treatment with nimesulide alone did not produce any significant change in any of the above measurements. However, nimesulide aggravated CP-induced renal tissue damage in SHRs, but not in WKY rats. The results show that administration nimesulide augmented the histopathological indices of nephrotoxicity in SHRs, but not in WKY rats.

  12. Nondestructive and rapid concurrent estimation of paracetamol and nimesulide in their combined dosage form using Raman spectroscopic technique.

    PubMed

    Lakhwani, Gargi R; Sherikar, O D; Mehta, Priti J

    2013-03-01

    A rapid, nondestructive Raman spectroscopic method was developed for quantitative estimation of paracetamol and nimesulide in their combined dosage form. A Raman univariate calibration model was developed by measuring the peak intensities of paracetamol and nimesulide at 853 cm(-1) and 1336 cm(-1), respectively. The developed method was successfully applied for in situ, concurrent estimation of paracetamol and nimesulide in their combined dosage and method was also validated according to International Conference on Harmonisation guidelines. Thus, the developed Raman spectroscopic method can be applied for simultaneous estimation of paracetamol and nimesulide in their combined dosage form as a process analytical technology tool by pharmaceutical industries for routine quality control.

  13. Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis).

    PubMed

    Colebatch, Alexandra N; Marks, Jonathan L; Edwards, Christopher J

    2011-11-09

    Methotrexate is routinely used in the treatment of inflammatory arthritis. There have been concerns regarding the safety of using concurrent non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, or paracetamol (acetaminophen), or both, in these people. To systematically appraise and summarise the scientific evidence on the safety of using NSAIDs, including aspirin, or paracetamol, or both, with methotrexate in inflammatory arthritis; and to identify gaps in the current evidence, assess the implications of those gaps and to make recommendations for future research to address these deficiencies. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, second quarter 2010); MEDLINE (from 1950); EMBASE (from 1980); the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE). We also handsearched the conference proceedings for the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) (2008 to 2009) and checked the websites of regulatory agencies for reported adverse events, labels and warnings. Randomised controlled trials and non-randomised studies comparing the safety of methotrexate alone to methotrexate with concurrent NSAIDs, including aspirin, or paracetamol, or both, in people with inflammatory arthritis. Two authors independently assessed the search results, extracted data and assessed the risk of bias of the included studies. Seventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis using various NSAIDs, including aspirin. There were no identified studies for other forms of inflammatory arthritis.For NSAIDs, 13 studies were included that used concurrent NSAIDs, of which nine studies examined unspecified NSAIDs. The mean number of participants was 150.4 (range 19 to 315), mean duration 2182.9 (range 183 to 5490) days, although the study duration was

  14. Controlled delivery of aspirin: effect of aspirin on polymer degradation and in vitro release from PLGA based phase sensitive systems.

    PubMed

    Tang, Yu; Singh, Jagdish

    2008-06-05

    The objective of this study was to develop poly (d,l-lactide-co-glycolide) (PLGA) based injectable phase sensitive in situ gel forming delivery system for controlled delivery of aspirin, and to characterize the effect of drug/polymer interaction on the in vitro release of aspirin and polymer degradation. Aspirin was dissolved into PLGA solution in 1-methyl-2-pyrrolidone. Poly(ethylene glycol)400 was used as plasticizer to reduce initial burst release. The solution formulation was injected into aqueous release medium to form a gel depot. Released samples were withdrawn periodically and assayed for aspirin content by high performance liquid chromatography. The effect of aspirin on the degradation of PLGA matrix was evaluated using Proton Nuclear Magnetic Resonance and Gel Permeation Chromatography. PLGA based in situ gel forming formulations controlled the in vitro release of aspirin for 7 days only. Analysis of PLGA matrix residuals revealed that PLGA in aspirin loaded formulations exhibited a significantly (p<0.05) faster degradation compared to blank formulations. These findings suggest that aspirin causes an unusually faster degradation of PLGA. Such faster degradation of PLGA has not been noticed for any other drugs reported in the literature.

  15. NCX-4040, a nitric oxide-releasing aspirin, sensitizes drug-resistant human ovarian xenograft tumors to cisplatin by depletion of cellular thiols.

    PubMed

    Bratasz, Anna; Selvendiran, Karuppaiyah; Wasowicz, Tomasz; Bobko, Andrey; Khramtsov, Valery V; Ignarro, Louis J; Kuppusamy, Periannan

    2008-02-26

    Ovarian carcinoma is the leading cause of mortality among gynecological cancers in the world. The high mortality rate is associated with lack of early diagnosis and development of drug resistance. The antitumor efficacy and mechanism of NCX-4040, a nitric oxide-releasing aspirin derivative, against ovarian cancer is studied. NCX-4040, alone or in combination with cisplatin (cis-diamminedichloroplatinum, cDDP), was studied in cisplatin-sensitive (A2780 WT) and cisplatin-resistant (A2780 cDDP) cell lines as well as xenograft tumors grown in nude mice. Electron paramagnetic resonance (EPR) was used for measurements of nitric oxide and redox state. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice was used for mechanistic studies. Cells treated with NCX-4040 (25 microM) showed a significant reduction of cell viability (A2780 WT, 34.9 +/- 8.7%; A2780 cDDP, 41.7 +/- 7.6%; p < 0.05). Further, NCX-4040 significantly enhanced the sensitivity of A2780 cDDP cells (cisplatin alone, 80.6 +/- 11.8% versus NCX-4040+cisplatin, 26.4 +/- 7.6%; p < 0.01) and xenograft tumors (cisplatin alone, 74.0 +/- 4.4% versus NCX-4040+cisplatin, 56.4 +/- 7.8%; p < 0.05), to cisplatin treatment. EPR imaging of tissue redox and thiol measurements showed a 5.5-fold reduction (p < 0.01) of glutathione in NCX-4040-treated A2780 cDDP tumors when compared to untreated controls. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice treated with NCX-4040 and cisplatin revealed significant downregulation of pEGFR (Tyr845 and Tyr992) and pSTAT3 (Tyr705 and Ser727) expression. The results suggested that NCX-4040 could resensitize drug-resistant ovarian cancer cells to cisplatin possibly by depletion of cellular thiols. Thus NCX-4040 appears to be a potential therapeutic agent for the treatment of human ovarian carcinoma and cisplatin-resistant malignancies.

  16. Aspirin and heart disease

    MedlinePlus

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

  17. Aspirin-Exacerbated Diseases: Advances in Asthma with Nasal Polyposis, Urticaria, Angioedema, and Anaphylaxis.

    PubMed

    Stevens, Whitney; Buchheit, Kathleen; Cahill, Katherine N

    2015-12-01

    Aspirin-exacerbated diseases are important examples of drug hypersensitivities and include aspirin-exacerbated respiratory disease (AERD), aspirin- or non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema, and aspirin- or NSAID-induced anaphylaxis. While each disease subtype may be distinguished by unique clinical features, the underlying mechanisms that contribute to these phenotypes are not fully understood. However, the inhibition of the cyclooxygenase-1 enzyme is thought to play a significant role. Additionally, eosinophils, mast cells, and their products, prostaglandins and leukotrienes, have been identified in the pathogenesis of AERD. Current diagnostic and treatment strategies for aspirin-exacerbated diseases remain limited, and continued research focusing on each of the unique hypersensitivity reactions to aspirin is essential. This will not only advance the understanding of these disease processes, but also lead to the subsequent development of novel therapeutics that patients who suffer from aspirin-induced reactions desperately need.

  18. Efficacy and Tolerability of Conventional Nimesulide Versus Beta-Cyclodextrin Nimesulide in Patients with Pain After Surgical Dental Extraction: A Multicenter, Prospective, Randomized, Double-Blind, Double-Dummy Study☆

    PubMed Central

    Bocanegra, Mildred; Seijas, Alberto; Yibirín, Maria González

    2003-01-01

    Background: Pain following extraction of an impacted third molar is widely used to assess analgesic efficacy, especially that of a single dose of a drug. The analgesic activity of conventional nimesulide (CN) has been documented in a variety of types of acute and chronic pain. Beta-cyclodextrin nimesulide (BN) is a new formulation in which nimesulide is included in a cyclodextrin molecule, which increases its solubility in water and its dilution rate, allowing extended, rapid absorption of the drug. Objective: The aim of this study was to assess the efficacy and tolerability of a single dose of BN compared with CN in patients with pain following extraction of an impacted third molar. Methods: This was a prospective, randomized, double-blind, double-dummy study conducted at 3 dentistry centers in Venezuela. The patients were randomized to 1 of 2 groups. One group received a single dose of BN (400-mg tablet, equivalent to 100 mg of nimesulide); the other group received a single dose of CN (100-mg tablet). Both groups also received a placebo. The efficacy variables were (1) pain intensity (PI), assessed on a visual analog scale (VAS) at the following times: 0, 5, 10, 15, 30, and 45 minutes and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration; (2) time to first measurable difference in PI from baseline (PID) (PID ≥1 cm on the VAS; ie, the beginning of analgesic action); (3) maximum PID (max PID); (4) sum of PIDs in the 12-hour observation period; (5) pain relief (PR), as rated on a 5-point scale; (6) maximum PR; and (7) sum of the PR scores in the 12-hour observation period (ie, total PR). For the tolerability analysis, all adverse events (AEs) were to be recorded, and the investigators were to assess whether each AE was drug related. Results: Seventy-two patients were enrolled in the study. Of these, 62 patients (40 women, 22 men; mean [SD] age, 20.1 [5.9] years) were assessed; 35 were treated with BN and 27 with CN. PI reduction was more rapid and greater

  19. Aspirin (acetylsalicylic acid) effects on behavioral thermoregulation with microwave radiation.

    PubMed

    Vitulli, W F; Laconsay, K L; Agnew, A C; Henderson, M E; Quinn, J M; Holland, B E; DePace, A N

    1993-08-01

    Aspirin is a widely used over-the-counter drug in our society which has wide therapeutic value, yet not all of the behavioral side effects have been studied. Different doses of aspirin solutions were administered (ip) prior to fixed-interval 2-min. schedules of microwave reinforcement in rats tested in a cold environment. Four Sprague-Dawley rats were conditioned to regulate their thermal environment with 5-sec. exposures of MW reinforcement. Friedman's nonparametric test showed significant differences among aspirin and saline-control doses. Post hoc sign tests showed that a moderate dose of aspirin increased operant behavior reinforced by MW radiation, yet lower and higher doses decreased and then increased the rate of responding which resulted in an inverted U-shaped trend. Possible multiple effects of aspirin in terms of its thermoregulatory as well as its pain-tolerance properties, and implications for hypothalamic "set point" are discussed.

  20. Does aspirin-induced oxidative stress cause asthma exacerbation?

    PubMed Central

    Kacprzak, Dorota

    2015-01-01

    Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflammatory disorders such as asthma. Moreover, increased levels of 8-isoprostanes, reliable biomarkers of oxidative stress in expired breath condensate in steroid-naïve patients with AIA compared to AIA patients treated with steroids and healthy volunteers, has been observed. This review is an attempt to cover aspirin-induced oxidative stress action in AIA and to suggest a possible related pathomechanism. PMID:26170841

  1. Aspirin-Exacerbated Respiratory Disease.

    PubMed

    Walgama, Evan S; Hwang, Peter H

    2017-02-01

    Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of asthma, sinonasal polyposis, and aspirin intolerance. The hallmark of the disease is baseline overproduction of cysteinyl leukotrienes via the 5-lipoxygenase pathway, exacerbated by ingestion of aspirin. Patients with AERD have high rates of recidivistic polyposis following sinus surgery, although the improvement in quality of life following surgery is similar to aspirin-tolerant patients. The diagnosis is secured by a positive aspirin provocation test, usually administered by a medical allergist. Aspirin therapy is a unique treatment consideration for patients with AERD.

  2. Risk of acute and serious liver injury associated to nimesulide and other NSAIDs: data from drug‐induced liver injury case–control study in Italy

    PubMed Central

    Donati, Monia; Conforti, Anita; Lenti, Maria Carmela; Capuano, Annalisa; Bortolami, Oscar; Motola, Domenico; Moretti, Ugo; Vannacci, Alfredo; Rafaniello, Concetta; Vaccheri, Alberto; Arzenton, Elena; Bonaiuti, Roberto; Sportiello, Liberata

    2016-01-01

    Aim Drug‐induced liver injury is one of the most serious adverse drug reactions and the most frequent reason for restriction of indications or withdrawal of drugs. Some nonsteroidal anti‐inflammatory drugs (NSAIDs) were withdrawn from the market because of serious hepatotoxicity. We estimated the risk of acute and serious liver injury associated with the use of nimesulide and other NSAIDs, with a prevalence of use greater than or equal to 5%. Methods This is a multicentre case–control study carried out in nine Italian hospitals from October 2010 to January 2014. Cases were adults, with a diagnosis of acute liver injury. Controls presented acute clinical disorders not related to chronic conditions, not involving the liver. Adjusted odds ratio (ORs) with 95% confidence interval (CI) were calculated initially with a bivariate and then multivariate analysis. Results We included 179 cases matched to 1770 controls. Adjusted OR for acute serious liver injury associated with all NSAIDs was 1.69, 95% CI 1.21–2.37. Thirty cases were exposed to nimesulide (adjusted OR 2.10, 95% CI 1.28–3.47); the risk increased according to the length of exposure (OR > 30 days: 12.55, 95% CI 1.73–90.88) and to higher doses (OR 10.69, 95% CI 4.02–28.44). Risk of hepatotoxicity was increased also for ibuprofen, used both at recommended dosages (OR 1.92, 95% CI 1.13–3.26) and at higher doses (OR 3.73, 95% CI 1.11–12.46) and for ketoprofen ≥ 150 mg (OR 4.65, 95% CI 1.33–10.00). Conclusion Among all NSAIDs, nimesulide is associated with the higher risk, ibuprofen and high doses of ketoprofen are also associated with a modestly increased risk of hepatotoxicity. PMID:26991794

  3. 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 ...

  4. Nimesulide-loaded nanoparticles for the potential coadjuvant treatment of prostate cancer.

    PubMed

    Huerta, Concepción; Aberturas, María del Rosario; Molpeceres, Jesús

    2015-09-30

    Nimesulide (NS)-loaded nanoparticles (NPNS) were prepared from polylactide-co-glycolide (PLGA) and eventually coated with chitosan (NPNSCS). Nanoparticles (NP) were spherical with sizes 379 ± 59 nm for NPNS and 393 ± 66 nm for NPNSCS and zeta potentials of -15 ± 3 mV for NPNS to 10 ± 4 mV for NPNSCS, suggesting an efficient coating. Drug encapsulation rate was high (88 ± 5% and 83 ± 7% of added drug) for NPNS and NPNSCS, respectively. After NP washing and re-suspension, 98 ± 2% and 99 ± 1% of the drug initially entrapped remained associated to NP. NS was dispersed in amorphous state within the polymeric matrix. Two-fold dilution of NP with pH 7.4 PBS provoked no drug release. However, 30-40% NS was released after a 1/10 dilution. NPNSCS and NPNS diluted 1/100 reduced the encapsulated drug to around 30% and 70%, respectively. In contrast, 100% NS was released from NP under sink conditions in less than 2h. The permeability of free-NS (1-1.5 × 10(-5)cm/s) was compared with NPNS (NPNS = 6.4-8.1 × 10(-6)cm/s and NPNSCS = 5.5-7.0 × 10(-6)cm/s) using the PAMPA assay. The cytotoxicity of free-NS and NS in NP on model prostate cancer cells PC-3 and DU-145 showed the highest cytotoxic effect with NPNSCS on PC-3 cells (IC50 = 89 μM).

  5. Cyclooxygenase-2 inhibitor nimesulide blocks ultraviolet B-induced photocarcinogenesis in SKH-1 hairless mice.

    PubMed

    Tang, Xiuwei; Kim, Arianna L; Kopelovich, Levy; Bickers, David R; Athar, Mohammad

    2008-01-01

    Cyclooxygenase-2 (COX-2) inhibition can inhibit UVB-induced carcinogenesis in the skin. We have shown that COX-2 is overexpressed in UVB-induced squamous cell carcinomas (SCCs). Celecoxib, a specific inhibitor of COX-2, blocks UVB-induced papillomas and carcinomas in murine skin. However, as COX-2 inhibitors of this type are associated with an increased risk of adverse cardiovascular events, we decided to study nimesulide, a different class of COX-2 inhibitor, an N-arylmethanesulfonamide derivative not known to have these untoward effects. To assess the antitumor-promoting effects of nimesulide, 90 mice were equally divided into three groups. Group I animals received no test agent or UVB and served as age-matched controls; group II animals were irradiated with UVB (180 mJ cm(-2), twice weekly for 35 weeks) and group III animals received 300 p.p.m. nimesulide in drinking water and were irradiated with UVB as described for group-II. Nimesulide treatment reduced the growth of UVB-induced tumors both in terms of tumor number and tumor volume. By weeks 25, 30 and 35, the tumor numbers in the nimesulide-treated group were 79%, 49% and 53% less than the number occurring in UVB-treated animals whereas tumor volume was reduced 69%, 54% and 53%, respectively, compared to the UVB-irradiated control group. Nimesulide also inhibited the malignant progression of SCCs. The reduction in tumorigenesis was paralleled by a decrease in cell cycle regulatory proteins (cyclins A, B1, D1, E, CDK2/4/6) and the antiapoptotic protein (Bcl2); concomitantly there was an increase in proapoptotic markers, poly (ADP-ribose) polymerase (PARP) and caspase-3. Nimesulide also decreased ornithine decarboxylase expression and the nuclear accumulation of nuclear factor kappa B transcriptionally active protein complexes. These results show that alternative classes of COX-2 inhibitors may likely be efficacious as cancer chemopreventive agents and may have an improved therapeutic index.

  6. Interaction of aspirin and vitamin C with bovine serum albumin.

    PubMed

    Nafisi, Shohreh; Bagheri Sadeghi, Golshan; PanahYab, Ataollah

    2011-12-02

    Vitamin C (L-ascorbic acid) has a major biological role as a natural antioxidant. Aspirin belongs to the nonsteroidal anti-inflammatory drugs and functions as an antioxidant via its ability to scavenge-OH radicals. Bovine serum albumin (BSA) is the major soluble protein constituent of the circulatory system and has many physiological functions including transport of a variety of compounds. In this report, the competitive binding of vitamin C and aspirin to bovine serum albumin has been studied using constant protein concentration and various drug concentrations at pH 7.2. FTIR and UV-Vis spectroscopic methods were used to analyze vitamin C and aspirin binding modes, the binding constants and the effects of drug complexation on BSA stability and conformation. Spectroscopic evidence showed that vitamin C and aspirin bind BSA via hydrophilic interactions (polypeptide and amine polar groups) with overall binding constants of K(vitamin C-BSA)=1.57×10(4)M(-1) and K(aspirin-BSA)=1.15×10(4)M(-1); assuming that there is one drug molecule per protein. The BSA secondary structure was altered with major decrease of α-helix from 64% (free protein) to 57% (BSA-vitamin C) and 54% (BSA-aspirin) and β-sheet from 15% (free protein) to 6-7% upon drug complexation, inducing a partial protein destabilization.

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

    PubMed Central

    Massimi, Isabella; Ciuffetta, Ambra; Temperilli, Flavia; Ferrandino, Francesca; Zicari, Alessandra; Pulcinelli, Fabio M.; Felli, Maria Pia

    2015-01-01

    Overexpression of efflux transporters, in human cells, is a mechanism of resistance to drug and also to chemotherapy. We found that multidrug resistance protein-4 (MRP4) overexpression has a role in reducing aspirin action in patients after bypass surgery and, very recently, we found that aspirin enhances platelet MRP4 levels through peroxisome proliferator activated receptor-α (PPARα). In the present paper, we verified whether exposure of human embryonic kidney-293 cells (Hek-293) to aspirin modifies MRP4 gene expression and its correlation with drug elimination and cell toxicity. We first investigated the effect of high-dose aspirin in Hek-293 and we showed that aspirin is able to increase cell toxicity dose-dependently. Furthermore, aspirin effects, induced at low dose, already enhance MRP4 gene expression. Based on these findings, we compared cell viability in Hek-293, after high-dose aspirin treatment, in MRP4 overexpressing cells, either after aspirin pretreatment or in MRP4 transfected cells; in both cases, a decrease of selective aspirin cell growth inhibition was observed, in comparison with the control cultures. Altogether, these data suggest that exposing cells to low nontoxic aspirin dosages can induce gene expression alterations that may lead to the efflux transporter protein overexpression, thus increasing cellular detoxification of aspirin. PMID:26491233

  8. NOSH-aspirin (NBS-1120), a dual nitric oxide and hydrogen sulfide-releasing hybrid, reduces inflammatory pain.

    PubMed

    Fonseca, Miriam D; Cunha, Fernando Q; Kashfi, Khosrow; Cunha, Thiago M

    2015-06-01

    The development of nitric oxide (NO)- and hydrogen sulfide (H2S)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) has generated more potent anti-inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H2S donors into aspirin (NOSH-aspirin) was recently developed. In the present study, the antinociceptive activity of this novel molecule was compared with aspirin in different models of inflammatory pain. It was found that NOSH-aspirin inhibits acetic acid-induced writhing response and carrageenan (Cg)-induced inflammatory hyperalgesia in a dose-dependent (5-150 μmol/kg, v.o.) manner, which was superior to the effect of the same doses of aspirin. NOSH-aspirin's antinociceptive effect was also greater and longer compared to aspirin upon complete Freund's adjuvant (CFA)-induced inflammatory hyperalgesia. Mechanistically, NOSH-aspirin, but not aspirin, was able to reduce the production/release of interleukin-1 beta (IL-1β) during Cg-induced paw inflammation. Furthermore, NOSH-aspirin, but not aspirin, reduced prostaglandin E2-induced hyperalgesia, which was prevented by treatment with a ATP-sensitive potassium channel (KATP) blocker (glibenclamide; glib.). Noteworthy, the antinociceptive effect of NOSH-aspirin was not associated with motor impairment. The present results indicate that NOSH-aspirin seems to present greater potency than aspirin to reduce inflammatory pain in several models. The enhanced effects of NOSH-aspirin seems to be due to its ability to reduce the production of pronociceptive cytokines such as IL-1 β and directly block hyperalgesia caused by a directly acting hyperalgesic mediator in a mechanism dependent on modulation of KATP channels. In conclusion, we would like to suggest that NOSH-aspirin represents a prototype of a new class of analgesic drugs with more potent effects than the traditional NSAID, aspirin.

  9. Comparative Evaluation of Nimesulide-Loaded Nanoparticles for Anticancer Activity Against Breast Cancer Cells.

    PubMed

    Sengel-Turk, Ceyda Tuba; Hascicek, Canan; Bakar, Filiz; Simsek, Elif

    2017-02-01

    Recent clinical and epidemiological researches have declared that non-steroidal anti-inflammatory agents may display as antineoplastic agents and indicate pro-apoptotic and antiproliferative effects on cancer cells. The major purpose of this research was to develop a novel poly(ethyleneglycol)-block-poly(ε-caprolactone) (PEG-b-PCL) nano-sized particles encapsulated with nimesulide (NMS), a selective COX-2 inhibitor, and to evaluate its anticancer activity against MCF-7 breast cancer cells. NMS-encapsulated PEG-b-PCL nanoparticles were fabricated using three different production techniques: (i) by emulsion-solvent evaporation using a high shear homogenizer, (ii) by emulsion-solvent evaporation using an ultrasonicator, and (iii) by nanoprecipitation. Nanoparticles were evaluated with respect to the entrapment efficiency, size characteristics, drug release rates, thermal behavior, cell viability assays, and apoptosis. The resulting nanoparticles were found to be spherical shapes with negative surface charges. The average diameter of all nanoparticles ranged between 148.5 and 307.2 nm. In vitro release profiles showed that all nanoparticles exhibited a biphasic release pattern. NMS-loaded PEG-b-PCL nanoparticles demonstrated significant anticancer activity against MCF-7 breast cancer cells in a dose-dependent manner, and the effects of nanoparticles on cell proliferation were significantly affected by the preparation techniques. The nanoparticles developed in this work displayed higher potential for the NMS delivery against breast cancer treatment for the future.

  10. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin...

  11. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin...

  12. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin...

  13. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin...

  14. 21 CFR 343.90 - Dissolution and drug release testing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin...

  15. [The concept of aspirin "resistance": mechanisms and clinical relevance].

    PubMed

    Reny, J-L; Bonvini, R F; Barazer, I; Berdagué, P; de Moerloose, P; Schved, J-F; Gris, J-C; Fontana, P

    2009-12-01

    Aspirin, a 110-year-old molecule, is a cornerstone in the treatment of atherothrombotic patients. The concept of aspirin "resistance" emerged approximately 15 years ago and is of growing interest. Aspirin resistance, defined as a lack of inhibition of cyclo-oxygenase-1 (COX-1), is a rare phenomenon and its clinical relevance can hardly be studied. On the contrary, residual platelet hyperactivity is more common and affects 20 to 30% of aspirin-treated patients. This latter phenomenon corresponds to sustained platelet reactivity despite a proper inhibition of COX-1 by aspirin. Several meta-analyses suggest that residual platelet hyperactivity could be a risk factor for the recurrence of ischemic events in aspirin-treated patients. Causes of biological non-responsiveness to aspirin are discussed, including the role of compliance, drug-drug interactions, genetic polymorphisms and diabetes mellitus. Ongoing studies are designed to find out the mechanisms of residual platelet hyperactivity, determine its potential clinical relevance and delineate the more appropriate assays in order to identify patients who may benefit of a tailored antiplatelet therapy.

  16. Aspirin treatment reduces platelet resistance to deformation.

    PubMed

    Burris, S M; Smith, C M; Rao, G H; White, J G

    1987-01-01

    The present investigation has evaluated the influence of aspirin, its constituents, and other nonsteroidal anti-inflammatory agents on the resistance of human platelets to aspiration into micropipettes. Aspirin increased the length of platelet extensions into the micropipette over the entire negative tension range of 0.04 to 0.40 dynes/cm after exposure to the drug in vitro or after ingestion of the agent. Other cyclooxygenase inhibitors, ibuprofen and indomethacin, did not increase platelet deformability. The influence of aspirin was mimicked to some degree by high concentrations of salicylic acid, but acetylation of platelets with acetic anhydride had little influence on platelet deformability. Incubation of platelets with both salicylic acid and acetic anhydride had no more effect than salicylic acid alone. Benzoic acid, chemically similar to salicylic acid, had a minimal effect. The studies demonstrate that aspirin makes platelets more deformable, while components of the drug or other nonsteroidal antiinflammatory agents and cyclooxygenase inhibitors do not have the same influence on resistance to deformation.

  17. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances

    PubMed Central

    Steinke, John W; Wilson, Jeff M

    2016-01-01

    Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. PMID:27022293

  18. Twisted aspirin crystals.

    PubMed

    Cui, Xiaoyan; Rohl, Andrew L; Shtukenberg, Alexander; Kahr, Bart

    2013-03-06

    Banded spherulites of aspirin have been crystallized from the melt in the presence of salicylic acid either generated from aspirin decomposition or added deliberately (2.6-35.9 mol %). Scanning electron microscopy, X-ray diffraction analysis, and optical polarimetry show that the spherulites are composed of helicoidal crystallites twisted along the <010> growth directions. Mueller matrix imaging reveals radial oscillations in not only linear birefringence, but also circular birefringence, whose origin is explained through slight (∼1.3°) but systematic splaying of individual lamellae in the film. Strain associated with the replacement of aspirin molecules by salicylic acid molecules in the crystal structure is computed to be large enough to work as the driving force for the twisting of crystallites.

  19. 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.

  20. Aspirin resistance and other aspirin-related concerns.

    PubMed

    Cai, Gaoyu; Zhou, Weijun; Lu, Ya; Chen, Peili; Lu, Zhongjiao; Fu, Yi

    2016-02-01

    Aspirin is a widely used medication and has become a cornerstone for treating cardiovascular disease. Aspirin can significantly reduce the incidence of cardiovascular ischemic events, recurrence and mortality, thereby improving the long-term prognosis of patients. However, there has been a staggering increase in the volume of literature addressing the issue of so-called "aspirin resistance" in recent years, and for some patients, it is difficult to avoid adverse reactions to aspirin. In this review, we present both the historical aspects of aspirin use and contemporary developments in its clinical use.

  1. A Reaction of Aspirin with Ferrous Gluconate.

    PubMed

    Zhang, Jian

    2015-12-01

    A color reaction of aspirin with ferrous gluconate was studied by UV-Vis spectrophotometry and HPLC-MS. It was found that the UV-Vis spectra of the two drugs were different before and after they were mixed in water at about 0.3 M (diluted by >20 times for analysis), indicating that a complexation reaction took place. The drug-iron complex dissociated when the reacting solution was diluted by 400 times. The by-products of the reaction identified by HPLC-MS were salicylic acid, acetylated gluconic acid, salicylate-gluconic acid conjugate, and an oxidized product of salicylic acid that was complexed with iron with a molecular weight of 212. This reaction may be used as an important consideration to optimize the dosing regime of the two drugs and to help explain some pharmacological reactions between aspirin and biomolecules.

  2. Nimesulide improves the symptomatic and disease modifying effects of leflunomide in collagen induced arthritis.

    PubMed

    Al-Abd, Ahmed M; Al-Abbasi, Fahad A; Nofal, Salwa M; Khalifa, Amani E; Williams, Richard O; El-Eraky, Wafaa I; Nagy, Ayman A; Abdel-Naim, Ashraf B

    2014-01-01

    Nimesulide is a COX-2 inhibitor used for symptomatic relief of rheumatoid arthritis. Leflunomide is an anti-pyrimidine used to manage the progression of rheumatoid arthritis. Herein we studied the influence of nimesulide and leflunomide combination in terms of disease symptoms and progression using collagen-induced arthritis model in mice, as a model for rheumatoid arthritis. Collagen induced arthritis was induced by immunization with type II collagen. Assessment of joint stiffness and articular hyperalgesia were evaluated using a locomotor activity cage and the Hargreaves method, respectively. Disease progression was assessed via arthritic index scoring, X-ray imaging, myeloperoxidase enzyme activity and histopathologic examination. Nimesulide induced only transient symptomatic alleviation on the top of decreased leucocytic infiltration compared to arthritis group. However, nimesulide alone failed to induce any significant improvement in the radiological or pathological disease progression. Leflunomide alone moderately alleviates the symptoms of arthritis and moderately retarded the radiological and pathological disease progression. Combination of nimesulide and leflunomide significantly improved symptomatic (analgesia and joint stiffness) and arthritic disease progression (radiological, pathological and Myeloperoxidase enzyme activity) in collagen induced arthritis animal model.

  3. Risk of gastrointestinal complications associated to NSAIDs, low-dose aspirin and their combinations: Results of a pharmacovigilance reporting system.

    PubMed

    Rafaniello, Concetta; Ferrajolo, Carmen; Sullo, Maria Giuseppa; Sessa, Maurizio; Sportiello, Liberata; Balzano, Antonio; Manguso, Francesco; Aiezza, Maria Luisa; Rossi, Francesco; Scarpignato, Carmelo; Capuano, Annalisa

    2016-02-01

    Gastrointestinal (GI) complications are one of the most limiting cause of use of NSAIDs. Beyond others well defined factors, history of peptic ulcer, older age, Helicobacter pylori infection and use of gastrotoxic drugs may affect their GI safety profile. In particular, the risk of GI complications associated to the use of antiplatelet drugs, especially low-dose acetylsalicylic acid (LDA) should deserve much attention. However, only few studies have focused on the effect of combination LDA/NSAIDs on the GI tract compared with the monotherapy and much less studies assessed this effect with multiple NSAIDs use. We aimed to characterize the GI safety profile of NSAIDs and LDA as monotherapy or their combinations in real-life conditions by analysing spontaneous adverse drug reactions (ADRs) reporting system in a Southern Italy. We used the case/non-case method in the Italian Pharmacovigilance Network (RNF). Cases were reports of GI events in the RNF between January 2007 and December 2011. Non-cases were all other reports during the same period. The association between NSAID and suspected GI ADRs was calculated using the reporting odds ratio (ROR) with 95% confidence intervals as a measure of disproportionality while adjusting for age, and concomitant use of antineoplastic agents or drugs for cardiovascular diseases. Sub-analysis were performed within the NSAID class. Among the 2816 adverse drug reactions recorded, we identified 374 (13.3%) cases of GI complications. Upper GI complications were the most frequently reported type of events. The highest associations were found for the combined use of NSAIDs and/or LDA, whilst the lowest associations were for their respective monotherapy. Looking at individual NSAIDs the highest association with GI events was observed for ketorolac exposure followed by nimesulide, diclofenac, aspirin, ketoprofen, and ibuprofen. This study highlights the primary role of the national spontaneous reporting system to bring out potential signals

  4. Metabolome analysis of effect of aspirin on Drosophila lifespan extension.

    PubMed

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

    2017-09-01

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

  5. Detection of aspirin resistance by PFA-100: prevalence and aspirin compliance in patients with chronic stable angina.

    PubMed

    Crowe, Basil; Abbas, Syed; Meany, Brendan; de Haan, Jacob; Cahill, Mary R

    2005-01-01

    Most acute coronary syndromes result from a platelet-rich occlusion of the coronary arteries. Antiplatelet drugs are of proven efficacy in preventing myocardial infarction, unstable angina, and stroke. However, not all patients on aspirin (ASA) benefit. We studied the phenomenon of aspirin resistance with a simple and reliable platelet function analyzer--the PFA-100. Studying 31 patients with unstable angina and 105 controls, we found aspirin resistance in 42% of patients, most of whom were shown to be compliant utilizing concomitant salicylate levels.

  6. 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.

  7. Nimesulide inhibits the growth of human esophageal carcinoma cells by inactivating the JAK2/STAT3 pathway.

    PubMed

    Liu, Jun-Ru; Wu, Wen-Juan; Liu, Shu-Xia; Zuo, Lian-Fu; Wang, Yuan; Yang, Jian-Zhu; Nan, Yue-Min

    2015-06-01

    Although selective COX-2 inhibitors have cancer-preventive effects and induce apoptosis, the mechanisms underlying these effects are not fully understood. This study investigated the effects of nimesulide, a selective COX-2 inhibitor, on apoptosis and on the JAK/STAT signaling pathway in Eca-109 human esophageal squamous carcinoma cells. The effects and mechanisms of nimesulide on Eca-109 cell growth were studied in culture and in nude mice with Eca-109 xenografts. Cells were cultured with or without nimesulide and/or the JAK2 inhibitor AG490. Cell proliferation was evaluated using the MTT assay, and apoptosis was investigated. COX-2 mRNA expression was measured using reverse transcription polymerase chain reaction, and protein expression was detected by Western blot analysis, immunohistochemistry, and flow cytometry. Nimesulide significantly inhibited Eca-109 cell viability in vitro in a dose- and time-dependent manner (P<0.05). Nimesulide also induced apoptosis, which was accompanied by a significant decrease in the expression of COX-2 and survivin and an increase in caspase-3 expression. Nimesulide downregulated the phosphorylation levels of JAK2 and STAT3, and JAK2 inhibition by AG490 significantly augmented both nimesulide-induced apoptosis and the downregulation of COX-2 and survivin (P<0.05). In vivo, nimesulide inhibited the growth of Eca-109 tumors and the expression of p-JAK2 and p-STAT3. Thus, nimesulide downregulates COX-2 and survivin expression and upregulates caspase-3 expression in Eca-109 cells, by inactivating the JAK2/STAT3 pathway. These effects may mediate nimesulide-induced apoptosis and growth inhibition in Eca-109 cells in vitro and in vivo.

