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Sample records for drugs aspirin nimesulide

  1. Drug/drug interaction of common NSAIDs with antiplatelet effect of aspirin in human platelets.

    PubMed

    Saxena, Aaruni; Balaramnavar, Vishal M; Hohlfeld, Thomas; Saxena, Anil K

    2013-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with the anti-platelet activity of aspirin at the level of the platelet cyclooxygenase-1 (COX-1) enzyme. In order to examine the interference of common NSAIDs with the anti-platelet activity of aspirin the human platelet rich plasma from voluntary donors was used for arachidonic acid-induced aggregation and determination of thromboxane synthesis. Further, docking studies were used to explain the molecular basis of the NSAID/aspirin interaction. The experimental results showed that celecoxib, dipyrone (active metabolite), ibuprofen, flufenamic acid, naproxen, nimesulide, oxaprozin, and piroxicam significantly interfere with the anti-platelet activity of aspirin, while diclofenac, ketorolac and acetaminophen do not. Docking studies suggested that NSAIDs forming hydrogen bonds with Ser530, Arg120, Tyr385 and other amino acids of the COX-1 hydrophobic channel interfere with antiplatelet activity of aspirin while non interfering NSAIDs do not form relevant hydrogen bond interactions within the aspirin binding site. In conclusion, docking analysis of NSAID interactions at the COX-1 active site appears useful to predict their interference with the anti-platelet activity of aspirin. The results, demonstrate that some NSAIDs do not interfere with the antiplatelet action of aspirin while many others do and provide a basis for understanding the observed differences among individual non-aspirin NSAIDs. PMID:24075938

  2. Effects of non-steroidal anti-inflammatory drugs on cyclo-oxygenase and lipoxygenase activity in whole blood from aspirin-sensitive asthmatics vs healthy donors

    PubMed Central

    Gray, P A; Warner, T D; Vojnovic, I; Del Soldato, P; Parikh, A; Scadding, G K; Mitchell, J A

    2002-01-01

    Cyclo-oxygenase (COX) and lipoxygenase (LO) share a common substrate, arachidonic acid. Aspirin and related drugs inhibit COX activity. In a subset of patients with asthma aspirin induces clinical symptoms associated with increased levels of certain LO products, a phenomenon known as aspirin-sensitive asthma. The pharmacological pathways regulating such responses are not known. Here COX-1 and LO activity were measured respectively by the formation of thromboxane B2 (TXB2) or leukotrienes (LT) C4, D4 and E4 in whole blood stimulated with A23187. COX-2 activity was measured by the formation of prostaglandin E2 (PGE2) in blood stimulated with lipopolysaccharide (LPS) for 18 h. No differences in the levels of COX-1, COX-2 or LO products or the potency of drugs were found in blood from aspirin sensitive vs aspirin tolerant patients. Aspirin, indomethacin and nimesulide inhibited COX-1 activity, without altering LO activity. Indomethacin, nimesulide and the COX-2 selective inhibitor DFP [5,5-dimethyl-3-(2-isopropoxy)-4-(4-methanesulfonylphenyl)-2(5H)-furanone] inhibited COX-2 activity. NO-aspirin, like aspirin inhibited COX-1 activity in blood from both groups. However, NO-aspirin also reduced LO activity in the blood from both patient groups. Sodium salicylate was an ineffective inhibitor of COX-1, COX-2 or LO activity in blood from both aspirin-sensitive and tolerant patients. Thus, when COX activity in the blood of aspirin-sensitive asthmatics is blocked there is no associated increase in LO products. Moreover, NO-aspirin, unlike other NSAIDs tested, inhibited LO activity in the blood from both aspirin sensitive and aspirin tolerant individuals. This suggests that NO-aspirin may be better tolerated than aspirin by aspirin-sensitive asthmatics. PMID:12429575

  3. Molecular Dynamics and Physical Stability of Amorphous Nimesulide Drug and Its Binary Drug-Polymer Systems.

    PubMed

    Knapik, J; Wojnarowska, Z; Grzybowska, K; Tajber, L; Mesallati, H; Paluch, K J; Paluch, M

    2016-06-01

    In this article we study the effectiveness of three well-known polymers: inulin, Soluplus, and PVP in stabilizing the amorphous form of nimesulide (NMS) drug. The recrystallization tendency of pure drug as well as measured drug-polymer systems were examined at isothermal conditions by broadband dielectric spectroscopy (BDS) and at nonisothermal conditions by differential scanning calorimetry (DSC). Our investigation has shown that the crystallization half-life time of pure NMS at 328 K is equal to 33 min. We found that this time can be prolonged to 40 years after adding 20% w/w PVP to NMS. This polymer proved to be the best NMS stabilizer, while the worst stabilization effect was exhibited by inulin. Additionally, our DSC, BDS, and FTIR studies indicate that for suppression of NMS recrystallization in the NMS-PVP system, the two mechanisms are responsible: the polymeric steric hindrances and the antiplastization effect exerted by the excipient. PMID:27149568

  4. Aspirin

    MedlinePlus

    ... the extended-release tablets whole with a full glass of water. Do not break, crush, or chew ... Swallow the delayed-release tablets with a full glass of water.Chewable aspirin tablets may be chewed, ...

  5. 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

  6. Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer.

    PubMed

    Lim, Wei-Yen; Chuah, Khoon Leong; Eng, Philip; Leong, Swan Swan; Lim, Elaine; Lim, Tow Keang; Ng, Alan; Poh, Wee Teng; Tee, Augustine; Teh, Ming; Salim, Agus; Seow, Adeline

    2012-08-01

    There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31-0.81 in non-smokers; OR 0.38, 95%CI 0.16-0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.

  7. 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

    2010-10-01

    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.

  8. 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.

  9. 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. PMID:3880531

  10. 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.

  11. 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

  12. Differential analgesic effects of aspirin-like drugs.

    PubMed

    Brune, K; Menzel-Soglowek, S; Zeilhofer, H U

    1992-01-01

    Tissue damage, including that due to surgical manipulation, results in 2 distinct but connected changes in the pain perception pathway. Firstly, cells disintegrate at the site of tissue damage and release mediators, including prostaglandins. These mediators transform fine nerve endings, particularly high-threshold mechanoceptors, into nociceptors. In other words, fine nerve endings that are not normally activated by mechanical pressure or temperature changes become very sensitive and are depolarised after minor mechanical or thermal changes. Secondly, in the central nervous system (CNS) and, particularly, in the dorsal horn of the spinal cord, reflex activity is increased, metabolic activity of the neuronal cells is enhanced and, chronically, major rearrangements of mediator production and electrical activity of the dorsal horn cells may be observed. Both types of change contribute to the well known phenomenon of hyperalgesia, which is regularly observed in connection with tissue damage, including that produced by surgical manipulation. It has been shown that aspirin-like drugs reduce the enhanced nociceptor activity in damaged tissue, probably as a result of prostaglandin synthesis inhibition. Recently, there have been indications that these drugs may have an additional mechanism of action in the spinal cord or higher parts of the CNS. Using the pure enantiomers of flurbiprofen in pharmacodynamic experiments in the rat, we have observed that the R- and S-enantiomers may exert differential analgesic effects. The R-enantiomer, which does not inhibit cyclo-oxygenase in vitro, was almost as effective as the S-enantiomer, which does inhibit prostaglandin synthesis in different models of pain and nociception.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. 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. PMID:27246782

  14. Aspirin, Nonsteroidal Anti-inflammatory Drug Use, and Risk for Crohn Disease Ulcerative Colitis

    PubMed Central

    Ananthakrishnan, Ashwin N.; Higuchi, Leslie M.; Huang, Edward S.; Khalili, Hamed; Richter, James M.; Fuchs, Charles S.; Chan, Andrew T.

    2012-01-01

    Background Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory but have been linked in some studies to Crohn disease (CD) and ulcerative colitis (UC). Objective To assess the association between aspirin and NSAID use and incident CD and UC. Design Prospective cohort study. Setting Nurses' Health Study I. Patients 76 795 U.S. women who provided biennially updated data about aspirin and NSAID use. Measurements Incident CD and UC between 1990 and 2008 (outcome) and NSAID and aspirin use (exposure). Results 123 incident cases of CD and 117 cases of UC occurred over 18 years and 1 295 317 person-years of follow-up. Compared with nonusers, women who used NSAIDs at least 15 days per month seemed to have increased risk for both CD (absolute difference in age-adjusted incidence, 6 cases per 100 000 person-years [95% CI, 0 to 13]; multivariate hazard ratio, 1.59 [CI, 0.99 to 2.56]) and UC (absolute difference, 7 cases per 100 000 person-years [CI, 1 to 12]; multivariate hazard ratio, 1.87 [CI, 1.16 to 2.99]). Less frequent NSAID use was not clearly associated with risk for CD or UC, and there was no clear association between aspirin use and disease. Limitations Cohort participants were exclusively women, most of whom were white. Aspirin and NSAID use were self-reported. Conclusion Frequent use of NSAIDs but not aspirin seemed to be associated with increased absolute incidence of CD and UC. The findings have more mechanistic than clinical implications, because the absolute incidence of CD or UC associated with NSAIDs was low and the increase in risk for CD or UC associated with NSAIDs is unlikely to alter the balance of more common and clinically significant risks and benefits associated with these agents. Primary Funding Source American Gastroenterological Association, IBD Working Group, Broad Medical Research Program, and National Institutes of Health. PMID:22393130

  15. Use of Aspirin or Nonsteroidal Anti-inflammatory Drugs Increases Risk for Diverticulitis and Diverticular Bleeding

    PubMed Central

    Strate, Lisa L.; Liu, Yan L.; Huang, Edward S.; Giovannucci, Edward L.; Chan, Andrew T.

    2011-01-01

    BACKGROUND & AIMS Nonsteroidal Anti-inflammatory Drugs (NSAIDs), including aspirin, have been implicated in diverticular complications. We examined the influence of aspirin and NSAID use on risk of diverticulitis and diverticular bleeding in a large prospective cohort. METHODS We studied 47,210 US men in the Health Professionals Follow-up Study cohort who were 40–75 years old at baseline, in 1986. We assessed use of aspirin, non-aspirin NSAIDs, and other risk factors biennially. We identified men with diverticulitis or diverticular bleeding based on responses to biennial and supplemental questionnaires. RESULTS We documented 939 cases of diverticulitis and 256 cases of diverticular bleeding during a 22-year period of follow-up. After adjustment for risk factors, men who used aspirin regularly (≥2 times per week) had a multivariable relative risk (RR) of 1.25 (95% confidence interval [CI], 1.05–1.47) for diverticulitis and RR of 1.70 (95% CI, 1.21–2.39) for diverticular bleeding, compared with non-users of aspirin and NSAIDs. Use of aspirin at intermediate doses (2–5.9 standard, 325 mg, tablets per week) and frequency (4–6 days per week) were associated with the highest risk of bleeding (multivariable RR=2.32; 95% CI, 1.34–4.02, and multivariable RR=3.13; 95% CI, 1.82–5.38, respectively). Regular users of non-aspirin NSAIDs also had an increased risk of diverticulitis (multivariable RR=1.72; 95% CI, 1.40–2.11) and diverticular bleeding (multivariable RR=1.74; 95% CI, 1.15–2.64), compared with men who denied use of these medications. CONCLUSIONS Regular use of aspirin or NSAIDs is associated with an increased risk for diverticulitis and diverticular bleeding. Patients at risk of diverticular complications should carefully consider the potential risks and benefits of using these medications. PMID:21320500

  16. 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.

  17. 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.

  18. 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

  19. 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. PMID:7469139

  20. 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

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

    PubMed

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

    1997-12-01

    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

  2. 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

  3. 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

  4. Long-term Use of Aspirin and Nonsteroidal Anti-inflammatory Drugs and Risk of Colorectal Cancer

    PubMed Central

    Chan, Andrew T.; Giovannucci, Edward L.; Meyerhardt, Jeffrey A.; Schernhammer, Eva S.; Curhan, Gary C.; Fuchs, Charles S.

    2005-01-01

    Context Randomized trials of short-term aspirin use for prevention of recurrent colorectal adenoma have provided compelling evidence of a causal relationship between aspirin and colorectal neoplasia. However, data on long-term risk of colorectal cancer according to dose, timing, or duration of therapy with aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) remain limited. Objective To examine the influence of aspirin and NSAIDs in prevention of colorectal cancer. Design, Setting, and Participants Prospective cohort study of 82 911 women enrolled in the Nurses’ Health Study providing data on medication use biennially since 1980 and followed up through June 1, 2000. Main Outcome Measure Incident colorectal cancer. Results Over a 20-year period, we documented 962 cases of colorectal cancer. Among women who regularly used aspirin (≥2 standard [325-mg] tablets per week), the multivariate relative risk (RR) for colorectal cancer was 0.77 (95% confidence interval [CI], 0.67–0.88) compared with nonregular users. However, significant risk reduction was not observed until more than 10 years of use (P≤.001 for trend). The benefit appeared related to dose: compared with women who reported no use, the multivariate RRs for cancer were 1.10 (95% CI, 0.92–1.31) for women who used 0.5 to 1.5 standard aspirin tablets per week, 0.89 (95% CI, 0.73–1.10) for 2 to 5 aspirin per week, 0.78 (95% CI, 0.62–0.97) for 6 to 14 aspirin per week, and 0.68 (95% CI, 0.49–0.95) for more than 14 aspirin per week (P<.001 for trend). Notably, women who used more than 14 aspirin per week for longer than 10 years in the past had a multivariate RR for cancer of 0.47 (95% CI, 0.31–0.71). A similar dose-response relationship was found for nonaspirin NSAIDs (P=.007 for trend). The incidence of reported major gastrointestinal bleeding events per 1000 person-years also appeared to be dose-related: 0.77 among women who denied any aspirin use; 1.07 for 0.5 to 1.5 standard aspirin

  5. Aspirin-sensitive asthma: significance of the cyclooxygenase-inhibiting and protein-binding properties of analgesic drugs.

    PubMed

    Williams, W R; Pawlowicz, A; Davies, B H

    1991-01-01

    The in vitro release of endogenous and exogenous PgF2 alpha from plasma and serum proteins by aspirin and other analgesic drugs has been studied by RIA and equilibrium-dialysis techniques, respectively. Before aspirin addition, the mean plasma level of PgF2 alpha measured by RIA was significantly lower in aspirin-sensitive asthma (ASA) patients (11.3 +/- 6.5 pg/ml; n = 8) than in aspirin-tolerant asthma (ATA) patients (25.0 +/- 11.4 pg/ml; n = 21). After aspirin addition (50 micrograms/ml) the mean PgF2 alpha level detected in plasma by RIA was higher in ASA patients (97.6 +/- 5.5 pg/ml) than in ATA patients (66.9 +/- 4.5). The binding of [3H]PgF2 alpha to serum protein was significantly inhibited by NSAIDs but not by paracetamol (0.2-1.0 mM). These results implicate PgF2 alpha and the protein-binding property of analgesic drugs in the pathogenesis of aspirin-sensitive asthma. PMID:1959973

  6. 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.

  7. [Nimesulide in the treatment of primary dysmenorrhea. Comparative clinical evaluation with mefenamic acid and fentiazac].

    PubMed

    López Rosales, C; Cisneros Lugo, J H; Romo Enciso, L J; García Sandoval, M G

    1989-07-01

    Sixty patients with primary dismenorrhea were treated: 20 with nimesulide, 20 with fentiazac and 20 with mefenamic acid during three consecutive cycles under double blind design. The doses used in each group were: nimesulide or fentiazac 100 mg, every 12 hrs., mefenamic acid 500 mg. every 8 hrs. in all cases during 5 days, beginning a day before the beginning, of the menstruation. The pain evolution and the symptoms were evaluated three times a day using a scale from 0 to 10, so measure its intensity. Concluding, the nimesulide is useful in the treatment of pain associated with primary dismenorrhea, answering with little statistical advantage over the fentiazac and with bigger statistical advantage over the mefenamic acid. The tolerance was excellent with the three drugs studied.

  8. 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. PMID:23287776

  9. Aspirin or Nonsteroidal Anti-inflammatory Drug-Exacerbated Chronic Rhinosinusitis.

    PubMed

    Ledford, Dennis K; Lockey, Richard F

    2016-01-01

    Aspirin (ASA)-exacerbated respiratory disease (AERD) is characterized by upper airway congestion due to eosinophilic inflammation of the nasal and sinus membranes and nasal polyposis, associated with increased leukotriene production that is further accentuated by ASA or other nonsteroidal anti-inflammatory drug (NSAID) ingestion. It occurs in 5% to 10% of subjects with chronic rhinosinusitis (CRS) and in 15% to 40% of those with nasal polyposis. Although AERD with CRS is usually associated with asthma, this is not always the case. The eosinophilic airway inflammation and symptoms precede clinical reactions to ASA or other NSAIDs, but ultimately affected subjects experience worsening of symptoms with ingestion of ASA/NSAIDs. The endotypic mechanism for this worsening is related to a chronic increase in leukotriene and a decrease in prostaglandin production, particularly prostaglandin E2, that is further aggravated by the inhibition of cycloxgenase I. IgE does not likely play a role in the pathogenesis of the disease although nasal and sinus staphylococcal infection increases local IgE level and may increase total IgE and specific IgE levels. Genetic studies suggest that multiple genes may be involved, but the genetic abnormalities may differ in affected subjects from different ethnicities and candidate genes have not been confirmed in multiple studies. Genome-wide association studies have not been revealing. The phenotype is recognized by the mucosal inflammation and worsening of symptoms acutely with ASA/NSAID. There is clinical improvement with ASA desensitization followed by regular ingestion of ASA or other NSAIDs. Further understanding of this unique phenotype and endotype of CRS will likely improve the understanding of other eosinophilic airway diseases. PMID:27393773

  10. Aspirin Desensitization

    MedlinePlus

    ... dust mites, cats, dogs, or pollen. Others believe sensitivity to aspirin results from a problem in certain ... examination is required to diagnose patients with aspirin sensitivity. Patients with severe asthma, chronic sinusitis, nasal polyps ...

  11. 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.

  12. 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.

  13. Simultaneous determination and pharmacokinetics of protein unbound aspirin and salicylic acid in rat blood and brain by microdialysis: an application to herbal-drug interaction.

    PubMed

    Shaw, Lee-Hsin; Tsai, Tung-Hu

    2012-05-01

    Aspirin is commonly used for the prevention of myocardial infarction and ischemic stroke; whereas the Chinese people employ the bu-yang-huan-wu-tang (BYHWT) as a routine herbal formulation for the treatment and prevention of transient ischemic stroke. The current study develops a microdialysis technique coupled to a validated liquid chromatography system to measure free-form aspirin and salicylic acid for herbal-drug interaction in rat blood and brain. The intra- and inter-day precisions in biological dialysates were within 0.1-9.4% in the concentration ranges of 0.1-50 μg/mL and the accuracies ranged from -4.7 to 6.1%. The pharmacokinetic data demonstrate that the area under the concentration time curve (AUC) of the aspirin was 2031 ± 266 min μg/mL after aspirin administration (100mg/kg, i.v.). The AUC of salicylic acid was 12660 ± 1799 min μg/mL, which suggests that aspirin is quickly hydrolyzed to salicylic acid in blood and the metabolite can also be detected within 15 min in brain dialysate. The herbal-drug pharmacokinetic interaction showed no significant effect in blood and brain. The results of pharmacodynamics for the bleeding time suggested that there were no significant differences between the aspirin alone group and the BYHWT pretreated group. However, the bleeding time has been prolonged when compared aspirin alone or the group pretreated with BYHWT to the blank control. The conclusion provides practical information for clinical practice for the herbal formulation BYHWT and aspirin used concurrently.

  14. Double-blind study of nimesulide in divers with inflammatory disorders of the ear, nose and throat.

    PubMed

    Banchini, G; Scaricabarozzi, I; Montecorboli, U; Ceccarelli, A; Chiesa, F; Ditri, L; Mazzer, G; Moroni, R; Viola, M; Roggia, F

    1993-01-01

    200 divers of either sex, aged 18 to 54 years, entered a double-blind study to compare the efficacy and tolerability of nimesulide 200 mg/day with those of seaprose S 60 mg/day in the treatment of nonbacterial inflammatory disorders of the ear, nose, and throat. At the end of the 1-week treatment period, both drugs were judged to be effective, with improvements and, in most cases, complete remission of all symptoms observed. Nimesulide showed greater clinical efficacy, and both drugs were well tolerated.

  15. Enhancement of Antinociception by Co-administrations of Nefopam, Morphine, and Nimesulide in a Rat Model of Neuropathic Pain

    PubMed Central

    Saghaei, Elham; Sabetkasaei, Masoumeh; Naseri, Kobra

    2012-01-01

    Background Neuropathic pain is a chronic pain due to disorder in the peripheral or central nervous system with different pathophysiological mechanisms. Current treatments are not effective. Analgesic drugs combined can reduce pain intensity and side effects. Here, we studied the analgesic effect of nimesulide, nefopam, and morphine with different mechanisms of action alone and in combination with other drugs in chronic constriction injury (CCI) model of neuropathic pain. Methods Male Wistar rats (n = 8) weighing 150-200 g were divided into 3 different groups: 1- Saline-treated CCI group, 2- Saline-treated sham group, and 3- Drug-treated CCI groups. Nimesulide (1.25, 2.5, and 5 mg/kg), nefopam (10, 20, and 30 mg/kg), and morphine (1, 3, and 5 mg/kg) were injected 30 minutes before surgery and continued daily to day 14 post-ligation. In the combination strategy, a nonanalgesic dose of drugs was used in combination such as nefopam + morphine, nefopam + nimesulide, and nimesulide + morphine. Von Frey filaments for mechanical allodynia and acetone test for cold allodynia were, respectively, used as pain behavioral tests. Experiments were performed on day 0 (before surgery) and days 1, 3, 5, 7, 10, and 14 post injury. Results Nefopam (30 mg/kg) and nimesulide (5 mg/kg) blocked mechanical and thermal allodynia; the analgesic effects of morphine (5 mg/kg) lasted for 7 days. Allodynia was completely inhibited in combination with nonanalgesic doses of nefopam (10 mg/kg), nimesulide (1.25 mg/kg), and morphine (3 mg/kg). Conclusions It seems that analgesic drugs used in combination, could effectively reduce pain behavior with reduced adverse effects. PMID:22259710

  16. 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

  17. 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

  18. Effects of indomethacin, nimesulide, and diclofenac on human MG-63 osteosarcoma cell line.

    PubMed

    Díaz-Rodríguez, Lourdes; García-Martínez, Olga; Morales, Manuel Arroyo-; Rodríguez-Pérez, Laura; Rubio-Ruiz, Belén; Ruiz, Concepción

    2012-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed drugs worldwide and serve as treatment of some degenerative inflammatory joint diseases. The aim of the present study was to investigate the influence of different concentrations of three NSAIDs on cell proliferation, differentiation, antigenic profile, and cell cycle in the human MG-63 osteosarcoma cell line, incubated for 24 hr. All NSAIDs had an inhibiting effect on osteoblastic proliferation. Treatments for 24 hr had small but significant effects on the antigenic profile. No treatment altered osteocalcin synthesis. Indomethacin and nimesulide treatments arrested the cell cycle at G(0)/G(1). These results suggest that indomethacin, nimesulide, and diclofenac appear to have no effects on osteocalcin synthesis and a slight effect on the antigenic profile. They may delay bone regeneration due to their inhibiting effect on osteoblast growth. Therefore, these drugs should only be used in situations that do not require rapid bone healing. PMID:21385796

  19. [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.

  20. [Low-dose aspirin (LDA)/nonsteroidal anti-inflammatory drugs(NSAIDs)-induced gastrointestinal injury in Japan].

    PubMed

    Sugano, Kentaro

    2011-06-01

    Low-dose aspirin (LDA) and nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed in Japan mostly due to increasing elderly population. Since LDA/NSAIDs cause gastrointestinal injury, serious side effects such as bleeding accompanied with their usage have been frequently reported. Awareness of such problems prompted clinical trials to facilitate a more effective approach to prevent LDA/NSAIDs-induced gastrointestinal ulcer. Two drugs recently approved for health insurance reimbursement, celecoxib, a cyclooxygenase (COX)-2 specific inhibitor and low-dose lansoprazole for prevention of recurrent peptic ulcer due to LDA/NSAIDs will be instrumental in mitigating the gastrointestinal injuries. However, continuous, intensive educational programs will be required to the change in the prescription behaviors of the general physicians. Furthermore, we need to search for effective measures to detect and prevent mid and lower gastrointestinal injury caused by LDA/NSAIDs which account for about 30% of all GI bleedings.

  1. 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.

  2. 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.

  3. Effects of Subchronic Treatment with Ibuprofen and Nimesulide on Spatial Memory and NMDAR Subunits Expression in Aged Rats.

    PubMed

    Ozturk Bilgin, Ozlem; Kumbul Doguc, Duygu; Altuntas, Irfan; Sutcu, Recep; Delibas, Namık

    2013-01-01

    Several studies point to an important function of cyclooxygenase (COX) and prostaglandin signaling in models of synaptic plasticity which is associated with N-methyl-D-aspartate receptors (NMDARs). Cyclooxygenase gene is suggested to be an immediate early gene that is tightly regulated in neurons by NMDA dependent synaptic activity. Nonsteroid Antiinflammatory Drugs (NSAIDs) exert their antiinflammatory effect by the inhibion of COX have controversial effects on learning and memory. We administered ibuprofen as a non-selective COX-2 inhibitor and nimesulide as a selective COX-2 inhibitor for 8 weeks for determining the cognitive impact of subchronic administration of NSAIDs to aged rats. Wistar albino rats (16 mo, n = 30) were separated into control (n = 10), ibuprofen (n = 10) and nimesulide (n = 10) treated groups. First we evaluated hippocampus-dependent spatial memory in the radial arm maze (RAM) and than we evaluated the expression of the NMDAR subunits, NR2A and NR2B by western blotting to see if their expressions are effected by subchronic administration with these drugs. Ibuprofen and nimesulide treated rats completed the task in a statistically significant shorter time when compared with control group (p < 0.01), but there was no statistically significant difference between groups about choice accuracy data in RAM. Furthermore, no statistically significant difference was detected for the protein expressions of NR2A and NR2B of the subjects. Oral administration of ibuprofen and nimesulide for 8 weeks showed no impairment but partly improved spatial memory. PMID:24523767

  4. 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.

  5. Interaction between enoxacin, a new antimicrobial, and nimesulide, a new non-steroidal anti-inflammatory agent in mice.

    PubMed

    Taniguchi, Y; Deguchi, Y; Noda, K

    1996-08-01

    Convulsions induced by the combination of enoxacin, a new antimicrobial, and nonsteroidal anti-inflammatory drugs including nimesulide, ketoprofen, pranoprofen and loxoprofen sodium, were investigated in mice. The oral administration of nimesulide alone induced clonic convulsions at more than 300 mg/kg. The oral administration of ketoprofen, pranoprofen or loxoprofen sodium induced no convulsion up to 1000 mg/kg, 500 mg/kg and 600 mg/kg, respectively, and that of enoxacin induced no convulsion at more than 5000 mg/kg. The combination of nimesulide at 200 mg/kg and enoxacin at 400 mg/kg induced no convulsion. In contrast, the combination of enoxacin at 100 mg/kg and either ketoprofen at 125 mg/kg or pranoprofen at 500 mg/kg induced clonic convulsions, while that of enoxacin at 400 mg/kg and loxoprofen sodium at 600 mg/kg induced no convulsion. These results suggest that the combination of nimesulide and enoxacin may possibly induce few or less convulsions in the clinical setting.

  6. Effect of caffeine, norfloxacin and nimesulide on heartbeat and VEGF expression of zebrafish larvae.

    PubMed

    Chakraborty, Chiranjib; Hsu, C H; Wen, Z H; Lin, C S; Agoramoorthy, Govindasamy

    2011-03-01

    The use of pharmaceuticals during pregnancy may causes abnormalities to the embryo. Sometime the drug also effect to the new born if the drug transferred through lactation. We have used zebrafish model to see the effect of some pharmaceuticals on embryos and larvae. Three drugs, caffeine, norfloxacin and nimesulide, were used for this study to see the effect mainly the hatching rate of eggs, heart beat rate and the vascular endothelial growth factor (VEGF) expression of the larvae. VEGF is an important signaling protein that involved generating the new blood vessels during embryonic development. We have used 10, 20, 50, 100 microg ml(-1) concentrations of all the drugs to see the effect. No significant mortality or malformations were observed in zebrafish embryos. Hatching was stared from 60 hr. In control group, 91% hatching rate was observed. Lowest hatching rate was observed using highest concentration of norfloxacin (100 microg ml(-1)) and nimesulide (100 microg ml(-1)) i.e. 55 and 56% respectively. In control group, 110 to 115 heart beat rate was counted per minute. Significantly higher heart beat was observed in caffeine treated group which is 125 to 140 min(-1) Lower heart beat was noted in nimesulide treated group which is 100 min(-1). We have tried to observe the possible effect of VEGF of the larvae by these three drugs. Expression of VEGF was very low in caffeine treated group. Almost no VGF expression was observe in 100 microg ml(-1) caffeine treated group. These studies suggest that there is a possibility that high dosage of caffeine can harm the unborn baby or new born babies, if the mothers use caffeine.

  7. 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

  8. [Pathogenesis and prevention tactics of aspirin resistance].

    PubMed

    Zhang, Ren-gang; Zhang, Jun-ping

    2007-05-01

    Aspirin (acetylsalicylic acid) is a nonsteroidal anti-inflammatory drug. Despite its wide uses for more than 100 years, knowledge about mechanism of action and therapeutic issues of aspirin are still under discussion. The use of aspirin has been changed from an analgesic, anti-pyretic and anti-inflammatory agent to an anti-thrombotic agent, especially in secondary prevention of cardiovascular events. Aspirin has reduced the risk of cardiovascular events by 25%. However, the phenomenon of "aspirin resistance" has been described that in 5%-60% of patients aspirin may not achieve adequate efficacy of suppressing platelet activity. The convinced causes of this phenomenon are still unknown. It is probably due to drugs interaction, inadequate dosage and so on. By far the existing studies of aspirin are insufficient to explain all phenomena of aspirin resistance. And the results are not always uniform about the same research. Therefore, the characteristics in different population with aspirin resistance may account for the complexity. It is unrealistic to elucidate all aspirin resistance by only one pathway. More studies are required to investigate the mechanisms in different population respectively. According to the theory of traditional Chinese medicine and the trait of cardiovascular disease, which often relapses and has a long history, aspirin resistance should be considered as collaterals disease. It can be treated with aspirin and traditional Chinese drugs which have the power to strengthen body resistance, reduce phlegm, remove blood stasis and toxic materials from meridians. The problem of aspirin resistance might be solved by this way, because the traditional Chinese medicine has the superiority of selecting appropriate therapeutic methods based on syndrome differentiation for different population and regulating the whole body's function. Subsequently, cardiovascular disease might be effectively prevented. PMID:17498483

  9. 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.

  10. [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.

  11. Aspirin, paracetamol, and haematemesis and melaena.

    PubMed Central

    Coggon, D; Langman, M J; Spiegelhalter, D

    1982-01-01

    Aspirin and paracetamol consumption have been compared in 346 matched pairs of patients with haematemesis and melaena, and control individuals in the general community. Both aspirin and paracetamol intake were more common in patients than in controls, but the association for aspirin was stronger and was apparent with both recent and habitual intake, whereas for paracetamol the association was not detectable for habitual intake. The results for paracetamol suggests that patients with bleeding take analgesic drugs in part because of symptoms associated with bleeding, and such intake is not necessarily causal of bleeding. Failure to control investigations to take account of this point has exaggerated the possible risks of aspirin consumption. PMID:7076011

  12. Immunomodulatory treatments for aspirin exacerbated respiratory disease

    PubMed Central

    Moebus, Rachel G.

    2012-01-01

    Background: Aspirin triad is a subclass of chronic sinusitis characterized by nasal polyposis, nonallergic induced asthma, and aspirin sensitivity. Also known as Samter's triad or aspirin-exacerbated respiratory disease, aspirin triad commonly affects the adult population and is seldom found in pediatric patients. Methods: This rhinosinusitis has multiple layers of pathological process, but the ultimate predicament is caused by cysteinyl leukotrienes (cysLTs). Results: Pharmacotherapies include oral steroid, lipoxygenase inhibitor, and cysLT receptor inhibitor drugs, which can provide some relief for these patients. Conclusion: Immunomodulation via aspirin desensitization is considered when pharmacotherapy has failed. When aspirin triad is unmanageable with medical treatment alone, endoscopic sinus surgery with polypectomy can alleviate the patient's symptoms, allowing for a better response to postoperative medical management such as topical medication as well as delivery of topical medications. PMID:22487291

  13. 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)...

  14. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c)...

  15. 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)...

  16. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c)...

  17. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c)...

  18. 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.

  19. 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.

  20. Aspirin Exacerbated Respiratory Disease.

    PubMed

    Fruth, Kai; Gosepath, Jan

    2016-01-01

    Aspirin exacerbated respiratory disease (AERD) has been defined as a non-steroidal anti-inflammatory drug (NSAID)-triggered hypersensitivity, non-allergic bronchial asthma and chronic rhinosinusitis (CRS) with nasal polyps. The underlying pathophysiology of AERD is not completely understood so far. An altered arachidonic acid metabolism and dysregulated enzyme activity are regarded to be causal. AERD is characterized by recalcitrant CRS with recurrent nasal polyps after sinus surgery, accompanied by difficult to treat bronchial asthma and adverse reaction after NSAID ingestion such as nasal blockage, itching, laryngospasm and severe asthma attacks. Affected individuals suffer from poor quality of life. Besides functional endoscopic sinus surgery, the application of topical and systemic steroids and symptomatic therapy, aspirin desensitization is the only causative treatment option. The diagnostic approach to AERD, the ideal desensitization protocol and especially the following daily maintenance dose is part of an ongoing debate. This article summarizes the current knowledge about the pathophysiology, focuses on modern diagnostic approaches of AERD and discusses various aspirin desensitization protocols with respect to efficacy as well as to undesirable side effects. PMID:27466843

  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. 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.

  3. A brief review on the mechanisms of aspirin resistance.

    PubMed

    Du, Gang; Lin, Qiang; Wang, Jinhua

    2016-10-01

    Aspirin is the most widely prescribed drug for the primary and secondary prevention of cardiovascular and cerebrovascular diseases. However, a large number of patients continue to experience thromboembolic events despite aspirin therapy, a phenomenon referred to as aspirin resistance or treatment failure. Aspirin resistance is often observed along with a high incidence of unstable plaque, cardiovascular events and cerebrovascular accident. Studies have shown that aspirin reduces the production of TXA2, but not totally inhibits the activation of platelets. In this review, we analyze current and past research on aspirin resistance, presenting important summaries of results regarding the potential contributive roles of single nucleotide polymorphisms, inflammation, metabolic syndrome and miRNAs. The aim of this article is to provide a brief review on aspirin resistance and platelet function, which will provide important insights into the research of aspirin resistance. PMID:27372038

  4. 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. PMID:26234512

  5. 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...

  6. Aspirin and colorectal cancer: the promise of precision chemoprevention.

    PubMed

    Drew, David A; Cao, Yin; Chan, Andrew T

    2016-03-01

    Aspirin (acetylsalicylic acid) has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis. Several decades of research have provided considerable evidence demonstrating its potential for the prevention of cancer, particularly colorectal cancer. Broader clinical recommendations for aspirin-based chemoprevention strategies have recently been established; however, given the known hazards of long-term aspirin use, larger-scale adoption of an aspirin chemoprevention strategy is likely to require improved identification of individuals for whom the protective benefits outweigh the harms. Such a precision medicine approach may emerge through further clarification of aspirin's mechanism of action. PMID:26868177

  7. Pharmacogenetics of the antiplatelet effect of aspirin.

    PubMed

    Würtz, Morten; Kristensen, Steen Dalby; Hvas, Anne-Mette; Grove, Erik Lerkevang

    2012-01-01

    The concept of "pharmacogenetics" addresses genetically determined variation in how individuals respond to drugs. Accordingly, specific genetic variants have been suggested as contributors to a reduced response to various antiplatelet drugs. Aspirin is a cornerstone in secondary cardiovascular prevention and has been thoroughly investigated. The efficacy of aspirin is well documented, although with considerable interindividual variation. According to meta-analyses, a reduced antiplatelet effect of aspirin confers an increased risk of cardiovascular events. The platelet response to aspirin is assessed by in vitro evaluation of thromboxane-dependent platelet function. A reduced antiplatelet effect of aspirin can be explained by several mechanisms, which are largely determined by clinical, pharmacodynamic, biological and genetic factors. During the past decade, numerous studies have identified genetic polymorphisms significantly associated with cardiovascular events and modulating the antiplatelet effect of aspirin. However, results have been contradictory allowing only few firm conclusions to be drawn. Polymorphisms in genes encoding glycoproteins (IIb/IIIa, Ia/IIa, VI and Ibα), cyclooxygenases (1 and 2), adenosine diphosphate receptors (P2Y1 and P2Y12) and proteins of importance for haemostasis (thromboxane A2 receptor, coagulation factor XIII, etc.) have been investigated. In particular, a polymorphism in the gene encoding glycoprotein IIb/IIIa has been associated with a reduced antiplatelet effect of aspirin. The additive value of an individual's genetic makeup in predicting the antiplatelet effect of aspirin and the risk of cardiovascular events remains controversial. The present review outlines the pharmacology of aspirin and provides an overview of specific genetic variations considered to influence the antiplatelet effect of aspirin.

  8. 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 ...

  9. 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…

  10. [Aspirin suppresses microsatellite instability].

    PubMed

    Wallinger, S; Dietmaier, W; Beyser, K; Bocker, T; Hofstädter, F; Fishel, R; Rüschoff, J

    1999-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit cancer preventive effects and have been shown to induce regression of adenomas in FAP patients. In order to elucidate the probable underlying mechanism, the effect of NSAIDs on mismatch repair related microsatellite instability was investigated. Six colorectal cancer cell lines all but one deficient for human mismatch repair (MMR) genes were examined for microsatellite instability (MSI) prior and after treatment with Aspirin or Sulindac. For rapid in vitro analysis of MSI a microcloning assay was developed by combining Laser microdissection and random (PEP-) PCR prior to specific MSI-PCR. Effects of NSAIDs on cell cycle and apoptosis were systematically investigated by using flow cytometry and cell-sorting. MSI frequency in cells deficient of MMR genes (hMSH2, hMLH1, hMSH6) was markedly reduced after long-term (> 10 weeks) NSAID treatment. This effect was reversible, time- and concentration dependent. However, in the hPMS2 deficient endometrial cancer cell line (HEC-1-A) the MSI phenotype kept unchanged. According to cell sorting, non-apoptotic cells were stable and apoptotic cells were unstable. These results suggest that aspirin/sulindac induces a genetic selection for microsatellite stability in a subset of MMR-deficient cells and may thus provide an effective prophylactic therapy for HNPCC related colorectal carcinomas.

  11. 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.

  12. Does aspirin use make it harder to collect seizures during elective video-EEG telemetry?

    PubMed

    Godfred, Rachel M; Parikh, Mihir S; Haltiner, Alan M; Caylor, Lisa M; Sepkuty, Jehuda P; Doherty, Michael J

    2013-04-01

    Aspirin has shown promise as an anticonvulsant drug in animal models. Whether aspirin alters seizure frequency in humans remains unstudied. We retrospectively looked at adults with focal onset epilepsy who took aspirin daily while undergoing elective video-EEG monitoring and compared them with similar age- and sex-matched controls to see if seizure frequencies were different between those two populations. Significantly fewer seizures were seen on day two of monitoring for patients on aspirin therapies. Higher aspirin doses were correlated with fewer seizures collected during the monitoring stay. Further prospective study is needed to determine whether aspirin affects more robust seizure control. PMID:23399946

  13. 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.

  14. 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.

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

    PubMed Central

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

    2014-01-01

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

  16. 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.

  17. Purine pathway implicated in mechanism of resistance to aspirin therapy: pharmacometabolomics-informed pharmacogenomics.

    PubMed

    Yerges-Armstrong, L M; Ellero-Simatos, S; Georgiades, A; Zhu, H; Lewis, J P; Horenstein, R B; Beitelshees, A L; Dane, A; Reijmers, T; Hankemeier, T; Fiehn, O; Shuldiner, A R; Kaddurah-Daouk, R

    2013-10-01

    Although 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 Heart Study. Many metabolites, including known aspirin catabolites, changed on exposure to aspirin, and pathway enrichment analysis identified purine metabolism as significantly affected by drug exposure. Furthermore, purines were associated with aspirin response, and poor responders had higher postaspirin adenosine and inosine levels than did good responders (n = 76; both P < 4 × 10(-3)). Using our established "pharmacometabolomics-informed pharmacogenomics" approach, we identified genetic variants in adenosine kinase 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

  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 and Cancer.

    PubMed

    Patrignani, Paola; Patrono, Carlo

    2016-08-30

    The place of aspirin in primary prevention remains controversial, with North American and European organizations issuing contradictory treatment guidelines. More recently, the U.S. Preventive Services Task Force recommended "initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years." This recommendation reflects increasing evidence for a chemopreventive effect of low-dose aspirin against colorectal (and other) cancer. The intent of this paper is to review the evidence supporting a chemopreventive effect of aspirin, discuss its potential mechanism(s) of action, and provide a conceptual framework for assessing current guidelines in the light of ongoing studies. PMID:27561771

  20. 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

  1. 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.

  2. 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. PMID:22057729

  3. Molecular targets of aspirin and cancer prevention.

    PubMed

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

    2014-07-01

    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

  4. 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. PMID:25789542

  5. 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.

  6. 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.

  7. Preparation and characterization of amorphous solid dispersions of nimesulide in cyclodextrin copolymers.

    PubMed

    Skiba, M; Skiba, M; Milon, N; Bounoure, F; Fessi, H

    2014-04-01

    A study to enhance the dissolution rate of nimesulide (NIM), a poorly water-soluble, non-steroidal anti-inflammatory drug, was carried out through developing new amorphous solid dispersions (ASD) based on soluble or insoluble water cyclodextrin copolymers (alpha-cyclodextrin, beta-cyclodextrin and y-cyclodextrin polymers) synthesized by direct melt polycondensation. Amorphous solid dispersions of NIM in cyclodextrin copolymers, obtained by solvent evaporation, were characterized by thermogravimetric analyzer (TGA), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and fourier transform-infrared spectroscopy (FT-IR). These analyses provided the existence of interactions between amorphous drug and its carrier. A burst release of more than 80% NIM within approximately 70 minutes was seen with soluble alpha-cyclodextrin polymers (poly-alpha-sol) and insoluble gamma-cyclodextrin polymers (poly-gamma-insol) where no significant differences were observed with the other copolymers. Mathematical kinetic models such as zero order, Higuchi and Korsmeyer-Peppas were used to evaluate the kinetic and mechanism of release of NIM from the different ASD compared to lactose reference matrix. The kinetic of release of NIM from different ASD followed a Higuchi model and the mechanism of release was explained by Korsmeyer-Peppas model in which a fickian diffusion for lactose and soluble beta-cyclodextrin polymers (poly-beta-sol) was observed. However, an anomalous non-Fickian transport was found for the other copolymers. PMID:24734689

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

    PubMed Central

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

    2008-01-01

    Background 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. Methods 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. Results Cells treated with NCX-4040 (25 μM) 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. Conclusion 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. PMID:18302761

  9. Aspirin, cyclooxygenase inhibition and colorectal cancer

    PubMed Central

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

    2014-01-01

    Colorectal cancer (CRC) is the third most common type of cancer worldwide. Screening measures are far from adequate and not widely available in resource-poor settings. Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC. Increasing evidence from epidemiological studies, randomized clinical trials and basic science supports the effectiveness of aspirin, as well as other non-steroidal anti-inflammatory drugs, for chemoprevention of several types of cancer, including CRC. This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality. The detectable benefit of daily low-dose aspirin (at least 75 mg), as used to prevent cardiovascular disease events, strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy. Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (about 20 minutes); nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses. PMID:24605250

  10. Aspirin, cyclooxygenase inhibition and colorectal cancer.

    PubMed

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

    2014-02-01

    Colorectal cancer (CRC) is the third most common type of cancer worldwide. Screening measures are far from adequate and not widely available in resource-poor settings. Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC. Increasing evidence from epidemiological studies, randomized clinical trials and basic science supports the effectiveness of aspirin, as well as other non-steroidal anti-inflammatory drugs, for chemoprevention of several types of cancer, including CRC. This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality. The detectable benefit of daily low-dose aspirin (at least 75 mg), as used to prevent cardiovascular disease events, strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy. Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (about 20 minutes); nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.

  11. 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.

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

    PubMed

    Kacprzak, Dorota; Pawliczak, Rafał

    2015-06-19

    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.

  13. 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

  14. Non-steroidal anti-inflammatory drug and aspirin use in relation to lung cancer risk among postmenopausal women

    PubMed Central

    Baik, Christina S; Brasky, Theodore M; Pettinger, Mary; Luo, Juhua; Gong, Zhihong; Wactawski-Wende, Jean; Prentice, Ross L

    2015-01-01

    Background Results from prospective studies suggest that non-steroidal anti-inflammatory drugs (NSAID) may decrease lung cancer risk; however, any protective effect appears to be most evident in men. Methods We evaluated the associations between NSAID use and lung cancer incidence in postmenopausal women in the Women’s Health Initiative (WHI) adjusting for female specific potential confounders such as hormone therapy in addition to smoking histories and other potential confounders. We identified 143,841 women from ages 50 to 79 and 1,902 centrally confirmed lung cancer cases were included in the analysis. We used Cox regression models to estimate hazard ratios and their 95% confidence intervals. Results Compared to non-use, regular NSAID use was not associated with overall lung cancer incidence (NSAID use >10 years HR 0.87, 95% CI 0.71–1.08, p-trend =0.13). No statistically significant associations were found when examined by histological subtypes and although there was a trend of decreased risk with longer duration of NSAID use in the adenocarcinoma subtype, this was not statistically significant (NSAID use >10 years HR 0.80, 95% CI 0.58–1.10, p trend = 0.07). Conclusion Our study did not show that NSAID use is associated with lung cancer risk in women even after adjusting for female-specific confounders. There was a trend of decreased risk in the adenocarcinoma subtype; however, this was not statistically significant. Impact Future studies will need to take in account the various molecular subtypes of non-small cell lung cancer to further elucidate the role of NSAIDS in lung cancer, especially for the adenocarcinoma subtype. PMID:25670808

  15. Medications Containing Aspirin (Acetylsalicylate) and Aspirin-Like Products

    MedlinePlus

    ... This listing shows products containing aspirin or salicylate compounds. THIS IS NOT A COMPLETE LIST! Some medication ... and Aspirin Tablets Par Damason-P 5 Darvon Compound-65 9 Lily Disalcid Capsules and Tablets 3M ...

  16. 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). PMID:26205513

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. Twisted aspirin crystals.

    PubMed

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

    2013-03-01

    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. PMID:23425247

  3. 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.

  4. Aspirin sensitivity of platelet aggregation in diabetes mellitus.

    PubMed

    Albert, Stewart G; Hasnain, Bibi I; Ritter, Detlef G; Joist, J Heinrich; Mooradian, Arshag D

    2005-11-01

    Although aspirin is cardioprotective in high-risk populations, many with diabetes mellitus (DM) are unresponsive to these benefits. We questioned whether cardiovascular unresponsiveness might be demonstrated by lack of aspirin sensitivity to in vitro platelet functions especially in subjects with poorly controlled diabetes. Six women and 4 men (48+/-8 years [mean+/-S.D.]), selected for poor control (glycohemoglobin 11.9+/-2.2%) and 10 sex-age (+/-5 years) matched controls received 81 mg aspirin daily. There was a 2-week washout from aspirin and related drugs. After the aspirin dose on day-7, blood for platelet aggregation assays, and 24-h urine for 2,3 dinor thromboxane B2 (TxB2) and 2,3 dinor 6-keto (PGF1alpha) were obtained. Aspirin sensitivity was defined as inhibition (i.e., lower than expected) platelet aggregation after exposure to an agonist. Those with diabetes and controls were sensitive to aspirin inhibition of platelet aggregation induced by 1.6 mM arachidonic acid (9.5+/-3.9% versus 9.1+/-3.1%, normal range 40-100%) and by 0.83 microg/mL collagen (17.4+/-13.9% versus 13.2+/-9.3%, normal range 60-93%), respectively. Aspirin sensitivity to 2 microM ADP was present in five with diabetes and five controls. Urinary prostaglandin metabolites were suppressed below reference ranges, without differences between those with DM or controls for TxB2 (350+/-149 pg/mg versus 348+/-93 pg/mg creatinine) and PGF1alpha (255+/-104 pg/mg versus 222+/-88 pg/mg creatinine). In conclusion, in poorly controlled diabetes, there was no differential lack of aspirin sensitivity to platelet aggregation, or lack of aspirin suppression of urinary TxB2 or PGF1alpha, compared with controls on aspirin. Despite suppression of urinary prostaglandin metabolites, aspirin resistance was most apparent to ADP-mediated platelet aggregation. It is not known what level of inhibition of in vitro tests is necessary for the cardioprotective benefits of aspirin in diabetes mellitus. Thus, the lack of

  5. 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

  6. Aspirin failure in patients presenting with acute cerebrovascular ischaemia.

    PubMed

    Halawani, Saeed H M; Williams, David J P; Adefurin, Abiodun; Webster, John; Greaves, Michael; Ford, Isobel

    2011-08-01

    Aspirin is the most commonly used antiplatelet drug for prevention of ischaemic stroke. In order to determine the prevalence and nature of aspirin failure, we studied 51 adults admitted with suspected ischaemic stroke and already prescribed daily aspirin. Within 48 hours (h) of onset, blood and urine samples were collected to assess platelet aggregation, activation and aspirin response by a range of methods. All tests were then repeated on a second sample taken 24 h after witnessed administration of 75 mg or 150 mg aspirin. At entry to the study, incomplete response to aspirin, measured by arachidonic acid (AA)-stimulated platelet aggregation, was found in 43% of patients. Following in-hospital aspirin administration, there was a significant decrease in AA-aggregation (p=0.001) suggesting poor adherence to therapy prior to admission. However, residual aggregation (10-15%) persisted in 11 subjects - suggesting alternative causes. In incomplete responders on admission, platelet aggregation with adenosine diphosphate (ADP) was significantly higher compared with responders (p<0.05) but there were no significant differences in collagen aggregation, platelet fibrinogen binding or P-selectin expression, plasma von Willebrand factor, fibrinogen, high-sensitivity C-reactive protein, or the urinary metabolite, 11-dehydro-TxB2. Incomplete platelet inhibition is common around the time of acute cerebrovascular ischaemic events in patients prescribed aspirin. Up to 50% of these observations appear due to incomplete adherence to aspirin therapy. Intervention studies are required to determine the clinical relevance of measured platelet response to aspirin in terms of outcome, and the effectiveness of improved pharmacotherapy for stroke prevention. PMID:21544317

  7. [Milestones of cardivascular pharmacotherapy: salicylates and aspirin].