  8. Poor awareness of preventing aspirin-induced gastrointestinal injury with combined protective medications.

    PubMed

    Zhu, Ling-Ling; Xu, Ling-Cheng; Chen, Yan; Zhou, Quan; Zeng, Su

    2012-06-28

    To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal (GI) injury with combined protective medications. A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital, School of Medicine, Zhejiang University. The hospital has 2300 beds and 2.5 million outpatient visits annually. Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011. Concomitant use of proton-pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RA) and mucoprotective drugs (MPs) were analyzed. A defined daily dose (DDD) methodology was applied to each MP. A further investigation was performed in aspirin users on combination use of GI injurious medicines [non-steoid anti-inflammatory drugs (NSAIDs), corticosteroids and clopidogrel and warfarin] or intestinal protective drugs (misoprostol, rebamipide, teprenone and gefarnate). Data of major bleeding episodes were derived from medical records and adverse drug reaction monitoring records. The annual incidence of major GI bleeding due to low-dose aspirin was estimated for outpatients. Prescriptions for aspirin users receiving PPIs, H2RA and MPs (n = 1039) accounted for only 3.46% of total aspirin prescriptions (n = 30 015). The ratios of coadministration of aspirin/PPI, aspirin/H2RA, aspirin/MP and aspirin/PPI/MP to the total aspirin prescriptions were 2.82%, 0.12%, 0.40% and 0.12%, respectively. No statistically significant difference was observed in age between patients not receiving any GI protective medications and patients receiving PPIs, H2RA or MPs. The combined medication of aspirin and PPI was used more frequently than that of aspirin and MPs (2.82% vs 0.40%, P < 0.05) and aspirin/H2RA (2.82% vs 0.12%, P < 0.05). The values of DDDs of MPs in descending order were as follows: gefarnate, hydrotalcite > teprenone > sucralfate oral suspension > L-glutamine and sodium gualenate granules

  9. Poor awareness of preventing aspirin-induced gastrointestinal injury with combined protective medications

    PubMed Central

    Zhu, Ling-Ling; Xu, Ling-Cheng; Chen, Yan; Zhou, Quan; Zeng, Su

    2012-01-01

    AIM: To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal (GI) injury with combined protective medications. METHODS: A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital, School of Medicine, Zhejiang University. The hospital has 2300 beds and 2.5 million outpatient visits annually. Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011. Concomitant use of proton-pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RA) and mucoprotective drugs (MPs) were analyzed. A defined daily dose (DDD) methodology was applied to each MP. A further investigation was performed in aspirin users on combination use of GI injurious medicines [non-steoid anti-inflammatory drugs (NSAIDs), corticosteroids and clopidogrel and warfarin] or intestinal protective drugs (misoprostol, rebamipide, teprenone and gefarnate). Data of major bleeding episodes were derived from medical records and adverse drug reaction monitoring records. The annual incidence of major GI bleeding due to low-dose aspirin was estimated for outpatients. RESULTS: Prescriptions for aspirin users receiving PPIs, H2RA and MPs (n = 1039) accounted for only 3.46% of total aspirin prescriptions (n = 30 015). The ratios of coadministration of aspirin/PPI, aspirin/H2RA, aspirin/MP and aspirin/PPI/MP to the total aspirin prescriptions were 2.82%, 0.12%, 0.40% and 0.12%, respectively. No statistically significant difference was observed in age between patients not receiving any GI protective medications and patients receiving PPIs, H2RA or MPs. The combined medication of aspirin and PPI was used more frequently than that of aspirin and MPs (2.82% vs 0.40%, P < 0.05) and aspirin/H2RA (2.82% vs 0.12%, P < 0.05). The values of DDDs of MPs in descending order were as follows: gefarnate, hydrotalcite > teprenone > sucralfate oral suspension > L-glutamine and sodium

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

    PubMed

    Chapman, Andrew R; Rushworth, Gordon F; Leslie, Stephen J

    2013-01-01

    Aspirin remains the mainstay of anti-platelet therapy in cardiac patients. However, if a patient is allergic to aspirin and dual anti-platelet therapy is indicated - such as with percutaneous coronary intervention (PCI), then there is no clear guidance. One possibility is aspirin desensitization. A variety of protocols exist for the rapid desensitization of patients with aspirin allergy. The aim of this survey was to assess current knowledge and practice regarding aspirin desensitization in the UK. We conducted a UK wide survey of all UK 116 PCI centers and obtained complete responses from 40 (35.4%) centers. Of these, just 7 (17.5%) centers had previously desensitised patients; 29 (87.9%) centers suggested a lack of a local protocol prevented them from desensitizing, with 10 (30.3%) unsure of how to conduct desensitization. Only 5 (12.5%) centers had a local policy for aspirin desensitization although 25 (64.1%) units had a clinical strategy for dealing with aspirin allergy; the majority (72%) giving higher doses of thienopyridine class drugs. In the UK, there appears to be no consistent approach to patients with aspirin allergy. Patients undergoing PCI benefit from dual anti-platelet therapy (including aspirin), and aspirin desensitization in those with known allergy may facilitate this. Sustained effort should be placed on encouraging UK centers to use desensitization as a treatment modality prior to PCI rather than avoiding aspirin altogether.

  11. Localization of cyclooxygenase-2 in mice vas deferens and its effects on fertility upon suppression using nimesulide: a preferential cyclooxygenase-2 inhibitor.

    PubMed

    Balaji, Thotakura; Ramanathan, Manickam; Menon, Venugopal Padmanabhan

    2007-05-05

    Accumulating evidence on constitutive expression of cyclooxygenase-2 (COX-2), one of the isoforms of enzyme cyclooxygenase (COX) the other isoform being cyclooxygenase-1 (COX-1), questions the safety profile of non-steroidal anti-inflammatory drugs (NSAIDs). This COX-2 isoform which is induced not only during inflammation but also by factors such as cytokines, steroid hormones and mitogenic stimuli is constitutively expressed in brain, kidney and reproductive organs. Present NSAIDs, particularly COX-2 inhibitors is no longer considered safe since suppression of COX-2 in tissues which it is constitutively expressed may lead to adverse effects. Though intense expression of COX-2 in vas deferens is proved, lack of information with respect to its function has attracted a wide scope for research as to whether COX-2 in vas deferens contributes to male fertility. In the present study, the authors investigated the localization of COX-2 as well as COX-1 in mice vas deferens and also assessed the activity of COX-2 and total prostaglandin (PG) levels in vas deferens. Further they suppressed the expression of COX-2 using a preferential COX-2 inhibitor nimesulide and analyzed the sperm from vas deferens for any defects. COX-2 was intensely expressed in the epithelial cells of mice vas deferens and nimesulide was able to effectively suppress most of COX-2 expression. A decrease in PG levels was observed initially but interestingly, the levels tend to rise on sustained suppression of COX-2. The motility of sperm was affected severely after 6h of nimesulide administration that suggested a crucial role of COX-2 towards fertility of mice sperm.

  12. Effect of nimesulide-a preferential COX-2 inhibitor on arterial blood pressure, compared to ketoprofen.

    PubMed

    Saran, Tomasz; Sodolski, Wojciech; Sodolska, Katarzyna; Danilkiewicz, Wit Cezary; Schabowski, Janusz

    2004-01-01

    Clinical and experimental studies have shown that renal and cardiovascular effects of most selective COX-2 inhibitors (rofecoxib, celecoxib) are similar to other traditional NSAIDs (dual COX inhibitors). In these study the effect of nimesulide--preferential COX-2 inhibitor, administration on 24-hour blood pressure profile was investigated in 40 adult individuals on antihypertensive therapy with pain states caused by osteoartritis. Nimesulide was administered orally, twice a day at the conventional dose of 0.1 g for five days. In the next (or previous) 5 days the same patients were administered with ketoprofen at the dose of 0.05 g three times a day. On the last day of the NSAID administration period, 24-hour blood pressure monitoring was performed. Our results indicate no difference between nimesulide and ketoprofen effects on mean blood pressure values during antihypertensive therapy.

  13. 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.

  14. [Risk and prevention of gastrointestinal complications due to low-dose aspirin and other antiplatelet agents].

    PubMed

    Bretagne, Jean-François

    2008-09-15

    Upper and lower gastrointestinal (GI) haemorrhages are the main complications associated with low-dose aspirin or anti-thrombotic drugs. In France, low-dose aspirin or anti-thrombotic agents use has been found in 30% of upper GI and 40% of lower GI bleeding episodes. Main causes of GI bleeding with low-dose aspirin are gastroduodenal peptic ulcer and colonic diverticulosis. Recent cohort studies have shown that the relative risk of GI bleeding with low-dose aspirin was comprised between 2 and 4 and the absolute risk comprised between 1 per 100 and 1 per 1000 aspirin users per year. Main risk factors for upper GI bleeding with low-dose aspirin are concomitant antiplatelet agents, anticoagulants, non steroidal anti-inflammatory drugs or steroids use, and recent history of complicated or non-complicated gastroduodenal ulcer. Helicobacter pylori infection increases the risk for upper GI bleeding with low-dose aspirin, but infection should be searched and treated only in patients with peptic ulcer. Despite eradication of H. pylori in the latter patients, gastroprotection with PPI is strongly recommended. In patients presenting with peptic ulcer bleeding with low-dose aspirin, aspirin should be continued in association with PPI rather than replaced with clopidogrel. Discontinuation of low-dose aspirin which exposes to increased cardiovascular complications and mortality should be avoided, even in cases of peptic ulcer bleeding.

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

    SciTech Connect

    Li, Xiaofei; Zhu, Yanshuang; He, Huabin; Lou, Lianqing; Ye, Weiwei; Chen, Yongxin; Wang, Jinghe

    2013-06-28

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

  16. Comparative effects of aspirin and enteric-coated aspirin on loss of chromium 51-labeled erythrocytes from the gastrointestinal tract

    SciTech Connect

    Robbins, D.C.; Schwartz, R.S.; Kutny, K.; Vallejo, G.; Horton, E.S.; Cotter, J.M.

    1984-01-01

    Sodium chromate Cr 51 was used to label red blood cells of 19 healthy male volunteers, whose stools were collected for four days before and four days during oral administration of either uncoated (N . 9) or enteric-coated (N . 10) aspirin. Each subject received 2.925 gm/day of aspirin, in three equal doses separated by eight-hour intervals, for a total of seven days. During drug use, stools were collected on days 4 through 7. Fecal blood content, estimated by measuring radioactivity in the stools, was significantly higher (P less than 0.001) during use of either type of aspirin than at baseline, but losses measured during use of the coated aspirin (mean, 1.54 ml/day) were significantly lower (P less than 0.001) than those measured during use of the uncoated aspirin (mean, 4.33 ml/day). The two types of aspirin produced equivalent serum concentrations of salicylates. We conclude that enteric-coated aspirin reduces gastrointestinal blood loss.

  17. The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein.

    PubMed Central

    Roth, G J; Majerus, P W

    1975-01-01

    Aspirin (acetylsalicylic acid) inhibits platelet prostaglandin synthesis and the ADP- and collagen-induced platelet release reaction. The mechanism of the inhibitory effect is unknown but may involve protein acetylation, since aspirin acetylates a variety of substrates, including platelet protein. We have examined the relationship between protein acetylation and aspirin's physiologic effect on platelets. Suspensions of washed human platelets were incubated at 37 degrees C with (3H)aspirin, and incorporation of radioactivity into protein was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Exposure to (acetyl-3H)aspirin but not (aromatic ring-3H)aspirin resulted in radioactive labeling of three platelet proteins, suggesting that the drug acetylates these three proteins. The acetylation of two of the proteins (located in the supernatant fraction) was not saturable, implying that these reactions may not be physiologically significant. Acetylation of the third protein, approximate mol wt 85,000 (located in the particulate fraction), saturated at an aspirin concentration of 30 muM and was complete within 20 min. Platelets prepared from aspirin-treated donors did not incorporate any (acetyl-3H)aspirin radioactivity into the particulate protein for 2 days after drug treatment and did not show full pretreatment uptake of radioactivity for 12 days thereafter. The course of increasing incorporation of (acetyl-3H)aspirin radioactivity parralleled that of platelet turnover. Therefore, in addition to its saturability, acetylation of the particulate fraction protein by aspirin was permanent. In two respects, the inhibition of platelet function by aspirin correlates well with the aspirin-mediated acetylation of the particulate fraction protein. Both persist for the life-span of the aspirin-treated platelet, and both occur at a similar saturating aspirin concentration. The evidence suggests that the physiologic effect of aspirin on human platelets is produced

  18. Targeting KSHV/HHV-8 latency with COX-2 selective inhibitor nimesulide: a potential chemotherapeutic modality for primary effusion lymphoma.

    PubMed

    Paul, Arun George; Sharma-Walia, Neelam; Chandran, Bala

    2011-01-01

    The significance of inflammation in KSHV biology and tumorigenesis prompted us to examine the role of COX-2 in primary effusion lymphoma (PEL), an aggressive AIDS-linked KSHV-associated non-Hodgkin's lymphoma (NHL) using nimesulide, a well-known COX-2 specific NSAID. We demonstrate that (1) nimesulide is efficacious in inducing proliferation arrest in PEL (KSHV+/EBV-; BCBL-1 and BC-3, KSHV+/EBV+; JSC-1), EBV-infected (KSHV-/EBV+; Raji) and non-infected (KSHV-/EBV-; Akata, Loukes, Ramos, BJAB) high malignancy human Burkitt's lymphoma (BL) as well as KSHV-/EBV+ lymphoblastoid (LCL) cell lines; (2) nimesulide is selectively toxic to KSHV infected endothelial cells (TIVE-LTC) compared to TIVE and primary endothelial cells (HMVEC-d); (3) nimesulide reduced KSHV latent gene expression, disrupted p53-LANA-1 protein complexes, and activated the p53/p21 tumor-suppressor pathway; (4) COX-2 inhibition down-regulated cell survival kinases (p-Akt and p-GSK-3β), an angiogenic factor (VEGF-C), PEL defining genes (syndecan-1, aquaporin-3, and vitamin-D3 receptor) and cell cycle proteins such as cyclins E/A and cdc25C; (5) nimesulide induced sustained cell death and G1 arrest in BCBL-1 cells; (6) nimesulide substantially reduced the colony forming capacity of BCBL-1 cells. Overall, our studies provide a comprehensive molecular framework linking COX-2 with PEL pathogenesis and identify the chemotherapeutic potential of nimesulide in treating PEL.

  19. The effect of nimesulide on oxidative damage inflicted by ischemia-reperfusion on the rat renal tissue.

    PubMed

    Suleyman, Zeynep; Sener, Ebru; Kurt, Nezahat; Comez, Mehmet; Yapanoglu, Turgut

    2015-03-01

    The objective of our study is to research biochemically and histopathologically the effect of nimesulide on oxidative damage inflicted by ischemia-reperfusion (I/R) on the rat renal tissue. Twenty-four albino Wistar type of male rats were used for the experiment. The animals were divided into groups as: renal ischemia-reperfusion control (RIR), nimesulide+renal ischemia-reperfusion of 50 mg/kg (NRIR-50), nimesulide+renal ischemia-reperfusion of 100 mg/kg (NRIR-100), and sham groups (SG). In NRIR-50 and NRIR-100 groups were given nimesulide, and RIR and SG groups were given distilled water, an hour after anesthesia. Groups, except for the SG group, 1-h-ischemia and then 6-h-reperfusion were performed. In the renal tissue of the RIR group in which the malondialdehyde (MDA), myeloperoxidase (MPO), and 8-hydroxyguanine (8-OHGua) levels were measured, the COX-1 and COX-2 activities were recorded. Nimesulide at 100 mg/kg doses reduced the oxidant parameters more significantly than 50 mg/kg doses; on the other hand, it raised the antioxidant parameters. It has been shown that 100 mg/kg doses of nimesulide prevented the renal I/R damage more significantly than a dose of 50 mg/kg, which shows that nimesulide, in clinics, could be used in the prevention of I/R damage.

  20. Guggulipid and nimesulide differentially regulated inflammatory genes mRNA expressions via inhibition of NF-kB and CHOP activation in LPS-stimulated rat astrocytoma cells, C6.

    PubMed

    Niranjan, Rituraj; Nath, Chandishwar; Shukla, Rakesh

    2011-07-01

    Neuroinflammation is an integral part of neurodegenerative diseases. Lipo-polysacharide (LPS) induces reactive astrogliosis, the cellular manifestation of neuroinflammation, in various models of neurological diseases, but its mechanism of action is still not properly known. The effect of guggulipid and nimesulide on LPS-induced neuroinflammatory changes is also not properly understood. This work demonstrated the mechanism of actions of guggulipid and nimesulide on inflammatory genes expressions in LPS-stimulated rat astrocytoma cells, C6. We observed that LPS (10 μg/ml) treatment of rat astrocytoma cells, C6, for 24 h significantly increased intracellular Ca(2+) ion and expression of inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NF-kB), C/EBP homologous protein 10 (CHOP), c-fos, and c-jun proteins. At transcriptional stage, LPS upregulated mRNA levels of cyclooxygenase-2 and IL-6 with downregulation in IL-1α, IL-1β, and microsomal prostaglandin E synthase-1 (mPGES-1) through activating NF-kB translocation. Treatment with guggulipid reversed these LPS-induced changes in rat astrocytoma cells. Treatment with nimesulide also attenuated LPS-induced Ca(2+) ion, iNOS, NF-kB, and c-fos expressions, but does not significantly influence CHOP, c-jun protein expressions, and mRNA levels of IL-6, IL-1α, IL-1β, and mPGES-1 genes. In conclusion, our findings elucidated the molecular mechanism of neuroinflammation in response to LPS and its modulation by guggulipid and nimesulide in rat astrocytoma cells (C6), which suggest the use of these drugs in the treatment of neuroinflammation-associated disorders.

  1. Functionalized bimodal mesoporous silicas as carriers for controlled aspirin delivery

    SciTech Connect

    Gao Lin; Sun Jihong; Li Yuzhen

    2011-08-15

    The bimodal mesoporous silica modified with 3-aminopropyltriethoxysilane was performed as the aspirin carrier. The samples' structure, drug loading and release profiles were characterized with X-ray diffraction, scanning electron microscopy, N{sub 2} adsorption and desorption, Fourier transform infrared spectroscopy, TG analysis, elemental analysis and UV-spectrophotometer. For further exploring the effects of the bimodal mesopores on the drug delivery behavior, the unimodal mesoporous material MCM-41 was also modified as the aspirin carrier. Meantime, Korsmeyer-Peppas equation f{sub t}=kt{sup n} was employed to analyze the dissolution data in details. It is indicated that the bimodal mesopores are beneficial for unrestricted drug molecules diffusing and therefore lead to a higher loading and faster releasing than that of MCM-41. The results show that the aspirin delivery properties are influenced considerably by the mesoporous matrix, whereas the large pore of bimodal mesoporous silica is the key point for the improved controlled-release properties. - Graphical abstract: Loading (A) and release profiles (B) of aspirin in N-BMMs and N-MCM-41 indicated that BMMs have more drug loading capacity and faster release rate than that MCM-41. Highlights: > Bimodal mesoporous silicas (BMMs) and MCM-41 modified with amino group via post-treatment procedure. > Loading and release profiles of aspirin in modified BMMs and MCM-41. > Modified BMMs have more drug loading capacity and faster release rate than that modified MCM-41.

  2. Oral aspirin for treating venous leg ulcers.

    PubMed

    de Oliveira Carvalho, Paulo Eduardo; Magolbo, Natiara G; De Aquino, Rebeca F; Weller, Carolina D

    2016-02-18

    published or ongoing trials. There were no language or publication date restrictions. We included randomised controlled trials (RCTs) that compared oral aspirin with placebo or no drug intervention (in the presence or absence of compression therapy) for treating people with venous leg ulcers. Our main outcomes were time to complete ulcer healing, rate of change in the area of the ulcer, proportion of ulcers healed in the trial period, major bleeding, pain, mortality, adverse events and ulcer recurrence (time for recurrence and proportion of recurrence). Two review authors independently selected studies for inclusion, extracted data, assessed the risk of bias of each included trial and assessed overall quality of evidence for the main outcomes in the 'Summary of findings' table. The electronic search located 62 studies. We included two RCTs of oral aspirin (300 mg/daily) given in addition to compression compared with compression and placebo, or compression alone. To date, the impact of aspirin on VLUs has been examined by only two randomised clinical trials, both with a small number of participants. The first RCT was conducted in the United Kingdom (n=20) and reported that daily administration of aspirin (300mg) in addition to compression bandages increased both the rate of healing, and the number of participants healed when compared to placebo in addition to compression bandaging over a four month period. Thirty-eight per cent of the participants given aspirin reported complete healing compared with 0% in the placebo group . Improvement (assessed by reduction in wound size) occurred in 52% of the participants taking aspirin compared with 26% in those taking placebo). The study identified potential benefits of taking aspirin as an adjunct to compression but the sample size was small, and neither the mechanism by which aspirin improved healing nor its effects on recurrence were investigated.In 2012 an RCT in Spain (n=51) compared daily administration of aspirin (300mg) in

  3. Prophylactic aspirin and risk of peptic ulcer bleeding.

    PubMed Central

    Weil, J.; Colin-Jones, D.; Langman, M.; Lawson, D.; Logan, R.; Murphy, M.; Rawlins, M.; Vessey, M.; Wainwright, P.

    1995-01-01

    OBJECTIVE--To determine the risks of hospitalisation for bleeding peptic ulcer with the current prophylactic aspirin regimens of 300 mg daily or less. DESIGN--A case-control study with hospital and community controls. SETTING--Hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth. SUBJECTS--1121 patients with gastric or duodenal ulcer bleeding matched with hospital and community controls. RESULTS--144 (12.8%) cases had been regular users of aspirin (taken at least five days a week for at least the previous month) compared with 101 (9.0%) hospital and 77 (7.8%) community controls. Odds ratios were raised for all doses of aspirin taken, whether compared with hospital or community controls (compared with combined controls: 75 mg, 2.3 (95% confidence interval 1.2 to 4.4); 150 mg, 3.2 (1.7 to 6.5); 300 mg, 3.9 (2.5 to 6.3)). Results were not explained by confounding influences of age, sex, prior ulcer history or dyspepsia, or concurrent non-aspirin non-steroidal anti-inflammatory drug use. Risks seemed particularly high in patients who took non-aspirin non-steroidal anti-inflammatory drugs concurrently. CONCLUSION--No conventionally used prophylactic aspirin regimen seems free of the risk of peptic ulcer complications. PMID:7711618

  4. Multivariate control charts based on net analyte signal and near infrared spectroscopy for quality monitoring of Nimesulide in pharmaceutical formulations

    NASA Astrophysics Data System (ADS)

    Fortunato de Carvalho Rocha, Wérickson; Luis Rosa, André; Antônio Martins, José; Poppi, Ronei Jesus

    2010-10-01

    Multivariate control charts based on the net analytical signal, in conjunction with near infrared spectroscopy, were developed to monitor the quality of a pharmaceutical formulation containing Nimesulide. Three control charts were developed: the NAS chart that corresponds to the analyte of interest (Nimesulide in this case), the interference chart that corresponds to the contribution of other compounds in the sample and the residual chart that corresponds to nonsystematic variation. From the limits estimated for each chart using samples inside the quality specifications, it was possible to identify the samples that were outside the specifications concerning Nimesulide concentration and to identify the presence of different constituents in the standard formulation.

  5. 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.

  6. 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 E2 (PGE2) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE2 stabilizes inflammatory mediator release. To examine whether misoprostol (oral prostaglandin E1 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 (FEV1), peak nasal inspiratory flow rate (PNIF), number of treatments received for induced reactions, and adverse gastrointestinal effects. A difference in FEV1 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 FEV1 (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.

  7. Serum cholesterol concentration associated with aspirin esterase activity in older people: preliminary data.

    PubMed

    Kotani, Kazuhiko; Caccavello, Russell; Hermo, Ricardo; Yamada, Toshiyuki; Taniguchi, Nobuyuki; Gugliucci, Alejandro

    2010-05-10

    Metabolism of aspirin (acetylsalicylic acid), commonly used in older people for the prevention of cardiovascular disease, is important to the effectiveness of this drug. Whereas part of aspirin hydrolysis occurs in blood, there is a paucity of information in regards to circulating aspirin esterase activity in various physiological and pathological conditions. High aspirin esterase activity, corresponding to faster aspirin hydrolysis (thus aspirin non-responsiveness), may occur in cardiovascular disease-prone states. The objective of this study was to investigate the effects of cardio-metabolic variables such as cholesterol on serum aspirin esterase activity in older people who participated in an intervention study on physical activity. A total of 18 non-medicated subjects (7 men/11 women, mean age 67.8 years, body mass index = 23.4 +/- 3.3 kg/m(2)), who completed a 3-month interventional program for a mild-to-moderate increase in physical activity, were analyzed. The body mass index, plasma glucose, serum total cholesterol and aspirin esterase activity were measured in the pre- and post-interventional phases of the study. During the interventional period, the changes in aspirin esterase activity correlated significantly and positively with those of total cholesterol concentrations (r = 0.542, P = 0.020; beta = 0.609, P = 0.035 in a multiple linear regression analysis after adjusting for all the measured variables). The results suggest that cholesterol metabolism alterations may be associated with aspirin metabolism in older people.

  8. Hydroxynimesulide, the main metabolite of nimesulide, prevents hydroperoxide/hemoglobin-induced hemolysis of rat erythrocytes.

    PubMed

    Maffei Facino, R; Carini, M; Aldini, G; Calloni, M T

    1997-01-01

    The protective effect of hydroxynimesulide, the main metabolite of the nonsteroidal antiinflammatory drug nimesulide, on red blood cells (RBCs, 0.2%; 3.5 x 10(7) cell/ml) hemolysis induced by cumene hydroperoxide (CuOOH; 50 microM) was evaluated by turbidimetric and morphological analyses. Hydroxynimesulide inhibits the CuOOH-induced hemolysis in a dose dependent fashion: the protective effect, calculated after 150 min incubation (100% hemolysis in the controls), starts at 1 micron (% hemolysis 85.2 +/- 3.4%) and increases at the higher concentrations (63.5 +/- 3.9% at 5 microM; 43.5 +/- 6.3% at 10 microM; and, 14.5 +/- 4.3% at 20 microM). In addition, in the samples protected with 10 microM and 20 microM, there is a significant delay (30 and 60 min) in the onset of the hemolytic response. Inhibition of hemolysis is the result of protection of RBC membrane integrity, both on lipid (cis-Parinaric acid fluorescence quenching was delayed by 53 +/- 10 sec vs. the controls at 1 micron, by 115 +/- 15 sec at 5 microM, with a lag phase of 240 +/C- 18 sec at 10 microM) and protein constituents, as determined by SDS-PAGE electrophoresis. In hemolysis experiments, the efficacy of hydroxynimesulide is comparable to that of alpha-tocopherol and a cooperative interaction between hydroxynimesulide and alpha-tocopherol (both at 10 microM) has been observed. These results indicate that hydroxynimesulide protects RBC membranes by directly quenching reactive oxygen species generated by hemoglobin/peroxide interaction. Evidence for a direct radical scavenging intervention of the metabolite comes from HPLC studies, which demonstrate a time-dependent consumption of hydroxynimesulide, with the concomitant formation of two main reaction (addition/oxidation) products.

  9. Aspirin intolerance--a review.

    PubMed

    Abrishami, M A; Thomas, J

    1977-07-01

    1. Association of bronchial asthma, nasal pathology and intolerance to aspirin is a unique syndrome. Aspirin-induced prolongation of bleeding time, and a tendency for diabetes, may exist with it. 2. The syndrome occurs most often in the middle-aged female. 3. Progression of asthma and nasal polyposis is not prevented by avoidance of aspirin. 4. Salicylates other than aspirin are well tolerated but cross-reactivity with other analgesics, and with tartrazine, may occur. 5. The underlying mechanism is unknown. An immunologic basic is most unlikely.

  10. Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity

    SciTech Connect

    Cosgrove, Benjamin D.; King, Bracken M.; Hasan, Maya A.; Alexopoulos, Leonidas G.; Farazi, Paraskevi A.; Hendriks, Bart S.; Griffith, Linda G.; Sorger, Peter K.; Tidor, Bruce; Xu, Jinghai J.

    2009-06-15

    Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFN{gamma}, IL-1{alpha}, and IL-6. Using this assay, we observed drug-cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug-cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1{alpha}, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug-cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.

  11. Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity.

    PubMed

    Cosgrove, Benjamin D; King, Bracken M; Hasan, Maya A; Alexopoulos, Leonidas G; Farazi, Paraskevi A; Hendriks, Bart S; Griffith, Linda G; Sorger, Peter K; Tidor, Bruce; Xu, Jinghai J; Lauffenburger, Douglas A

    2009-06-15

    Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFN gamma, IL-1 alpha, and IL-6. Using this assay, we observed drug-cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug-cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1 alpha, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug-cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.

  12. [Analgetic drug intolerance].

    PubMed

    Merk, H; Goerz, G

    1983-04-15

    Reactions as intolerance to aspirin and food additives were diagnosed in 41 cases during November 1979 -- March 1982. Allergy to pyrazolone-drugs were observed in 20 cases during the same period. 24% of the patients with intolerance to aspirin had also an intolerance to tartrazine. There were no familial occurrence of aspirin intolerance. Four patients had mainly asthma, 37 patients urticaria. New aspects of the pathogenesis of aspirin intolerance -- modulation of arachidonate metabolism and complement activation -- are discussed.

  13. Review of pharmacokinetic and pharmacodynamic modeling and safety of proton pump inhibitors and aspirin.

    PubMed

    Gesheff, Martin G; Franzese, Christopher J; Bliden, Kevin P; Contino, Chase J; Rafeedheen, Rahil; Tantry, Udaya S; Gurbel, Paul A

    2014-09-01

    The efficacy of aspirin in primary and secondary prevention of cardiovascular diseases has been convincingly demonstrated. Gastrointestinal (GI) adverse effects with aspirin may lead to poor adherence and/or discontinuation of treatment. Proton pump inhibitors (PPIs) have been used for more than 20 years as the first choice for treating peptic ulcers and their bleeding complications, gastroesophageal reflux disease, non-steroidal anti-inflammatory drug-induced GI lesions and dyspepsia. Adherence becomes a major concern when aspirin is co-prescribed with PPIs to prevent GI adverse effects. Combining aspirin and PPIs into one tablet is an effective approach to address aspirin-related GI adverse effects and increase adherence to aspirin therapy for the prevention of cardiovascular diseases.

  14. The anti-tumor effect of aspirin: What we know and what we expect.

    PubMed

    Ma, Ji; Cai, Zhonglin; Wei, Hongliang; Liu, Xinlan; Zhao, Qingli; Zhang, Tao

    2017-09-04

    Aspirin has been widely used as an antipyretic analgesic drug. More and more evidences have shown that aspirin may be play some role on anti-tumor. In this article, we reviewed the research history of aspirin in the treatment and prevention of cancer. Many epidemiological and clinical studies have shown that aspirin can reduce the risk of a variety of malignant tumors and reduce cancer mortality. In addition, we discuss the specific mechanisms of aspirin in the anti-tumor effects. It has been found that aspirin mainly depends on the COX pathway and non-COX pathway to inhibit tumor cell growth and to curb tumor development. In this article, clinical studies and anti-tumor mechanism studies published in recent years are reviewed. Copyright © 2017. Published by Elsevier Masson SAS.

  15. Salicylic acid: a link between aspirin, diet and the prevention of colorectal cancer.

    PubMed

    Paterson, J R; Lawrence, J R

    2001-08-01

    Aspirin was introduced into clinical practice more than 100 years ago. This unique drug belongs to a family of compounds called the salicylates, the simplest of which is salicylic acid, the principal metabolite of aspirin. Salicylic acid is responsible for the anti-inflammatory action of aspirin, and may cause the reduced risk of colorectal cancer observed in those who take aspirin. Yet salicylic acid and other salicylates occur naturally in fruits and plants, while diets rich in these are believed to reduce the risk of colorectal cancer. Serum salicylic acid concentrations are greater in vegetarians than non-vegetarians, and there is overlap between concentrations in vegetarians and those taking low-dose aspirin. We propose that the cancer-preventive action of aspirin is due to its principal metabolite, salicylic acid, and that dietary salicylates can have the same effect. It is also possible that natural salicylates contribute to the other recognized benefits of a healthy diet.

  16. Functionalized bimodal mesoporous silicas as carriers for controlled aspirin delivery

    NASA Astrophysics Data System (ADS)

    Gao, Lin; Sun, Jihong; Li, Yuzhen

    2011-08-01

    The bimodal mesoporous silica modified with 3-aminopropyltriethoxysilane was performed as the aspirin carrier. The samples' structure, drug loading and release profiles were characterized with X-ray diffraction, scanning electron microscopy, N 2 adsorption and desorption, Fourier transform infrared spectroscopy, TG analysis, elemental analysis and UV-spectrophotometer. For further exploring the effects of the bimodal mesopores on the drug delivery behavior, the unimodal mesoporous material MCM-41 was also modified as the aspirin carrier. Meantime, Korsmeyer-Peppas equation ft= ktn was employed to analyze the dissolution data in details. It is indicated that the bimodal mesopores are beneficial for unrestricted drug molecules diffusing and therefore lead to a higher loading and faster releasing than that of MCM-41. The results show that the aspirin delivery properties are influenced considerably by the mesoporous matrix, whereas the large pore of bimodal mesoporous silica is the key point for the improved controlled-release properties.

  17. Effect of the 5-lipoxygenase inhibitor ZD2138 on aspirin-induced asthma.

    PubMed Central

    Nasser, S. M.; Bell, G. S.; Foster, S.; Spruce, K. E.; MacMillan, R.; Williams, A. J.; Lee, T. H.; Arm, J. P.

    1994-01-01

    BACKGROUND--The cysteinyl leukotrienes may play a central part in the mechanisms of aspirin-sensitive asthma. Previous work has shown that individuals with aspirin-sensitive asthma have high basal urinary LTE4 levels which increase further upon aspirin ingestion, and that sulphidopeptide leukotriene receptor antagonists attenuate aspirin-induced airflow obstruction. If the cysteinyl leukotrienes cause aspirin-induced asthmatic reactions, inhibition of the 5-lipoxygenase pathway should prevent aspirin-induced bronchospasm. This hypothesis has been tested with ZD2138, a specific non-redox 5-lipoxygenase inhibitor. METHODS--Seven subjects (four men) with aspirin-sensitive asthma with baseline FEV1 values > 67% were studied. ZD2138 (350 mg) or placebo was given on two separate occasions two weeks apart in a randomised double blind fashion. A single dose of aspirin was administered four hours after dosing and FEV1 was measured for six hours. Inhibition of the 5-lipoxygenase pathway by ZD2138 was assessed by measurements of urinary LTE4 levels and ex vivo calcium ionophore stimulated LTB4 generation in whole blood, before administration of drug or placebo and at regular time intervals after dosing and aspirin administration. RESULTS--ZD2138 protected against the aspirin-induced reduction in FEV1 with a 20.3 (4.9)% fall in FEV1 following placebo compared with 4.9 (2.9)% following ZD2138. This was associated with 72% inhibition of ex vivo LTB4 generation in whole blood at 12 hours and a 74% inhibition of the rise in urinary LTE4 excretion at six hours after aspirin ingestion. CONCLUSIONS--In aspirin-sensitive asthma the 5-lipoxygenase inhibitor ZD2138 inhibits the fall in FEV1 induced by aspirin and this is associated with substantial inhibition of 5-lipoxygenase. PMID:8091318

  18. Formulation development of intermediate release Nimesulide tablets by CCRD for IVIVC studies.

    PubMed

    Hanif, Muhammad; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Sattar, Shahnila; Nadeem, Muhammad; Hussain, Liaqat; MZia, Muhammad Usman; Muhammad, Iyad Naeem; Uzair, Muhammad; Qadir, Imran

    2014-07-01

    Simple and cost effective study consisting of three steps, comparison of micromeritic properties of different blends i.e. placebo without API and Nimesulide containing, Use of central composite design (CCRD) for intermediate release Nimesulide tablets and stability results of three selected Nimesulide tablet formulations which were calculated by using R Gui. Different concentrations of Avicel, hydroxypropyl methyl cellulose (HPMC) and magnesium stearate were used as variables in central composite design and two types blend i.e., with or without Nimesulide were selected for bulk density, tap density, percentage compressibility; angle of repose and Hausner's ratio. Blending rate constant was performed after applying the different mixing times like 3, 6, 9 and 12 minutes. Twenty intermediate release formulations were designed and three formulations were chosen for compression by direct compression method on the basis of compressibility index. Physicochemical properties and best release pattern in four hours in different dissolution medium were successfully measured. Relative densities, porosity of tablets were compared with tensile strength of tablet and weight variation, hardness, friability and dissolution was performed by simple experiments. Presence of Nimesulide in the bulk increased all micromeratic tests while 9 minutes was best mixing time. The hardness of NM containing tablets increased with the increase of relative density. The release pattern was further analyzed by model dependent i.e. zero order, first order and Higuchi, Korse-meyer and Pappas, Hixson Crowell and model independent kinetic model i.e., f2 value respectively. R Gui explained the F16 formulation shows the best result in stability studies with shelf life 72 months.

  19. Affordability Calculations on a Health Education Campaign to Promote the Use of Aspirin in Wales

    ERIC Educational Resources Information Center

    Morgan, Gareth

    2008-01-01

    Aspirin has far-reaching public health potential in reducing the risk of heart attacks, ischemic strokes and possibly cancer. Balanced against this potential are undesirable effects of the drug. It seems reasonable to allow every individual over the age of 50 years to make an informed choice about whether or not to take aspirin. A health education…

  20. 75 FR 61503 - Determination That AZDONE (Hydrocodone Bitartrate and Aspirin) Tablet, 5 Milligrams/500...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... Aspirin) Tablet, 5 Milligrams/500 Milligrams, Was Not Withdrawn From Sale for Reasons of Safety or... Administration (FDA) has determined that AZDONE (hydrocodone bitartrate and aspirin) Tablet, 5 milligrams (mg... allow FDA to approve abbreviated new drug applications (ANDAs) for hydrocodone bitartrate and...

  1. Affordability Calculations on a Health Education Campaign to Promote the Use of Aspirin in Wales

    ERIC Educational Resources Information Center

    Morgan, Gareth

    2008-01-01

    Aspirin has far-reaching public health potential in reducing the risk of heart attacks, ischemic strokes and possibly cancer. Balanced against this potential are undesirable effects of the drug. It seems reasonable to allow every individual over the age of 50 years to make an informed choice about whether or not to take aspirin. A health education…

  2. MACULAR DEGENERATION AND ASPIRIN USE.

    PubMed

    Small, Kent W; Garabetian, Christine A; Shaya, Fadi S

    2017-09-01

    To review current literature of the benefits that aspirin provides for patients' cardiovascular health compared with the risk of AMD worsening. We performed a review and critically analyzed six cardiovascular and four ophthalmological trials regarding risks and benefits of aspirin use. The prospective randomized cardiovascular trials had a cumulative 167,580 while the 3 smaller ophthalmological data sets had a cumulative 12,015 subjects. The reviewed meta-analysis literature demonstrated a statistically significant 32% reduction in the risk of nonfatal stroke with regular aspirin users. The study also documented that aspirin users decreased the risk of fatal vascular deaths by 15%. Of the three ophthalmological studies highlighting the adverse affects of aspirin association with AMD, all suggested an exacerbation of AMD without statistical significance and broad confidence bands. Overall, the number, size, and quality of the cardiovascular studies recommending aspirin use are far superior to the fewer, smaller and conflicting studies suggesting a possible adverse effect of aspirin use in relation to AMD. The benefits of aspirin usage include preserving the duration and quality of life by decreasing stroke and heart attack risk. These benefits seem to far outweigh the theoretical risks of possibly exacerbating wet AMD, which can be reasonably controlled with anti-VEGF therapy.

  3. Aspirin: from a historical perspective.

    PubMed

    Ugurlucan, Murat; Caglar, Ilker M; Caglar, Fatma N Turhan; Ziyade, Sedat; Karatepe, Oguzhan; Yildiz, Yahya; Zencirci, Ertugrul; Ugurlucan, Funda Gungor; Arslan, Ahmet H; Korkmaz, Semra; Filizcan, Ugur; Cicek, Sertac

    2012-04-01

    Aspirin is one of the oldest medicines. Due to its wide range usage in different fields of medicine, we aimed to present the history, effects and different uses of aspirin in this review. Furthermore, recent patents of novel pharmaceutical interventions in the field of acetylsalicylic acid, expanding treatment options are presented. Literature search was performed in order to reach data and present information about aspirin from a historical perspective. Since its first use as a pain killer, aspirin has found a broad range of use in general medicine, cardiovascular medicine, neurology, obstetrics and gynecology, dentistry, gastroenterology, oncology with its different effects. Aspirin, a painkilling gift of history to mankind, with a history dating back to BC and various healing effects, promises to be of greater use in different fields of medicine with the light of recent studies, inspiring more research and gaining more popularity.

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

    PubMed

    Schapowal, A G; Simon, H U; Schmitz-Schumann, M

    1995-01-01

    don't work well enough, we combine them with aspirin desensitizations at a maintenance dose of 500 mg a day. Gastrointestinal side effects occur in 20% of the patients with a dose of 500 mg aspirin a day, in 46% with a mean dose of 1300 mg a day. The combined treatment of topical nasal steroids and aspirin-desensitization is effective in 65% of the patients with improvement in the symptoms of hyper-secretion, irritation and blockage, while 73% show improvement of polyps, hyposmia and anosmia. Endonasal endoscopic surgery of the ethmoids, turbinectoms and septoplasty should be done if necessary, especially in cases where conservative treatment fails. After surgery a further antiinflammatory treatment is absolutely necessary otherwise polyps reoccur in 90% of the cases after weeks or months. Unfortunately there is so far no curative treatment. New drugs like cytokine or leukotriene receptor antagonists give hope for better results in treatment of aspirin intolerance in the future.

  5. 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.

  6. 378 Aspirin Desensitization Treatment: A Case Report

    PubMed Central

    Alvarez, Mirta; Osoria, Lludenich; Ronquillo, Mercedes; Castro, Raúl; Perez, Doguerti; Rodríguez, José; Irarragorri, Catalina

    2012-01-01

    Background Aspirin (ASA) is one of the best known and most widely used drugs in the world. Patients with coronary artery disease require prolonged treatments with this drug, which is denied to those patients with histories of adverse reactions to it. Methods In a rapid desensitization protocol a patient with a history of ASA-induced urticaria-angioedema was treated with escalating doses of aspirin administered orally every 25 minutes. Results The patient completed the desensitization protocol in few hours without complications, and currently is able to take 125 mg of ASA per day without adverse reactions. Conclusions This report describes the first desensitization treatment with aspirin carried out in our hospital. No other case was found in the national bibliography.

  7. 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 ...

  8. Per aspirin ad astra...

    PubMed

    Hartung, Thomas

    2009-12-01

    Taking the 110th anniversary of marketing of aspirin as starting point, the almost scary toxicological profile of aspirin is contrasted with its actual use experience. The author concludes that we are lucky that, in 1899, there was no regulatory toxicology. Adding, for the purpose of this article, a fourth R to the Three Rs, i.e. Realism, three reality-checks are carried out. The first one comes to the conclusion that the tools of toxicology are hardly adequate for the challenges ahead. The second one concludes that, specifically, the implementation of the EU REACH system is not feasible with these tools, mainly with regard to throughput. The third one challenges the belief that classical alternative methods, i.e. replacing animal test-based tools one by one, is actually leading to a new toxicology - it appears to change only patches of the patchwork, but not to overcome any inherent limitations other than ethical ones. The perspective lies in the Toxicology for the 21st Century initiatives, which aim to create a new approach from the scratch, by an evidence-based toxicology and a global "Human Toxicology Programme". 2009 FRAME.

  9. [Epidemiology of digestive complications associated with use of low-dose aspirin].

    PubMed

    Czernichow, Pierre; Merle, Véronique

    2004-04-01

    Low-dose aspirin (< 330 mg/d) is recommended for the prevention of myocardial infarction or ischemic stroke. Six to 12% of the general population is exposed to low-dose aspirin. The most frequently studied digestive complications are bleeding peptic ulcers, whose risk is increased twofold by low-dose aspirin treatment, and non-complicated peptic ulcers. History of bleeding or non-complicated peptic ulcer, alcohol intake, concomitant treatment with NSAID or calcic inhibitors are demonstrated risk factors of bleeding ulcer associated with low-dose aspirin. The role of enteric coating, of low-dose aspirin dose, of delay since low-dose aspirin treatment onset, and of Helicobacter pylori infection, remains controversial. Antisecretory drugs (H2 inhibitors, proton pump inhibitors), and nitroglycerin are associated with a decreased risk of bleeding ulcer. The protective effect of COX-2 inhibitors on the risk of bleeding ulcer is suppressed by concomitant treatment with low-dose aspirin. The risk of no- complicated peptic ulcer was increased by low-dose aspirin intake by a factor 2.9 in one study. Low-dose aspirin dose, infection by Helicobacter pylori, NSAID intake, and absence of enteric coating, are possible risk factors for non-complicated peptic ulcer. No association was retrieved with alcohol intake and peptic ulcer history.

  10. 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

  11. A Proteomic Approach to Analyze the Aspirin-mediated Lysine Acetylome.

    PubMed

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

    2017-02-01

    Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-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.

  12. Higher rate of microscopic hematuria in elderly patients who take regular doses of aspirin: Result from AHAP Study

    PubMed Central

    Moudi, Emadouddin; Hosseini, Seyed-Reza; Bijani, Ali

    2016-01-01

    Background: Aspirin is the most widely used drug in medicine for cardiovascular and as recently for its role in cancer prevention. Although the risk of bleeding events increased following regular use of aspirin, little is known about the association of aspirin and hematuria. The present study aimed to evaluate the association of regular aspirin use and microscopic hematuria in elderly. Methods: In this study, we have extracted the data of elderly people who participated in Amirkola Health and Aging Project (AHAP) and taking regular doses of aspirin. The prevalence of microscopic hematuria was compared between the elderly who took aspirin regularly and those who did not take it. Results: A total of 1243 individuals (54.22% males, 45.78% females) were entered in to the study. Two hundred and eighty-four (23%) elderly took regular doses of aspirin. Microscopic hematuria was seen in 305 (24.54%) elderly. The prevalence of microscopic hematuria was 27.27% in regular users of aspirin and 23.72% in non-users of aspirin (P=0.126). The prevalence of microscopic hematuria was significantly higher among the regular users of aspirin compared to non-users in multiple logistic regression analysis (P=0.035, OR=1.40, 95%CI: 1.02-1.92). Conclusion: Taking regular doses of aspirin was accompanied with higher rate of microscopic hematuria in the elderly. PMID:27999646

  13. Higher rate of microscopic hematuria in elderly patients who take regular doses of aspirin: Result from AHAP Study.

    PubMed

    Moudi, Emadouddin; Hosseini, Seyed-Reza; Bijani, Ali

    2016-01-01

    Aspirin is the most widely used drug in medicine for cardiovascular and as recently for its role in cancer prevention. Although the risk of bleeding events increased following regular use of aspirin, little is known about the association of aspirin and hematuria. The present study aimed to evaluate the association of regular aspirin use and microscopic hematuria in elderly. In this study, we have extracted the data of elderly people who participated in Amirkola Health and Aging Project (AHAP) and taking regular doses of aspirin. The prevalence of microscopic hematuria was compared between the elderly who took aspirin regularly and those who did not take it. A total of 1243 individuals (54.22% males, 45.78% females) were entered in to the study. Two hundred and eighty-four (23%) elderly took regular doses of aspirin. Microscopic hematuria was seen in 305 (24.54%) elderly. The prevalence of microscopic hematuria was 27.27% in regular users of aspirin and 23.72% in non-users of aspirin (P=0.126). The prevalence of microscopic hematuria was significantly higher among the regular users of aspirin compared to non-users in multiple logistic regression analysis (P=0.035, OR=1.40, 95%CI: 1.02-1.92). Taking regular doses of aspirin was accompanied with higher rate of microscopic hematuria in the elderly.

  14. Aspirin metabolites are GPR35 agonists.

    PubMed

    Deng, Huayun; Fang, Ye

    2012-07-01

    Aspirin is widely used as an anti-inflammatory, anti-platelet, anti-pyretic, and cancer-preventive agent; however, the molecular mode of action is unlikely due entirely to the inhibition of cyclooxygenases. Here, we report the agonist activity of several aspirin metabolites at GPR35, a poorly characterized orphan G protein-coupled receptor. 2,3,5-Trihydroxybenzoic acid, an aspirin catabolite, was found to be the most potent GPR35 agonist among aspirin metabolites. Salicyluric acid, the main metabolite of aspirin, was also active. These results suggest that the GPR35 agonist activity of certain aspirin metabolites may contribute to the clinical features of aspirin.

  15. Aspirin activation of eosinophils and mast cells: implications in the pathogenesis of aspirin-exacerbated respiratory disease.

    PubMed

    Steinke, John W; Negri, Julie; Liu, Lixia; Payne, Spencer C; Borish, Larry

    2014-07-01

    Reactions to aspirin and nonsteroidal anti-inflammatory drugs in patients with aspirin-exacerbated respiratory disease (AERD) are triggered when constraints upon activated eosinophils, normally supplied by PGE2, are removed secondary to cyclooxygenase-1 inhibition. However, the mechanism driving the concomitant cellular activation is unknown. We investigated the capacity of aspirin itself to provide this activation signal. Eosinophils were enriched from peripheral blood samples and activated with lysine ASA (LysASA). Parallel samples were stimulated with related nonsteroidal anti-inflammatory drugs. Activation was evaluated as Ca2+ flux, secretion of cysteinyl leukotrienes (CysLT), and eosinophil-derived neurotoxin (EDN) release. CD34+ progenitor-derived mast cells were also used to test the influence of aspirin on human mast cells with measurements of Ca2+ flux and PGD2 release. LysASA induced Ca2+ fluxes and EDN release, but not CysLT secretion from circulating eosinophils. There was no difference in the sensitivity or extent of activation between AERD and control subjects, and sodium salicylate was without effect. Like eosinophils, aspirin was able to activate human mast cells directly through Ca2+ flux and PGD2 release. AERD is associated with eosinophils maturing locally in a high IFN-γ milieu. As such, in additional studies, eosinophil progenitors were differentiated in the presence of IFN-γ prior to activation with aspirin. Eosinophils matured in the presence of IFN-γ displayed robust secretion of both EDN and CysLTs. These studies identify aspirin as the trigger of eosinophil and mast cell activation in AERD, acting in synergy with its ability to release cells from the anti-inflammatory constraints of PGE2.

  16. Aspirin and acetaminophen: should they be available over the counter?

    PubMed

    Brune, Kay; Hinz, Burkhard; Otterness, Ivan

    2009-02-01

    Traditional nonsteroidal anti-inflammatory drugs block cyclooxygenase (COX). They are the most widely used drugs for pain relief. They are indispensable for their effects but are condemned for their adverse drug reactions. Two COX inhibitors, acetaminophen and aspirin, are the most widely used over-the-counter drugs. They have low (but useful) therapeutic activity, but they are endowed with specific risks that are not seen with most other COX inhibitors. Both are lethal if taken in overdose. Each is stigmatized by severe adverse effects. Aspirin results in prolonged inhibition of blood coagulation, and acetaminophen can result in liver toxicity at normal dose and liver failure at higher dose. Both drugs cause many deaths every year. We recommend that the status of both drugs be changed to prescription only. Their continued availability over the counter poses an unacceptable risk to the general population.

  17. Safety, tolerability, pharmacodynamics, and pharmacokinetics of rivaroxaban--an oral, direct factor Xa inhibitor--are not affected by aspirin.

    PubMed

    Kubitza, Dagmar; Becka, Michael; Mueck, Wolfgang; Zuehlsdorf, Michael

    2006-09-01

    Rivaroxaban (BAY 59-7939) is an oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. This was a randomized, 2-way crossover study in healthy male subjects, with an aspirin run-in period, to examine whether aspirin influences the safety, tolerability, pharmacodynamics, and pharmacokinetics of rivaroxaban. All treatments were well tolerated; drug-related adverse events were mild and transient. Aspirin did not alter the effects of rivaroxaban on Factor Xa activity or clotting tests. Platelet aggregation and bleeding time were not affected by rivaroxaban, and rivaroxaban did not influence the effects of aspirin on these parameters to a clinically relevant extent. Aspirin did not affect the pharmacokinetics of rivaroxaban, including the fraction unbound. This study suggests that there is no clinically relevant interaction between rivaroxaban and aspirin and that the 2 drugs could be administered concomitantly at the doses used in this study.

  18. Use of Aspirin postdiagnosis improves survival for colon cancer patients

    PubMed Central

    Bastiaannet, E; Sampieri, K; Dekkers, O M; de Craen, A J M; van Herk-Sukel, M P P; Lemmens, V; van den Broek, C B M; Coebergh, J W; Herings, R M C; van de Velde, C J H; Fodde, R; Liefers, G J

    2012-01-01

    Background: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients. Methods: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998–2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure. Results: In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63–0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50–0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46–0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79–1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70–2.20; P<0.001). Conclusion: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of

  19. Variability in the Responsiveness to Low-Dose Aspirin: Pharmacological and Disease-Related Mechanisms

    PubMed Central

    Rocca, Bianca; Petrucci, Giovanna

    2012-01-01

    The main pharmacological aspects of pharmacodynamics (PD) and pharmacokinetics (PK) of aspirin as antiplatelet agent were unravelled between the late sixties and the eighties, and low-dose aspirin given once daily has been shown to be a mainstay in the current treatment and prevention of cardiovascular disorders. Nevertheless, several PD and PK aspects of aspirin in selected clinical conditions have recently emerged and deserve future clinical attention. In 1994, the term “aspirin resistance” was used for the first time, but, until now, no consensus exists on definition, standardized assay, underlying mechanisms, clinical impact, and possible efficacy of alternative therapeutic interventions. At variance with an undefined aspirin-resistant status, in the last 5 years, the concept of variability in response to aspirin due to specific pathophysiological mechanisms and based on PK and/or PD of the drug has emerged. This growing evidence highlights the existence and possible clinical relevance of an interindividual variability of pharmacological aspirin response and calls for new, large studies to test new low-dose aspirin-based regimens which may ameliorate platelet acetylation, reduce variability in drug responsiveness, and improve clinical efficacy on selected populations. PMID:22288010

  20. Variability in the responsiveness to low-dose aspirin: pharmacological and disease-related mechanisms.

    PubMed

    Rocca, Bianca; Petrucci, Giovanna

    2012-01-01

    The main pharmacological aspects of pharmacodynamics (PD) and pharmacokinetics (PK) of aspirin as antiplatelet agent were unravelled between the late sixties and the eighties, and low-dose aspirin given once daily has been shown to be a mainstay in the current treatment and prevention of cardiovascular disorders. Nevertheless, several PD and PK aspects of aspirin in selected clinical conditions have recently emerged and deserve future clinical attention. In 1994, the term "aspirin resistance" was used for the first time, but, until now, no consensus exists on definition, standardized assay, underlying mechanisms, clinical impact, and possible efficacy of alternative therapeutic interventions. At variance with an undefined aspirin-resistant status, in the last 5 years, the concept of variability in response to aspirin due to specific pathophysiological mechanisms and based on PK and/or PD of the drug has emerged. This growing evidence highlights the existence and possible clinical relevance of an interindividual variability of pharmacological aspirin response and calls for new, large studies to test new low-dose aspirin-based regimens which may ameliorate platelet acetylation, reduce variability in drug responsiveness, and improve clinical efficacy on selected populations.

  1. Comparison of aspirin and indobufen in healthy volunteers.

    PubMed

    Lee, Jong-Young; Sung, Ki-Chul; Choi, Hyo-In

    2016-01-01

    The aim of this study is to quantify the extent and recovery of platelet inhibition after administration of indobufen and aspirin in healthy volunteers. Indobufen inhibits platelet aggregation by reversibly inhibiting the platelet cyclooxygenase enzyme, thereby suppressing thromboxane synthesis. Twenty healthy volunteers completed the study and received aspirin (200 mg/day for 2 weeks) followed by a 4-week washout period and then indobufen (200 mg twice a day for 2 weeks). The percent (%) inhibition of platelet aggregation (IPA) was assessed using arachidonic acid (0.5 mg/ml) and adenosine diphosphate (5 µM) at 4, 12, 24 and 48 hours after last dose of each drug. IPA assessed using arachidonic acid as the agonist was similar at 4 hours after the last dose of indobufen (81.07 ± 9.36%) and aspirin (96.99 ± 0.29%, p = 0.10), but significantly lower at 12 hours (74.04 ± 9.55% vs. 97.94 ± 0.28%, p = 0.02), 24 hours (33.39 ± 11.13% vs. 97.48 ± 0.32%, p < 0.001) and 48 hours (14.12 ± 9.74% vs. 98.22 ± 0.31%, p < 0.001) after indobufen, compared to the relative values for aspirin. IPA assessed using adenosine diphosphate as the agonist was similar in the two groups at 4, 12 and 24 hours after the last dose, but significantly lower 48 hours after the last dose of indobufen, compared to the relative value for aspirin (1.98 ± 3.57% vs. 12.61 ± 2.71%, p = 0.002). Indobufen (200 mg twice a day) caused equivalent initial inhibition of platelet aggregation to aspirin (200 mg daily), and the anti-aggregation effect diminished faster than after aspirin.

  2. Aspirin Intolerance: Experimental Models for Bed-to-Bench

    PubMed Central

    Yamashita, Masamichi

    2016-01-01

    Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents leads to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms. As the bed-to-bench approach, to confirm the clinical discussion in experimental cellular models, we have tried to develop a cellular model of AERD using activated RBL-2H3 cells, a rat mast cell like cell line. Indomethacin (another NSAID and also causes AERD), enhances in vitro cysLTs production by RBL-2H3 cells, while there is no induction of cysLTs production in the absence of inflammatory activation. Since this suggests that all inflammatory cells with activation of prostaglandin and cysLT metabolism should respond to NSAIDs, and then I have concluded that aspirin intolerance should be separated from subsequent bronchoconstriction. Evidence about the cellular mechanisms of NSAIDs may be employed for development of in vitro AERD models as the approach from bench-to-bed. PMID:27719658

  3. Aspirin-induced peptic ulcer and genetic polymorphisms.

    PubMed

    Shiotani, Akiko; Sakakibara, Takashi; Nomura, Maki; Yamanaka, Yoshiyuki; Nishi, Ryuji; Imamura, Hiroshi; Tarumi, Ken-ichi; Kamada, Tomoari; Hata, Jiro; Haruma, Ken

    2010-05-01

    There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)-induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX-1-1676T alleles was a significant risk factor for peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non-aspirin NSAID-related GI bleeding. The polymorphisms of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-511 T allele was significantly associated with peptic ulcer among low-dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro-inflammatory cytokines seems to reduce NSAIDs or aspirin-related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large-scale clinical studies are required.

  4. Oral anticoagulant treatment with and without aspirin.

    PubMed

    Altman, R; Rouvier, J; Gurfinkel, E

    1995-07-01

    For preventing thromboembolic events, the concurrent use of oral anticoagulant and antiplatelet drugs has been proposed. In prosthetic heart valves the use of moderate intensity anticoagulants [International Normalized Ratio (INR) 2-3] plus aspirin (100 mg/day) decreases the amount and severity of embolic episodes. The possibility that the same regimen could provide benefit in the prevention of thrombotic events in other arterial diseases is also indicated by the ATACS trial in unstable angina. The ongoing studies in ischemic heart diseases will also give the answer to this possibility.

  5. The historical analysis of aspirin discovery, its relation to the willow tree and antiproliferative and anticancer potential.

    PubMed

    Mahdi, J G; Mahdi, A J; Mahdi, A J; Bowen, I D

    2006-04-01

    For several millennia, the willow tree and salicin have been associated with salicylic acid, the key precursor molecule that has contributed to the discovery of acetylsalicylic acid, traded as aspirin. These molecules have been shown to possess phyto- and chemotherapeutic activities as analgesic drugs. In recent decades, aspirin has become the focus of extensive investigation into antiproliferative and anticancer activities. The historical steps that led to the discovery of aspirin, and its antiproliferative and anticancer potential are highlighted in this review.

  6. 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.

  7. Aspirin for Reducing Cancer Metastases?

    PubMed Central

    Henschke, Ulrich K.; Luande, G. Jeff; Choppala, Johnson D.

    1977-01-01

    Distant metastases are the principal cause of death from cancer. Many animal experiments in the last 25 years have shown consistently that distant metastases can be significantly reduced by anticoagulants and fibrinolytic agents. Since aspirin inhibits platelet function and increases fibrinolytic activity in humans, it may be effective in preventing metastases in cancer patients. It is suggested that aspirin be offered as an option to cancer patients who are at risk for distant metastases. PMID:904011

  8. 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.

  9. Influence of ethanol on aspirin release from hypromellose matrices.

    PubMed

    Roberts, Matthew; Cespi, Marco; Ford, James L; Dyas, A Mark; Downing, James; Martini, Luigi G; Crowley, Patrick J

    2007-03-06

    Release profiles of aspirin from hypromellose matrices in hydro-ethanolic media were studied. Percent aspirin released increased with increasing levels of ethanol in the dissolution media, correlating with the drug's solubility, however, dose dumping of aspirin did not occur. An initial rapid release was observed in media comprising 40% ethanol. Release in these conditions was considered to be both erosion and diffusion-mediated, in contrast to the release in 0, 10, 20 and 30% ethanol media, where erosion-controlled release dominated. Image analysis of matrix swelling indicated a slower initial interaction between ethanol and hypromellose accounting for the initial rapid release. Cloud point studies suggested that ethanol retarded hydration of the polymer.

  10. Antiplatelet drugs - P2Y12 inhibitors

    MedlinePlus

    ... prevent blood clots from forming in your arteries. Aspirin is an antiplatelet drug that may be used. ... Plavix, generic) may be used in place of aspirin for patients who have narrowing of the coronary ...

  11. Separation of the impairment of haemostasis by aspirin from mucosal injury in the human stomach.

    PubMed

    Hawkey, C J; Hawthorne, A B; Hudson, N; Cole, A T; Mahida, Y R; Daneshmend, T K

    1991-10-01

    1. An increasing body of data suggests that the antihaemostatic as well as the ulcerogenic actions of aspirin and other non-steroidal anti-inflammatory drugs may be operative when patients present with haematemesis and melaena. 2. We therefore developed methods to allow separate evaluation of the erosive and anti-haemostatic actions of aspirin in the human gastric mucosa. Volunteer subjects took 300 mg of aspirin daily in the morning or 600 mg of aspirin four times a day for 5 days under blinded randomized conditions. Changes in spontaneous gastric microbleeding, endoscopic signs of injury, spontaneous bleeding per gastric erosion, biopsy-induced bleeding and eicosanoids were studied. 3. Both doses of aspirin significantly inhibited gastric mucosal synthesis of prostaglandin E2 and reduced the serum thromboxane concentration. Erosions developed and regressed rapidly; compared with baseline 300 mg of aspirin daily in the morning caused substantial numbers of gastric erosions to develop (mean 5.3, 95% confidence limits 2.7-10.2) but this was significantly less than that caused by 600 mg of aspirin four times a day (10.9, 7.2-16.5, P less than 0.05). The presence of erosions was associated with enhanced spontaneous bleeding, but only during aspirin administration. 4. Aspirin significantly increased bleeding induced by mucosal biopsy and was associated with significant enhancements in the rate of bleeding per gastric erosion. Bleeding rate per erosion but not biopsy-induced bleeding showed a significant dose-related increase with 600 mg of aspirin four times a day. Enteric coating reduced endoscopic signs of injury, but did not affect the impaired haemostasis caused by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Deposition and aggregation of aspirin molecules on a phospholipid bilayer pattern.

    PubMed

    Mao, Guangzhao; Chen, Dongzhong; Handa, Hitesh; Dong, Wenfei; Kurth, Dirk G; Möhwald, Helmuth

    2005-01-18

    Aspirin and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) are deposited from their alcoholic mixed solution onto highly oriented pyrolytic graphite (HOPG) by spin coating. The film structure and morphology are characterized by atomic force microscopy (AFM). The barely soluble DMPE forms a highly oriented stripe phase as a result of its one-dimensional epitaxy with the HOPG lattice. The bilayer stripe pattern exposes the cross section of the lipid bilayer lamellae and enables the direct visualization of the molecular interactions of drug or biological molecules with either the hydrophobic or the hydrophilic part of the phospholipid bilayer. The bilayer pattern affects the aspirin molecular deposition and aggregation. AFM shows that the aspirin molecules prefer to deposit and aggregate along the aliphatic interior part of the bilayer pattern, giving rise to parallel dimer rods in registry with the underlying pattern. The nonpolar interactions between aspirin and the phospholipid bilayer are consistent with the lipophilic nature of aspirin. The bilayer pattern not only stabilizes the rodlike aggregate structure of aspirin at low aspirin concentration but also inhibits crystallization of aspirin at high aspirin concentration. Molecular models show that the width of the DMPE aliphatic chain interior can accommodate no more than two aspirin dimers. The bilayer confinement may prevent aspirin from reaching its critical nucleus size. This study illustrates a general method to induce a metastable or amorphous form of an active pharmaceutical ingredient (API) by chemical confinement under high undercooling conditions. Metastable and amorphous solids often display better solubility and bioavailability than the stable crystalline form of the API.

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

    PubMed

    Li, Sainan; Dai, Weiqi; Mo, Wenhui; Li, Jingjing; Feng, Jiao; Wu, Liwei; Liu, Tong; Yu, Qiang; Xu, Shizan; Wang, Wenwen; Lu, Xiya; Zhang, Qinghui; Chen, Kan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Fan, Xiaoming; Xu, Ling; Guo, Chuanyong

    2017-08-31

    Hepatocellular carcinoma (HCC) is one of the few cancers with a continuous increase in incidence and mortality. Drug resistance is a major problem in the treatment of HCC. In this study, two sorafenib-resistant HCC cell lines and a nude mouse subcutaneously tumor model were used to explore the possible mechanisms leading to sorafenib resistance, and to investigate whether aspirin could increase the sensitivity of hepatoma cells to sorafenib. The combination of aspirin and sorafenib resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo. High glycolysis and PFKFB3 overexpression occupied a dominant position in sorafenib resistance, and can be targeted and overcome by aspirin. Aspirin plus sorafenib induced apoptosis in tumors without inducing weight loss, hepatotoxicity or inflammation. Our results suggest that aspirin overcomes sorafenib resistance and their combination may be an effective treatment approach for HCC. © 2017 UICC.

  14. Effects of nimesulide, a selective COX-2 inhibitor, on cardiovascular function in 2 rat models of diabetes.

    PubMed

    Leung, Joanne Y T; Pang, Catherine C Y

    2014-07-01

    Cyclooxygenase-2 (COX-2) has been found to be activated in diabetes. We investigated whether nimesulide (selective COX-2 inhibitor) alters cardiovascular responses to adrenaline in 2 rat models of diabetes. Wistar rats (5-week old) were continuously fed a normal or high-fructose diet (60% of caloric intake). At week 2, half of the rats in each diet regimen were given streptozotocin (STZ) (60 mg/kg, intravenously). At week 6, cardiovascular effects of adrenaline (6 and 16 × 10 mol·kg·min, intravenously) were measured in 4 groups of thiobutabarbital-anesthetized rats (control, fructose, STZ, and fructose-streptozotocin [F-STZ]) before and after the injection of nimesulide (3 mg/kg, intravenously). Both the STZ and F-STZ groups exhibited hyperglycemia and significantly (P < 0.05) reduced left ventricular contractility, mean arterial pressure, arterial and venous resistance, and mean circulatory filling pressure (index of venous tone) responses to adrenaline, relative to the control and fructose groups. Nimesulide did not affect responses in the control and fructose groups but increased the venous and, to a less extent, arterial constriction to adrenaline in both the groups of diabetic rats. The cardiac contractile responses, however, were not altered after nimesulide treatment. The results show that nimesulide partially restored arterial and venous constriction to adrenaline in rats with STZ- and F-STZ-induced diabetes.

  15. Antihypertensive efficacy of angiotensin converting enzyme inhibition and aspirin counteraction.

    PubMed

    Guazzi, M D; Campodonico, J; Celeste, F; Guazzi, M; Santambrogio, G; Rossi, M; Trabattoni, D; Alimento, M

    1998-01-01

    Blockade of bradykinin breakdown and enhancement of prostaglandin release probably participate in the antihypertensive activity of angiotensin converting enzyme (ACE) inhibitors. Cyclooxygenase blockers may attenuate the efficacy of ACE inhibitors by interfering with prostaglandin synthesis, and patients taking aspirin may not benefit from ACE inhibition. This study was designed to evaluate the incidence of the counteractive phenomenon and to define minimal aspirin dosage that causes an antagonistic effect. These were 26 patients with mild to moderate hypertension (group 1) and 26 patients with severe untreated primary hypertension (group 2). Enalapril (20 mg twice a day) was used as a single drug in group 1 and was added to the combination of long-acting nifedipine (30 mg/day) and atenolol (50 mg/day) in group 2. Aspirin was tested at doses of 100 and 300 mg/day, and an attenuation of more than 20% of the mean blood pressure decrease produced by enalapril was the criteria that defined antagonism. The 100 mg dose was ineffective. However, 300 mg aspirin had an antagonistic effect in 57% of patients in group 1 and 50% of patients in group 2: mean arterial pressure was lowered by 63% and 91% less, respectively. Results were independent of the drug administration order. In "responders," aspirin significantly attenuated the renin rise associated with ACE inhibition. These findings suggest that a number of ACE-inhibited patients are susceptible to 300 mg/day aspirin, regardless of hypertension severity. Antagonism may be mediated through prostaglandin inhibition according to predominance, in an individual patient, of prostaglandin activation (also as a renin secretory stimulus) or angiotensin blockade by enalapril.

  16. Riociguat (BAY 63-2521) and aspirin: a randomized, pharmacodynamic, and pharmacokinetic interaction study

    PubMed Central

    Reber, Michael; Krätzschmar, Jörn; Unger, Sigrun; Mück, Wolfgang; Wensing, Georg

    2016-01-01

    Abstract In preclinical studies, drugs that increase cyclic guanosine monophosphate levels have been shown to influence platelet function/aggregation; however, the effect of riociguat on human platelets is unclear. Aspirin, a platelet inhibitor, is likely to be given concomitantly in patients receiving riociguat. It is therefore important to establish clinically whether (1) riociguat affects platelet function and (2) aspirin and riociguat interact. This randomized, open-label, crossover study investigated potential pharmacodynamic and pharmacokinetic interactions between these drugs in healthy male volunteers (N = 18). There were 3 treatment regimens: a single morning dose of riociguat 2.5 mg, aspirin 500 mg on 2 consecutive mornings, and both treatments together, with riociguat given on the second morning. Fifteen participants were available for pharmacodynamic/pharmacokinetic analysis. There was no effect of riociguat alone on bleeding time, platelet aggregation, and serum thromboxane B2 levels. The effects of aspirin on these parameters were not influenced by concomitant administration of riociguat. The pharmacokinetic profile of riociguat showed interindividual variability, which was independent of aspirin coadministration. Six of 17 participants available for safety evaluation reported at least 1 treatment-emergent adverse event. All adverse events were of mild severity, apart from 1 report of moderate headache. No serious adverse events occurred. In conclusion, riociguat demonstrated no clinically relevant pharmacodynamic or pharmacokinetic interactions with aspirin at the doses used in this study in healthy men; coadministration of riociguat and aspirin should therefore not require any dose adjustment for either drug. PMID:27162625

  17. Non-steroidal anti-inflammatory drugs activate NADPH oxidase in adipocytes and raise the H2O2 pool to prevent cAMP-stimulated protein kinase a activation and inhibit lipolysis

    PubMed Central

    2013-01-01

    Background Non-steroidal anti-inflammatory drugs (NSAIDs) —aspirin, naproxen, nimesulide, and piroxicam— lowered activation of type II cAMP-dependent protein kinase A (PKA-II) in isolated rat adipocytes, decreasing adrenaline- and dibutyryl cAMP (Bt2cAMP)-stimulated lipolysis. The molecular bases of insulin-like actions of NSAID were studied. Results Based on the reported inhibition of lipolysis by H2O2, catalase was successfully used to block NSAID inhibitory action on Bt2cAMP-stimulated lipolysis. NSAID, at (sub)micromolar range, induced an H2O2 burst in rat adipocyte plasma membranes and in whole adipocytes. NSAID-mediated rise of H2O2 was abrogated in adipocyte plasma membranes by: diphenyleneiodonium, an inhibitor of NADPH oxidase (NOX); the NOX4 antibody; and cytochrome c, trapping the NOX-formed superoxide. These three compounds prevented the inhibition of Bt2cAMP-stimulated lipolysis by NSAIDs. Inhibition of aquaporin-mediated H2O2 transport with AgNO3 in adipocytes allowed NOX activation but prevented the lipolysis inhibition promoted by NSAID: i.e., once synthesized, H2O2 must reach the lipolytic machinery. Since insulin inhibits adrenaline-stimulated lipolysis, the effect of aspirin on isoproterenol-stimulated lipolysis in rat adipocytes was studied. As expected, isoproterenol-mediated lipolysis was blunted by both insulin and aspirin. Conclusions NSAIDs activate NOX4 in adipocytes to produce H2O2, which impairs cAMP-dependent PKA-II activation, thus preventing isoproterenol-activated lipolysis. H2O2 signaling in adipocytes is a novel and important cyclooxygenase-independent effect of NSAID. PMID:23718778

  18. Non-steroidal anti-inflammatory drugs activate NADPH oxidase in adipocytes and raise the H2O2 pool to prevent cAMP-stimulated protein kinase a activation and inhibit lipolysis.

    PubMed

    Vázquez-Meza, Héctor; de Piña, Martha Zentella; Pardo, Juan Pablo; Riveros-Rosas, Héctor; Villalobos-Molina, Rafael; Piña, Enrique

    2013-05-30

    Non-steroidal anti-inflammatory drugs (NSAIDs) -aspirin, naproxen, nimesulide, and piroxicam- lowered activation of type II cAMP-dependent protein kinase A (PKA-II) in isolated rat adipocytes, decreasing adrenaline- and dibutyryl cAMP (Bt2cAMP)-stimulated lipolysis. The molecular bases of insulin-like actions of NSAID were studied. Based on the reported inhibition of lipolysis by H2O2, catalase was successfully used to block NSAID inhibitory action on Bt2cAMP-stimulated lipolysis. NSAID, at (sub)micromolar range, induced an H2O2 burst in rat adipocyte plasma membranes and in whole adipocytes. NSAID-mediated rise of H2O2 was abrogated in adipocyte plasma membranes by: diphenyleneiodonium, an inhibitor of NADPH oxidase (NOX); the NOX4 antibody; and cytochrome c, trapping the NOX-formed superoxide. These three compounds prevented the inhibition of Bt2cAMP-stimulated lipolysis by NSAIDs. Inhibition of aquaporin-mediated H2O2 transport with AgNO3 in adipocytes allowed NOX activation but prevented the lipolysis inhibition promoted by NSAID: i.e., once synthesized, H2O2 must reach the lipolytic machinery. Since insulin inhibits adrenaline-stimulated lipolysis, the effect of aspirin on isoproterenol-stimulated lipolysis in rat adipocytes was studied. As expected, isoproterenol-mediated lipolysis was blunted by both insulin and aspirin. NSAIDs activate NOX4 in adipocytes to produce H2O2, which impairs cAMP-dependent PKA-II activation, thus preventing isoproterenol-activated lipolysis. H2O2 signaling in adipocytes is a novel and important cyclooxygenase-independent effect of NSAID.