    PubMed

    Jerie, P

    2006-01-01

    The analgesic and antipyretic effect of the bark of willow has been known in Egypt and Greece for canturies. The modem era of salicylates starts with a letter sent 1758 by Reverend Edward Stone to The Royal Society in London. He described "an account of the success of the bark of willow in the cure of agues". His report. erroneously attributed to Edmond Stone. was published five years later. The active ingredient of willow bark. "salicine". was first isolated 1828 by Joseph Buchner, then by Henri Leroux, and also prepared from the oil of wintergreen (Gaultheria) and meadowsweet (Spirea ulmaria) by J. W. Lowig 1833. and called "Spirsäure", which was already pure acetylsalicylic acid. It was also synthetised 1853 by Ch. Gerhardt and finally 1897 in Bayer's laboratoires by Felix Hoffman, who also demonstrated its antiinflammatory efficacy. After two years of clinical trials with low doses, Bayer's management decided to start the productions and launched Aspirin as an analgetic worldwide in summer 1899. The first ASPIRIN ERA bagun. A completely new epoch started when J. N. Vane and Priscilla Piner demonstrated 1971 that the main mechanism of action of aspirin-like drugs is the inhibition of prostaglandin synthesis. In later studies the potency to inhibit platelet aggregation with small doses of aspirin (30-125 mg) was demonstrated. The Physicians'Health Study 1988 confirmed this effect: aspirin significantly reduced the risk of both, fatal and non-fatal myocardial infarction. and is now used in primary and secondary prevention of atherosclerosis. However the idea was not new: The use of salicylates and aspirin was throughly discussed more than 50 years ago: Paul C. Gibson published 1949 a well-documented case report on efficacy of aspirin in patients with angina, and Kl. Weber and P. Klein in Prague used Gibson's mixture successfully for patients with acute myocardial infarction (1951). Recently, the efficacy and security, the interactions and side-effects of low

  8. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26236481

  10. 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.

  11. 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.

  12. 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.

  13. Effect of Aspirin on Spinal Cord Injury: An Experimental Study.

    PubMed

    Kermani, Hamed Reihani; Nakhaee, Nouzar; Fatahian, Reza; Najar, Ahmad Gholamhosseinian

    2016-05-01

    Aspirin is an anti-inflammatory drug, peroxyl radical scavenger, and antioxidant agent that inhibits phospholipases, nitric oxide synthetases, and cyclooxygenase enzymes. The existing literature contains no studies on the effects of various doses of aspirin on spinal cord injury (SCI). Therefore, we sought to investigate the putative effects of aspirin on experimental SCI. The weight-drop injury model was used to produce SCI in 100 albino Wistar rats. The animals were allocated to five groups: a control group, where the rats did not undergo any surgical or medical intervention except for anesthesia; a sham-treated group, where laminectomy was performed without SCI and no further therapy was administered; and three other groups, where the rats with SCI received low-dose aspirin [20 mg/kg], high-dose aspirin [80 mg/kg], and a vehicle, respectively. Half of the rats were sacrificed 24 hours later, and their spinal cords were excised for biochemical studies. The other rats were subjected to Basso, Beattie, and Bresnahan (BBB) locomotor rating scale scoring once a week for 6 consecutive weeks. Aspirin decreased lipid peroxidation following SCI as the mean (± standard error) catalase level was significantly higher in the high-dose aspirin group (46.10±12.01) than in the sham-treated group (16.07±2.42) and the vehicle-treated group (15.31±3.20) (P<0.05; P<0.05, respectively). Both of the groups treated with high-dose and low-dose aspirin demonstrated a higher mean BBB score than did the control group (P<0.001) and the sham-treated group (P<0.001). Our data provide evidence in support of the potential effects of aspirin in biochemical and neurobehavioral recovery after SCI. PMID:27217606

  14. Effect of Aspirin on Spinal Cord Injury: An Experimental Study

    PubMed Central

    Kermani, Hamed Reihani; Nakhaee, Nouzar; Fatahian, Reza; Najar, Ahmad Gholamhosseinian

    2016-01-01

    Aspirin is an anti-inflammatory drug, peroxyl radical scavenger, and antioxidant agent that inhibits phospholipases, nitric oxide synthetases, and cyclooxygenase enzymes. The existing literature contains no studies on the effects of various doses of aspirin on spinal cord injury (SCI). Therefore, we sought to investigate the putative effects of aspirin on experimental SCI. The weight-drop injury model was used to produce SCI in 100 albino Wistar rats. The animals were allocated to five groups: a control group, where the rats did not undergo any surgical or medical intervention except for anesthesia; a sham-treated group, where laminectomy was performed without SCI and no further therapy was administered; and three other groups, where the rats with SCI received low-dose aspirin [20 mg/kg], high-dose aspirin [80 mg/kg], and a vehicle, respectively. Half of the rats were sacrificed 24 hours later, and their spinal cords were excised for biochemical studies. The other rats were subjected to Basso, Beattie, and Bresnahan (BBB) locomotor rating scale scoring once a week for 6 consecutive weeks. Aspirin decreased lipid peroxidation following SCI as the mean (± standard error) catalase level was significantly higher in the high-dose aspirin group (46.10±12.01) than in the sham-treated group (16.07±2.42) and the vehicle-treated group (15.31±3.20) (P<0.05; P<0.05, respectively). Both of the groups treated with high-dose and low-dose aspirin demonstrated a higher mean BBB score than did the control group (P<0.001) and the sham-treated group (P<0.001). Our data provide evidence in support of the potential effects of aspirin in biochemical and neurobehavioral recovery after SCI. PMID:27217606

  15. 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.

  16. 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

  17. New Chemometrics Mode Based on Adjacent Data Points’ Differences for the Simultaneous Determination of Clopidogrel, Atorvastatin, and Aspirin in their Combined Ternary Drug Formulation

    PubMed Central

    Nejem, R’afat Mahmoud; Issa, Mahmoud Mohamed; Shanab, Alaa Abu; Stefan-Van Staden, Raluca-Ioana; Aboul-Enein, Hassan Y.

    2014-01-01

    Abstract A new method is proposed for the analysis of a ternary mixture composed of clopidogrel, atorvastatin, and aspirin without prior separation steps. The method combines the advantages of the mean centering of ratio spectra and derivative spectrophotometric methods. It is based on using the difference between adjacent data points in the absorbance spectra. The principal advantage of this method is the use of absorbance data, and not derivative data; hence the signal-to-noise ratio is not diminished. The mathematical explanation of the procedure is illustrated. Beer’s law was valid in the concentration range 0.3–35 μg.mL-1 for CLOP, 0.5–30 μg.mL-1 for ATOR, and 1–40 μg.mL-1 for ASP. Mean recoveries were obtained as 100.2, 100.1, and 100.2% for CLOP, ATOR, and ASP, respectively, in the prepared synthetic mixtures. The method has been successfully applied to the simultaneous determination of ternary mixtures of aspirin, clopidogrel bisulphate, and atorvastatin calcium. The analytical characteristics of the method were calculated. The results showed that the new method is simple, rapid, accurate, and precise. PMID:25853071

  18. Physicochemical profile of nimesulide. Exploring the interplay of lipophilicity, solubility and ionization.

    PubMed

    Dellis, Demetris; Giaginis, Costas; Tsantili-Kakoulidou, Anna

    2007-05-01

    The lipophilicity and solubility profile of nimesulide was investigated over a broad pH range. Lipophilicity was assessed by direct partitioning experiments in the octanol-water system using the shake flask method, as well as by reversed-phase HPLC using methanol as organic modifier with or without addition of n-octanol. In the latter case the extrapolated retention factors logk(w) were considered as lipophilicity indices. The presence of n-octanol in the mobile phase proved to be a crucial factor for the establishment of a logk(w)/pH profile very similar to the logD/pH profile of nimesulide. Solubility was determined by the shake flask method using saturated buffer solutions. Both lipophilicity and solubility--pH profiles of nimesulide showed deviations from the theoretically expected behavior as dictated by the Henderson-Hasselbach equation and the usually recorded difference of 4 log units between the corresponding values of the neutral and ionized species in the case of a weak acid. As a consequence the lipophilicity and solubility profiles were found not to be mirror images of each other. However, the pK(a) value of nimesulide could be accurately calculated using part of both lipophilicity and solubility profiles since deviations affected mostly the values at increased ionization. PMID:17336024

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

    PubMed

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

    2015-08-01

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

  20. Two cases of oral aspirin overdose.

    PubMed

    Kato, Hideaki; Yoshimoto, Kanji; Ikegaya, Hiroshi

    2010-07-01

    A 30-year-old woman and a 27-year-old man were found in a parked car after the man had telephoned his father to tell him of their suicide attempt. In spite of emergent hospitalization and intensive care, the woman died. Due to the possibility of his assisting her suicide, medicolegal autopsy and toxicological analysis were performed. On forensic autopsy, no external injuries or pathological findings were detected. The man recovered after 5 days of hospitalization. In spite of a negative toxicological screening test, the police investigation revealed that they may have taken 120 tablets (330 mg/tablet; 39,600 mg total dose) of aspirin (acetylsalicylic acid) orally; therefore, we analyzed the concentrations of acetylsalicylic acid and two kinds of metabolite in specimens obtained at autopsy and on emergent hospitalization using high performance liquid chromatography. Acetylsalicylic acid and/or the two metabolites were found in the woman's specimens. These substances were also present in the man's specimens. It is still unclear why the man survived in spite of what appeared to be a fatal aspirin overdose. It was very straightforward to diagnose aspirin poisoning in these cases; however, we have to be aware of poisoning by drugs which are not included in simple drug screening examinations. PMID:20569957

  1. Aspirin Often Wrongly Prescribed for Atrial Fibrillation

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159459.html Aspirin Often Wrongly Prescribed for Atrial Fibrillation Blood thinners -- not aspirin -- dramatically cut the risk of stroke, researchers say ...

  2. 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.

  3. 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.

  4. 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

  5. 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…

  6. 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...

  7. Endobronchial biopsies on aspirin and prasugrel.

    PubMed

    Harris, Kassem; Kebbe, Jad

    2015-06-01

    Patients are generally required to stop antiplatelet therapy prior to elective invasive procedures. Some patients receive dual antiplatelet therapy for recent vascular procedures such as drug-eluting coronary stenting, and early discontinuation of antiplatelet agents could lead to a significant risk of stent thrombosis. Most bronchoscopic procedures are performed on patients using Aspirin but not on those using Clopidogrel or Prasugrel. In this report, we describe a unique case of a patient with a recent placement of drug-eluting stents, who required endobronchial biopsies for evaluation of lung cancer recurrence. The procedure was performed successfully and safely with no complications. PMID:25697386

  8. Can We Select Patients for Colorectal Cancer Prevention with Aspirin?

    PubMed

    Kraus, Sarah; Sion, Daniel; Arber, Nadir

    2015-01-01

    Aspirin has been extensively investigated in the context of the prevention of cardiovascular disease. It has one of the strongest cumulative evidence supporting its use in colorectal cancer (CRC) chemoprevention. Epidemiological, clinical, and observational studies have demonstrated that aspirin and non-steroidal antiinflammatory drugs (NSAIDs), including COX-2 inhibitors, can protect against CRC and significantly reduce its incidence. Moreover, prospective randomized controlled trials of colorectal polyp recurrence and in patients with hereditary CRC syndromes have shown that aspirin can produce regression of existing colorectal adenomas and prevent the formation of new polyps. However, the lowest effective doses, treatment duration, target populations, and the effects on survival are not entirely clear. Although not common serious side effects and in particular gastrointestinal and intracerebral hemorrhage do occur, better selection of individuals who might benefit the most from aspirin use must be carefully performed in order to maximize their risk/benefit ratio. In the era of precision medicine, genetic information, blood and/or urinary biomarkers, could potentially help in tailoring chemopreventive therapeutic strategies, based on aspirin use, while limiting adverse toxic effects. The current review will cover the use of aspirin for the prevention of colorectal adenomas and CRC, potential markers for chemoprevention, and patient stratification. PMID:26369678

  9. 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.

  10. [Physiopathology of aspirin intolerant asthma].

    PubMed

    Carsin, A; Bienvenu, J; Pacheco, Y; Devouassoux, G

    2012-02-01

    Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in individuals with asthma following the ingestion of aspirin. AERD affects up to 20 % of adults with asthma. At present, no reliable in vitro test is available to confirm the diagnosis. The confirmation of the diagnosis of AERD therefore depends on the response to challenge testing with aspirin. The pathogenesis of AERD is linked to abnormalities in arachidonic acid metabolism. Prior to exposure to aspirin, respiratory mucosal inflammation is the result of a cell infiltration, an overproduction of leukotrienes, prostaglandins D2, 5-oxo-eicosatetraenoic acid and an underproduction of lipoxins. After aspirin ingestion, patients with AERD synthesize excessive amounts of cysteinyl leukotrienes and prostaglandin metabolites involved in bronchoconstriction. New hypotheses concerning AERD pathogenesis have been added to the initial cyclooxygenase theory. These propose that AERD may be linked to the complement system, adenosine metabolism or angiotensin converting enzyme gene and IgE receptor gene polymorphisms. PMID:22405107

  11. Antiplatelet effect of aspirin in patients with coronary artery disease.

    PubMed

    Grove, Erik Lerkevang

    2012-09-01

    Cardiovascular disease is the number one cause of death globally, and atherothrombosis is the underlying cause of most cardiovascular events. Several studies have shown that antiplatelet therapy, including aspirin (acetylsalicylic acid), reduces the risk of cardiovascular events and death. However, it is well-known that many patients experience cardiovascular events despite treatment with aspirin, often termed "aspirin low-responsiveness". This fact has caused considerable debate: does biochemical aspirin low-responsiveness have prognostic value? Can low-responders be reliably identified? And if so, should antithrombotic treatment be changed? Is the whole discussion of antiplatelet drug response merely a result of low compliance? Compliance should be carefully optimised, before evaluating the pharmacological effect of a drug. It is well-known that cardiovascular disease is multifactorial, and, therefore, total risk reduction is not feasible. Aetiological factors to the variable platelet inhibition by aspirin seem to include genetic factors, pharmacological interactions, smoking, diabetes mellitus, and increased platelet turnover. It is a captivating thought that antiplatelet therapy may be improved by individually tailored therapy based on platelet function testing. Ongoing studies are challenging the current one-size-fits-all dosing strategy, but the preceding evaluation of platelet function assays has not been adequate. The overall objective of this thesis was to evaluate the reproducibility of and aggreement between a number of widely used platelet function tests and to explore the importance of platelet turnover for the antiplatelet effect of aspirin in patients with coronary artery disease. In the intervention studies (studies 1, 3, and 4), optimal compliance was confirmed by measurements of serum thromboxane, which is the most sensitive assay to confirm compliance with aspirin. In study 1, platelet function tests widely used to measure the antiplatelet effect

  12. 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. PMID:26548565

  13. 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. PMID:22526472

  14. 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

  15. 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

  16. Aspirin inhibits androgen response to chorionic gonadotropin in humans.

    PubMed

    Conte, D; Romanelli, F; Fillo, S; Guidetti, L; Isidori, A; Franceschi, F; Latini, M; di Luigi, L

    1999-12-01

    Eicosanoids play an important role in the regulation of the hypothalamic-pituitary axis; less clear is their role in testicular steroidogenesis. To evaluate the involvement of cyclooxygenase metabolites, such as prostaglandins, in the regulation of human testicular steroidogenesis, we examined the effects of a prostaglandin-blocker, aspirin, on plasma testosterone, pregnenolone, progesterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol response to human chorionic gonadotropin (hCG) in normal male volunteers in a placebo-controlled, single-blinded study. To test the efficacy of aspirin, seminal prostaglandin E(2) levels were also determined. hCG stimulation increased peripheral levels of testosterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol, without affecting circulating pregnenolone and progesterone values. Aspirin significantly lowered seminal prostaglandin E(2) levels, whereas it did not modify steroid concentrations not exposed to exogenous hCG. Moreover, the drug significantly reduced the response of testosterone, 17OH-progesterone, androstenedione, and dehydroepiandrosterone to hCG, as assessed by the mean integrated area under the curve, whereas it did not influence 17beta-estradiol response. In conclusion, aspirin treatment inhibits androgen response to chorionic gonadotropin stimulation in normal humans. The action of aspirin is probably mediated via an effective arachidonate cyclooxygenase block.

  17. Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.

    PubMed

    Ellero-Simatos, S; Lewis, J P; Georgiades, A; Yerges-Armstrong, L M; Beitelshees, A L; Horenstein, R B; Dane, A; Harms, A C; Ramaker, R; Vreeken, R J; Perry, C G; Zhu, H; Sànchez, C L; Kuhn, C; Ortel, T L; Shuldiner, A R; Hankemeier, T; Kaddurah-Daouk, R

    2014-01-01

    While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways implicated in variation of response to treatment. We profiled serum samples from healthy subjects pre- and postaspirin (14 days, 81 mg/day) using mass spectrometry. We established a strong signature of aspirin exposure independent of response (15/34 metabolites changed). In our discovery (N = 80) and replication (N = 125) cohorts, higher serotonin levels pre- and postaspirin correlated with high, postaspirin, collagen-induced platelet aggregation. In a third cohort, platelets from subjects with the highest levels of serotonin preaspirin retained higher reactivity after incubation with aspirin than platelets from subjects with the lowest serotonin levels preaspirin (72 ± 8 vs. 61 ± 11%, P = 0.02, N = 20). Finally, ex vivo, serotonin strongly increased platelet reactivity after platelet incubation with aspirin (+20%, P = 4.9 × 10(-4), N = 12). These results suggest that serotonin is implicated in aspirin response variability. PMID:25029353

  18. Development of Poly Unsaturated Fatty Acid Derivatives of Aspirin for Inhibition of Platelet Function.

    PubMed

    Roy, Jahnabi; Adili, Reheman; Kulmacz, Richard; Holinstat, Michael; Das, Aditi

    2016-10-01

    The inhibition of platelet aggregation is key to preventing conditions such as myocardial infarction and ischemic stroke. Aspirin is the most widely used drug to inhibit platelet aggregation. Aspirin absorption can be improved further to increase its permeability across biologic membranes via esterification or converting the carboxylic acid to an anhydride. There are several reports indicating that ω-3 and ω-6 fatty acids such as linoleic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) separately inhibit platelet aggregation. Herein, we synthesize anhydride conjugates of aspirin with linoleic acid, EPA, and DHA to form aspirin anhydrides that are expected to have higher permeability across cellular membranes. These aspirin-fatty acid anhydrides inhibited platelet aggregation in washed human platelets and platelet-rich plasma in a dose-dependent manner. In particular, the aspirin-DHA anhydride displayed similar effectiveness to aspirin. Platelet aggregation studies conducted in the presence of various platelet agonists indicated that the aspirin-lipid conjugates act through inhibition of the cyclooxygenase (COX)-thromboxane synthase (TXAS) pathway. Hence, we performed detailed biochemical studies using purified COX-1 as well as TXAS stabilized in nanoscale lipid bilayers of nanodiscs to confirm results from the platelet aggregation studies. We show that although all of the aspirin conjugates act through the COX-TXAS pathway by inhibiting COX-1, the parent fatty acids do not act via this pathway. Finally, we studied the hydrolysis of these compounds in buffer and human plasma, and we demonstrate that all of the aspirin-fatty acid conjugates hydrolyze to the parent molecules aspirin and fatty acid in a controlled manner. PMID:27488919

  19. 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

  20. A comparison of nimesulide and paracetamol in the treatment of fever due to inflammatory diseases of the upper respiratory tract in children.

    PubMed

    Polidori, G; Titti, G; Pieragostini, P; Comito, A; Scaricabarozzi, I

    1993-01-01

    The efficacy and tolerability of nimesulide were compared with those of paracetamol in a nonblind randomised study that recruited 110 children (64 males, 46 females; aged 3 to 6 years) with inflammation of the upper respiratory tract and fever. Nimesulide suspension (1.5 mg/kg 3 times daily) or paracetamol syrup (10 mg/kg 4 times daily) were administered orally until fever resolved. Body temperature was recorded and local pain and general discomfort assessed. Three patients treated with nimesulide and 6 patients treated with paracetamol withdrew from the study as a result of adverse events, and 1 paracetamol-treated patient discontinued because of a requirement for therapy with steroids. Nimesulide was as effective as paracetamol in reducing fever, local pain, and general discomfort. Nimesulide therefore appears to be at least as effective as paracetamol in terms of antipyretic and anti-inflammatory activity in children with inflammation of the upper respiratory tract and fever. PMID:7506180

  1. 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

  2. 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). PMID:24211052

  3. Nimesulide Silver Metallodrugs, Containing the Mitochondriotropic, Triaryl Derivatives of Pnictogen; Anticancer Activity against Human Breast Cancer Cells.

    PubMed

    Banti, Christina N; Papatriantafyllopoulou, Constantina; Manoli, Maria; Tasiopoulos, Anastasios J; Hadjikakou, Sotiris K

    2016-09-01

    Novel silver(I) metallo-drugs of the nonsteroidal anti-inflammatory drug nimesulide (nim) and the mitochondriotropic triaryl derivatives of pnictogen ligands (tpE, E = P (tpp, tptp, or totp), As (tpAs), Sb (tpSb)) with the formulas {[Ag(nim) (tpp)2]DMF} (1), [Ag(nim) (tptp)2] (2), [Ag(nim) (totp)] (3), [Ag(nim) (tpAs)2] (4), and [Ag(nim) (tpSb)3] (5) ((tpp = triphenyphosphine, tptp = tri(p-tolyl)phosphine, totp = tri(o-tolyl)phosphine, tpAs = triphenylarsine, tpSb = triphenylantimony, and DMF = dimethylformamide) were synthesized and characterized by melting point, vibrational spectroscopy (mid-Fourier transform IR), (1)H NMR, UV-visible spectroscopic techniques, and X-ray crystallography. The in vitro cytotoxic activity of 1-5 against human breast adenocarcinoma cancer cell lines: MCF-7 (estrogen receptor (ER) positive) and MDA-MB-231 (ER negative) was determined. The genotoxicity on normal human fetal lung fibroblast cells (MRC-5) caused by 1-5 was evaluated by fluorescence microscopy. The absence of micronucleus in MRC-5 cells confirms the in vitro non toxicity behavior of the compounds. Because of the morphology of the cells, an apoptotic pathway was concluded for the cell death. The apoptotic pathway, especially though the mitochondrion damage, was confirmed by DNA fragmentation, cell cycle arrest, and permeabilization of the mitochondrial membrane tests. The molecular mechanism of action of 1-5 was further studied by (i) the binding affinity of 1-5 toward the calf thymus (CT) DNA, (ii) the inhibitory activity of 1-5 against lipoxygenase (an enzyme that oxidizes polyunsaturated fatty acids to leukotrienes or prostaglandins), and (iii) the catalytic activity of 1-5 on the oxidation of linoleic acid (an acid that partakes in membrane fluidity, membrane enzyme activities, etc.) to hyperoxolinoleic acid by oxygen. PMID:27513311

  4. Aspirin and clopidogrel resistance: possible mechanisms and clinical relevance. Part II: Potential causes and laboratory tests.

    PubMed

    Vadász, Dávid; Sztriha, László K; Sas, Katalin; Vécsei, László

    2013-01-30

    Recent meta-analyses have indicated that patients with vascular disease demonstrated by laboratory tests to be aspirin or clopidogrel-resistant are at an increased risk of major vascular events. The suggested mechanisms of aspirin resistance include genetic polymorphism, alternative pathways of platelet activation, aspirin-insensitive thromboxane biosynthesis, drug interactions, or a low aspirin dose. Clopidogrel resistance is likely to develop as a result of a decreased bioavailability of the active metabolite, due to genetic variation or concomitant drug treatment. Additional work is required to improve and validate laboratory tests of platelet function, so that they may become useful tools for selection of the most appropriate antiplatelet therapy for an individual patient. Improvements in antiplatelet treatment strategies in the future should lead to a reduction in premature vascular events. PMID:23607225

  5. Comparative evaluation of antipyretic activity of ibuprofen and aspirin in children with pyrexia of varied aetiology.

    PubMed

    Kandoth, P W; Joshi, M K; Joshi, V R; Satoskar, R S

    1984-01-01

    The antipyretic activity of ibuprofen and aspirin was compared in sixteen children with pyrexia due to upper respiratory tract infection and in twelve with fever due to other causes. All 28 children received ibuprofen (7 mg/kg of body-weight) and aspirin (15 mg/kg of body-weight) in a single dose on 2 consecutive days in a crossover manner. Rectal temperature was recorded prior to and at regular intervals up to 8 hours after drug administration. Analysis of the results indicate that ibuprofen and aspirin effectively lower temperature and the two drugs are comparable in their antipyretic activity. In conclusion, significant antipyretic activity, good tolerance profile and availability in syrup form make ibuprofen a useful substitute for aspirin in children with fever. PMID:6500169

  6. 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.

  7. 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. PMID:27489545

  8. 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

  9. Double-blind study comparing the long-term efficacy of the COX-2 inhibitor nimesulide and naproxen in patients with osteoarthritis.

    PubMed

    Kriegel, W; Korff, K J; Ehrlich, J C; Lehnhardt, K; Macciocchi, A; Moresino, C; Pawlowski, C

    2001-10-01

    This double-blind one-year study compares the long-term efficacy and safety of nimesulide with naproxen in patients with osteoarthritis (OA) of the knee or hip. Patients were randomised to nimesulide 100 mg twice daily (n = 183) or naproxen 250 mg morning, 500 mg evening (n = 187). The primary efficacy variable was change in pain intensity (WOMAC A scale) at 6 months. Nimesulide tablets showed at least equivalent efficacy to naproxen tablets in reducing pain intensity at 6 and 12 months (nimesulide -22.5% at 6 and 12 months; naproxen -22.4% at 6 months, -19.9% at 12 months; non-inferiority proven). At 6 months the investigator assessed efficacy as 'good' or 'excellent' in 59.3% of nimesulide and 56.4% of naproxen-treated patients, with corresponding values for patient assessment of 57% and 52.7%. Both treatments were well tolerated, with fewer related gastrointestinal adverse events reported with nimesulide (77 cases, 47.5%) than with naproxen (96 cases, 54.5%). This study shows nimesulide to be as effective as naproxen in the long-term treatment of OA and to be associated with fewer gastrointestinal side-effects.

  10. Aspirin influences megakaryocytic gene expression leading to up-regulation of multidrug resistance protein-4 in human platelets

    PubMed Central

    Massimi, Isabella; Guerriero, Raffaella; Lotti, Lavinia Vittoria; Lulli, Valentina; Borgognone, Alessandra; Romani, Federico; Barillà, Francesco; Gaudio, Carlo; Gabbianelli, Marco; Frati, Luigi; Pulcinelli, Fabio M

    2014-01-01

    Aim The aim of the study was to investigate whether human megakaryocytic cells have an adaptive response to aspirin treatment, leading to an enhancement of multidrug resistance protein-4 (MRP4) expression in circulating platelets responsible for a reduced aspirin action. We recently found that platelet MRP4 overexpression has a role in reducing aspirin action in patients after by-pass surgery. Aspirin enhances MRP4-mRNA levels in rat liver and drug administration transcriptionally regulates MRP4 gene expression through peroxisome proliferator-activated receptor-α (PPARα). Methods The effects induced by aspirin or PPARα agonist (WY14643) on MRP4 modulation were evaluated in vitro in a human megakaryoblastic DAMI cell line, in megakaryocytes (MKs) and in platelets obtained from human haematopoietic progenitor cell (HPC) cultures, and in vivo platelets obtained from aspirin treated healthy volunteers (HV). Results In DAMI cells, aspirin and WY14643 treatment induced a significant increase in MRP4 and PPARα expression. In human MKs grown in the presence of either aspirin or WY14643, MRP4 and PPARα-mRNA were higher than in control cultures and derived platelets showed an enhancement in MRP4 protein expression. The ability of aspirin to modulate MRP4 expression in MKs and to transfer it to platelets was also confirmed in vivo. In fact, we found the highest MRP4 mRNA and protein expression in platelets obtained from HV after 15 days' aspirin treatment. Conclusions The present study provides evidence, for the first time, that aspirin treatment affects the platelet protein pattern through MK genomic modulation. This work represents an innovative and attractive approach, useful both to identify patients less sensitive to aspirin and to improve pharmacological treatment in cardiovascular high-risk patients. PMID:24902864

  11. [A case of aspirin-induced asthma which developed due to rubbing a lotion containing a non-steroidal anti-inflammatory drug, ketoprofen, on the skin].

    PubMed

    Tanaka, N; Kobayashi, H; Mitsufuji, H; Sato, T; Ogura, T; Takada, N; Abe, T; Tomita, T

    1994-04-01

    A forty-year-old woman was admitted to our hospital because of a severe attack of bronchial asthma. The asthmatic attack developed 3 hours after her rubbing a large amount of a lotion containing a non-steroidal anti-inflammatory drug (NSAID), ketoprofen, over her skin. The patient had a past history of asthmatic attack induced by another NSAID (Sedes-G) given per os. The previous asthmatic attack developed about 3 hours after her rubbing the lotion containing the NSAID over her skin. The relatively long interval between the per cutaneous NSAID administration and the onset of the asthmatic attack indicates that the time delay is dependent on the absorption route of the administered NSAID. The severity of the attack is considered to be related to the amount of NSAID absorbed.

  12. 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

  13. 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. PMID:25833406

  14. 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.

  15. 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.

  16. 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.

  17. Separation and determination of nimesulide related substances for quality control purposes by micellar electrokinetic chromatography.

    PubMed

    Zacharis, Constantinos K; Tzanavaras, Paraskevas D; Notou, Maria; Zotou, Anastasia; Themelis, Demetrius G

    2009-02-20

    A micellar electrokinetic chromatography (MEKC) method has been developed and validated for the determination of nimesulide related compounds in pharmaceutical formulations. Electrophoretic separation of six European Pharmacopoeia (EP) impurities (A-F) was performed using a fused silica capillary (L(eff.)=50 cm, L(tot.)=57 cm, 50 microm i.d.) with a background electrolyte (BGE) containing 25 mM borate buffer (pH 9.5), 30 mM sodium dodecyl sulphate and phi=3% (v/v) acetonitrile. The influence of several factors (surfactant and buffer concentration, pH, organic modifier, applied voltage, capillary temperature and injection time) was studied. The method was suitably validated with respect to linearity, limit of detection and quantification, accuracy, precision and selectivity. The calibration curves obtained for the six compounds were linear over the range 5-12 microgml(-1) (0.05-0.12%). The relative standard deviations (s(r)) of intra- and inter-day experiments were less than 5.0%. The detection limits ranged between 0.7 and 1.6 microgml(-1) depending on the impurity. The proposed method was applied successfully to the quantification of nimesulide impurities in its pharmaceutical formulation.

  18. Esophageal mucosal injury with low-dose aspirin and its prevention by rabeprazole.

    PubMed

    Sugimoto, Mitsushige; Nishino, Masafumi; Kodaira, Chise; Yamade, Mihoko; Ikuma, Mutsuhiro; Tanaka, Tatsuo; Sugimura, Haruhiko; Hishida, Akira; Furuta, Takahisa

    2010-03-01

    Aspirin is used widely as an antithrombotic drug for the prevention of cardiovascular and cerebrovascular events. Although aspirin increases the risk for gastrointestinal mucosal injury, the effect on esophageal mucosa is unclear. This study investigates whether aspirin induces esophageal mucosal injury and whether a proton-pump inhibitor can prevent such injury in relation to CYP2C19 genotypes. Fifteen healthy Japanese volunteers are dosed for 7 days in a 5-way randomly crossover trial: placebo, aspirin 100 mg, rabeprazole 10 mg, and aspirin 100 mg plus rabeprazole 10 mg either once daily or 4 times per day. All subjects undergo endoscopy and 24-hour intragastric pH monitoring on day 7. With the aspirin regimen, esophageal mucosal disorders occur in 7 patients (46.7%) (5, grade M; 2, grade A). The median 24-hour pH differs significantly among subjects who develop grade M or A gastroesophageal reflux disease and those who do not develop gastroesophageal reflux disease; the median pH in grade A gastroesophageal reflux disease is significantly lower (1.5 [range, 1.1-1.9]) than that in patients without gastroesophageal reflux disease (5.6 [range, 0.8-8.4], P = .04). Rabeprazole significantly inhibits acid secretion irrespective of CYP2C19 genotypes and decreases the incidence of aspirin-related esophageal injury and symptoms according to increasing pH value. Aspirin induces esophageal mucosal injury in an acid-dependent manner. Concomitant proton-pump inhibitor therapy may prevent advanced effects of low-dose aspirin. PMID:19940233

  19. 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.

  20. 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. PMID:23285660

  1. 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. PMID:671247

  2. Effect of Opium Addiction on Aspirin Resistance in Stable Angina Pectoris

    PubMed Central

    Forood, Afsaneh; Malekpour-Afshar, Reza; Sarnevesht, Jamshid

    2014-01-01

    Background The rate of cardiovascular diseases in developing countries is approximately 60% and it is still has an increasing trend. The clinical effectiveness of aspirin in preventing cardiovascular events has been well proven. Although aspirin is an effective and inexpensive drug, its consumption is not equally beneficial for all patients. Many factors can be affective on the efficacy of antiplatelet drugs such as aspirin. Methods This study was carried out on 260 patients who had stable angina pectoris and coronary artery disease was approved by coronary angiography. Based on opium addiction, the patients were divided into two groups. Opium addiction was diagnosed base on Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. The mid-stream morning urinary sample were collected for measuring the urinary 11-dehydroxy thromboxane B2 level (UTXB2). Urinary level of UTXB2 was considered as an aspirin resistance index. Findings The mean age of patients was 57.3 ± 8.9; and 44.6% of them were females. The aspirin resistance rate was 41.5%. Significant difference in aspirin resistance was observed between the opium addicts and non-addicts. (51.5% vs. 31.5%) (P = 0.001). The effects of confounding variables such as diabetes, hypertension, and hyperlipidemia were eliminated by regression logistic multivariable analysis. Conclusion The prevalence of aspirin resistance in patients with stable angina pectoris was 41.5%. The prevalence of aspirin resistance in patients with stable angina pectoris who had opium addiction was significantly higher them non-addicts. PMID:25140212

  3. Talk with Your Doctor about Taking Aspirin Every Day

    MedlinePlus

    ... Talk with Your Doctor about Taking Aspirin Every Day Browse Sections The Basics Overview Benefits and Risks ... sure why this works. Can taking aspirin every day cause any side effects? Taking aspirin daily isn' ...

  4. Anti-platelet therapy and aspirin resistance - clinically and chemically relevant?

    PubMed

    Rafferty, M; Walters, M R; Dawson, J

    2010-01-01

    Platelets play a central role in the pathogenesis of the atherothrombosis which ultimately causes myocardial infarction, stroke and peripheral vascular disease. Commonly used oral anti-platelet drugs include aspirin (an irreversible inhibitor of cyclo-oxygenase), clopidogrel (an ADP receptor antagonist), other thienopyridines such as ticlopidine and prasgruel, and dipyridamole (an inhibitor of adenosine reuptake and platelet phosphodiesterase). Newer agents are in development and one, ticagrelor, a reversible ADP receptor antagonist has shown promise. Despite their proven benefit, recurrent vascular events still occur in those taking anti-platelet drugs. This has led to the concept of anti-platelet resistance, most commonly aspirin resistance as this drug is the cornerstone of most regimens. The causes of aspirin resistance are numerous but potential mechanisms include lack of patient adherence, non COX-1 mediated thromboxane A2 synthesis, increased activity of alternate platelet activation pathways, interference of aspirin action by other drugs and probably pharmacogenetic factors. Measurement of platelet response to aspirin is made possible using a number of in-vitro laboratory assays of platelet function which include measurement of thromboxane A2 metabolites as well as newer point-of-care assays of platelet aggregation. The phenomenon of aspirin resistance is important as it raises the possibility of developing strategies to identify those who respond best to a particular anti-platelet regimen, or to development of newer anti-platelet therapies to which more patients respond. This review discusses important aspects of aspirin resistance both in terms of clinical medicine, alternative anti-platelet strategies, and the potential to overcome its various causes. PMID:21062249

  5. 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.

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

    PubMed

    Pasero, G; Marson, P

    2010-01-01

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

  7. Aspirin resistance or variable response or both?

    PubMed

    Cheng, Xi; Chen, Wai-Hong; Simon, Daniel I

    2006-11-20

    Numerous clinical trials have demonstrated that aspirin is effective in secondary prevention and in high-risk primary prevention of adverse cardiovascular events. However, a constellation of clinical and laboratory evidence exists that demonstrates diminished or absent response to aspirin in some patients. This has led to the concept of "aspirin resistance," which is a poorly defined, somewhat misleading term. The mechanism for aspirin resistance has not been fully established, but it is almost certainly due to a combination of clinical, biological, and genetic properties affecting platelet function. There are no criteria for distinguishing true resistance from treatment failure, and there is no consensus on whether the definition of aspirin resistance should be based on clinical outcomes, laboratory evidence, or both. Studies in large populations are needed to define antiplatelet resistance using consistent and reproducible assays and correlate the measurements with clinical outcomes. One such prospective randomized trial is completed, and 2 others are under way: the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial compared clopidogrel and aspirin with placebo and aspirin for high-risk primary or secondary prevention, and the Aspirin Nonresponsiveness and Clopidogrel Endpoint Trial (ASCET) is evaluating whether switching to clopidogrel will be superior to continued aspirin therapy in improving clinical outcomes in aspirin-resistant patients with angiographically documented coronary artery disease. The Research Evaluation to Study Individuals Who Show Thromboxane or P2Y(12) Receptor Resistance (RESISTOR) trial is investigating whether modifying antiplatelet regimens could prevent myonecrosis after percutaneous coronary intervention in patients with aspirin and clopidogrel resistance. PMID:17097412

  8. Effects of aspirin on gastroduodenal permeability in alcoholics and controls.

    PubMed

    Farhadi, Ashkan; Keshavarzian, Ali; Kwasny, Mary J; Shaikh, Maliha; Fogg, Louis; Lau, Cynthia; Fields, Jeremy Z; Forsyth, Christopher B

    2010-08-01

    Alcohol and nonsteroidal anti-inflammatory drugs 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 5-12h after 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 1,300 mg aspirin twice, 12 and 1h 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=.003 and +2.25%, P=.011, respectively), but the magnitude of these increases was 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). Our data show that alcoholics

  9. 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

  10. 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.

  11. Extrabronchial symptoms and late phase reaction enhance the diagnostic value of aspirin bronchial challenge

    PubMed Central

    Zielińska-Wyderkiewicz, Ewa; Górski, Paweł; Kuna, Piotr

    2015-01-01

    Introduction Lysine aspirin (l-ASA) bronchial challenge can be used in the diagnostics of aspirin exacerbated respiratory disease. It is safer than oral challenge, however it is characterized by a lower sensitivity. Aim We sought to investigate whether additional indicators of the positive result of l-ASA bronchial challenge, i.e. late phase reaction (LPR) and extrabronchial symptoms (EBS), may enhance its diagnostic value. Material and methods Sixty-seven patients with a positive history of asthma exacerbated by aspirin and/or other non-steroidal inflammatory drugs underwent l-ASA bronchial challenge. The control groups comprised 15 aspirin tolerant asthmatics and 15 healthy subjects. Forced expiratory volume in 1 s (FEV1) and 24-hour peak expiratory flow (PEF) measurements were performed in all subjects in order to recognize early and late response to l-ASA. All subjects underwent oral ASA challenge 2 weeks after l-ASA bronchial challenge. Results Basing on FEV1 and PEF results, early reaction was present in 50.7% of patients, early and LPR in 29.9% and LPR in only 10.4% of aspirin exacerbated respiratory disease patients. The EBS were noted in 31.3% of subjects. Inclusion of LPR and EBS as positive criteria of the challenge increased sensitivity to 94.0%. Conclusions These results indicate that both LPR and EBS should be considered as positive criteria of aspirin bronchial challenge as they enhance its diagnostic value. PMID:26755906

  12. An evaluation of different doses of soluble aspirin and aspirin tablets in postoperative dental pain.

    PubMed Central

    Holland, I S; Seymour, R A; Ward-Booth, R P; Ord, R A; Lim, K L; Hoare, R C

    1988-01-01

    1. The efficacy of three different single doses (600, 900 and 1200 mg of soluble aspirin and aspirin tablets) was determined in a randomized placebo-controlled parallel study in 140 patients (70 females) with postoperative pain after removal of impacted third molars. 2. Patients treated with soluble aspirin 600 mg, 900 mg, 1200 mg and aspirin tablet 1200 mg reported significantly less pain (P less than 0.01) throughout the investigation period than those treated with placebo. 3. Overall pain scores after treatment with aspirin tablets 600 and 900 mg did not differ significantly from those after treatment with placebo (P greater than 0.05). 4. On a comparative dose basis, soluble aspirin was significantly more potent (P less than 0.05) than aspirin tablets. PMID:3190996

  13. Mechanisms of aspirin sensitivity.

    PubMed

    Picado, César

    2006-05-01

    In some asthma patients, nonsteroidal anti-inflammatory drugs (NSAIDs) induce bronchospasm, rhinorrhea, and nasal obstruction. NSAID-induced reactions appear to be caused by the inhibition of cyclooxygenase-1 (Cox-1); this in turn activates the lipoxygenase pathway, which eventually increases the release of cysteinyl leukotrienes (Cys-LTs) that induces bronchospasm and nasal obstruction. With regard to the metabolism of arachidonic acid (AA) in NSAID-intolerant asthmatic patients, the following changes have been observed: 1) A low production of prostaglandin E2, seemingly due to deficient Cox-2 regulation; 2) an increased expression of leukotriene-C4 synthase; and 3) a reduced production of metabolites (lipoxins) released through the transcellular metabolism of AA. NSAID-intolerant asthmatics have higher basal levels of Cys-LT than NSAID-tolerant asthmatics. Moreover, Cys-LT levels in NSAID-intolerant asthmatics increase remarkably following NSAID provocation testing. There has been no explanation to date that connects all these findings, although an anomaly in the regulation of Cox-2 is probably accountable. PMID:16579869

  14. Positive influence of aspirin on coronary endothelial function: Importance of the dose

    PubMed Central

    Teragawa, Hiroki; Mitsuba, Naoya; Ishibashi, Ken; Kurisu, Satoshi; Kihara, Yasuki

    2013-01-01

    AIM: To investigate the effects of different doses of aspirin on coronary endothelial function. METHODS: The study included 139 Japanese subjects (mean age, 60 years; 53 women) with angiographically normal coronary arteries. Patients were distributed into Group I (n = 63), who was administered aspirin and Group II (n = 76), the control, who were not administered aspirin. Group I was further divided into Group Ia (n = 50, low-dose aspirin, 100 mg) and Group Ib (n = 13, high-dose aspirin, 500 mg). After a routine coronary angiography, acetylcholine (ACh; 3 and 30 μg/min successively) and nitroglycerin (NTG) were infused into the left coronary ostium over 2 min. The change in the diameter of the coronary artery in response to each drug was expressed as the percentage change from baseline values. RESULTS: The patient characteristics did not differ between the two groups. The change in coronary diameter in response to ACh was greater in Group I than in Group II (P = 0.0043), although the NTG-induced coronary vasodilation was similar between groups. ACh-induced dilation was greater in Group Ia than in Group Ib (P = 0.0231). Multivariate regression analysis showed that a low-dose of aspirin (P = 0.0004) was one of the factors associated with ACh-induced dilation at 30 μg/min. CONCLUSION: In subjects with angiographically normal coronary arteries, aspirin only had a positive influence on coronary endothelial function at the low dose of 100 mg. This improvement of coronary endothelial function may be involved in the preventive effect of aspirin against future coronary events. PMID:24340141

  15. Aspirin to Zoloft: Ways Medicines Work

    MedlinePlus

    ... Aspirin to Zoloft: Ways Medicines Work Inside Life Science View All Articles | Inside Life Science Home Page Aspirin to Zoloft: Ways Medicines Work ... For Proteins, Form Shapes Function This Inside Life Science article also appears on LiveScience . Learn about related ...

  16. Aspirin-triggered metabolites of EFAs.

    PubMed

    Makriyannis, Alexandros; Nikas, Spyros P

    2011-10-28

    Aspirin triggers the biosynthesis of oxygenated metabolites from arachidonic, eicosapentaenoic, and docosahexaenoic (DHA) acids. In a preceding issue, Serhan et al. (2011) describe a novel aspirin-triggered DHA pathway for the biosynthesis of a potent anti-inflammatory and proresolving molecule. PMID:22035788

  17. Efficacy of nimesulide versus meloxicam in the control of pain, swelling and trismus following extraction of impacted lower third molar.

    PubMed

    De Menezes, S A F; Cury, P R

    2010-06-01

    This study compared the efficacy of nimesulide and meloxicam in the control of pain, swelling and trismus, following the extraction of impacted inferior third molars. Twenty patients with two impacted inferior third molars, in similar positions, were selected. The patients were designated randomly to the meloxicam group (MEL: 7.5mg twice a day for 5 days) or the nimesulide group (NIM: 100mg for 5 days). Following the extractions, swelling was more pronounced in the MEL group than in the NIM group (P0.05). At the 72-h evaluation, reduction was significantly larger in mouth opening in the MEL group compared with the NIM group (P<0.05). In conclusion, pain control was similar in both treatment groups. NIM was more effective than MEL in the control of swelling and trismus following the extraction of impacted lower third molars.

  18. 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. PMID:27127038

  19. 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.

  20. 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. PMID:26394025

  1. Inhibition by metoprolol of the antihypertensive effect of aspirin in young rats.

    PubMed

    Tuttle, R S; Banziger, V; Patel, S; Northrup, N

    1985-07-01

    A group of 21-day-old, spontaneous hypertensive rats (SHR) received either aspirin (75-100 mg/kg), metoprolol (1.0-1.5 mg/kg) or both in their drinking water for 56 days. Controls received plain water. Groups of normotensive Wistar-Kyoto rats (WKY) received the same drug treatment as did the SHR. Blood pressure, heart rate and body weight were determined weekly, and water consumption was monitored on a daily basis. Renal prostaglandin (PG) activities were determined in a separate group of rats at 7 and at 56 days on each protocol. Blood pressures in the SHRs remained in the range of the WKY during 56 days of treatment with aspirin or metoprolol, but increased to hypertensive levels after exposure to plain water. Blood pressures in the WKY receiving aspirin or metoprolol were also lower than those receiving plain water, but the antihypertensive effect was somewhat slower in onset. The antihypertensive effects of aspirin and of metoprolol were lost in the SHR but not in the WKY when both drugs were given simultaneously in the drinking water. In comparison to rats receiving plain water, renal PG activity (PGF1 alpha and PGF2 alpha) was lower in rats receiving aspirin, metoprolol or both together. The mechanism for the antihypertensive effect of aspirin in the young SHR may be related to a decline in renal PG content, or to the release of other hormones controlling water and electrolyte balance. Reports that the cyclooxygenase inhibitors, such as aspirin, can block the antihypertensive effect of the beta adrenoceptor antagonists is confirmed in chronic studies using the SHR model.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. 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. PMID:23246457

  3. 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.

  4. 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.

  5. 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. PMID:26826555

  6. Differences in Esterase Activity to Aspirin and p-Nitrophenyl Acetate among Human Serum Albumin Preparations.

    PubMed

    Tatsumi, Akitoshi; Okada, Masaya; Inagaki, Yoshihiro; Inoue, Sachiyo; Hamaguchi, Tsuneo; Iwakawa, Seigo

    2016-01-01

    Human serum albumin (HSA) has two major ligand-binding sites, sites I and II, and also hydrolyzes some compounds at both sites. In the present study, we investigated differences in esterase activity among HSA preparations, and also the effects of warfarin, indomethacin, and naproxen on the hydrolytic activities of HSA to aspirin and p-nitrophenyl acetate. The esterase activities of HSA to aspirin or p-nitrophenyl acetate were measured from the pseudo-first-order formation rate constant (kobs) of salicylic acid or p-nitrophenol by HSA. Inter-lot variations were observed in the esterase activities of HSA to aspirin and p-nitrophenyl acetate; however, the esterase activity of HSA to aspirin did not correlate with that to p-nitrophenyl acetate. The inhibitory effects of warfarin and indomethacin on the esterase activity of HSA to aspirin were stronger than that of naproxen. In contrast, the inhibitory effect of naproxen on the esterase activity of HSA to p-nitrophenyl acetate was stronger than those of warfarin and indomethacin. These results suggest that the administration of different commercial HSA preparations and the co-administration with site I or II high-affinity binding drugs may change the pharmacokinetic profiles of drugs that are hydrolyzed by HSA. PMID:27476944

  7. Management of low-dose aspirin and clopidogrel in clinical practice: a gastrointestinal perspective.

    PubMed

    Lanas, Angel; Gargallo, Carla J

    2015-06-01

    Low-dose aspirin, alone or combined with other antiplatelet agents, is increasingly prescribed for cardiovascular prevention. However, the cardiovascular benefits should be evaluated together with the gastrointestinal risks. Low-dose aspirin is associated with upper and lower gastrointestinal injury, although lower gastrointestinal effects are poorly characterized. This gastrointestinal risk differs among antiplatelets drugs users. The most important risk factors are history of peptic ulcer, older age, and concomitant use of non-steroidal anti-inflammatory drugs or dual antiplatelet therapy. Effective upper gastrointestinal prevention strategies are available and should be used in at-risk patients taking low-dose aspirin or clopidogrel. Proton pump inhibitors seem to be the best gastroprotective agents, whereas the benefits of Helicobacter pylori eradication are still unclear. Low-dose aspirin has additional effects in the gastrointestinal tract. A large body of evidence indicates that it can protect against different cancers, in particular colorectal cancer. This effect could modify the future indications for use of low-dose aspirin and the risk-benefit balance. PMID:25595209

  8. Aspirin, diabetes, and amyloid: re-examination of the inhibition of amyloid formation by aspirin and ketoprofen.

    PubMed

    Tu, Ling-Hsien; Noor, Harris; Cao, Ping; Raleigh, Daniel P

    2014-07-18

    The loss of β-cell function and β-cell death are key features of diabetes. A range of mechanisms are thought to contribute to β-cell loss, including islet amyloid formation by the neuropancreatic hormone amylin (islet amyloid polypeptide, IAPP). Islet amyloid deposition also contributes to the failure of islet transplants. There are no therapeutic strategies for the treatment or prevention of islet amyloidosis. Aspirin and the nonsteroid anti-inflammatory drug (NSAID) ketoprofen, at clinically relevant doses, have been proposed to inhibit amyloid formation by amylin and thus may hold promise for treatment of islet amyloidosis. These compounds are potentially attractive given the importance of inflammation in islet amyloidosis and given the fact that there are no anti-islet amyloid agents in the clinic. We show that aspirin, even in 20-fold excess, has no effect on the kinetics of amyloid formation by amylin as judged by thioflavin-T binding, right angle light scattering, and transmission electron microscopy, nor does it alter the morphology of resulting amyloid fibrils. Aspirin showed no ability to disaggregate preformed amylin amyloid fibrils under the conditions of these studies, 25 °C and pH 7.4. Ketoprofen is similarly ineffective at inhibiting amylin amyloid formation. The compounds do, however, interfere with circular dichroism- and Congo Red-based assays of amylin amyloid formation. This study highlights the importance of using multiple methods to follow amyloid formation when screening inhibitors.

  9. Chemopreventive effects of aspirin at a glance.

    PubMed

    Usman, Muhammad Waqas; Luo, Fuwen; Cheng, Hailing; Zhao, Jean J; Liu, Pixu

    2015-04-01

    Experimental, epidemiological, and clinical data from the last two decades have each supported the hypothesis that aspirin possesses anticancer properties, and that its use may also reduce the lifetime probability of developing or dying from a number of cancers. Aspirin's ability to act on multiple key metabolic and signaling pathways via inhibition of the cyclooxygenase (COX) enzyme, as well as through COX-independent mechanisms, makes it particularly relevant in the fight against cancer. A growing body of evidence indicates that aspirin may not only reduce cancer risk, but also prevent metastasis and angiogenesis while slowing the rate of mutation-inducing DNA damage. These emerging benefits of aspirin are offset to some extent by the known risks of treatment, such as cardiovascular events and gastrointestinal bleeding. However, it has been shown that pre-treatment risk assessment of individual patients and the use of proton pump inhibitors or Helicobacter pylori eradication therapy concomitantly with aspirin treatment can reduce these potential risks. Thus, the significant benefits of aspirin treatment, coupled with recent data concerning its risks, may prove to tip the balance in favor of aspirin use in cancer prevention.

  10. Chemopreventive effects of aspirin at a glance.

    PubMed

    Usman, Muhammad Waqas; Luo, Fuwen; Cheng, Hailing; Zhao, Jean J; Liu, Pixu

    2015-04-01

    Experimental, epidemiological, and clinical data from the last two decades have each supported the hypothesis that aspirin possesses anticancer properties, and that its use may also reduce the lifetime probability of developing or dying from a number of cancers. Aspirin's ability to act on multiple key metabolic and signaling pathways via inhibition of the cyclooxygenase (COX) enzyme, as well as through COX-independent mechanisms, makes it particularly relevant in the fight against cancer. A growing body of evidence indicates that aspirin may not only reduce cancer risk, but also prevent metastasis and angiogenesis while slowing the rate of mutation-inducing DNA damage. These emerging benefits of aspirin are offset to some extent by the known risks of treatment, such as cardiovascular events and gastrointestinal bleeding. However, it has been shown that pre-treatment risk assessment of individual patients and the use of proton pump inhibitors or Helicobacter pylori eradication therapy concomitantly with aspirin treatment can reduce these potential risks. Thus, the significant benefits of aspirin treatment, coupled with recent data concerning its risks, may prove to tip the balance in favor of aspirin use in cancer prevention. PMID:25842298

  11. (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. PMID:20560642

  12. Oral administration of ethanol with aspirin increases the concentration of salicylic acid in plasma and organs, especially the brain, in mice.

    PubMed

    Kato, Hideaki; Yoshimoto, Kanji; Kobayashi, Masaki; Sakabe, Masaaki; Funaki, Hironao; Ikegaya, Hiroshi

    2010-06-10

    Aspirin (acetylsalicylic acid) has been widely used as an over-the-counter drug to relieve pain throughout the world. In suicide attempts, aspirin is one of the most common drugs taken in large quantities. The concentration of salicylic acid shows a low-level distribution in the mouse brain, a site that may be critical regarding the expression of symptoms (e.g. hyperpnea, coma, convulsion and tremor) during acute aspirin toxicity. Therefore, it was suggested that sensitivity to salicylic acid concerning acute toxicity was higher in the brain than in other organs. Moreover, it is thought that it is common for aspirin and ethanol to be ingested at the same time. Therefore, the present study was designed to investigate the influence of ethanol on the distribution of salicylic acid, which is a primary metabolite of aspirin, and its related metabolite, salicyluric acid. The oral co-administration of aspirin (0.5g/kg) and ethanol (2.5g/kg; 10ml/kg of 25% (w/v)) enhanced the concentrations of salicylic acid in the plasma and organs, especially in the brain, compared with the aspirin alone-treated group. On the other hand, ethanol did not influence the concentrations of salicyluric acid in the plasma and kidney compared with the aspirin alone-treated group. These results suggest that ethanol enhances aspirin absorption from the gastrointestinal tract but has no influence on its metabolism. Thus, it is dangerous to ingest the alcohol and aspirin at the same time, as this may exacerbate the acute toxicity of aspirin.

  13. 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.

  14. Differential pulse voltammetric determination of nimesulide in pharmaceutical formulation and human serum at glassy carbon electrode modified by cysteic acid/CNTs base on electrochemical oxidation of L-cysteine.

    PubMed

    Wang, Chengyin; Shao, Xiaoqiu; Liu, Qingxiu; Qu, Qishu; Yang, Gongjun; Hu, Xiaoya

    2006-09-18

    Carbon nanotubes (CNTs) and cysteic acid based on electrochemical oxidation of L-cysteine (CySH) to form a novel composite thin film material at a glassy carbon electrode (GCE) for electroanalytical determination of nimesulide. The determination of nimesulide at the composite modified electrode with strong accumulation of nimesulide was studied by differential pulse voltammetry (DPV). The peak current obtained at +1.251 V (versus SCE) from DPV was linearly dependent on the nimesulide concentration in the range of 1.0 x 10(-7) -1.0 x 10(-5) M in 0.05 M H(2)SO(4) solution with a correlation coefficient of 0.997. The detection limit (S/N = 3) was found to be 5.0 x 10(-8) M. The low-cost modified electrode showed good sensitivity, selectivity, stability and had been applied to the determination of nimesulide in pharmaceutical formulation and human serum samples with satisfactory results.

  15. Aspirin

    MedlinePlus

    ... Guidelines . Circulation . 2011 ; 123 : 2022 – 2060 . OpenUrl FREE Full Text 4. ↵ Antithrombotic Trialists' (ATT) Collaboration , Baigent C , Blackwell ... BMJ . 2002 ; 324 : 71 – 86 . OpenUrl Abstract / FREE Full Text 6. ↵ Furie KL , Kasner SE , Adams RJ , Albers ...

  16. 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.

  17. 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

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

    PubMed

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

    2016-01-01

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

  19. Aspirin may influence cellular energy status.

    PubMed

    Kamble, Pratibha; Litvinov, Dmitry; Aluganti Narasimhulu, Chandrakala; Jiang, Xueting; Parthasarathy, Sampath

    2015-02-15

    In our previous findings, we have demonstrated that aspirin/acetyl salicylic acid (ASA) might induce sirtuins via aryl hydrocarbon receptor (Ah receptor). Induction effects included an increase in cellular paraoxonase 1 (PON1) activity and apolipoprotein A1 (ApoA1) gene expression. As predicted, ASA and salicylic acid (SA) treatment resulted in generation of H2O2, which is known to be an inducer of mitochondrial gene Sirt4 and other downstream target genes of Sirt1. Our current mass spectroscopic studies further confirm the metabolism of the drugs ASA and SA. Our studies show that HepG2 cells readily converted ASA to SA, which was then metabolized to 2,3-DHBA. HepG2 cells transfected with aryl hydrocarbon receptor siRNA upon treatment with SA showed the absence of a DHBA peak as measured by LC-MS/MS. MS studies for Sirt1 action also showed a peak at 180.9 m/z for the deacetylated and chlorinated product formed from N-acetyl lε-lysine. Thus an increase in Sirt4, Nrf2, Tfam, UCP1, eNOS, HO1 and STAT3 genes could profoundly affect mitochondrial function, cholesterol homeostasis, and fatty acid oxidation, suggesting that ASA could be beneficial beyond simply its ability to inhibit cyclooxygenase. PMID:25557764

  20. Aspirin may influence cellular energy status

    PubMed Central

    Kamble, Pratibha; Litvinov, Dmitry; Narasimhulu, Chandrakala Aluganti; Jiang, Xueting; Parthasarathy, Sampath

    2015-01-01

    In our previous findings, we have demonstrated that aspirin/acetyl salicylic acid (ASA) might induce sirtuins via aryl hydrocarbon receptor (Ah receptor). Induction effects included an increase in cellular paraoxonase 1 (PON1) activity and apolipoprotein A1 (ApoA1) gene expression. As predicted, ASA and salicylic acid (SA) treatment resulted in generation of H2O2, which is known to be an inducer of mitochondrial gene Sirt4 and other downstream target genes of Sirt1. Our current mass spectroscopic studies further confirm the metabolism of the drugs ASA and SA. Our studies show that HepG2 cells readily converted ASA to SA, which was then metabolized to 2,3-DHBA. HepG2 cells transfected with aryl hydrocarbon receptor siRNA upon treatment with SA showed the absence of a DHBA peak as measured by LC-MS/MS. MS studies for Sirt1 action also showed a peak at 180.9 m/z for the deacetylated and chlorinated product formed from N-acetyl Lε-lysine. Thus an increase in Sirt4, Nrf2, Tfam, UCP1, eNOS, HO1 and STAT3 genes could profoundly affect mitochondrial function, cholesterol homeostasis, and fatty acid oxidation, suggesting that ASA could be beneficial beyond simply its ability to inhibit cyclooxygenase. PMID:25557764

  1. 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.

  2. 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)

  3. [Aspirin-induced angioedema of the nape of the neck with naproxen cross-reaction: a case report].

    PubMed

    Ghislain, P D; Ghislain, E

    2000-05-01

    We report a case of angioedema limited to the nape of the neck. The symptoms occurred every morning for fifteen days, two or three hours after taking aspirin. The patient took salicylic acid, 100mg per day, orally for two years. The angioedema occurred alone, without urticaria. When aspirin was stopped, the symptoms disappeared. A few weeks later, the patient took napoxen, with occurrence of more pronounced symptoms. The causality score was I3 for both drugs. The most common side-effects of aspirin intake are asthma and urticaria/angioedema. The mechanism of this hypersensitivity is unknown. There are numerous cross-reactions between aspirin and other NSAIDs. This case points out the importance of accurate history taking concerning self-medication for the diagnosis of angioedema.

  4. 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

  5. In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes.

    PubMed

    Zaccardi, Francesco; Rizzi, Alessandro; Petrucci, Giovanna; Ciaffardini, Flavia; Tanese, Luigi; Pagliaccia, Francesca; Cavalca, Viviana; Ciminello, Angela; Habib, Aida; Squellerio, Isabella; Rizzo, Paola; Tremoli, Elena; Rocca, Bianca; Pitocco, Dario; Patrono, Carlo

    2016-02-01

    Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation. PMID:26470782

  6. 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

  7. Long-term treatment of rheumatoid arthritis comparing nabumetone with aspirin.

    PubMed

    Bernhard, G C; Appelrouth, D J; Bankhurst, A D; Biundo, J; Bockow, B I; Brobyn, R D; Brodsky, A L; Burch, F X; Chang, R W; Cohen, M H

    1987-10-30

    This report summarizes the results of a 17-investigator multicenter six-month randomized double-blind parallel group study. The safety and efficacy of nabumetone 1,000 mg taken at bedtime was compared with that of aspirin 900 mg four times daily in the treatment of adult patients with active class II or III classical or definite rheumatoid arthritis. Two hundred sixty-four patients were entered into the study. Two hundred fifty-seven (126 nabumetone and 131 aspirin) patients were evaluable for safety. Two hundred thirty-four (113 nabumetone and 121 aspirin) patients were evaluable for efficacy. There was significant improvement in each of six clinical measurements of efficacy in both treatment groups and little difference between groups. The somewhat greater improvement in articular index and duration of morning stiffness in the nabumetone-treated group did not reach statistical significance. There was an equal percentage of patient withdrawal for lack of efficacy in each group. Overall, the rate of patient withdrawal due to adverse experiences was greater (p = 0.01) for aspirin-treated patients. These experiences were usually dispepsia, abdominal pain, and tinnitus. It was concluded that nabumetone was an effective anti-inflammatory drug in the treatment of rheumatoid arthritis with less toxicity than aspirin.

  8. New Insights into the Mechanism of Action of Aspirin in the Prevention of Colorectal Neoplasia.

    PubMed

    Di Francesco, Luigia; López Contreras, Luilli Antonio; Sacco, Angela; Patrignani, Paola

    2015-01-01

    The results of clinical studies have shown that the chronic administration of aspirin, even at the lowdoses (75-100 mg daily) recommended for the prevention of cardiovascular disease, is associated with a reduction of cancer incidence and mortality, in particular colorectal cancer (CRC). The mechanism of action of aspirin as an antineoplastic agent remains controversial. However, data of clinical pharmacology and several features of the chemopreventive effect of aspirin, emerged from clinical trials, suggest that the antiplatelet effect of aspirin plays a central role in its anticancer effects. In addition to their contribution to tumor metastasis, platelets may play a role in the early phases of tumorigenesis. In response to lifestyle and environment factors, intestinal epithelial damage/ dysfunction may be associated with platelet activation, initially as a mechanism to repair the damage. However, if the platelet response is unconstrained, it may contribute to the development of chronic inflammation. Altogether these events lead to alter the normal functions of intestinal epithelial cells and may translate into cellular transformation through several mechanisms, including the overexpression of cyclooxygenase(COX)-2 and epidermal growth factor receptor (EGFR), which are considered early events in colorectal tumorigenesis. Thus, antiplatelet agents may play a role in the prevention of CRC by modifying epigenetic events involved in early phases of colorectal tumorigenesis. Finally, we carried out a critical review of the literature on off-target mechanisms of aspirin action as anticancer drug. PMID:26369679

  9. Protection of vascular endothelium by aspirin in a murine model of chronic Chagas' disease.

    PubMed

    Molina-Berríos, Alfredo; Campos-Estrada, Carolina; Lapier, Michel; Duaso, Juan; Kemmerling, Ulrike; Galanti, Norbel; Ferreira, Jorge; Morello, Antonio; López-Muñoz, Rodrigo; Maya, Juan Diego

    2013-07-01

    Chronic Chagas' disease affects 10-30 % of patients infected with Trypanosoma cruzi, and it mainly manifests as cardiomyopathy. Important pathophysiological mechanisms involved in the cardiac lesions include activation of the endothelium and induced microvascular alterations. These processes involve the production of endothelial adhesion molecules and thromboxane A2, which are involved in inflammatory cell recruitment and platelet aggregation, respectively. Cyclooxygenase inhibitors such as aspirin decrease thromboxane production and alter the course of Chagas' disease, both in the acute and chronic phases. We studied the effects of the administration of low and high doses of aspirin during the early phase of T. cruzi infection, following microvascular damage in the context of a chronic murine model of Chagas' disease. The effects of both schedules were assessed at 24 and 90 days postinfection by evaluating parasitemia, mortality, and cardiac histopathological changes as well as the expression of ICAM, VCAM, and E-selectin in cardiac tissue. Thromboxane A2, soluble ICAM, and E-selectin blood levels were also measured. While aspirin did not affect parasitemia or mortality in the infected mice, it decreased both cardiac inflammatory infiltrates and thromboxane levels. Additionally, at 90 days postinfection, aspirin normalized sICAM and sE-selectin levels. Considering the improved endothelial function induced by aspirin, we propose the possibility of including this drug in clinical therapy to treat chronic Chagas' disease.

  10. In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes.

    PubMed

    Zaccardi, Francesco; Rizzi, Alessandro; Petrucci, Giovanna; Ciaffardini, Flavia; Tanese, Luigi; Pagliaccia, Francesca; Cavalca, Viviana; Ciminello, Angela; Habib, Aida; Squellerio, Isabella; Rizzo, Paola; Tremoli, Elena; Rocca, Bianca; Pitocco, Dario; Patrono, Carlo

    2016-02-01

    Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation.

  11. 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.

  12. 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.

  13. Low-dose aspirin use does not diminish the immune response to monovalent H1N1 influenza vaccine in older adults.

    PubMed

    Jackson, M L; Bellamy, A; Wolff, M; Hill, H; Jackson, L A

    2016-03-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) may inhibit antibody production by peripheral blood mononuclear cells; one consequence of this could be decreased effectiveness of vaccines in NSAID users. Because many older adults use low-dose aspirin for primary or secondary prevention of coronary events, any inhibitory effect of aspirin on vaccine immune response could reduce the benefits of vaccination programmes in older adults. We tested whether immune response to vaccination differed between users vs. non-users of low-dose aspirin, using data from four randomized trials of monovalent 2009 pandemic influenza A(H1N1) vaccine. Geometric mean haemagglutination inhibition antibody titres were not significantly lower in low-dose aspirin users compared to non-users. Our results provide reassurance that influenza vaccination effectiveness is probably not reduced in older adults taking chronic low-dose aspirin.

  14. 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.

  15. 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. PMID:23588001

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

    PubMed Central

    Nanra, Ranjit S.; Kincaid-Smith, Priscilla

    1970-01-01

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

  17. 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

  18. Are the current recommendations for the use of aspirin in primary prevention of cardiovascular disease applicable in low-income countries?

    PubMed

    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

  19. Aspirin inhibits osteoclastogenesis by suppressing the activation of NF-κB and MAPKs in RANKL-induced RAW264.7 cells

    PubMed Central

    Zeng, Yan-Ping; Yang, Chao; Li, Yuan; Fan, Yong; Yang, Hong-Jun; Liu, Bin; Sang, Hong-Xun

    2016-01-01

    Aspirin is a commonly used medicine as an effective antipyretic, analgesic and anti-inflammatory drug. Previous studies have demonstrated its potential effects of anti-postmenopausal osteoporosis, while the molecular mechanisms remain unclear. The effects of aspirin on receptor-activator of nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclasts were investigated in RAW264.7 cells in the current study. Using tartrate-resistant acid phosphatase (TRAP) staining, it was observed that aspirin inhibited the differentiation of RANKL-induced RAW264.7 cells. The mRNA expression of osteoclastic marker genes, including cathepsin K, TRAP, matrix metalloproteinase 9 and calcitonin receptor, were suppressed by aspirin as identified using reverse transcription-quantitative polymerase chain reaction analysis. The immunofluorescence assay indicated that aspirin markedly inhibited NF-κB p65 translocation to the nucleus in RANKL-induced RAW264.7 cells. In addition, aspirin also suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), observed by western blot analysis. Taken together, these data identified that aspirin inhibits osteoclastogenesis by suppressing the activation of NF-κB and MAPKs in RANKL-induced RAW264.7 cells, implying that aspirin may possess therapeutic potential for use in the prevention and treatment of osteoporosis. PMID:27430169

  20. Aspirin inhibits osteoclastogenesis by suppressing the activation of NF-κB and MAPKs in RANKL-induced RAW264.7 cells.

    PubMed

    Zeng, Yan-Ping; Yang, Chao; Li, Yuan; Fan, Yong; Yang, Hong-Jun; Liu, Bin; Sang, Hong-Xun

    2016-09-01

    Aspirin is a commonly used medicine as an effective antipyretic, analgesic and anti-inflammatory drug. Previous studies have demonstrated its potential effects of anti-postmenopausal osteoporosis, while the molecular mechanisms remain unclear. The effects of aspirin on receptor‑activator of nuclear factor κB (NF‑κB) ligand (RANKL)‑induced osteoclasts were investigated in RAW264.7 cells in the current study. Using tartrate‑resistant acid phosphatase (TRAP) staining, it was observed that aspirin inhibited the differentiation of RANKL‑induced RAW264.7 cells. The mRNA expression of osteoclastic marker genes, including cathepsin K, TRAP, matrix metalloproteinase 9 and calcitonin receptor, were suppressed by aspirin as identified using reverse transcription‑quantitative polymerase chain reaction analysis. The immunofluorescence assay indicated that aspirin markedly inhibited NF‑κB p65 translocation to the nucleus in RANKL‑induced RAW264.7 cells. In addition, aspirin also suppressed the phosphorylation of mitogen‑activated protein kinases (MAPKs), observed by western blot analysis. Taken together, these data identified that aspirin inhibits osteoclastogenesis by suppressing the activation of NF‑κB and MAPKs in RANKL‑induced RAW264.7 cells, implying that aspirin may possess therapeutic potential for use in the prevention and treatment of osteoporosis. PMID:27430169

  1. Are the current recommendations for the use of aspirin in primary prevention of cardiovascular disease applicable in low-income countries?

    PubMed

    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.

  2. 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. PMID:26656902

  3. [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. PMID:11878097

  4. [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.

  5. 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. PMID:26314861

  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. 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.

  8. [The use of nimesulide in the treatment of acute low back pain].

    PubMed

    Shikhkerimov, R K

    2016-01-01

    The objective is to study the efficacy and safety of nimesulide (nemulex) in the treatment of acute low back pain (LBP). The medical documentation of 54 patients with primary syndrome of LBP, which were treated in a polyclinic with nemulex at a dose of 200 mg per day had been studied. The assessment of patients' condition and efficacy and safety of the treatment was conducted based on the information after three visits (1-st, 5-th and 10-th day). The analysis took into account the data of clinical-neurological examination and the assessment of pain intensity at rest and at movement according to the visual analogue scale (VAS) and the severity of Lasegue symptom and limitation of movements in the lumbar spine. Safety of the therapy was evaluated on the basis of accounting of undesirable side reactions and data analysis and physical examination and laboratory testing. Cardiovascular safety was assessed by blood pressure and blood lipid profile on day 10. The use of nemulex at a dose of 200 mg per day resulted in relief of pain and increase of mobility in the lumbar spine on the 5th day of treatment that indicates the effectiveness of anti-inflammatory therapy to restore the previous functional status of patients with LBP. The use of nemulex was accompanied not only by statistically significant analgesic effect (0,78±0,14 points alone; 1,12±0,18 points when moving by VAS on the 10th day of the treatment) and high security (only 1 of the 54 patients was recorded to have elevation of hepatic transaminases; and 2 patients with dyspepsia without endoscopic changes of gastrointestinal tract). PMID:27240177

  9. [The use of nimesulide in the treatment of acute low back pain].

    PubMed

    Shikhkerimov, R K

    2016-01-01

    The objective is to study the efficacy and safety of nimesulide (nemulex) in the treatment of acute low back pain (LBP). The medical documentation of 54 patients with primary syndrome of LBP, which were treated in a polyclinic with nemulex at a dose of 200 mg per day had been studied. The assessment of patients' condition and efficacy and safety of the treatment was conducted based on the information after three visits (1-st, 5-th and 10-th day). The analysis took into account the data of clinical-neurological examination and the assessment of pain intensity at rest and at movement according to the visual analogue scale (VAS) and the severity of Lasegue symptom and limitation of movements in the lumbar spine. Safety of the therapy was evaluated on the basis of accounting of undesirable side reactions and data analysis and physical examination and laboratory testing. Cardiovascular safety was assessed by blood pressure and blood lipid profile on day 10. The use of nemulex at a dose of 200 mg per day resulted in relief of pain and increase of mobility in the lumbar spine on the 5th day of treatment that indicates the effectiveness of anti-inflammatory therapy to restore the previous functional status of patients with LBP. The use of nemulex was accompanied not only by statistically significant analgesic effect (0,78±0,14 points alone; 1,12±0,18 points when moving by VAS on the 10th day of the treatment) and high security (only 1 of the 54 patients was recorded to have elevation of hepatic transaminases; and 2 patients with dyspepsia without endoscopic changes of gastrointestinal tract).

  10. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice.

    PubMed

    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

    2008-10-01

    The National Institute on Aging's Interventions Testing Program 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, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex,with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p=0.0006) and aspirin (p=0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan;neither NDGA (p=0.12) nor aspirin (p=0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on life span in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses,might prove to postpone death and various age-related outcomes reproducibly in mice. PMID:18631321

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

    NASA Astrophysics Data System (ADS)

    Kurniati, Neng Fisheri; Permatasari, Anita

    2015-09-01

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

  12. New formulation of old aspirin for better delivery.

    PubMed

    Kalathil, Akil A; Kumar, Anil; Banik, Bhabatosh; Ruiter, Timothy A; Pathak, Rakesh K; Dhar, Shanta

    2016-01-01

    For better use of cyclooxygenase dependent anti-inflammatory properties and mitochondrial activities of aspirin, new hydrophobic analogues of aspirin were developed and successfully encapsulated in polymeric nanoparticles (NPs). In vivo anti-inflammatory effects of these NPs using a mouse model demonstrated unique properties of an optimized aspirin analogue to inhibit production of pro-inflammatory and enrichment of anti-inflammatory cytokines.

  13. Aspirin may inhibit angiogenesis and induce autophagy by inhibiting mTOR signaling pathway in murine hepatocarcinoma and sarcoma models

    PubMed Central

    Zhao, Qianqian; Wang, Zhaopeng; Wang, Zhaoxia; Wu, Licun; Zhang, Weidong

    2016-01-01

    Aspirin is known to have inhibitory effects on growth development in various types of tumor. In previous studies, it was observed to inhibit angiogenesis by downregulating the expression of vascular endothelial growth factor-A (VEGF-A). In the present study, murine H22 hepatocarcinoma and S180 sarcoma models were used to ascertain whether aspirin could inhibit angiogenesis and promote autophagy in tumors. Tumor-bearing mice were randomly divided into four groups with 10 mice per group: i) no treatment; ii) low-dose aspirin (100 mg/kg); iii) high-dose aspirin (400 mg/kg); iv) everolimus group (4 mg/kg). The effects of high-dose aspirin were validated through preliminary experiments. The drug treatment was administered every day for 14 days. The tumor size was measured every other day and then the tumor growth curve was plotted, and the tumor inhibitory rates were calculated. The expression levels of phosphorylated mammalian target of rapamycin (p-mTOR), hypoxia-inducible factor-1α (HIF-1α), VEGF-A, UNC-51-like kinase-1 (ULK1) and microtubule-associated protein 1 light chain 3A (LC3A) were detected by immunohistochemistry and western blot analysis, respectively. We observed that tumor growth delay was achieved in both H22 hepatocarcinoma and S180 sarcoma models following treatment with aspirin. The tumor growth inhibition rates induced by low and high-dose aspirin and everolimus were 19.6, 33.6 and 53.7% (P<0.05) in H22 hepatocarcinoma, and 25.7, 40.6 and 48.7% (P<0.05) in S180 sarcoma. The immunohistochemistry and western blot analysis data from the models revealed that the expression of p-mTOR, HIF-1α and VEGF-A was decreased, while the expression of ULK1 and LC3A was increased following treatment with aspirin and everolimus. The changes were more apparent in the high-dose aspirin and everolimus groups (P<0.01). The inhibitory action of aspirin and everolimus on tumor angiogenesis may be through inhibiting the expression of p-mTOR, HIF-1α and VEGF

  14. Aspirin may inhibit angiogenesis and induce autophagy by inhibiting mTOR signaling pathway in murine hepatocarcinoma and sarcoma models

    PubMed Central

    Zhao, Qianqian; Wang, Zhaopeng; Wang, Zhaoxia; Wu, Licun; Zhang, Weidong

    2016-01-01

    Aspirin is known to have inhibitory effects on growth development in various types of tumor. In previous studies, it was observed to inhibit angiogenesis by downregulating the expression of vascular endothelial growth factor-A (VEGF-A). In the present study, murine H22 hepatocarcinoma and S180 sarcoma models were used to ascertain whether aspirin could inhibit angiogenesis and promote autophagy in tumors. Tumor-bearing mice were randomly divided into four groups with 10 mice per group: i) no treatment; ii) low-dose aspirin (100 mg/kg); iii) high-dose aspirin (400 mg/kg); iv) everolimus group (4 mg/kg). The effects of high-dose aspirin were validated through preliminary experiments. The drug treatment was administered every day for 14 days. The tumor size was measured every other day and then the tumor growth curve was plotted, and the tumor inhibitory rates were calculated. The expression levels of phosphorylated mammalian target of rapamycin (p-mTOR), hypoxia-inducible factor-1α (HIF-1α), VEGF-A, UNC-51-like kinase-1 (ULK1) and microtubule-associated protein 1 light chain 3A (LC3A) were detected by immunohistochemistry and western blot analysis, respectively. We observed that tumor growth delay was achieved in both H22 hepatocarcinoma and S180 sarcoma models following treatment with aspirin. The tumor growth inhibition rates induced by low and high-dose aspirin and everolimus were 19.6, 33.6 and 53.7% (P<0.05) in H22 hepatocarcinoma, and 25.7, 40.6 and 48.7% (P<0.05) in S180 sarcoma. The immunohistochemistry and western blot analysis data from the models revealed that the expression of p-mTOR, HIF-1α and VEGF-A was decreased, while the expression of ULK1 and LC3A was increased following treatment with aspirin and everolimus. The changes were more apparent in the high-dose aspirin and everolimus groups (P<0.01). The inhibitory action of aspirin and everolimus on tumor angiogenesis may be through inhibiting the expression of p-mTOR, HIF-1α and VEGF

  15. Aspirin metabolism and efficacy in postoperative dental pain.

    PubMed Central

    Seymour, R A; Williams, F M; Ward, A; Rawlins, M D

    1984-01-01

    Aspirin 1200 mg was compared with placebo in a randomised, double-blind, crossover study in 15 patients with postoperative pain after removal of impacted lower third molars. Over a 5 h investigation period, patients reported significantly less pain (P less than 0.01) after treatment with aspirin, than after treatment with placebo. Peak concentrations of aspirin occurred at 15 min after dosage. Significant negative correlations were observed between plasma aspirin esterase activity and both AUC aspirin (r = -0.904, P less than 0.001) and AUC analgesia (r = -0.91, P less than 0.001). Similarly, a significant correlation was observed between AUC aspirin and AUC analgesia (r = 0.96, P less than 0.001). Evidence from this study would suggest that an individual's pain relief in postoperative dental pain is determined by the rate of aspirin hydrolysis to salicylate. PMID:6378231

  16. A General Chemistry Laboratory Theme: Spectroscopic Analysis of Aspirin

    NASA Astrophysics Data System (ADS)

    Byrd, Houston; O'Donnell, Stephen E.

    2003-02-01

    In this paper, we describe the introduction of spectroscopy into the general chemistry laboratory using a series of experiments based on a common substance, aspirin. In the first lab the students synthesize and recrystallize aspirin and take melting points of their product, an aspirin standard, and salicylic acid. The students perform the remaining experiments on a rotating basis where the following four labs run simultaneously: structural characterization of the synthesized aspirin by IR and NMR; analysis of synthesized aspirin and commercial products by UV vis spectroscopy; analysis of synthesized aspirin and commercial products by HPLC; and analysis of calcium in commercial buffered aspirin tablets by AAS. In each of the analysis experiments, students collect, graph, and analyze their data using a spreadsheet. We have found that this series of labs has been very beneficial to our students. From the course evaluations, students indicate that they are beginning to understand how chemistry is applied outside of the classroom.

  17. Aspirin Use Associated With Amyotrophic Lateral Sclerosis: a Total Population-Based Case-Control Study

    PubMed Central

    Tsai, Ching-Piao; Lin, Feng-Cheng; Lee, Johnny Kuang-Wu; Lee, Charles Tzu-Chi

    2015-01-01

    Background The association of aspirin use and nonsteroid anti-inflammatory drug (NSAID) use with amyotrophic lateral sclerosis (ALS) risk is unclear. This study determined whether use of any individual compound is associated with ALS risk by conducting a total population-based case-control study in Taiwan. Methods A total of 729 patients with newly diagnosed ALS who had a severely disabling disease certificate between January 1, 2002, and December 1, 2008, comprised the case group. These cases were compared with 7290 sex-, age-, residence-, and insurance premium-matched controls. Drug use by each Anatomical Therapeutic Chemical code was analyzed using conditional logistic regression models. False discovery rate (FDR)-adjusted P values were reported in order to avoid inflating false positives. Results Of the 1336 compounds, only the 266 with use cases exceeding 30 in our database were included in the screening analysis. Without controlling for steroid use, the analysis failed to reveal any compound that was inversely associated with ALS risk according to FDR criteria. After controlling for steroid use, we found use of the following compounds to be associated with ALS risk: aspirin, diphenhydramine (one of the antihistamines), and mefenamic acid (one of the NSAIDs). A multivariate analysis revealed that aspirin was independently inversely associated with ALS risk after controlling for diphenhydramine, mefenamic acid, and steroid use. The inverse association between aspirin and ALS was present predominately in patients older than 55 years. Conclusions The results of this study suggested that aspirin use might reduce the risk of ALS, and the benefit might be more prominent for older people. PMID:25721071

  18. Antiplatelet drug interactions.

    PubMed

    Mackenzie, I S; Coughtrie, M W H; MacDonald, T M; Wei, L

    2010-12-01

    Both laboratory studies in healthy volunteers and clinical studies have suggested adverse interactions between antiplatelet drugs and other commonly used medications. Interactions described include those between aspirin and ibuprofen, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), and the thienopyridine, clopidogrel, and drugs inhibiting CYP2C19, notably the proton pump inhibitors (PPI) omeprazole and esomeprazole. Other interactions between thienopyridines and CYP3A4/5 have also been reported for statins and calcium channel blockers. The ibuprofen/aspirin interaction is thought to be caused by ibuprofen blocking the access of aspirin to platelet cyclo-oxygenase. The thienopyridine interactions are caused by inhibition of microsomal enzymes that metabolize these pro-drugs to their active metabolites. We review the evidence for these interactions, assess their clinical importance and suggest strategies of how to deal with them in clinical practice. We conclude that ibuprofen is likely to interact with aspirin and reduce its anti-platelet action particularly in those patients who take ibuprofen chronically. This interaction is of greater relevance to those patients at high cardiovascular risk. A sensible strategy is to advise users of aspirin to avoid chronic ibuprofen or to ingest aspirin at least 2 h prior to ibuprofen. Clearly the use of NSAIDs that do not interact in this way is preferred. For the clopidogrel CYP2C19 and CYP3A4/5 interactions, there is good evidence that these interactions occur. However, there is less good evidence to support the clinical importance of these interactions. Again, a reasonable strategy is to avoid the chronic use of drugs that inhibit CYP2C19, notably PPIs, in subjects taking clopidogrel and use high dose H2 antagonists instead. Finally, anti-platelet agents probably interact with other drugs that affect platelet function such as selective serotonin reuptake inhibitors, and clinicians should probably judge

  19. Analysis of a Suspected Drug Sample

    ERIC Educational Resources Information Center

    Schurter, Eric J.; Zook-Gerdau, Lois Anne; Szalay, Paul

    2011-01-01

    This general chemistry laboratory uses differences in solubility to separate a mixture of caffeine and aspirin while introducing the instrumental analysis methods of GCMS and FTIR. The drug mixture is separated by partitioning aspirin and caffeine between dichloromethane and aqueous base. TLC and reference standards are used to identify aspirin…

  20. Relief of Dental Pain: A Controlled 12-Hour Comparison of Etodolac, Aspirin, and Placebo

    PubMed Central

    Nelson, Sharon L.; Bergman, Stewart A.

    1985-01-01

    Single doses of the study drugs were evaluated for 12 hours by 201 out-patients reporting moderate or severe pain following oral surgery. The results of this double-blind study indicated that 50, 100, and 200 mg of etodolac as well as 650 mg of aspirin were significantly more effective than placebo. A dose-response relationship was found for the three doses of etodolac, which was significant for summed pain relief scores for up to 8 hours. In terms of total analgesic effect, etodolac 200 mg was significantly superior to placebo for 8 hours, while aspirin and the two lower doses of etodolac were similarly effective in the range of 3-6 hours postdrug. All doses showed a favorable onset of analgesia (½-1 hour). Etodolac 200 mg resulted in a duration of action which was approximately twice as long as aspirin's and also produced a peak pain relief which was significantly greater than the lower doses of etodolac and aspirin. All study medications were well tolerated with no reports of significant adverse side effects. No dose-related effects were observed with etodolac PMID:2934008

  1. A case of chlorpheniramine maleate-induced hypersensitivity with aspirin intolerance.

    PubMed

    Kim, Min-Hye; Lee, Sang-Min; Lee, So-Hee; Kwon, Hyouk-Soo; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Chang, Yoon-Seok

    2011-01-01

    Antihistamines are commonly used to treat allergic disease, such as allergic rhinitis, urticaria, and angioedema. Although several previous reports describe hypersensitivity to antihistamines such as cetirizine and hydroxyzine, documented cases of chlorpheniramine hypersensitivity are extremely rare. Here, we report the case of a 45-year-old Korean woman who presented with urticaria after ingesting a cold medication. Over the previous 5 years, she had also experienced a food allergy to crab and shrimp, allergic rhinitis, and repeated urticaria after ingesting cold medication. Provocation with aspirin elicited generalized urticaria. Intravenous chlorpheniramine and methylprednisolone was injected for symptom control, but in fact appeared to aggravate urticaria. A second round of skin and provocation tests for chlorpheniramine and methylprednisolone showed positive results only for chlorpheniramine. She was diagnosed with aspirin intolerance and chlorpheniramine hypersensitivity, and was instructed to avoid these drugs. To date, this is the second of only two cases of chlorpheniramine-induced type I hypersensitivity with aspirin intolerance. Although the relationship between aspirin intolerance and chlorpheniramine-induced type I hypersensitivity is unclear, physicians should be aware of the possibility of urticaria or other allergic reactions in response to antihistamines.

  2. A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension.

    PubMed

    Robbins, I M; Kawut, S M; Yung, D; Reilly, M P; Lloyd, W; Cunningham, G; Loscalzo, J; Kimmel, S E; Christman, B W; Barst, R J

    2006-03-01

    Idiopathic pulmonary arterial hypertension (IPAH) is characterised by in situ thrombosis and increased thromboxane (Tx) A2 synthesis; however, there are no studies of antiplatelet therapy in IPAH. The aim of the current study was to determine the biochemical effects of aspirin (ASA) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH. A randomised, double-blind, placebo-controlled crossover study of ASA 81 mg once daily and clopidogrel 75 mg once daily was performed. Plasma P-selectin levels and aggregometry were measured after exposure to adenosine diphosphate, arachidonic acid and collagen. Serum levels of TxB2 and urinary metabolites of TxA2 and prostaglandin I2 (Tx-M and PGI-M, respectively) were assessed. A total of 19 IPAH patients were enrolled, of whom nine were being treated with continuous intravenous epoprostenol. ASA and clopidogrel significantly reduced platelet aggregation to arachidonic acid and adenosine diphosphate, respectively. ASA significantly decreased serum TxB2, urinary Tx-M levels and the Tx-M/PGI-M ratio, whereas clopidogrel had no effect on eicosanoid levels. Neither drug significantly lowered plasma P-selectin levels. Epoprostenol use did not affect the results. In conclusion, aspirin and clopidogrel inhibited platelet aggregation, and aspirin reduced thromboxane metabolite production without affecting prostaglandin I2 metabolite synthesis. Further clinical trials of aspirin in patients with idiopathic pulmonary arterial hypertension should be performed. PMID:16507859

  3. Aspirin- and Indomethacin-Induced Ulcers and their Antagonism by Anthihistamines

    NASA Technical Reports Server (NTRS)

    Brown, Patricia A.; Sawrey, James M.; Vernikos, Joan

    1978-01-01

    Gastric ulceration produced by aspirin and indomethacin was compared in acutely stressed and non-stressed rats. We found a synergism between these anti-inflammatory agents and acute stress in the production of gastric ulcers. Even at relatively high doses, neither agent caused appreciable gastric damage in non-stressed rats, whereas moderate doses of both agents produced massive ulceration in stressed rats. The synergism appears unrelated to the effect of these agents on the pituitary-adrenal response. The size and regional distribution of ulcers produced by aspirin and indomethacin in stressed rats were comparable. However, the dose--response curves of the two drugs were markedly dissimilar. Furthermore, the ulceration produced by indomethacin was attenuated by both H(sub 1) and H(sub 2) histamine receptor antagonists, whereas ulceration produced by aspirin was attenuated only by an H(sub 2) antagonist. The results suggest that the ulcerogenic mechanism of indomethacin may differ from that of aspirin and add to the growing evidence on the importance of endogenous histamine in various forms of gastric ulceration.

  4. Vascular smooth muscle, endothelial regulation and effects of aspirin in hypertension.

    PubMed

    Rahmani, M A

    1998-04-27

    Dysfunction of vascular smooth muscle (VSM) is at the center of occlusive disorders of the cardiovascular system such as hypertension, atherosclerosis, coronary artery disease and hypoxia. In addition to circulating biogenic amines and various neurotransmitters originating from the central nervous system and endocrine system, various autocoids of arachidonic acid metabolism in the blood as well as in the endothelium play an important regulatory role in the maintenance of the tone and the contractile function of VSM. A monolayer of endothelial cells lining the heart and large blood vessels is responsible for producing and releasing both endocrine and paracrine substances such as endothelins, nitric oxide, prostaglandins and prostacyclins. Aspirin, (acetylsalicylic acid/ASA) an ancient remedy against fever and pain, is emerging as an effective drug not only against occlusive disorders but also against various cancers and the AIDs virus. During pregnancy induced hypertension (PIH) and in occlusive disorders, aspirin provides relief through inhibition of cyclooxygenase, an enzyme required for the metabolism of arachidonic acid to produce prostaglandins and prostacyclins in platelets and in endothelial cells. Because of its unique molecular constitution, synergistic ability and solubility in the lipidic environment, various mechanisms of aspirin's actions are being currently investigated. In this review, the effect of aspirin on the regulation of VSM in the presence and absence of endothelium are discussed.

  5. Development and validation of two multiresidue liquid chromatography tandem mass spectrometry methods based on a versatile extraction procedure for isolating non-steroidal anti-inflammatory drugs from bovine milk and muscle tissue.

    PubMed

    Gentili, Alessandra; Caretti, Fulvia; Bellante, Simona; Mainero Rocca, Lucia; Curini, Roberta; Venditti, Alessandro

    2012-09-01

    The main difficulties in analysing non-steroidal anti-inflammatory drugs (NSAIDs) in food and biological samples are due to the tight non-covalent interactions established with matrix proteins and the amount of occurring fatty material. The present paper describes an effective extraction procedure able to isolate fifteen NSAIDs (acetaminophen, salicylic acid, ibuprofen, diclofenac, flunixin and its metabolite 5-hydroxy-flunixin, nimesulide, phenylbutazone, meclofenamic acid, tolfenamic acid, meloxicam, carprofen, ketoprofen, naproxen and etodolac) from bovine milk and muscle tissue through two succeeding steps: (a) deproteinisation/extraction with organic solvent, essential to lower the medium dielectric constant and, therefore, to release the analytes from matrix; (b) SPE clean-up on OASIS cartridges. Lipids were easily removed during low-temperature centrifugations. The advantages of the developed procedure pertain to the efficient removal of the fat substances (very low matrix effect and high recovery yields) and its versatility, since it can be applied both to milk and muscle with few adjustments due to the diversity of the two matrices. Ion-pairing reversed-phase chromatography combined with the negative electrospray detection was able to achieve low detection capabilities (CCβs) for all analytes and, in particular, for diclofenac whose Maximum Residue Limit (MRL) in milk is 0.1 μg kg(-1). The methods were validated according to the guidelines of the Commission Decision 2002/657/EC and then applied for a small monitoring study. A number of samples showed traces of salicylic acid (SA), but its occurrence was not ascribed to a misuse of drugs (aspirin, salicylic acid) since SA, accumulating in plants in response to a pathogen attack, may be introduced into the food chain.

  6. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    NASA Astrophysics Data System (ADS)

    Kan, Xianwen; Geng, Zhirong; Zhao, Yao; Wang, Zhilin; Zhu, Jun-Jie

    2009-04-01

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe3O4 nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

  7. Neuroprotection by Aspirin and Sodium Salicylate Through Blockade of NF-kappaB Activation

    NASA Astrophysics Data System (ADS)

    Grilli, Mariagrazia; Pizzi, Marina; Memo, Maurizio; Spano, Pierfranco

    1996-11-01

    Aspirin (acetylsalicylic acid) is a commonly prescribed drug with a wide pharmacological spectrum. At concentrations compatible with amounts in plasma during chronic anti-inflammatory therapy, acetylsalicylic acid and its metabolite sodium salicylate were found to be protective against neurotoxicity elicited by the excitatory amino acid glutamate in rat primary neuronal cultures and hippocampal slices. The site of action of the drugs appeared to be downstream of glutamate receptors and to involve specific inhibition of glutamate-mediated induction of nuclear factor kappa B. These results may contribute to the emerging theme of anti-inflammatory drugs and neurodegeneration.

  8. In search of pure liquid salt forms of aspirin: ionic liquid approaches with acetylsalicylic acid and salicylic acid.

    PubMed

    Bica, Katharina; Rijksen, Christiaan; Nieuwenhuyzen, Mark; Rogers, Robin D

    2010-02-28

    We present an ionic liquid (IL) approach towards a dual functional liquid salt form of aspirin using different pharmaceutically active cations composed of antibacterials, analgesics, local anesthetics, and antiarrhythmic drugs in combination with acetylsalicylic acid or its metabolite salicylic acid and discuss stability of these ILs in comparison to solid salts. Several low-melting or liquid salts of salicylic acid with dual functionality and promising properties were isolated and characterized; however, although such ILs with aspirin could be prepared, they suffer from limited stability and slowly decompose into the corresponding salicylate ILs when exposed to moisture.