  19. Persantine-Aspirin Reinfarction Study. Part II. Secondary coronary prevention with persantine and aspirin.

    PubMed

    Klimt, C R; Knatterud, G L; Stamler, J; Meier, P

    1986-02-01

    In the Persantine-Aspirin Reinfarction Study, Part II (PARIS II), 3,128 persons who had recovered from myocardial infarction, suffered from 4 weeks to 4 months previously, were randomized into two groups: dipyridamole (Persantine) plus aspirin (n = 1,563) and placebo (n = 1,565). The average length of follow-up was 23.4 months. Prespecified primary end points were coronary incidence (definite nonfatal myocardial infarction plus death due to recent or acute cardiac event), coronary mortality (death due to recent or acute cardiac event) and total mortality, each at 1 year of patient follow-up and at the end of the study. Coronary incidence in the Persantine plus aspirin group was significantly lower than in the placebo group, both at 1 year (30% reduction) and at the end of the study (24% reduction). The statistically significant differences in coronary incidence, at 1 year and at the end of the study, in favor of the combination treatment remained after adjustment for multiple baseline variables and adjustment for multiple testing (three end points for two time periods). Although there were reductions for other end points, these differences were not statistically significant. Coronary mortality was 20% lower in the Persantine plus aspirin group compared with the placebo group at 1 year, and 6% lower overall. Total mortality in the treated group compared with the placebo group was 11% lower at 1 year and 3% lower overall. The reduced rates of coronary incidence largely reflected lower rates of definite nonfatal myocardial infarction in the Persantine plus aspirin group. Several subgroups were defined a priori and at the end of the study. The beneficial effect of Persantine plus aspirin compared with placebo for coronary incidence tended to be greater for the following groups of patients: those who had a non-Q wave infarct; those who were not taking digitalis; those who were receiving beta-receptor blocking drugs at baseline; those who were in New York Heart

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

    PubMed Central

    Hernández-Díaz, Sonia; García Rodríguez, Luis A

    2006-01-01

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

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

    PubMed

    Hernández-Díaz, Sonia; García Rodríguez, Luis A

    2006-09-20

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

  2. A novel co-drug of aspirin and ursolic acid interrupts adhesion, invasion and migration of cancer cells to vascular endothelium via regulating EMT and EGFR-mediated signaling pathways: multiple targets for cancer metastasis prevention and treatment

    PubMed Central

    Tang, Qiao; Liu, Yajun; Li, Tao; Yang, Xiang; Zheng, Guirong; Chen, Hongning; Jia, Lee; Shao, Jingwei

    2016-01-01

    Metastasis currently remains the predominant cause of breast carcinoma treatment failure. The effective targeting of metastasis-related-pathways in cancer holds promise for a new generation of therapeutics. In this study, we developed an novel Asp-UA conjugate, which was composed of classical “old drug” aspirin and low toxicity natural product ursolic acid for targeting breast cancer metastasis. Our results showed that Asp-UA could attenuate the adhesion, migration and invasion of breast cancer MCF-7 and MDA-MB-231 cells in a more safe and effective manner in vitro. Molecular and cellular study demonstrated that Asp-UA significantly down-regulated the expression of cell adhesion and invasion molecules including integrin α6β1, CD44, MMP-2, MMP-9, COX-2, EGFR and ERK proteins, and up-regulated the epithelial markers “E-cadherin” and “β-catenin”, and PTEN proteins. Furthermore, Asp-UA (80 mg/kg) reduced lung metastasis in a 4T1 murine breast cancer metastasis model more efficiently, which was associated with a decrease in the expression of CD44. More importantly, we did not detect side effects with Asp-UA in mice such as weight loss and main viscera tissues toxicity. Overall, our research suggested that co-drug Asp-UA possessed potential metastasis chemoprevention abilities via influencing EMT and EGFR-mediated pathways and could be a more promising drug candidate for the prevention and/or treatment of breast cancer metastasis. PMID:27683033

  3. Aspirin prevents bone loss with little mechanical improvement in high-fat-fed ovariectomized rats.

    PubMed

    Lin, Sien; Lee, Wayne Y W; Huang, Meiling; Fu, Ziwei; Liang, Yanlong; Wu, Haiyou; Xu, Liangliang; Suen, Chun Wai; Huang, Jianping; Wu, Tie; Cui, Liao; Li, Gang

    2016-11-15

    Obesity and osteoporosis are often concurrently happened in the menopausal women. Obesity in menopausal women is not only related to a high risk of cardiovascular disease, but also results in a detrimental effect on bone health. This study aimed to investigate the effects of aspirin, a popular anti-thrombosis drug, on bone quantity and quality in the high-fat-fed animal model. Adult female rats were subjected to either sham operations or ovariectomized operations. The ovariectomized rats were orally administered with deionized water or standardized high fat emulsion with or without aspirin. All rats were injected with calcein before killed for the purpose of double in vivo labeling. Biochemistry, histomorphometry, micro-computed tomography analysis, mechanical test, and component analysis were performed after 12 weeks. In vitro cell culture was also performed to observe the effect of aspirin in osteogenesis. We found that high fat remarkably impaired bone formation and bone biomechanics. Aspirin treatment significantly prevented bone loss by increasing bone formation. In vitro studies also validated the enhancement of osteogenic differentiation. However, aspirin presented no significant improvement in bone mechanical properties. Component analysis shown aspirin could significantly increase the content of mineral, but had limited effect on the content of collagen. In conclusion, aspirin is beneficial for the prevention of bone loss; meanwhile, it may cause an imbalance in the components of bone which may weaken the mechanical properties. The current study provided further evidence that aspirin might not be powerful for the prevention of fracture in osteoporotic patients.

  4. Gastrointestinal ulcers, role of aspirin, and clinical outcomes: pathobiology, diagnosis, and treatment

    PubMed Central

    Cryer, Byron; Mahaffey, Kenneth W

    2014-01-01

    Peptic ulcer disease is a major cause of morbidity and mortality in the US with more than six million diagnoses annually. Ulcers are reported as the most common cause of hospitalization for upper gastrointestinal (GI) bleeding and are often a clinical concern due to the widespread use of aspirin and nonsteroidal anti-inflammatory drugs, both of which have been shown to induce ulcer formation. The finding that Helicobacter pylori infection (independent of aspirin use) is associated with the development of ulcers led to a more thorough understanding of the causes and pathogenesis of ulcers and an improvement in therapeutic options. However, many patients infected with H. pylori are asymptomatic and remain undiagnosed. Complicating matters is a current lack of understanding of the association between aspirin use and asymptomatic ulcer formation. Low-dose aspirin prescriptions have increased, particularly for cardioprotection. Unfortunately, the GI side effects associated with aspirin therapy continue to be a major complication in both symptomatic and asymptomatic patients. These safety concerns should be important considerations in the decision to use aspirin and warrant further education. The medical community needs to continue to improve awareness of aspirin-induced GI bleeding to better equip physicians and improve care for patients requiring aspirin therapy. PMID:24741318

  5. Two cases of wheat-dependent anaphylaxis induced by aspirin administration but not by exercise.

    PubMed

    Matsukura, S; Aihara, M; Sugawara, M; Kunimi, Y; Matsuki, M; Inoue, Y; Kambara, T; Ikezawa, Z

    2010-04-01

    Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to enhance the symptoms of wheat-dependent exercise-induced anaphylaxis (WDEIA). In contrast to many reports on WDEIA, there have been only a few reports of wheat-dependent aspirin-induced anaphylaxis not induced by the combination of wheat and exercise. Two patients with wheat-dependent anaphylaxis underwent provocation tests to clarify the cause of their symptoms. Skin-prick testing (SPT) was also performed with and without administration of aspirin. Specific IgE antibody to wheat, gluten, and omega-5 gliadin were examined. In the provocation tests, anaphylactic reactions were not induced by wheat or aspirin alone or by the combination of wheat and exercise, but were induced by the combination of wheat and aspirin. An increase in the blood histamine level was detected after provocation in both patients. Pretreatment with aspirin enhanced the SPT reactions to wheat and gluten in both patients. Specific IgE antibodies to wheat and gluten were expressed in the serum of both patients, and specific omega-5 gliadin IgE antibody was detected in the serum of one patient. We present two cases of specific wheat-dependent anaphylaxis induced by aspirin but not by exercise. We suggest that pretreatment with aspirin under controlled conditions is useful to confirm the diagnosis of food allergy when a challenge test with food alone or with food and exercise fails to induce positive reactions.

  6. Aspirin in the primary prevention of cardiovascular disease: current knowledge and future research needs.

    PubMed

    Hennekens, Charles H; Dalen, James E

    2014-11-01

    In secondary prevention, among a very wide range of survivors of prior occlusive cardiovascular disease (CVD) events and those suffering acute myocardial infarction (MI) or occlusive stroke, aspirin decreases risks of MI, stroke, and CVD death. In these high risk patients, the absolute benefits are large and absolute risks are far smaller so aspirin should be more widely prescribed. In contrast, in primary prevention, aspirin reduces risks of first MI but the evidence on stroke and CVD death remain inconclusive. Based on the current totality of evidence from predominantly low risk subjects where the absolute benefits is low and side effects the same as in secondary prevention, any decision to prescribe aspirin for primary prevention should be an individual clinical judgment by the healthcare provider that weighs the absolute benefit in reducing the risk of a first MI against the absolute risk of major bleeding. If the ongoing trials of intermediate risks subjects show net benefits then general guidelines may be justified with several caveats. First, any decision to use aspirin should continue to be made by the healthcare provider. Second, therapeutic lifestyle changes and other drugs of life saving benefit such as statins should be considered with aspirin as an adjunct, not alternative. The more widespread and appropriate use of aspirin in primary prevention is particularly attractive, especially in developing countries where CVD is emerging as the leading cause of death. In addition, aspirin is generally widely available over the counter and is extremely inexpensive.

  7. Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice.

    PubMed

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

    2017-08-01

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

  8. Cyclooxygenase-independent effects of aspirin on HT-29 human colon cancer cells, revealed by oligonucleotide microarrays.

    PubMed

    Yin, Hongying; Xu, Hao; Zhao, Yongchao; Yang, Weiping; Cheng, Jing; Zhou, Yuxiang

    2006-08-01

    Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) inhibit proliferation of human colon cancer cells in vitro. Transmission electron microscope detected morphological features of apoptosis in the aspirin-treated (5 mM, 72 h) HT-29 cells in which cyclooxygenoase-2 is catalytically inactive. We investigated aspirin-induced genome-wide expression changes in HT-29 cells and further studied the time- and concentration-dependent expression changes in 374 apoptosis-related genes, which is the first to show stimulation of genome-wide expression of HT-29 cells by aspirin. The most marked effects of aspirin are on ribosome assembly and rRNA metabolism, which could explain why the quasi-apoptotic morphological changes are not accompanied by a classical DNA ladder. These findings demonstrate that aspirin induces apoptosis in HT-29 cells, bolstering the hypothesis that apoptosis may be a mechanism by which NSAIDs inhibit colon carcinogenesis.

  9. Stress-responsive JNK mitogen-activated protein kinase mediates aspirin-induced suppression of B16 melanoma cellular proliferation

    PubMed Central

    Ordan, Orly; Rotem, Ronit; Jaspers, Ilona; Flescher, Eliezer

    2003-01-01

    Available anticancer drugs do not seem to modify the prognosis of metastatic melanoma. Salicylate and acetyl salicylic acid (aspirin) were found to suppress growth in a number of transformed cells, that is, prostate and colon. Therefore, we studied the direct effects of aspirin on metastatic B16 melanoma cells. Aspirin at a plasma-attainable and nontoxic level suppressed the proliferation of B16 cells. Aspirin induced the activation of p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases. Inhibition of JNK, but not p38, decreased the suppressive effect of aspirin upon the proliferation of B16 cells. The aspirin-induced reduction in B16 proliferation was cumulative over time. Aspirin and the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) induced B16 cell death synergistically. In addition to the murine B16 cell line, the proliferation of SK-28 human melanoma cells was also suppressed by aspirin. In conclusion, aspirin suppresses the proliferation of metastatic B16 cells in a JNK-dependent mechanism. PMID:12684272

  10. 1,2,3-Triazole-nimesulide hybrid: Their design, synthesis and evaluation as potential anticancer agents.

    PubMed

    Mareddy, Jyoti; Suresh, N; Kumar, C Ganesh; Kapavarapu, Ravikumar; Jayasree, A; Pal, Sarbani

    2017-02-01

    A new hybrid template has been designed by integrating the structural features of nimesulide and the 1,2,3-triazole moiety in a single molecular entity at the same time eliminating the problematic nitro group of nimesulide. The template has been used for the generation of a library of molecules as potential anticancer agents. A mild and greener CuAAC approach has been used to synthesize these compounds via the reaction of 4-azido derivative of nimesulide and terminal alkynes in water. Three of these compounds showed promising growth inhibition (IC50 ∼6-10μM) of A549, HepG2, HeLa and DU145 cancer cell lines but no significant effects on HEK293 cell line. They also inhibited PDE4B in vitro (60-70% at 10μM) that was supported by the docking studies (PLP score 87-94) in silico.

  11. Aspirin to Zoloft: Ways Medicines Work

    MedlinePlus

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

  12. Aspirin resistant patients with recent ischemic stroke.

    PubMed

    Castilla-Guerra, L; Navas-Alcántara, M S; Fernández-Moreno, M C

    2014-04-01

    Some patients with a recent ischemic stroke who are being treated with aspirin as an antiaggregant suffer a new ischemic stroke. These patients (15-25%) have been called unresponsive to aspirin or aspirin resistant. The aspirin-resistant patients have a four-time greater risk of suffering a stroke. Furthermore, these strokes are generally more severe, with increased infarct volume and greater risk of recurrence. There is currently no ideal laboratory test to detect the resistance to the antiaggregant effect of aspirin. The study of resistance to aspirin would only be indicated in selected cases. In these patients, one should first rule out any "pseudo-resistance" to aspirin (lack of compliance, concomitant treatments that interfere with the action of the aspirin). Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. Aspirin and Extended-Release Dipyridamole

    MedlinePlus

    Do not substitute the individual components of aspirin and dipyridamole (Persantine) for the combination product of aspirin and extended-release dipyridamole.Keep all appointments with your doctor and the laboratory. Your doctor may ...

  14. Aspirin during Pregnancy: Is It Safe?

    MedlinePlus

    Healthy Lifestyle Pregnancy week by week Is it safe to take aspirin during pregnancy? Answers from Yvonne Butler Tobah, M. ... 2015 Original article: http://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/expert-answers/aspirin-during-pregnancy/ ...

  15. Phytoremediation of aspirin and tetracycline by Brassica juncea.

    PubMed

    Gahlawat, Sonal; Gauba, Pammi

    2016-09-01

    With the increasing release of pharmaceutical drugs in the environment, research is in progress for investigating alternative methods for their remediation. Various studies have shown the phytoremediation potential of Brassica juncea for metals. The current study was aimed at evaluating the phytoremediation potential of B. juncea for two different pharmaceutical drugs i.e. aspirin and tetracycline in in-vitro conditions. The seeds of B. juncea were germinated and grown for a period of 28 and 24 days for aspirin and tetracycline, respectively. The study analyzed the remediation rate of B. juncea for the selected drugs in three different sets of varying concentration along with any phytotoxic effects exerted by the drugs on the seeds. Preliminary results showed that the average remediation rate of aspirin and tetracycline at the end of experiment was approximately 90% and 71%, respectively. As initial drug concentrations were increased in the media, the remediation rate also improved. However, at higher concentrations, the plants showed phytotoxicity as depicted by the decrease in shoot length of the germinated seeds. These preliminary results indicated that B. juncea could tolerate and remediate pharmaceutical drugs such as analgesics and antibiotics.

  16. Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects.

    PubMed

    Pérez-Alzate, Diana; Blanca-López, Natalia; Doña, Inmaculada; Agúndez, José A; García-Martín, Elena; Cornejo-García, José A; Perkins, James R; Blanca, Miguel; Canto, Gabriela

    2016-01-01

    In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation.

  17. Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects

    PubMed Central

    Pérez-Alzate, Diana; Blanca-López, Natalia; Doña, Inmaculada; Agúndez, José A.; García-Martín, Elena; Cornejo-García, José A.; Perkins, James R.; Blanca, Miguel; Canto, Gabriela

    2016-01-01

    In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation. PMID:27489545

  18. Aspirin sensitivity: acetylsalicylate or excipients.

    PubMed

    Hebron, B S; Hebron, H J

    2009-08-01

    We present three patients who developed urticaria while taking an enteric formulation of aspirin, confirmed on a second exposure. Although hypersensitivity reactions to aspirin, especially in asthmatic patients or those with nasal polyps, are well reported, our patients did not exhibit any underlying history of atopy. Furthermore, two of the patients were able to tolerate a soluble formulation. We review the literature and discuss whether these symptoms might be caused by pharmaceutical excipients, present in very small amounts in the enteric coating, rather than the active ingredient acetylsalicylate. Adverse reactions to excipients are fortunately rare but are occasionally reported.

  19. 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

  20. Tooth erosion caused by chewing aspirin.

    PubMed

    Grace, Edward G; Sarlani, Eleni; Kaplan, Sarit

    2004-07-01

    Although the effects of aspirin on the oral mucosa are well-documented, there is little documentation of the effects of aspirin-chewing on the enamel and dentin. The authors present two cases of patients with damage to their tooth enamel and dentin. Both patients had similiar symptoms, but had not been told that chewing aspirin could harm tooth structure. The authors identify clinical signs and symptoms and discuss ways to prevent erosion. The common factor in these cases is that aspirin was the only possible cause of the tooth erosion. Dentists should be aware of the effects of aspirin-chewing on tooth structure and advise their patients accordingly.

  1. Aspirin for Prevention of Cardiovascular Disease.

    PubMed

    Mendy, Vincent L; Vargas, Rodolfo; Zhang, Lei

    2017-09-07

    We used data from the 2013 Mississippi Behavioral Risk Factor Surveillance System to examine aspirin use for the prevention of primary and secondary cardiovascular disease (CVD), based on the 2009 US Preventive Services Task Force (USPSTF) guidelines, among Mississippi men (aged 45-79 y) and women (aged 55-79 y) and to explore differences in aspirin use by sociodemographic characteristics. Among those without CVD, 39.1% of men and 45.9% of women reported taking aspirin, and among those with CVD, 85.9% of men and 85.1% of women reported taking aspirin. Data on preventive use of aspirin by sociodemographic characteristics yielded mixed results.

  2. Stability-indicating HPLC Method for Simultaneous Determination of Aspirin and Prasugrel

    PubMed Central

    Patel, Shital M.; Patel, C. N.; Patel, V. B.

    2013-01-01

    A simple, sensitive, specific, accurate, and stability-indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of aspirin and prasugrel, using a Kromasil 100 C18 (150×4.6 mm, 5 μ) column and a mobile phase composed of acetonitrile:methanol:water (30:10:60, v/v), pH 3.0 adjusted with o-phosphoric acid. The retention times of aspirin and prasugrel were found to be 3.28 min and 6.61 min, respectively. Linearity was established for aspirin and prasugrel in the range of 15-150 and 2-20 μg/ml, respectively. The percentage recoveries of aspirin and prasugrel were found to be in the range of 99.34-100.32% and 98.92-102.09%, respectively. Both the drugs were subjected to acid, alkali and neutral hydrolysis, oxidation, dry heat, and UV degradation. The degradation studies indicated aspirin to be more susceptible to alkaline hydrolysis, while prasugrel to be more susceptible to neutral hydrolysis. The degradation products were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of aspirin and prasugrel in bulk drugs and formulations. PMID:24302795

  3. Comparison of effects of aspirin and indomethacin on human platelet prostaglandin synthetase.

    PubMed Central

    Crook, D; Collins, A J

    1977-01-01

    Human platelets were incubated in vitro with either aspirin or indomethacin and the prostaglandin synthetase activity of the resultant microsomal fraction from each incubation measured using a radiometric technique. Whereas aspirin produced a dose-related inhibition of the enzyme, indomethacin produced little or no inhibition over the same concentration range (10(-6) mol/l--10(-3) mol/l). Furthermore, administration of aspirin (600 mg) to volunteers produced a highly significant, prolonged inhibition of platelet microsomal prostaglandin synthetase whereas no inhibition was found with indomethacin (50 mg). As indomethacin is considerably more potent than aspirin as an inhibitor of human platelet prostaglandin synthetase in vitro, the results suggest a fundamental difference in the nature of the inhibition produced by each drug, aspirin being an essentially irreversible inhibitor whereas the inhibition produced by indomethacin is reversible. Studies with [3H-acetyl] aspirin have confirmed previous findings (Roth and Majerus, 1975) that aspirin produces an irreversible acetylation of a particulate fraction protein from human platelets. PMID:411427

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

    PubMed Central

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

    2016-01-01

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

  5. Impacts of metformin and aspirin on life history features and longevity of crickets: trade-offs versus cost-free life extension?

    PubMed

    Hans, Harvir; Lone, Asad; Aksenov, Vadim; Rollo, C David

    2015-01-01

    We examined the impacts of aspirin and metformin on the life history of the cricket Acheta domesticus (growth rate, maturation time, mature body size, survivorship, and maximal longevity). Both drugs significantly increased survivorship and maximal life span. Maximal longevity was 136 days for controls, 188 days (138 % of controls) for metformin, and 194 days (143 % of controls) for aspirin. Metformin and aspirin in combination extended longevity to a lesser degree (163 days, 120 % of controls). Increases in general survivorship were even more pronounced, with low-dose aspirin yielding mean longevity 234 % of controls (i.e., health span). Metformin strongly reduced growth rates of both genders (<60 % of controls), whereas aspirin only slightly reduced the growth rate of females and slightly increased that of males. Both drugs delayed maturation age relative to controls, but metformin had a much greater impact (>140 % of controls) than aspirin (~118 % of controls). Crickets maturing on low aspirin showed no evidence of a trade-off between maturation mass and life extension. Remarkably, by 100 days of age, aspirin-treated females were significantly larger than controls (largely reflecting egg complement). Unlike the reigning dietary restriction paradigm, low aspirin conformed to a paradigm of "eat more, live longer." In contrast, metformin-treated females were only ~67 % of the mass of controls. Our results suggest that hormetic agents like metformin may derive significant trade-offs with life extension, whereas health and longevity benefits may be obtained with less cost by agents like aspirin that regulate geroprotective pathways.

  6. Rapid Aspirin Challenge in Patients with Aspirin Allergy and Acute Coronary Syndromes.

    PubMed

    Cook, Kevin A; White, Andrew A

    2016-02-01

    Aspirin allergy in a patient with acute coronary syndrome represents one of the more urgent challenges an allergist may face. Adverse reactions to aspirin are reported in 1.5% of patients with coronary artery disease. A history of adverse reaction to aspirin often leads to unnecessary withholding of this medication or use of alternative antiplatelet therapy which may be inferior or more costly. Aspirin therapy has been shown to reduce morbidity and mortality in patients with coronary artery disease. Rapid aspirin challenge/desensitization in the aspirin allergic patient has been consistently shown to be both safe and successful in patients with acute coronary syndromes.

  7. Aspirin inhibits the proliferation of human uterine leiomyoma cells by downregulation of K‑Ras‑p110α interaction.

    PubMed

    Gao, Min; Guo, Kai-Min; Wei, Ying-Mei; Ma, Ming-Ming; Cai, Jia-Rong; Xia, Ting-Ting; Ye, Qing-Jian

    2017-10-01

    Aspirin has been confirmed as an effective antitumor drug in various cancers. However, the relationship between aspirin and uterine leiomyoma is still underexplored. Here, we explored the effects of aspirin on human uterine leiomyoma cells and provide insights into the underlying mechanisms. Cell Counting Kit-8 (CCK-8) and flow cytometry analysis showed that aspirin treatment inhibited cell proliferation and promoted cell cycle arrest at G0/G1 phase in a dose- and time‑dependent manner of human uterine leiomyoma cells. Further studies revealed that aspirin blocked the interaction between K-Ras and p110α by co-immunoprecipitation and immunofluorescence. Western blotting demonstrated K‑Ras‑p110α interaction was required for the effects of aspirin‑induced inhibition on cell growth and cell cycle transition via cell cycle regulators, including cyclin D1 and cyclin-dependent kinase 2 (CDK2). PI3K/Akt/caspase signaling pathway was involved in human uterine leiomyoma cell growth under aspirin treatment. Taken together, these results suggest that aspirin inhibited human uterine leiomyoma cell growth by regulating K‑Ras‑p110α interaction. Aspirin which targeting on interaction between K-Ras and p110α may serve as a new therapeutic drug for uterine leiomyoma treatment.

  8. Accelerated Hydrolysis of Aspirin Using Alternating Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Reinscheid, Uwe M.

    2009-08-01

    The major problem of current drug-based therapy is selectivity. As in other areas of science, a combined approach might improve the situation decisively. The idea is to use the pro-drug principle together with an alternating magnetic field as physical stimulus, which can be applied in a spatially and temporarily controlled manner. As a proof of principle, the neutral hydrolysis of aspirin in physiological phosphate buffer of pH 7.5 at 40 °C was chosen. The sensor and actuator system is a commercially available gold nanoparticle (NP) suspension which is approved for animal usage, stable in high concentrations and reproducibly available. Applying the alternating magnetic field of a conventional NMR magnet system accelerated the hydrolysis of aspirin in solution.

  9. Aspirin: The Mechanism of Action Revisited in the Context of Pregnancy Complications

    PubMed Central

    Cadavid, Angela P.

    2017-01-01

    Aspirin is one of the most frequently used and cheapest drugs in medicine. It belongs to the non-steroidal anti-inflammatory drugs with a wide range of pharmacological activities, including analgesic, antipyretic, and antiplatelet properties. Currently, it is accepted to prescribe a low dose of aspirin to pregnant women who are at high risk of preeclampsia (PE) because it reduces the onset of this complication. Another pregnancy alteration in which a low dose of aspirin is recommended is the obstetric antiphospholipid syndrome (APS). The most recognized mechanism of action of aspirin is to inhibit the synthesis of prostaglandins but this by itself does not explain the repertoire of anti-inflammatory effects of aspirin. Later, another mechanism was described: the induction of the production of aspirin-triggered lipoxins (ATLs) from arachidonic acid by acetylation of the enzyme cyclooxygenase-2. The availability of a stable analog of ATL has stimulated investigations on the use of this analog and it has been found that, similar to endogenously produced lipoxins, ATL resolves inflammation and acts as antioxidant and immunomodulator. If we consider that in PE and in the obstetric APS, there is an underlying inflammatory process, aspirin might be used based on the induction of ATL. The objective of this review is to revisit the old and new mechanisms of action of aspirin. In particular, it intends to show other potential uses of this drug to prevent certain pregnancy complications in the light of its ability to induce anti-inflammatory and pro-resolving lipid-derived mediators. PMID:28360907

  10. Pyrazolinone analgesics prevent the antiplatelet effect of aspirin and preserve human platelet thromboxane synthesis.

    PubMed

    Hohlfeld, T; Zimmermann, N; Weber, A-A; Jessen, G; Weber, H; Schrör, K; Höltje, H-D; Ebel, R

    2008-01-01

    Anti-inflammatory analgesics, including ibuprofen and naproxen, are known to interfere with the antiplatelet effect of aspirin, presumably as a result of a drug-drug interaction at the level of platelet cyclooxygenase-1 (COX-1). We studied whether dipyrone, which has recently been reported to inhibit COX isoforms by a mechanism different from conventional non-steroidal anti-inflammatory drugs (NSAIDs), also interferes with the antiplatelet effect of aspirin. Arachidonic acid- and collagen-induced aggregation, as well as thromboxane formation, were measured in human platelet-rich plasma. Platelet P-selectin expression was determined by flow cytometry and cell-free COX enzyme activity was quantified by luminol-enhanced luminescence of human platelet microsomes. In addition, computerized docking was performed based on the crystal structure of COX-1. 4-Methylaminoantipyrine (MAA), the active metabolite of dipyrone, largely attenuated or even completely abolished the inhibition of arachidonic acid-induced platelet aggregation, thromboxane formation and P-selectin expression by aspirin. Similar results were obtained for other pyrazolinones, as well as for the conventional NSAIDs ibuprofen and naproxen. Moreover, MAA attenuated the effect of aspirin on COX activity of platelet microsomes, suggesting a competition with aspirin at the COX-1 enzyme. This was confirmed by docking studies, which revealed that MAA forms a strong hydrogen bond with serine 530 within the COX-1, thereby preventing enzyme acetylation by aspirin. This study demonstrates for the first time that dipyrone and other pyrazolinones have a high potential to attenuate or prevent the antiplatelet effect of aspirin. This should be considered if pyrazolinone analgesics are administered to patients with cardiovascular disease requiring antiplatelet aspirin therapy.

  11. Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique.

    PubMed

    Gohel, Mukesh; Patel, Madhabhai; Amin, Avani; Agrawal, Ruchi; Dave, Rikita; Bariya, Nehal

    2004-04-26

    The purpose of this research was to develop mouth dissolve tablets of nimesulide. Granules containing nimesulide, camphor, crospovidone, and lactose were prepared by wet granulation technique. Camphor was sublimed from the dried granules by exposure to vacuum. The porous granules were then compressed. Alternatively, tablets were first prepared and later exposed to vacuum. The tablets were evaluated for percentage friability, wetting time, and disintegration time. In the investigation, a 32 full factorial design was used to investigate the joint influence of 2 formulation variables: amount of camphor and crospovidone. The results of multiple linear regression analysis revealed that for obtaining a rapidly disintegrating dosage form, tablets should be prepared using an optimum concentration of camphor and a higher percentage of crospovidone. A contour plot is also presented to graphically represent the effect of the independent variables on the disintegration time and percentage friability. A checkpoint batch was also prepared to prove the validity of the evolved mathematical model. Sublimation of camphor from tablets resulted in superior tablets as compared with the tablets prepared from granules that were exposed to vacuum. The systematic formulation approach helped in understanding the effect of formulation processing variables.

  12. Nanosized aspirin-Arg-Gly-Asp-Val: delivery of aspirin to thrombus by the target carrier Arg-Gly-Asp-Val tetrapeptide.

    PubMed

    Jin, Shaoming; Wang, Yaonan; Zhu, Haimei; Wang, Yuji; Zhao, Shurui; Zhao, Ming; Liu, Jiawang; Wu, Jianhui; Gao, Wen; Peng, Shiqi

    2013-09-24

    Resistance and nonresponse to aspirin dramatically decreases its therapeutic efficacy. To overcome this issue, a small-molecule thrombus-targeting drug delivery system, aspirin-Arg-Gly-Asp-Val (A-RGDV), is developed by covalently linking Arg-Gly-Asp-Val tetrapeptide with aspirin. The 2D ROESY NMR and ESI-MS spectra support a molecular model of an A-RGDV tetramer. Transmission electron microscopy images suggest that the tetramer spontaneously assembles to nanoparticles (ranging from 5 to 50 nm in diameter) in water. Scanning electron microscopy images and atomic force microscopy images indicate that the smaller nanoparticles of A-RGDV further assemble to bigger particles that are stable in rat blood. The delivery investigation implies that in rat blood A-RGDV is able to keep its molecular integrity, while in a thrombus it releases aspirin. The in vitro antiplatelet aggregation assay suggests that A-RGDV selectively inhibits arachidonic acid induced platelet aggregation. The mechanisms of action probably include releasing aspirin, modifying cyclic oxidase, and decreasing the expression of GPIIb/IIIa. The in vivo assay demonstrates that the effective antithrombotic dose of A-RGDV is 16700-fold lower than the nonresponsive dose of aspirin.

  13. Eutectic, monotectic and immiscibility systems of nimesulide with water-soluble carriers: phase equilibria, solid-state characterisation and in-vivo/pharmacodynamic evaluation.

    PubMed

    Abdelkader, Hamdy; Abdallah, Ossama Y; Salem, Hesham; Alani, Adam W G; Alany, Raid G

    2014-10-01

    The solid-state interactions of fused mixtures nimesulide (ND) with polyethylene glycol (PEG) 4000, urea or mannitol were studied through constructing thaw-melt phase equilibrium diagrams. The solid-state characteristics were investigated using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Various types of interactions were identified such as the formation of a eutectic system of ND-PEG 4000, monotectic system of ND-urea and complete solid immiscibility of ND with mannitol. The effects of carrier concentrations on the equilibrium solubility and in-vitro dissolution characteristics were studied. Linear increases (R(2)  > 0.99) in the aqueous solubility of ND in various concentrations of PEG 4000 and urea were obtained, whereas mannitol did not exhibit any effect on the solubility of ND. Similar trends were obtained with the dissolution efficiency of the fused mixtures of ND with PEG 4000 and urea compared with the corresponding physical mixtures and untreated drug. The analgesic effects of untreated ND and the selected formulations were investigated by evaluating the drug's ability to inhibit the acetic acid-induced writhing response. The analgesic effect of ND in a eutectic mixture with PEG 4000 and a monotectic mixture with urea was potentiated by 3.2 and 2.7-fold respectively compared with the untreated drug. © 2014 Royal Pharmaceutical Society.

  14. Development and validation of RP-HPLC method for simultaneous estimation of nimesulide, phenylephrine hydrochloride, chlorpheniramine maleate and caffeine anhydrous in pharmaceutical dosage form.

    PubMed

    Kumar, Ashok; Sharma, Rishbha; Nair, Anroop; Saini, Gautam

    2012-01-01

    In this study, a simple, specific and accurate reverse phase high performance liquid chromatographic method was developed for the simultaneous determination of nimesulide (NS), phenylephrine hydrochloride (PE), chlorpheniramine maleate (CPM) and caffeine anhydrous (CF) in pharmaceutical dosage forms. A reversed phase Hypersil phenyl column (4.6 mm x 25 cm) with mobile phase having pH 5.5 consisting of methanol and buffer (55:45, v/v) was used. The flow rate was 1.0 mL per minute and the effluents were monitored at 214 nm. The retention times of all the drugs were found to be 7.47 min (NS), 3.944 min (PE), 4.55 min (CF) and 17.15 min (CPM), respectively. The linearity for all the drugs was obtained in the range of 300-800 microg/mL (NS), 15-32 microg/mL (PE), 16-32 microg/mL (CPM) and 30-180 microg/mL (CF), respectively. The results of analysis have been well validated according to guidelines of International Conference of Harmonisation of technical requirements for registration of pharmaceuticals for human use. The method was found to be simple, precise, economical, less time consuming and reproducible. Hence, the suggested procedure could be used for the determination of all the four drugs in commercial preparations.

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

    PubMed

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

    2017-08-07

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

  16. Decreased sensitivity to tartrazine after aspirin desensitization in an asthmatic patient intolerant to both aspirin and tartrazine.

    PubMed

    Michel, O; Naeije, N; Bracamonte, M; Duchateau, J; Sergysels, R

    1984-05-01

    An aspirin- and tartrazine-sensitive asthmatic patient underwent a desensitization to the adverse effects of aspirin by oral aspirin challenges. After a month of daily aspirin ingestion, the patient's reactivity to tartrazine, tested by oral challenge, was observed to the blunted. This report suggests that desensitization to the adverse effects of aspirin might protect the patient against the adverse effects of tartrazine.

  17. Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats.

    PubMed

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

    2004-09-16

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

  18. Gastric-sparing nitric oxide-releasable 'true' prodrugs of aspirin and naproxen.

    PubMed

    Gund, Machhindra; Gaikwad, Parikshit; Borhade, Namdev; Burhan, Aslam; Desai, Dattatraya C; Sharma, Ankur; Dhiman, Mini; Patil, Mohan; Sheikh, Javed; Thakre, Gajanan; Tipparam, Santhosh G; Sharma, Somesh; Nemmani, Kumar V S; Satyam, Apparao

    2014-12-15

    Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as potentially gastric-sparing NSAIDs. Herein, we report a novel class of '1-(nitrooxy)ethyl ester' group-containing NSAIDS as efficient NO releasing 'true' prodrugs of aspirin and naproxen. While an aspirin prodrug exhibited comparable oral bioavailability and antiplatelet activity (i.e., TXB2 inhibition) to those of aspirin, a naproxen prodrug exhibited better bioavailability than naproxen. These promising NO-NSAIDs protected experimental rats from gastric damage. We therefore believe that these promising NO-NSAIDs could represent a new class of potentially 'Safe NSAIDs' for the treatment of arthritic pain, inflammation and cardiovascular disorders in the case of NO-aspirin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Solid dispersion of pharmaceutical ternary systems I: Phase diagram of aspirin-acetaminophen-urea system.