  9. Aspirin's Active Metabolite Salicylic Acid Targets High Mobility Group Box 1 to Modulate Inflammatory Responses.

    PubMed

    Choi, Hyong Woo; Tian, Miaoying; Song, Fei; Venereau, Emilie; Preti, Alessandro; Park, Sang-Wook; Hamilton, Keith; Swapna, G V T; Manohar, Murli; Moreau, Magali; Agresti, Alessandra; Gorzanelli, Andrea; De Marchis, Francesco; Wang, Huang; Antonyak, Marc; Micikas, Robert J; Gentile, Daniel R; Cerione, Richard A; Schroeder, Frank C; Montelione, Gaetano T; Bianchi, Marco E; Klessig, Daniel F

    2015-01-01

    Salicylic acid (SA) and its derivatives have been used for millennia to reduce pain, fever and inflammation. In addition, prophylactic use of acetylsalicylic acid, commonly known as aspirin, reduces the risk of heart attack, stroke and certain cancers. Because aspirin is rapidly de-acetylated by esterases in human plasma, much of aspirin's bioactivity can be attributed to its primary metabolite, SA. Here we demonstrate that human high mobility group box 1 (HMGB1) is a novel SA-binding protein. SA-binding sites on HMGB1 were identified in the HMG-box domains by nuclear magnetic resonance (NMR) spectroscopic studies and confirmed by mutational analysis. Extracellular HMGB1 is a damage-associated molecular pattern molecule (DAMP), with multiple redox states. SA suppresses both the chemoattractant activity of fully reduced HMGB1 and the increased expression of proinflammatory cytokine genes and cyclooxygenase 2 (COX-2) induced by disulfide HMGB1. Natural and synthetic SA derivatives with greater potency for inhibition of HMGB1 were identified, providing proof-of-concept that new molecules with high efficacy against sterile inflammation are attainable. An HMGB1 protein mutated in one of the SA-binding sites identified by NMR chemical shift perturbation studies retained chemoattractant activity, but lost binding of and inhibition by SA and its derivatives, thereby firmly establishing that SA binding to HMGB1 directly suppresses its proinflammatory activities. Identification of HMGB1 as a pharmacological target of SA/aspirin provides new insights into the mechanisms of action of one of the world's longest and most used natural and synthetic drugs. It may also provide an explanation for the protective effects of low-dose aspirin usage. PMID:26101955

  10. Aspirin's Active Metabolite Salicylic Acid Targets High Mobility Group Box 1 to Modulate Inflammatory Responses.

    PubMed

    Choi, Hyong Woo; Tian, Miaoying; Song, Fei; Venereau, Emilie; Preti, Alessandro; Park, Sang-Wook; Hamilton, Keith; Swapna, G V T; Manohar, Murli; Moreau, Magali; Agresti, Alessandra; Gorzanelli, Andrea; De Marchis, Francesco; Wang, Huang; Antonyak, Marc; Micikas, Robert J; Gentile, Daniel R; Cerione, Richard A; Schroeder, Frank C; Montelione, Gaetano T; Bianchi, Marco E; Klessig, Daniel F

    2015-06-18

    Salicylic acid (SA) and its derivatives have been used for millennia to reduce pain, fever and inflammation. In addition, prophylactic use of acetylsalicylic acid, commonly known as aspirin, reduces the risk of heart attack, stroke and certain cancers. Because aspirin is rapidly de-acetylated by esterases in human plasma, much of aspirin's bioactivity can be attributed to its primary metabolite, SA. Here we demonstrate that human high mobility group box 1 (HMGB1) is a novel SA-binding protein. SA-binding sites on HMGB1 were identified in the HMG-box domains by nuclear magnetic resonance (NMR) spectroscopic studies and confirmed by mutational analysis. Extracellular HMGB1 is a damage-associated molecular pattern molecule (DAMP), with multiple redox states. SA suppresses both the chemoattractant activity of fully reduced HMGB1 and the increased expression of proinflammatory cytokine genes and cyclooxygenase 2 (COX-2) induced by disulfide HMGB1. Natural and synthetic SA derivatives with greater potency for inhibition of HMGB1 were identified, providing proof-of-concept that new molecules with high efficacy against sterile inflammation are attainable. An HMGB1 protein mutated in one of the SA-binding sites identified by NMR chemical shift perturbation studies retained chemoattractant activity, but lost binding of and inhibition by SA and its derivatives, thereby firmly establishing that SA binding to HMGB1 directly suppresses its proinflammatory activities. Identification of HMGB1 as a pharmacological target of SA/aspirin provides new insights into the mechanisms of action of one of the world's longest and most used natural and synthetic drugs. It may also provide an explanation for the protective effects of low-dose aspirin usage.

  11. Aspirin delays mesothelioma growth by inhibiting HMGB1-mediated tumor progression.

    PubMed

    Yang, H; Pellegrini, L; Napolitano, A; Giorgi, C; Jube, S; Preti, A; Jennings, C J; De Marchis, F; Flores, E G; Larson, D; Pagano, I; Tanji, M; Powers, A; Kanodia, S; Gaudino, G; Pastorino, S; Pass, H I; Pinton, P; Bianchi, M E; Carbone, M

    2015-01-01

    High-mobility group box 1 (HMGB1) is an inflammatory molecule that has a critical role in the initiation and progression of malignant mesothelioma (MM). Aspirin (acetylsalicylic acid, ASA) is the most widely used nonsteroidal anti-inflammatory drug that reduces the incidence, metastatic potential and mortality of many inflammation-induced cancers. We hypothesized that ASA may exert anticancer properties in MM by abrogating the carcinogenic effects of HMGB1. Using HMGB1-secreting and -non-secreting human MM cell lines, we determined whether aspirin inhibited the hallmarks of HMGB1-induced MM cell growth in vitro and in vivo. Our data demonstrated that ASA and its metabolite, salicylic acid (SA), inhibit motility, migration, invasion and anchorage-independent colony formation of MM cells via a novel HMGB1-mediated mechanism. ASA/SA, at serum concentrations comparable to those achieved in humans taking therapeutic doses of aspirin, and BoxA, a specific inhibitor of HMGB1, markedly reduced MM growth in xenograft mice and significantly improved survival of treated animals. The effects of ASA and BoxA were cyclooxygenase-2 independent and were not additive, consistent with both acting via inhibition of HMGB1 activity. Our findings provide a rationale for the well documented, yet poorly understood antitumorigenic activity of aspirin, which we show proceeds via HMGB1 inhibition. Moreover, the use of BoxA appears to allow a more efficient HMGB1 targeting while eluding the known gastrointestinal side effects of ASA. Our findings are directly relevant to MM. Given the emerging importance of HMGB1 and its tumor-promoting functions in many cancer types, and of aspirin in cancer prevention and therapy, our investigation is poised to provide broadly applicable information. PMID:26068794

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

    SciTech Connect

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

    2010-02-11

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

  13. Pilot study of the safety of starting administration of low-dose aspirin and cilostazol in acute ischemic stroke.

    PubMed

    Fujita, Keishi; Komatsu, Yoji; Sato, Naoaki; Higuchi, Osamu; Kujiraoka, Yuji; Kamezaki, Takao; Suzuki, Kensuke; Matsumura, Akira

    2011-01-01

    Progressive stroke is a serious problem due to the associated morbidity and mortality. Aspirin is recommended for acute ischemic stroke, but does not reduce the frequency of stroke progression. No standard treatment has been approved for the prevention of stroke progression. Cilostazol, which reduces platelet aggregation about 3 hours after single administration, does not increase the frequency of bleeding events when compared with aspirin or a placebo. Moreover, the combination of 100 mg aspirin and 200 mg cilostazol does not increase the frequency of bleeding events compared with only 100 mg aspirin, and thus is expected to prevent stroke progression with a high degree of safety. The present study investigated the safety of this combination of two drugs administered at the above concentrations in 54 patients with acute ischemic stroke within 48 hours of stroke onset. Modified National Institutes of Health Stroke Scale (NIHSS) measurements were performed at baseline and again on day 4 to 7. Progressive stroke was defined as an increase greater than or equal to 1 point on NIHSS. Patient scores on the modified Rankin Scale (mRS) were evaluated at baseline and 3 months after enrollment. Stroke progression occurred in 11.1% of the patients. The percentages of patients with mRS score from 0 to 2 were 42.6% and 75% at baseline and 3 months, respectively. No symptomatic intracranial hemorrhage or major extracranial hemorrhage occurred. These results suggest that administration of aspirin and cilostazol is safe for acute ischemic stroke.

  14. Spontaneous Early Recanalization after Acute Innominate Artery Thromboembolic Occlusion Secondary to Abrupt Aspirin and Statin Discontinuation A Case Report

    PubMed Central

    Tsai, C-K; Lee, J-T; Wu, Y-C; Peng, G-S

    2014-01-01

    ABSTRACT Statin and antiplatelet drugs are widely used for prevention of ischaemic stroke and other cardiovascular diseases in high-risk patients. We report a rare case of a 49-year old man with a history of myocardial infarction and hyperlipidaemia who suffered an acute occlusion of his innominate artery (IA) accompanied by subclavian steal syndrome and cerebral infarction, on day seven after abrupt cessation of aspirin and statin, as confirmed by magnetic resonance and computed tomographic angiography of head and neck, and colour-coded Duplex ultrasonography (CCDU). Aspirin and atorvastatin were immediately re-started on admission. Spontaneous recanalization of IA was shown on repeat CCDU and digital subtraction angiography on day 10 after stroke onset. This case serves as a reminder that abrupt discontinuation of both aspirin and statin in patients with previous history of cardiovascular disease may increase the risk of ischaemic stroke. PMID:25781297

  15. Radial basis function neural networks in non-destructive determination of compound aspirin tablets on NIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Dou, Ying; Mi, Hong; Zhao, Lingzhi; Ren, Yuqiu; Ren, Yulin

    2006-09-01

    The application of the second most popular artificial neural networks (ANNs), namely, the radial basis function (RBF) networks, has been developed for quantitative analysis of drugs during the last decade. In this paper, the two components (aspirin and phenacetin) were simultaneously determined in compound aspirin tablets by using near-infrared (NIR) spectroscopy and RBF networks. The total database was randomly divided into a training set (50) and a testing set (17). Different preprocessing methods (standard normal variate (SNV), multiplicative scatter correction (MSC), first-derivative and second-derivative) were applied to two sets of NIR spectra of compound aspirin tablets with different concentrations of two active components and compared each other. After that, the performance of RBF learning algorithm adopted the nearest neighbor clustering algorithm (NNCA) and the criterion for selection used a cross-validation technique. Results show that using RBF networks to quantificationally analyze tablets is reliable, and the best RBF model was obtained by first-derivative spectra.

  16. [Aspirin treatment for patients with Kawasaki disease].

    PubMed

    Hamada, Hiromichi

    2014-09-01

    Aspirin was first used for patients with Kawasaki disease(KD) at 1970s. Favorable outcomes of KD patients treated with aspirin were reported in 1970-80s and now it is one of the standard therapeutic agents for KD. Its anti-inflammation effects suppress vascular wall inflammation of KD at acute phase. In addition, its antiplatelet effects heal endothelial dysfunction and prevent clot formation in coronary arteries at sub-acute and convalescent phase. Long-term dosage for patients with coronary artery aneurysms(CAA) is also important, however, there are few evidences of risk-benefit assessment for its long-term use especially for middle-aged and senior adults with KD and CAA. PMID:25518411

  17. Metformin combined with aspirin significantly inhibit pancreatic cancer cell growth in vitro and in vivo by suppressing anti-apoptotic proteins Mcl-1 and Bcl-2.

    PubMed

    Yue, Wen; Zheng, Xi; Lin, Yong; Yang, Chung S; Xu, Qing; Carpizo, Darren; Huang, Huarong; DiPaola, Robert S; Tan, Xiang-Lin

    2015-08-28

    Metformin and aspirin have been studied extensively as cancer preventive or therapeutic agents. However, the effects of their combination on pancreatic cancer cells have not been investigated. Herein, we evaluated the effects of metformin and aspirin, alone or in combination, on cell viability, migration, and apoptosis as well as the molecular changes in mTOR, STAT3 and apoptotic signaling pathways in PANC-1 and BxPC3 cells. Metformin and aspirin, at relatively low concentrations, demonstrated synergistically inhibitory effects on cell viability. Compared to the untreated control or individual drug, the combination of metformin and aspirin significantly inhibited cell migration and colony formation of both PANC-1 and BxPC-3 cells. Metformin combined with aspirin significantly inhibited the phosphorylation of mTOR and STAT3, and induced apoptosis as measured by caspase-3 and PARP cleavage. Remarkably, metformin combined with aspirin significantly downregulated the anti-apoptotic proteins Mcl-1 and Bcl-2, and upregulated the pro-apoptotic proteins Bim and Puma, as well as interrupted their interactions. The downregulation of Mcl-1 and Bcl-2 was independent of AMPK or STAT3 pathway but partially through mTOR signaling and proteasome degradation. In a PANC-1 xenograft mouse model, we demonstrated that the combination of metformin and aspirin significantly inhibited tumor growth and downregulated the protein expression of Mcl-1 and Bcl-2 in tumors. Taken together, the combination of metformin and aspirin significantly inhibited pancreatic cancer cell growth in vitro and in vivo by regulating the pro- and anti-apoptotic Bcl-2 family members, supporting the continued investigation of this two drug combination as chemopreventive or chemotherapeutic agents for pancreatic cancer.

  18. Talk With Your Health Care Provider About Taking Aspirin to Prevent Heart Attack

    MedlinePlus

    ... q What are my chances of having a heart attack? q Would I benefit from taking aspirin? q ... Health Care Provider About Taking Aspirin to Prevent Heart Attacks Did you know that aspirin can be an ...

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

    MedlinePlus

    ... of Aspirin Aspirin for Reducing Your Risk of Heart Attack and Stroke: Know the Facts Share Tweet Linkedin ... example, using aspirin to lower the risk of heart attack and clot-related strokes. In these cases, the ...

  20. Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION (provided by applicant): Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain;numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. |

  1. Aspirination of α-Aminoalcohol (Sarpogrelate M1).

    PubMed

    Park, Sunhwa; Lee, Jiyun; Shin, Kye Jung; Seo, Jae Hong

    2016-01-01

    Aspirination of α-aminoalcohol (sarpogrelate M1) has been performed under various general esterification conditions. In most cases, the desired aspirinate ester was obtained at a low yield with unexpected byproducts, the formation of which was mostly derived from the chemical properties of the tertiary α-amino group. After systematic analysis of those methods, the aspirinated sarpogrelate M1 was prepared using a two-step approach combining salicylate ester formation and acetylation. PMID:27571053

  2. Evaluation of the pharmaceutical characteristics of various enteric-coated aspirin tablets under different storage conditions.

    PubMed

    Abe, Toshihide; Yanagihara, Yoshitsugu; Uchino, Tomonobu; Oriyama, Toyohito; Komatsu, Mamoru; Nakajima, Katsuyoshi; Suzuki, Hiroshi

    2014-01-01

    The formulation characteristics of 6 brands of enteric-coated aspirin tablets under unpackaged conditions at 40°C and 60°C for 4 weeks were analyzed. Appearance, salicylic acid content, dissolution rates, and surface properties (by Raman microscopy) were evaluated to determine stability data, taking into account the clinical use of generic drugs. No change in appearance, decomposition, or dissolution rates was observed in unpackaged aspirin tablets stored at 40°C for 4 weeks. However, when stored at 60°C, tablets of 5 of the 6 brands showed whiskers on their surfaces along with an increase in salicylic acid content and a decrease in dissolution rate. Results of Raman mapping on the surface and cross sectional surface of the tablets with whiskers showed a salicylic acid peak associated with storage at 60°C for 4 weeks. However, for tablets from 1 of the 6 brands, no salicylic acid peaks were observed. For this tablet, Raman microscopy revealed 2 layers of film coating, and talc, which greatly affected the stability of the acetylsalicylic acid, was found only in the outer layer film. These results indicated that the protection of compatibility with talc is one of the important factors in enhancement of aspirin tablet stability in this tablet. We concluded that certification of the characteristics associated with stability and formulation is essential for generic drugs, which are not required to undergo stability testing under extreme storage conditions.

  3. Radiochromium (chromium-51) evaluation of gastrointestinal blood loss associated with placebo, aspirin, and nabumetone

    SciTech Connect

    Lussier, A.; LeBel, E.

    1987-10-30

    Gastrointestinal blood loss is one of the most serious clinical events induced by drugs. To date, almost no nonsteroidal anti-inflammatory drug has been shown to be devoid of that side effect in a strictly controlled study. The objective of this study was to assess quantitatively, by use of radioactive chromium (chromium-51)-labeled red blood cells, gastrointestinal blood loss associated with nabumetone (1000 mg daily), aspirin (3.6 g daily), and placebo. A total of 37 normal subjects, divided among the three treatment groups and a fourth group that received no treatment, were assessed clinically and quantitatively for gastrointestinal blood loss over a period of 28 days of active treatment. The results with chromium-51, analyzed on a logarithmic scale, revealed no statistically significant differences between the nabumetone, placebo, and control groups. Gastrointestinal blood loss in the aspirin group, however, was elevated when compared with all other groups at a high level of statistical significance (p less than 0.001). It is concluded that, under conditions in which aspirin causes substantial gastrointestinal microbleeding, nabumetone is not significantly different from placebo.

  4. Effects of administration route on pharmacokinetics of aspirin in the rabbit.

    PubMed

    Kergueris, M F; Bourin, M; Larousse, C; Lasserre, M P; Ortega, A

    1988-03-01

    The absorption of aspirin used in the form of lysine acetylsalicylate was studied in the rabbit. Each animal received the drug by three routes: intravenous, gastric and duodenal. Plasma concentrations of acetylsalicylic acid (ASA) and salicylic acid (SA) were compared. ASA plasma concentrations obtained after gastric or duodenal administration were low compared to those after intravenous injection. Concentrations were 2 to 5 times higher after gastric than duodenal administration. SA plasma concentrations were lower at the beginning of the experiment for gastric than for duodenal administration; after 90 min the concentrations were similar. A better absorption of aspirin (as lysine acetylsalicylate) after administration occurred in the stomach than in the duodenum, but the amount of ASA which reached the central compartment was quite poor.

  5. Management of patients with nonaspirin-exacerbated respiratory disease aspirin hypersensitivity reactions.

    PubMed

    Saff, Rebecca R; Banerji, Aleena

    2015-01-01

    Because of widespread use, nonsteroidal anti-inflammatory drugs (NSAIDs) are the second most common cause of all adverse drug reactions, with hypersensitivity reported in ∼1% of the population. NSAID hypersensitivity can be categorized into five types by the underlying disease, symptoms of reaction, and timing of reaction. These include rhinitis and asthma induced by NSAIDs (also known as aspirin-exacerbated respiratory disease), NSAID-exacerbated cutaneous disease (NECD), urticaria or angioedema induced by multiple NSAIDs, single NSAID-induced reactions, and delayed NSAID reactions. NECD occurs in one-third of patients with chronic urticaria who develop an exacerbation of their urticaria, sometimes with angioedema, typically beginning 30-90 minutes after ingestion of NSAIDs that inhibit cyclooxygenase (COX)-1. In urticaria or angioedema induced by multiple NSAIDs, patients without underlying disease develop urticaria or angioedema 30-90 minutes after ingestion of COX-1-inhibiting NSAIDs including aspirin. Single NSAID-induced reactions are immediate and specific to a single NSAID and are thought to occur because of an IgE-mediated reaction against a specific epitope of the NSAID. Delayed NSAID reactions occur days to weeks after initiating an NSAID. These are T-cell mediated and not amenable to desensitization or rechallenge. Classifying the type of NSAID hypersensitivity is important because many patients with a prior history of urticaria or angioedema induced by multiple NSAIDs will often tolerate aspirin test dose. This would allow the use of an aspirin for primary or secondary prevention in patients with coronary artery disease despite a presumed history of NSAID hypersensitivity.

  6. Reduction of indium-111 platelet deposition on Dacron vascular grafts in humans by aspirin plus dipyridamole

    SciTech Connect

    Stratton, J.R.; Ritchie, J.L.

    1986-02-01

    Aspirin plus dipyridamole reduces platelet accumulation on short-term Dacron vascular grafts in man. To determine whether drug inhibition of platelet deposition is sustained on older grafts, we studied 18 men aged 41 to 87 years who had Dacron aortic bifurcation grafts in place a mean of 43.4 months (range 9.8 to 121.0) before and during short-term therapy with aspirin (325 mg tid) plus dipyridamole (75 mg tid). During both the baseline and drug studies, indium-111 (/sup 111/In) platelet deposition was quantitated by two techniques, standard planar imaging performed at 24, 48, and 72 hr after injection of platelets and single photon emission computed tomographic imaging performed at 24 and 72 hr after injection. All analyses were performed in a blinded fashion. On both the planar and tomographic images, platelet accumulation on the graft was quantitated by a graft/blood ratio that compared activity in the graft to simultaneously collected whole blood /sup 111/In platelet activity. Aspirin plus dipyridamole reduced the tomographic graft/blood ratio at 24 hr (20.6 +/- 3.5 vs 17.3 +/- 2.5) (+/-SEM) and at 72 hr (29.0 +/- 4.8 vs 25.0 +/- 4.1) after injection of platelets (p = .02). Dacron vascular grafts. Similarly, the planar graft/blood ratio was reduced at 24 hr (2.7 +/- 0.5 vs 2.4 +/- 0.5), 48 hr (3.7 +/- 0.9 vs 3.1 +/- 0.7), and 72 hr (4.0 +/- 0.9 vs 3.6 +/- 0.8) (p = .04). We conclude that aspirin (325 mg tid) plus dipyridamole (75 mg tid) reduces platelet accumulation on long-term Dacron vascular grafts.

  7. Aspirin absorption rates and platelet inhibition times with 325-mg buffered aspirin tablets (chewed or swallowed intact) and with buffered aspirin solution.

    PubMed

    Feldman, M; Cryer, B

    1999-08-15

    Large clinical trials such as the second International Study of Infarct Survival routinely gave patients with myocardial infarction a chewed aspirin, yet there are no data to show whether chewing of aspirin is better, or worse, than swallowing a whole tablet. We performed a randomized, placebo-controlled study to determine whether chewing aspirin or administering it in solution accelerates its absorption and antiplatelet activity. On separate days, 12 fasting volunteers ingested 325 mg of buffered aspirin, either by chewing a tablet for 30 seconds before swallowing it with 4 ounces of water, swallowing a whole tablet with 4 ounces of water, or drinking 4 ounces of Alka Seltzer. Frequent blood samples were obtained for serum aspirin, salicylate, and thromboxane B2 (TxB2) concentrations. With all formulations of aspirin, serum TxB2 decreased 50% when the plasma aspirin concentration reached approximately 1,000 ng/ml. A 50% and 90% decrease in serum TxB2 occurred more quickly after chewing a tablet than after a tablet was swallowed whole. For example, the t 50% for serum TxB2 inhibition was 5.0 +/- 0.6 minutes with the chewed tablet versus 12.0 +/- 2.3 minutes when the tablet was swallowed (p = 0.01). A 50% decrease in serum TxB2 occurred 7.6 +/- 1.2 minutes after Alka Seltzer solution (p = 0.04 vs chewing a tablet; p = 0.13 vs swallowing a whole tablet). Chewing an aspirin tablet is the most effective way of accelerating absorption of aspirin into the blood and shortening the time required for an antiplatelet effect. PMID:10468077

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

    PubMed

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

    2016-08-15

    Polyunsaturated fatty acids (PUFAs) are vital for normal growth and development and physiological function of various tissues in humans. PUFAs have immunomodulatory actions in addition to their ability to modulate inflammation, vascular reactivity, neurotransmission and stem cell biology. PUFAs and their metabolites possess both pro- and anti-inflammatory properties that underlie their actions and involvement in several diseases. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), possesses both cyclo-oxygenase (COX) and lipoxygenase (LOX) inhibitory action and enhances the production of anti-inflammatory lipoxin A4 {(called as epi-lipoxin A4, aspirin-triggered lipoxins (ATLs))}. In addition, at low doses aspirin may not interfere with the production of prostacyclin (PGI2). Both lipoxin A4 and PGI2 have vasodilator, platelet anti-aggregator and anti-inflammatory actions that may underlie the beneficial actions of aspirin. Paradoxically, other NSAIDs may not have the same actions as that of aspirin on PUFA metabolism. Similar anti-inflammatory compounds are formed from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by the action of aspirin termed as resolvins (from EPA and DHA) and protectins and maresins from DHA. PUFAs: arachidonic acid (AA), EPA and DHA and their various products modulate not only inflammation and immune response but also possess actions on various genes, nuclear factors, cyclic AMP and GMP, G-protein coupled receptors (GPRs), hypothalamic neurotransmitters, hormones, cytokines and enzymes, and interact with nitric oxide, carbon monoxide, and hydrogen sulfide to regulate their formation and action and to form new compounds that have several biological actions. These pleiotropic actions of PUFAs and their metabolites may explain their ability to play a role in several physiological actions and diseases. The big challenge is to harness these actions to prevent and manage clinical conditions. PMID:26335394

  9. Aspirin and lipid mediators in the cardiovascular system.

    PubMed

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

    Aspirin is an unique compound because it bears two active moieties within one and the same molecule: a reactive acetyl group and the salicylate metabolite. Salicylate has some effects similar to aspirin, however only at higher concentrations, usually in the millimolar range, which are not obtained at conventional antiplatelet aspirin doses of 100-300 mg/day. Pharmacological actions of aspirin in the cardiovascular system at these doses are largely if not entirely due to target structure acetylation. Several classes of lipid mediators become affected: Best known is the cyclooxygenase-1 (COX-1) in platelets with subsequent inhibition of thromboxane and, possibly, thrombin formation. By this action, aspirin also inhibits paracrine thromboxane functions on other lipid mediators, such as the platelet storage product sphingosine-1-phosphate (S1P), an inflammatory mediator. Acetylation of COX-2 allows for generation of 15-(R)HETE and subsequent formation of "aspirin-triggered lipoxin" (ATL) by interaction with white cell lipoxygenases. In the cardiovascular system, aspirin also acetylates eNOS with subsequent upregulation of NO formation and enhanced expression of the antioxidans heme-oxygenase-1. This action is possibly also COX-2/ATL mediated. Many more acetylation targets have been identified in live cells by quantitative acid-cleavable activity-based protein profiling and might result in discovery of even more aspirin targets in the near future. PMID:26201059

  10. Aspirin and coronary heart disease: findings of a prospective study.

    PubMed Central

    Hammond, E C; Garfinkel, L

    1975-01-01

    Over 1 000 000 men and women answered a confidential questionnaire and were traced for up to six years afterwards. Among other questions each person was asked how often he or she took aspirin-"never", "seldom," or "often." Coronary heart disease death rates were no lower among people who took aspirin often than among those who did not do so. PMID:1131582

  11. Aspirin and lipid mediators in the cardiovascular system.

    PubMed

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

    Aspirin is an unique compound because it bears two active moieties within one and the same molecule: a reactive acetyl group and the salicylate metabolite. Salicylate has some effects similar to aspirin, however only at higher concentrations, usually in the millimolar range, which are not obtained at conventional antiplatelet aspirin doses of 100-300 mg/day. Pharmacological actions of aspirin in the cardiovascular system at these doses are largely if not entirely due to target structure acetylation. Several classes of lipid mediators become affected: Best known is the cyclooxygenase-1 (COX-1) in platelets with subsequent inhibition of thromboxane and, possibly, thrombin formation. By this action, aspirin also inhibits paracrine thromboxane functions on other lipid mediators, such as the platelet storage product sphingosine-1-phosphate (S1P), an inflammatory mediator. Acetylation of COX-2 allows for generation of 15-(R)HETE and subsequent formation of "aspirin-triggered lipoxin" (ATL) by interaction with white cell lipoxygenases. In the cardiovascular system, aspirin also acetylates eNOS with subsequent upregulation of NO formation and enhanced expression of the antioxidans heme-oxygenase-1. This action is possibly also COX-2/ATL mediated. Many more acetylation targets have been identified in live cells by quantitative acid-cleavable activity-based protein profiling and might result in discovery of even more aspirin targets in the near future.

  12. Aspirin Risks in Perspective: A Comparison against Marathon Running

    ERIC Educational Resources Information Center

    Morgan, Gareth

    2014-01-01

    Aspirin has public health potential to reduce the risk of ischaemic vascular events and sporadic cancer. One objection to the wider use of aspirin for primary prevention, however, is the undesirable effects of the medicine, which include increasing risk of bleeding and haemorrhagic stroke. Marathons also carry risks of serious events such as…

  13. Aspirin dosing in cardiovascular disease prevention and management: an update.

    PubMed

    Ganjehei, Leila; Becker, Richard C

    2015-11-01

    Aspirin has been in use for prevention and management of cardiovascular diseases for several decades. Clinical and epidemiological literature suggests that while net benefits of aspirin in primary prevention of CVDs are less clear, the benefits of aspirin in acute scenarios and secondary prevention settings are well established. However, its optimum dosing requirements have been up for debate especially in various settings of acute coronary syndrome and stable ischemic heart disease. The role of clinician in stratifying individual risk score to achieve net clinical benefit is an important determinant of initiating aspirin therapy. The purpose of this article is to review association of aspirin and CVD in general, and to review its dosing regimens in acute settings as well as primary and secondary prevention as suggested by various established guidelines. We also aim to provide the readers an update on recent changes and current evidence based practice trends.

  14. Aspirin decreases platelet uptake on Dacron vascular grafts in baboons

    SciTech Connect

    Mackey, W.C.; Connolly, R.J.; Callow, A.D.; Keough, E.M.; Ramberg-Laskaris, K.; McCullough, J.L.; O'Donnell, T.F. Jr.; Melaragno, A.; Valeri, C.R.; Weiblen, B.

    1984-07-01

    The influence of a single dose of aspirin (5.4-7.4 mg/kg) on platelet uptake on 4-mm Dacron interposition grafts was studied in a baboon model using gamma camera scanning for 111-Indium labeled platelets. In vitro assessment of platelet function after aspirin administration revealed that in the baboon, as in the human, aspirin abolished arachidonic acid-induced platelet aggregation, prolonged the lag time between exposure to collagen and aggregation, and decreased plasma thromboxane B2 levels. Aspirin also prolonged the template bleeding time. Scans for 111-Indium labeled platelets revealed that pretreatment with a single dose of aspirin decreased platelet uptake on 4-mm Dacron carotid interposition grafts. This decrease in platelet uptake was associated with a significant improvement in 2-hour graft patency and with a trend toward improved 2-week patency.

  15. Comparison of Three Aspirin Formulations in Human Volunteers

    PubMed Central

    Nordt, Sean Patrick; Clark, Richard F; Castillo, Edward M; Guss, David A

    2011-01-01

    Introduction The treatment of acute coronary syndrome (ACS) includes the administration of aspirin. Current guidelines recommend chewing aspirin tablets to increase absorption. While this is intuitive, there are scant data supporting this recommendation. The purpose of this study is to assess which of 3 different aspirin formulations is most rapidly absorbed after ingestion. Methods A prospective, open-label, 3-way crossover volunteer study at a tertiary university medical center with human subjects 18 years or older. Fasted subjects were randomly assigned to receive aspirin 1,950 mg as (1) solid aspirin tablets swallowed whole, (2) solid aspirin tablet chewed then swallowed, or (3) a chewable aspirin formulation chewed and swallowed. Serum salicylate measurements were obtained over a period of 180 minutes. Pharmacokinetic parameters were determined. Results Thirteen males and 1 female completed all 3 arms of study. Peak serum salicylate concentrations were seen at 180 minutes in all groups. Mean peaks were 10.4, 11.3, and 12.2 mg/dL in groups 1, 2, and 3, respectively. Mean area under the time concentration was 1,153, 1,401, and 1,743 mg-min/dL in groups 1, 2, and 3, respectively. No measurable salicylate concentrations were seen in 6 subjects in group 1 at 60 minutes as compared to 1 subject in group 2. All subjects in group 3 had measurable levels at 45 minutes. There were no adverse effects in any of the subjects during the study period. Conclusion Our data demonstrate that the chewable aspirin formulation achieved the most rapid rate of absorption. In addition, the chewable formulation absorption was more complete than the other formulations at 180 minutes. These data suggest that in the treatment of ACS, a chewable aspirin formulation may be preferable to solid tablet aspirin, either chewed or swallowed. PMID:22224124

  16. Modulation of carcinogen metabolism by nitric oxide-aspirin 2 is associated with suppression of DNA damage and DNA adduct formation.

    PubMed

    MacDonald, Christopher J; Cheng, Robert Y S; Roberts, David D; Wink, David A; Yeh, Grace Chao

    2009-08-14

    Nitric oxide (NO)-donating non-steroidal anti-inflammatory drugs (NSAIDs) represent a promising new class of drugs developed to provide a safer alternative than their conventional NSAID counterparts in chemoprevention. We tested the effects of NO-aspirin 2 on Phase I and Phase II carcinogen-metabolizing enzymes. In HepG2 human hepatoma cells and in LS180 colonic adenocarcinoma cells, NO-aspirin 2 inhibited 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD)-induced cytochrome P450 (CYP) enzyme activity and CYP1A1 and CYP1A2 mRNA expression. These effects were further characterized as being mediated through transcriptional regulation: NO-aspirin 2 inhibited binding of ligand (TCDD)-activated aryl hydrocarbon receptor to the CYP1A1 enhancer sequence; additionally, NO-aspirin 2 suppressed carcinogen-induced expression of CYP1A heterogeneous nuclear RNA. The fate of carcinogen metabolites depends not only on activation by CYP enzymes but also detoxification by Phase II enzymes. Both HepG2 and LS180 cells treated with NO-aspirin 2 showed an increase in glutathione S-transferase-P1 (GST-P1), glutamate-cysteine ligase (GCL), and NAD(P)H:quinone oxidoreductase-1 (NQO1) expression. Compared with two other NO-releasing compounds, diethylenetriamine-NO and the organic nitrate, isosorbide dinitrate, the inhibitory effects of NO-aspirin 2 on TCDD-induced CYP activity and mRNA expression were considerably more potent. Furthermore, aspirin alone had no inhibitory effect on TCDD-induced CYP activity, nor did aspirin up-regulate GCL, GST-P1, or NQO1 expression. Consequent to the effects on carcinogen-metabolizing enzymes, NO-aspirin 2 inhibited [3H]benzo[a]pyrene-DNA adduct formation and DNA damage elicited by TCDD or benzo[a]pyrene. Our results demonstrate that NO-aspirin 2 may be an effective chemopreventive agent by favorably affecting the inhibitory and enhancing effects of Phase I and Phase II carcinogen metabolism, thereby protecting DNA from carcinogenic insult. PMID:19542225

  17. Effect of Quaternary Ammonium Carboxymethylchitosan on Release Rate In-vitro of Aspirin Sustained-release Matrix Tablets

    PubMed Central

    Meng, Lingbin; Teng, Zhongqiu; Zheng, Nannan; Meng, Weiwei; Dai, Rongji; Deng, Yulin

    2013-01-01

    The aim of this study was to develop a derivative of chitosan as pharmaceutical excipient used in sustained-release matrix tablets of poorly soluble drugs. A water-soluble quaternary ammonium carboxymethylchitosan was synthesized by a two-step reaction with carboxymethylchitosan (CMCTS), decylalkyl dimethyl ammonium and epichlorohydrin. The elemental analysis showed that the target product with 10.27% of the maximum grafting degree was obtained. To assess the preliminary safety of this biopolymer, cell toxicity assay was employed. In order to further investigate quaternary ammonium carboxymethylchitosan application as pharmaceutical excipient, aspirin was chosen as model drug. The effect of quaternary ammonium CMCTS on aspirin release rate from sustained-release matrix tablets was examined by in-vitro dissolution experiments. The results showed that this biopolymer had a great potential in increasing the dissolution of poorly soluble drug. With the addition of CMCTS-CEDA, the final cumulative release rate of drug rose up to 90%. After 12 h, at the grade of 10, 20 and 50 cps, the drug release rate increased from 58.1 to 90.7%, from 64.1 to 93.9%, from 69.3 to 96.1%, respectively. At the same time, aspirin release rate from sustainedrelease model was found to be related to the amount of quaternary ammonium CMCTS employed. With the increase of CMCTS-CEDA content, the accumulated release rate increased from 69.1% to 86.7%. The mechanism of aspirin release from sustained-release matrix tablets was also preliminary studied to be Fick diffusion. These data demonstrated that the chitosan derivative has positive effect on drug release from sustained-release matrix tablets. PMID:24250627

  18. Combination of Praziquantel and Aspirin Minimizes Liver Pathology of Hamster Opisthorchis viverrini Infection Associated Cholangiocarcinoma.

    PubMed

    Sudsarn, Pakkayanee; Boonmars, Thidarut; Ruangjirachuporn, Wipaporn; Namwat, Nisana; Loilome, Watcharin; Sriraj, Pranee; Aukkanimart, Ratchadawan; Nadchanan, Wonkchalee; Jiraporn, Songsri

    2016-01-01

    Opisthorchiasis is one of the major risk factors for cholangiocarcinoma (CCA) in northeastern Thailand. An effective drug for killing this parasite is praziquantel. Recently, several reports have shown that with frequent use, praziquantel may itself be a CCA risk and can cause liver cell damage from an immunopathological response after parasite death. Aspirin has many properties including anti-inflammation and anti-cancer. Therefore, we use of aspirin (As) and praziquantel (Pz) to improve hepatobiliary system function in hamsters infected with Opisthorchis viverrini (OV) and or administered N-nitrosodimethylamine (ND). Livers of OVNDAsPz, appeared healthy macroscopically, suggesting slow progression of cholangiocarcinoma evident by extent of fibrosis and bile duct cell proliferation was less than OVND although aggregations of inflammatory cells remained. Proliferating cell nuclear antigen (PCNA), cytokeratin 19 (CK19), and cancer antigen (CA19-9) staining were strongly positive in OVND, but were only slight in OVNDAs. Moreover, OVNDAsPz, appeared a few inflammatory infiltrations, bile duct proliferation, fibrosis and CCA area than the OVNDAs group. Thirty seven point five percent of hamster in this group could not develop CCA. These findings suggest that using aspirin combination with praziquantel treatment can improve the hepatobiliary system after O. viverrini infection and reduce the risk of CCA.

  19. Experimental impact of aspirin exposure on rat intestinal bacteria, epithelial cells and cell line.

    PubMed

    Upreti, Raj K; Kannan, A; Pant, A B

    2010-10-01

    Aspirin, a commonly used therapeutic non-steroidal anti-inflammatory drug (NSAID) is known to cause gastric mucosal damage. Intestinal bacteria having a regulatory effect on intestinal homeostasis play significant role in NSAID-induced intestinal injury. Bacteria and specific cell lines are considered to be suitable for toxicity screening and testing of chemicals. Therefore, to evaluate and compare in vitro toxicity, cultures of rat intestinal epithelial cells (IEC), isolated bacteria and IEC-6 cell line were assessed for viability, morphometric analysis, membrane transport enzymes and structural constituents for membrane damage, dehydrogenase activity test for respiratory and energy producing processes and esterase activity test for intra- and extra-cellular degradation, following the post exposure to aspirin (0-50 µg mL(- 1)). Similar pattern of dose-dependent changes in these parameters were observed in three types of cells. Similar in situ effects on IEC validated the in vitro findings. These findings indicate that higher aspirin concentrations may alter cellular functions of IEC and gut bacteria. Furthermore, results suggest that gut bacteria and IEC-6 cell line can be used for the initial screening of gastrointestinal cellular toxicity caused by NSAIDs. PMID:20167629

  20. Probing Vitamine C, Aspirin and Paracetamol in the Gas Phase: High Resolution Rotational Studies

    NASA Astrophysics Data System (ADS)

    Mata, S.; Cabezas, C.; Varela, M.; Pena, I.; Nino, A.; López, J. C.; Alonso, J. L.; Grabow, J.-U.

    2011-06-01

    A solid sample of Vitamin C (m.p. 190°C) vaporized by laser ablation has been investigated in gas phase and characterized through their rotational spectra. Two spectroscopy techniques has been used to obtain the spectra: a new design of broadband chirped pulse Fourier transform microwave spectroscopy with in-phase/quadrature-phase-modulation passage-acquired-coherence technique (IMPACT) and conventional laser ablation molecular beam Fourier transform microwave spectroscopy (LA-MB-FTMW). Up to now, two low-energy conformer have been observed and their rotational constants determined. Ab initio calculations at the MP2/6-311++G (d,p) level of theory predicted rotational constants which helped us to identify these conformers unequivocally. Among the molecules to benefit from the LA-MB-FTMW technique there are common important drugs never observed in the gas phase through rotational spectroscopy. We present here the results on acetyl salicylic acid and acetaminophen (m.p. 136°C), commonly known as aspirin and paracetamol respectively. We have observed two stable conformers of aspirin and two for paracetamol. The internal rotation barrier of the methyl group in aspirin has been determined for both conformers from the analysis of the A-E splittings due to the coupling of internal and overall rotation. J. L. Alonso, C. Pérez, M. E. Sanz, J. C. López, S. Blanco, Phys. Chem. Chem. Phys. 11,617-627 (2009)and references therein

  1. Microwave-assisted activated carbon from cocoa shell as adsorbent for removal of sodium diclofenac and nimesulide from aqueous effluents.

    PubMed

    Saucier, Caroline; Adebayo, Matthew A; Lima, Eder C; Cataluña, Renato; Thue, Pascal S; Prola, Lizie D T; Puchana-Rosero, M J; Machado, Fernando M; Pavan, Flavio A; Dotto, G L

    2015-05-30

    Microwave-induced chemical activation process was used to prepare an activated carbon from cocoa shell for efficient removal of two anti-inflammatories, sodium diclofenac (DFC) and nimesulide (NM), from aqueous solutions. A paste was obtained from a mixture of cocoa shell and inorganic components; with a ratio of inorganic: organic of 1 (CSC-1.0). The mixture was pyrolyzed in a microwave oven in less than 10 min. The CSC-1.0 was acidified with a 6 mol L(-1) HCl under reflux to produce MWCS-1.0. The CSC-1.0 and MWCS-1.0 were characterized using FTIR, SEM, N2 adsorption/desorption curves, X-ray diffraction, and point of zero charge (pHpzc). Experimental variables such as initial pH of the adsorbate solutions and contact time were optimized for adsorptive characteristics of MWCS-1.0. The optimum pH for removal of anti-inflammatories ranged between 7.0 and 8.0. The kinetic of adsorption was investigated using general order, pseudo first-order and pseu do-second order kinetic models. The maximum amounts of DCF and NM adsorbed onto MWCS-1.0 at 25 °C are 63.47 and 74.81 mg g(-1), respectively. The adsorbent was tested on two simulated hospital effluents. MWCS-1.0 is capable of efficient removal of DCF and NM from a medium that contains high sugar and salt concentrations.

  2. Survival of heparins, oral anticoagulants, and aspirin after the year 2010.

    PubMed

    Fareed, Jawed; Hoppensteadt, Debra A; Fareed, Daniel; Demir, Muzaffer; Wahi, Rakesh; Clarke, Melaine; Adiguzel, Cafer; Bick, Rodger

    2008-02-01

    The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants, and aspirin. Despite remarkable progress in life sciences, these drugs still remain a challenge and a mystery to us, and their use is far from optimized. The development of low-molecular-weight heparins and the synthesis of heparinomimetics, such as the chemically synthesized pentasaccharide, represent a refined use of heparin. Additional drugs from this knowledge will continue to develop; however, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, glycoprotein IIb/IIIa inhibitors, and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains as the approach of choice to manage thrombotic disorders. The new anticoagulant targets, including specific sites in the hemostatic network such as tissue factor, individual clotting factors (IIa, VIIa, IXa, Xa, XIIa, and XIIIa), recombinant forms of serpins (antithrombin, heparin cofactor II, and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin, and site-specific serine protease inhibitor complexes have also been developed. There is a major thrust on the development of orally bioavailable anticoagulant drugs (anti-Xa and anti-IIa agents), which are slated to replace oral anticoagulants. Both the anti-factor Xa and antithrombin agents have been developed for oral use and have provided impressive clinical outcomes in sponsor trials for the postsurgical prophylaxis of venous thrombosis; however, safety concerns related to liver enzyme elevations and

  3. Clinical Risk Factors for Gastroduodenal Ulcer in Romanian Low-Dose Aspirin Consumers.

    PubMed

    Negovan, Anca; Iancu, Mihaela; Moldovan, Valeriu; Voidazan, Septimiu; Bataga, Simona; Pantea, Monica; Sarkany, Kinga; Tatar, Cristina; Mocan, Simona; Banescu, Claudia

    2016-01-01

    Background. Aspirin use for cardiovascular or cancer prevention is limited due to its gastrointestinal side effects. Objective. Our prospective, observational case-control study aims to identify the predictive factors for ulcers in low-dose aspirin consumers (75-325 mg/day). Methods. The study included patients who underwent an upper digestive endoscopy and took low-dose aspirin treatment. Results. We recruited 51 patients with ulcer (ulcer group) and 108 patients with no mucosal lesions (control group). In univariate analysis, factors significantly associated with ulcers were male gender (p = 0.001), anticoagulants (p = 0.029), nonsteroidal anti-inflammatory drugs (p = 0.013), heart failure (p = 0.007), liver (p = 0.011) or cerebrovascular disease (p = 0.004), diabetes mellitus (p = 0.043), ulcer history (p = 0.044), and alcohol consumption (p = 0.018), but not Helicobacter pylori infection (p = 0.2). According to our multivariate regression analysis results, history of peptic ulcer (OR 3.07, 95% CI 1.06-8.86), cotreatment with NSAIDs (OR 8, 95% CI 2.09-30.58) or anticoagulants (OR 4.85, 95% CI 1.33-17.68), male gender (OR 5.2, 95% CI 1.77-15.34), and stroke (OR 7.27, 95% CI 1.40-37.74) remained predictors for ulcer on endoscopy. Conclusions. Concomitant use of NSAIDs or anticoagulants, comorbidities (cerebrovascular disease), and male gender are the most important independent risk factors for ulcer on endoscopy in low-dose aspirin consumers, in a population with a high prevalence of H. pylori infection. PMID:27579036

  4. Clinical Risk Factors for Gastroduodenal Ulcer in Romanian Low-Dose Aspirin Consumers

    PubMed Central

    Moldovan, Valeriu; Bataga, Simona; Pantea, Monica; Sarkany, Kinga; Tatar, Cristina; Mocan, Simona

    2016-01-01

    Background. Aspirin use for cardiovascular or cancer prevention is limited due to its gastrointestinal side effects. Objective. Our prospective, observational case-control study aims to identify the predictive factors for ulcers in low-dose aspirin consumers (75–325 mg/day). Methods. The study included patients who underwent an upper digestive endoscopy and took low-dose aspirin treatment. Results. We recruited 51 patients with ulcer (ulcer group) and 108 patients with no mucosal lesions (control group). In univariate analysis, factors significantly associated with ulcers were male gender (p = 0.001), anticoagulants (p = 0.029), nonsteroidal anti-inflammatory drugs (p = 0.013), heart failure (p = 0.007), liver (p = 0.011) or cerebrovascular disease (p = 0.004), diabetes mellitus (p = 0.043), ulcer history (p = 0.044), and alcohol consumption (p = 0.018), but not Helicobacter pylori infection (p = 0.2). According to our multivariate regression analysis results, history of peptic ulcer (OR 3.07, 95% CI 1.06–8.86), cotreatment with NSAIDs (OR 8, 95% CI 2.09–30.58) or anticoagulants (OR 4.85, 95% CI 1.33–17.68), male gender (OR 5.2, 95% CI 1.77–15.34), and stroke (OR 7.27, 95% CI 1.40–37.74) remained predictors for ulcer on endoscopy. Conclusions. Concomitant use of NSAIDs or anticoagulants, comorbidities (cerebrovascular disease), and male gender are the most important independent risk factors for ulcer on endoscopy in low-dose aspirin consumers, in a population with a high prevalence of H. pylori infection. PMID:27579036

  5. Aspirin therapy and thromboxane biosynthesis in systemic lupus erythematosus.

    PubMed

    Avalos, Ingrid; Chung, Cecilia P; Oeser, Annette; Milne, Ginger L; Borntrager, Holly; Morrow, Jason D; Raggi, Paolo; Solus, Joseph; Stein, C Michael

    2007-01-01

    Incomplete suppression of thromboxane biosynthesis during aspirin therapy is associated with increased cardiovascular risk. Since systemic lupus erythematosus (SLE) is associated with platelet activation and increased cardiovascular mortality, we compared thromboxane and prostacyclin biosynthesis in patients with SLE and control subjects, and measured inhibition of thromboxane excretion in aspirin-treated subjects. We measured the urinary excretion of 11-dehydro thromboxane B( 2) (TXB(2)) and 2,3-dinor 6-ketoPGF(1alpha) (PGI-M), the stable metabolites of thromboxane A(2) and prostacyclin, respectively, in 74 patients with SLE and 70 controls. In subjects who were not receiving aspirin, TXB(2) excretion was higher in patients with SLE [0.40 ng/mg creatinine (0.26-0.64), median (interquartile range)] than controls [0.31 ng/mg creatinine (0.23-0.44)] (P = 0.04), and in these patients, TXB(2) excretion correlated with disease activity (rho = 0.28, P = 0.03) and tumor necrosis factor alpha (rho = 0.48, P < 0.001). Aspirin therapy resulted in significantly lower TXB(2) excretion in controls (P = 0.01), but not in patients with SLE (P = 0.10), compared with subjects not receiving aspirin. Prostacyclin biosynthesis did not differ among patients and controls, and was not affected by aspirin (P all >0.35). Thromboxane biosynthesis is increased in SLE and is associated with disease activity. Additionally, response to aspirin may be attenuated in some patients with SLE. PMID:18042592

  6. Dose- and time-dependent antiplatelet effects of aspirin.

    PubMed

    Perneby, Christina; Wallén, N Håkan; Rooney, Cathy; Fitzgerald, Desmond; Hjemdahl, Paul

    2006-04-01

    Aspirin is widely used, but dosages in different clinical situations and the possible importance of "aspirin resistance" are debated. We performed an open cross-over study comparing no treatment (baseline) with three aspirin dosage regimens--37.5 mg/day for 10 days, 320 mg/day for 7 days, and, finally, a single 640 mg dose (cumulative dose 960 mg)--in 15 healthy male volunteers. Platelet aggregability was assessed in whole blood (WB) and platelet rich plasma (PRP). The urinary excretions of stable thromboxane (TxM) and prostacyclin (PGI-M) metabolites, and bleeding time were also measured. Platelet COX inhibition was nearly complete already at 37.5 mg aspirin daily, as evidenced by >98% suppression of serum thromboxane B2 and almost abolished arachidonic acid (AA) induced aggregation in PRP 2-6 h after dosing. Bleeding time was similarly prolonged by all dosages of aspirin. Once daily dosing was associated with considerable recovery of AA induced platelet aggregation in WB after 24 hours, even after 960 mg aspirin. Collagen induced aggregation in WB with normal extracellular calcium levels (hirudin anticoagulated) was inhibited <40% at all dosages. TxM excretion was incompletely suppressed, and increased <24 hours after the cumulative 960 mg dose. Aspirin treatment reduced PGI-M already at the lowest dosage (by approximately 25%), but PGI-M excretion and platelet aggregability were not correlated. Antiplatelet effects of aspirin are limited in WB with normal calcium levels. Since recovery of COX-dependent platelet aggregation occurred within 24 hours, once daily dosing of aspirin might be insufficient in patients with increased platelet turnover. PMID:16601836

  7. Comparative Effectiveness of Prestroke Aspirin on Stroke Severity and Outcome

    PubMed Central

    Park, Jong‐Moo; Kang, Kyusik; Cho, Yong‐Jin; Hong, Keun‐Sik; Lee, Kyung Bok; Park, Tai Hwan; Lee, Soo Joo; Ko, Youngchai; Han, Moon‐Ku; Lee, Jun; Cha, Jae‐Kwan; Kim, Dae‐Hyun; Kim, Dong‐Eog; Kim, Joon‐Tae; Choi, Jay Chol; Yu, Kyung‐Ho; Lee, Byung‐Chul; Lee, Ji Sung; Lee, Juneyoung; Gorelick, Philip B.