    PubMed

    el-Banna, H M

    1978-08-01

    The phase diagram of an aspirin-acetaminophen-urea system was constructed. The data obtained by the thermomicroscopic method showed that the binary systems of aspirin-acetaminophen, aspirin-urea, and acetaminophen-urea are simple eutectic mixtures with negligible formation of solid solutions or molecular compounds. The equilateral triangular phase diagram of the ternary system revealed that it forms, upon solidification, solid dispersions of the mechanical mixture type. The ternary eutectic corresponded to a composition of 60% aspirin, 20% acetaminophen, and 20% urea at 72 degrees. The method of calculating the composition finally solidified melts, lying within any area of the phase diagram, is presented. Use of the phase diagram in selecting the optimum ratio of components to enhance dissolution rates of these drugs may be possible.

  20. Inhibition of premature labor in sheep by a combined treatment of nimesulide, a prostaglandin synthase type 2 inhibitor, and atosiban, an oxytocin receptor antagonist.

    PubMed

    Grigsby, P L; Poore, K R; Hirst, J J; Jenkin, G

    2000-09-01

    The aim of this study was to compare the effects of the selective prostaglandin synthase type 2 inhibitor nimesulide, alone or in combination with the oxytocin receptor antagonist atosiban, on the progression of glucocorticoid-induced premature labor in sheep. Effects on circulating maternal and fetal prostaglandin concentrations and on fetal well-being were also examined. Premature labor was induced in ewes with long-term catheterized fetuses by infusion of dexamethasone (1 mg/d) starting at 138 +/- 1 days' gestation. Ewes also received an infusion of either nimesulide and atosiban (20.0 and 4.12 mg/kg per day, respectively; n = 5), nimesulide alone (20.0 mg/kg per day; n = 5), or vehicle only (n = 9). Plasma 13,14-dihydro-15-keto-prostaglandin F(2)(alpha) and prostaglandin E(2) concentrations were measured before and during infusions in plasma samples obtained from the maternal and fetal carotid arteries and the utero-ovarian vein. No fetuses from ewes treated with nimesulide and atosiban were delivered during treatment. These animals were killed electively 98.0 +/- 6.8 hours after the commencement of dexamethasone induction. This was significantly longer than the delivery times for those ewes treated with nimesulide alone (71.2 +/- 3.9 hours; n = 5) and for vehicle-treated ewes (51.4 +/- 1.7 hours; n = 9). Both maternal and fetal plasma 13, 14-dihydro-15-keto-prostaglandin F(2alpha) and prostaglandin E(2) concentrations in nimesulide and atosiban-treated ewes and in nimesulide-treated ewes decreased during treatment. In contrast, vehicle-treated ewes showed a significant increase in maternal and fetal plasma 13,14-dihydro-15-keto-prostaglandin F(2alpha) and prostaglandin E(2) concentrations during dexamethasone induction. Uterine electromyographic activity observed in nimesulide and atosiban-treated ewes was significantly suppressed with respect to activities in both vehicle- and nimesulide-treated ewes during the treatment period. All fetuses were alive at

  1. Differential effect of aspirin on platelet aggregation in IDDM.

    PubMed

    Mori, T A; Vandongen, R; Douglas, A J; McCulloch, R K; Burke, V

    1992-03-01

    Diabetes mellitus is associated with a high incidence of cardiovascular diseases not directly attributable to hyperlipidemia, smoking, or hypertension, but which in part may be explained by an enhanced tendency to thrombosis due to increased platelet activity. The aim of this study was to evaluate platelet function and compare the effectiveness of the antiplatelet drug aspirin on platelet aggregation in diabetic and nondiabetic subjects. Platelet aggregation and composition were examined in 20 male insulin-dependent diabetes mellitus (IDDM) patients and 20 nondiabetic control subjects matched for age and body mass index. All were normotensive with serum total cholesterol less than 6.5 mM. Although within the clinically acceptable normal range, blood pressure was significantly higher in diabetic patients (130/75 mmHg) than in control subjects (123/70 mmHg) (P less than 0.05). Serum thromboxane B2 and ex vivo aggregation of platelets in response to two doses of the agonists collagen and platelet-activating factor (PAF) were similar to nondiabetic subjects. However, after taking 100 mg/day aspirin for 5 days, platelet aggregation to collagen was reduced by 76% in control subjects compared to 56% in IDDM patients (P less than 0.001). Aspirin treatment also reduced the slope of the aggregation curve and increased the lag time (the period between the addition of collagen and the start of irreversible aggregation) significantly more in control than in diabetic platelets. This difference in platelet aggregation could not be attributed to differences in platelet serotonin or thromboxane A2 secretion, the latter being almost completely suppressed by aspirin in each group. Platelet aggregation to PAF was similar in both groups and was not affected by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Simultaneous determination of nimesulide and its four possible metabolites in human plasma by LC-MS/MS and its application in a study of pharmacokinetics.

    PubMed

    Sun, Xiao; Xue, Kai-Lu; Jiao, Xin-Yue; Chen, Qian; Xu, Li; Zheng, Heng; Ding, Yu-Feng

    2016-08-01

    In this study, it was the first time that we simultaneously quantified nimesulide and its possible metabolites M1, M2, M3 and M4 by employing liquid chromatography-tandem mass spectrometry (LC-MS/MS). Nimesulide-d5 was used as internal standard (IS) for validation. Analytes and IS were recovered from human plasma by protein precipitation with acetonitrile. Prepared plasma samples were analyzed under the same LC-MS/MS conditions, and chromatographic separation was realized by using an Ultimate C18 column, with run time being 5min for each sample. Our results showed that various analytes within their concentration ranges could be quantified accurately by using the method. Mean intra- and inter-day accuracies ranged from -4.8% to 4.8% (RE), and intra- and inter-assay precision ≤6.2% (RSD). The following parameters were validated: specificity, recovery, matrix effects, dilution integrity, carry-over, sample stability under a variety of storage and handling conditions (room temperature, freezer, freeze-thaw and post-preparative) and stock solution stability. Pharmacokinetics of nimesulide and its metabolites were calculated based on the analysis of samples collected from twelve Chinese healthy volunteers after single oral dose of 100mg nimesulide tablets. By applying the pharmacokinetic determination into human samples, we preliminarily detected a new metabolite of nimesulide (M4*), and the concentration of M4* was relatively higher in plasma. Furthermore, we predicted part of conceivable metabolism pathway in plasma of after oral administration of 100mg nimesulide tablets. This research provided an experimental basis for further studies on metabolic activation and biotransformation of nimesulide, and for more comprehensive conjecture of its metabolic pathways.

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

    PubMed

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

    2007-04-01

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

  4. Talk with Your Doctor about Taking Aspirin Every Day

    MedlinePlus

    ... En español Talk with Your Doctor about Taking Aspirin Every Day Browse Sections The Basics Overview Benefits ... and Risks What are the benefits of taking aspirin daily? Aspirin can reduce your risk of heart ...

  5. Effects of aspirin & simvastatin and aspirin, simvastatin, & lipoic acid on heme oxygenase-1 in healthy human subjects.

    PubMed

    Bharucha, Adil E; Choi, Kyoung Moo; Saw, Jessica J; Gibbons, Simon J; Farrugia, Gianrico F; Carlson, David A; Zinsmeister, Alan R

    2014-10-01

    Heme oxygenase 1 (HO-1) degrades heme and protects against oxidative stress. In vitro and animal models suggest that HO-1 is beneficial in several diseases (e.g., postoperative ileus, gastroparesis, acute pancreatitis, and colitis). However, the only drugs (i.e., hemin and heme arginate) which pharmacologically upregulate HO-1 in humans are expensive and can only be administered intravenously. Our aims were to compare the effects of placebo, aspirin, and simvastatin alone, and with α-lipoic acid, on HO-1 protein concentration and activity in humans. This randomized, double-blind, placebo-controlled study compared the effects of three oral regimens administered for 7 days, i.e., placebo; aspirin (325 mg twice daily) and simvastatin (40 mg twice daily); aspirin, simvastatin, and the sodium salt of R- α-lipoic acid (NaRLA, 600 mg three times daily) on markers of HO-1 activation (i.e., plasma HO-1 protein concentration and venous monocyte HO-1 protein activity) in 18 healthy subjects (14 females). Markers of HO-1 activation were evaluated at baseline, days 2, and 7. Baseline HO-1 protein concentrations and activity were similar among the three groups. Compared to placebo, aspirin and simvastatin combined, or together with NaRLA did not affect HO-1 protein concentration or activity at 2 or 7 days. HO-1 protein concentrations and activity were correlated on day 7 (r = 0.75, p = 0.0004) but not at baseline and on day 2. At therapeutic doses, aspirin, simvastatin, and α-lipoic acid do not increase plasma HO-1 protein concentration or venous monocyte HO-1 activity in healthy humans. © 2014 John Wiley & Sons Ltd.

  6. EFFECTS OF ASPIRIN& SIMVASTATIN AND ASPIRIN, SIMVASTATIN & LIPOIC ACID ON HEME OXYGENASE-1 IN HEALTHY HUMAN SUBJECTS

    PubMed Central

    Bharucha, Adil E.; Choi, Kyoung Moo; Saw, Jessica; Gibbons, Simon J.; Farrugia, Gianrico; Carlson, David; Zinsmeister, Alan R

    2014-01-01

    SUMMARY Background Heme-oxygenase 1 (HO-1) degrades heme and protects against oxidative stress. In vitro and animal models suggest that HO-1 is beneficial in several diseases (e.g., post-operative ileus, gastroparesis, acute pancreatitis, and colitis). However the only drugs (i.e., hemin and heme arginate) which pharmacologically up-regulate HO-1 in humans are expensive and can only be administered intravenously. Our aims were to compare the effects of placebo, aspirin and simvastatin alone, and with α-lipoic acid, on HO-1 protein concentration and activity in humans. Methods This randomized, double-blind, placebo-controlled study compared the effects of 3 oral regimens administered for 7 days, ie, placebo; aspirin (325 mg twice daily) and simvastatin (40 mg twice daily); aspirin, simvastatin, and the sodium salt of R-α-lipoic acid (NaRLA, 600 mg three times daily) on markers of HO-1 activation (i.e., plasma HO-1 protein concentration and venous monocyte HO-1 protein activity) in 18 healthy subjects (14 females). Markers of HO-1 activation were evaluated at baseline, days 2 and 7. Key Results Baseline HO-1 protein concentrations and activity were similar amongst the three groups. Compared to placebo, aspirin and simvastatin combined, or together with NaRLA did not affect HO-1 protein concentration or activity at 2 or 7 days. HO-1 protein concentrations and activity were correlated on day 7 (r = 0.75, p = 0.0004) but not at baseline and on day 2. Conclusions At therapeutic doses, aspirin, simvastatin, and α-lipoic acid do not increase plasma HO-1 protein concentration or venous monocyte HO-1 activity in healthy humans. PMID:25093998

  7. Efficacy of the selective prostaglandin synthase type 2 inhibitor nimesulide in blocking basal prostaglandin production and delaying glucocorticoid-induced premature labor in sheep.

    PubMed

    Poore, K R; Young, I R; Hirst, J J

    1999-05-01

    The purpose of the study was to determine the effects of selective prostaglandin synthase type 2 inhibitors on basal prostaglandin concentrations in the fetal and maternal circulations and on the labor-associated increase in prostaglandin production in sheep. The effects of maternal nimesulide (0.01, 0.1, and 1 mg/kg) and 6-methoxy-2-naphthylacetic acid (1, 5, and 10 mg/kg) administration were examined (n = 5) at 134 +/- 1 days' gestation. At 138 days' gestation premature labor was induced by fetal dexamethasone infusion (1 mg/d). Ewes were treated with either vehicle or nimesulide infusion (20 mg. d-1. kg-1, n = 5 per group). Nimesulide and 6-methoxy-2-naphthylacetic acid decreased basal prostaglandin production in a concentration-dependent manner. Delivery of nimesulide-treated ewes was delayed by >/=17 hours with respect to that of control ewes (53.9 +/- 2.6 hours). In 2 nimesulide-treated ewes labor did not progress to delivery despite membrane rupture. The increase in prostaglandin concentrations usually seen during dexamethasone-induced labor was abolished in nimesulide-treated ewes and also in their fetuses. Highly selective inhibitors of prostaglandin endoperoxidase H synthase 2 may be required to spare fetal prostaglandin production and limit potential side effects during the suppression of preterm labor.

  8. Aspirin inhibits hepatitis C virus entry by downregulating claudin-1.

    PubMed

    Yin, P; Zhang, L

    2016-01-01

    Aspirin has previously been reported to inhibit hepatitis C virus (HCV) replication. The aim of this study was to investigate whether aspirin is involved in blocking HCV entry. We found that aspirin inhibits the entry of HCVpp and infectious HCV. The level of claudin-1, an HCV receptor, is reduced by aspirin. Our results extend the anti-HCV effect of aspirin to the HCV entry step and further reinforce the anti-HCV role of aspirin.

  9. Aspirin increases mitochondrial fatty acid oxidation.

    PubMed

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

    2017-01-08

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

  10. Comparison of current platelet functional tests for the assessment of aspirin and clopidogrel response. A review of the literature.

    PubMed

    Le Quellec, Sandra; Bordet, Jean-Claude; Negrier, Claude; Dargaud, Yesim

    2016-09-27

    The two most widely used antiplatelet drugs in the world are aspirin and clopidogrel. However, some patients on aspirin and/or clopidogrel therapy do not respond appropriately to either aspirin or clopidogrel. This phenomenon is usually called "aspirin/clopidogrel resistance". Several platelet function tests have been used in various studies for the assessment of aspirin and clopidogrel resistance in healthy individuals and patients admitted in cardiology departments. An accurate assessment of platelet response to aspirin/clopidogrel could benefit patients by proposing tailored-antiplatelet therapy based on test results. However, there is a clear lack of standardisation of such techniques and their analytical variability may induce misinterpretation. After a quick report of the mechanisms responsible for aspirin/clopidogrel resistance, we describe the pre-analytical aspects and the analytical performances of current platelet function tests (Light-transmission aggregometry, whole-blood aggregometry, VerifyNow®, Platelet Function Analyzer®, thromboelastography, VASP assay) that are used for the assessment of aspirin/clopidogrel resistance in clinical studies. Considering the different variables that have to be taken into account with each of the platelet function tests, a particular attention should be paid when interpreting results.

  11. Induction of spermidine/spermine N1-acetyltransferase (SSAT) by aspirin in Caco-2 colon cancer cells.

    PubMed

    Babbar, Naveen; Gerner, Eugene W; Casero, Robert A

    2006-02-15

    Epidemiological, experimental and clinical results suggest that aspirin and other NSAIDs (non-steroidal anti-inflammatory drugs) inhibit the development of colon cancer. It has been shown that the NSAID sulindac induces apoptosis and suppresses carcinogenesis, in part, by a mechanism leading to the transcriptional activation of the gene encoding SSAT (spermidine/spermine N1-acetyltransferase), a rate-limiting enzyme in polyamine catabolism. In the present study, we show that a variety of NSAIDs, including aspirin, sulindac, ibuprofen and indomethacin, can induce SSAT gene expression in Caco-2 cells. Aspirin, at physiological concentrations, can induce SSAT mRNA via transcriptional initiation mechanisms. This induction leads to increased SSAT protein levels and enzyme activity. Promoter deletion analysis of the 5' SSAT promoter-flanking region led to the identification of two NF-kappaB (nuclear factor kappaB) response elements. Electrophoretic mobility-shift assays showed binding of NF-kappaB complexes at these sequences after aspirin treatment. Aspirin treatment led to the activation of NF-kappaB signalling and increased binding at these NF-kappaB sites in the SSAT promoter, hence providing a potential mechanism for the induction of SSAT by aspirin in these cells. Aspirin-induced SSAT ultimately leads to a decrease in cellular polyamine content, which has been associated with decreased carcinogenesis. These results suggest that activation of SSAT by aspirin and different NSAIDs may be a common property of NSAIDs that plays an important role in their chemopreventive actions in colorectal cancer.

  12. A randomized clinical trial comparing long-term clopidogrel vs aspirin monotherapy beyond dual antiplatelet therapy after drug-eluting coronary stent implantation: Design and rationale of the Harmonizing Optimal Strategy for Treatment of coronary artery stenosis-Extended Antiplatelet Monotherapy (HOST-EXAM) trial.

    PubMed

    Lee, Heesun; Koo, Bon-Kwon; Park, Kyung Woo; Shin, Eun-Seok; Lim, Sang Wook; Rha, Seung-Woon; Bae, Jang-Whan; Jeon, Dong Woon; Oh, Seok-Kyu; Hur, Seung-Ho; Kim, Bum-Su; Lee, Jung-Hee; Park, Tae-Ho; Lee, Nam Ho; Kim, Hyo-Soo

    2017-03-01

    Percutaneous coronary intervention (PCI) has been developed by drug-eluting stent (DES), but stent implantation has brought the issue of stent thrombosis and optimal antiplatelet therapy. Guidelines recommend at least 6- to 12 months of dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor such as clopidogrel. Beyond DAPT after PCI with DES, however, there has been still a debate for antiplatelet regimen. Therefore, we report on the upcoming HOST-EXAM trial (NCT02044250), which will evaluate the efficacy and safety of aspirin and clopidogrel monotherapies beyond DAPT after DES implantation. The HOST-EXAM is a prospective, randomized, open-label, multicenter, comparative effectiveness trial, to compare between clopidogrel (75 mg once daily) and aspirin (100 mg once daily) as long-term antiplatelet agents. A total of 5,530 patients with no clinical events during combined antiplatelet therapy for 12±6 months after index PCI will be screened, enrolled, and randomized to either group (1:1 ratio) receiving antiplatelet monotherapy for 2 years. The primary endpoint will be the rate of clinical events defined as a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, or major bleeding at 24 months after randomization. The HOST-EXAM will be the first large-scale randomized controlled study to directly compare the efficacy and safety of long-term antiplatelet monotherapy beyond DAPT after DES implantation. This study will provide clinical evidence to establish optimal regimen for long-term antiplatelet therapy after DES implantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Rationale and design of The Intracoronary Stenting and Antithrombotic Regimen-Testing of a six-week versus a six-month clopidogrel treatment Regimen In Patients with concomitant aspirin and oraL anticoagulant therapy following drug-Eluting stenting (ISAR-TRIPLE) study.

    PubMed

    Fiedler, K Anette; Byrne, Robert A; Schulz, Stefanie; Sibbing, Dirk; Mehilli, Julinda; Ibrahim, Tareq; Maeng, Michael; Laugwitz, Karl-Ludwig; Kastrati, Adnan; Sarafoff, Nikolaus

    2014-04-01

    An increasing number of patients undergoing coronary stenting need lifelong anticoagulation and therefore require a triple therapy typically consisting of aspirin, clopidogrel, and a vitamin K antagonist. Triple therapy confers an elevated bleeding risk as compared with dual therapy; however, omission of either antiplatelet or anticoagulation therapy might increase the risk of stent thrombosis or thrombembolic events. Although guidelines recommend a duration of dual antiplatelet therapy of 6 to 12months after drug-eluting stent (DES) implantation, the optimal duration of dual antiplatelet therapy in patients receiving oral anticoagulation is not known. We postulate that 6-week clopidogrel therapy after DES implantation as compared with 6-month therapy is associated with improved clinical outcomes in patients undergoing DES implantation receiving concomitant aspirin and vitamin K antagonists. The ISAR-TRIPLE is a randomized, open-label trial that examines the restriction of clopidogrel therapy from 6 months to 6 weeks after DES implantation in the setting of concomitant aspirin and oral anticoagulant. Patients are randomized in a 1:1 fashion to either 6-week or 6-month clopidogrel therapy. The primary end point is a composite of death, myocardial infarction, definite stent thrombosis, stroke, or major bleeding. The secondary end point comprises ischemic and bleeding complications. According to sample size calculations, a total of 600 patients are required to be enrolled. Clinical follow-up is scheduled at 6 weeks and at 6 and 9 months after randomization. There is clinical equipoise regarding the optimal duration of triple therapy after DES implantation in patients who need vitamin K antagonist therapy. The ISAR-TRIPLE trial aims to test the hypothesis that a 6-week triple therapy compared with a 6-month triple therapy improves net clinical outcomes. Copyright © 2014 Mosby, Inc. All rights reserved.

  14. Aspirin-loaded electrospun poly(ε-caprolactone) tubular scaffolds: potential small-diameter vascular grafts for thrombosis prevention.

    PubMed

    Del Gaudio, Costantino; Ercolani, Enrico; Galloni, Pierluca; Santilli, Federico; Baiguera, Silvia; Polizzi, Leonardo; Bianco, Alessandra

    2013-02-01

    Thrombosis is the main cause of failure of small-diameter synthetic vascular grafts when used for by-pass procedures. The development of bioresorbable vascular scaffolds with localized and sustained intra-luminal antithrombotic drug release could be considered a desirable improvement towards a valuable solution for this relevant clinical need. For this aim, we present the fabrication and characterization of aspirin-loaded electrospun poly(ε-caprolactone) tubular scaffolds as a vascular drug-delivery graft. Three different drug concentrations were considered (i.e., 1, 5 or 10 % w/w). Although a fibrous structure was clearly observed for all the collected scaffolds, aspirin content was directly implied in the final microstructure leading to a bimodal fiber diameter distribution and fused fibers at crossing-points (5 or 10 % w/w). Mechanical response highlighted a direct relationship for modulus and stress at break with the aspirin content, while the elongation at break was not remarkably different for the investigated cases. The temporal drug release was strongly dependent from the amount of loaded aspirin, reaching a steady state release after about 50 h. Finally, the adhesion assay confirmed the capability of the electrospun scaffolds to reduce platelet adhesion/aggregation onto aspirin loaded polymeric fibers. Aspirin-loaded electrospun tubular scaffold could represent a feasible candidate to develop a novel bioresorbable drug-releasing graft for small-diameter vessel replacements.

  15. Aspirin induces its anti-inflammatory effects through its specific binding to phospholipase A2: crystal structure of the complex formed between phospholipase A2 and aspirin at 1.9 angstroms resolution.

    PubMed

    Singh, Rajendra Kumar; Ethayathulla, A S; Jabeen, Talat; Sharma, Sujata; Kaur, Punit; Singh, Tej P

    2005-02-01

    Phospholipase A2 is potentially an important target for structure-based rational drug design. In order to determine the involvement of phospholipase A2 in the action of non-steroidal anti-inflammatory drugs (NSAIDs), the crystal structure of the complex formed between phospholipase A2 and aspirin has been determined at 1.9 angstroms resolution. The structure contains 915 protein atoms, 1 calcium ion, 13 atoms of aspirin and 105 water molecules. The observed electron density of the aspirin molecule in the structure was of very high quality thus allowing the precise determination of its atomic coordinates leading to the clear description of its interactions with the enzyme. The structure of the complex clearly shows that aspirin is literally embedded in the hydrophobic environment of PLA2. It is so placed in the substrate binding channel that it forms several important attractive interactions with calcium ion, His 48 and Asp 49. Thus, the structure of the complex clearly shows that aspirin occupies a favourable place in the specific binding site of PLA2. The binding studies have shown that acetyl salicylate (aspirin) binds to PLA2 enzyme specifically with a dissociation constant of 6.4 x 10(-6) M. The structural details and binding data suggest that the inhibition of PLA2 by aspirin is of pharmacological

  16. Adsorption of diclofenac and nimesulide on activated carbon: Statistical physics modeling and effect of adsorbate size

    NASA Astrophysics Data System (ADS)

    Sellaoui, Lotfi; Mechi, Nesrine; Lima, Éder Cláudio; Dotto, Guilherme Luiz; Ben Lamine, Abdelmottaleb

    2017-10-01

    Based on statistical physics elements, the equilibrium adsorption of diclofenac (DFC) and nimesulide (NM) on activated carbon was analyzed by a multilayer model with saturation. The paper aimed to describe experimentally and theoretically the adsorption process and study the effect of adsorbate size using the model parameters. From numerical simulation, the number of molecules per site showed that the adsorbate molecules (DFC and NM) were mostly anchored in both sides of the pore walls. The receptor sites density increase suggested that additional sites appeared during the process, to participate in DFC and NM adsorption. The description of the adsorption energy behavior indicated that the process was physisorption. Finally, by a model parameters correlation, the size effect of the adsorbate was deduced indicating that the molecule dimension has a negligible effect on the DFC and NM adsorption.

  17. Effects of Aspirin on Gastroduodenal Permeability in Alcoholics and Controls

    PubMed Central

    Farhadi, Ashkan; Keshavarzian, Ali; Kwasny, Mary J.; Shaikh, Maliha; Fogg, Louis; Lau, Cynthia; Fields, Jeremy Z.; Forsyth, Christopher B.

    2010-01-01

    Alcohol and non-steroidal anti-inflammatory drugs (NSAIDS) are noxious agents that can disrupt the integrity of the gastroduodenal mucosal and damage the epithelial barrier, and lead to increased gastroduodenal permeability. Moreover, it is not uncommon that patients are exposed to these two barrier stressors at the same time. It is thus important to know how simultaneous exposure affects the gastroduodenal barrier, and acquiring that knowledge was the goal of this study. We used a method that has been widely used for the assessment of injury to the gastroduodenal barrier induced by these noxious agents – measurement of gastroduodenal permeability as indicated by urinary excretion of ingested sucrose. We used gas chromatography to measure the amount of sucrose excreted in the urine over the 5–12 h following ingestion of a bolus of sucrose. The 148 participants in the study included 92 alcoholics and 56 healthy controls. All study subjects had a baseline permeability test. To determine whether addition of a second noxious agent, in addition to chronic alcohol, further decreases gastroduodenal barrier integrity, a subset of 118 study subjects participated in another permeability test in which they were exposed to aspirin. For this test, participants ingested 1300 mg aspirin twice, 12 hours and 1 hour before the final permeability test. The baseline permeability test showed that alcoholics have significantly higher gastroduodenal permeability than controls. Aspirin caused a significant within group absolute increase in gastroduodenal permeability in both alcoholics and controls (+7.72%, p=0.003 and +2.25%, p = 0.011, respectively) but the magnitude of these increases were not significantly different from each other. Baseline permeability did vary by gender, self-reported illegal drug use, and employment type. The extent of the permeability increase after aspirin ingestion varied with illegal drug use and recruitment site (a surrogate marker of socioeconomic status

  18. Gastroduodenal mucosal damage with salsalate versus aspirin: results of experimental models and endoscopic studies in humans.

    PubMed

    Scheiman, J M; Elta, G H

    1990-10-01

    Animal models have identified multiple mechanisms of aspirin toxicity. Aspirin inhibits cyclooxygenase in the gastroduodenal mucosa leading to a decrease in endogenous prostaglandins. Prostaglandin mediated mucus and bicarbonate secretion, epithelial hydrophobicity, blood flow, and cellular proliferation are all decreased. Salicylates may cause direct cellular toxicity via inhibition of energy metabolism and membrane transport properties. Salicylate preparations have been designed to decrease gastroduodenal absorption. Endoscopic studies in humans have confirmed that buffering of aspirin does not ameliorate damage, but enteric coating does. Salicylsalicylic acid (salsalate) is an effective antirheumatic drug that bypasses gastric absorption and also avoids cyclooxygenase inhibition. In a randomized, single-blind, endoscopic comparison of salsalate versus enteric-coated aspirin, significantly less gastroduodenal damage was observed in volunteers after salsalate administration compared to enteric-coated aspirin. An endoscopic study in rheumatoid arthritics also confirmed the ability of salsalate to spare gastroduodenal mucosa when compared to naproxen administration. Salsalate may cause less gastroduodenal damage than enteric-coated aspirin based on the results of animal models and endoscopic studies in humans.

  19. Immunological mechanisms in aspirin hypersensitivity. Studies on the immunogenicity of free aspirin.

    PubMed

    Cîrstea, M; Suhaciu, G; Cîrje, M; Ciontescu, L

    1976-10-01

    Anti-aspiryl antibodies were produced in rabbits and guinea pigs by inoculation of aspirin incorporated in complete or incomplete Freund's adjuvant. These antibodies were readily detected by passive haemagglutination using rabbit erythrocytes incubated with aspirin at alkaline pH. Aspiryl conjugates with ovalbumin, human gamma-globulin, bovine gamma-globulin and rabbit serum were also prepared by incubating the proteins with aspirin at alkaline pH. Aspiryl conjugates prepared by this technique behaved, immunologically, identically with the conjugates prepared from aspirin chloride. By contrast, the molar absorbance at 305 nm of the conjugates prepared from aspirin was about 25 times lower than the molar absorbance of the conjugates prepared from aspirin chloride. Since the absorbance of salicylic acid is about eight times greater than that of aspirin, the conclusion is drawn that the aspiryl/salicylyl ratio is significantly higher in the conjugates prepared by incubating proteins with aspirin at alkaline pH than in the conjugates prepared from aspirin chloride. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with aspirin- or salicylic acid-treated red cells. Sera giving positive passive haemagglutination with aspirin-treated erythrocytes did not react with erythrocytes treated with salicylic acid or acetic anhydride.

  20. Locust bean gum as superdisintegrant--formulation and evaluation of nimesulide orodispersible tablets.

    PubMed

    Malik, Karan; Arora, Gurpreet; Singh, Inderbir

    2011-01-01

    Orodispersible tablets disperse instantaneously in the mouth so that they can be swallowed without the aid of water. The aim of the present study was to formulate nimesulide orodispersible tablets using locust bean gum as a natural superdisintegrant. The gum was evaluated for powder flow properties, swelling index and loss on drying. Excellent powder flow properties were observed, swelling index was found to be 20 which indicated appreciable capability of locust bean gum to be used as superdisintegrant. The prepared tablets were evaluated against standard superdisintegrant i.e. cross-carmellose sodium. Disintegration time of tablets containing 10 % locust bean gum was found to be 13 seconds. The prepared batches were also evaluated for wetting time, water absorption ratio, effective pore radius, porosity, in vitro and in vivo disintegration time, in vitro release and stability studies. Wetting time was found to reduce from 19 +/- 2 to 11 +/- 3 sec (A1-A4) and 51 +/- 2 to 36 +/- 3 sec (B1-B4). Effective pore radius and porosity were found to be increase with increase in polymer concentration. The superdisintegrant property of locust bean gum may be due to concentration dependent wicking action leading to formation of porous structure which disintegrates the tablet within seconds. In-vivo results were complementary to in-vitro disintegration time results. The in-vitro release studies were compared against marketed nimesulide fast dissolving tablets (Nimulid MD). Stability studies showed that there was no significant change in hardness, friability, tensile strength and assay of the prepared formulations. The f2 values (in comparison with Nimulid MD) of 92.27 and 98.19 were obtained with A3 and A4 batches respectively.

  1. Nonsteroidal anti-inflammatory drugs modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways

    PubMed Central

    Mozolewski, Paweł; Moskot, Marta; Jakóbkiewicz-Banecka, Joanna; Węgrzyn, Grzegorz; Bocheńska, Katarzyna; Banecki, Bogdan; Gabig-Cimińska, Magdalena

    2017-01-01

    In this report, selected non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin and nimesulide, and analgesics acetaminophen, alone, as well as in combination with isoflavone genistein as potential glycosaminoglycan (GAG) metabolism modulators were considered for the treatment of mucopolysaccharidoses (MPSs) with neurological symptoms due to the effective blood-brain barrier (BBB) penetration properties of these compounds. We found that indomethacin and nimesulide, but not acetaminophen, inhibited GAG synthesis in fibroblasts significantly, while the most pronounced impairment of glycosaminoglycan production was observed after exposure to the mixture of nimesulide and genistein. Phosphorylation of the EGF receptor (EGFR) was inhibited even more effective in the presence of indomethacin and nimesulide than in the presence of genistein. When examined the activity of phosphatidylinositol-3-kinase (PI3K) production, we observed its most significant decrease in the case of fibroblast exposition to nimesulide, and afterwards to indomethacin and genistein mix, rather than indomethacin used alone. Some effects on expression of individual GAG metabolism-related and lysosomal function genes, and significant activity modulation of a number of genes involved in intracellular signal transduction pathways and metabolism of DNA and proteins were detected. This study documents that NSAIDs, and their mixtures with genistein modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways. PMID:28240227

  2. Gastroduodenal tolerance of 75 mg clopidogrel versus 325 mg aspirin in healthy volunteers. A gastroscopic study.

    PubMed

    Fork, F T; Lafolie, P; Tóth, E; Lindgärde, F

    2000-05-01

    Clopidogrel is a new antiplatelet agent that offers increased protection over aspirin in preventing vascular ischaemic events in patients with symptomatic atherosclerosis. In a large, randomized, international study of clopidogrel and aspirin (n = 19,185 patients) clopidogrel was associated with a lower incidence of gastrointestinal adverse events, including gastrointestinal haemorrhage and hospitalizations because of gastrointestinal haemorrhage. The aim of the study was to determine whether macroscopic differences in the gastric mucosa between aspirin- and clopidogrel-treated subjects could be detected by gastroscopy after short-term treatment. Thirty-six healthy volunteers were randomized in a double-blind, double-dummy, parallel design, to 75 mg/day of clopidogrel or 325 mg/day of aspirin for 8 days. Gastroscopy was performed at base line before administration of study drug and directly after treatment completion. Gastroduodenal effects were measured in accordance with a modified Lanza scale. At base line no difference between the groups was detected (median Lanza score, 0.0 in both groups). At the end of treatment the aspirin group showed a median score of 7.5, and the clopidogrel group showed an unchanged median score of 0.0 (P < 0.001). In the aspirin group 13 individuals reported 19 adverse events versus 8 individuals and 13 adverse events for clopidogrel, with approximately half of the adverse events being gastrointestinal in each group. No serious adverse events were reported. In contrast to aspirin, short-term treatment with clopidogrel does not induce macroscopic changes in the gastroduodenal mucosa. The study results show that in patients without gastroduodenal disease clopidogrel, but not aspirin, does not induce any gastroscopically evident erosions during short-term treatment.

  3. Aspirin and proton pump inhibitor combination therapy for prevention of cardiovascular disease and Barrett's esophagus.

    PubMed

    Peura, David A; Wilcox, C Mel

    2014-01-01

    Aspirin, used at low doses (75-325 mg daily), prevents aggregation of platelets and is prescribed for patients as pharmacologic prevention of cardiovascular disease. Despite the well-documented beneficial effects of aspirin, prolonged use is associated with damage to the gastrointestinal (GI) mucosa in the upper and lower GI tract. Patient risk of hemorrhage and peptic ulcer formation is increased with older age, previous ulcer history, Helicobacter pylori infection, and concomitant use of nonsteroidal anti-inflammatory drugs, corticosteroids, or antithrombotic agents. As termination of aspirin therapy can precipitate a cardiovascular event, patients at risk need co-therapy with gastroprotective agents, such as proton pump inhibitors (PPIs), to reduce the GI side effects of aspirin treatment. Fixed-dose combinations of low-dose aspirin and gastroprotective agents have been designed to increase medication compliance, improve clinical outcomes, and reduce the overall cost of therapy. Prolonged use of PPIs may, however, lead to serious adverse effects or, in some cases, reduce the cardioprotective effects of aspirin. Hence, physicians need to carefully consider the benefits and risks associated with the condition of each patient to optimize clinical outcomes of combination therapy. A growing body of clinical evidence indicates that aspirin may decrease the risk of colorectal and other GI cancers, as well as reduce progression from Barrett's esophagus (BE) to esophageal adenocarcinoma. Furthermore, PPIs have recently been shown to reduce neoplastic transformation in patients with BE. Thus, the use of a fixed-dose aspirin/PPI combination could potentially provide chemopreventive benefit to patients with BE, and, at the same time, treat the underlying gastroesophageal reflux responsible for the condition.

  4. Effect of allopurinol, sulphasalazine, and vitamin C on aspirin induced gastroduodenal injury in human volunteers.

    PubMed Central

    McAlindon, M E; Muller, A F; Filipowicz, B; Hawkey, C J

    1996-01-01

    BACKGROUND--The mechanisms of aspirin induced gastroduodenal injury are not fully understood. Aspirin induces the release of reactive oxygen metabolites in animal models, which may contribute to mucosal injury. AIMS--To investigate the effects of aspirin administered with placebo or antioxidants on gastric mucosal reactive oxygen metabolite release and gastroduodenal injury in human volunteers. SUBJECTS--Fourteen healthy volunteers participated in the study (seven male; mean age 27 years, range 20-40). METHODS--In a double blind, randomised, crossover study, volunteers received aspirin 900 mg twice daily and either placebo, allopurinol 100 mg twice daily, sulphasalazine 1 g twice daily or vitamin C 1 g twice daily for three days. Injury was assessed endoscopically and by quantifying mucosal reactive oxygen metabolite release by measuring chemiluminescence before and after each treatment. The effect on prostanoids was determined by measuring ex vivo antral prostaglandin E2 (PGE2) synthesis and serum thromboxane B2 (TXB2). RESULTS--No drug reduced any parameter of gastric injury but vitamin C reduced duodenal injury assessed by Lanza score (p < 0.005). Chemiluminescence increased after aspirin both with placebo (p < 0.05) and vitamin C (p < 0.05). Post-treatment chemiluminescence was lower in subjects taking allopurinol (p < 0.05) or sulphasalazine (p < 0.005) than in those taking placebo with aspirin. CONCLUSIONS--In this study, aspirin induced gastric injury was associated with reactive oxygen metabolite release. This was reduced by sulphasalazine and allopurinol, although macroscopic injury was not affected. Vitamin C, however, was shown to have a previously unrecognised protective effect against aspirin induced duodenal injury. PMID:8707080

  5. Aspirin use and mortality in two contemporary U.S. cohorts.

    PubMed

    Huang, Wen-Yi; Daugherty, Sarah E; Shiels, Meredith S; Purdue, Mark P; Freedman, Neal D; Abnet, Christian C; Hollenbeck, Albert R; Hayes, Richard B; Silverman, Debra T; Berndt, Sonja I

    2017-08-31

    Daily aspirin use has been recommended for secondary prevention of cardiovascular disease, but its use for primary prevention remains controversial. We followed 440,277 men and women from the NIH-AARP Diet and Health Study (ages 50-71) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (ages 55-74) for mortality for 13 years on average. Frequency of aspirin use was ascertained through self-report, and cause of death by death certificates. We calculated multivariate hazard ratios (HRs) and 95% confidence intervals (CI) for mortality using Cox proportional hazards models for each cohort and combined by meta-analysis. We found a consistent U-shaped relationship between aspirin use and mortality in both studies, with differential risk patterns for cardiovascular mortality by disease history. Among individuals with a history of cardiovascular disease, daily aspirin use was associated with reduced cardiovascular mortality [HR=0.78 (95% CI 0.74-0.82)]. However, among those without a previous history, we observed no protection for daily aspirin users [HR=1.06 (1.02-1.11)], and elevated risk of cardiovascular mortality for those taking aspirin twice daily or more [HR=1.29 (1.19-1.39)]. Elevated risk persisted even among participants who lived beyond 5 years of follow-up and used aspirin without other nonsteroidal anti-inflammatory drugs [HR=1.31 (1.17-1.47)]. Results from these two large population-based U.S. cohorts confirm the utility of daily aspirin use for secondary prevention of cardiovascular mortality; however, our data suggest that caution should be exercised in more frequent use, particularly among individuals without a history of cardiovascular disease.

  6. Novel Application of Hydrotropic Solubilizing Additives in the Estimation of Aspirin in Tablets

    PubMed Central

    Maheshwari, R. K.; Saxena, M.; Gahlot, M.; Chaki, R.; Kinariwala, M.; Jagwani, Y.

    2010-01-01

    Highly concentrated aqueous solutions of various hydrotropic agents like sodium benzoate, sodium salicylate, sodium acetate, sodium citrate, nicotinamide and sodium ascorbate have been observed to enhance aqueous solubilities of a large number of poorly water-soluble drugs. In the present investigation hydrotropic solubilization technique has been employed to solubilize poorly water-soluble aspirin (analgesic and antipyretic drug) by 0.5 M ibuprofen sodium solution to carry out titrimetric analysis of aspirin in tablet dosage form. Results of analysis by proposed method and Phamacopoeial method are very comparable. Proposed method is new, rapid, simple, accurate, and reproducible. Statistical data proved the accuracy, reproducibility and the precision of proposed method. PMID:21695002

  7. Aspirin-induced asthma in children.

    PubMed

    Tan, Y; Collins-Williams, C

    1982-01-01

    Aspirin-sensitive asthma is not well documented in children. It may present as a triad of (1) allergic rhinitis, (2) nasal polyps and/or sinusitis and (3) bronchial asthma precipitated by aspirin. Four cases in children are presented. The pathophysiology probably involves the biosynthesis of prostaglandins.

  8. Synthesis of monodisperse nimesulide nanoparticles in microemulsions E170/isopropyl myristate/water/n-butanol (or isopropanol).

    PubMed

    Debuigne, F; Cuisenaire, J; Jeunieau, L; Masereel, B; Nagy, J B

    2000-01-01

    Nanoparticles of nimesulide have been synthesized in two systems of microemulsion: E170/isopropyl myristate/water/n-butanol (or isopropanol). Nanoparticles are monodisperse. In the two microemulsions, the size of the nanoparticles is comprised between 45 and 60 A and also seems to be independent of the factor R ([water]/[E170]) and of the concentration of the nimesulide solubilized in chloroform. The constancy of the size suggests that the size is controlled by thermodynamic stabilization of the nanoparticles with the surfactant. The nature of the cosurfactant does not have an obvious influence on the nanoparticle size. The nanoparticles are instantaneously formed and stay stable during a long period of time (several months).

  9. Impact of concomitant low-dose aspirin on the safety and tolerability of naproxen and esomeprazole magnesium delayed-release tablets in patients requiring chronic nonsteroidal anti-inflammatory drug therapy: an analysis from 5 Phase III studies.

    PubMed

    Angiolillo, Dominick J; Datto, Catherine; Raines, Shane; Yeomans, Neville D

    2014-07-01

    Patients receiving chronic nonsteroidal anti-inflammatory drugs (NSAIDs) and concomitant low-dose aspirin (LDA) are at increased risk of gastrointestinal (GI) toxicity. A fixed-dose combination of enteric-coated (EC) naproxen and immediate-release esomeprazole magnesium (NAP/ESO) has been designed to deliver a proton-pump inhibitor followed by an NSAID in a single tablet. To examine safety data from 5 Phase III studies of NAP/ESO in LDA users (≤ 325 mg daily, administered at any time during the study), and LDA non-users, data were analyzed from 6-month studies assessing NAP/ESO versus EC naproxen in patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis (n = 2), 3-month studies assessing NAP/ESO vs celecoxib or placebo in patients with knee osteoarthritis (n = 2), and a 12-month, open-label, safety study of NAP/ESO (n = 1). In an analysis of two studies, incidences of endoscopically confirmed gastric ulcers (GUs) and duodenal ulcers (DUs) were summarized by LDA subgroups. In the pooled analysis from all five studies, incidences of treatment-emergent adverse events (AEs) (including prespecified NSAID-associated upper GI AEs and cardiovascular AEs), serious AEs, and AE-related discontinuations were stratified by LDA subgroups. Overall, 2,317 patients received treatment; 1,157 patients received NAP/ESO and, of these, 298 received LDA. The cumulative incidence of GUs and DUs in the two studies with 6-month follow-up was lower for NAP/ESO vs EC naproxen in both LDA subgroups [GUs: 3.0 vs 27.9%, respectively, for LDA users, 6.4 vs 22.4%, respectively, for LDA non-users (both P < 0.001); DUs: 1.0 vs 5.8% for LDA users, 0.6 vs 5.3% for LDA non-users]. The incidence of erosive gastritis was lower in NAP/ESO- vs EC naproxen-treated patients for both LDA users [18.2 vs 36.5%, respectively (P = 0.004)] and LDA non-users [19.8 vs 38.5%, respectively (P < 0.001)]. Among LDA users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 16.1%; EC

  10. Comparative evaluation of the pain-relieving properties of a lecithinized formulation of curcumin (Meriva(®)), nimesulide, and acetaminophen.

    PubMed

    Di Pierro, Francesco; Rapacioli, Giuliana; Di Maio, Eleonora Adriana; Appendino, Giovanni; Franceschi, Federico; Togni, Stefano

    2013-01-01

    In addition to its anti-inflammatory activity, Meriva(®), a proprietary lecithin formulation of curcumin, has been anecdotally reported to decrease acute pain in patients with various chronic diseases. Given that curcumin can desensitize transient receptor potential A1, a nociceptor seemingly also mediating the analgesic effect of acetaminophen, as well as inhibiting and downregulating the expression of cyclo-oxygenase 2, the selective target of nimesulide, a nonsteroidal anti-inflammatory agent, we carried out a pilot comparative study of the acute pain-relieving properties of these three agents. At a dose of 2 g (corresponding to 400 mg of curcumin), Meriva showed clear analgesic activity, comparable with that of a standard dose (1 g) of acetaminophen, but lower than that of a therapeutic (100 mg) dose of nimesulide. The analgesic activity of lower (1.5 g) doses of Meriva was less satisfactory, and the onset of activity was longer than that of nimesulide for both doses. On the other hand, gastric tolerability was significantly better than that of nimesulide and comparable with that of acetaminophen. Taken together, our results show that the preclinical analgesic properties of curcumin have clinical relevance, at least at a dose of 2 g as the Meriva formulation. While this dose is significantly higher than that used to relieve chronic inflammatory conditions (1-1.2 g/day), its pain-relieving activity could benefit from the general downregulation of the inflammatory response induced by curcumin, considering that the transient receptor potential channel-mediated mechanisms of analgesia are magnified by attenuation of inflammation. In patients on treatment with Meriva, this would also translate into better control of acute pain, providing a rationale for the analgesic properties associated with this curcumin formulation.

  11. Sustained release of aspirin and vitamin C from titanium nanotubes: An experimental and stimulation study.

    PubMed

    Yang, Weihu; Deng, Conghui; Liu, Peng; Hu, Yan; Luo, Zhong; Cai, Kaiyong

    2016-07-01

    Anodization is a promising method to change the topography and wettability of titanium (Ti) implant. The formed TiO2 nanotubes (TiNTs) arrays could enhance the biological properties of Ti implants. In this study, to investigate the possibility of TiNTs arrays on a Ti implant surface as nano-reservoirs for small molecular drugs when using in orthopedic and dental prosthesis, TiNTs on a Ti implant surface were prepared. Then, aspirin and/or vitamin C were loaded into TiNTs as model drugs. Meanwhile, low molecular weight polylactic acid (PLA, Mw=3000) was synthesized and loaded alternately along with aspirin or vitamin C. The release rates of aspirin and vitamin C with/or without PLA loading were investigated by using a UV-Vis spectrometer. The results showed that when loading without PLA, drugs released quickly with presence of burst release. However, when loading with PLA, the cumulative release duration of aspirin and vitamin C was prolonged to over 240h. Molecular dynamics (MD) simulation and dissipative particle dynamics (DPD) simulation results proved that when loading with PLA, PLA molecules aggregated gradually and formed clusters or micelles in these nanotubes. Meanwhile, drug molecules were captured and distributed inside the PLA matrix, which retarding the release of drugs. Only when PLA micelles degrade gradually in body fluid, drugs could be released slowly from nanotubes. These knowledge laid ground basis for the following biological experiments.

  12. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications.

    PubMed

    Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A; Kashfi, Khosrow

    2015-12-15

    Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass.

  13. Challenge-proven aspirin hypersensitivity in children with chronic spontaneous urticaria.

    PubMed

    Cavkaytar, Ozlem; Arik Yilmaz, Ebru; Buyuktiryaki, Betul; Sekerel, Bulent E; Sackesen, Cansin; Soyer, Ozge U

    2015-02-01

    Nonsteroidal anti-inflammatory drug (NSAID) exacerbated cutaneous disease is defined as the exacerbation of wheals and/or angioedema in patients with a history of chronic spontaneous urticaria (CSU). The objective of this study was to define 'aspirin-hypersensitive' children and adolescents in a clearly defined group of patients with CSU and to describe their clinical features. Eighty-one children with a history of CSU were enrolled over a 3-year period. The daily or almost daily (>4 days a week) presence of urticaria was defined as 'chronic persistent urticaria' (CPU), while the presence of urticaria for 2-4 days a week was defined as 'chronic recurrent urticaria' (CRU). Single-blind, placebo-controlled provocation tests (SBPCPTs) with aspirin were performed for children with CSU. Patients with CRU had a longer duration of cutaneous symptoms [1.6 (0.5-4) vs 0.6 (0.3-1.5) years], and stress was less frequently experienced as an eliciting factor in patients with CRU compared with the patients with CPU (P < 0.016, P = 0.024, respectively). SBPCPTs with aspirin revealed that 14 of 58 patients (24%) with CPU and one of 10 patients with CRU (10%) were aspirin hypersensitive. Aspirin hypersensitivity rate was 26.5% in patients <12 years of age. All of the 15 aspirin-hypersensitive patients (aged between 6.6 and 17.4 years), except for three, experienced an unequivocal angioedema of the lips as a positive reaction in SBPCPT. Nearly a quarter of children and adolescents with CSU were hypersensitive to aspirin. For children with chronic urticaria, determination of NSAID hypersensitivity in a well-controlled clinical setting will help to avoid severe drug hypersensitivity reactions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Evaluation of antioxidant activity and electronic structure of aspirin and paracetamol

    NASA Astrophysics Data System (ADS)

    Motozaki, W.; Nagatani, Y.; Kimura, Y.; Endo, K.; Takemura, T.; Kurmaev, E. Z.; Moewes, A.

    2011-01-01

    We present a study of electronic structure, chemical bonding, and antioxidant activity of phenolic antioxidants (aspirin and paracetamol). X-ray photoelectron and emission spectra of the antioxidants have been simulated by deMon density functional theory (DFT) calculations of the molecules. The chemical bonding of aspirin is characterized by the formation of oxygen 'lone-pair' π-orbitals which can neutralize free radicals and thus be related to antioxidant properties of the drug. In the case of paracetamol the additional nitrogen 'lone pair' is formed which can explain toxicity of the drug. We propose an evaluation method of antioxidant activity based on the relationship between experimental half-wave oxidation potential ( Ep/2 ) and calculated ionization potentials ( IP) by the DFT calculations, and can conclude that paracetamol has the higher antioxidant activity than aspirin.

  15. Biochemical pathogenesis of aspirin exacerbated respiratory disease (AERD).

    PubMed

    Narayanankutty, Arun; Reséndiz-Hernández, Juan Manuel; Falfán-Valencia, Ramcés; Teran, Luis M

    2013-05-01

    Aspirin exacerbated respiratory disease (AERD) is a distinct clinical entity characterized by eosinophilic rhinosinusitis, asthma and often nasal polyposis. Exposure to aspirin or other nonsteroid anti-inflammatory drugs (NSAIDs) exacerbates bronchospasms with asthma and rhinitis. Disease progression suggests a skewing towards TH2 type cellular response along with moderate to severe eosinophil and mast cell infiltration. Alterations in upper and lower airway cellular milieu with abnormalities in eicosanoid metabolism and altered eicosanoid receptor expression are the key features underlying AERD pathogenesis. Dysregulation of arachidonic acid (AA) metabolism, notably reduced prostaglandin E2 (PGE2) synthesis compared to their aspirin tolerant counterpart and relatively increased PGD2 production, a TH2/eosinophil chemoattractant are reported in AERD. Underproduced PGE2 is metabolized by overexpression of 15 prostaglandin dehydrogenase (15-PGDH) to inactive products further reducing PGE2 at real time. This relives the inhibitory effect of PGE2 on 5-lipoxygenase (5-LOX) resulting in overproduction of cysteinyl leukotrienes (CysLTs). Diminished formation of CysLT antagonists called lipoxins (LXs) also augments CysLTs responsiveness. Occasional intake of NSAIDs favors even more 5-LOX product formation, further narrowing the bronchoconstrictive bottle neck, resulting in acute asthmatic exacerbations along with increased mucus production. This review focuses on abnormalities in biochemical and molecular mechanisms in eicosanoid biosynthesis, eicosanoid receptor dysregulation and associated polymorphisms with special reference to arachidonic acid metabolism in AERD.

  16. Acid-NSAID/aspirin interaction in peptic ulcer disease.

    PubMed

    Hunt, Richard H; Yuan, Yuhong

    2011-01-01

    The presence of gastric acid plays a critical role in the mechanisms of NSAIDs/aspirin-associated gastric and duodenal mucosal injury and ulceration. The role of gastric acid and its relationship to NSAIDs/aspirin in mucosal damage, ulcer and ulcer complications continues to be an important concern because of the increasing worldwide use of NSAIDs and aspirin. Acid suppression continues to be an important prevention strategy for NSAID-associated gastric and duodenal ulcer and ulcer complications. While a coxib or an NSAID and PPI in combination are considered to have comparable safety profiles, the evidence from direct comparisons in high-risk patients is limited, and the cardiovascular safety of coxibs and NSAIDs remains a concern especially in patients with a high risk of cardiovascular disease. An evaluation of individual gastrointestinal and cardiovascular risks and benefits, selection of the most appropriate NSAID and dose for each particular patient should always be emphasized. Twice daily PPI is more appropriate to protect a patient who is taking NSAIDs twice daily. PPI co-therapy is still recommended in patients receiving dual antiplatelet treatment, although conflicting results have been reported about adverse drug interactions between PPIs and clopidogrel.

  17. Erythromelalgia: An Uncommon Presentation Precipitated by Aspirin Withdrawal

    PubMed Central

    Khalid, Fatima; Hassan, Syed; Qureshi, Sophia; Qureshi, Waqas; Amer, Syed

    2012-01-01

    Erythromelalgia is a rare disorder frequently associated with myeloproliferative disorders. We describe a case of elderly patient diagnosed with myeloproliferative disorder in remission. The patient was on aspirin for secondary prevention of stroke and was taken off aspirin and developed erythromelalgia within two weeks of withdrawal of aspirin. After restarting aspirin, patient's symptoms improved within 2 weeks. PMID:22844295

  18. Aspirin in patients undergoing noncardiac surgery.

    PubMed

    Devereaux, P J; Mrkobrada, Marko; Sessler, Daniel I; Leslie, Kate; Alonso-Coello, Pablo; Kurz, Andrea; Villar, Juan Carlos; Sigamani, Alben; Biccard, Bruce M; Meyhoff, Christian S; Parlow, Joel L; Guyatt, Gordon; Robinson, Andrea; Garg, Amit X; Rodseth, Reitze N; Botto, Fernando; Lurati Buse, Giovanna; Xavier, Denis; Chan, Matthew T V; Tiboni, Maria; Cook, Deborah; Kumar, Priya A; Forget, Patrice; Malaga, German; Fleischmann, Edith; Amir, Mohammed; Eikelboom, John; Mizera, Richard; Torres, David; Wang, C Y; VanHelder, Tomas; Paniagua, Pilar; Berwanger, Otavio; Srinathan, Sadeesh; Graham, Michelle; Pasin, Laura; Le Manach, Yannick; Gao, Peggy; Pogue, Janice; Whitlock, Richard; Lamy, André; Kearon, Clive; Baigent, Colin; Chow, Clara; Pettit, Shirley; Chrolavicius, Susan; Yusuf, Salim

    2014-04-17

    There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata. Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

  19. 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

  20. Aspirin treatment exacerbates oral infections by Trypanosoma cruzi.

    PubMed

    Cossentini, Luana Aparecida; Da Silva, Rosiane Valeriano; Yamada-Ogatta, Sueli Fumie; Yamauchi, Lucy Megumi; De Almeida Araújo, Eduardo José; Pinge-Filho, Phileno

    2016-05-01

    Oral transmission of the protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas disease, has been documented in Latin American countries. The reported cases of infection were due to the ingestion of contaminated fresh fruit, juices, or sugar cane juice. There have been few studies on the physiopathology of the disease in oral transmission cases. Gastritis is a common ailment that can be caused by poor dietary habits, intake of alcohol or other gastric irritants, bacterial infection, or by the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated in a mouse model whether gastric mucosal injury, induced by aspirin, would affect the course of disease in animals infected with T. cruzi by the oral route. The CL14 and G strains of T. cruzi, both of low infectivity, were used. To this end, groups of BALB/c mice were treated during 5 days with aspirin (100 mg kg(-1)) before oral infection with T. cruzi metacyclic forms (4 × 10(5) or 5 × 10(7) parasites/mouse). Histological analysis and determination of nitric oxide and TNF-α were performed in gastric samples obtained 5 days after infection. Parasitemia was monitored from the thirteenth day after infection. The results indicate that aspirin treatment of mice injured their gastric mucosa and facilitated invasion by both CL14 and G strains of T. cruzi. Strain CL14 caused more severe infection compared to the G strain, as larger numbers of amastigote nests were found in the stomach and parasitemia levels were higher. Our study is novel in that it shows that gastric mucosal damage caused by aspirin, a commonly used NSAID, facilitates T. cruzi infection by the oral route. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Amelioration of aspirin induced oxidative impairment and apoptotic cell death by a novel antioxidant protein molecule isolated from the herb Phyllanthus niruri.

    PubMed

    Bhattacharyya, Sudip; Ghosh, Shatadal; Sil, Parames C

    2014-01-01

    Aspirin has been used for a long time as an analgesic and anti-pyretic drug. Limitations of its use, however, remain for the gastro-intestinal side effects and erosions. Although the role of aspirin on gastro-intestinal injury has been extensively studied, the molecular mechanisms underlying aspirin-induced liver and spleen pathophysiology are poorly defined. The present study has been conducted to investigate whether phyllanthus niruri protein (PNP) possesses any protective role against aspirin mediated liver and spleen tissue toxicity, and if so, what signaling pathways it utilizes to convey its protective action. Aspirin administration in mice enhanced serum marker (ALP) levels, reactive oxygen species (ROS) generation, reduced antioxidant power and altered oxidative stress related biochemical parameters in liver and spleen tissues. Moreover, we observed that aspirin intoxication activated both the extrinsic and intrinsic apoptotic pathways, as well as down regulated NF-κB activation and the phosphorylation of p38 and JNK MAPKs. Histological assessments and TUNEL assay also supported that aspirin induced tissue damages are apoptotic in nature. PNP treatment after aspirin exposure effectively neutralizes all these abnormalities via the activation of survival PI3k/Akt pathways. Combining all results suggest that PNP could be a potential protective agent to protect liver and spleen from the detrimental effects of aspirin.

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

    PubMed

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

    2017-10-01

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

  3. Amelioration of Aspirin Induced Oxidative Impairment and Apoptotic Cell Death by a Novel Antioxidant Protein Molecule Isolated from the Herb Phyllanthus niruri

    PubMed Central

    Bhattacharyya, Sudip; Ghosh, Shatadal; Sil, Parames C.

    2014-01-01

    Aspirin has been used for a long time as an analgesic and anti-pyretic drug. Limitations of its use, however, remain for the gastro-intestinal side effects and erosions. Although the role of aspirin on gastro-intestinal injury has been extensively studied, the molecular mechanisms underlying aspirin-induced liver and spleen pathophysiology are poorly defined. The present study has been conducted to investigate whether phyllanthus niruri protein (PNP) possesses any protective role against aspirin mediated liver and spleen tissue toxicity, and if so, what signaling pathways it utilizes to convey its protective action. Aspirin administration in mice enhanced serum marker (ALP) levels, reactive oxygen species (ROS) generation, reduced antioxidant power and altered oxidative stress related biochemical parameters in liver and spleen tissues. Moreover, we observed that aspirin intoxication activated both the extrinsic and intrinsic apoptotic pathways, as well as down regulated NF-κB activation and the phosphorylation of p38 and JNK MAPKs. Histological assessments and TUNEL assay also supported that aspirin induced tissue damages are apoptotic in nature. PNP treatment after aspirin exposure effectively neutralizes all these abnormalities via the activation of survival PI3k/Akt pathways. Combining all results suggest that PNP could be a potential protective agent to protect liver and spleen from the detrimental effects of aspirin. PMID:24586486

  4. Comparative efficacy of nimesulide and ketoprofen on inflammatory events in third molar surgery: a split-mouth, prospective, randomized, double-blind study.

    PubMed

    Pouchain, E C; Costa, F W G; Bezerra, T P; Soares, E C S

    2015-07-01

    This study aimed to compare the effect of nimesulide and ketoprofen on inflammatory parameters related to the surgical removal of third molars. A split-mouth, prospective, randomized, double-blind study was conducted in patients undergoing removal of four third molars. Eighteen eligible patients were allocated to one of two groups to receive treatment two times a day with either ketoprofen 100 mg or nimesulide 100 mg for a period of 3 days. The rescue medication intake (number) and pain intensity were evaluated at 6, 12, 24, and 48 h, and at 7 days postoperatively. Swelling and maximum mouth opening were evaluated at 24 h, 72 h, and 7 days postoperatively. The peak pain score occurred at 6h after surgery in the nimesulide group and at 12h in the ketoprofen group. There was no statistically significant difference between the groups, although pain relief was observed after 48 h in the nimesulide group and after 7 days in the ketoprofen group. For each group, there was a statically significant difference in pain scores among the studied periods (P<0.0001). None of the patients required rescue medication. There was a statistically significant difference in maximum mouth opening between the preoperative and postoperative periods (P<0.0001). Ketoprofen and nimesulide were effective at controlling pain, swelling, and trismus after the surgical removal of third molars.

  5. Hollow fiber liquid-phase microextraction for the determination of nimesulide in human plasma and its application to a pharmacokinetic study.

    PubMed

    Yang, W W; Zhang, H F; Jia, Y R; Zhao, T; Zhao, Y L; Tong, L J; Sun, L X

    2011-08-01

    A hollow fiber liquid-phase microextraction (HF-LPME) method in combination with HPLC-UV for the determination of nimesulide in human plasma was developed and validated. A small volume of dihexyl ether contained within a polypropylene hollow fiber was used for the extraction of nimesulide from acidified plasma solutions. Factors affecting the extraction efficiency were optimized and discussed. With HPLC-UV as the end analysis technique, the procedure was validated for nimesulide in the concentration range of 50-5000 ng/mL. The intra- and inter-assay precisions were less than 9.1%, and accuracy was within 3.2%. The lower limit of quantification (LLOQ) was 50 ng/mL. Enrichment factor from 144-fold to 156-fold was achieved at three quality control (QC) concentrations. The mean extraction recovery was greater than 41.2%. This method was successfully applied for the evaluation of pharmacokinetics of nimesulide after single oral doses of 100 mg nimesulide to six healthy Chinese volunteers.

  6. Aspirin and clopidogrel resistance using the cone and plate(let) analyser in Indian patients with coronary artery disease.

    PubMed

    Koshy, Sudeep Kurien; Salahuddin, Salman; Karunakaran, Bijoy; Nalakath, Sajid Yoonus; Bhaskaran, Jayesh; Haridas, Padinjare Veloor; Mandalay, Asishkumar; Faizal, Ali

    2014-01-01

    Resistance to antiplatelet drugs is a well-known entity. However, data for aspirin and clopidogrel resistance, and its clinical significance, in Indian patients are meagre. We sought to determine the prevalence of resistance to aspirin and clopidogrel in Indian patients with stable coronary heart disease (CHD), using the cone and plate(let) analyser (CPA) technology. A single centre prospective study in a cohort of patients with stable CHD on chronic aspirin and clopidogrel therapy attending the cardiology outpatient clinic of a tertiary care hospital in Southern India. Platelet function was measured using the Impact-R device (DiaMed, Cressier, Switzerland). Resistance to aspirin and clopidogrel was measured in a cohort of 100 patients with stable documented CHD. Relation of antiplatelet resistance to various clinical comorbidities was also assessed. Of the 100 patients, 85% were men, and 15% were above 65 years of age. 47% patients had diabetes, 29% of patients were hypertensive and 16% were smokers. Using the CPA, 12 patients (12%) were found to be resistant to aspirin and 19 patients (19%) were clopidogrel resistant. In addition, 10 patients (10%) were resistant to both aspirin and clopidogrel. There was no significant correlation between the presence of antiplatelet resistance and several baseline clinical variables, including age, sex, diabetes, hypertension and smoking. Resistance to aspirin and clopidogrel and dual antiplatelet resistance are prevalent in Indian patients, comparable with the prevalence worldwide. The CPA is a feasible assay to determine antiplatelet resistance.

  7. Cost effectiveness of apixaban versus aspirin for stroke prevention in patients with non-valvular atrial fibrillation in Belgium.

    PubMed

    Kongnakorn, Thitima; Lanitis, Tereza; Lieven, Annemans; Annemans, Lievens; Thijs, Vincent; Marbaix, Sophie

    2014-10-01

    Evidence indicates that vitamin K antagonists (VKAs) and oral anticoagulant therapy are under-utilised for stroke prevention in patients with non-valvular atrial fibrillation (AF), and patients who decline or cannot tolerate such treatment are often prescribed aspirin instead. Apixaban has been shown in the AVERROES trial to be superior to aspirin in preventing stroke and systemic embolism without significantly increasing the risk of major bleeding among patients with AF who are unsuitable for VKA therapy. This study estimates the economic implications and potential cost effectiveness of apixaban compared with aspirin in such individuals from the perspective of healthcare payers in Belgium. A Markov model was developed to evaluate the clinical and economic impact of apixaban compared with aspirin in patients unsuitable for VKA therapy. The clinical events modelled include ischaemic and haemorrhagic stroke, systemic embolism, intracranial haemorrhage, other major bleeding, clinically relevant non-major bleeding, myocardial infarction, cardiovascular hospitalisation and treatment discontinuations obtained from AVERROES. Outcomes included life-years and quality-adjusted life-years (QALYs) gained, costs and incremental cost-effectiveness ratios (ICERs) over a lifetime. Apixaban was projected to increase life expectancy and QALYs compared with aspirin, with an associated increase in drug acquisition costs. The estimated ICER was 7,334 per QALY gained with apixaban compared with aspirin. Apixaban is a cost-effective alternative to aspirin for patients with AF in Belgium who decline or cannot tolerate VKA treatment.

  8. (Nitrooxyacyloxy)methyl esters of aspirin as novel nitric oxide releasing aspirins.

    PubMed

    Lazzarato, Loretta; Donnola, Monica; Rolando, Barbara; Chegaev, Konstantin; Marini, Elisabetta; Cena, Clara; Di Stilo, Antonella; Fruttero, Roberta; Biondi, Stefano; Ongini, Ennio; Gasco, Alberto

    2009-08-27

    A series of (nitrooxyacyloxy)methyl esters of aspirin were synthesized and evaluated as new NO-donor aspirins. Different amounts of aspirin were released in serum from these products according to the nature of nitrooxyacyloxy moiety present. In the aromatic series, there is a rather good linear correlation between the amount of aspirin released and the potencies of the products in inhibiting platelet aggregation induced by collagen. Both the native compounds and the related nitrooxy-substituted acid metabolites were able to relax rat aorta strips precontracted with phenylephrine, in keeping with a NO-induced activation of the sGC as a mechanism that underlies the vasodilator effect. The products here described are new improved examples of NO-donor aspirins containing nitrooxy groups. They could represent an alternative to the use of aspirin in a variety of clinical applications.

  9. Decreased cyclooxygenase inhibition by aspirin in polymorphic variants of human prostaglandin H synthase-1

    PubMed Central

    Liu, Wen; Poole, Elizabeth M.; Ulrich, Cornelia M.; Kulmacz, Richard J.

    2012-01-01

    Objectives Aspirin, a major anti-platelet and cancer preventing drug, irreversibly blocks the cyclooxygenase activity of prostaglandin H synthase-1 (PGHS-1). Considerable differences in aspirin effectiveness are observed between individuals, and some of this variability may be due to PGHS-1 protein variants. Our overall aim is to determine which, if any, of the known variants in the mature PGHS-1 protein lead to functional alterations in cyclooxygenase catalysis or inhibition by aspirin. The present study targeted four PGHS-1 variants: R53H, R108Q, L237M and V481I. Methods Wildtype human PGHS-1 and the four polymorphic variants were expressed as histidine-tagged, homodimeric proteins in insect cells using baculovirus vectors, solubilized with detergent, and purified by affinity chromatography. The purified proteins were characterized in vitro to evaluate cyclooxygenase and peroxidase catalytic parameters and the kinetics of cyclooxygenase inhibition by aspirin and NS-398. Results Compared to wildtype, several variants exhibited a higher COX/POX ratio (up to 1.5-fold, for R108Q), an elevated arachidonate Km (up to 1.9-fold, for R108Q), and/or a lower aspirin reactivity (up to 60% less, for R108Q). The decreased aspirin reactivity in R108Q reflected both a 70% increase in the Ki for aspirin and a 30% decrease in the rate constant for acetyl group transfer to the protein. Computational modeling of the brief aspirin pulses experienced by PGHS-1 in circulating platelets during daily aspirin dosing predicted that the 60% lower aspirin reactivity in R108Q gives a 15-fold increase in surviving cyclooxygenase activity; smaller, ~2-fold increases in surviving cyclooxygenase activity were predicted for L237M and V481I. NS-398 competitively inhibited cyclooxygenase catalysis of the wildtype (Ki = 6 μM) and inhibited cyclooxygenase inactivation by 1.0 mM aspirin in both wildtype (IC50 = 0.8 μM) and R108Q (IC50 = 2.1 μM). Conclusions Of the four PGHS-1 variants examined, R108

  10. Chronic aspirin use suppresses CDH1 methylation in human gastric mucosa.

    PubMed

    Tahara, Tomomitsu; Shibata, Tomoyuki; Nakamura, Masakatsu; Yamashita, Hiromi; Yoshioka, Daisuke; Okubo, Masaaki; Maruyama, Naoko; Kamano, Toshiaki; Kamiya, Yoshio; Fujita, Hiroshi; Nagasaka, Mitsuo; Iwata, Masami; Takahama, Kazuya; Watanabe, Makoto; Hirata, Ichiro; Arisawa, Tomiyasu

    2010-01-01

    There have been reports showing a protective role of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) against gastrointestinal cancers. E-cadherin (CDH1) is an adhesion molecule involved in tumour invasion/metastasis. Silencing of CDH1 by promoter CpG island methylation was shown in gastric cancer, precancerous lesion, and Helicobacter pylori-infected chronic gastritis. We investigated the methylation status of CDH1 in noncancerous gastric mucosa in chronic aspirin user, and assessed its effect on methylation-associated carcinogenesis. Gastric mucosa samples from antrum were obtained from 217 cancer-free subjects, including 37 chronic aspirin users and 180 subjects with no history of chronic or occasional intake of aspirin. Methylation-specific polymerase chain reaction (PCR), i.e., MSP, was performed for CDH1 gene promoter. In all 217 subjects, CDH1 methylation was detected for 69 subjects (31.7%). CDH1 methylation more frequently occurred in H. pylori-infection-positive subjects (P < 0.0001), while chronic aspirin users had a significantly lower risk of CDH1 methylation [nonuser versus user 36.1% versus 10.8%; odds ratio (OR) = 0.21, 95% confidence interval (CI) = 0.07-0.63, P = 0.005]. Logistic regression analysis showed that chronic aspirin use was the independent factor for lower risk of CDH1 methylation (adjusted OR = 0.21, 95%CI = 0.07-0.66, P = 0.008). Chronic aspirin use was associated with lower risk of CDH1 methylation in H. pylori-positive subjects (nonuser versus user 49.5% versus 19.0%; OR = 0.24, 95%CI = 0.08-0.76, P = 0.01). Similar trend was also found in H. pylori-negative subjects (P = 0.07). No association was found between CDH1 methylation status, and duration and dose of aspirin. Our data suggest that chronic aspirin use is associated with reduced risk of CDH1 methylation in human gastric mucosa. Aspirin may have suppressive role against methylation-related gastric carcinogenesis.

  11. [Effect of aspirin administration for the treatment of osteoporosis in ovariectomized rat model].

    PubMed

    Chen, Zhi-wen; Wu, Zi-xiang; Sang, Hong-xun; Qin, Guo-liang; Wang, Li-song; Feng, Jing; Wang, Jun; Li, Xiao-juan; Wang, Jian-chao; Zhang, Da

    2011-04-05

    To explore the therapeutic effects of aspirin on postmenopausal osteoporosis and understand its action mechanism. Forty three-month-old female SD rats were randomly divided into 5 groups (n = 8 each): sham group, OVX group and aspirin groups (A1, A2 & A3). The OVX and aspirin groups were ovariectomized (OVX). All rats underwent BMD (bone mineral density) scan at the time of OVX and 3 months after OVX. After the animal model of osteoporosis was established, aspirin groups were intragastrically administered at a dose of 8.93 mg×kg(-1)×d(-1) (A1), 26.79 mg×kg(-1)×d(-1) (A2) and 80.36 mg×kg(-1)×d(-1) (A3) daily in OVX rats. Three months later, the BMD and micro-architecture of vertebrae were measured by dual-energy X-ray absorptiometry and microtomography. Alkaline phosphatase and osteocalcin were measured in peripheral blood. The trabecular architecture changes were observed by histomorphology. Axial compression tests were used to evaluate the mechanical properties of vertebral specimens and three-point bending tests used for femur shaft. Three months after ovariectomy, BMD was significantly lower than preoperative. BMD in aspirin treated groups was significantly higher than that in OVX group. Alkaline phosphatase in peripheral blood decreased significantly in aspirin groups than those in OVX, but osteocalcin had no significant difference between aspirin and OVX groups. The microtomography reconstruction analysis also showed that the trabecular thickness, trabecular number and BMD increased significantly in aspirin groups than those in OVX. And there was no significant difference between A3 and sham groups. The results of biomechanical test showed that the maximum compression load of lumbar spine and three-point bending load of femur shaft were significantly higher in aspirin groups than those in OVX group. Aspirin can promote trabecular bone remodeling, improve three-dimensional structure of trabecular bone and increase bone density of cancellous in

  12. Aspirin for primary prevention in diabetes mellitus: from the calculation of cardiovascular risk and risk/benefit profile to personalised treatment.