    2016-01-01

    Objective The effect of prestroke aspirin use on initial severity, hemorrhagic transformation, and functional outcome of ischemic stroke is uncertain. Methods Using a multicenter stroke registry database, patients with acute ischemic stroke of three subtypes (large artery atherosclerosis [LAA], small vessel occlusion [SVO], or cardioembolism [CE]) were identified. NIH stroke scale (NIHSS) and hemorrhagic transformation at presentation and discharge modified Rankin Scale (mRS) were compared between prestroke aspirin users and nonusers. Results Among the 10,433 patients, 1,914 (18.3%) reported prestroke aspirin use. On crude analysis, initial NIHSS scores of aspirin users were higher than nonusers (mean difference: 0.35; 95% confidence interval [CI]: 0.04–0.66). However, a multivariable analysis with an application of inverse probability of treatment weighting based on a propensity score of prestroke aspirin, having an interaction effect of prestroke aspirin use and stroke subtype in the model, showed less stroke severity for aspirin users in LAA, but not in SVO and CE than for nonusers; mean difference in NIHSS scores in LAA was –0.97 (95% CI: –1.45 to –0.49). With respect to hemorrhagic transformation and mRS, no significant interaction effects were found. Prestroke aspirin use increased the risk of hemorrhagic transformation (adjusted odd ratio: 1.34; 95% CI: 1.05–1.73), but decreased the odds of the higher discharge mRS (0.86; 0.76–0.96). Interpretation Prestroke aspirin use may reduce initial stroke severity in atherothrombotic stroke and can improve functional outcome at discharge despite an increase of hemorrhagic transformation irrespective of stroke subtype. Ann Neurol 2016;79:560–568 PMID:26754410

  8. The postulated mechanism of the protective effect of ginger on the aspirin induced gastric ulcer: Histological and immunohistochemical studies.

    PubMed

    Salah Khalil, Mahmoud

    2015-07-01

    There are many available drugs for treating gastric ulcer, but they have various side effects. Ginger is a folk, herbal medicine, which is used for treatment of various diseases including gastric ulcer. This study investigates the possible mechanism of the protective effect of ginger on aspirin induced gastric ulcer. Forty adult male albino rats were randomized into four groups (10 animal per each group) and orally received the followings once daily for 5 days: Group I: 3 ml of 1% carboxymethyl cellulose; Group II: ginger powder (200 mg/kg body weight) suspended in 3 mL of 1% carboxymethylcellulose; Group III: aspirin (400 mg/kg body weight) suspended in 3 ml of 1% carboxymethylcellulose in water. Group IV: ginger and 30 minutes later, received aspirin suspended in 1% carboxymethylcellulose, in similar doses as received in groups II and III. On day 6, rats were sacrificed. The animals were anesthetized and the stomach was removed for the macroscopic, histological (Haematoxylin & Eosin and Periodic Acid Shiff) and immunohistochemical investigations (Bax, inducible nitric oxide synthase and heat shock protein 70). Aspirin induced a significant increase of the macroscopic ulcer score, shed and disrupted epithelium, mucosal hemorrhage, submucosal edema and leukocyte infiltration, loss of the mucus of the mucosal surface significantly increased expression of apoptosis regulator Bax, inducible nitric oxide synthase (iNOS) and heat shock protein 70 (HSP70). Ginger ameliorated the histological changes by reducing Bax and iNOS and increasing HSP70 expressions.

  9. Esomeprazole and 325 mg/d Aspirin Reduce Tissue Concentrations of Prostaglandin E2 in Patients with Barrett’s Esophagus

    PubMed Central

    Falk, Gary W.; Buttar, Navtej S.; Foster, Nathan R.; Ziegler, Katie L. Allen; DeMars, Catherine J.; Romero, Yvonne; Marcon, Norman E.; Schnell, Thomas; Corley, Douglas A.; Sharma, Prateek; Cruz-Correa, Marcia R.; Hur, Chin; Fleischer, David E.; Chak, Amitabh; DeVault, Kenneth R.; Weinberg, David S.; Della’Zanna, Gary; Richmond, Ellen; Smyrk, Thomas C.; Mandrekar, Sumithra J.; Limburg, Paul J.

    2012-01-01

    Background & Aims Proton pump inhibitors (PPIs) and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett’s esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled phase II trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin E2 (PGE2) in patients with BE with no dysplasia or low-grade dysplasia. Methods Participants were recruited through the multi-center Cancer Prevention Network and randomly assigned to groups that were given esomeprazole (40 mg, twice daily) in combination with an aspirin placebo (once daily) (Arm A; n=42), with 81 mg aspirin (once daily) (Arm B; n=63), or with 325 mg aspirin (once daily) (Arm C; n=63) for 28 days. We collected esophageal biopsies before and after the intervention period, to determine the absolute change in mean concentrations of PGE2 (the primary endpoint). Results Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentrations of PGE2 was reduced by 67.6±229.68 pg/mL in Arm A, was reduced by 123.9±284.0 pg/mL in Arm B (P=.10 vs Arm A), and was reduced by 174.9 ±263.62 pg/mL in Arm C (P=.02 vs Arm A). Conclusions In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE2 patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. PMID:22796132

  10. Plasma histamine after methacholine, allergen, and aspirin challenges.

    PubMed

    Kinsella, M; Salari, H; Chan, H; Tse, K S; Chan-Yeung, M

    1987-01-01

    Plasma histamine levels were measured by radio-enzymatic technique in seven patients following 10 challenges: five methacholine challenge tests, four antigen inhalation challenge tests, and one oral aspirin challenge test. Baseline plasma histamine was the same in all patients except in the aspirin-challenged patient, who had a higher baseline histamine level. There was no statistical change in the level of histamine throughout the test in either the methacholine-challenged or the antigen-challenged patients, whereas there was a marked increase in histamine levels in the aspirin challenged patient. A possible explanation is that methacholine and antigen are inhaled and therefore have primarily local effects on the lung, whereas oral aspirin has a systemic effect with consequently systemic changes in histamine which are detectable as changes in plasma level.

  11. Effects of Low-Dose Aspirin Therapy on Thermoregulation in Firefighters

    PubMed Central

    McEntire, Serina J.; Reis, Steven E.; Suman, Oscar E.; Hostler, David

    2015-01-01

    Background Heart attack is the most common cause of line-of-duty death in the fire service. Daily aspirin therapy is a preventative measure used to reduce the morbidity of heart attacks but may decrease the ability to dissipate heat by reducing skin blood flow. Methods In this double-blind, placebo-controlled, crossover study, firefighters were randomized to receive 14 days of therapy (81-mg aspirin or placebo) before performing treadmill exercise in thermal-protective clothing in a hot room [38.8 ± 2.1°C, 24.9 ± 9.1% relative humidity (RH)]. Three weeks without therapy was provided before crossing to the other arm. Firefighters completed a baseline skin blood-flow assessment via laser Doppler flowmetry; skin was heated to 44°C to achieve maximal cutaneous vasodilation. Skin blood flow was measured before and after exercise in a hot room, and at 0 minutes, 10 minutes, 20 minutes, and 30 minutes of recovery under temperature conditions (25.3 ± 1.2°C, 40.3 ± 13.7% RH). Platelet clotting time was assessed before drug administration, and before and after exercise. Results Fifteen firefighters completed the study. Aspirin increased clotting time before and after exercise compared with placebo (p = 0.003). There were no differences in absolute skin blood flow between groups (p = 0.35). Following exercise, cutaneous vascular conductance (CVC) was 85 ± 42% of maximum in the aspirin and 76 ± 37% in the placebo groups. The percentage of maximal CVC did not differ by treatment before or after recovery. Neither maximal core body temperature nor heart rate responses to exercise differed between trials. Conclusion There were no differences in skin blood flow during uncompensable heat stress following exercise after aspirin or placebo therapy. PMID:26929836

  12. An Efficient Microscale Procedure for the Synthesis of Aspirin

    NASA Astrophysics Data System (ADS)

    Pandita, Sangeeta; Goyal, Samta

    1998-06-01

    The synthesis of aspirin is a part of many undergraduate organic synthesis labs and is frequently used in qualitative organic analysis laboratory for the identification of salicylic acid. We have found that aspirin can be synthesized on microscale by a simple and efficient procedure that eliminates the heating step employed in literature procedures and gives a pure, ferric-negative product (no purple color with alcoholic ferric chloride solution).

  13. Synthesis, spectroscopic characterization, crystallographic studies and antibacterial assays of new copper(II) complexes with sulfathiazole and nimesulide

    NASA Astrophysics Data System (ADS)

    Nunes, Julia Helena Bormio; de Paiva, Raphael Enoque Ferraz; Cuin, Alexandre; da Costa Ferreira, Ana Maria; Lustri, Wilton Rogério; Corbi, Pedro Paulo

    2016-05-01

    New ternary copper(II) complexes of sulfathiazole (SFT, C9H8N3O2S2) or nimesulide (NMS, C13H11N2O5S) and 2,2‧-bipyridine (bipy) were synthesized, and characterized by chemical and spectroscopic techniques. Elemental analyses indicated a 2:1:1 sulfonamide/copper/bipy composition for both complexes. Mass spectrometric measurements permitted identifying the molecular ions [Cu(SFT)2(bipy)+H]+ and [Cu(NMS)2(bipy)+H]+ at m/z 728 and 835, respectively, confirming the proposed compositions. Crystal structure of the [Cu(SFT)2(bipy)] complex was solved by powder X-ray diffraction analysis (PXRD), attesting that the Cu(II) ion is hexacoordinated in a distorted octahedral geometry. Each SFT molecule coordinates to the metal ion by the nitrogen atoms of the SO2-N group and of the heterocyclic ring. The coordination sphere is completed by a bipyridine. Electronic paramagnetic resonance (EPR) studies were carried out for the [Cu(NMS)2(bipy)] complex, indicating a tetragonal environment around the metal ion. It was suggested that NMS coordinates to Cu(II) by the nitrogen and oxygen atoms of the SO2-N group, which was confirmed by infrared spectroscopic studies. Biological studies showed the antibacterial activity of both Cu-SFT and Cu-NMS complexes, with the minimum inhibitory concentration (MIC) values ranging from 0.10 to 0.84 mmol L-1 against Gram-negative bacteria for [Cu(SFT)2(bipy)], and from 1.50 to 3.00 mmol L-1 against Gram-positive and -negative bacteria for [Cu(NMS)2(bipy)].

  14. Novel Resveratrol-Based Aspirin Prodrugs: Synthesis, Metabolism, and Anticancer Activity.

    PubMed

    Zhu, Yingdong; Fu, Junsheng; Shurlknight, Kelly L; Soroka, Dominique N; Hu, Yuhui; Chen, Xiaoxin; Sang, Shengmin

    2015-08-27

    Regular aspirin use has been convincingly shown to reduce the risk of colorectal cancer. However, long-term use of aspirin leads to gastrotoxicity. Herein, we designed and synthesized a novel class of resveratrol-based aspirin prodrugs to simultaneously release aspirin and resveratrol to attenuate the side effects caused by aspirin. Prodrug RAH exerted enhanced anticancer activities which are better than a physical mixture of aspirin and resveratrol as well as each individually. Metabolism of RAH in mice showed that the majority of RAH is decomposed to release resveratrol and aspirin or salicylic acid either in the intestine or after absorption. Mechanistic studies demonstrate RAH inhibits cell cycle arrest through downregulation of cyclins and induces apoptosis by activation of caspase-3 in cancer cells. These findings highlighted the improved anticancer properties of resveratrol-based aspirin prodrugs. RAH may represent novel and safe alternatives of aspirin for the purpose of daily use in the future.

  15. Searching for new NO-donor aspirin-like molecules: a new class of nitrooxy-acyl derivatives of salicylic acid.

    PubMed

    Lazzarato, Loretta; Donnola, Monica; Rolando, Barbara; Marini, Elisabetta; Cena, Clara; Coruzzi, Gabriella; Guaita, Elena; Morini, Giuseppina; Fruttero, Roberta; Gasco, Alberto; Biondi, Stefano; Ongini, Ennio

    2008-03-27

    A new class of products in which the phenol group of salicylic acid is linked to alkanoyl moieties bearing nitrooxy functions has been synthesized and studied for their polyvalent actions. The products were stable in acid and neutral media, while they were hydrolyzed in human serum. Their half-lives were dependent upon the structure of alkanoyl moieties. The products showed anti-inflammatory activities similar to aspirin when tested in the carrageenan-induced paw edema assay in the rat. Interestingly, unlike aspirin, they showed reduced or no gastrotoxicity in a lesion model in rats at equimolar doses. A number of them were able to inhibit platelet aggregation induced by collagen in human platelet-rich plasma. All of the products were capable of relaxing rat aortic strips precontracted with phenylephrine in a concentration-dependent manner. Selected members of this new class of nonsteroidal anti-inflammatory drugs might represent possible safer alternatives to aspirin in different clinical settings.

  16. Aspirin resistance in cerebrovascular disease and the role of glycoprotein IIIa polymorphism in Turkish stroke patients.

    PubMed

    Derle, Eda; Öcal, Ruhsen; Kibaroğlu, Seda; Çelikkol, Ceyda; Bayraktar, Nilüfer; Verdi, Hasibe; Ataç, Belgin F; Can, Ufuk

    2016-03-01

    Aspirin resistance occurs in 5-45% of high-risk patients, with various mechanisms proposed for its development. This study aimed to determine the relationships among aspirin resistance, aspirin dosage, type of aspirin and glycoprotein IIIa P1A1/A2 polymorphism in patients with vascular risk factors. Two hundred and eight (75 symptomatic, 133 asymptomatic) patients with vascular risk factors who were using aspirin for primary or secondary prevention were prospectively included. The symptomatic group was further classified into two groups according to aspirin use at the time of stroke. Aspirin resistance was measured by the PFA-100 system (collagen/epinephrine cartridge) and glycoprotein IIIa P1A1/A2 polymorphism was determined by PCR. The overall prevalence of aspirin resistance was 32.2%. The mean age of patients with aspirin resistance was significantly higher than that in those who did not have resistance (P = 0.009). The prevalence of aspirin resistance was similar for the symptomatic and asymptomatic under aspirin therapy groups. The resistance rate was found to be highest with 100 mg enteric-coated preparation use (39.3%). Increasing the aspirin dosage and/or shifting to uncoated preparations caused a change in aspirin sensitivity of 36-60%. Repeated measurements showed development of aspirin resistance in 14% of patients who were sensitive to aspirin in previous measurements. Glycoprotein IIIaP1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke were not significantly related. The effect of aspirin can change by time, dosage and type of preparation used. There are no relationships among glycoprotein IIIa P1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke.

  17. Combination therapy with aspirin plus clopidogrel versus aspirin plus ticlopidine for prevention of subacute thrombosis after successful native coronary stenting.

    PubMed

    Dangas, G; Mehran, R; Abizaid, A S; Curry, B H; Lansky, A J; Kent, K M; Pichard, A D; Satler, L F; Paliou, M; Stone, G W; Leon, M B

    2001-02-15

    We compared the combination of aspirin plus clopidrogrel (A+C) with aspirin and ticlopidine (A+T) for prevention of subacute stent thrombosis in 827 patients. At 30-day follow-up, there were trends toward increased subacute thrombosis with A+C compared with A+T (1.3% vs 0.2%, p = 0.10). These results suggest that A+C may have marginally higher subacute stent thrombosis than A+T. PMID:11179539

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

    MedlinePlus

    ... Before Using Aspirin to Lower Your Risk of Heart Attack or Stroke, What You Should Know Share Tweet ... use of aspirin will help to prevent a heart attack or stroke in your particular case. Aspirin can ...

  19. Inhaled lysine-aspirin as a bronchoprovocation procedure in aspirin-sensitive asthma: its repeatability, absence of a late-phase reaction, and the role of histamine.

    PubMed

    Phillips, G D; Foord, R; Holgate, S T

    1989-08-01

    Inhalation of an aerosolized solution of lysine-aspirin has previously been described as a safer technique than oral challenge with aspirin for the diagnosis of aspirin-sensitive asthma. We describe a modification of this method that involves inhalation of serially doubling incremental concentrations of lysine-aspirin by a standardized technique and allows construction of concentration-response curves. In 11 subjects with asthma, mean (SEM) age 48.2 (2.9) years, the geometric mean (range) provocation concentrations of histamine and lysine-aspirin required to produce a 20% decrease in FEV1 from baseline were 0.6 (0.04 to 3.2) and 48.3 (15.5 to 219) mg/ml, respectively. No relationship was found between these values. In seven of nine subjects investigated on two consecutive occasions, bronchoconstriction with lysine-aspirin was repeatable to within a single doubling concentration difference. Bronchoconstriction provoked by lysine-aspirin was more rapid than with oral aspirin and was not followed by any late asthmatic reaction or increase in nonspecific airway hyperresponsiveness. In six subjects, premedication with the selective H1 histamine-receptor antagonist, terfenadine, had no significant effect on bronchoconstriction provoked by inhaled lysine-aspirin, indicating little role for release of histamine in the response. We conclude that inhalation of lysine-aspirin may be used as a bronchoprovocation procedure for the diagnosis and investigation of aspirin-sensitive asthma. PMID:2503553

  20. Can aspirin prevent gallstone recurrence after successful extracorporeal shockwave lithotripsy?

    PubMed

    Adamek, H E; Buttmann, A; Weber, J; Riemann, J F

    1994-04-01

    Extracorporeal shockwave lithotripsy (ESWL) is a feasible procedure for the treatment of gallbladder stones in humans. Well-selected patients can achieve stone-free rates in a high percentage. With the gallbladder in situ, these patients are at risk of stone recurrence. There is considerable evidence that aspirin prevents cholesterol gallstone formation in animal models and may prevent gallstone recurrence in man. We attempted to clarify the risk of gallstone recurrence after successful piezoelectric lithotripsy in patients taking either low-dose aspirin or no medication. The first 45 patients shown to be completely free from stones after ESWL were randomized into two groups. One group received 100 mg aspirin daily; the other group did not receive any further medical therapy. Patients were further examined on an average of 19.6 months and 21.9 months, respectively. In the aspirin group the recurrence rate was 18.2%, whereas 21.7% of the patients in the control group developed recurrent stones. Seventy-eight per cent of these patients also had a recurrence of biliary pain. By life-table analysis we had, after a follow-up period of 24 months, a stone recurrence rate of 25% (+/- 11) in the aspirin group and 34% (+/- 14) in the control group. Our results indicate that recurrence prophylaxis remains one of the central questions in ESWL. In this preliminary study, 100 mg of aspirin daily was not able to reduce the recurrence rate after successful ESWL. Further studies will have to show whether higher doses of aspirin or other ways of preventing gallstone after ESWL are possible.

  1. Aspirin resistance: a clinical review focused on the most common cause, noncompliance.

    PubMed

    Schwartz, Kenneth A

    2011-04-01

    Aspirin is an inexpensive, readily available medication that reduces the risk of subsequent vascular disease by about 25% in patients with known occlusive vascular disease. Aspirin's beneficial effect is mediated via inhibition of arachidonic acid (AA) activation of platelets and is detected by demonstrating a decrease in platelet function and/or a decrease in prostaglandin metabolites. Patients who are assumed to be taking their aspirin, but who do not demonstrate an aspirin effect are labeled as, "aspirin resistant." This is an unfortunate designation as the vast majority of patients labeled as "aspirin resistant" are noncompliant. Noncompliance is demonstrated in multiple studies that use repeat testing for platelet inhibition in patients with an initial inadequate response to aspirin. When the test is repeated under condition where ingestion of the test aspirin is assured, the patients' platelets are inhibited. Instead of using the term "aspirin resistance," this review will use "inadequate response to aspirin." Patients with an inadequate aspirin response have an increased likelihood for subsequent vascular events. Detection and treatment of an inadequate aspirin response would be facilitated by the development of a bedside assay that uses whole blood, is technically simple, inexpensive, sensitive, specific, reproducible, and provides an answer in a few minutes. Future research in patients with an inadequate response to aspirin should focus on mechanisms to improve compliance, which should decrease their risk of future vascular events. PMID:23983843

  2. Histopathological evaluation of gastro protective effect of Berberis vulgaris (Zereshk) seeds against aspirin induced ulcer in albino mice.

    PubMed

    Majeed, Wafa; Aslam, Bilal; Javed, Ijaz; Khaliq, Tanweer; Muhammad, Faqir; Ali, Asghar; Raza, Ahmed

    2015-11-01

    The present study was carried out to investigate the antiulcer activity of Berberis vulgaris (Zereshk) seeds in albino mice. After acclimatization, animals were divided into six equal groups. Aspirin 150 mg/kg was used to induce gastric ulcer in all groups except normal control. Omeprazole 20mg/kg was used as synthetic anti ulcer drug in study. Three dose levels of B. vulgaris seed powder 300 mg/kg, 600 mg/kg and 900 mg/kg were used respectively orally. Histopathological analysis was carried out to evaluate the gastroprotective activity of B. vulgaris seed powder. Results of the study showed that in case of aspirin treated mice gastric luminal mucosa villi were decreased in height or were absent. In the glandular region there was connective tissue proliferation and also infiltration of cells. Similar infiltration of cells was present on muscularis mucosa. In esophageal region tumor cells were present. However three dose levels of B. vulgaris significantly reduced the tissue proliferation, infiltration of cells and sloughing induced by aspirin. Highest dose of B. vulgaris (900 mg/kg) showed similar results as synthetic antiulcer drug omeprazole.

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

    PubMed Central

    Mahmoud, Fatma Abd Elhalim; Hashem, Khalid S; Hussein Elkelawy, Asmaa Mohammed M

    2015-01-01

    Background No dose of aspirin is free of bleeding risk. Even at a dose as low as 75 mg/day, the risk of upper gastrointestinal bleeding is twice as high as among nonusers. Nanoemulsions (NEs) are emulsion systems with droplet size in nanometer scale in which oil or water droplets are finely dispersed in the opposite phase with the help of a suitable surfactant to stabilize the system. Objectives The objective of this study was to determine the effect of aspirin NE in comparison to conventional aspirin. Materials and methods A total of 24 male rats were used in the study and arbitrarily assigned to four groups. Group 1 was the control group, and was given saline. Group 2 was given blank NE 1.5 mL/kg orally. Group 3 was given aspirin 30 mg/kg body weight orally. Group 4 was given aspirin NE 30 mg/kg body weight orally. Rats were killed, and gastric tissue was quickly excised after dissection of the animals. The tissues were divided into three pieces. The first one was kept in formalin 10% for pathological investigation. The second piece was kept in liquid nitrogen for molecular investigation. The third piece was homogenized in ten volumes of ice-cold phosphate-buffered saline (pH 7) using a Teflon homogenizer until a uniform suspension was obtained. The homogenate was centrifuged at 4,000 rpm for 30 minutes at 4°C to separate the supernatant from cellular debris. The supernatant was then used for the estimation of biochemical assays. Results The present study shows that aspirin has a toxic effect on the stomach as a result of inducing marked oxidative damage and the release of reactive oxygen species. This was shown by the significant increase in TNFα, iNOS, prostaglandin E2, and malondialdehyde levels, and also a significant decrease in glutathione, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase. In the aspirin-treated group compared to the control group, the NE had a protective effect on the stomach and caused less injury than

  4. Antiplatelet Drugs

    PubMed Central

    Hirsh, Jack; Spencer, Frederick A.; Baglin, Trevor P.; Weitz, Jeffrey I.

    2012-01-01

    The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

  5. In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid chromatography tandem mass spectrometry.

    PubMed

    Shen, Youming; Liu, Xiwang; Yang, Yajun; Li, Jianyong; Ma, Ning; Li, Bing

    2015-01-01

    Aspirin eugenol ester (AEE) is a promising drug candidate for treatment of inflammation, pain and fever and prevention of cardiovascular diseases with fewer side effects than its precursor, aspirin. Investigation into its metabolic process in target animal species will help to illustrate its mechanism of action and to establish its residual mark compound to formulate its dosage. Six beagle dogs were orally given a dose of 20 mg kg(-1) of AEE and one dog was used to prepare blank liver microsomes. Their liver microsomes were prepared for in vitro study and their plasma and urine were collected for in vivo metabolic analysis using liquid chromatography tandem mass spectrometry. In this study we identified 10 metabolites, M1, M2, M3, M4, M5 in phase I and M6, M7, M8, M9, M10 in phase II. Based on the metabolites of AEE, the pathways of AEE metabolism in dog were demonstrated.

  6. In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid chromatography tandem mass spectrometry.

    PubMed

    Shen, Youming; Liu, Xiwang; Yang, Yajun; Li, Jianyong; Ma, Ning; Li, Bing

    2015-01-01

    Aspirin eugenol ester (AEE) is a promising drug candidate for treatment of inflammation, pain and fever and prevention of cardiovascular diseases with fewer side effects than its precursor, aspirin. Investigation into its metabolic process in target animal species will help to illustrate its mechanism of action and to establish its residual mark compound to formulate its dosage. Six beagle dogs were orally given a dose of 20 mg kg(-1) of AEE and one dog was used to prepare blank liver microsomes. Their liver microsomes were prepared for in vitro study and their plasma and urine were collected for in vivo metabolic analysis using liquid chromatography tandem mass spectrometry. In this study we identified 10 metabolites, M1, M2, M3, M4, M5 in phase I and M6, M7, M8, M9, M10 in phase II. Based on the metabolites of AEE, the pathways of AEE metabolism in dog were demonstrated. PMID:24935248

  7. Aspirin inhibits glucose-6-phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites

    PubMed Central

    Ai, Guoqiang; Dachineni, Rakesh; Kumar, D. Ramesh; Alfonso, Lloyd F.; Marimuthu, Srinivasan; Bhat, G. Jayarama

    2016-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first reaction in the pentose phosphate pathway, and generates ribose sugars, which are required for nucleic acid synthesis, and nicotinamide adenine dinucleotide phosphate (NADPH), which is important for neutralization of oxidative stress. The expression of G6PD is elevated in several types of tumor, including colon, breast and lung cancer, and has been implicated in cancer cell growth. Our previous study demonstrated that exposure of HCT 116 human colorectal cancer cells to aspirin caused acetylation of G6PD, and this was associated with a decrease in its enzyme activity. In the present study, this observation was expanded to HT-29 colorectal cancer cells, in order to compare aspirin-mediated acetylation of G6PD and its activity between HCT 116 and HT-29 cells. In addition, the present study aimed to determine the acetylation targets of aspirin on recombinant G6PD to provide an insight into the mechanisms of inhibition. The results demonstrated that the extent of G6PD acetylation was significantly higher in HCT 116 cells compared with in HT-29 cells; accordingly, a greater reduction in G6PD enzyme activity was observed in the HCT 116 cells. Mass spectrometry analysis of aspirin-acetylated G6PD (isoform a) revealed that aspirin acetylated a total of 14 lysine residues, which were dispersed throughout the length of the G6PD protein. One of the important amino acid targets of aspirin included lysine 235 (K235, in isoform a) and this corresponds to K205 in isoform b, which has previously been identified as being important for catalysis. Acetylation of G6PD at several sites, including K235 (K205 in isoform b), may mediate inhibition of G6PD activity, which may contribute to the ability of aspirin to exert anticancer effects through decreased synthesis of ribose sugars and NADPH. PMID:27356773

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

    PubMed

    Ma, Ning; Liu, Xi-Wang; Yang, Ya-Jun; Li, Jian-Yong; Mohamed, Isam; Liu, Guang-Rong; Zhang, Ji-Yu

    2015-01-01

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

  9. Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat.

    PubMed

    Wang, Chong; Wang, Changyuan; Liu, Qi; Meng, Qiang; Cang, Jian; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi; Huo, Xiaokui; Liu, Kexin

    2014-06-01

    This study aimed to evaluate the transporter-mediated renal excretion mechanism for cilostazol and to characterize the mechanism of drug-drug interaction (DDI) between cilostazol and aspirin or probenecid. Concentrations of cilostazol and its metabolites OPC-13015 [6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-2(1H)-quinolinone] and OPC-13213 [3,4-dihydro-6-[4-[1-(trans-4-hydroxycyclohexyl)-1H-tetrazol-5-yl]butoxy]-2-(1H)-quinolinone] in rat biologic or cell samples were measured by liquid chromatography-tandem mass spectrometry. Coadministration with probenecid, benzylpenicillin, or aspirin decreased the cumulative urinary excretion of cilostazol and renal clearance. Concentrations of cilostazol and OPC-13213 in plasma decreased, and the concentration of OPC-13015 increased in the presence of probenecid. By contrast, rat plasma cilostazol, in combination with benzylpenicillin or aspirin, sharply increased, and concentrations of OPC-13015 and OPC-13213 did not change. In urine, OPC-13015 was below the level of detection. The cumulative urinary excretion of OPC-13213 decreased in the presence of probenecid, benzylpenicillin, or aspirin. Cilostazol was distributed in the kidney and liver, with tissue to plasma partition coefficient (Kp) values of 8.4 ml/g and 16.3 ml/g, respectively. Probenecid and aspirin reduced cilostazol distribution in the kidney. Probenecid did not affect cilostazol metabolism in the kidney but increased cilostazol metabolism in the liver, and aspirin had no effect on cilostazol metabolism. Benzylpenicillin, aspirin, and cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) reduced cilostazol uptake in kidney slices and human organic anion transporter 3 (hOAT3)-human embryonic kidney 293 (HEK293) cells, whereas p-aminohippuric acid did not. Compared with the vector, hOAT3-HEK293 cells accumulated more cilostazol, whereas hOAT1-HEK293 cells did not. OAT3 and Oat3 play a major role in cilostazol renal excretion, whereas OAT1 and Oat1 do not. Oat3 and Cyp

  10. Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat.

    PubMed

    Wang, Chong; Wang, Changyuan; Liu, Qi; Meng, Qiang; Cang, Jian; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi; Huo, Xiaokui; Liu, Kexin

    2014-06-01

    This study aimed to evaluate the transporter-mediated renal excretion mechanism for cilostazol and to characterize the mechanism of drug-drug interaction (DDI) between cilostazol and aspirin or probenecid. Concentrations of cilostazol and its metabolites OPC-13015 [6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-2(1H)-quinolinone] and OPC-13213 [3,4-dihydro-6-[4-[1-(trans-4-hydroxycyclohexyl)-1H-tetrazol-5-yl]butoxy]-2-(1H)-quinolinone] in rat biologic or cell samples were measured by liquid chromatography-tandem mass spectrometry. Coadministration with probenecid, benzylpenicillin, or aspirin decreased the cumulative urinary excretion of cilostazol and renal clearance. Concentrations of cilostazol and OPC-13213 in plasma decreased, and the concentration of OPC-13015 increased in the presence of probenecid. By contrast, rat plasma cilostazol, in combination with benzylpenicillin or aspirin, sharply increased, and concentrations of OPC-13015 and OPC-13213 did not change. In urine, OPC-13015 was below the level of detection. The cumulative urinary excretion of OPC-13213 decreased in the presence of probenecid, benzylpenicillin, or aspirin. Cilostazol was distributed in the kidney and liver, with tissue to plasma partition coefficient (Kp) values of 8.4 ml/g and 16.3 ml/g, respectively. Probenecid and aspirin reduced cilostazol distribution in the kidney. Probenecid did not affect cilostazol metabolism in the kidney but increased cilostazol metabolism in the liver, and aspirin had no effect on cilostazol metabolism. Benzylpenicillin, aspirin, and cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) reduced cilostazol uptake in kidney slices and human organic anion transporter 3 (hOAT3)-human embryonic kidney 293 (HEK293) cells, whereas p-aminohippuric acid did not. Compared with the vector, hOAT3-HEK293 cells accumulated more cilostazol, whereas hOAT1-HEK293 cells did not. OAT3 and Oat3 play a major role in cilostazol renal excretion, whereas OAT1 and Oat1 do not. Oat3 and Cyp

  11. Talk With Your Health Care Provider About Taking Aspirin to Prevent Strokes

    MedlinePlus

    ... Heart and Circulation For Women Talk With Your Health Care Provider About Taking Aspirin to Prevent Strokes Did ... attacks. Please see the brochure Talk with Your Health Care Provider About Taking Aspirin to Prevent Heart Attacks ...

  12. Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters.

    PubMed

    Kanani, Kunal; Gatoulis, Sergio C; Voelker, Michael

    2015-01-01

    Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer's clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA) is rapidly converted into its main active metabolite, salicylic acid (SA). Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters. PMID:26247959

  13. Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters

    PubMed Central

    Kanani, Kunal; Gatoulis, Sergio C.; Voelker, Michael

    2015-01-01

    Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer’s clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA) is rapidly converted into its main active metabolite, salicylic acid (SA). Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters. PMID:26247959

  14. Stability of aspirin in liquid and semisolid bases V: polyglycerol esters.

    PubMed

    Whitworth, C W; Asker, A F

    1975-12-01

    The stability of aspirin in decaglycerol tetraoleate, decaglycerol octaoleate, and decaglycerol decaoleate was studied at 4, 26, and 45 degrees. Degradation of aspirin in these polyglycerol esters was temperature dependent. Aspirin demonstrated the greatest stability in decaglycerol octaoleate and the lowest stability in decaglycerol tetraoleate at all temperatures studied. The hydroxyl value and the viscosity of the polyglycerol ester appeared to influence the stability of aspirin.

  15. Drugs.

    ERIC Educational Resources Information Center

    Hurst, Hunter, Ed.; And Others

    1984-01-01

    This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

  16. Esophageal mucosal lesion with low-dose aspirin and prasugrel mimics malignancy: A case report

    PubMed Central

    Ma, Gui-Fen; Gao, Hong; Chen, Shi-Yao

    2011-01-01

    Dual antiplatelet therapy consisting of low-dose aspirin (LDA) and other antiplatelet medications is recommended in patients with coronary heart disease, but it may increase the risk of esophageal lesion and bleeding. We describe a case of esophageal mucosal lesion that was difficult to distinguish from malignancy in a patient with a history of ingesting LDA and prasugrel after implantation of a drug-eluting stent. Multiple auxiliary examinations were performed to make a definite diagnosis. The patient recovered completely after concomitant acid-suppressive therapy. Based on these findings, we strongly argue for the evaluation of the risk of gastrointestinal mucosal injury and hemorrhage if LDA therapy is required, and we stress the paramount importance of using drug combinations in individual patients. PMID:22046096

  17. Effervescent metoclopramide and aspirin (Migravess) versus effervescent aspirin or placebo for migraine attacks: a double-blind study.

    PubMed

    Tfelt-Hansen, P; Olesen, J

    1984-06-01

    Aspirin 650 mg and metoclopramide 10 mg in an effervescent preparation (Migravess) were compared with effervescent aspirin 650 mg (Alka-Seltzer) and placebo for common migraine attacks with a double-blind cross-over design. One hundred and eighteen patients with common migraine were entered. Eighty-five patients completed all three forms of treatment, eleven completed two, and six completed one. Medicine was taken when patients were sure they had a migraine attack and not just interval headache. After each form of treatment, they mailed a report form to the investigators. Additional medication was allowed after 2 h and was taken for 79/95 placebo treated attacks, 63/92 Migravess treated attacks, and 51/86 aspirin treated attacks (p less than 0.01). Aspirin was significantly better than placebo for pain but not quite significant for nausea. Migravess was significantly better than placebo for pain and for nausea. There was no significant difference between aspirin and Migravess with regard to analgesic effectiveness (p = 0.33) or to antinausea effect (p = 0.18). PMID:6375873

  18. Stability of aspirin in propoxyphene compound dosage forms.

    PubMed

    Goldberg, R; Nightingale, C H

    1977-03-01

    The stability of aspirin in propoxyphene compound capsules made by three manufacturers, stored under a variety of temperature and humidity conditions, was compared. The cotton packing was removed from 100-capsule bottles, and the containers were stored (capped) under the following conditions: 25 c37 C and 50 C at both high (90%) and low (10%) humidity. No desiccant was removed from the bottles if originally present. The products tested were Darvon Compound-65 (two formulations) (Lilly), SK-65 Compound (Smith Kline & French) and Dolene Compound-65 (Lederle). Under all conditions, the stability of aspirin in the SK-65 Compound product was greater than that of Darvon Compound-65 which in turn was greater than Dolene Compound-65. Further, the rate of aspirin decomposition was greater in the latter product than in the others.

  19. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    NASA Astrophysics Data System (ADS)

    Alsop, Richard; Barrett, Matthew; Zheng, Sonbo; Dies, Hannah; Rheinstadter, Maikel

    2014-03-01

    Aspirin (ASA) is often prescribed for patients with high levels of cholesterol for the secondary prevention of myocardial events, a regimen known as the Low-Dose Aspirin Therapy. We have recently shown that Aspirin partitions in lipid bilayers. However, a direct interplay between ASA and cholesterol has not been investigated. Cholesterol is known to insert itself into the membrane in a dispersed state at moderate concentrations (under ~37.5%) and decrease fluidity of membranes. We prepared model lipid membranes containing varying amounts of both ASA and cholesterol molecules. The structure of the bilayers as a function of ASA and cholesterol concentration was determined using high-resolution X-ray diffraction. At cholesterol levels of more than 40mol%, immiscible cholesterol plaques formed. Adding ASA to the membranes was found to dissolve the cholesterol plaques, leading to a fluid lipid bilayer structure. We present first direct evidence for an interaction between ASA and cholesterol on the level of the cell membrane.

  20. High-pressure polymorphism of acetylsalicylic acid (aspirin): Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Crowell, Ethan L.; Dreger, Zbigniew A.; Gupta, Yogendra M.

    2015-02-01

    Micro-Raman spectroscopy was used to elucidate the high-pressure polymorphic behavior of acetylsalicylic acid (ASA), an important pharmaceutical compound known as aspirin. Using a diamond anvil cell (DAC), single crystals of the two polymorphic phases of aspirin existing at ambient conditions (ASA-I and ASA-II) were compressed to 10 GPa. We found that ASA-I does not transform to ASA-II, but instead transforms to a new phase (ASA-III) above ∼2 GPa. It is demonstrated that this transformation primarily introduces structural changes in the bonding and arrangement of the acetyl groups and is reversible upon the release of pressure. In contrast, a less dense ASA-II shows no transition in the pressure range studied, though it appears to exhibit a disordered structure above 7 GPa. Our results suggest that ASA-III is the most stable polymorph of aspirin at high pressures.

  1. Should Aspirin be Continued in Patients Started on Warfarin?

    PubMed Central

    Larson, Robin J; Fisher, Elliott S

    2004-01-01

    BACKGROUND AND OBJECTIVE Clinicians frequently face the decision of whether to continue aspirin when starting patients on warfarin. We performed a meta-analysis to characterize the tradeoffs involved in this common clinical dilemma. DATA SOURCES Multiple computerized databases (1966 to 2003), reference lists of relevant articles, conference proceedings, and queries of primary authors. STUDY SELECTION Randomized trials comparing warfarin plus aspirin versus warfarin alone. Studies with target international normalized ratios (INRs) <2 were excluded. DATA EXTRACTION Two reviewers independently extracted baseline data and major outcomes: rates of thromboembolism, hemorrhage, and all-cause mortality. DATA SYNTHESIS Nine studies met the inclusion criteria. Of the five that enrolled patients with mechanical heart valves, four used the same target INR in both groups, while one used a reduced target INR for the warfarin plus aspirin group. Pooling the results of the first four studies demonstrated that combination of warfarin plus aspirin significantly decreased thromboembolic events (relative risk [RR], 0.33; 95% confidence interval [CI], 0.19 to 0.58), increased major bleeding (RR, 1.58; 95% CI, 1.02 to 2.44), and decreased all-cause mortality (RR, 0.43; 95% CI, 0.23 to 0.81) compared to warfarin alone. The one valve trial using a reduced INR in the warfarin plus aspirin group reported no difference in thromboembolic outcomes but found decreased major bleeding and a significant mortality benefit with combination therapy. Of the remaining trials, three evaluated a warfarin indication not routinely used in the United States (post-myocardial infarction), and the only trial that considered atrial fibrillation was terminated early due to inadequate enrollment. CONCLUSIONS For mechanical heart valve patients, the benefits of continuing aspirin when starting warfarin therapy are clear. For other routine warfarin indications, there are not adequate data to guide this common

  2. Aspirin resistance as cardiovascular risk after kidney transplantation

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

    International surveys have shown that the leading cause of death after kidney transplantation has cardiovascular origin with a prevalence of 35-40%. As a preventive strategy these patients receive aspirin (ASA) therapy, even though their rate of aspirin resistance is still unknown. In our study, platelet aggregation measurements were performed between 2009 and 2012 investigating the laboratory effect of low-dose aspirin (100 mg) treatment using a CARAT TX4 optical aggregometer. ASA therapy was considered clinically effective in case of low ( i.e., below 40%) epinephrine-induced (10 μM) platelet aggregation index. Rate of aspirin resistance, morbidity and mortality data of kidney transplanted patients (n = 255, mean age: 49 ± 12 years) were compared to a patient population with cardio- and cerebrovascular diseases (n = 346, mean age: 52.6 ± 11 years). Rate of aspirin resistance was significantly higher in the renal transplantation group (RT) compared to the positive control group (PC) (35.9% vs. 25.6%, p < 0.002). Morbidity analysis demonstrated significantly higher incidence of myocardial infarction, hypertension and diabetes mellitus in the RT group (p < 0.05). The subgroup analysis revealed significantly higher incidence of infarction and stroke in the ASA resistant RT group compared to the RT patients without ASA resistance (p < 0.05). Furthermore, the incidence of myocardial infarction and hypertension was significantly higher in the non-resistant RT group than in the group of PC patients without ASA resistance (p < 0.05). These results may suggest that the elevated rate of aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

  3. Newer drugs for arthritis.

    PubMed

    McGillivray, D C

    1977-01-01

    The major area of new drug discoveries for the treatment of arthritis is in non-steroidal anti-inflammatory agents (NSAIA). Unfortunately, as yet no new and safe drug of major significance has appeared. Aspirin still ranks high beside the newcomers. Indomethacin, ibuprofen, naproxen, fenoprofen and tolmetin are described and their roles in therapy are discussed. A further group of older drugs receiving new application in the treatment of arthritis is presented. These include penicillamine and the immunosuppressive drugs. Gold and chloroquin are also discussed to put these agents in their proper perspective.

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

    SciTech Connect

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

    2012-03-15

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

  5. [Melatonin production in thrombocytes and their functional activity in patients with aspirin asthma].

    PubMed

    Evsiukova, E V; Muraia, E V; Zubzhitskaia, L B; Kveshnoĭ, I M

    2007-01-01

    The aim of the investigation was to study melatonin production in thrombocytes and their functional activity in correlation with 6-sulfatoximelatonin (6-SOM) urinary excretion in patients with aspirin-induced bronchial asthma (AIBA). Forty-three patients with bronchial asthma (BA) were examined. The main group consisted of 26 AIBA patients; the comparison group consisted of 17 BA patients with no intolerance to aspirin or other non-steroidal anti-inflammatory drugs; 30 practically healthy individuals constituted the control group. The study found no melatonin production in thrombocytes of AIBA patients: only 13.0 +/- 1.3% of platelets expressed melatonin, while in healthy people 97.7 +/- 0.6% of the cells did. Besides, daytime urinary excretion of 6-SOM, the main melatonin metabolite, was lower in AIBA patients. Lower daytime and higher nighttime melatonin production in AIBA patients correlated with the acceleration of the 1st phase and increased intensity of thrombocyte aggregation, which evidences high thrombocyte reactivity to the inducing agent. The presence of a pathologic reaction of thrombocytes to exogenous melatonin, manifesting by changes in the 1st stage of aggregation, suggests the presence of pathology in thrombocyte membrane-receptor complex and the calcium homeostasis of the cell, which determines constant activation and the participation of thrombocytes in the development of asthmatic syndrome. PMID:18154178

  6. Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites.

    PubMed

    Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I

    2011-01-01

    Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) to lipoxin A₄ (LXA₄) and 15-epi-LXA₄. However, it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE₂, TXB₂ and leukotriene B₄ (LTB₄) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE₂, but increased LTB₄, LXA₄ and 15-epi-LXA₄ concentrations. Both doses attenuated the LPS effects on PGE₂, and TXB₂. The increments in LXA₄ and 15-epi-LXA₄ caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA₄ and 15-epi-LXA₄ and reduce pro-inflammatory PGE₂ and TXB₂ suggests considering aspirin further for treating clinical neuroinflammation. PMID:20981485

  7. Erosive gastritis with special reference to the role of aspirin and bile.

    PubMed

    Reynolds, K W

    1974-11-01

    The high mortality associated with the surgical treatment of erosive gastritis is related to the postoperative continuing haemorrhage rate. Immediate gastroscopy has significantly improved preoperative diagnosis, and in 30 cases treated by the Billroth I operation continuing haemorrhage was seen on only one occasion.The frequent association of chronic gastritis and drug-associated erosive gastritis suggests that the gastritic mucosa is unusually susceptible to aspirin. Experiments designed to investigate the effect of biliary diversion on aspirin-induced gastric mucosal damage demonstrated a significant increase in such damage.Intestinal metaplasia and chronic gastritis of the gastric mucosa develop when upper intestinal secretions are diverted into the stomach either surgically or by pyloric regurgitation. Postoperative gastric aspiration indicates that the Billroth I operation is associated with far less regurgitation of upper intestinal secretions postoperatively than either the Polya operation or vagotomy and drainage. It is suggested that the efficacy of the Billroth I operation in controlling haemorrhage in the immediate postoperative period is related to this. In the long term the reduced incidence of intestinal metaplasia in the Billroth I gastric remnant reflects a minimal tendency to biliary reflux.

  8. The Role of Aspirin, Vitamin D, Exercise, Diet, Statins, and Metformin in the Prevention and Treatment of Colorectal Cancer.

    PubMed

    Sehdev, Amikar; O'Neil, Bert H

    2015-09-01

    Colorectal cancer (CRC) is a worldwide health problem leading to significant morbidity and mortality. Several strategies based on either lifestyle modifications or pharmacological interventions have been developed in an attempt to reduce the risk of CRC. In this review article, we discuss these interventions including aspirin (and other non-steroidal anti-inflammatory drugs), vitamin D, exercise, diet, statins, and metformin. Depending upon the risk of developing CRC, the current evidence supports the beneficial role of aspirin, vitamin D, diet, and exercise especially in high-risk individuals (advanced adenoma or CRC). However, even with these established interventions, there are significant knowledge gaps such as doses of aspirin and 25-hydroxy vitamin D are not well established. Similarly, there is no convincing data from randomized controlled trials that a high fiber diet or a low animal fat diet reduces the risk of CRC. Some potential interventions, such as statins and metformin, do not have convincing data for clinical use even in high-risk individuals. However, these may have emerging roles in the prevention and treatment of CRC. Greater understanding of molecular mechanisms and the application of genomic tools to risk stratify an individual and tailor the interventions based on that individual's risk will help further advance the field. Some of this work is already underway and is a focus of this article. PMID:26187794

  9. Validation of low‐dose aspirin prescription data in The Health Improvement Network: how much misclassification due to over‐the‐counter use?