    PubMed

    Santilli, Francesca; Pignatelli, Pasquale; Violi, Francesco; Davì, Giovanni

    2015-11-01

    Type 2 diabetes mellitus is characterised by persistent thromboxane (TX)-dependent platelet activation, regardless of disease duration. Low-dose aspirin, that induces a permanent inactivation of platelet cyclooxygenase (COX)-1, thus inhibiting TXA2 biosynthesis, should be theoretically considered the drug of choice. The most up-to-date meta-analysis of aspirin prophylaxis in this setting, which includes three trials conducted in patients with diabetes and six other trials in which such patients represent a subgroup within a broader population, reported that aspirin is associated with a non-significant decrease in the risk of vascular events, although the limited amount of available data precludes a precise estimate of the effect size. An increasing body of evidence supports the concept that less-than-expected response to aspirin may underlie mechanisms related to residual platelet hyper-reactivity despite anti-platelet treatment, at least in a fraction of patients. Among the proposed mechanisms, the variable turnover rate of the drug target (platelet COX-1) appears to represent the most convincing determinant of the inter-individual variability in aspirin response. This review intends to develop the idea that the understanding of the determinants of less-than-adequate response to aspirin in certain individuals, although not changing the paradigm of the indication to low-dose aspirin prescription in primary prevention, may help identifying, in terms of easily detectable clinical or biochemical characteristics, individuals who would attain inadequate protection from aspirin, and for whom different strategies should be challenged.

  13. 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

  14. Etodolac, aspirin, and placebo in patients with degenerative joint disease: a twelve-week study.

    PubMed

    Andelman, S Y

    1983-01-01

    Thirty patients from a private practice were enrolled in an investigation designed to compare the efficacy and safety of a new nonsteroidal anti-inflammatory drug, etodolac, with those of aspirin and placebo in ameliorating pain, inflammation, and functional deficits associated with degenerative joint disease. The 12-week, double-blind, parallel-group study was divided into drug-titration and maintenance periods and was preceded by a washout period of up to two weeks. There were ten patients in each of the three treatment groups. The mean daily maintenance dosages of etodolac and aspirin were 384 mg and 4,322 mg, respectively. Etodolac was significantly (less than or equal to 0.05) more effective than placebo according to 11 of 15 clinical indexes of efficacy: three assessments of the range of motion of the knee joint, and one each of pain while standing, pain while walking, pain while climbing stairs, the average of pains while bearing weight, pain at night, joint tenderness, patient's self-evaluation, and the time required to walk 50 feet. Aspirin was significantly more effective than placebo in only three assessments: two of the range of motion of the knee joint and one of pain while standing. One patient taking etodolac, three patients taking aspirin, and six patients taking placebo withdrew from the trial because of insufficient therapeutic response. There were four withdrawals due to adverse effects, two in the aspirin group and two in the placebo group. Adverse effects (tinnitus and hearing loss) leading to withdrawal of one of the two aspirin patients were probably due to drug administration. No significant side effects were reported by patients in the etodolac group.

  15. How to test the effect of aspirin and clopidogrel in patients on dual antiplatelet therapy?

    PubMed

    Bagoly, Zsuzsa; Homoródi, Nóra; Kovács, Emese Gyöngyvér; Sarkady, Ferenc; Csiba, László; Édes, István; Muszbek, László

    2016-01-01

    Dual antiplatelet therapy with clopidogrel and aspirin is frequently used for the prevention of recurrent ischemic events. Various laboratory methods are used to detect the effect of these drugs administered in monotherapy, however their value in dual therapy has not been explored. Here, we determined which methods used for testing the effect of clopidogrel or aspirin are influenced by the other antiplatelet agent. One arm of the study included 53 ischemic stroke patients being on clopidogrel monotherapy showing effective inhibition of the P2Y12 ADP receptor. Laboratory tests routinely used for the detection of aspirin resistance (arachidonic acid (AA)-induced platelet aggregation/secretion, AA-induced thromboxane B2 (TXB2) production in platelet-rich plasma and VerifyNow Aspirin assay) were carried out on samples obtained from these patients. The other arm of the study involved 52 patients with coronary artery disease being on aspirin monotherapy. Methods used for testing the effect of clopidogrel (ADP-induced platelet aggregation and secretion, flow cytometric analysis of vasodilator-stimulated phosphoprotein (VASP) phosphorylation and a newly developed P2Y12-specific platelet aggregation (ADP[PGE1] test)) were performed on samples obtained from these patients. Clopidogrel monotherapy significantly inhibited AA-induced platelet aggregation and secretion, moreover, AA-induced TXB2 production was also significantly decreased. VASP phosphorylation and AA-induced platelet aggregation showed fair correlation in patients taking clopidogrel only. Clopidogrel did not inhibit the VerifyNow Aspirin test significantly. Aspirin monotherapy influenced ADP-induced platelet aggregation and secretion, but did not have an effect on VASP phosphorylation and on the ADP[PGE1] platelet aggregation test.

  16. Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells.

    PubMed

    He, Yan; Huang, Huarong; Farischon, Chelsea; Li, Dongli; Du, Zhiyun; Zhang, Kun; Zheng, Xi; Goodin, Susan

    2017-02-01

    Epidemiologic studies indicate the use of either statins or aspirin have beneficial effects in prostate cancer patients. The present study was undertaken to evaluate the effects and mechanisms of atorvastatin and aspirin alone or in combination in human prostate cancer cells cultured in vitro and grown as xenograft tumors in severe combined immune-deficient (SCID) mice. The growth and apoptosis in prostate cancer cells were determined by the trypan blue exclusion and propidium iodide staining assays. Activation of the nuclear factor κB (NF-κB) was measured by luciferase reporter assay, and the levels of phospho-signal transducer and activator of transcription (Stat)3 and phospho-extracellular signal-regulated kinase (Erk)1/2 were determined by western blot analysis. Mice were injected subcutaneously with PC-3 cells in Matrigel. After 4-6 weeks, mice with PC-3 tumors received i.p. injections of vehicle, atorvastatin (5 mg/kg), aspirin (80 mg/kg), or atorvastatin (5 mg/kg) + aspirin (80 mg/kg) three times a week for 30 days. Our results demonstrated the combination of atorvastatin and aspirin had more potent effects on growth inhibition and apoptosis stimulation in prostate cancer cells than either drug alone. Mechanistic studies indicated the induction of apoptosis in PC-3 cells was associated with strong inhibition of NF-κB and decreases in the levels of phospho-Stat3 and phospho-Erk1/2. Results of the present study demonstrated a strong combined effect of atorvastatin and aspirin on inhibiting the growth of prostate cancer cells in vitro and in vivo. The findings provide a strong rationale for clinical evaluation of the combination of atorvastatin and aspirin in patients with prostate cancer.

  17. Post-study aspirin intake and factors motivating participation in a colorectal cancer chemoprevention trial.

    PubMed

    Sample, Dory A; Sinicrope, Pamela S; Wargovich, Michael J; Sinicrope, Frank A

    2002-03-01

    We conducted an exploratory, cross-sectional study examining motivators for study participation and post-study aspirin intake in a chemoprevention trial. The parent clinical trial aimed to determine the optimal aspirin dose for colorectal cancer chemoprevention using prostaglandin E(2) as a mucosal biomarker. This trial was randomized and double-blinded in 60 subjects with prior sporadic colorectal adenoma(s) and evaluated three aspirin doses or placebo taken once daily for 4 weeks. A cross-section of 55 evaluable participants who completed the chemoprevention trial were mailed a 16-item, self-administered questionnaire evaluating subject demographics, motivational factors, and health-related behaviors within the framework of Pender's Health Promotion Model (HPM). Forty-three (78%) of 55 participants returned the questionnaire. The most important motivators for study participation were altruistic, i.e., a desire to help future generations at risk of colorectal cancer and personal factors including a desire to reduce one's own risk. Nineteen (44%) of 43 respondents reported that they chose to take daily aspirin post-study without knowledge of study results. At a mean follow-up of 17.3 months, 18 of these 19 subjects continued to take aspirin regularly. Regular use of vitamin supplements pre-study was found to correlate with post-study aspirin use (Mann-Whitney U test, U = 154.0; P = 0.04). We demonstrate, for the first time, that participation in a chemoprevention study can influence the decision to continue the study drug, if available, to reduce perceived cancer risk. Continued post-study aspirin intake indicates an impact of study participation on a health-related behavior and underscores the importance of patient education to guide such decision-making.

  18. The effect of prostaglandin synthase inhibitor, aspirin on the rat intestinal membrane structure and function.

    PubMed

    Kaur, G; Kaur, J; Mittal, N; Nath Sanyal, S

    2010-01-01

    Aspirin at a dose of 50 mg/kg body weight was found to decrease the activity of the rat intestinal brush border membrane (BBM) - associated enzymes such as the sucrase, lactase, maltase and alkaline phosphatase. Aspirin treatment also led to a decrease in the microviscosity in the native as well as the benzyl alcohol treated membrane which might be due to the lipid peroxidative damage in the membrane. Physical correlation of the membrane oxidative damage was evident as the Fourier Transformation Infra Red (FTIR) study of the Aspirin treated membrane, which include an increased proportion of gauche to trans conformer, shift in the methylene C-H asymmetric and symmetric stretching frequencies, C = O double bond stretching, NH bending, antisymmetric (N)-CH3 bending, C-N stretching and antisymmetric CNC stretching while there was no change in the CH2 wagging and twisting as well as in NH-bending amide bond I and II. Aspirin treatment also caused an alteration in the glucose and histidine transport, as evident by a decreased Vmax value while the apparent Km remaining unchanged in the control and Aspirin-treated animals confirming that there was no change in the substrate affinity constant of the membrane transport proteins for the glucose and the basic amino acid, although the rate of transport decreased considerably. There was a decrease noted in the energy of activation of glucose and histidine transport when studied at different temperature but no change in the temperature of phase transition in the BBM with Aspirin treatment, thus implying that perhaps the thermotropic phase transition in the membrane may have relatively little effect on the transport processes. The result suggests an underlying molecular mechanism indicating the implied membrane damage by Aspirin, an important member of the non-steroidal antiinflammatory drug (NSAID) family which could possibly through an oxidative damage may lead to an altered molecular structure, physical state and biological

  19. Lipid Mediators in Aspirin-Exacerbated Respiratory Disease.

    PubMed

    Parker, Andrew R; Ayars, Andrew G; Altman, Matthew C; Henderson, William R

    2016-11-01

    Aspirin-exacerbated respiratory disease (AERD) is a syndrome of severe asthma and rhinosinusitis with nasal polyposis with exacerbations of baseline eosinophil-driven and mast cell-driven inflammation after nonsteroidal antiinflammatory drug ingestion. Although the underlying pathophysiology is poorly understood, dysregulation of the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism is thought to be key. Central features of AERD pathogenesis are overproduction of proinflammatory and bronchoconstrictor cysteinyl leukotrienes and prostaglandin (PG) D2 and inhibition of bronchoprotective and antiinflammatory PGE2. Imbalance in the ratio of these lipid mediators likely leads to the increased eosinophilic and mast cell inflammatory responses in the respiratory tract.

  20. Aspirin resistance: truth or dare.

    PubMed

    Lordkipanidzé, Marie; Pharand, Chantal; Palisaitis, Donald A; Diodati, Jean G

    2006-12-01

    Acetylsalicylic acid, or aspirin (ASA), is widely used in patients with cardiovascular disease to prevent acute ischemic events. However, platelet response to ASA is not equal in all individuals, and a high variability in the prevalence of ASA resistance is reported in the literature (0.4-83%). Actually, ASA resistance is poorly understood; this stems from the fact that its definition is unclear, its presence can be evaluated by a number of assays that are not equivalent, and its prevalence may vary widely based on the population studied. This article (1) exposes the difficulties in defining ASA resistance; (2) discusses the mechanisms by which ASA resistance may occur; (3) presents the characteristics that may put patients at greater risk of exhibiting ASA resistance; and (4) discusses the clinical impact of ASA resistance in patients requiring chronic therapy.

  1. Effects of antiaggregant and antiinflammatory doses of aspirin on coronary hemodynamics and myocardial reactive hyperemia in conscious dogs.

    PubMed

    Andrieu, S; Lebret, M; Maclouf, J; Bévérelli, F; Giudicelli, J F; Berdeaux, A

    1999-02-01

    Clinical studies have shown that low doses of aspirin (<300 mg/day) inhibit thromboxane A2 production and platelet aggregation but preserve prostacyclin synthesis. In contrast, high doses of aspirin (>1,000 mg/day) suppress the synthesis of both eicosanoids. Because the consequences of aspirin administration have never been investigated on coronary vasomotor tone in vivo, we investigated the effects of low and high doses of aspirin on systemic and coronary hemodynamics under basal conditions and after myocardial reactive hyperemia in conscious dogs. Dogs were instrumented with a Doppler flow probe and a hydraulic occluder. Coronary blood flow was measured in the conscious state at baseline and during myocardial reactive hyperemia after 10, 20, and 30 s of coronary occlusion. Thromboxane B2 serum concentrations, an index of platelet aggregation, decreased by >90% after long-term i.v. administration of aspirin, 100 mg/day for 7 days (low dose). Neither systemic and coronary hemodynamics nor reactive hyperemia were affected by the drug. After combined administration of this low dose of aspirin and of the nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine (L-NNA, 30 mg/kg/day/7 days), reactive hyperemia decreased to the same extent as when L-NNA was administered alone. After administration of a unique high-dose aspirin (1,000 mg, i.v.), myocardial reactive hyperemia was markedly reduced, and this effect was still observed after previous blockade of NOS and cyclooxygenase by L-NNA and diclofenac, respectively. Thus long-term treatment with a low antiaggregant dose of aspirin does not alter the ability of coronary vessels to dilate during myocardial reactive hyperemia in conscious dogs. In contrast, short-term administration of a high antiinflammatory dose of aspirin severely blunts myocardial reactive hyperemia through a mechanism that is independent of both cyclooxygenase and nitric oxide metabolic pathways.

  2. Analysis of the mechanism for the development of allergic skin inflammation and the application for its treatment: aspirin modulation of IgE-dependent mast cell activation: role of aspirin-induced exacerbation of immediate allergy.

    PubMed

    Suzuki, Yoshihiro; Ra, Chisei

    2009-07-01

    Aspirin (acetylsalicylic acid) is a well-known nonsteroidal anti-inflammatory drug that can potentiate some acute allergies and causes adverse immunological reactions collectively referred to as aspirin intolerance, a disorder that induces urticaria, asthma, and anaphylaxis in response to oral administration of the drug. Aspirin also potentiates some acute allergies such as food-dependent exercise-induced anaphylaxis (FDEIA), a food allergy induced by physical exercise. The anti-inflammatory actions as well as the adverse immunological effects have been thought to be primarily due to inhibition of cyclooxygenase activity. However, a growing body of evidence suggests that mechanisms unrelated to inhibition of prostaglandin synthesis are involved. One key feature of aspirin intolerance is the overproductions of cysteinyl leukotrienes (LTs), in which mast cells have been implicated to play a role. In this review, we provide an overview of our current knowledge about the regulatory mechanisms of LTC(4) secretion in mast cells and its modulation by aspirin, with a special emphasis on the role of Ca(2+) signals. We also introduced our recent findings that mast cells express dihydropyridine-sensitive L-type Ca(2+) channels (LTCCs) and that Ca(2+) channels of this kind mediate aspirin modulation of LTC(4) secretion in mast cells.

  3. Method Development for Analysis of Aspirin Tablets.

    ERIC Educational Resources Information Center

    Street, Kenneth W., Jr.

    1988-01-01

    Develops a lab experiment for introductory instrumental analysis that requires interference studies and optimizing of conditions. Notes the analysis of the aspirin is by visible spectrophotometric assay. Gives experimental details and discussion. (MVL)

  4. Method Development for Analysis of Aspirin Tablets.

    ERIC Educational Resources Information Center

    Street, Kenneth W., Jr.

    1988-01-01

    Develops a lab experiment for introductory instrumental analysis that requires interference studies and optimizing of conditions. Notes the analysis of the aspirin is by visible spectrophotometric assay. Gives experimental details and discussion. (MVL)

  5. Arachidonic acid metabolism and inhibition of cyclooxygenase in platelets from asthmatic subjects with aspirin intolerance.

    PubMed

    Bonne, C; Moneret-Vautrin, D A; Wayoff, M; Descharmes, A; Gazel, P; Legrand, A; Kalt, C

    1985-02-01

    Exaggerated inhibition of cyclooxygenase has been proposed as a mechanism of drug-induced bronchospasm in aspirin-intolerant patients. This study, using platelets, shows that inhibition of prostaglandin biosynthesis by aspirin is unmodified in patients when compared with healthy subjects. The ratio of cyclooxygenase:lipoxygenase products is similar in platelets from patients and control subjects. We conclude that the cyclooxygenase alteration observed in cells from the respiratory tract is not generalised to other cells such as platelets. We also propose that the major abnormality in NSAID-intolerant patients would affect receptivity to lipoxygenase products more than their biosynthesis.

  6. Intestinal toxicity of non-steroidal anti-inflammatory drugs with differential cyclooxygenase inhibition selectivity.

    PubMed

    Chopra, S; Saini, R Kishore; Sanyal, S Nath

    2007-01-01

    The present study was designed to investigate the gastrointestinal side effects of cycloxygenase (COX) inhibitor with varying selectivity, called the non-steroidal antiinflammatory drugs (NSAIDs) viz., non-selective COX-1 & 2 inhibitor--aspirin, prefentially selective COX-2 inhibitor--nimesulide and highly selective COX-2 inhibitor-celecoxib. Treatment with NSAIDs exhibited a decrease in the activity of rat intestinal brush border membrane associated enzymes such as sucrase, lactase, maltase and alkaline phosphatase as compared to the control in the duodenum, jejunum and ileum. The uptake of D-glucose and L-histidine in the everted intestinal sac was found to be decreased. Also the decease of glucose and histidine uptake was found to be dependent on the substrate concentration, temperature and the time interval of incubation. The physical state and composition of brush border membrane was found to be altered as evident in the FTIR spectrum, by appearance of new peaks while disappearance of certain peaks occurred which were characteristics of the control membrane. The changes in wave number as well as peaks height were also noticed. Alterations in protein profile of the membrane were demonstrated using SDS-PAGE analysis where disappearance of few bands and change in the relative intensities of the bands were noticed and correlated with the alterations that have taken place at the molecular level. Histological studies have depicted a marked decrease in the absorption surface area such as the villi height of the intestinal segment. In addition, crypt number also deceased in the treated animals, an indication that such changes also correlate well with the changes in the transport of the end product nutrients.

  7. [The effect of aspirin, antacids, alcohol, and bile acids on transmural potential difference of the human stomach (author's transl)].

    PubMed

    Caspary, W F

    1975-06-06

    The effect of orally administered buffered and unbuffered aspirin, antacids, alcohol and bile salts on functional changes in the gastric mucosal barrier was assessed by measuring gastric transmural potential differences (PD) in healthy subjects. In contrast to buffered aspirin, unbuffered aspirin caused a marked decrease in transmural PD due to its known effect of enhancing H+ back-diffusion. Simultaneous administration of antacids prevented the aspirin-induced drop of transmural PD. Ethanol (20% w/v), whisky (45% w/v), wine (6-7% ethanol), bile salts and ox-bile reduced transmural PD in healthy subjects. The measurement of transmural PD is a simple and sensitive method for detecting functional changes in the gastric mucosal barrier induced by drugs known to alter mucosal permeability.

  8. Aspirin and clopidogrel: a sweeping combination in cardiology.

    PubMed

    Manolis, Antonis S; Tzeis, Stylianos; Andrikopoulos, George; Koulouris, Spyros; Melita, Helen

    2005-07-01

    Platelets play a pivotal role in the pathogenesis of atherothrombosis, believed to be integrally involved in both the development and progression of atherosclerotic heart disease, as well as in its acute thrombotic complications. Antiplatelet therapy constitutes the cornerstone in the management of patients with acute coronary syndromes and generally high-risk patients with atherothrombosis. Until recently, long-term antiplatelet therapy for the treatment and prevention of the complications of atherothrombotic disease was traditionally limited to aspirin. The availability of the thienopyridines, in particular clopidogrel, represents an important addition to the physician's armamentarium. Clopidogrel is currently one of the most widely prescribed drugs for the treatment of symptomatic coronary artery disease. Aspirin and clopidogrel interfere with platelet activation in complementary, but separate pathways. Aspirin irreversibly inhibits cyclooxygenase, thus preventing the production of thromboxane A(2), which is a prothrombotic and vasoconstrictive substance. Clopidogrel, a newer thienopyridine which has largely supplanted ticlopidine due to a more favorable safety profile, irreversibly prevents platelet activation by blocking one of the three known adenosine 5'-diphosphate (ADP) receptors (the P2Y(12) receptor) on the platelet surface, thus interfering with platelet activation, degranulation and aggregation. Both these antiplatelet agents have a potent protective effect against adverse vascular events, but the combination of these two agents has an even stronger antiplatelet effect translating into superior antithrombotic protection in coronary, cerebral or peripheral arterial disease, without an inordinate increase in bleeding complications. A number of seminal clinical trials have demonstrated and confirmed the incremental benefit and efficacy of the combination of clopidogrel and aspirin therapy above and beyond that of aspirin alone, with multiple other

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

    SciTech Connect

    Zhang, Yang; Tyagi, M.; Mamontov, Eugene; Chen, Sow-hsin H

    2011-01-01

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

  10. 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.

  11. Aspirin-induced small bowel injuries and the preventive effect of rebamipide

    PubMed Central

    Mizukami, Kazuhiro; Murakami, Kazunari; Abe, Takashi; Inoue, Kunimitsu; Uchida, Masahiro; Okimoto, Tadayoshi; Kodama, Masaaki; Fujioka, Toshio

    2011-01-01

    AIM: To evaluate the influence of taking low-dose aspirin for 4 wk on small intestinal complications and to examine the preventive effect of rebamipide. METHODS: This study was conducted as a single-center, randomized, double-blind, cross-over, placebo-controlled study. Eleven healthy male subjects were enrolled. Each subject underwent video capsule endoscopy after 1 and 4 wk of taking aspirin and omeprazole, along with either rebamipide or placebo therapy. The primary endpoint was to evaluate small bowel damage in healthy subjects before and after taking low-dose aspirin for 4 wk. RESULTS: The number of subjects with mucosal breaks (defined as multiple erosions and/or ulcers) were 1 at 1 wk and 1 at 4 wk on the jejunum, and 6 at 1 wk (P = 0.0061) and 7 at 4 wk on the ileum (P = 0.0019). Rebamipide significantly prevented mucosal breaks on the ileum compared with the placebo group (P = 0.0173 at 1 wk and P = 0.0266 at 4 wk). CONCLUSION: Longer-term, low-dose aspirin administration induced damage in the small bowel. Rebamipide prevented this damage, and may be a candidate drug for treating aspirin-induced small bowel complications. PMID:22171147

  12. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin

    PubMed Central

    Xie, Yanming; Wang, Lianxin; Zhang, Yingying; Gu, Hao; Chai, Yan

    2016-01-01

    The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin's related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71) and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed. PMID:27069488

  13. Ibuprofen, aspirin and acetaminophen toxicosis and treatment in dogs and cats.

    PubMed

    Villar, D; Buck, W B; Gonzalez, J M

    1998-06-01

    Toxicosis to 3 commonly available analgesics--ibuprofen, aspirin and acetaminophen--occurs in dogs and cats after acute ingestion or repetitive administration of therapeutic or excessive doses. Whereas in acute exposure, where the clinical course of an overdose to all 3 drugs is predictable in relation to the amount ingested, in chronic exposure to therapeutic doses of aspirin and ibuprofen, the development of gastric ulcers and analgesic nephropathy is unpredictable. Ibuprofen is not recommended for prolonged treatment in dogs and cats due to the likelihood of ulcer formation. Although gastric mucosal adaptation usually occurs with repeated therapeutic doses of aspirin, some individuals nevertheless develop gastric ulcers; simultaneous administration of the prostaglandin analogue misoprostol can reduce the risk. Following acute ingestion of aspirin or ibuprofen, treatment is essentially symptomatic and supportive following early decontamination procedures. Gastrointestinal protectants and i.v. fluids with sodium bicarbonate are generally recommended. Acetaminophen toxicosis is usually associated with single acute ingestion, and the primary target organs affected are the liver and the red blood cells in dogs and cats respectively. Because signs can progress rapidly with acute acetaminophen overdose, administration of N-acetylcysteine is always recommended, even when the history is unclear. This report summarizes the common clinical presentations of dogs and cats exposed to therapeutic or excessive doses of ibuprofen, aspirin or acetaminophen, and describes the treatment procedures advised by the ASPCA-National Animal Poison Control Center.

  14. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin.

    PubMed

    Li, Yuan; Xie, Yanming; Wang, Lianxin; Zhang, Yingying; Gu, Hao; Chai, Yan

    2016-01-01

    The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin's related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71) and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed.

  15. Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness

    PubMed Central

    2013-01-01

    There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). These may represent new pathways for therapy. Aspirin is a non-steroidal anti-inflammatory drug that is an irreversible inhibitor of both cyclooxygenase (COX)-1 and COX-2, It stimulates endogenous production of anti-inflammatory regulatory 'braking signals', including lipoxins, which dampen the inflammatory response and reduce levels of inflammatory biomarkers, including C-reactive protein, tumor necrosis factor-α and interleukin (IL)--6, but not negative immunoregulatory cytokines, such as IL-4 and IL-10. Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia, and epidemiological data suggests that high-dose aspirin is associated with a reduced risk of AD. Aspirin, one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders, and may provide proof-of-principle support for the role of inflammation and O&NS in the pathophysiology of this diverse group of disorders. PMID:23506529

  16. Activation of elements in HERV-W family by caffeine and aspirin.

    PubMed

    Liu, Chunlan; Chen, Yatang; Li, Shan; Yu, Honglian; Zeng, Jie; Wang, Xiuling; Zhu, Fan

    2013-10-01

    Caffeine and aspirin have been suggested to be involved in neurologic diseases, such as schizophrenia, and previous data have revealed that abnormal expression of HERV-W elements may be an important factor in the etiopathogenesis of those diseases. In this article, we reported that caffeine and aspirin contributed to the expression of HERV-W env and gag in Human SH-SY5Y neuroblastoma cells. Semi-quantitative RT-PCR and quantitative Real-time PCR were used to detect the mRNA of HERV-W env and gag in cells exposed to caffeine or aspirin. Western blotting was used to detect the protein of HERV-W env. Luciferase activity assay was employed to detect the activity of HERV-W env promoter. It was found that both caffeine and aspirin could increase the expression of HERV-W env and gag in human SH-SY5Y neuroblastoma cells. Caffeine could activate the HERV-W env promoter, while aspirin could not. With previous studies we can conjecture that HERVs might play a bridging role between environmental factors, such as drugs and neurologic diseases.

  17. Vasorelaxant effects of a nitric oxide-releasing aspirin derivative in normotensive and hypertensive rats

    PubMed Central

    Muscará, Marcelo N; Lovren, Fina; McKnight, Webb; Dicay, Michael; Soldato, Piero del; Triggle, Christopher R; Wallace, John L

    2001-01-01

    Nonsteroidal anti-inflammatory drugs have been reported to exacerbate hypertension and to interfere with the effectiveness of some anti-hypertensive therapies. In this study, we tested the effects of a gastric-sparing, nitric oxide-releasing derivative of aspirin (NCX-4016) on hypertension in rats. Hypertension was induced by administering L-NAME in the drinking water (400 mg l−1). Groups of rats were treated daily with aspirin, NCX-4016 or vehicle. NCX-4016 significantly reduced blood pressure relative to the aspirin-treated group over the 2-week period of treatment. Aspirin and, to a lesser extent, NCX-4016 suppressed whole blood thromboxane synthesis. In anaesthetized rats, acute intravenous administration of NCX-4016 caused a significant fall in mean arterial pressure in hypertensive rats, but was devoid of such effects in normotensive controls. In vitro, NCX-4016 relaxed phenylephrine-pre-contracted aortic rings obtained from both normotensive and hypertensive rats, and significantly reduced their responsiveness to the contractile effects of phenylephrine. These results suggest that NCX-4016 reduces blood pressure in hypertensive rats, not simply through the direct vasodilatory actions of the nitric oxide released by this compound, but also through possible interference with the effects of endogenous pressor agents. These properties, added to its anti-thrombotic effects, suggest that NCX-4016 may be a safer alternative to aspirin for use by hypertensive patients. PMID:11498517

  18. Aspirin, platelets, and cancer: The point of view of the internist.

    PubMed

    Santilli, F; Boccatonda, A; Davì, G

    2016-10-01

    Growing evidence suggests the beneficial effect of aspirin against some types of cancer, particularly of the gastrointestinal tract, and it has been provided for an effect both in cancer prevention as well as in survival improvement of cancer patients. Aspirin benefits increase with duration of treatment, especially after 10years of treatment. The inhibition of platelet activation at sites of gastrointestinal mucosal lesions could be the primary mechanism of action of low-dose aspirin. Indeed, the formation of tumor cell-induced platelet aggregates may favor immune evasion, by releasing angiogenic and growth factors, and also by promoting cancer cell dissemination. Moreover, platelets may contribute to aberrant COX-2 expression in colon carcinoma cells, thereby contributing to downregulation of oncosuppressor genes and upregulation of oncogenes, such as cyclin B1. Platelet adhesion to cancer cells leads also to an increased expression of genes involved in the EMT, such as the EMT-inducing transcription factors ZEB1 and TWIST1 and the mesenchymal marker vimentin. The aspirin-mediated inactivation of platelets may restore antitumor reactivity by blocking the release of paracrine lipid and protein mediators that induce COX-2 expression in adjacent nucleated cells at sites of mucosal injury. Thus, recent findings suggest interesting perspectives on "old" aspirin and NSAID treatment and/or "new" specific drugs to target the "evil" interactions between platelets and cancer for chemoprevention. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  19. Potential therapeutic applications of aspirin and other cyclo-oxygenase inhibitors

    PubMed Central

    Farah, A. E.; Rosenberg, F.

    1980-01-01

    1 The ubiquitous actions of the cyclo-oxygenase inhibitors are described. 2 These include the inhibitory effect on prostaglandin synthesis and the direct effect of aspirin on lymphocytes and their ability to produce lymphokines. 3 Aspirin reduces some types of platelet aggregation possibly involving inhibition of the precursors of thromboxane A2 and prostacyclin. 4 The therapeutic implications in relation to transient ischaemic attacks, coronary artery disease and reno-allograft rejection are discussed. 5 The beneficial and adverse effects on the gastro-intestinal tract are described. 6 The effects of aspirin-like drugs on the genito-urinary tract are described with particular reference to their adverse effects on labour and their therapeutic effect on dysmenorrhoea. PMID:6776977

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

    PubMed

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

    2014-01-30

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

  1. Quantitative Analysis of Clopidogrel Bisulphate and Aspirin by First Derivative Spectrophotometric Method in Tablets

    PubMed Central

    Game, Madhuri D.; Gabhane, K. B.; Sakarkar, D. M.

    2010-01-01

    A simple, accurate and precise spectrophotometric method has been developed for simultaneous estimation of clopidogrel bisulphate and aspirin by employing first order derivative zero crossing method. The first order derivative absorption at 232.5 nm (zero cross point of aspirin) was used for clopidogrel bisulphate and 211.3 nm (zero cross point of clopidogrel bisulphate) for aspirin.Both the drugs obeyed linearity in the concentration range of 5.0 μg/ml to 25.0 μg/ml (correlation coefficient r2<1). No interference was found between both determined constituents and those of matrix. The method was validated statistically and recovery studies were carried out to confirm the accuracy of the method. PMID:21969765

  2. Aspirin-induced asthma: a tribute to John Vane as a source of inspiration.

    PubMed

    Szczeklik, Andrzej

    2010-01-01

    Aspirin-induced asthma is a distinct clinical syndrome consisting of inflammation, characterized by chronic eosinophilic rhinosinusitis with asthma and often nasal polyposis. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) exacerbate asthma, resulting in violent attacks. This is the hallmark of the clinical syndrome as explained by the cyclooxygenase theory. This theory, which is now generally accepted, states that asthma attacks precipitated by aspirin and other NSAIDs have no allergic background; instead, they occur due to the inhibition of cyclooxygenase-1 in sensitive patients. This paper describes how the discoveries of John Vane inspired the authors of the cyclooxygenase theory and led to further insight into the biology of eicosanoid metabolism in this relatively common type of asthma.

  3. Direct Determination of Nimesulide in Natural Waters and Wastewater by Cathodic Stripping Voltammetry.

    PubMed

    Miranda, Luciane; Pereira, Vanessa C; Machado, Christiane S; Torres, Yohandra R; Dos Anjos, Vanessa E; Quináia, Sueli P

    2017-06-29

    Pharmaceuticals are included in a group of compounds considered as contaminants of emerging concern (CECs) in environmental matrices. The quantification of CECs is typically accomplished using chromatographic methods that require several sample pretreatment steps. The current study proposes a voltammetric method to quantify directly nimesulide (NIM) in aqueous samples. The voltammetric parameters were optimized and chosen based on the profile of the voltammograms and peak current intensity. The adequacy of the analytical method was evaluated using validation criteria, such as accuracy, selectivity, linearity, detection, and quantification limits. Linearity was assessed by a standard addition curve at a concentration range of 0.5-130 µg L(-1) of NIM. The limit of quantification was 0.50 µg L(-1), with 60 s of preconcentration time. Accuracy was expressed as recovery percentages of NIM and ranged from 111.4 to 119.8%. The voltammetric method herein proposed has several advantages over others already used to determine NIM, such as fewer sample pretreatment steps, faster, and cheaper analyses. NIM was detected in wastewater samples at concentration levels ranging from 101.7 to 385.0 µg L(-1). This result is the first evidence about NIM occurrences in environmental matrices in the area surrounding the Itaipu Lake reservoir in Brazil.

  4. The genotoxic and cytotoxic effects of nimesulide in the mouse bone marrow.

    PubMed

    Tripathi, Rina; Tripathi, Pankaj; Pancholi, Shyam S; Patel, Chhagan N

    2014-07-01

    Genotoxicity of nimesulide (NM) was evaluated by employing bone marrow (BM) chromosomal aberration (CA) and micronucleus assays in Swiss albino mice. For BM CA assay, mice of either sex were treated orally with 1.5, 2.5 and 5 mg body weight solution of NM in 0.2 mL of 0.05% CMC (carboxy methyl cellulose) daily for 4, 13, 28 and 40 weeks. Treatment induced dose-dependent and significantly depressed mitotic activity and increase in CAs per cell in the BM cells after 13 weeks of treatment at all dose levels. In micronucleus assay, male mice were treated orally with the same dose levels and sampling durations as for CA assay. Treatment increased the percentage of micronucleated polychromatic erythrocytes frequency and showed a statistically significant reduction in polychromatic erythrocyte/normochromatic erythrocyte ratio, as compared to control groups. Cyclophosphamide (40 mg/kg) was used as clastogen (positive control) and yielded the expected positive results. Cytotoxicity was observed in the 8-week recovery period after 40 weeks of dosing, but it was not significant. On the basis of these findings, it may be concluded that in the long term, NM, or its biotransformed product, is genotoxic and cytotoxic for BM cells of mice in vivo.

  5. Lallemantia reylenne seeds as superdisintegrant: Formulation and evaluation of nimesulide orodispersible tablets

    PubMed Central

    Malik, Karan; Arora, Gurpreet; Singh, Inderbir; Arora, Sandeep

    2011-01-01

    Aim: Orodispersible tablets also known as fast dissolving tablets disintegrate instantaneously within the mouth and thus can be consumed without water. The present study was aimed to formulate orodispersible tablets of nimesulide by using Lallemantia reylenne seeds as natural superdisintegrant. Materials and Methods: Powdered lallemantia seeds were characterized for powder flow properties (bulk density, tapped density, carr's consolidation index, hausner ratio, angle of repose), swelling index, viscosity, pH, and loss on drying. The prepared tablets were evaluated for different tablet parametric tests, wetting time, water absorption ratio, effective pore radius, porosity, packing fraction, in vitro and in vivo disintegration time, in vitro dissolution and stability studies. Results and Discussion: Increase in Lallementia reylenne concentration had an appreciable effect on tablet hardness and friability which clearly indicated binding potential of the seeds. Water absorption ratio increased with increase in Lallemantia reylenne concentration from batch A1 to A4. Water uptake coupled natural polymer swelling could be the most probable mechanism for concentration dependent reduction in disintegration time by the Lallemantia reylenne seeds. Porosity of the formulated tablets was found to increase from batch A1-A4. The in vitro disintegration results were in line with in vivo disintegration results. Conclusion: It could be concluded that Lallemantia reylenne seeds could be used as natural superdisintegrant in the formulation of orodispersible tablets. PMID:23071942

  6. Mucosal adaptation to aspirin induced gastric damage in humans. Studies on blood flow, gastric mucosal growth, and neutrophil activation.