    PubMed Central

    Cea Soriano, Lucía; Soriano‐Gabarró, Montse

    2015-01-01

    Abstract Purpose We aimed to quantify the extent of over‐the‐counter (OTC) low‐dose aspirin use among patients in The Health Improvement Network (THIN) in the UK. Methods In September 2013, a random sample of low‐dose aspirin users (75 past users and 75 never users) was identified based on prescriptions recorded in THIN. Primary care practitioners (PCPs) were sent questionnaires to provide information on patients' use of OTC low‐dose aspirin. Results One hundred and forty valid questionnaires were received (93.30% [95%CI: 88.16–96.34] response rate). Current use of low‐dose aspirin was reported by PCPs in 4.23% (95%CI: 1.45–11.70) (n = 3) of past users (OTC use in one patient) and in 2.9% (95%CI: 0.78–9.70) (n = 2) of never users (OTC use in one patient). In addition, PCPs reported past use of low‐dose aspirin in 88.70% (95%CI: 79.31–94.18) (n = 63) of past users (all prescribed; none as OTC) and in 2.82% (95%CI: 0.78–9.70) (n = 2) of never users (as OTC). Among past users, PCPs reported the indication for low‐dose aspirin as primary cardiovascular disease (CVD) prevention in 63.16% (95%CI: 50.18–74.48) of patients and secondary CVD prevention in 31.58% (95%CI: 21.00–44.48) of patients. Corresponding percentages based on THIN were 78.95% (95%CI: 66.71–87.53) and 21.1% (95%CI: 12.47–33.29), respectively. Conclusion Our findings show the small impact of potential misclassification of low‐dose aspirin use in THIN due to unrecorded OTC use. The small proportion of false negatives confirms the utility of THIN for utilization and outcome studies of low‐dose aspirin. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. PMID:26660710

  10. Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry.

    PubMed

    Lucido, Michael J; Orlando, Benjamin J; Vecchio, Alex J; Malkowski, Michael G

    2016-03-01

    Aspirin and other nonsteroidal anti-inflammatory drugs target the cyclooxygenase enzymes (COX-1 and COX-2) to block the formation of prostaglandins. Aspirin is unique in that it covalently modifies each enzyme by acetylating Ser-530 within the cyclooxygenase active site. Acetylation of COX-1 leads to complete loss of activity, while acetylation of COX-2 results in the generation of the monooxygenated product 15(R)-hydroxyeicosatetraenoic acid (15R-HETE). Ser-530 has also been shown to influence the stereochemistry for the addition of oxygen to the prostaglandin product. We determined the crystal structures of S530T murine (mu) COX-2, aspirin-acetylated human (hu) COX-2, and huCOX-2 in complex with salicylate to 1.9, 2.0, and 2.4 Å, respectively. The structures reveal that (1) the acetylated Ser-530 completely blocks access to the hydrophobic groove, (2) the observed binding pose of salicylate is reflective of the enzyme-inhibitor complex prior to acetylation, and (3) the observed Thr-530 rotamer in the S530T muCOX-2 crystal structure does not impede access to the hydrophobic groove. On the basis of these structural observations, along with functional analysis of the S530T/G533V double mutant, we propose a working hypothesis for the generation of 15R-HETE by aspirin-acetylated COX-2. We also observe differential acetylation of COX-2 purified in various detergent systems and nanodiscs, indicating that detergent and lipid binding within the membrane-binding domain of the enzyme alters the rate of the acetylation reaction in vitro.

  11. Role of antiplatelet drugs in the prevention of cardiovascular events.

    PubMed

    Tendera, Michal; Wojakowski, Wojciech

    2003-06-15

    Antiplatelet drugs have an established place in the prevention of vascular events in a variety of clinical conditions, such as myocardial infarction, stroke and cardiovascular death. Both European and American guidelines recommend the use of antiplatelet drugs in patients with established coronary heart disease and other atherosclerotic disease. In high-risk patients, such as those with post-acute myocardial infarction (AMI), ischaemic stroke or transient ischaemic attack, and in patients with stable or unstable angina, peripheral arterial occlusive disease or atrial fibrillation, antiplatelet treatment may reduce the risk of a serious cardiovascular event by approximately 25%, including reduction of non-fatal myocardial infarction by 1/6, non-fatal stroke by 1/4 and cardiovascular death by 1/6. Some data indicate that antiplatelet drugs may also have a role in primary prevention. In people who are aged over 65 years, or have hypertension, hypercholesterolaemia, diabetes, obesity or familial history of myocardial infarction at young age, aspirin may reduce both cardiovascular deaths and total cardiovascular events. Aspirin has been studied and used most extensively. It may exert its beneficial effect not only by acting on platelets, but also by other mechanisms, such as preventing thromboxane A2 (TXA2)-induced vasoconstriction or reducing inflammation. Indeed, experimental data show that low-dose aspirin may suppress vascular inflammation and thereby increase the stability of atherosclerotic plaque. Moreover, in human studies, aspirin seems to be most effective in those with elevated C-reactive protein levels. Vascular events, however, do occur despite aspirin administration. This may be due to platelet activation by pathways not blocked by aspirin, intake of drugs that interfere with aspirin effect or aspirin resistance. In the CAPRIE (Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events) study, long-term clopidogrel administered to patients with

  12. The effect of the non-steroidal anti-inflammatory drug choline magnesium trisalicylate on gastric mucosal cell exfoliation.

    PubMed Central

    Mitchell, K G; Hearns, J; Crean, G P

    1984-01-01

    Gastric mucosal cell exfoliation was measured in 10 normal subjects taking choline magnesium trisalicylate (CMT), aspirin and placebo. Both drugs resulted in significantly elevated rates of exfoliation although the serum salicylate levels achieved with aspirin were lower than those achieved by CMT. Side-effects of tinnitus, nausea and increased faecal blood loss were more common while subjects were taking CMT. PMID:6691886

  13. In vivo prostacyclin biosynthesis and effects of different aspirin regimens in patients with essential thrombocythaemia.

    PubMed

    Cavalca, V; Rocca, B; Squellerio, I; Dragani, A; Veglia, F; Pagliaccia, F; Porro, B; Barbieri, S S; Tremoli, E; Patrono, C

    2014-07-01

    Essential thrombocythaemia (ET) is characterised by enhanced platelet generation and thrombosis. Once daily (od) aspirin incompletely inhibits platelet thromboxane (TX)A2 production in ET. A twice daily (bid) dosing is necessary to fully inhibit TXA2. Whether this dosing regimen affects in vivo prostacyclin (PGI2) biosynthesis is unknown. PGI2 biosynthesis was characterised in 50 ET patients on enteric-coated (EC) aspirin 100 mg od, by measuring its urinary metabolite, 2,3-dinor-6-keto-PGF1α (PGI-M). Moreover, in a crossover study 22 patients poorly responsive to standard aspirin based on serum TXB2 levels (≥4 ng/ml) were randomised to different seven-day aspirin regimens: EC aspirin 100 mg od, 100 mg bid, 200 mg od, or plain aspirin 100 mg od. PGI-M measured 24 hours after the last aspirin intake (EC, 100 mg od) was similar in patients and healthy subjects both on (n=10) and off (n=30) aspirin. PGI-M was unrelated to in vivo TXA2 biosynthesis, and not affected by EC aspirin 100 mg bid or 200 mg od as compared to EC 100 mg od. PGI2 biosynthesis in aspirin-treated ET patients appears unrelated to TXA2 biosynthesis, and not affected by an improved aspirin regimen, demonstrating its vascular safety for future trials. PMID:24671522

  14. Endothelial dysfunction in young healthy men is associated with aspirin resistance.

    PubMed

    Doroszko, Adrian; Szahidewicz-Krupska, Ewa; Janus, Agnieszka; Jakubowski, Maciej; Turek, Aleksandra; Ilnicka, Paulina; Szuba, Andrzej; Mazur, Grzegorz; Derkacz, Arkadiusz

    2015-01-01

    The aim of this study was to investigate the relation between endothelial dysfunction and aspirin response in a young healthy population (102 men aged 18-40). Initial concentrations of the NO pathway metabolites (ADMA, l-arginine, SDMA), cardiovascular risk markers, oxidative stress markers (MDA, thiol index), sICAM1, sVCAM1, PAI-1, sE-selectin, sP-selectin, VEGF, thromboxane B2, 6-keto-PGF1α and arachidonate-induced platelet aggregation (to separate aspirin resistant from sensitive group) were measured. Flow-mediated-vasodilation (FMD) was measured before and after intravenous infusion of 16.0 g of l-arginine. Measurements were repeated following aspirin administration (75 mg/24 h) for 4 days. Both groups were homogenous regarding demographic and biochemical characteristics reflecting cardiovascular risk. Aspirin resistant subjects were characterized by lower baseline FMD and higher FMD following aspirin and l-arginine treatment, as compared to aspirin sensitive control. MDA and nitrotyrosine were greater, whereas thiol index was lower in aspirin resistant men. The sICAM1, sVCAM1, PAI-1, sE-selectin, sP-selectin and VEGF levels were similar in the analyzed groups. Thromboxane in aspirin resistant subjects was greater both at baseline and following aspirin therapy. However, a significant decrease following aspirin treatment was present in both groups. Aspirin resistance in young men is associated with endothelial dysfunction, which could be due to oxidative stress resulting from lipid peroxidation. PMID:25697550

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

    SciTech Connect

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

    1985-02-01

    Inhibition of endogenous prostacyclin and thromboxane biosynthesis by aspirin is critically dose-dependent in humans. Gastrointestinal and hepatic hydrolysis may limit systemic availability of aspirin, especially in low doses, perhaps contributing to the biochemical selectivity of aspirin. Existing analytical methods do not permit determination of systemic bioavailability when low (less than 100 mg) doses of aspirin are administered. Deuterium-labeled aspirin (2-acetoxy(3,4,5,6-/sup 2/H4)benzoic acid) was synthesized from salicylic acid by catalytic exchange and subsequent acetylation. Analysis of the compounds as benzyl esters by GC-MS followed extractive alkylation from plasma. Heptadeuterated compounds were used as internal standards. Simultaneous administration of tetradeuterated aspirin intravenously with native aspirin orally to anesthetized dogs permitted kinetic studies of both aspirin and salicylic acid. The sensitivity of the method is superior to published methods using HPLC and, thus, more applicable to studies of low dose aspirin. Pulse administration of stable isotope-labeled aspirin permits detailed and repeated studies of dose-related aspirin pharmacokinetics in humans.

  16. Aspirin resistance in children and young adults with splenectomized thalassemia diseases.

    PubMed

    Sirachainan, Nongnuch; Wijarn, Piyathida; Chuansumrit, Ampaiwan; Kadegasem, Praguywan; Wongwerawattanakoon, Pakawan; Soisamrong, Anucha

    2015-05-01

    Aspirin is now recommended for splenectomized thalassemia patients with high platelet counts. However, aspirin resistance defined by arachinodic acid (ACA) induced platelet aggregation ≥20%, has never been reported in this group of patients. In this study, twenty-four splenectomized thalassemia patients (15.7±4.1years), with platelet counts ≥800x10(9)/L, and 21 non-splenectomized severe thalassemia patients (14.3±3.2years), were enrolled. After taking aspirin (2mg/kg/day), seven patients (29.2%) displayed aspirin resistance. Serum thromboxane B2 (TXB2) levels in the aspirin responsive group decreased significantly [52.6(8.8-174.6) vs 4.0(1.6-7.3) mcg/mL, p<0.001], while no change was demonstrated in the aspirin resistant group. Having increased aspirin to 4mg/kg/day, three of the seven aspirin resistant patients responded, while one developed upper GI bleeding from esophageal varices and was withdrawn from the study. For the three remaining patients, their doses were increased to the maximum of 300mg/day, and two of the three responded. Thrombin antithrombin complex and D-dimer levels were significantly decreased after taking aspirin (2mg/kg/day), although D-dimer level was still significantly higher than that in non-splenectomized group. Therefore, aspirin dosage can be adjusted individually to reach maximum effect of platelet inhibition. In addition, aspirin can reduce the levels of coagulation markers.

  17. Aspirin use for primary prevention in elderly patients.

    PubMed

    Terrosu, Pierfranco

    2016-01-01

    The net clinical benefit of aspirin in primary prevention is uncertain as the reduction in occlusive events needs to be balanced against the increase in gastro-intestinal and cerebral bleedings. The meta-analysis of ATT (Anti Thrombotic Trialists) Collaboration in 2009 showed that aspirin therapy in primary prevention was associated with 12% reduction in cardio-vascular events, due mainly to a reduction in non-fatal myocardial infarction (0.18% vs 0.23% per year, p<0.0001). However, the benefit in term of coronary events was almost balanced by the increase in major bleedings. The balance between potential benefit and harm of aspirin differs in each person and appears to be favorable in subjects at higher cardio-vascular risk. Older people have increased risk of hemorrhage as well as increased risk of heart attack and stroke. As a consequence, it is important consider both likelihoods of benefits as well as harm within the lifespan and functioning of the person. The older people who most likely benefit from aspirin in primary prevention are those at higher cardio-vascular risk, with preserved functional abilities, low comorbidity, low risk of bleeding and a prolonged life expectancy. PMID:27374042

  18. The role of aspirin in colorectal cancer chemoprevention.

    PubMed

    Singh Ranger, Gurpreet

    2016-08-01

    Considerable interest has emerged over the last decade regarding the role of aspirin in prevention of colorectal cancer. This disease is one of the commonest cancers in the Western World, therefore, the existence of a simple "everyday" agent, which could have the ability to prevent the disease, represents an invaluable opportunity clinicians may be able to exploit. Evidence from case-control and cohort studies, and recent updates of randomised controlled trials have been very encouraging-indicating benefit from long term use of aspirin at low dose. Possible mechanisms of chemoprevention include inhibition of the cyclooxygenase (COX) pathway, or COX-independent mechanisms, for example, the PIK3CA pathway, or therapy-induced senescence of cancer cells. The most serious side effect of prolonged aspirin treatment is haemorrhage, especially from the GI tract. This is likely to be less of a problem with chemoprevention at lower doses. One also needs to consider the impact if aspirin resistance, an increasingly recognised clinical entity. PMID:27289249

  19. Class Projects in Physical Organic Chemistry: The Hydrolysis of Aspirin

    ERIC Educational Resources Information Center

    Marrs, Peter S.

    2004-01-01

    An exercise that provides a hands-on demonstration of the hydrolysis of aspirin is presented. The key to understanding the hydrolysis is recognizing that all six process may occur simultaneously and that the observed rate constant is the sum of the rate constants that one rate constant dominates the overall process.

  20. Aspirin-induced asthma: clinical aspects, pathogenesis and management.

    PubMed

    Hamad, Ahmed M; Sutcliffe, Amy M; Knox, Alan J

    2004-01-01

    Aspirin (acetylsalicylic acid)-induced asthma (AIA) consists of the clinical triad of asthma, chronic rhinosinusitis with nasal polyps, and precipitation of asthma and rhinitis attacks in response to aspirin and other NSAIDs. The prevalence of the syndrome in the adult asthmatic populations is approximately 4-10%. Respiratory disease in these patients may be aggressive and refractory to treatment. The aetiology of AIA is complex and not fully understood, but most evidence points towards an abnormality of arachidonic acid (AA) metabolism. Cyclo-oxygenase (COX), the rate-limiting enzyme in AA metabolism, exists as two main isoforms. COX-1 is the constitutive enzyme responsible for synthesis of protective prostanoids, whereas COX-2 is induced under inflammatory conditions. A number of theories regarding its pathogenesis have been proposed. The shunting hypothesis proposes that inhibition of COX-1 shunts AA metabolism away from production of protective prostanoids and towards cysteinyl leukotriene (cys-LT) biosynthesis, resulting in bronchoconstriction and increased mucus production. The COX-2 hypothesis proposes that aspirin causes a structural change in COX-2 that results in the generation of products of the lipoxygenase pathway. It is speculated that this may result in the formation of mediators that cause respiratory reactions in AIA. Related studies provide evidence for abnormal regulation of the lipoxygenase pathway, demonstrating elevated levels of cys-LTs in urine, sputum and peripheral blood, before and following aspirin challenge in AIA patients. These studies suggest that cys-LTs are continually and aggressively synthesised before exposure to aspirin and, during aspirin-induced reactions, acceleration of synthesis occurs. A genetic polymorphism of the LTC4S gene has been identified consisting of an A to C transversion 444 nucleotides upstream of the first codon, conferring a relative risk of AIA of 3.89. Furthermore, carriers of the C444 allele demonstrate a

  1. Protection of leukotriene receptor antagonist against aspirin-induced bronchospasm in asthmatics

    PubMed Central

    Park, Jong Sook; Jang, An Soo; Park, Sung Woo; Lee, Young Mok; Uh, Soo Taek; Kim, Yong Hoon; Cha, Ji Yean; Park, Se Min

    2010-01-01

    Purpose Leukotriene receptor antagonists (LTRAs) are used to treat aspirin-intolerant asthma (AIA); however, the protective effects of long-term LTRA administration against aspirin-induced bronchospasm have not been evaluated. Objectives We investigated the efficacy of a 12-week treatment with a LTRA in protecting against aspirin-induced asthma in AIA patients. Methods Fifty-two adult patients with AIA underwent an aspirin challenge test just before administration of montelukast (10 mg/day) and just after 12 weeks of treatment. The protective effect was assessed as the disappearance of aspirin-induced bronchospasm after 12 weeks of treatment. The results were compared according to the patients' clinical and physiological parameters. Results The decline in FEV1 following aspirin challenge was significantly reduced from 28.6±1.9% to 10.2±1.7% (P=0.0001) after 12 weeks of montelukast treatment. However, 14 subjects (30%) still showed a positive response (>15% decline in FEV1) to aspirin challenge. Grouping the subjects into good and poor responders according to post-treatment responses revealed that the pretreatment aspirin-induced FEV1 decline was significantly greater in the poor responders and that the triggering dose of aspirin and the induction time for a positive response were lower and shorter, respectively, in the poor responders. Histories of aspirin hypersensitivity and sinusitis were more prevalent among the poor responders than among the good responders. Conclusions Twelve weeks of treatment with montelukast protected against aspirin-induced bronchospasm in 70% of the AIA cases. A poor response was associated with more severe aspirin-induced bronchospasms before treatment and a history of aspirin hypersensitivity or sinusitis. Clinical implications A severe response to aspirin challenge may be a predictor of poor responsiveness to leukotriene antagonist treatment. PMID:20224678

  2. Metabolism of aspirin and procaine in mice pretreated with O-4-nitrophenyl methyl(phenyl)phosphinate or O-4-nitrophenyl diphenylphosphinate

    SciTech Connect

    Joly, J.M.; Brown, T.M.

    1986-07-01

    Concentrations of (carboxyl-/sup 14/C)procaine in blood of mice were increased threefold for 27 min by exposure to O-4-nitrophenyl diphenylphosphinate 2 hr prior to (carboxyl-/sup 14/C)procaine injection ip, while there was no effect of O-4-nitrophenyl methyl(phenyl)phosphinate pretreatment. There was no effect of either organophosphinate on the primary hydrolysis of (acetyl-l-/sup 14/C)aspirin when assessed by the expiration of (/sup 14/C)carbon dioxide; however, O-4-nitrophenyl diphenylphosphinate pretreatment produced transient increases in blood concentrations of both (carboxyl-/sup 14/C)aspirin and (carboxyl-/sup 14/C)salicylic acid following administration of (carboxyl-/sup 14/C)aspirin. Liver carboxylesterase activity in O-4-nitrophenyl diphenylphosphinate pretreated mice was 11% of control activity. These results indicate the potential for drug interaction with O-4-nitrophenyl diphenylphosphinate but not with O-4-nitrophenyl methyl(phenyl)phosphinate. It appears that liver carboxylesterase activity has a minor role in hydrolysis of aspirin in vivo, but may be more important in procaine metabolism.

  3. Differential inhibition of tumour cell-induced platelet aggregation by the nicotinate aspirin prodrug (ST0702) and aspirin

    PubMed Central

    Medina, Carlos; Harmon, Shona; Inkielewicz, Iwona; Santos-Martinez, Maria Jose; Jones, Michael; Cantwell, Paula; Bazou, Despina; Ledwidge, Mark; Radomski, Marek W; Gilmer, John F

    2012-01-01

    BACKGROUND AND PURPOSE Tumour cell-induced platelet aggregation (TCIPA) facilitates cancer cell invasion, angiogenesis and the formation of metastatic foci. TCIPA can be modulated by pharmacological inhibitors of MMP-2 and ADP; however, the COX inhibitor aspirin did not prevent TCIPA. In this study, we have tested the pharmacological effects of a new group of isosorbide-based aspirin prodrugs on TCIPA. EXPERIMENTAL APPROACH TCIPA was induced in human platelets by mixing with human adenocarcinoma or fibrosarcoma cells under no flow and flow conditions. The release of gelatinases and P-selectin expression during TCIPA were studied by zymography and flow cytometry respectively. KEY RESULTS Tumour cells caused platelet aggregation. This aggregation resulted in the release of MMP-2 and a significant up-regulation of P-selectin on platelets, indicative of platelet activation. Pharmacological modulation of TCIPA revealed that ST0702, one of the aspirin prodrugs, down-regulated TCIPA while aspirin was ineffective. The deacetylated metabolite of ST0702, 5-nicotinate salicylate (ST0702 salicylate), down-regulated both ADP-stimulated platelet aggregation and TCIPA. CONCLUSIONS AND IMPLICATIONS Our results show that ST0702 was an effective inhibitor of TCIPA in vitro. Its deacetylated metabolite may contribute to the effects of ST0702 by inhibiting ADP-mediated TCIPA. PMID:22122360

  4. [Controlled clinical trial of the effect of aspirin and aspirin + dipyridamole on the development of diabetic retinopathy. II. Ophthalmologic protocol].

    PubMed

    1982-12-01

    A description is given of the ophthalmological protocol of the DAMAD (aspirin and dipyridamole + Aspirin) controlled clinical trial in diabetic retinopathy. The 450 patients included in this trial were insulin or noninsulin treated diabetics with an early diabetic retinopathy (i.e. at least five microaneurysms in the posterior pole and/or one zone of capillary non-perfusion). They were randomized in a double blind fashion to treatment with either placebo or aspirin 330 mg or aspirin 330 mg + dipyridamole 75 mg three times daily. A full ophthalmologic examination was performed annually on both eyes of each patient and followed at least three years. Data were recorded on a special form. The main assessment criteria were orientated toward the quantification of the retinal vascular micro-abnormalities, counting of microaneurysm and measurement of the central and peripheral avascular zones. Angiofluorographic photographs were standardized. The two eyes were photographed but only one reference eye was kept for the whole length of this study. A standard reading technique is now used by a technician in charge of coding the quality of the films, the dotting and numbering of the lesions.

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

    PubMed

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

    2015-10-01

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

  6. Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid

    PubMed Central

    SORIANO-HERNANDEZ, ALEJANDRO D.; MADRIGAL-PÉREZ, DANIELA; GALVAN-SALAZAR, HECTOR R.; MARTINEZ-FIERRO, MARGARITA L.; VALDEZ-VELAZQUEZ, LAURA L.; ESPINOZA-GÓMEZ, FRANCISCO; VAZQUEZ-VUELVAS, OSCAR F.; OLMEDO-BUENROSTRO, BERTHA A.; GUZMAN-ESQUIVEL, JOSE; RODRIGUEZ-SANCHEZ, IRAM P.; LARA-ESQUEDA, AGUSTIN; MONTES-GALINDO, DANIEL A.; DELGADO-ENCISO, IVAN

    2015-01-01

    Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluated in vitro. Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10–40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50–90% of cell death corresponding to 100 µM). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug. PMID:26622892

  7. Differential effects of flurbiprofen and aspirin on acetazolamide disposition in humans.

    PubMed Central

    Sweeney, K R; Chapron, D J; Antal, E J; Kramer, P A

    1989-01-01

    The plasma concentration-time profile of acetazolamide (AZ) following an intravenous bolus dose (5 mg kg-1) was determined during control, aspirin and flurbiprofen (FLU) treatment periods. The unbound fraction of AZ in plasma increased three-fold in the presence of salicylate (SA) while, in contrast, FLU produced consistent, but statistically insignificant, increases in binding. SA caused a two-fold decrease in both unbound AZ renal clearance and apparent volume of distribution at steady-state, while FLU produced a small, but significant, increase only in the latter. The area under the concentration-time curve for AZ in erythrocytes was increased by about 40% during SA treatment while FLU had no effect. Our results suggest that on a pharmacokinetic basis FLU may be a safer nonsteroidal anti-inflammatory drug (NSAID) to co-administer with AZ. PMID:2757898

  8. Aspirin for cancer is no mere antiplatelet prototype. There is potential in its ancient roots.

    PubMed

    Lawrence, James R; Baxter, Gwendoline J; Paterson, John R

    2016-09-01

    Aspirin (ASA), increasingly accepted as predominantly a cyclooxygenase (COX)-1 inhibitor, is a prodrug for salicylic acid (SA) which has no such activity. SA is widespread in nature, vital in plants, and present in drug free serum from animals and man. Evolutionary conserved SA receptors are found in human tissues. Very low doses of ASA will, on repeat dosing, produce near maximal platelet COX-1 inhibition. Evidence for cancer prophylaxis is based on ASA doses of at least 75mg/day. Pleiotropic mechanisms underlie low dose ASA's undoubted efficacy in preventive medicine but the key barrier to its more widespread use is gastrointestinal toxicity. ASA/SA combination formulations may improve the current risk/benefit ratio of chemo-prophylactic preparations. There is well established methodology for, and should be few regulatory barriers to, their evaluation. PMID:27515206

  9. Network reconstruction of platelet metabolism identifies metabolic signature for aspirin resistance

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

  10. Aspirin in combination with TACE in treatment of unresectable HCC: a matched-pairs analysis

    PubMed Central

    Li, Jing-Huan; Wang, Yan; Xie, Xiao-Ying; Yin, Xin; Zhang, Lan; Chen, Rong-Xin; Ren, Zheng-Gang

    2016-01-01

    Transarterial chemoembolization (TACE) is the principal therapy for unresectable hepatocellular carcinoma (HCC). However, its efficacy is currently limited owing to tumor progression or treatment failure. It has been shown that aspirin reduces the incidence of multiple malignant tumors including HCC and plays a synergistic role with chemotherapy in the treatment of colon cancer. Therefore, we aimed to investigate the adjuvant effect of aspirin on patients with unresectable HCC who underwent TACE therapy. A retrospective matched-pairs analysis was performed to evaluate the efficacy of aspirin in combination with TACE therapy. A total of 120 patients with HCC, including 60 patients treated with aspirin for treatment of cardiovascular disease, transient ischemic attack, and arthritis, and 60 paired matching HCC patients without aspirin treatment in the same period, were enrolled. Compared with non-aspirin users, patients treated with aspirin showed improved OS (P = 0.050). Specifically, patients treated with a full dose of aspirin showed prolonged OS (P = 0.027), which was an independent factor associated with OS in multivariate analysis (hazard ratio 0.498, 95% confidence interval 0.280-0.888, P = 0.018). Aspirin in combination with TACE might improve OS in patients with unresectable HCC. Thus, the impact of aspirin on patients with HCC warrants further investigation prospectively. PMID:27725915

  11. Ascorbic Acid may Exacerbate Aspirin-Induced Increase in Intestinal Permeability.

    PubMed

    Sequeira, Ivana R; Kruger, Marlena C; Hurst, Roger D; Lentle, Roger G

    2015-09-01

    Ascorbic acid in combination with aspirin has been used to prevent aspirin-induced oxidative GI damage. We aimed to determine whether ascorbic acid reduces or prevents aspirin-induced changes in intestinal permeability over a 6-hr period using saccharidic probes mannitol and lactulose. The effects of administration of 600 mg aspirin alone, 500 mg ascorbic acid alone and simultaneous dosage of both agents were compared in a cross-over study in 28 healthy female volunteers. These effects were also compared with that of a placebo. The ability of ascorbic acid to mitigate the effects of aspirin when administered either half an hour before or after dosage with aspirin was also assessed in 19 healthy female volunteers. The excretion of lactulose over the 6-hr period was augmented after consumption of either aspirin or ascorbic acid compared with that after consumption of placebo. Dosage with ascorbic acid alone augmented the excretion of lactulose more than did aspirin alone. Simultaneous dosage with both agents augmented the excretion of lactulose in an additive manner. The timing of dosage with ascorbic acid in relation to that with aspirin had no significant effect on the excretion of the two sugars. These findings indicate that ascorbic acid does not prevent aspirin-induced increase in gut permeability rather that both agents augment it to a similar extent. The additive effect on simultaneous dosage with both agents in augmenting the absorption of lactulose suggests that each influences paracellular permeability by different pathways.

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

    SciTech Connect

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

    1986-03-01

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

  13. [Induced sputum supernatant prostaglandin E2 during oral aspirin challenge of asthmatic patients with and without aspirin hypersensitivity and healthy controls--pilot study].

    PubMed

    Ignacak, Maria; Celejewska-Wójcik, Natalia; Wójcik, Krzysztof; Sałapa, Kinga; Konduracka, Ewa; Sanak, Marek; Tyrak, Katarzyna; Sładek, Krzysztof; Musiał, Jacek; Mastalerz, Lucyna

    2016-01-01

    The aim of this pilot study was to evaluate changes in the concentration of prostaglandin E2 (PGE2) in induced sputum supernatant in 3 groups: sub- jects with NSAID-exacerbated respira- tory disease (NERD), aspirin tolerant asthma (ATA) and healthy controls (HC), before and after oral aspirin chal- lenge test. The study was conducted in the years 2014-2015 at the Clinical Department of the Pulmonology Clinic at the University Hospital in Cracow. 43 patients were enrolled in the study (NERD - n = 15, ATA - n = 15 and HC - n = 13). All of them underwent a placebo-controlled oral aspirin challenge. Sputum was induced 24 hours before the challenge and immediately after the test. Induced sputum was processed in order to obtain cystospin slides to depict inflammatory cell patterns and supernatants, in which PGE2 was measured. The concentration of PGE2 was determined using mass spectrometry coupled with gas chromatography (gas chromatography/mass spectrometry - GC/MS). After aspirin challenge, the concentration of PGE2 in induced sputum supernatant decreased in both asthmatics hypersensitive to aspirin (p = 0.01) and those who tolerated aspirin well (p = 0.17). The change in the healthy control group was not statistically significant. These results support the cyclooxygenase theory of PGE2 inhibition by aspirin. However, the mechanism of bronchoconstriction after aspirin administration alone in patients with NSAID-exacerbated respiratory disease remains unclear.

  14. [Induced sputum supernatant prostaglandin E2 during oral aspirin challenge of asthmatic patients with and without aspirin hypersensitivity and healthy controls--pilot study].

    PubMed

    Ignacak, Maria; Celejewska-Wójcik, Natalia; Wójcik, Krzysztof; Sałapa, Kinga; Konduracka, Ewa; Sanak, Marek; Tyrak, Katarzyna; Sładek, Krzysztof; Musiał, Jacek; Mastalerz, Lucyna

    2016-01-01

    The aim of this pilot study was to evaluate changes in the concentration of prostaglandin E2 (PGE2) in induced sputum supernatant in 3 groups: sub- jects with NSAID-exacerbated respira- tory disease (NERD), aspirin tolerant asthma (ATA) and healthy controls (HC), before and after oral aspirin chal- lenge test. The study was conducted in the years 2014-2015 at the Clinical Department of the Pulmonology Clinic at the University Hospital in Cracow. 43 patients were enrolled in the study (NERD - n = 15, ATA - n = 15 and HC - n = 13). All of them underwent a placebo-controlled oral aspirin challenge. Sputum was induced 24 hours before the challenge and immediately after the test. Induced sputum was processed in order to obtain cystospin slides to depict inflammatory cell patterns and supernatants, in which PGE2 was measured. The concentration of PGE2 was determined using mass spectrometry coupled with gas chromatography (gas chromatography/mass spectrometry - GC/MS). After aspirin challenge, the concentration of PGE2 in induced sputum supernatant decreased in both asthmatics hypersensitive to aspirin (p = 0.01) and those who tolerated aspirin well (p = 0.17). The change in the healthy control group was not statistically significant. These results support the cyclooxygenase theory of PGE2 inhibition by aspirin. However, the mechanism of bronchoconstriction after aspirin administration alone in patients with NSAID-exacerbated respiratory disease remains unclear. PMID:27197430

  15. Potentiation of LPS-Induced Apoptotic Cell Death in Human Hepatoma HepG2 Cells by Aspirin via ROS and Mitochondrial Dysfunction: Protection by N-Acetyl Cysteine

    PubMed Central

    Raza, Haider; John, Annie; Shafarin, Jasmin

    2016-01-01

    Cytotoxicity and inflammation-associated toxic responses have been observed to be induced by bacterial lipopolysaccharides (LPS) in vitro and in vivo respectively. Use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, has been reported to be beneficial in inflammation-associated diseases like cancer, diabetes and cardiovascular disorders. Their precise molecular mechanisms, however, are not clearly understood. Our previous studies on aspirin treated HepG2 cells strongly suggest cell cycle arrest and induction of apoptosis associated with mitochondrial dysfunction. In the present study, we have further demonstrated that HepG2 cells treated with LPS alone or in combination with aspirin induces subcellular toxic responses which are accompanied by increase in reactive oxygen species (ROS) production, oxidative stress, mitochondrial respiratory dysfunction and apoptosis. The LPS/Aspirin induced toxicity was attenuated by pre-treatment of cells with N-acetyl cysteine (NAC). Alterations in oxidative stress and glutathione-dependent redox-homeostasis were more pronounced in mitochondria compared to extra- mitochondrial cellular compartments. Pre-treatment of HepG2 cells with NAC exhibited a selective protection in redox homeostasis and mitochondrial dysfunction. Our results suggest that the altered redox metabolism, oxidative stress and mitochondrial function in HepG2 cells play a critical role in LPS/aspirin-induced cytotoxicity. These results may help in better understanding the pharmacological, toxicological and therapeutic properties of NSAIDs in cancer cells exposed to bacterial endotoxins. PMID:27441638

  16. Aspirin prevents diabetic oxidative changes in rat lacrimal gland structure and function.

    PubMed

    Jorge, Angélica Gobbi; Módulo, Carolina Maria; Dias, Ana Carolina; Braz, Alexandre Martins; Filho, Rubens Bertazolli; Jordão, Alceu A; de Paula, Jayter Silva; Rocha, Eduardo Melani

    2009-04-01

    The aim of this study is to evaluate whether aspirin reduces Diabetis Mellitus (DM) oxidative damage in the lacrimal gland (LG), and ocular surface (OS). Ten weeks after streptozotocin induced DM and aspirin treatment, LG and OS of rats were compared for tear secretion, hidtology, peroxidase activity, and expression of uncoupling proteins (UCPs). DM reduction of tear secretion was prevented by aspirin (P < 0.01). Alterations of LG morphology and increased numbers of lipofucsin-like inclusions were observed in diabetic but not in aspirin-treated diabetic rats. Peroxidase activity levels were higher and UCP-2 was reduced in DM LG but not in aspirin treated (P = 0.0025 and P < 0.05, respectively). The findings prevented by aspirin indicate a direct inhibitory effect on oxidative pathways in LG and their inflammatory consequences, preserving the LG structure and function against hyperglycemia and/or insulin deficiency damage.

  17. A Balanced View of Efficacy and Safety of Aspirin in Cardiovascular Diseases.

    PubMed

    Casado-Arroyo, Rubén; Lanas, Angel; Brugada, Pedro

    2015-01-01

    This review highlights practical aspects related to aspirin therapy in cardiovascular diseases, specifically, the benefits and hazards in different clinical settings. Aspirin reduces one fourth of all major cardiovascular events but also increases major gastrointestinal bleeds by about half. As with other cardiovascular prevention strategies, the absolute benefit of aspirin is linearly related to the cardiovascular risk of the patient. The risk-benefit of aspirin can vary substantially in different settings: in secondary prevention, the benefits usually outweigh the excess of major bleeding complications. In primary prevention, it is not unusual that the number of vascular events avoided equals the number of major bleeds induced by aspirin. Finally, there is a growing body of evidence suggesting that aspirin may interfere with the early stages of cancer, metastasis and mortality. For all these reasons, in this article new developments in the field directed towards individualized risk assessment strategies are also discussed. PMID:26369681

  18. Statins and aspirin: do they really work in women?

    PubMed

    Desai, Hemal; Hollingsworth, Paula W; Chugh, Atul R

    2015-06-01

    Cardiovascular disease continues to be the most common cause of mortality in women in the USA. As a result, greater emphasis has been placed on preventive measures. Studies examining the role of aspirin and HMG-CoA reductase inhibitors (statins) have shown important clinical differences in men versus women in the preventive realm. This has led to inconsistent recommendations by guideline committees and clinicians alike. This review presents a summary of the past and current guidelines. In addition, important clinical trials influencing current era practice are also discussed. Both strengths and limitations of these studies are described in detail, along with recommendations regarding future directions and the scope of aspirin and statin use for primary and secondary prevention of cardiovascular disease. PMID:25812803

  19. Aspirin Prevention of Cholesterol Gallstone Formation in Prairie Dogs

    NASA Astrophysics Data System (ADS)

    Lee, Sum P.; Carey, Martin C.; Lamont, J. Thomas

    1981-03-01

    When prairie dogs (Cynomys ludovicianus) are fed a diet containing cholesterol, a marked increase in gallbladder mucin secretion parallels the evolution of cholesterol supersaturated bile. Gelation of mucin precedes the precipitation of cholesterol liquid and solid crystals and the development of gallstones. Aspirin given to prairie dogs inhibited mucin hypersecretion and gel accumulation and prevented gallstone formation without influencing the cholesterol content of supersaturated bile. This suggests that gallbladder mucin is a nucleation matrix for cholesterol gallstones.

  20. Cyclooxygenase Expression and Platelet Function in Healthy Dogs Receiving Low Dose Aspirin

    PubMed Central

    Dudley, Alicia; Thomason, John; Fritz, Sara; Grady, Jesse; Stokes, John; Wills, Robert; Pinchuk, Lesya; Mackin, Andrew; Lunsford, Kari

    2014-01-01

    Background Low dose aspirin is used to prevent thromboembolic complications in dogs, but some animals are non-responsive to the anti-platelet effects of aspirin (‘aspirin resistance’). Hypothesis/Objectives That low dose aspirin would inhibit platelet function, decrease thromboxane synthesis, and alter platelet cyclooxygenase (COX) expression. Animals Twenty-four healthy dogs Methods A repeated measures study. Platelet function (PFA-100® closure time, collagen/epinephrine), platelet COX-1 and COX-2 expression, and urine 11-dehydro-thromboxane B2 (11-dTXB2) was evaluated prior to and during aspirin administration (1 mg/kg Q24 hours PO, 10 days). Based on prolongation of closure times after aspirin administration, dogs were divided into categories according to aspirin responsiveness: responders, non-responders, and inconsistent responders. Results Low dose aspirin increased closure times significantly (62% by Day 10, P<0.001), with an equal distribution among aspirin responsiveness categories, 8 dogs per group. Platelet COX-1 mean fluorescent intensity (MFI) increased significantly during treatment, 13% on Day 3 (range, −29.7%–136.1%) (P=0.047) and 72% on Day 10 (range, −0.37–210.36%) (P<0.001). Platelet COX-2 MFI increased significantly by 34% (range, −29.2–270.4%) on Day 3 (P = 0.003) and 74% (range, −19.7–226.2%) on Day 10 (P<0.001). Urinary 11-dTXB2 concentrations significantly (P=0.005, P<0.001) decreased at both time points. There was no difference between aspirin responsiveness and either platelet COX expression or thromboxane production. Conclusions and Clinical Importance Low dose aspirin consistently inhibits platelet function in approximately one third of healthy dogs, despite decreased thromboxane synthesis and increased platelet COX expression in most dogs. Pre-treatment COX isoform expression did not predict aspirin resistance. PMID:23278865

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

    SciTech Connect

    Cuningham, D.A.; Kumar, B.; Siegel, B.A.; Gilula, L.A.; Totty, W.G.; Welch, M.J.

    1984-05-01

    In-111 platelet scintigraphy was used to evaluate the effects of prior aspirin administration on the accumulation of In-111-labeled autologous platelets at sites of arterial injury resulting from iliac, femoral, or popliteal transluminal angioplasty in a nonrandomized study of 17 men. The degree of platelet localization at angioplasty sites was significantly less in nine men who had received aspirin in varying doses within the 4 days before angioplasty than in eight men who had not received aspirin for at least two weeks. The results suggest that aspirin treatment before angioplasty limits the early platelet deposition at the angioplasty site in men.

  2. Role of aspirin for prevention and treatment of perioperative cardiovascular events.

    PubMed

    Duceppe, E; Mrkobrada, M; Thomas, S; Devereaux, P J

    2015-06-01

    Among adults undergoing non-cardiac surgery who are at risk of a myocardial infarction, a long-standing question has been whether these patients should receive aspirin throughout the perioperative period. A large (n = 10,010 patients) international trial (POISE-2) demonstrated that perioperative aspirin did not prevent myocardial infarction, and the result was consistent both for patients who had been taking aspirin before the trial (continuation stratum, 4382 patients) and for patients who had not been taking aspirin before the trial (initiation stratum, 5628 patients). Aspirin did, however, increase the risk of major bleeding. Therefore, the best evidence does not support the use of aspirin for the prevention of myocardial infarction in patients undergoing non-cardiac surgery. In patients who have an indication for long-term aspirin usage and have their aspirin held during the perioperative period, it is important to ensure aspirin is restarted after the high-risk period for bleeding has passed (i.e., 8-10 days after surgery).

  3. High prevalence of aspirin resistance in elderly patients with cardiovascular disease and metabolic syndrome

    PubMed Central

    Liu, Lin; Gao, Ying-Hui; Cao, Jian; Zhang, Hua-Xin; Fan, Li; Hu, Guo-Liang; Hu, Yi-Xin; Li, Xiao-Li; Zou, Xiao; Li, Jian-Hua

    2016-01-01

    Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential determinants of aspirin resistance in patients with cardiovascular disease (CVD). Methods A total of 469 elderly patients with CVD were recruited. One hundred and seventy-two patients with metabolic syndrome and 297 without metabolic syndrome (control group) received daily aspirin therapy (≥ 75 mg) over one month. Platelet aggregation was measured by light transmission aggregometry (LTA). Aspirin resistance was defined as ≥ 20% arachidonic acid (AA)- and ≥ 70% adenosine diphosphate (ADP)-induced aggregation according to LTA. Aspirin semi-responders were defined as meeting one (but not both) of these criteria. Results By LTA, 38 of 469 (8.1%) patients were aspirin resistant. The prevalence of aspirin resistance was higher in the metabolic syndrome group compared with the control group [11.6 % vs. 6.6%, odds ratio (OR) = 2.039; 95% confidence interval (CI): 1.047–3.973]. In the multivariate logistic regression analysis, metabolic syndrome (OR = 4.951, 95% CI: 1.440–17.019, P = 0.011) was a significant risk factor for aspirin resistance. Conclusions A significant number of patients with CVD and metabolic syndrome are resistant to aspirin therapy. This might further increase the risk of cardiovascular morbidity and mortality in these patients. PMID:27582771

  4. Use of aspirin associates with longer primary patency of hemodialysis grafts.

    PubMed

    Dixon, Bradley S; Beck, Gerald J; Dember, Laura M; Vazquez, Miguel A; Greenberg, Arthur; Delmez, James A; Allon, Michael; Himmelfarb, Jonathan; Hu, Bo; Greene, Tom; Radeva, Milena K; Davidson, Ingemar J; Ikizler, T Alp; Braden, Gregory L; Lawson, Jeffrey H; Cotton, James R; Kusek, John W; Feldman, Harold I

    2011-04-01

    Extended-release dipyridamole plus low-dose aspirin (ERDP/ASA) prolongs primary unassisted graft patency of newly created hemodialysis arteriovenous grafts, but the individual contributions of each component are unknown. Here, we analyzed whether use of aspirin at baseline associated with primary unassisted graft patency among participants in a randomized trial that compared ERDP/ASA and placebo in newly created grafts. We used Cox proportional hazards regression, adjusting for prespecified baseline comorbidities and covariates. Of all participants, 43% reported use of aspirin at baseline; of these, 82% remained on nonstudy aspirin (i.e., excluding ERDP/ASA) at 1 year. After 1 year of follow-up, the incidence of primary unassisted patency among participants using aspirin at baseline was 30% (95% CI: 24 to 35%) and among those not using aspirin was 23% (95% CI: 18 to 27%). Use of aspirin at baseline associated with a dose-dependent prolongation of primary unassisted graft patency that approached statistical significance (adjusted HR, 0.83; 95% CI: 0.68 to 1.01; P=0.06). Use of aspirin at baseline did not associate with prolongation of cumulative graft patency or participant survival. In conclusion, use of aspirin associates with a trend toward longer primary unassisted patency of newly placed hemodialysis grafts similar to that observed for ERDP/ASA.

  5. Coformer selection in pharmaceutical cocrystal development: a case study of a meloxicam aspirin cocrystal that exhibits enhanced solubility and pharmacokinetics.

    PubMed

    Cheney, Miranda L; Weyna, David R; Shan, Ning; Hanna, Mazen; Wojtas, Lukasz; Zaworotko, Michael J

    2011-06-01

    Meloxicam is a nonsteroidal anti-inflammatory drug with low aqueous solubility and high permeability. Because of its low solubility under acidic conditions (e.g., pH 1-5), it can take more than 2 h for meloxicam to reach its therapeutic concentration in humans. Although the slow onset of meloxicam does not necessarily impact the current label indications, the slow onset does prevent meloxicam from its potential application for the relief of mild-to-medium-level acute pain. Pharmaceutical cocrystallization of meloxicam, which represents a promising approach to generate diverse novel crystal forms, could be used to improve the aqueous solubility and accelerate the onset of action. In this contribution, we describe how a novel method can be used for coformer selection to enable the efficient and effective development of a pharmaceutical cocrystal with desired physicochemical and pharmacokinetic properties. Aspirin was selected as the coformer for meloxicam based upon this alternative route, which combines the supramolecular synthon approach with findings in the previous pharmacological and toxicological studies of meloxicam. The resulting cocrystal of meloxicam and aspirin exhibited superior kinetic solubility and possessed the potential to significantly decrease the time required to reach the human therapeutic concentration compared with the parent drug, meloxicam.

  6. Long-term use of ticagrelor in patients with prior heart attack: ticagrelor plus aspirin versus aspirin monotherapy.

    PubMed

    Amico, Frank; Schlesinger, Alex; Mazzoni, Jennifer

    2016-01-01

    Review of: Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-1800. This Practice Pearl reviews the recent study Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared With Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54). It challenges the current standard of care of 12 months of dual antiplatelet followed by aspirin indefinitely. The study demonstrated that patients who received ticagrelor, either the 60 mg or 90 mg twice daily plus aspirin, showed a decreased risk of cardiovascular death, myocardial infarction, or stroke. The PEGASUS-TIMI 54 trial also proved that the benefit of ticagrelor was seen early and continued to accrue over time, with a median of 33 months of follow-up, meaning that the benefit persists over time. It is important to note that both doses of the ticagrelor were associated with higher incidence of bleeding, but the rates of fatal bleeding did not show any difference between the ticagrelor or placebo. PMID:26689345

  7. Long-term use of ticagrelor in patients with prior heart attack: ticagrelor plus aspirin versus aspirin monotherapy.

    PubMed

    Amico, Frank; Schlesinger, Alex; Mazzoni, Jennifer

    2016-01-01

    Review of: Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-1800. This Practice Pearl reviews the recent study Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared With Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54). It challenges the current standard of care of 12 months of dual antiplatelet followed by aspirin indefinitely. The study demonstrated that patients who received ticagrelor, either the 60 mg or 90 mg twice daily plus aspirin, showed a decreased risk of cardiovascular death, myocardial infarction, or stroke. The PEGASUS-TIMI 54 trial also proved that the benefit of ticagrelor was seen early and continued to accrue over time, with a median of 33 months of follow-up, meaning that the benefit persists over time. It is important to note that both doses of the ticagrelor were associated with higher incidence of bleeding, but the rates of fatal bleeding did not show any difference between the ticagrelor or placebo.

  8. Glucuronidation of the aspirin metabolite salicylic acid by expressed UDP-glucuronosyltransferases and human liver microsomes.

    PubMed

    Kuehl, Gwendolyn E; Bigler, Jeannette; Potter, John D; Lampe, Johanna W

    2006-02-01

    Acetylsalicylic acid (aspirin) is a common nonsteroidal anti-inflammatory drug used for treatment of pain and arthritis. In the body, acetylsalicylic acid is rapidly deacetylated to form salicylic acid. Both compounds have been proposed as anti-inflammatory agents. Major metabolites of salicylic acid are its acyl and phenolic glucuronide conjugates. Formation of these conjugates, catalyzed by UDP-glucuronosyltransferases (UGTs), decreases the amount of pharmacologically active salicylic acid present. We aimed to identify the UGTs catalyzing the glucuronidation of salicylic acid using both heterologously expressed enzymes and pooled human liver microsomes (HLMs) and to develop a liquid chromatography-tandem mass spectrometry method to quantify glucuronidation activity of UGTs 1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15, and 2B17 Supersomes. All UGTs tested, except 1A4, 2B15, and 2B17, catalyzed salicylic acid phenolic and acyl glucuronidation. Ratios of salicylic acid phenolic to acyl glucuronide formation varied more than 12-fold from 0.5 for UGT1A6 to 6.1 for UGT1A1. These results suggest that all UGTs except 1A4, 2B15, and 2B17 might be involved in the glucuronidation of salicylic acid in vivo. From comparisons of apparent Km values determined in pooled HLMs and in expressed UGTs, UGT2B7 was suggested as a likely catalyst of salicylic acid acyl glucuronidation, whereas multiple UGTs were suggested as catalysts of phenolic glucuronidation. The results of this UGT screening may help target future evaluation of the effects of UGT polymorphisms on response to aspirin in clinical and population-based studies.

  9. Glucuronidation of the aspirin metabolite salicylic acid by expressed UDP-glucuronosyltransferases and human liver microsomes.