    PubMed Central

    Konturek, J W; Dembinski, A; Stoll, R; Domschke, W; Konturek, S J

    1994-01-01

    The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess the extent of mucosal damage by aspirin and subsequent adaptation the effects of 14 days of continuous, oral administration of aspirin (2 g per day) to eight healthy male volunteers was studied. To estimate the rate of mucosal damage, gastroscopy was performed before (day 0) and at days 3, 7, 14 of aspirin treatment. Gastric microbleeding and gastric mucosal blood flow were measured using laser Doppler flowmeter and mucosal biopsy specimens were taken for the estimation of tissue DNA synthesis and RNA and DNA concentration. In addition, the activation of neutrophils in peripheral blood was assessed by measuring their ability to associate with platelets. Aspirin induced acute damage mainly in gastric corpus, reaching at day 3 about 3.5 on the endoscopic Lanza score but lessened to about 1.5 at day 14 pointing to the occurrence of gastric adaptation. Mucosal blood flow increased at day 3 by about 50% in the gastric corpus and by 88% in the antrum. The in vitro DNA synthesis and RNA concentration, an index of mucosal growth, were reduced at day 3 but then increased to reach about 150% of initial value at the end of aspirin treatment. It is concluded that the treatment with aspirin in humans induces gastric adaptation to this agent, which entails the increase in mucosal blood flow, the rise in neutrophil activation, and the enhancement in mucosal growth. PMID:7959223

  7. NSAID and aspirin use by the elderly in general practice: effect on gastrointestinal symptoms and therapies.

    PubMed

    Pilotto, Alberto; Franceschi, Marilisa; Leandro, Gioacchino; Di Mario, Francesco

    2003-01-01

    The relationship between NSAID use and gastrointestinal (GI) symptoms and their treatment in elderly patients is not well defined. To identify the prevalence of specific drug use in elderly outpatients and to identify the relationship between NSAID use and GI disturbances and treatments in elderly subjects treated by their general practitioner (GP). The study was carried out by 63 GPs in north-eastern Italy; 3154 elderly subjects were included in the study over a 2-week period. By using a structured interview, subjects' medical histories and current medication were identified. In particular, the presence and use pattern (i.e. occasional, 'acute' or 'chronic') of NSAIDs and/or aspirin (acetylsalicylic acid) were recorded. In all subjects, the presence of upper GI symptoms, i.e. abdominal pain, reflux symptoms and indigestion syndrome, were noted. The prevalence of drug use was 96.4% (males 96%, females 96.7%). The most prescribed drugs were ACE inhibitors (38%), diuretics (26.7%), NSAIDs and regular-dose aspirin (24.7%), GI drugs (20.6%), and anxiolytics/hypnotics (20.3%). Of 779 subjects who had taken NSAIDs or regular-dose aspirin, 32.9% were 'chronic' users, 24.9% were 'acute' users and 42.1% occasional users. A significantly higher prevalence of upper GI symptoms was observed in elderly NSAID and low-dose aspirin users compared with non-users (24.9% vs 28% vs 16.6% respectively, p < 0.0001). GI symptoms were reported by 27.6% of 'chronic' NSAID users, 22.9% of 'acute' users and 24.7% of occasional users. A significantly higher prescription rate for any GI drug was found in NSAID users than in low-dose aspirin users and non-users (24.0% vs 19.6% vs 19.4% respectively, p = 0.007). This difference was mainly because of a higher number of upper GI drugs taken by NSAID users than by low-dose aspirin users and non-users (18.1% vs 16% vs 13.7% respectively, p = 0.004). Multivariate analysis demonstrated that female gender (odds ratio [OR] = 1.32, 95% CI = 1

  8. [Progress of research on aspirin resistance and its related course of integrative medical research].

    PubMed

    Lu, Xiao-Yan; Xu, Hao; Chen, Ke-Ji

    2010-06-01

    Aspirin is the most classic anti-platelet drug, plays its important role in preventing and treating cardio- and cerebro-vascular diseases for its excellent potency ratio; however, there exists individual difference in its anti-platelet effect, aspirin resistance (AR) presented in about 25%-40% of patients, which seriously influences the intervention effect of aspirin. So AR has become a clinical problem that attached more attention. In this paper, the authors put forward a new thinking for clinical studying and inventing new effective Chinese drugs on AR by means of screen out AR suffered from cardio/cerebro-vascular patients long-term received aspirin; find their gene difference sites from MtSNP to establish a foundation for AR predication and reasonable strategy formation; meantime, through platelet intervention in vitro adopting uniform design optimization method to explore the best compatibility and matching relationship of anti-platelet Chinese medicine for AR prevention and treatment, so as to fully display the multi-target intervening effects of Chinese drug-therapy.

  9. Modified tamarind kernel polysaccharide: a novel matrix for control release of aspirin.

    PubMed

    Ghosh, Sandipta; Pal, Sagar

    2013-07-01

    pH dependent hydrogels of modified tamarind kernel polysaccharide (TKP) were synthesized by grafting with polyacrylamide chains on TKP backbone in presence of microwave irradiation and initiator. The present study is carried out to design oral controlled drug delivery systems for aspirin using synthesized hydrogels as carrier in form of tablets. TKP-g-PAM based hydrogels show significant enhancement for control release of aspirin. Release behavior of aspirin has been evaluated using USP type I apparatus in 900 mL of buffer solutions (pH 1.2, 6.8, 7.4), maintained at 37°C at 100 rpm. It is observed that with increase in percentage of grafting (% G), swelling of matrices increases whereas erosion and rate of drug release decrease. The effect of % G onto t50 value (time taken for release of 50% drug) has also been discussed. The release characteristics from the matrices under study show non-Fickian diffusion mechanism, suggesting the controlled release of aspirin.

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

    PubMed

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

    2017-01-01

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

  11. 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

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

    PubMed

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

    2016-04-01

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

  13. Are the current recommendations for the use of aspirin in primary prevention of cardiovascular disease applicable in low-income countries?

    PubMed Central

    Noubiap, Jean Jacques N; Nansseu, Jobert Richie N

    2015-01-01

    Although evidence has accumulated that long-term aspirin therapy is beneficial in secondary prevention of cardiovascular disease (CVD), a lot of controversies persist regarding the benefit of aspirin use in primary prevention of CVD. In low-income countries (LIC) specifically, the decision to prescribe aspirin for primary CVD prevention is more problematic, as there is a dearth of evidence in this regard. Aspirin has been shown to have relative beneficial effects in preventing a first myocardial infarction, but not stroke. However, as stroke is the prevailing CVD in many LIC, especially in Africa, the benefit of aspirin in these settings is therefore questionable. Indeed, there is no published trial that has evaluated the benefits and risks of continuous aspirin therapy in populations of LIC. Furthermore, though cardiovascular risk assessment is crucial in decision-making for the use of aspirin in primary prevention of CVD, there are no risk assessment tools that have been validated in African populations. Studies are urgently warranted, to determine the usefulness of aspirin in primary prevention of CVD in low-income settings where the drug is highly available and affordable, as CVD is becoming the leading cause of deaths in LIC. PMID:26345154

  14. Comparison of the pharmacokinetic profiles of soluble aspirin and solid paracetamol tablets in fed and fasted volunteers.

    PubMed

    Stillings, M; Havlik, I; Chetty, M; Clinton, C; Schall, R; Moodley, I; Muir, N; Little, S

    2000-01-01

    The aim of this study was to investigate the absorption of popular preparations of two common analgesics--soluble aspirin and solid paracetamol tablets. An open, randomised, crossover study design was used to compare the pharmacokinetic parameters of soluble aspirin and solid paracetamol tablets in 16 healthy, male volunteers from the University of the Witwatersrand, South Africa, in both fed and fasted states. Plasma concentrations of paracetamol, aspirin and salicylic acid were measured. It was found that the rate of absorption was significantly faster for soluble aspirin than for solid paracetamol, regardless of fed or fasting state, considering time to maximum concentration (p < 0.01), time to first quantifiable concentrations (p < 0.05) and absorption rate (p < 0.01). Absorption rate was significantly affected by food for both soluble aspirin (p = 0.028) and for solid paracetamol (p = 0.0003). Time to maximum concentration was not significantly affected by food for soluble aspirin (p = 0.17) but significantly lengthened for solid paracetamol (p = 0.0003). The extent of absorption was affected by food in terms of maximum concentration for both drugs (p = 0.0001), with a reduction of 49% in the fed state for solid paracetamol compared to 18% for soluble aspirin, the difference between the drugs being statistically significant (p = 0.0024). The overall bioavailability of soluble aspirin was unaffected by food and the bioavailability of salicylic acid was increased in the fed state, whereas that of solid paracetamol was lowered in the fed state. Greater inter-individual variation was seen in paracetamol concentrations compared with aspirin or salicylic acid levels. In conclusion, these results show that the absorption of soluble aspirin is largely unaffected by food, whereas, in the same volunteers, the absorption of solid paracetamol tablets is greatly affected. In some volunteers, maximum plasma concentrations of paracetamol following food did not reach levels

  15. A comparison of the anti-inflammatory and anti-nociceptive activity of nitroaspirin and aspirin

    PubMed Central

    al-Swayeh, O A; Clifford, R H; del Soldato, P; Moore, P K

    2000-01-01

    Nitroaspirin (2.5–50 mg kg−1, i.p. or 2.5–100 mg kg−1, p.o.) and aspirin (2.5–100 mg kg−1, i.p. or p.o.) exhibit anti-inflammatory activity in the carrageenan-induced hindpaw oedema model in the rat. When administered i.p., nitroaspirin was a more effective anti-oedema agent than aspirin particularly in the ‘early' phase (i.e. up to 60 min) of the response. The ED50 values for nitroaspirin and aspirin as inhibitors of the ‘late' phase response (measured at 180 min) were 64.3 μmol kg−1 and >555 μmol kg−1, respectively. When administered p.o., neither nitroaspirin nor aspirin exhibited significant anti-inflammatory activity in the ‘early' phase and were of similar potency in the ‘late' phase. Thus, at the highest dose used (100 mg kg−1, 360 min) orally administered nitroaspirin (aspirin in parenthesis) inhibited oedema formation by 46.9±1.6% (47.2±3.8%, both n=6, P<0.05). Nitroaspirin and aspirin (25–200 mg kg−1, p.o.) caused dose-related inhibition of the hyperalgesia to mechanical stimulation following intraplantar injection of carrageenan in the rat. ED50 values were 365 μmol kg−1 and 784 μmol kg−1, respectively. Neither drug influenced the threshold for mechanical stimulation in the contralateral (i.e. untreated) hindpaw. Nitroaspirin and aspirin (2.5–100 mg kg−1, p.o.) caused dose-related inhibition of acetic acid induced abdominal constrictions in the mouse (ED50 values of 154.7 μmol kg−1 and 242.8 μmol kg−1, respectively). Nitroaspirin and aspirin (>200 mg kg−1, p.o.) reduced the ‘late' phase (but not the ‘early' phase) of the formalin-induced hindpaw licking assay in the mouse. Similarly, nitroaspirin and aspirin (>50 mg kg−1, p.o.) prolonged tail withdrawal latency following application of a noxious heat stimulus in the mouse. PMID:10694241

  16. Magnitude and time course of platelet inhibition with extended release dipyridamole with or without aspirin in healthy Japanese volunteers. The AGgrenox versus Aspirin Therapy Evaluation (AGATE-Japan).

    PubMed

    Serebruany, Victor L; Malinin, Alex I; Hanley, Dan F

    2008-01-01

    Randomized trials showed greater stroke prevention with extended release dipyridamole in combination with low dose aspirin than with either aspirin or dipyridamole alone. However, most studies with this formulation (Aggrenox) were carried out in Europe and North America. Considering potential inter-racial differences in drug response, we conducted a small randomized study in healthy Japanese volunteers to compare antiplatelet regimens with regard to the changes in the platelet biomarkers. Thirty healthy volunteers (18-40 years old, 15 male and 15 female) of Japanese descent were randomized to Aggrenox (n = 17) or aspirin 81 mg (n = 13 volunteers) for 30 days. Platelet function was assessed at baseline, and on days 15, and 30 by conventional aggregometry, whole blood flow cytometry, and cartridge-based analyzer. Both Aggrenox and aspirin provided sustained platelet inhibition at Day 15 and Day 30. Therapy with Aggrenox, however, was associated with more prominent and significant inhibition of collagen-induced aggregation (p = 0.08, Day 15), as well as prolongation of the closure time (p = 0.001, Day 30); diminished expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) (p = 0.02, Day 30), glycoprotein IIb (GPIIb) antigen (p = 0.001 and 0.024 for Day 15 and Day 30), and GPIIb/IIIa activity by PAC-1 antibody (p = 0.014 and 0.03), CD62 (P-selectin) (p = 0.03 for Day 15 and Day 30), as well as inhibition of protease activated receptors (PAR-1) associated with intact WEDE-15 (p = 0.002 and 0.003) and SPAN-12 (p = 0.002 and 0.04) thrombin receptors when compared with aspirin. The magnitude and durability of platelet response after Aggrenox in healthy Japanese is similar to those effects observed in Caucasians and African-Americans. A larger study to assess drug efficacy and safety in the Japanese post-stroke patients is warranted.

  17. 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.

  18. Does high serum uric acid level cause aspirin resistance?

    PubMed

    Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun

    2016-06-01

    In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage.

  19. [The saga of aspirin: centuries-old ancestors of an old lady who doesn't deserve to die].

    PubMed

    Queneau, P

    2001-01-01

    Where do analgics come from? If their ancestors are many centuries old, we observe that the four main drugs of modern analgesia, morphine (1816), codeine (1832), paracetamol (1893) and aspirin (1897) were discovered during the 19th century. And through what 'sagas'! The first known prescriptions, written on earthenware shelves in Mesopotamia 3 centuries BC, already mentioned medications derived from willow to cure headaches. The Greeks dedicated to Asclepios, god of therapeutics, a statue carved in a willow trunk as a symbol! Thus, before becoming a drug, aspirin was born from the willow, which grows with its feet in water 'without suffering', as the ancestors put it. But before it walked on the moon with Neil Armstrong in 1969, the discovery of aspirin as a drug was the consequence of the filial love of a young researcher, Felix Hoffmann, who wanted to decrease the resistant pain of his rheumatic old father.

  20. 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.

  1. Daily Aspirin May Help Prevent Some Recurrent Miscarriages

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_163515.html Daily Aspirin May Help Prevent Some Recurrent Miscarriages Approach seemed ... as simple as taking a daily low-dose aspirin could help prevent a recurrence. The intervention appears ...

  2. Aspirin to Prevent a First Heart Attack or Stroke

    MedlinePlus

    ... Share this page from the NHLBI on Twitter. Aspirin to Prevent a First Heart Attack or Stroke ... immediate medical attention. What if I’m taking aspirin to prevent another heart attack or stroke? The ...

  3. Daily Aspirin Therapy: Understand the Benefits and Risks

    MedlinePlus

    ... which can include asthma caused by aspirin Bleeding stomach ulcers Your doctor will discuss what dose is right ... aspirin use increases your risk of developing a stomach ulcer. And, if you have a bleeding ulcer or ...

  4. Can an Aspirin a Day Keep a Pregnancy Complication Away?

    MedlinePlus

    ... news/fullstory_166926.html Can an Aspirin a Day Keep a Pregnancy Complication Away? Odds of preeclampsia ... simple as taking a low-dose aspirin every day may protect pregnant women from the life-threatening ...

  5. Aspirin Safe for Heart Failure Patients, Study Finds

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_167498.html Aspirin Safe for Heart Failure Patients, Study Finds Large trial comparing it to warfarin finds aspirin not tied to more hospitalizations or deaths To ...

  6. Aspirin and salicylic acid decrease c-Myc expression in cancer cells: a potential role in chemoprevention.

    PubMed

    Ai, Guoqiang; Dachineni, Rakesh; Muley, Pratik; Tummala, Hemachand; Bhat, G Jayarama

    2016-02-01

    Epidemiological studies have demonstrated a significant correlation between regular aspirin use and reduced colon cancer incidence and mortality; however, the pathways by which it exerts its anti-cancer effects are still not fully explored. We hypothesized that aspirin's anti-cancer effect may occur through downregulation of c-Myc gene expression. Here, we demonstrate that aspirin and its primary metabolite, salicylic acid, decrease the c-Myc protein levels in human HCT-116 colon and in few other cancer cell lines. In total cell lysates, both drugs decreased the levels of c-Myc in a concentration-dependent fashion. Greater inhibition was observed in the nucleus than the cytoplasm, and immunofluorescence studies confirmed these observations. Pretreatment of cells with lactacystin, a proteasome inhibitor, partially prevented the downregulatory effect of both aspirin and salicylic acid, suggesting that 26S proteasomal pathway is involved. Both drugs failed to decrease exogenously expressed DDK-tagged c-Myc protein levels; however, under the same conditions, the endogenous c-Myc protein levels were downregulated. Northern blot analysis showed that both drugs caused a decrease in c-Myc mRNA levels in a concentration-dependent fashion. High-performance liquid chromatography (HPLC) analysis showed that aspirin taken up by cells was rapidly metabolized to salicylic acid, suggesting that aspirin's inhibitory effect on c-Myc may occur through formation of salicylic acid. Our result suggests that salicylic acid regulates c-Myc level at both transcriptional and post-transcription levels. Inhibition of c-Myc may represent an important pathway by which aspirin exerts its anti-cancer effect and decrease the occurrence of cancer in epithelial tissues.

  7. Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks

    PubMed Central

    Meek, Inger L.; van de Laar, Mart A.F.J.; Vonkeman, Harald E.

    2010-01-01

    While aspirin may offer protection, other non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) can cause serious cardiovascular side effects and complications. This has led to a general "black box" warning for cardiovascular adverse events for NSAIDs. This review explores the different mechanisms underlying the protective effects of aspirin, the NSAID associated renovascular effects causing hypertension, edema and heart failure, the cardiovascular effects causing myocardial infarction and stroke, and the possible deleterious interaction between NSAIDs and aspirin. PMID:27713346

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

    PubMed

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

    2017-05-01

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

  9. Synthesis of Aspirin: A General Chemistry Experiment

    NASA Astrophysics Data System (ADS)

    Olmsted, John A., III

    1998-10-01

    An experiment is described that is suitable for the early portion of the laboratory in a general chemistry course and integrates organic examples. It is the two-step synthesis of aspirin starting from oil of wintergreen. The mechanism for this synthesis provides examples of three major classes of chemical reactions: hydrolysis, condensation, and proton transfer. To understand the chemistry, the student must be able to recognize the common molecular framework shared by oil of wintergreen, salicylic acid, and aspirin and to identify the -OH and -CO2 sites where chemical changes occur. The experiment differs in three ways from traditional aspirin synthesis experiments for general chemistry. It is designed to be performed early rather than late; it starts from a naturally occurring material and requires two steps rather than one; and it utilizes FTIR spectroscopy to distinguish among oil of wintergreen starting material, salicylic acid intermediate, and aspirin product. The use of FTIR spectroscopy introduces students to a modern analytical technique that is currently used in research involving aspirin.

  10. Aspirin-sensitive asthma due to diffuse neuroendocrine system pathology.

    PubMed

    Evsyukova, Helen V

    2002-08-01

    Available clinical data on aspirin-sensitive asthma (ASA) indicate that ASA patients have certain disturbances in the nervous, endocrine, immune and other body systems. It has been found that such patients have a lower melatonin (MT) production in daytime, a pathology of the platelet membrane-receptor complex, and a pathological response to exogenic MT and acetylsalicylic acid. A hypothesis has been suggested in which ASA is considered as apudopathy caused by dysfunction of MT-producing cells. The decreased MT production and the disturbed cell sensitivity to MT lead to pathological changes in individual organs and functional systems. As a result, there is an enhanced lipid peroxidation, an excessive production of reactive oxygen radicals, and a reduced inhibitory action of MT on the 5-lipoxygenase and NO-synthase activities. The lower MT content also results in an intense aggregation of platelets, activating these cells and increasing the production of leukotrienes and nitric oxide. These changes disturb the pulmonary microcirculation, causing the bronchial obturation syndrome even in patient who do not take aspirin or other nonsteroidal anti-inflammatory drugs. The lower basic production of MT is also responsible for a lower content of its metabolite-endogenic acetylsalicylic acid, thereby increasing the sensitivity of melatonin-producing cells, in particular of platelets, to this acid. So, even minimal aspirin doses inhibit the activity of COX-1, which shunts the already abnormal metabolism of arachidonic acid. This, in turn, leads to a greater production of leukotrienes and, hence, to a severe course of the disease. This hypothesis has become the basis for a new pathogenetic approach to the treatment of ASA patients by correcting the melatonin content with peptide bioregulators--the epiphysis extracts--Epithalamin and Epiphamin.

  11. Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device.

    PubMed

    Sheriff, Jawaad; Girdhar, Gaurav; Chiu, Wei-Che; Jesty, Jolyon; Slepian, Marvin J; Bluestein, Danny

    2014-05-01

    Ventricular assist devices (VADs) are implanted in patients with end-stage heart failure to provide both short- and long-term hemodynamic support. Unfortunately, bleeding and thromboembolic complications due to the severely disturbed, dynamic flow conditions generated within these devices require complex, long-term antiplatelet and anticoagulant therapy. While several studies have examined the effectiveness of one such agent, aspirin, under flow conditions, data comparing the efficacy of in vitro and in vivo metabolized aspirin is lacking. Two sets of studies were conducted in vitro with purified human platelets circulating for 30 min in a flow loop containing the DeBakey VAD (MicroMed Cardiovascular, Houston, TX, USA): (a) 20 μM aspirin was added exogenously in vitro to platelets isolated from aspirin-free subjects, and (b) platelets were obtained from donors 2 h (n = 14) and 20 h (n = 13) after ingestion of 1,000 mg aspirin. Near real-time platelet activation state (PAS) was measured with a modified prothrombinase-based assay. Platelets exposed to aspirin in vitro and in vivo (metabolized) showed 28.2 and 25.3 % reduction in platelet activation rate, respectively, compared to untreated controls. Our results demonstrate that in vitro treatment with antiplatelet drugs such as aspirin is as effective as in vivo metabolized aspirin in testing the effect of reducing shear-induced platelet activation in the VAD. Using the PAS assay provides a practical in vitro alternative to in vivo testing of antiplatelet efficacy, as well as for testing the thrombogenic performance of devices during their research and development.

  12. Low Dose Aspirin Therapy Decreases Blood Glucose Levels but Does not Prevent Type I Diabetes-induced Bone Loss

    PubMed Central

    Coe, Lindsay M.; Denison, Jeffery D.; McCabe, Laura R.

    2011-01-01

    Backgroud: Diabetes is strongly associated with increased fracture risk. During T1-diabetes onset, levels of blood glucose and pro-inflammatory cytokines (including TNFα) are increased. At the same time, levels of osteoblast markers are rapidly decreased and stay decreased 40 days later at which point bone loss is clearly evident. Inflammation is known to suppress bone formation and induce bone loss. Previous co-culture studies indicate that diabetic bone is inflamed and diabetic bone marrow is capable of enhancing osteoblast death in vitro. Here we investigate a commonly used non-steroidal anti-inflammatory drug, aspirin, to prevent T1-diabetic bone loss in vivo. Methods: We induced diabetes in 16-week-old male C57BL/6 mice and administered aspirin in the drinking water. Results: Our results demonstrate that aspirin therapy reduced diabetic mouse non-fasting blood glucose levels to less than 400 mg/dl, but did not prevent trabecular and cortical bone loss. In control mice, aspirin treatment increased bone formation markers but did not affect markers of bone resorption or bone density/volume. In diabetic mice, bone formation markers and bone density/volume are decreased and unaltered by aspirin treatment. Bone resorption markers, however, are increased and 2-way ANOVA analysis demonstrates an interaction between aspirin treatment and diabetes (p<0.007). Aspirin treatment did not prevent the previously reported diabetes-induced marrow adiposity. Conclusion: Taken together, our results suggest that low dose aspirin therapy does not negatively impact bone density in control and diabetic mice, but could potentially increase bone resorption in T1-diabetic mice. PMID:22178944

  13. Aspirin-induced post-gingivectomy haemorrhage: a timely reminder.

    PubMed

    Thomason, J M; Seymour, R A; Murphy, P; Brigham, K M; Jones, P

    1997-02-01

    A case report is described of significant aspirin-induced haemorrhage following a gingivectory procedure in an organ transplant patient. Aspirin-induced platelet impairment secondary to low-dose aspirin was implicated as the cause of the haemorrhage. Haemostasis was eventually achieved after platelet transfusion. The case illustrates the problems that can arise when carrying out gingival surgery on patients medicated with low-dose aspirin.

  14. Isomeric methoxy analogs of nimesulide for development of brain cyclooxygense-2 (COX-2)-targeted imaging agents: Synthesis, in vitro COX-2-inhibitory potency, and cellular transport properties.

    PubMed

    Yamamoto, Yumi; Hisa, Takuya; Arai, Jun; Saito, Yohei; Yamamoto, Fumihiko; Mukai, Takahiro; Ohshima, Takashi; Maeda, Minoru; Ohkubo, Yasuhito

    2015-11-01

    Nimesulide analogs bearing a methoxy substituent either at the ortho-, meta- or para-position on the phenyl ring, were designed, synthesized, and evaluated for potential as radioligands for brain cyclooxygenase-2 (COX-2) imaging. The synthesis of nimesulide and regioisomeric methoxy analogs was based on the copper-mediated arylation of phenolic derivatives for the construction of diaryl ethers. These isomeric methoxy analogs displayed lipophilicity similar to that of nimesulide itself, as evidenced by their HPLC logP7.4 values. In vitro inhibition studies using a colorimetric COX (ovine) inhibitor-screening assay demonstrated that the para-methoxy substituted analog retains the inhibition ability and selectivity observed for parent nimesulide toward COX-2 enzyme, whereas the meta- and ortho-methoxy substituents detrimentally affected COX-2-inhibition activity, which was further supported by molecular docking studies. Bidirectional transport cellular studies using Caco-2 cell culture model in the presence of the P-glycoprotein (P-gp) inhibitor, verapamil, showed that P-gp did not have a significant effect on the efflux of the para-methoxy substituted analog. Further investigations using the radiolabeled form of the para-methoxy substituted analog is warranted for in vivo characterization.

  15. Effects of co-administered dexamethasone and nimesulide on pain, swelling, and trismus following third molar surgery: a randomized, triple-blind, controlled clinical trial.

    PubMed

    Barbalho, J C; Vasconcellos, R J H; de Morais, H H; Santos, L A M; Almeida, R de A C; Rêbelo, H L; Lucena, E E; de Araújo, S Q

    2017-02-01

    This study aimed to determine the effect of the co-administration of dexamethasone 8mg and nimesulide 100mg given 1h before mandibular third molar surgery. A prospective, randomized, triple-blind, split-mouth clinical trial was developed at the study institution in Pernambuco, Brazil. A pilot study was first performed (95% confidence interval, 80% test power, and 5% error), and a sample of 40 patients aged between 18 and 40 years was selected. The patients were randomized and divided into two groups: dexamethasone+placebo and dexamethasone+nimesulide. The following parameters were evaluated: pain (visual analogue scale), total number of rescue analgesics taken, time taken to first rescue analgesic consumption, oedema, trismus, and patient satisfaction. The paired t-test and the Wilcoxon test were used to compare means. Statistically significant differences were found between the groups in pain values at 2, 4, and 12h postoperative, and in the total number of rescue analgesics and time taken to first rescue analgesic ingestion (P<0.05), with results in favour of dexamethasone+nimesulide administration. Oedema and trismus were similar in the two treatment groups and decreased over time postoperatively. The co-administration of dexamethasone and nimesulide reduces pain intensity and the need for rescue medication after third molar surgery.

  16. Feasibility of clinoptilolite application as a microporous carrier for pH-controlled oral delivery of aspirin.

    PubMed

    Tondar, Mahdi; Parsa, Mohammad Javad; Yousefpour, Yaser; Sharifi, Ali Mohammad; Shetab-Boushehri, Seyed Vahid

    2014-01-01

    Clinoptilolite is a natural zeolite which due to high surface area/volume ratio has found many applications in industries and medicine. Aspirin is a non-steroidal anti-inflammatory drug which is currently used as an anticoagulant, antinociceptive, antipyretic, and anti-inflammatory drug. It is an acidic drug which induces gastric irritation due to inhibition of cyclooxygenase I located in gastric mucosa. In the present work, adsorption and desorption of aspirin on Iranian clinoptilolite micronized particles were studied in acidic and relatively alkaline pHs. Effect of particle size of clinoptilolite was also investigated on adsorption and desorption of aspirin. Specific surfaces, particle sizes, and zeta potentials of clinoptilolite particles were also determined. Scanning electron micrograph was used to study the morphology and crystallinity of clinoptilolite particles. The results showed that adsorption and desorption of aspirin on clinoptilolite are particle size- and pH-dependent. The present work proposes clinoptilolite as an inexpensive, efficient, and non-toxic natural available microporous material for aspirin oral delivery.

  17. Effectiveness of Aspirin on Double Lumen Permanent Catheter Efficacy in ESRD

    PubMed Central

    Mozafar, Mohammad; Samsami, Majid; Sobhiyeh, Mohammad Reza; Jabbehdari, Sayena; Fallah Zavareh, Mahtab

    2013-01-01

    Background The complications of vascular access are the most imperative etiology for hospitalization, morbidity and mortality in chronic hemodialysis. The most prevalent complication of central catheter is dysfunction due to thrombosis. Aspirin is an anti-aggregative platelet drug that may increase the patency of permanent catheters (perm-cath). Objectives The aim of this study was to evaluate the role of Aspirin in perm-cath survival. Patients and Methods This study included a total of 185 ESRD cases according to the inclusion criteria for perm-cath insertion in hemodialysis. One hundred and eighty patients following perm-cath insertion had proper blood flow through perm-cath during hemodialysis. Patients were randomly divided between intervention (80 mg/day Aspirin initiated a day following catheter insertion) and control (placebo) groups. The average time that the perm-cath was functional was noted. Demographic characteristics included comorbidities and past history were also used to address probable influence on perm-cath function and patency. Results The mean survival time of the catheter in Aspirin group was significantly higher than the control group (5.3 ± 4.7 month versus 3.9 ± 2.7 month, P = 0.012). No significant difference in major complications of Aspirin use (such as GI bleeding) was noted between two groups (P = 0.52). In terms of the patient’s demographic characteristics, those of the female gender and a history of diabetes mellitus were found to have significant influence on median survival rate of the catheters (P = 0.021, 0.043 respectively). Conclusions These results suggest that Aspirin use following perm-cath insertion might be beneficial for catheter survival. This increased survival time might enable patient’s use of AVF maturation for long term dialysis access. PMID:23841041

  18. Prostate Cancer and Aspirin Use: Synopsis of the Proposed Molecular Mechanisms

    PubMed Central

    Bilani, Nadeem; Bahmad, Hisham; Abou-Kheir, Wassim

    2017-01-01

    Background: Prostate cancer (PCa) is a critical health burden, impacting the morbidity and mortality of millions of men around the world. Most of the patients with PCa have their disease at first sensitive to androgen deprivation treatments, but later they develop resistance to therapy and eventually die of metastatic castration-resistant prostate cancer (CRPC). Although the newly developed anti-androgen therapies are effectively alleviating symptoms and prolonging lives of patients, there are still no curable treatments for CRPC. Recently, statistical studies have shown that the chronic use of aspirin might be significantly associated with better outcomes in PCa patients. Through this review, we aim to identify the different proposed molecular mechanisms relating aspirin to the pathobiology of PCa neoplasms, with a major focus on basic research done in this context. Methods: Articles were retrieved via online database searching of PubMed and MEDLINE between 1946 and September 2016. Keywords and combinations related to PCa and aspirin were used to perform the search. Abstracts of the articles were studied by two independent reviewers and then data extraction was performed on the relevant articles that met our review objectives. Results: Aspirin, a non-steroidal anti-inflammatory drug (NSAID), affects the proliferation, apoptosis, resistance and metastasis of PCa cell lines, through both COX-dependent and COX-independent mechanisms. It also lowers levels of the PCa diagnostic marker prostate specific antigen (PSA), suggesting that clinicians need to at least be aware if their patients are using Aspirin chronically. Conclusion: This review strongly warrants further consideration of the signaling cascades activated by aspirin, which may lead to new knowledge that might be applied to improve diagnosis, prognosis and treatment of PCa. PMID:28377721

  19. Modulating the inflammatory properties of activated microglia with Docosahexaenoic acid and Aspirin.

    PubMed

    Pettit, Lauren K; Varsanyi, Christopher; Tadros, James; Vassiliou, Evros

    2013-02-11

    Microglia are considered the "resident macrophages" of the brain. When in their resting state, microglia perform routine maintenance and immune surveillance. Once activated, either by injury or an immune stimulus, microglia secrete a variety of pro-inflammatory molecules, such as Nitric Oxide, superoxide, and inflammatory cytokines. Up-regulation of pro-inflammatory molecules is transient, and does not cause neurodegeneration. However, if up-regulation lasts for an extended period of time, neurodegeneration ensues.Many neurodegenerative diseases are characterized by chronic inflammation due to microglial activation. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been proposed as possible preventative treatments for neurodegenerative diseases, due to their anti-inflammatory properties. Docosahexaenoic Acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that has potent anti-inflammatory properties.This research work sought to elucidate whether microglial activation can be modulated by combining Aspirin, a classical NSAID, with Docosahexaenoic Acid, a natural anti-inflammatory agent. The combined ability of Aspirin and DHA to modulate microglial activation was determined in the context of pro-inflammatory cytokines, Nitric Oxide levels, as well as total Glutathione levels. Docosahexaenoic Acid increased total Glutathione levels in microglia cells and enhanced their anti-oxidative capacity. It reduced production of the pro-inflammatory cytokines TNF-α and IL-6 induced through TLR-3 and TLR-4 activation. Furthermore, it reduced production of Nitric Oxide. Aspirin showed similar anti-inflammatory effects with respect to TNF-α during TLR-3 and TLR-7 stimulation. Aspirin did not show any redection in terms of Nitric Oxide production. Combination of Aspirin and Docosahexaenoic Acid showed augmentation in total Glutathione production during TLR-7 stimulation as well as a reduction in IL-6, TNF-α and Nitric Oxide. Collectively, these findings highlight the

  20. Aspirin intolerance and the need for dual antiplatelet therapy after stent implantation: a proposed alternative regimen.

    PubMed

    Latib, Azeem; Ielasi, Alfonso; Ferri, Luca; Chieffo, Alaide; Godino, Cosmo; Carlino, Mauro; Montorfano, Matteo; Colombo, Antonio

    2013-05-25

    Dual antiplatelet therapy (DAT, i.e. aspirin+thienopyridine) has been shown to reduce the risk of stent thrombosis (ST) and myocardial infarction (MI) after coronary stent implantation. Data regarding alternative antiplatelet therapy in patients with allergy or intolerance to aspirin are lacking. This study is a retrospective analysis of consecutive patients with adverse reactions to aspirin who received an alternative combination of DAT (indobufen, trapidil, or triflusal in association with a thienopyridine) after elective implantation of either drug-eluting (DES) or bare-metal stents (BMS). Endpoints analyzed were cardiac death, MI, ST and bleeding. A total of 127 patients undergoing stenting of 267 lesions (DES 84%, BMS 16%), were identified between June'99 and November'08. Reasons for not taking aspirin included gastrointestinal intolerance (53.5%), allergy (39.4%), non-gastrointestinal bleeding (5.5%) and others (1.6%). Aspirin was substituted with indobufen (64.6%), trapidil (26.8%), triflusal (6.3%), or a combination of indobufen+trapidil (2.4%). Median duration of DAT was 369 days [IQR 273-1053] after DES and 46.5 days [IQR 30-699] after BMS implantation. Only 3.1% of patients prematurely discontinued DAT. During a median follow-up of 1161 days [IQR 781-1538], rates of cardiac death and MI were 3.1% and minor bleeding occurred in 1.5%. There was 1 very late definite ST occurring 2 days after DAT discontinuation and no probable ST. In this cohort of patients with aspirin intolerance undergoing coronary stent implantation, the combination of a thienopyridine with indobufen, trapidil, or triflusal was associated with a low rate of cardiac death, ST and MI. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice

    PubMed Central

    Strong, Randy; Miller, Richard A.; Astle, Clinton M.; Floyd, Robert A.; Flurkey, Kevin; Hensley, Kenneth L.; Javors, Martin A.; Leeuwenburgh, Christiaan; Nelson, James F.; Ongini, Ennio; Nadon, Nancy L.; Warner, Huber R.; Harrison, David E.

    2009-01-01

    The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, TJL; University of Michigan, UM; and University of Texas Health Science Center, San Antonio, UT). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen (NFP), 4-OH-α-phenyl-N-te