    PubMed

    Kuehl, Gwendolyn E; Bigler, Jeannette; Potter, John D; Lampe, Johanna W

    2006-02-01

    Acetylsalicylic acid (aspirin) is a common nonsteroidal anti-inflammatory drug used for treatment of pain and arthritis. In the body, acetylsalicylic acid is rapidly deacetylated to form salicylic acid. Both compounds have been proposed as anti-inflammatory agents. Major metabolites of salicylic acid are its acyl and phenolic glucuronide conjugates. Formation of these conjugates, catalyzed by UDP-glucuronosyltransferases (UGTs), decreases the amount of pharmacologically active salicylic acid present. We aimed to identify the UGTs catalyzing the glucuronidation of salicylic acid using both heterologously expressed enzymes and pooled human liver microsomes (HLMs) and to develop a liquid chromatography-tandem mass spectrometry method to quantify glucuronidation activity of UGTs 1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15, and 2B17 Supersomes. All UGTs tested, except 1A4, 2B15, and 2B17, catalyzed salicylic acid phenolic and acyl glucuronidation. Ratios of salicylic acid phenolic to acyl glucuronide formation varied more than 12-fold from 0.5 for UGT1A6 to 6.1 for UGT1A1. These results suggest that all UGTs except 1A4, 2B15, and 2B17 might be involved in the glucuronidation of salicylic acid in vivo. From comparisons of apparent Km values determined in pooled HLMs and in expressed UGTs, UGT2B7 was suggested as a likely catalyst of salicylic acid acyl glucuronidation, whereas multiple UGTs were suggested as catalysts of phenolic glucuronidation. The results of this UGT screening may help target future evaluation of the effects of UGT polymorphisms on response to aspirin in clinical and population-based studies. PMID:16258079

  10. In Vitro Cytotoxic Effects of Celecoxib, Mefenamic Acid, Aspirin and Indometacin on Several Cells Lines

    PubMed Central

    Hashemipour, Maryam Alsadat; Mehrabizadeh Honarmand, Hoda; Falsafi, Farideh; Tahmasebi Arashlo, Mehrnaz; Rajabalian, Saied; Gandjalikhan Nassab, Sayed Amir Hossein

    2016-01-01

    Statement of the Problem Use of cyclooxygenase inhibitors as chemotherapy agents has attracted the attention of a large number of investigators in recent years. Given the importance of cancer therapy, only a limited number of studies have been carried out to investigate the effects of cyclooxygenase inhibitors on specific cell lines. Purpose This research aimed to determine the in vitro cytotoxic effects of cyclooxygenase inhibitors (COX-1 and COX-2 inhibitors) on KB, Saos-2, 1321N, U-87MG, SFBF-PI 39 cell lines. Materials and Method Powders of celecoxib, mefenamic acid, aspirin and indometacin were dissolved in the appropriate solvent. The viability of cell lines was carried out by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay technique. Data gathered from four separate experiments were expressed as mean±SD. Statistical significance was defined at p< 0.05 by using analysis of variance. Significant treatment mean values were subjected to post-hoc Tukey’s test. Results Celecoxib showed marked cytotoxic effects on KB, Saos-2, and 1321N cells, which was significant in comparison with the control group. Celecoxib was not effective in killing U-87MG cell line. Mefenamic acid exerted cytotoxic effects on KB, Saos-2, and 1321N cells, where the viability was approximately 75%. U-87MG cells were resistant to mefenamic acid. Indometacin had the highest rate of activity on U-87MG cells, which was significant in comparison with the control group. Aspirin did not exhibit any activity on these cell lines and was not effective in killing U-87MG, KB, Saos-2, and 1321N cells. Conclusion This research showed that celecoxib, indometacin, and mefenamic acid have the cytotoxic effects on KB, Saos-2, 1321N and U-87MG cell lines. Therefore, it appears that these drugs can be considered as anti-neoplastic agents in the experimental phase. PMID:27602398

  11. In Vitro Cytotoxic Effects of Celecoxib, Mefenamic Acid, Aspirin and Indometacin on Several Cells Lines

    PubMed Central

    Hashemipour, Maryam Alsadat; Mehrabizadeh Honarmand, Hoda; Falsafi, Farideh; Tahmasebi Arashlo, Mehrnaz; Rajabalian, Saied; Gandjalikhan Nassab, Sayed Amir Hossein

    2016-01-01

    Statement of the Problem Use of cyclooxygenase inhibitors as chemotherapy agents has attracted the attention of a large number of investigators in recent years. Given the importance of cancer therapy, only a limited number of studies have been carried out to investigate the effects of cyclooxygenase inhibitors on specific cell lines. Purpose This research aimed to determine the in vitro cytotoxic effects of cyclooxygenase inhibitors (COX-1 and COX-2 inhibitors) on KB, Saos-2, 1321N, U-87MG, SFBF-PI 39 cell lines. Materials and Method Powders of celecoxib, mefenamic acid, aspirin and indometacin were dissolved in the appropriate solvent. The viability of cell lines was carried out by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay technique. Data gathered from four separate experiments were expressed as mean±SD. Statistical significance was defined at p< 0.05 by using analysis of variance. Significant treatment mean values were subjected to post-hoc Tukey’s test. Results Celecoxib showed marked cytotoxic effects on KB, Saos-2, and 1321N cells, which was significant in comparison with the control group. Celecoxib was not effective in killing U-87MG cell line. Mefenamic acid exerted cytotoxic effects on KB, Saos-2, and 1321N cells, where the viability was approximately 75%. U-87MG cells were resistant to mefenamic acid. Indometacin had the highest rate of activity on U-87MG cells, which was significant in comparison with the control group. Aspirin did not exhibit any activity on these cell lines and was not effective in killing U-87MG, KB, Saos-2, and 1321N cells. Conclusion This research showed that celecoxib, indometacin, and mefenamic acid have the cytotoxic effects on KB, Saos-2, 1321N and U-87MG cell lines. Therefore, it appears that these drugs can be considered as anti-neoplastic agents in the experimental phase.

  12. Studies on Aspirin Crystals Generated by a Modified Vapor Diffusion Method.

    PubMed

    Mittal, Amit; Malhotra, Deepak; Jain, Preeti; Kalia, Anupama; Shunmugaperumal, Tamilvanan

    2016-08-01

    The objectives of the current investigation were (1) to study the influence of selected two different non-solvents (diethylether and dichloromethane) on the drug crystal formation of a model drug, aspirin (ASP-I) by the modified vapor diffusion method and (2) to characterize and compare the generated crystals (ASP-II and ASP-III) using different analytical techniques with that of unprocessed ASP-I. When compared to the classical vapor diffusion method which consumes about 15 days to generate drug crystals, the modified method needs only 12 h to get the same. Fourier transform-infrared spectroscopy (FT-IR) reveals that the internal structures of ASP-II and ASP-III crystals were identical when compared with ASP-I. Although the drug crystals showed a close similarity in X-ray diffraction patterns, the difference in the relative intensities of some of the diffraction peaks (especially at 2θ values of around 7.7 and 15.5) could be attributed to the crystal habit or crystal size modification. Similarly, the differential scanning calorimetry (DSC) study speculates that only the crystal habit modifications might occur but without involving any change in internal structure of the generated drug polymorphic form I. This is further substantiated from the scanning electron microscopy (SEM) pictures that indicated the formation of platy shape for the ASP-II crystals and needle shape for the ASP-III crystals. In addition, the observed slow dissolution of ASP crystals should indicate polymorph form I formation. Thus, the modified vapor diffusion method could routinely be used to screen and legally secure all possible forms of other drug entities too.

  13. High On-Aspirin Platelet Reactivity and Clinical Outcome in Patients With Stable Coronary Artery Disease: Results From ASCET (Aspirin Nonresponsiveness and Clopidogrel Endpoint Trial)

    PubMed Central

    Pettersen, Alf-Åge R.; Seljeflot, Ingebjørg; Abdelnoor, Michael; Arnesen, Harald

    2012-01-01

    Background Patients with stable coronary artery disease on single-antiplatelet therapy with aspirin are still at risk for atherothrombotic events, and high on-aspirin residual platelet reactivity (RPR) has been suggested as a risk factor. Methods and Results In this randomized trial, the association between platelet function determined by the PFA100 platelet function analyzer system (Siemens Healthcare Diagnostics, Germany) and clinical outcome in 1001 patients, all on single-antiplatelet therapy with aspirin (160 mg/d) was studied. Patients were randomized to continue with aspirin 160 mg/d or change to clopidogrel 75 mg/d. A composite end point of death, myocardial infarction, ischemic stroke, and unstable angina was used. At 2-year follow-up, 106 primary end points were registered. The prevalence of high RPR was 25.9%. High on-aspirin RPR did not significantly influence the primary end point in the aspirin group (13.3% versus 9.9%, P=0.31). However, in post hoc analysis, patients with von Willebrand factor levels or platelet count below median values and high on-aspirin RPR had a statistically significant higher end point rate than that of patients with low RPR (20% versus 7.5%, P=0.014, and 18.2% versus 10.8%, P=0.039, respectively). The composite end point rate in patients with high on-aspirin RPR treated with clopidogrel was not different from that of patients treated with aspirin (7.6% versus 13.3%, P=0.16). Conclusions In stable, aspirin-treated patients with coronary artery disease, high on-aspirin RPR did not relate to clinical outcome and did not identify a group responsive to clopidogrel. Post hoc subgroup analysis raised the possibility that high on-aspirin RPR might be predictive in patients with low von Willebrand factor or platelet count, but these findings will require confirmation in future studies. Clinical Trial Registration URL: http://www.clinicaltrials.gov Unique identifier: NCT00222261. (J Am Heart Assoc. 2012;1:e000703 doi: 10.1161/JAHA.112

  14. Differential Sex Response to Aspirin in Decreasing Aneurysm Rupture in Humans and Mice.

    PubMed

    Chalouhi, Nohra; Starke, Robert M; Correa, Tatiana; Jabbour, Pascal M; Zanaty, Mario; Brown, Robert D; Torner, James C; Hasan, David M

    2016-08-01

    We previously found that aspirin decreases the risk of cerebral aneurysm rupture in humans. We aim to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin and confirm these observations in a mouse model of cerebral aneurysm. A nested case-control analysis from the International Study of Unruptured Intracranial Aneurysms was performed to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin. A series of experiments were subsequently performed in a mouse model of cerebral aneurysms. Aneurysms were induced with hypertension and elastase injection into mice basal cisterns. We found that aspirin decreased the risk of aneurysm rupture more significantly in men than in women in the International Study of Unruptured Intracranial Aneurysms. In mice, aspirin and cyclooxygenase-2 inhibitor did not affect cerebral aneurysm formation but significantly decreased the incidence of rupture. The incidence of rupture was significantly lower in male versus female mice on aspirin. Gene expression analysis from cerebral arteries showed higher 15-hydroxyprostaglandin dehydrogenase levels in male mice. The rate of cerebral aneurysm rupture was similar in male mice receiving aspirin and 15-hydroxyprostaglandin dehydrogenase inhibitor compared with females receiving aspirin and 15-hydroxyprostaglandin dehydrogenase agonist, signaling a reversal of the sex-differential response to aspirin. Aspirin decreases aneurysm rupture in human and mice, in part through cyclooxygenase-2 pathways. Evidence from animal and human studies suggests a consistent differential effect by sex. 15-Hydroxyprostaglandin dehydrogenase activation in females reduces the incidence of rupture and eliminates the sex-differential response to aspirin. PMID:27296993

  15. The Use of Drugs in Sports.

    ERIC Educational Resources Information Center

    Roy, Steven

    Indications, precautions, contraindications, and side effects of drugs most frequently used by athletic trainers in treating injuries are discussed: (1) aspirin; (2) arylalkanoic derivatives; (3) butazolidin and tandearil; (4) corticosteroids; (5) oral corticosteroids; (6) muscle relaxants; (7) analgesics; (8) cold medications; (9) antidiarrheal…

  16. Aspirin induces cell death and caspase-dependent phosphatidylserine externalization in HT-29 human colon adenocarcinoma cells

    PubMed Central

    Castaño, E; Dalmau, M; Barragán, M; Pueyo, G; Bartrons, R; Gil, J

    1999-01-01

    The induction of cell death by aspirin was analysed in HT-29 colon carcinoma cells. Aspirin induced two hallmarks of apoptosis: nuclear chromatin condensation and increase in phosphatidylserine externalization. However, aspirin did not induce either oligonucleosomal fragmentation of DNA, decrease in DNA content or nuclear fragmentation. The effect of aspirin on Annexin V binding was inhibited by the caspase inhibitor Z-VAD.fmk, indicating the involvement of caspases in the apoptotic action of aspirin. However, aspirin did not induce proteolysis of PARP, suggesting that aspirin does not increase nuclear caspase 3-like activity in HT-29 cells. This finding may be related with the ‘atypical’ features of aspirin-induced apoptosis in HT-29 cells. © 1999 Cancer Research Campaign PMID:10496355

  17. Asplatin enhances drug efficacy by altering the cellular response.

    PubMed

    Cheng, Qinqin; Shi, Hongdong; Wang, Hongxia; Wang, Jun; Liu, Yangzhong

    2016-07-13

    Aspirin, a widely used anti-inflammatory drug, has been shown to be effective for the prevention and remission of cancers (Science, 2012, 337(21) 1471-1473). Asplatin, a Pt(iv) prodrug of cisplatin with the ligation of aspirin (c,c,t-[PtCl2(NH3)2(OH)(aspirin)]), demonstrates significantly higher cytotoxicity than cisplatin towards tumor cells and almost fully overcomes the drug resistance of cisplatin resistant cells. In this work, we have studied the molecular mechanism of asplatin by investigating the cellular response to this compound in order to understand the prominent inhibitory effect on the proliferation of cancer cells. The apoptosis analyses and the related gene expression measurements show that aspirin released from asplatin significantly modulates the cellular response to the platinum agent. Asplatin promotes the apoptosis via the BCL-2 associated mitochondrial pathway. The down-regulation of BCL-2 along with the up-regulation of BAX and BAK enhances the mitochondrial outer membrane permeability, resulting in the cytochrome c release from mitochondria into the cytosol. This event promotes the apoptosis by activation of caspase processing. Consequently, the ligation of aspirin significantly enhances the drug efficacy of the platinum complex in the low micromolar range. The alteration of the cellular response is probably responsible for the circumvention of the cisplatin resistance by asplatin. These results provide an insight into the mechanism of asplatin and provide information for designing new classic platinum drugs. PMID:27125788

  18. Selective inhibition by aspirin and naproxen of mainstream cigarette smoke-induced genotoxicity and lung tumors in female mice.

    PubMed

    Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Micale, Rosanna T; La Maestra, Sebastiano; D'Oria, Chiara; Steele, Vernon E; De Flora, Silvio

    2016-05-01

    The role of nonsteroidal anti-inflammatory drugs (NSAIDs) in smoke-related lung carcinogenesis is still controversial. We have developed and validated a murine model for evaluating the tumorigenicity of mainstream cigarette smoke (MCS) and its modulation by chemopreventive agents. In the present study, the protective effects of the nonselective cyclooxygenase inhibitors aspirin and naproxen were investigated by using a total of 277 Swiss H neonatal mice of both genders. Groups of mice were exposed whole-body to MCS during the first 4 months of life, followed by an additional 3.5 months in filtered air in order to allow a better growth of tumors. Aspirin (1600 mg/kg diet) and naproxen (320 mg/kg diet) were given after weanling until the end of the experiment. After 4 months of exposure, MCS significantly enhanced the frequency of micronucleated normochromatic erythrocytes in the peripheral blood of mice, and naproxen prevented such systemic genotoxic damage in female mice. After 7.5 months, exposure of mice to MCS resulted in the formation of lung tumors, both benign and malignant, and in several other histopathological lesions detectable both in the respiratory tract and in the urinary tract. Aspirin and, even more sharply, naproxen significantly inhibited the formation of lung tumors in MCS-exposed mice, but this protective effect selectively occurred in female mice only. These results lend support to the views that estrogens are involved in smoke-related pulmonary carcinogenesis and that NSAIDs have antiestrogenic properties. The two NSAIDs proved to be safe and efficacious in the experimental model used. PMID:26104855

  19. Thumbnail Sketches: Consumer Application of Chemical Principles: Drugs.

    ERIC Educational Resources Information Center

    Hill, John W.; Jones, Susan M.

    1985-01-01

    Acid-base chemistry can be made more meaningful to beginning students by using familiar drugs as examples. They include: (1) drugs (nicotine, cocaine, and aspirin); (2) general anesthesia (nitrous oxide, enflurane, isoflurane, and halothane); (3) local anesthetics (procaine, lidocaine, and cocaine); and (4) intravenous anesthetics (thiopental,…

  20. Nimesulide, a cyclooxygenase-2 selective inhibitor, suppresses obesity-related non-alcoholic fatty liver disease and hepatic insulin resistance through the regulation of peroxisome proliferator-activated receptor γ

    PubMed Central

    Tsujimoto, Shunsuke; Kishina, Manabu; Koda, Masahiko; Yamamoto, Yasutaka; Tanaka, Kohei; Harada, Yusuke; Yoshida, Akio; Hisatome, Ichiro

    2016-01-01

    Cyclooxygenase (COX)-2 selective inhibitors suppress non-alcoholic fatty liver disease (NAFLD); however, the precise mechanism of action remains unknown. The aim of this study was to examine how the COX-2 selective inhibitor nimesulide suppresses NAFLD in a murine model of high-fat diet (HFD)-induced obesity. Mice were fed either a normal chow diet (NC), an HFD, or HFD plus nimesulide (HFD-nime) for 12 weeks. Body weight, hepatic COX-2 mRNA expression and triglyceride accumulation were significantly increased in the HFD group. Triglyceride accumulation was suppressed in the HFD-nime group. The mRNA expression of hepatic peroxisome proliferator-activated receptor γ (PPARγ) and the natural PPARγ agonist 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) were significantly increased in the HFD group and significantly suppressed in the HFD-nime group. Glucose metabolism was impaired in the HFD group compared with the NC group, and it was significantly improved in the HFD-nime group. In addition, the plasma insulin levels in the HFD group were increased compared with those in the NC group, and were decreased in the HFD-nime group. These results indicate that HFD-induced NAFLD is mediated by the increased hepatic expression of COX-2. We suggest that the production of 15d-PGJ2, which is mediated by COX-2, induces NAFLD and hepatic insulin resistance by activating PPARγ. Furthermore, the mRNA expression of tissue inhibitor of metalloproteinases-1 (TIMP-1), procollagen-1 and monocyte chemoattractant protein-1 (MCP-1), as well as the number of F4/80-positive hepatic (Kupffer) cells, were significantly increased in the HFD group compared with the NC group, and they were reduced by nimesulide. In conclusion, COX-2 may emerge as a molecular target for preventing the development of NAFLD and insulin resistance in diet-related obesity. PMID:27431935

  1. Reduction of bacterial titers by low-dose aspirin in experimental aortic valve endocarditis.

    PubMed Central

    Nicolau, D P; Freeman, C D; Nightingale, C H; Quintiliani, R; Coe, C J; Maderazo, E G; Cooper, B W

    1993-01-01

    Using a rabbit model of Staphylococcus aureus endocarditis, we studied the effects of aspirin on the natural progression of this infection. Compared with untreated animals, the aspirin-treated animals showed a 30% (P = 0.11) reduction in the weight of the vegetations and an 84% (P = 0.03) reduction in the bacterial titer of the vegetations. PMID:8454370

  2. Aspirin and atenolol enhance metformin activity against breast cancer by targeting both neoplastic and microenvironment cells.

    PubMed

    Talarico, Giovanna; Orecchioni, Stefania; Dallaglio, Katiuscia; Reggiani, Francesca; Mancuso, Patrizia; Calleri, Angelica; Gregato, Giuliana; Labanca, Valentina; Rossi, Teresa; Noonan, Douglas M; Albini, Adriana; Bertolini, Francesco

    2016-01-01

    Metformin can induce breast cancer (BC) cell apoptosis and reduce BC local and metastatic growth in preclinical models. Since Metformin is frequently used along with Aspirin or beta-blockers, we investigated the effect of Metformin, Aspirin and the beta-blocker Atenolol in several BC models. In vitro, Aspirin synergized with Metformin in inducing apoptosis of triple negative and endocrine-sensitive BC cells, and in activating AMPK in BC and in white adipose tissue (WAT) progenitors known to cooperate to BC progression. Both Aspirin and Atenolol added to the inhibitory effect of Metformin against complex I of the respiratory chain. In both immune-deficient and immune-competent preclinical models, Atenolol increased Metformin activity against angiogenesis, local and metastatic growth of HER2+ and triple negative BC. Aspirin increased the activity of Metformin only in immune-competent HER2+ BC models. Both Aspirin and Atenolol, when added to Metformin, significantly reduced the endothelial cell component of tumor vessels, whereas pericytes were reduced by the addition of Atenolol but not by the addition of Aspirin. Our data indicate that the addition of Aspirin or of Atenolol to Metformin might be beneficial for BC control, and that this activity is likely due to effects on both BC and microenvironment cells. PMID:26728433

  3. Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers | Division of Cancer Prevention

    Cancer.gov

    This randomized phase II trial studies the effects of aspirin and zileuton on genes related to tobacco use in current smokers. Smokers are at increased risk for developing lung and other cancers. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers. |

  4. The effect of prolonged aspirin therapy on experimental balloon-catheter arterial wall injury.

    PubMed

    Yeager, R A; Trune, D R; Jacobson, S; Connell, R S; Galey, W T; Shoemake, R G; Vetto, R M

    1990-01-01

    Indications for aspirin following percutaneous transluminal angioplasty are not well defined. Although aspirin's early antithrombotic effect is believed to be beneficial, the long-term influence of aspirin on myointimal proliferative response following balloon-catheter angioplasty is still being investigated. This study quantitates arterial wall thickening, including intimal hyperplasia, at 4 months following balloon-catheter aortic injury in New Zealand white rabbits (n = 12), comparing aspirin treatment (30 mg/kg) with controls. Aspirin was administered daily for 1 month prior and 4 months following aortic injury. Myointimal proliferation was noted in both groups. The mean area of the intima and media as well as the maximum thickness of the intima were similar (p greater than .05) in both the aspirin treatment and control groups. Cellular hyperplasia was evaluated by media smooth muscle cell counts using an ocular reticle. There was a trend toward higher cell counts with aspirin treatment, although there was no significant difference between the two groups. Prolonged aspirin therapy did not alter the degree of myointimal hyperplasia at 4 months postinjury in our model. PMID:2282348

  5. Aspirin-intolerant asthma: a comprehensive review of biomarkers and pathophysiology.

    PubMed

    Velazquez, Juan R; Teran, Luis M

    2013-08-01

    Aspirin-exacerbated respiratory disease is a tetrad of nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to aspirin. Unawareness of this clinical condition by patients and physicians may have grave consequences because of its association with near-fatal asthma. The pathogenesis of aspirin-intolerant asthma is not related with an immunoglobin E mechanism, but with an abnormal metabolism of the lipoxygenase (LO) and cyclooxygenase (COX) pathways. At present, a diagnosis of aspirin sensitivity can be established only by provocative aspirin challenge, which represents a health risk for the patient. This circumstance has encouraged the search for aspirin intolerance-specific biomarkers. Major attempts have focused on mediators related with inflammation and eicosanoid regulation. The use of modern laboratory techniques including high-throughput methods has facilitated the detection of dozens of biological metabolites associated with aspirin-intolerant asthma disease. Not surprisingly, the majority of these is implicated in the LO and COX pathways. However, substantial amounts of data reveal the participation of many genes deriving from different ontologies. Biomarkers may represent a powerful, noninvasive tool in the diagnosis of aspirin sensitivity; moreover, they could provide a new way to classify asthma phenotypes.

  6. Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats

    PubMed Central

    Ghosh, Arijit; Dhumal, V. R.; Tilak, A. V.; Das, Nina; Singh, Amarinder; Bondekar, Abhijit A.

    2011-01-01

    Objective: To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Materials and Methods: Retention of conditioned avoidance response (CAR) and central 5-HT-mediated behavior (lithium-induced head twitches) were assessed using repeated electroconvulsive shock (ECS) in rats. Rats were divided into eight groups: control (pretreated with distilled water), scopolamine (0.5 mg/kg i.p.), ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s) pretreated, aspirin (6.75 mg/kg orally) pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally) pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Results: Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches) and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Conclusion: Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions. PMID:21701638

  7. Aspirin-intolerant asthma: a comprehensive review of biomarkers and pathophysiology.

    PubMed

    Velazquez, Juan R; Teran, Luis M

    2013-08-01

    Aspirin-exacerbated respiratory disease is a tetrad of nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to aspirin. Unawareness of this clinical condition by patients and physicians may have grave consequences because of its association with near-fatal asthma. The pathogenesis of aspirin-intolerant asthma is not related with an immunoglobin E mechanism, but with an abnormal metabolism of the lipoxygenase (LO) and cyclooxygenase (COX) pathways. At present, a diagnosis of aspirin sensitivity can be established only by provocative aspirin challenge, which represents a health risk for the patient. This circumstance has encouraged the search for aspirin intolerance-specific biomarkers. Major attempts have focused on mediators related with inflammation and eicosanoid regulation. The use of modern laboratory techniques including high-throughput methods has facilitated the detection of dozens of biological metabolites associated with aspirin-intolerant asthma disease. Not surprisingly, the majority of these is implicated in the LO and COX pathways. However, substantial amounts of data reveal the participation of many genes deriving from different ontologies. Biomarkers may represent a powerful, noninvasive tool in the diagnosis of aspirin sensitivity; moreover, they could provide a new way to classify asthma phenotypes. PMID:23184151

  8. Aspirin Use on Incidence and Mortality of Gastrointestinal Cancers: Current State of Epidemiological Evidence.

    PubMed

    Huang, Wen-Kuan; Tu, Hui-Tzu; See, Lai-Chu

    2015-01-01

    Aspirin has been one of the most widely used medications since its first synthesis more than 100 years ago. In addition to short-term use for pain and fever relief, regular use of aspirin has been shown to reduce the risk of cardiovascular diseases and strokes. The issue of regular aspirin use in cancer prevention is definitely promising, which has been supported by growing evidence from a number of observational studies and post-trial follow-up data. Among all cancers, aspirin is showing to be the most effective in reducing the risk of colorectal cancer, and even at lower doses demonstrates a 30-40% effectiveness in preventing colorectal cancer. Esophagus and stomach cancers are two cancers getting increased attention from emerging evidence of meta-analyses. Given the common side effects of aspirin, such as gastrointestinal complications, whether it is ready to take aspirin regularly for general population remains controversial since more studies are needed to clarify the net balance between harm and benefit. The decision might become more complicated since recently one molecular epidemiology study showed that different genetic traits may impact the effect of aspirin on colorectal cancer. Here we summarize recent evidence from meta-analyses related to gastrointestinal cancers. We reviewed updated observational studies and post-trial follow up data from randomized controlled trials focusing on the role of aspirin in the incidence and mortality of gastrointestinal cancers. PMID:26369680

  9. Aspirin and atenolol enhance metformin activity against breast cancer by targeting both neoplastic and microenvironment cells

    PubMed Central

    Talarico, Giovanna; Orecchioni, Stefania; Dallaglio, Katiuscia; Reggiani, Francesca; Mancuso, Patrizia; Calleri, Angelica; Gregato, Giuliana; Labanca, Valentina; Rossi, Teresa; Noonan, Douglas M.; Albini, Adriana; Bertolini, Francesco

    2016-01-01

    Metformin can induce breast cancer (BC) cell apoptosis and reduce BC local and metastatic growth in preclinical models. Since Metformin is frequently used along with Aspirin or beta-blockers, we investigated the effect of Metformin, Aspirin and the beta-blocker Atenolol in several BC models. In vitro, Aspirin synergized with Metformin in inducing apoptosis of triple negative and endocrine-sensitive BC cells, and in activating AMPK in BC and in white adipose tissue (WAT) progenitors known to cooperate to BC progression. Both Aspirin and Atenolol added to the inhibitory effect of Metformin against complex I of the respiratory chain. In both immune-deficient and immune-competent preclinical models, Atenolol increased Metformin activity against angiogenesis, local and metastatic growth of HER2+ and triple negative BC. Aspirin increased the activity of Metformin only in immune-competent HER2+ BC models. Both Aspirin and Atenolol, when added to Metformin, significantly reduced the endothelial cell component of tumor vessels, whereas pericytes were reduced by the addition of Atenolol but not by the addition of Aspirin. Our data indicate that the addition of Aspirin or of Atenolol to Metformin might be beneficial for BC control, and that this activity is likely due to effects on both BC and microenvironment cells. PMID:26728433

  10. A study into the genetic basis of aspirin resistance in Pakistani patients with coronary artery disease.

    PubMed

    Mukarram, Osama; Akhtar, Naveed; Junaid, Ayesha; Mohyuddin, Aisha

    2016-07-01

    Aspirin is a key player in the management and prevention of stroke and myocardial infarction in patients with atherothrombosis. About 12% of Pakistanis suffering from coronary artery disease are resistant to aspirin's effects. Clinical, biochemical and genetic factors are known to be responsible for this phenomenon. We conducted this study to investigate whether previously studied polymorphisms in COX-1, GPIIIa, GPIa and P2RYI genes could be the cause of aspirin resistance in our population. Blood samples were collected from 29 aspirin non-responders and 60 ethnically matched responders. Aspirin response assay was performed on IMPACT-R and DNA prepared from blood using the phenol: chloroform method. Genotyping was carried out for four SNPS including COX-1 C50T (rs3842787), GPIIIA PIA1/A2 polymorphism (rs5918), GPIA C807T (rs1126643) and p2RY1 C893T (rs1065776). No statistically significant differences were observed in the allele or genotype frequencies between the aspirin non responders and responders indicating the possible involvement of different genetic determinants of aspirin resistance in our population. This study paves the way for further research into the field of aspirin resistance in Pakistan. PMID:27393450

  11. Aspirin in the prevention of cardiovascular events in patients with diabetes.

    PubMed

    Bell, David S H

    2016-01-01

    Diabetes imparts a substantial increased risk for cardiovascular disease-related mortality and morbidity. Because of this, current medical guidelines recommend prophylactic treatment with once-daily, low-dose aspirin (acetylsalicylic acid) for primary and secondary prevention of cardiovascular (CV) events in high-risk patients. However, only modest reductions in CV events and mortality have been observed with once-daily aspirin treatment in patients with diabetes, including patients with a previous CV event, perhaps because of disparity between aspirin pharmacokinetics and diabetes-related platelet abnormalities. Once-daily aspirin irreversibly inactivates platelets for only a short duration (acetylsalicylic acid half-life, approximately 15-20 minutes), after which time newly generated, active platelets enter the circulation and weaken aspirin's effect. Platelets from patients with diabetes are more reactive and are turned over more rapidly than platelets from normal individuals; the short inhibitory window provided by once-daily aspirin may therefore be insufficient to provide 24-h protection against CV events. Alternative conventional aspirin regimens (e.g. higher daily dose, twice-daily dosing, combination with clopidogrel) and newer formulations (e.g. 24-h, extended-release) have been proposed to overcome the apparent limited efficacy of conventional aspirin in patients with diabetes; however, tolerability concerns and limited clinical efficacy data need to be taken into account when considering the use of such regimens.

  12. A study into the genetic basis of aspirin resistance in Pakistani patients with coronary artery disease.

    PubMed

    Mukarram, Osama; Akhtar, Naveed; Junaid, Ayesha; Mohyuddin, Aisha

    2016-07-01

    Aspirin is a key player in the management and prevention of stroke and myocardial infarction in patients with atherothrombosis. About 12% of Pakistanis suffering from coronary artery disease are resistant to aspirin's effects. Clinical, biochemical and genetic factors are known to be responsible for this phenomenon. We conducted this study to investigate whether previously studied polymorphisms in COX-1, GPIIIa, GPIa and P2RYI genes could be the cause of aspirin resistance in our population. Blood samples were collected from 29 aspirin non-responders and 60 ethnically matched responders. Aspirin response assay was performed on IMPACT-R and DNA prepared from blood using the phenol: chloroform method. Genotyping was carried out for four SNPS including COX-1 C50T (rs3842787), GPIIIA PIA1/A2 polymorphism (rs5918), GPIA C807T (rs1126643) and p2RY1 C893T (rs1065776). No statistically significant differences were observed in the allele or genotype frequencies between the aspirin non responders and responders indicating the possible involvement of different genetic determinants of aspirin resistance in our population. This study paves the way for further research into the field of aspirin resistance in Pakistan.

  13. Syrup formulations for post-tonsillectomy analgesia: a double-blind study comparing ibuprofen, aspirin and placebo.

    PubMed

    Parker, D A; Gibbin, K P; Noyelle, R M

    1986-09-01

    Post-tonsillectomy analgesia from ibuprofen, aspirin and placebo is compared in a double-blind study. The results are reported showing ibuprofen to have greater therapeutic benefit than placebo whereas aspirin did not. Methods of providing pain relief after tonsillectomy and the relative clinical merits of ibuprofen and aspirin are discussed. PMID:3531373

  14. The in vitro effects of Xancor, a synthetic astaxanthine derivative, on hemostatic biomarkers in aspirin-naïve and aspirin-treated subjects with multiple risk factors for vascular disease.

    PubMed

    Serebruany, Victor; Malinin, Alex; Goodin, Thomas; Pashkow, Fredric

    2010-01-01

    Astaxanthine is a polar carotenoid metabolite derived from a proprietary prodrug, Xancor, which aligns parallel with the membrane phospholipids exhibiting potent antioxidant, anti-inflammatory, and cell protective properties, although the precise mechanism of action is unknown. This prodrug is currently under development for hepatic, neurologic, and vascular disease indications. Considering established links between heart disease and stroke with platelets, coagulation cascade, and fibrinolysis, the aim of the study was to assess the effect of asthaxantine on human biomarkers of hemostasis. The rationale was to test a hypothesis that the drug may diminish activation of hemostasis, making it a potentially attractive addition to treat patients with vascular disease. In vitro effects of whole blood preincubation with escalating concentrations of asthaxantine (0.3 microM, 1 microM, 3 microM, 10 microM, 30 microM, and 100 microM) were assessed from 12 aspirin-naïve and eight aspirin-treated volunteers with multiple risk factors for vascular disease. A total of 25 biomarkers were measured, of which 12 were related to platelet function, 10 to coagulation, and three to fibrinolysis. Platelet aggregation induced by ADP, collagen, and arachidonic acid and expression of CD31, CD41, GP IIb/IIIa, CD51/61, P-selectin, CD63, CD107a, CD151+CD14, and CD154 were not affected. Coagulation indices such as aPTT, prothrombin time, thrombin time, fibrinogen, antithrombin III (antigen and activity), Protein C, Protein S (free and activity), and von Willebrand factor remained unchanged after incubation with astaxanthine. Fibrinolytic activity biomarkers such as plasminogen, D-dimer, and FDP were also not affected after in vitro pretreatment of blood samples with astaxanthine. In the projected subclinical (less than 1 microM), therapeutic (3 microM to 30 microM), and supratherapeutic concentration (100 microM), astaxanthine in vitro does not affect platelet, coagulation, or fibrinolytic

  15. Use of aspirin for primary and secondary prevention of cardiovascular disease in diabetic patients in an ambulatory care setting in Spain

    PubMed Central

    Sicras-Mainar, Antoni; Navarro-Artieda, Ruth; Rejas-Gutiérrez, Javier; Fernández-de-Bobadilla, Jaime; Frías-Garrido, Xavier; Ruiz-Riera, Rafael

    2007-01-01

    Background This study was conducted in order to determine the use of aspirin and to assess the achievement of therapeutic targets in diabetic patients according to primary (PP) or secondary prevention (SP). Methods This is a retrospective, observational study including patients ≥18 years with diabetes mellitus followed in four primary care centers. Measurements included demographics, use of aspirin and/or anticoagulant drugs, co-morbidities, clinical parameters and proportion of patient at therapeutic target (TT). Descriptive statistics, chi-square test and logistic regression model were used for significance. Results A total of 4,140 patients were analyzed, 79.1% (95% confidence intervals [CI]: 77.7–80.5%) in PP and 20.9% (95% CI: 18.2–23.7%) in SP. Mean age was 64.1 (13.8) years, and 49.3% of patient were men (PP: 46.3, SP: 60.7, p = 0.001). Aspirin was prescribed routinely in 20.8% (95% CI: 19.4–22.2%) in PP and 60.8% (95% CI: 57.6–64.0%) in SP. Proportion of patient at TT was 48.0% for blood pressure and 59.8% for cholesterol. Use of aspirin was associated to increased age [OR = 1.01 (95% CI: 1.00–1.02); p = 0.011], cardiovascular-risk factors [OR = 1.14 (95% CI: 1.03–1.27); p = 0.013], LDL-C [OR = 1.42 (95% CI: 1.06–1.88); p = 0.017] and higher glycated hemoglobin [OR = 1.51 (95% CI: 1.22–1.89); p = 0.000] were covariates associated to the use of aspirin in PP. Conclusion Treatment with aspirin is underused for PP in patients with diabetes mellitus in Primary Care. Achievement of TT should be improved. PMID:17941978

  16. Cost-effective prophylaxis against venous thromboembolism after total joint arthroplasty: warfarin versus aspirin.

    PubMed

    Mostafavi Tabatabaee, Reza; Rasouli, Mohammad R; Maltenfort, Mitchell G; Parvizi, Javad

    2015-02-01

    Although recent guidelines suggest aspirin for venous thromboembolism (VTE) prophylaxis in low risk patients following total hip arthroplasty (THA) and total knee arthroplasty (TKA), there are no cost-effectiveness studies comparing aspirin and warfarin. In a Markov cohort cost-effectiveness analysis, we found that aspirin cost less and saved more quality-adjusted life-years (QALYs) than warfarin in all age groups. Cost per QALY gained by aspirin was $24,506.20 at age of 55 and $47,148.10 at the age of 85 following THA and $15,117.20 and $24,458.10 after TKA, which were greater than warfarin. In patients undergoing THA/TKA without prior VTE, aspirin is more cost-effective prophylactic agent than warfarin. Warfarin might be a better prophylaxis in TKA patients with high probability of VTE and very low probability of bleeding. PMID:25534862

  17. Direct Costs of Aspirin versus Warfarin for Venous Thromboembolism Prophylaxis after Total Knee or Hip Arthroplasty.

    PubMed

    Gutowski, Christina J; Zmistowski, Benjamin M; Lonner, Jess H; Purtill, James J; Parvizi, Javad

    2015-09-01

    Interest in aspirin as an alternative strategy for venous thromboembolism prophylaxis after arthroplasty has grown, as studies have suggested improved clinical efficacy and lower complication rates with aspirin compared to warfarin. The goal of this study was to compare the direct costs of an episode of arthroplasty care, when using aspirin instead of warfarin. The charts of patients who either received aspirin or warfarin after arthroplasty from January 2008 to March 2010 were retrospectively reviewed. Charges were recorded for their index admission, and for subsequent admissions related to either VTE or complications of prophylaxis. Multivariate analysis revealed that aspirin was an independent predictor of decreased cost of index hospitalization, and total episode of care charges, achieved largely through a shorter length of hospitalization. PMID:26073347

  18. Low-dose aspirin in polycythaemia vera: a pilot study. Gruppo Italiano Studio Policitemia (GISP).

    PubMed

    1997-05-01

    In this pilot study, aimed at exploring the feasibility of a large-scale trial of low-dose aspirin in polycythaemia vera (PV), 112 PV patients (42 females, 70 males. aged 17-80 years) were selected for not having a clear indication for, or contraindication to, aspirin treatment and randomized to receive oral aspirin (40 mg/d) or placebo. Follow-up duration was 16 +/- 6 months. Measurements of thromboxane A2 production during whole blood clotting demonstrated complete inhibition of platelet cyclooxygenase activity in patients receiving aspirin. Aspirin administration was not associated with any bleeding complication. Within the limitations of the small sample size, this study indicates that a biochemically effective regimen of antiplatelet therapy is well tolerated in patients with polycythaemia vera and that a large-scale placebo-controlled trial is feasible.

  19. Direct Costs of Aspirin versus Warfarin for Venous Thromboembolism Prophylaxis after Total Knee or Hip Arthroplasty.

    PubMed

    Gutowski, Christina J; Zmistowski, Benjamin M; Lonner, Jess H; Purtill, James J; Parvizi, Javad

    2015-09-01

    Interest in aspirin as an alternative strategy for venous thromboembolism prophylaxis after arthroplasty has grown, as studies have suggested improved clinical efficacy and lower complication rates with aspirin compared to warfarin. The goal of this study was to compare the direct costs of an episode of arthroplasty care, when using aspirin instead of warfarin. The charts of patients who either received aspirin or warfarin after arthroplasty from January 2008 to March 2010 were retrospectively reviewed. Charges were recorded for their index admission, and for subsequent admissions related to either VTE or complications of prophylaxis. Multivariate analysis revealed that aspirin was an independent predictor of decreased cost of index hospitalization, and total episode of care charges, achieved largely through a shorter length of hospitalization.

  20. Regular aspirin use and nasopharyngeal cancer risk: A case-control study in Italy.

    PubMed

    Di Maso, Matteo; Bosetti, Cristina; La Vecchia, Carlo; Garavello, Werner; Montella, Maurizio; Libra, Massimo; Serraino, Diego; Polesel, Jerry

    2015-08-01

    Regular aspirin use has been associated to decreased risk of several cancers, but evidence on nasopharyngeal carcinoma is scanty. We conducted a hospital-based case-control study in Italy, enrolling 198 Caucasian patients with nasopharyngeal carcinoma. Controls were 592 cancer-free Caucasian patients admitted to the same catchment areas as cases; controls were frequency matched according to sex, age, and area of residence. Regular aspirin use was defined as taking at least one aspirin a week for at least 6 months. Three cases (1.5%) and 27 controls (4.5%) reported regular aspirin use (odds ratio=0.24; 95% CI: 0.07-0.87). The median duration of consumption was 15 months among cases and 60 months among controls. Although study findings should be considered with caution due to limited sample size, they provide further evidence on the protective effect of aspirin use in head and neck cancers.

  1. EKG at triage slashes door-to-aspirin time.

    PubMed

    2006-09-01

    Giving all chest pain patients an electrocardiogram (EKG) in triage can significantly improve treatment times and quality of care and it eliminates the need to prioritize patients and takes undue pressure off the nurses, ED managers say. Triage delays in chest pain evaluation are eliminated by giving all patients the same treatment. Time to first aspirin at one hospital was slashed from 67 minutes to eight minutes. Asking nurses to differentiate patients on the basis of an interview and a set of vitals is unrealistic, managers say.

  2. β-Cyclodextrin inclusion complex: preparation, characterization, and its aspirin release in vitro

    NASA Astrophysics Data System (ADS)

    Zhou, Hui-Yun; Jiang, Ling-Juan; Zhang, Yan-Ping; Li, Jun-Bo

    2012-09-01

    In this work, the optimal clathration condition was investigated for the preparation of aspirin-β-cyclodextrin (Asp-β-CD) inclusion complex using design of experiment (DOE) methodology. A 3-level, 3-factor Box-Behnken design with a total of 17 experimental runs was used. The Asp-β-CD inclusion complex was prepared by saturated solution method. The influence on the embedding rate was investigated, including molar ratio of β-CD to Asp, clathration temperature and clathration time, and the optimum values of such three test variables were found to be 0.82, 49°C and 2.0 h, respectively. The embedding rate could be up to 61.19%. The formation of the bonding between -COOH group of Asp and O-H group of β-CD might play an important role in the process of clathration according to FT-IR spectra. Release kinetics of Asp from inclusion complex was studied for the evaluation of drug release mechanism and diffusion coefficients. The results showed that the drug release from matrix occurred through Fickian diffusion mechanism. The cumulative release of Asp reached only 40% over 24 h, so the inclusion complex could potentially be applied as a long-acting delivery system.

  3. Estimates of benefits and harms of prophylactic use of aspirin in the general population

    PubMed Central

    Cuzick, J.; Thorat, M. A.; Bosetti, C.; Brown, P. H.; Burn, J.; Cook, N. R.; Ford, L. G.; Jacobs, E. J.; Jankowski, J. A.; La Vecchia, C.; Law, M.; Meyskens, F.; Rothwell, P. M.; Senn, H. J.; Umar, A.

    2015-01-01

    Background Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. Methods The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer. Results The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50–65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. Conclusions Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit–harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening–eradication before starting aspirin prophylaxis. PMID:25096604

  4. Aspirin use for primary prophylaxis: Adverse outcomes in non-variceal upper gastrointestinal bleeding

    PubMed Central

    Souk, Karina M; Tamim, Hani M; Abu Daya, Hussein A; Rockey, Don C; Barada, Kassem A

    2016-01-01

    AIM: To compare outcomes of patients with non-variceal upper gastrointestinal bleeding (NVUGIB) taking aspirin for primary prophylaxis to those not taking it. METHODS: Patients not known to have any vascular disease (coronary artery or cerebrovascular disease) who were admitted to the American University of Beirut Medical Center between 1993 and 2010 with NVUGIB were included. The frequencies of in-hospital mortality, re-bleeding, severe bleeding, need for surgery or embolization, and of a composite outcome defined as the occurrence of any of the 4 bleeding related adverse outcomes were compared between patients receiving aspirin and those on no antithrombotics. We also compared frequency of in hospital complications and length of hospital stay between the two groups. RESULTS: Of 357 eligible patients, 94 were on aspirin and 263 patients were on no antithrombotics (control group). Patients in the aspirin group were older, the mean age was 58 years in controls and 67 years in the aspirin group (P < 0.001). Patients in the aspirin group had significantly more co-morbidities, including diabetes mellitus and hypertension [25 (27%) vs 31 (112%) and 44 (47%) vs 74 (28%) respectively, (P = 0.001)], as well as dyslipidemia [21 (22%) vs 16 (6%), P < 0.0001). Smoking was more frequent in the aspirin group [34 (41%) vs 60 (27%), P = 0.02)]. The frequencies of endoscopic therapy and surgery were similar in both groups. Patients who were on aspirin had lower in-hospital mortality rates (2.1% vs 13.7%, P = 0.002), shorter hospital stay (4.9 d vs 7 d, P = 0.01), and fewer composite outcomes (10.6% vs 24%, P = 0.01). The frequencies of in-hospital complications and re-bleeding were similar in the two groups. CONCLUSION: Patients who present with NVUGIB while receiving aspirin for primary prophylaxis had fewer adverse outcomes. Thus aspirin may have a protective effect beyond its cardiovascular benefits. PMID:27462392

  5. Prediagnosis aspirin use and outcomes in a prospective cohort of esophageal cancer patients

    PubMed Central

    Araujo, James L.; Altorki, Nasser K.; Sonett, Joshua R.; Rodriguez, Adriana; Sungur-Stasik, Kivilcim; Spinelli, Cathy F.; Neugut, Alfred I.; Abrams, Julian A.

    2016-01-01

    Background: Esophageal cancer remains associated with poor outcomes, yet little is known regarding factors that influence survival. Aspirin use prior to cancer diagnosis may influence outcomes. We aimed to assess the effects of prediagnosis aspirin use in patients with esophageal cancer. Methods: We conducted a prospective cohort study of newly-diagnosed esophageal cancer patients at two tertiary care centers. We assessed history of prediagnosis aspirin use, and prospectively followed patients and assessed mortality, cause of death, and development of metastases. Results: We enrolled 130 patients, the majority of whom were male (81.5%) and had adenocarcinoma (80.8%). Overall, 57 patients (43.9%) were regular aspirin users. In unadjusted analyses, we found no difference in all-cause mortality between aspirin users and nonusers. In multivariate analyses, prediagnosis aspirin use was not associated with all-cause mortality [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.48–1.57] or esophageal cancer-specific mortality (HR 1.07, 95% CI 0.52–2.21). Prediagnosis aspirin use was associated with a significantly increased risk of interval metastasis (HR 3.59, 95% CI 1.08–11.96). Conclusions: In our cohort of esophageal cancer patients, prediagnosis aspirin use was not associated with all-cause or cancer-specific mortality. However, risk of interval metastatic disease was increased among those who took aspirin regularly prediagnosis. Future studies are warranted to assess whether aspirin influences the molecular characteristics of esophageal tumors, with potential prognostic and therapeutic implications. PMID:27803735

  6. Effect of Several Drugs on Gastric Potential Difference in Man

    PubMed Central

    Murray, H. S.; Strottman, M. P.; Cooke, A. R.

    1974-01-01

    Measurement of gastric mucosal potential difference was used to study the effect on the gastric mucosal barrier in six volunteer subjects of several drugs known to provoke ulcers. Potential differences were also recorded in nine patients with rheumatoid arthritis being treated with long-term aspirin and five patients on long-term prednisone. Unbuffered aspirin and ethanol “broke” the barrier as shown by a rapid fall in potential difference. The effects of aspirin were dose related, with 600 mg causing a greater reduction than 300 mg. The effects of aspirin and ethanol given together were additive and caused the greatest fall in potential difference. Sodium acetylsalicylate did not alter the normal potential difference. Indomethacin, phenylbutazone, and prednisone all failed to cause any change in potential difference. The patients on long-term aspirin and prednisone had readings within the normal range and responded the same as normal subjects to an acute challenge. These studies show that aspirin and ethanol will damage the gastric mucosal barrier but that indomethacin, phenylbutazone, and prednisone do not. PMID:4808815

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

    PubMed Central

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

    2013-01-01

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

  8. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin.

    PubMed

    Bozzi, Laura M; Mitchell, Braxton D; Lewis, Joshua P; Ryan, Kathy A; Herzog, William R; O'Connell, Jeffrey R; Horenstein, Richard B; Shuldiner, Alan R; Yerges-Armstrong, Laura M

    2016-01-01

    Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti-platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days. One hour after the last dose of clopidogrel, 325 mg of aspirin was given. Ex vivo platelet aggregometry was performed at baseline, post-clopidogrel, and post-DAPT. Platelet aggregation measurements were significantly lower after both interventions for all agonists tested (p <0.05), although there was large inter-individual variation in the magnitude of anti-platelet response. Female sex and older age were associated with higher platelet aggregation at all three time-points. Change in aggregation was correlated among the various agonists at each time point. Heritability (h2) of change in platelet aggregation was significant for most traits at all time-points (range h2=0.14-0.57). Utilization of a standardized, short-term intervention provided a powerful approach to investigate sources of variation in platelet aggregation response due to drug therapy. Further, this short-term intervention approach may provide a useful paradigm for pharmacogenomics studies.

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

    SciTech Connect

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

    2012-03-16

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

  10. Resveratrol and aspirin eliminate tetraploid cells for anticancer chemoprevention.

    PubMed

    Lissa, Delphine; Senovilla, Laura; Rello-Varona, Santiago; Vitale, Ilio; Michaud, Mickaël; Pietrocola, Federico; Boilève, Alice; Obrist, Florine; Bordenave, Chloé; Garcia, Pauline; Michels, Judith; Jemaà, Mohamed; Kepp, Oliver; Castedo, Maria; Kroemer, Guido

    2014-02-25

    Tetraploidy constitutes a genomically metastable state that can lead to aneuploidy and genomic instability. Tetraploid cells are frequently found in preneoplastic lesions, including intestinal cancers arising due to the inactivation of the tumor suppressor adenomatous polyposis coli (APC). Using a phenotypic screen, we identified resveratrol as an agent that selectively reduces the fitness of tetraploid cells by slowing down their cell cycle progression and by stimulating the intrinsic pathway of apoptosis. Selective killing of tetraploid cells was observed for a series of additional agents that indirectly or directly stimulate AMP-activated protein kinase (AMPK) including salicylate, whose chemopreventive action has been established by epidemiological studies and clinical trials. Both resveratrol and salicylate reduced the formation of tetraploid or higher-order polyploid cells resulting from the culture of human colon carcinoma cell lines or primary mouse epithelial cells lacking tumor protein p53 (TP53, best known as p53) in the presence of antimitotic agents, as determined by cytofluorometric and videomicroscopic assays. Moreover, oral treatment with either resveratrol or aspirin, the prodrug of salicylate, repressed the accumulation of tetraploid intestinal epithelial cells in the Apc(Min/+) mouse model of colon cancer. Collectively, our results suggest that the chemopreventive action of resveratrol and aspirin involves the elimination of tetraploid cancer cell precursors. PMID:24516128

  11. Can Aspirin and Cancer Prevention be Ageless Companions?

    PubMed

    Farag, Mohamed

    2015-01-01

    Over the past few decades, the rate of cancer diagnosis has increased worldwide due to the increase in population and average life expectancy, and also, due to the advances in diagnostic medical technology that facilitate early cancer detection and recognition. Nonetheless, the treatment options have not been developed proportional to this increase, with a huge number of patients frequently being diagnosed with different types of fatal cancer. This has prompted different health organizations to search for novel strategies to prevent cancer, or even halt its progression. Having failed to provide optimum vascular protection benefits, especially with the introduction of relatively superior antiplatelets, such as adenosine diphosphate (ADP) receptor inhibitors; clopidogrel and ticagrelor, regular aspirin use was proposed to reduce the risk of common cancers like colorectal cancer, gastric cancer, breast cancer, lung cancer, prostate cancer and haematological malignancies, as suggested by epidemiological studies. However, it is difficult to draw any firm conclusions on such weak data, as this could raise false hopes among patients and physicians and could potentially mislead scientific research. Clearly, current evidence highlights a gap in medical research and emphasizes the need to carry out interventional studies in high risk for cancer patients using specific aspirin doses in order to validate the data. This should also shed some light on the risk-benefit profile in view of the potential for bleeding complications, especially with the higher doses. PMID:25738074

  12. Aspirin with or without an antiemetic for acute migraine headaches in adults

    PubMed Central

    Kirthi, Varo; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine headaches. Objectives To determine the efficacy and tolerability of aspirin, alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine headaches in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 10 March 2010. Selection criteria We included randomised, double-blind, placebo- or active-controlled studies using aspirin to treat a discrete migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Main results Thirteen studies (4222 participants) compared aspirin 900 mg or 1000 mg, alone or in combination with metoclopramide 10 mg, with placebo or other active comparators, mainly sumatriptan 50 mg or 100 mg. For all efficacy outcomes, all active treatments were superior to placebo, with NNTs of 8.1, 4.9 and 6.6 for 2-hour pain-free, 2-hour headache relief, and 24-hour headache relief with aspirin alone versus placebo, and 8.8, 3.3 and 6.2 with aspirin plus metoclopramide versus placebo. Sumatriptan 50 mg did not differ from aspirin alone for 2-hour pain-free and headache relief, while sumatriptan 100 mg was better than the combination of aspirin plus metoclopramide for 2-hour pain-free, but not headache relief; there were no data for 24-hour headache relief. Associated symptoms of nausea, vomiting

  13. Use of Health Care System-Supplied Aspirin by Veterans With Postoperative Heart Attack or Unstable Angina.

    PubMed

    Rivera, Cathleen M; Copeland, Laurel A; McNeal, Catherine J; Mortensen, Eric M; Pugh, Mary J; MacCarthy, Daniel J

    2015-10-01

    Evidence-based guidelines for the use of aspirin in secondary prevention of cardiovascular disease events are well established. Despite this, the prevalence of aspirin use for secondary prevention is suboptimal. The study aimed to determine the prevalence of aspirin use for secondary prevention of cardiovascular disease events when it is dispensed as a prescription, as is performed in the Veterans Affairs (VA) managed care system. VA patients who had undergone major surgery and experienced a postoperative myocardial infarction (MI) or unstable angina between the years 2005 and 2009 were identified from administrative databases. VA pharmacy records were used to determine whether a prescription for aspirin was filled after the postoperative MI or unstable angina. Multivariable logistic regression models estimated odd ratios of filling aspirin prescriptions for the predictors of interest. Of the 321,131 men and women veterans who underwent major surgery, 7,700 experienced a postoperative MI or unstable angina. Among those 7,700, 47% filled an aspirin prescription. Only 59% of veterans with no co-pay filled an aspirin prescription. Aspirin fills were more common in younger veterans, Blacks, Hispanics, males, hypertensive veterans, mentally ill patients, those with no co-pay and those prescribed antiplatelets/anticoagulants in addition to aspirin postoperatively. These findings suggest that the impact of dispensing aspirin as a prescription may not be significant in increasing the appropriate use of aspirin for secondary prevention. PMID:26351774

  14. Use of Health Care System-Supplied Aspirin by Veterans With Postoperative Heart Attack or Unstable Angina.

    PubMed

    Rivera, Cathleen M; Copeland, Laurel A; McNeal, Catherine J; Mortensen, Eric M; Pugh, Mary J; MacCarthy, Daniel J

    2015-10-01

    Evidence-based guidelines for the use of aspirin in secondary prevention of cardiovascular disease events are well established. Despite this, the prevalence of aspirin use for secondary prevention is suboptimal. The study aimed to determine the prevalence of aspirin use for secondary prevention of cardiovascular disease events when it is dispensed as a prescription, as is performed in the Veterans Affairs (VA) managed care system. VA patients who had undergone major surgery and experienced a postoperative myocardial infarction (MI) or unstable angina between the years 2005 and 2009 were identified from administrative databases. VA pharmacy records were used to determine whether a prescription for aspirin was filled after the postoperative MI or unstable angina. Multivariable logistic regression models estimated odd ratios of filling aspirin prescriptions for the predictors of interest. Of the 321,131 men and women veterans who underwent major surgery, 7,700 experienced a postoperative MI or unstable angina. Among those 7,700, 47% filled an aspirin prescription. Only 59% of veterans with no co-pay filled an aspirin prescription. Aspirin fills were more common in younger veterans, Blacks, Hispanics, males, hypertensive veterans, mentally ill patients, those with no co-pay and those prescribed antiplatelets/anticoagulants in addition to aspirin postoperatively. These findings suggest that the impact of dispensing aspirin as a prescription may not be significant in increasing the appropriate use of aspirin for secondary prevention.

  15. Why does aspirin decrease the risk of venous thromboembolism? On old and novel antithrombotic effects of acetyl salicylic acid.

    PubMed

    Undas, A; Brummel-Ziedins, K; Mann, K G

    2014-11-01

    It is well established that aspirin, an irreversible inhibitor of platelet cyclooxygenase activity, is effective in secondary prevention of arterial thromboembolic events. The pooled results of the recent randomized, multicenter WARFASA and ASPIRE aspirin trials showed a 32% reduction in the rate of recurrence of venous thromboembolism (VTE) in patients receiving aspirin following VTE. These clinical data support evidence that platelets contribute to the initiation and progression of venous thrombosis and aspirin inhibits thrombin formation and thrombin-mediated coagulant reactions. In addition to the known acetylation of serine 529 residue in platelet cyclooxygenase-1, the postulated mechanisms of aspirin-induced antithrombotic actions also involve the acetylation of other proteins in blood coagulation, including fibrinogen, resulting in more efficient fibrinolysis. This review summarizes current knowledge on the aspirin-induced antithrombotic effects that potentially explain clinical studies showing reduced rates of VTE events in aspirin-treated subjects.

  16. Bioavailability of aspirin and salicylamide following oral co-administration in human volunteers.

    PubMed

    Abdel-Rahman, M S; Reddi, A S; Curro, F A; Turkall, R M; Kadry, A M; Hansrote, J A

    1991-10-01

    BC powder (I) is a commercially available analgesic containing the active ingredients aspirin and salicylamide. The kinetics of I, BC powder minus aspirin (II), and BC powder minus salicylamide (III) were evaluated in 13 volunteers. Ten minutes after administration of I, aspirin reached a maximum concentration of 12.9 micrograms/mL, while salicylamide concentration reached a peak value of 3.4 micrograms/mL. However, when III was administered, aspirin was not detected at 10 min and only reached a concentration of 0.4 microgram/mL at 2 and 6 h. Furthermore, the area under the plasma concentration versus time curve for aspirin when III was administered was sixfold less compared with treatment with I. The area under the curve for aspirin metabolites was significantly different in I versus III. After treatment with II, a delay in salicylamide peak concentration was observed. Gentisamide was not detected throughout the study. This study demonstrates that salicylamide significantly enhances plasma levels of aspirin with potential therapeutic implications. PMID:1777842

  17. Zeta-crystallin displays strong selectivity for salicylic acid over aspirin.

    PubMed

    Bazzi, Mohammad D

    2002-04-26

    Interaction of camel lens zeta-crystallin with aspirin was investigated by activity and fluorescence measurements. Aspirin minimally inhibited the oxidoreductase activity of the enzyme and weakly quenched its fluorescence. However, significant fluorescence quenching of zeta-crystallin coincided with the appearance of a fluorescence signal characteristic of salicylic acid thereby raising the possibility that salicylic acid might have been the moiety responsible for inhibition and fluorescence quenching. Direct fluorescence measurements showed that zeta-crystallin had a much higher affinity for salicylic acid than aspirin (K(i) of about 24 microM for salicylic acid versus 630 microM for aspirin). Salicylic acid was also far more effective in inhibiting zeta-crystallin than aspirin (K(i) values were 23 microM versus 820 microM, respectively). Inhibition kinetics suggested that salicylic acid interacted with zeta-crystallin via a binding site that was distinct from that of NADPH. Salicylic acid also interacted with and quenched the fluorescence of camel lens alpha-crystallin suggesting a general mode of interaction with lens proteins. Within the normal therapeutic concentrations of salicylic acid or aspirin, only crystallin-salicylic acid interactions might be significant. These results showed that camel lens zeta- and alpha-crystallin exhibited remarkable selectivity for salicylic acid over aspirin, and thus, could be considered as salicylate-binding proteins.

  18. Mutations in PIK3CA sensitize breast cancer cells to physiologic levels of aspirin.

    PubMed

    Turturro, Sanja B; Najor, Matthew S; Ruby, Carl E; Cobleigh, Melody A; Abukhdeir, Abde M

    2016-02-01

    A review of the literature finds that women diagnosed with breast cancer, who were on an aspirin regimen, experienced a decreased risk of distant metastases and death. Several recent studies have reported an improvement in overall survival in colorectal cancer patients who harbored mutations in the oncogene PIK3CA and received a daily aspirin regimen. Breast cancer patients on a daily aspirin regimen experienced decreased risk of distant metastases and death. PIK3CA is the most frequently mutated oncogene in breast cancer, occurring in up to 45 % of all breast cancers. In order to determine if mutations in PIK3CA sensitized breast cancers to aspirin treatment, we employed the use of isogenic cellular clones of the non-tumorigenic, breast epithelial cell line MCF-10A that harbored mutations in either PIK3CA or KRAS or both. We report that mutations in both PIK3CA and KRAS are required for the greatest aspirin sensitivity in breast cancer, and that the GSK3β protein was hyperphosphorylated in aspirin-treated double knockin cells, but not in other clones/treatments. A more modest effect was observed with single mutant PIK3CA, but not KRAS alone. These observations were further confirmed in a panel of breast cancer cell lines. Our findings provide the first evidence that mutations in PIK3CA sensitize breast cancer cells to aspirin. PMID:26915040

  19. Pharmacokinetics of salicylic acid following administration of aspirin tablets and three different forms of soluble aspirin in normal subjects.

    PubMed

    Gatti, G; Barzaghi, N; Attardo Parrinello, G; Vitiello, B; Perucca, E

    1989-01-01

    The pharmacokinetic profile of an innovative formulation of soluble aspirin (l-ornithine acetylsalicylate, ldB 1003) was compared with that of conventional tablets and two other soluble dosage forms (d, l-lysine acetylsalicylate and a buffered effervescent formulation of acetylsalicylic acid) after administration of single oral doses in six normal volunteers. All soluble forms showed a rapid absorption profile, peak plasma salicylic acid levels being attained after about 30 min on average and without statistically significant differences among the solutions tested. As compared to the soluble formulations, acetylsalicylic acid given as tablets resulted in slower absorption, with peak plasma salicylic acid levels being reached more than 1 h after dosing. Despite these differences in time course of plasma level profiles, the extent of absorption was similar for all formulations. Apart from the potential advantages in terms of improved gastric tolerability, the increased rate of absorption of aspirin solutions is therapeutically useful whenever a rapid onset of action is required. In this respect, the kinetic pattern of the innovative formulation compares favourably with that of other available soluble dosage forms.

  20. Pharmacokinetics of salicylic acid following administration of aspirin tablets and three different forms of soluble aspirin in normal subjects.

    PubMed

    Gatti, G; Barzaghi, N; Attardo Parrinello, G; Vitiello, B; Perucca, E

    1989-01-01

    The pharmacokinetic profile of an innovative formulation of soluble aspirin (l-ornithine acetylsalicylate, ldB 1003) was compared with that of conventional tablets and two other soluble dosage forms (d, l-lysine acetylsalicylate and a buffered effervescent formulation of acetylsalicylic acid) after administration of single oral doses in six normal volunteers. All soluble forms showed a rapid absorption profile, peak plasma salicylic acid levels being attained after about 30 min on average and without statistically significant differences among the solutions tested. As compared to the soluble formulations, acetylsalicylic acid given as tablets resulted in slower absorption, with peak plasma salicylic acid levels being reached more than 1 h after dosing. Despite these differences in time course of plasma level profiles, the extent of absorption was similar for all formulations. Apart from the potential advantages in terms of improved gastric tolerability, the increased rate of absorption of aspirin solutions is therapeutically useful whenever a rapid onset of action is required. In this respect, the kinetic pattern of the innovative formulation compares favourably with that of other available soluble dosage forms. PMID:2517497

  1. Platelet inhibition by aspirin 81 and 325 mg/day in men versus women without clinically apparent cardiovascular disease.

    PubMed

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

    2008-05-01

    Compared with men, women have greater platelet aggregation before and after low-dose aspirin. It is not known whether high-dose aspirin therapy brings residual platelet aggregation in women closer to that in men. Our objective was to compare inhibition of platelet aggregation in women and men after low- and high-dose aspirin. We enrolled healthy subjects (n=106) in a trial of 14 days of aspirin 81 mg/day followed by 14 days of 325 mg/day. Platelet function was measured at baseline and after the 2 aspirin doses. Women had greater baseline platelet activation measurements. After the 2 aspirin doses, men and women had near complete suppression of platelet aggregation to arachidonic acid in whole blood and in platelet-rich plasma (PRP), the direct cyclo-oxygenase-1 pathway affected by aspirin. For indirect pathways, women had significantly greater residual platelet activation to collagen and adenosine diphosphate (ADP) in whole blood after the 2 aspirin doses and in response to collagen and ADP in PRP after aspirin 325 mg/day only. After aspirin 325 mg/day, women continued to have greater residual platelet aggregation compared with men after aspirin 81 mg/day in response to collagen (p=0.016 in whole blood, p=0.037 in PRP), ADP (p<0.001 in whole blood, p=0.012 in PRP), and epinephrine (p=0.03 in PRP). Excretion of urinary thromboxane metabolite (urinary 11-dehydrothromboxane B2) decreased after aspirin to a similar extent in men and women. In conclusion, women continue to have greater residual platelet activity after high-dose aspirin compared with men treated with a lower dose of aspirin. PMID:18435972

  2. Long Term Use of Aspirin and the Risk of Gastrointestinal Bleeding

    PubMed Central

    Huang, Edward S.; Strate, Lisa L.; Ho, Wendy W.; Lee, Salina S.; Chan, Andrew T.

    2011-01-01

    Background In short-term trials, aspirin is associated with gastrointestinal bleeding. However, the effect of dose and duration of aspirin use on risk remains unclear. Methods We conducted a prospective study of 87,680 women enrolled in the Nurses' Health Study in 1990 who provided biennial data on aspirin use. We examined the relative risk (RR) of major gastrointestinal bleeding requiring hospitalization or blood transfusion. Results Over a 24-year follow-up, 1537 women reported a major gastrointestinal bleeding. Among women who used aspirin regularly (≥2 standard [325-mg] tablets/week), the multivariate RR of gastrointestinal bleeding was 1.43 (95% confidence interval [CI], 1.29-1.59) compared with non-regular users. Compared with women who denied any aspirin use, the multivariate RRs of gastrointestinal bleeding were 1.03 (95% CI, 0.85-1.24) for women who used 0.5 to 1.5 standard aspirin tablets/week, 1.30 (95% CI, 1.07-1.58) for 2 to 5 tablets/week, 1.77 (95% CI, 1.44-2.18) for 6-14 tablets/week, and 2.24 (95% CI, 1.66-3.03) for >14 tablets/week (Ptrend<.001). Similar dose-response relationships were observed among short-terms users (≤ 5 years; Ptrend<.001) and long-term users (>5 years; Ptrend<.001). In contrast, after adjustments were made for dose, increasing duration of use did not confer greater risk of bleeding (Ptrend=0.28). Conclusions Regular aspirin use is associated with gastrointestinal bleeding. Risk appears more strongly related to dose than duration of aspirin use. Efforts to minimize adverse effects of aspirin therapy should emphasize using the lowest effective dose among both short-term and long-term users. PMID:21531232

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

    PubMed

    Landolfi, R; Patrono, C

    1996-09-01

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

  4. Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers.

    PubMed

    Teng, Renli; Maya, Juan; Butler, Kathleen

    2013-01-01

    The results of two independent, randomized, two-period crossover, single-center studies, conducted to assess the pharmacokinetics of ticagrelor ± aspirin, inhibition of platelet aggregation (IPA) with ticagrelor/aspirin vs. clopidogrel/aspirin, and safety, tolerability, and bleeding times are reported here. In Study A (open-label), 16 volunteers received ticagrelor (50 mg bid Days 1-5; 200 mg bid Days 6-9; one 200 mg dose on Day 10) ± 300 mg qd aspirin (Days 1-10). In Study B (double-blind, double-dummy), 16 volunteers received aspirin (300 mg loading dose/75 mg qd Days 2-9) with either ticagrelor (200 mg bid Days 4-8, one 200 mg dose on Day 9) or clopidogrel (300 mg loading dose Day 4, 75 mg qd Days 5-9). At steady-state ticagrelor (50 mg bid, or 200 mg bid), concomitant aspirin (300 mg qd) had no effect on mean maximum plasma concentration (Cmax), median time to Cmax (tmax), or mean area under the plasma concentration-time curve for the dosing interval (AUC0-τ) for ticagrelor and its primary metabolite, AR-C124910XX. Following 200 mg bid ticagrelor, mean Cmax and AUC0-τ for both parent and metabolite were comparable with co-administration of aspirin at 75 mg and 300 mg qd. Aspirin (300 mg qd) had no effect on IPA (ADP-induced) by ticagrelor. However, aspirin and ticagrelor had an additive effect on IPA (collagen-induced). Ticagrelor/aspirin increased bleeding times vs. baseline. Ticagrelor/aspirin co-administration was well tolerated at all dose combinations evaluated. In summary, the findings of this study demonstrate that co-administration of aspirin (300 mg qd) with ticagrelor (50 mg bid, or 200 mg bid) had no effect on ticagrelor pharmacokinetics or IPA (ADP-induced) by ticagrelor. PMID:23249161

  5. Trace metal content in aspirin and women's cosmetics via proton induced x-ray emission (PIXE)

    SciTech Connect

    Hichwa, B.P.; Pun, D.D.; Wang, D.

    1981-04-01

    A multielemental analysis to determine the trace metal content of generic and name-brand aspirins and name-brand lipsticks was done via proton induced x-ray (PIXE) measurements. The Hope College PIXE system is described as well as the target preparation methods. The trace metal content of twelve brands of aspirin and aspirin substitutes and fourteen brands of lipstick are reported. Detection limits for most elements are in the range of 100 parts per billion (ppb) to 10 parts per million (ppm).

  6. Elastic properties of aspirin in its crystalline and glassy phases studied by micro-Brillouin scattering

    NASA Astrophysics Data System (ADS)

    Ko, Jae-Hyeon; Lee, Kwang-Sei; Ike, Yuji; Kojima, Seiji

    2008-11-01

    The acoustic waves propagating along the direction perpendicular to the (1 0 0) cleavage plane of aspirin crystal were investigated using micro-Brillouin spectroscopy from which C11, C55 and C66 were obtained. The temperature dependence of the longitudinal acoustic waves could be explained by normal anharmonic lattice models, while the transverse acoustic waves showed an abnormal increase in the hypersonic attenuation at low temperatures indicating their coupling to local remnant dynamics. The sound velocity as well as the attenuation of the longitudinal acoustic waves of glassy aspirin showed a substantial change at ˜235 K confirming a transition from glassy to supercooled liquid state in vitreous aspirin.

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

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

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

  8. Management of type-2 diabetes with anti-platelet therapies: special reference to aspirin.

    PubMed

    Rao, Gundu H R

    2011-01-01

    Adult onset diabetes currently affects 380 million individuals worldwide and is expected to affect 380 million by 2025. Major defects contributing to this complex disease are insulin resistance and beta cell dysfunction. More than 80% of patients professing to type-2 diabetes are insulin resistant. Recent studies have shown that the Indian subcontinent ranks very high in the occurrence of Diabetes and Coronary artery disease (1, 2, 3). Patients with Type 2 diabetes carry an equivalent cardiovascular risk to that of a non-diabetic individual who has already experienced a coronary event. The risk of coronary artery disease in any given population seems to be 2-3 times higher in diabetics than non-diabetics. Inflammation, platelet activation, endothelial dysfunction and coagulation are the four processes, whose interplay determines the development of cardiovascular disease. In this article, we provide a brief overview on platelet physiology, vascular dysfunction, platelet hyper-function, and the role of platelet related clinical complications in diabetes mellitus and what is know about the management of this complex disease with anti-platelet drugs such as aspirin and Clopidogrel.

  9. Human GAPDH Is a Target of Aspirin's Primary Metabolite Salicylic Acid and Its Derivatives.

    PubMed

    Choi, Hyong Woo; Tian, Miaoying; Manohar, Murli; Harraz, Maged M; Park, Sang-Wook; Schroeder, Frank C; Snyder, Solomon H; Klessig, Daniel F

    2015-01-01

    The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA's multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson's drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA) and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice), glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death.

  10. Aspirin inhibits human coronary artery endothelial cell proliferation by upregulation of p53.

    PubMed

    Ranganathan, Subramanian; Joseph, Jacob; Mehta, Jawahar L

    2003-01-31

    Aspirin (acetylsalicylic acid, ASA) is effective in the primary and secondary prevention of vascular events. This effect is mediated in large part by platelet inhibition; however, non-platelet-mediated effects may also be relevant in the overall efficacy of ASA. We determined the effect of ASA on the synthesis of DNA and total proteins in cultured human coronary endothelial cells (HCAECs). Fourth generation HCAECs were cultured and treated with ASA and rate of synthesis of DNA and total proteins was determined by incorporation of [3H]thymidine and [3H]proline, respectively. ASA inhibited DNA synthesis by 50% at a concentration of 1mM and protein synthesis by 50% at a concentration of 2mM. The inhibitory effect of ASA was observed as early as 2h after treatment of HCAECs. The inhibition of DNA and protein synthesis could be reversed within 24h after removal of the drug from the culture medium. Indomethacin also inhibited DNA and protein synthesis. Western blot analysis revealed that the expression of p53 protein was increased after treatment of the cells with ASA. These observations indicate that ASA decreases endothelial cell proliferation through cell cycle arrest mediated by enhanced p53 expression. Arrest of endothelial proliferation and activation may be an important mechanism of the beneficial effect of ASA in acute coronary syndromes.

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

    SciTech Connect

    Lussier, A.; Davis, A.; Lussier, Y.; Lebel, E.

    1989-03-01

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

  12. Spectroscopic structural studies of salicylic acid, salicylamide and aspirin

    NASA Astrophysics Data System (ADS)

    El-Shahawy, Anwar S.

    The electronic absorption spectra of the salicylic acid and the salicylamide molecules have been studied using SCF—CL calculations. The singlet and the triplet electronic transition energies have been calculated. The state functions of eight excited states for these molecules have been calculated in addition to the oscillator strengths, charge densities, ionization potentials and electron affinities. Our calculations lead to the presence of salicylic acid and salicylamide in the β-forms in which the carboxylic hydroxyl group or the amino group is directed toward the enolic hydroxyl group. The salicylic acid and the salicylamide molecules have the Cs point group symmetry, but the aspirin molecule has the C1 point group symmetry, in which the acetyl group does not lie in the plane of the salicylic acid molecule.

  13. Thermodynamics of surface defects at the aspirin/water interface

    NASA Astrophysics Data System (ADS)

    Schneider, Julian; Zheng, Chen; Reuter, Karsten

    2014-09-01

    We present a simulation scheme to calculate defect formation free energies at a molecular crystal/water interface based on force-field molecular dynamics simulations. To this end, we adopt and modify existing approaches to calculate binding free energies of biological ligand/receptor complexes to be applicable to common surface defects, such as step edges and kink sites. We obtain statistically accurate and reliable free energy values for the aspirin/water interface, which can be applied to estimate the distribution of defects using well-established thermodynamic relations. As a show case we calculate the free energy upon dissolving molecules from kink sites at the interface. This free energy can be related to the solubility concentration and we obtain solubility values in excellent agreement with experimental results.

  14. Effect of sodium bicarbonate on aspirin-induced damage and potential difference changes in human gastric mucosa.

    PubMed

    Bowen, B K; Krause, W J; Ivey, K J

    1977-10-22

    Two aspirin tablets in 100 ml fluid will produce microscopical damage to the human stomach. A study was performed to determine whether a small amount of sodium bicarbonate (equivalent to one-third of a teaspoonful of baking soda) could protect against this damage. Sequential gastric biopsy specimens were taken from 15 healthy subjects before, during, and after intragastric instillation of one of the following isotonic solutions: saline; sodium bicarbonate; 600 mg aspirin suspended in sodium bicarbonate; and aspirin suspended in saline. On a separate day the same solutions were instilled, but gastric transmucosal potential differences were monitored. Light microscopy and scanning electron microscopy of the biopsy specimens showed occasional mucous degranulation of mucosal surface cells, but no cell damage during instillation of sodium bicarbonate. Light microscopy studies 10 minutes after aspirin in saline showed damage in 20% of surface cells, with focal areas of cellular disruption and microscopic erosions, but only 3.4% of cells were damaged after aspirin in bicarbonate and there were no erosions. Electron microscopy showed a damaged honeycombed appearance of surface epithelium after aspirin in saline and a normal cobblestone appearance after aspirin in bicarbonate. Aspirin dissolved in bicarbonate failed to induce the usual fall in potential difference.These findings indicate that sodium bicarbonate in amounts equivalent to one-third of a teaspoonful of baking soda protects the gastric mucosa against aspirin-induced damage and prevents the usual fall in potential difference after aspirin. PMID:922417

  15. Effect of sodium bicarbonate on aspirin-induced damage and potential difference changes in human gastric mucosa

    PubMed Central

    Bowen, Bruce K; Krause, William J; Ivey, Kevin J

    1977-01-01

    Two aspirin tablets in 100 ml fluid will produce microscopical damage to the human stomach. A study was performed to determine whether a small amount of sodium bicarbonate (equivalent to one-third of a teaspoonful of baking soda) could protect against this damage. Sequential gastric biopsy specimens were taken from 15 healthy subjects before, during, and after intragastric instillation of one of the following isotonic solutions: saline; sodium bicarbonate; 600 mg aspirin suspended in sodium bicarbonate; and aspirin suspended in saline. On a separate day the same solutions were instilled, but gastric transmucosal potential differences were monitored. Light microscopy and scanning electron microscopy of the biopsy specimens showed occasional mucous degranulation of mucosal surface cells, but no cell damage during instillation of sodium bicarbonate. Light microscopy studies 10 minutes after aspirin in saline showed damage in 20% of surface cells, with focal areas of cellular disruption and microscopic erosions, but only 3·4% of cells were damaged after aspirin in bicarbonate and there were no erosions. Electron microscopy showed a damaged honeycombed appearance of surface epithelium after aspirin in saline and a normal cobblestone appearance after aspirin in bicarbonate. Aspirin dissolved in bicarbonate failed to induce the usual fall in potential difference. These findings indicate that sodium bicarbonate in amounts equivalent to one-third of a teaspoonful of baking soda protects the gastric mucosa against aspirin-induced damage and prevents the usual fall in potential difference after aspirin. ImagesFIG 2FIG 3FIG 4 PMID:922417

  16. Study Shows Aspirin Reduces Colorectal Cancer in Those at High Risk

    Cancer.gov

    Findings from the first large clinical trial of its kind indicate that taking high doses of aspirin daily for at least 2 years substantially reduces the risk of colorectal cancer among people at increased risk of the disease.

  17. Evaluation of aspirin metabolites as inhibitors of hypoxia-inducible factor hydroxylases.

    PubMed

    Lienard, Benoit M; Conejo-García, Ana; Stolze, Ineke; Loenarz, Christoph; Oldham, Neil J; Ratcliffe, Peter J; Schofield, Christopher J

    2008-12-21

    Known and potential aspirin metabolites were evaluated as inhibitors of oxygen-sensing hypoxia-inducible transcription factor (HIF) hydroxylases; some of the metabolites were found to stabilise HIF-alpha in cells. PMID:19048166

  18. Aspirin promotes TFF2 gene activation in human gastric cancer cell lines.

    PubMed

    Azarschab, P; Al-Azzeh, E; Kornberger, W; Gött, P

    2001-01-19

    Trefoil factor family (TFF) peptides promote cell migration, heal the mucosa and may suppress tumor growth. In reporter gene assays we show that aspirin (1-12 mM) evokes a six-fold up-regulation of TFF2, but not TFF1 and TFF3 transcription in human gastrointestinal cell lines. 6 h after application up-regulation of endogenous TFF2 mRNA was observed. TFF2 transcription was enhanced by indomethacin and arachidonic acid but repressed by staurosporine, suggesting mediation via protein kinase C. We mapped an aspirin responding element -546 to -758 bp upstream of TFF2. Up-regulation of TFF2 by aspirin may partially explain the chemopreventive potential of low dose aspirin in gastrointestinal carcinogenesis.

  19. Role of Dispersion Interactions in the Polymorphism and Entropic Stabilization of the Aspirin Crystal

    NASA Astrophysics Data System (ADS)

    Reilly, Anthony M.; Tkatchenko, Alexandre

    2014-08-01

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

  20. Aspirin augments the expression of Adenomatous Polyposis Coli protein by suppression of IKKβ

    SciTech Connect

    Ashida, Noboru; Kishihata, Masako; Tien, Dat Nguyen; Kamei, Kaeko; Kimura, Takeshi; Yokode, Masayuki

    2014-04-04

    Highlights: • Clinical studies revealed aspirin inhibits cancer, but the mechanism is not known. • Adenomatous Polyposis Coli (APC) is a well-known tumor-suppressing gene. • We found aspirin up-regulates the protein of APC. • Aspirin suppressed the expression of IKKβ, an essential kinase in NFκB activation. • The deletion of IKKβ significantly increases the expression of APC protein. - Abstract: Aspirin has been widely used as analgesic, antipyretic and anti-inflammatory medicine for long. In addition to these traditional effects, clinical studies suggest that aspirin can protect against cancer, but its mechanism has not been explored. To unveil it, we identified the proteins up- or down-regulated after incubation with aspirin by using proteomics analysis with Nano-flow LC/MALDI-TOF system. Interestingly, the analysis identified the protein of Adenomatous Polyposis Coli (APC) as one of the most up-regulated protein. APC regulates cell proliferation or angiogenesis, and is widely known as a tumor-suppressing gene which can cause colorectal cancer when it is mutated. Western blots confirmed this result, and real-time PCR indicated it is transcriptionally regulated. We further tried to elucidate the molecular mechanism with focusing on IKKβ. IKKβ is the essential kinase in activation of nuclear factor-kappa B (NF-κB), major transcriptional factors that regulate genes responsible for inflammation or immune response. Previous reports indicated that aspirin specifically inhibits IKKβ activity, and constitutively active form of IKKβ accelerates APC loss. We found that aspirin suppressed the expression of IKKβ, and the deletion of IKKβ by siRNA increases the expression of APC in HEK294 cells. Finally, we observed similar effects of aspirin in human umbilical vein endothelial cells. Taken together, these results reveal that aspirin up-regulates the expression of APC via the suppression of IKKβ. This can be a mechanism how aspirin prevents cancer at

  1. Risk of asthma exacerbation associated with nonsteroidal anti-inflammatory drugs in childhood asthma

    PubMed Central

    Lo, Pei-Chia; Tsai, Yueh-Ting; Lin, Shun-Ku; Lai, Jung-Nien

    2016-01-01

    Abstract Patients allergic to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) who develop respiratory reactions such as bronchospasm or asthma exacerbation have aspirin-induced asthma or NSAIDs-exacerbated respiratory disease. However, large-scale studies have not been conducted to investigate the risk of aspirin/NSAIDs exposure in children with asthma. Therefore, this study evaluated the relationship between aspirin/NSAIDs and the risk of asthma exacerbation in children with asthma. This retrospective cohort study was conducted using the data of 1 million random beneficiaries of the Taiwan National Health Insurance program between 1997 and 2012. Children aged ≦18 years diagnosed with asthma by physicians were enrolled. The study population was divided into the index group (concurrently using antiasthmatic agents and NSAIDs patients) and reference group (using antiasthmatic drugs alone), and the relative risks (RRs) of hospitalizations resulting from asthma exacerbation in both groups were estimated. The rate of asthma exacerbation was higher in the index group than the reference group, resulting in asthma-related hospitalizations (RR: 1.49, 95% confidence interval [CI]: 1.37–1.61; adjusted RR: 1.41, 95% CI: 1.30–1.53). Short-term aspirin, ibuprofen, and diclofenac use probably correlated with asthma exacerbation in children with asthma. No association between long-term aspirin, ibuprofen, and diclofenac consumption and the risk of asthma exacerbation was identified in this study. PMID:27741128

  2. Bleeding Risk and Antithrombotic Strategy in Patients With Sinus Rhythm and Heart Failure With Reduced Ejection Fraction Treated With Warfarin or Aspirin.

    PubMed

    Ye, Siqin; Cheng, Bin; Lip, Gregory Y H; Buchsbaum, Richard; Sacco, Ralph L; Levin, Bruce; Di Tullio, Marco R; Qian, Min; Mann, Douglas L; Pullicino, Patrick M; Freudenberger, Ronald S; Teerlink, John R; Mohr, J P; Graham, Susan; Labovitz, Arthur J; Estol, Conrado J; Lok, Dirk J; Ponikowski, Piotr; Anker, Stefan D; Thompson, John L P; Homma, Shunichi

    2015-09-15

    We sought to assess the performance of existing bleeding risk scores, such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score or the Outpatient Bleeding Risk Index (OBRI), in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell C-statistic and net reclassification improvement index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly greater C-statistic (0.72 vs 0.61; p = 0.03) compared to HAS-BLED, although the net reclassification improvement for comparing OBRI to HAS-BLED was not significant (0.32, 95% confidence interval [CI] -0.18 to 0.37). Performance of the OBRI and HAS-BLED risk scores was similar for the aspirin arm. For participants with OBRI scores of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (hazard ratio [HR] 0.51, 95% CI 0.26 to 0.98, p = 0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66 to 2.30, p = 0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27 to 1.15, p = 0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99 to 8.22, p <0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in patients with HFrEF in SR and could be tested for potentially identifying patients with a favorable risk/benefit profile for antithrombotic therapy with warfarin. PMID:26189039

  3. Hydrogen sulfide releasing aspirin, ACS14, attenuates high glucose-induced increased methylglyoxal and oxidative stress in cultured vascular smooth muscle cells.

    PubMed

    Huang, Qian; Sparatore, Anna; Del Soldato, Piero; Wu, Lingyun; Desai, Kaushik

    2014-01-01

    Hydrogen sulfide is a gasotransmitter with vasodilatory and anti-inflammatory properties. Aspirin is an irreversible cyclooxygenase inhibitor anti-inflammatory drug. ACS14 is a novel synthetic hydrogen sulfide releasing aspirin which inhibits cyclooxygenase and has antioxidant effects. Methylglyoxal is a chemically active metabolite of glucose and fructose, and a major precursor of advanced glycation end products formation. Methylglyoxal is harmful when produced in excess. Plasma methylglyoxal levels are significantly elevated in diabetic patients. Our aim was to investigate the effects of ACS14 on methylglyoxal levels in cultured rat aortic vascular smooth muscle cells. We used cultured rat aortic vascular smooth muscle cells for the study. Methylglyoxal was measured by HPLC after derivatization, and nitrite+nitrate with an assay kit. Western blotting was used to determine NADPH oxidase 4 (NOX4) and inducible nitric oxide synthase (iNOS) protein expression. Dicholorofluorescein assay was used to measure oxidative stress. ACS14 significantly attenuated elevation of intracellular methylglyoxal levels caused by incubating cultured vascular smooth muscle cells with methylglyoxal (30 µM) and high glucose (25 mM). ACS14, but not aspirin, caused a significant attenuation of increase in nitrite+nitrate levels caused by methylglyoxal or high glucose. ACS14, aspirin, and sodium hydrogen sulfide (NaHS, a hydrogen sulfide donor), all attenuated the increase in oxidative stress caused by methylglyoxal and high glucose in cultured cells. ACS14 prevented the increase in NOX4 expression caused by incubating the cultured VSMCs with MG (30 µM). ACS14, aspirin and NaHS attenuated the increase in iNOS expression caused by high glucose (25 mM). In conclusion, ACS14 has the novel ability to attenuate an increase in methylglyoxal levels which in turn can reduce oxidative stress, decrease the formation of advanced glycation end products and prevent many of the known deleterious effects

  4. Studies on the hydrolysis of biocompatible acrylic polymers having aspirin-moieties.

    PubMed

    Gu, Z W; Li, F M; Feng, X D; Voong, S T

    1983-01-01

    Both the homogeneous and heterogeneous hydrolysis of five new acrylic polymers having aspirin-moieties, i.e. polymers of beta-(acetylsalicylyloxy)ethyl methacrylate, beta-(acetylsalicylyloxy) propyl methacrylate,beta-(acetylsalicylyloxy) ethyl acrylate, beta-hydroxy-gamma-(acetylsalicylyloxy) propyl methacrylate, beta-hydroxy-gamma-(acetylsalicylyloxy) propyl acrylate were investigated in acidic or alkaline medium at 30 degrees C or 60 degrees C, respectively. It was observed that the chief hydrolyzed product is always aspirin with minor amount of salicylic acid.

  5. The inhibitory effect of simvastatin and aspirin on histamine responsiveness in human vascular endothelial cells.

    PubMed

    Absi, Mais; Bruce, Jason I; Ward, Donald T

    2014-04-01

    Statins and aspirin deliver well-established cardiovascular benefits resulting in their increased use as combined polypills to decrease risk of stroke and heart disease. However, the direct endothelial effect of combined statin/aspirin cotreatment remains unclear. Histamine is an inflammatory mediator that increases vascular permeability, and so we examined the effect of treating human umbilical vein endothelial cells (HUVECs) for 24 h with 1 μM simvastatin and 100 μM aspirin on histamine responsiveness. Subsequent histamine (1 μM) challenge increased intracellular calcium (Ca(2+)i) concentration, an effect that was significantly inhibited by combined simvastatin/aspirin pretreatment but not when then the compounds were given separately, even at 10-fold higher concentrations. In contrast, the Ca(2+)i mobilization response to ATP challenge (10 μM) was not inhibited by combined simvastatin/aspirin pretreatment. The H1 receptor antagonist pyrilamine significantly inhibited both histamine-induced Ca(2+)i mobilization and extracellular signal-regulated kinase (ERK) activation, whereas ranitidine (H2 receptor antagonist) was without effect. However, combined simvastatin/aspirin pretreatment failed to decrease H1 receptor protein expression ruling out receptor downregulation as the mechanism of action. Histamine-induced ERK activation was also inhibited by atorvastatin pretreatment, while simvastatin further inhibited histamine-induced vascular endothelial cadherin phosphorylation as well as altered HUVEC morphology and inhibited actin polymerization. Therefore, in addition to the known therapeutic benefits of statins and aspirin, here we provide initial cellular evidence that combined statin/aspirin treatment inhibits histamine responsiveness in HUVECs.

  6. The association between regular use of aspirin and the prevalence of prostate cancer

    PubMed Central

    Huang, Wan-Ting; Erickson, Steven R.; Hansen, Richard A.; Wu, Chung-Hsuen

    2016-01-01

    Abstract Prostate cancer is prevalent with significant morbidity in the United States. Aspirin previously has been found to be associated with reduced carcinogenesis of prostate cells. However, it remains unclear whether regularly taking aspirin could lower the risk of prostate cancer. Therefore, our aim was to examine the association between self-reported regular use of aspirin and the prevalence of prostate cancer in a national sample of the US adult population. The National Health Interview Survey is an annual survey conducted by the National Center for Health Statistics to investigate health and healthcare use of the US population. The current study is a population-based cross-sectional study using the 2010 National Health Interview Survey data. Adult male respondents who self-reported regularly taking aspirin at least 3 times per week were grouped as regular users. The prostate cancer prevalence was measured by respondents’ self-report of prostate cancer. Multivariable logistic regression models were used to evaluate the association between these 2 factors by adjusting for covariates selected based on Andersen Behavioral Model of Health Services Use. An estimated 23 million (23.7%) males in the United States reported that they took aspirin regularly. Of them, 5.0% had prostate cancer. Regular aspirin use was significantly associated with a lower self-reported prevalence of prostate cancer after adjusting for predisposing, enabling, and need factors (odds ratio 0.60, 95% confidence interval 0.38–0.94). Regular aspirin use was found to be significantly associated with a lower self-reported prevalence of prostate cancer in the United States in 2010. Further clinical trials and longitudinal studies are needed to confirm the causality between regular aspirin use and prostate cancer. PMID:27336878

  7. Association between aspirin and upper gastrointestinal complications: Systematic review of epidemiologic studies

    PubMed Central

    Rodríguez, Luis A García; Hernández-Díaz, Sonia; de Abajo, Francisco J

    2001-01-01

    Aims Because of the widespread use of aspirin for prevention of cardiovascular diseases, side-effects associated with thromboprophylactic doses are of interest. This study summarizes the relative risk (RR) for serious upper gastrointestinal complications (UGIC) associated with aspirin exposure in general and with specific aspirin doses and formulations in particular. Methods After a systematic review, 17 original epidemiologic studies published between 1990 and 2001 were selected according to predefined criteria. Heterogeneity of effects was explored. Pooled estimates were calculated according to different study characteristics and patterns of aspirin use. Results The overall relative risk of UGIC associated with aspirin use was 2.2 (95% confidence interval (CI): 2.1, 2.4) for cohort studies and nested case-control studies and 3.1 (95% CI: 2.8, 3.3) for non-nested case-control studies. Original studies found a dose–response relationship between UGIC and aspirin, although the risk was still elevated for doses lower or up to 300 mg day−1. The summary RR was 2.6 (95% CI: 2.3, 2.9) for plain, 5.3 (95% CI: 3.0, 9.2) for buffered, and 2.4 (95% CI: 1.9, 2.9) for enteric-coated aspirin formulations. Conclusions Aspirin was associated with UGIC even when used at low doses or in buffered or enteric-coated formulations. The latter findings may be partially explained by channeling of susceptible patients to these formulations. PMID:11736865

  8. Oxidative stress-related mechanisms affecting response to aspirin in diabetes mellitus.

    PubMed

    Santilli, Francesca; Lapenna, Domenico; La Barba, Sara; Davì, Giovanni

    2015-03-01

    Type 2 diabetes mellitus (T2DM) is a major cardiovascular risk factor. Persistent platelet activation plays a key role in atherothrombosis in T2DM. However, current antiplatelet treatments appear less effective in T2DM patients vs nondiabetics at similar risk. A large body of evidence supports the contention that oxidative stress, which characterizes DM, may be responsible, at least in part, for less-than-expected response to aspirin, with multiple mechanisms acting at several levels. This review discusses the pathophysiological mechanisms related to oxidative stress and contributing to suboptimal aspirin action or responsiveness. These include: (1) mechanisms counteracting the antiplatelet effect of aspirin, such as reduced platelet sensitivity to the antiaggregating effects of NO, due to high-glucose-mediated oxidative stress; (2) mechanisms interfering with COX acetylation especially at the platelet level, e.g., lipid hydroperoxide-dependent impaired acetylating effects of aspirin; (3) mechanisms favoring platelet priming (lipid hydroperoxides) or activation (F2-isoprostanes, acting as partial agonists of thromboxane receptor), or aldose-reductase pathway-mediated oxidative stress, leading to enhanced platelet thromboxane A2 generation or thromboxane receptor activation; (4) mechanisms favoring platelet recruitment, such as aspirin-induced platelet isoprostane formation; (5) modulation of megakaryocyte generation and thrombopoiesis by oxidative HO-1 inhibition; and (6) aspirin-iron interactions, eventually resulting in impaired pharmacological activity of aspirin, lipoperoxide burden, and enhanced generation of hydroxyl radicals capable of promoting protein kinase C activation and platelet aggregation. Acknowledgment of oxidative stress as a major contributor, not only of vascular complications, but also of suboptimal response to antiplatelet agents in T2DM, may open the way to designing and testing novel antithrombotic strategies, specifically targeting

  9. Gastroprotective Effect of Combination of Hot Water Extracts of Licorice (Glycyrrhiza glabra), Pulasari Stem Bark (Alyxia reinwardtii), and Sembung Leaf (Blumea balsamifera) Against Aspirin-Induced Gastric Ulcer Model Rats.

    PubMed

    Nugroho, Agung Endro; Wijayanti, Agustin; Mutmainah, Mutmainah; Susilowati, Rina; Rahmawati, Nuning

    2016-10-01

    Licorice (Glycyrrhiza glabra), Pulasari stem bark (Alyxia reinwardtii) and Sembung leaf (Blumea balsamifera) are traditionally used to treat gastrointestinal disorders. The aim of the study was to investigate gastroprotective effect of hot water extracts combination of those herbal against aspirin-induced gastric ulcer model in rats. The combination consisted of fixed doses of Licorice 273 mg/kg BW and Sembung leaf 457.5 mg/kg BW, and also consisted of Pulasari stem in various doses i.e. 100 mg/kg BW (first group), 200 mg/kg BW (second and sixth group) and 300 mg/kg BW (third group). The fourth grup rats received sucralfate 360 mg/kg BW. Ten minute after seven consecutive days of drug administration, the rats were induced with aspirin 450 mg/kg BW except sixth group rats. The fifth group rats only received aspirin without any protective agents. The number and area of gastric ulcers were evaluated macroscopically. Whereas, histopatological observation was used for evaluation of mucosal damage score, and the number of eosinophils and mast cells. In the study, herbal extracts combination markedly exhibited protective effects indicated by less number and smaller area of gastric ulcers in comparison to those of aspirin group (P < 0.05). The score of mucosal damages were also decreased in herbal extracts combination groups. The number of eosinophils and mast cells of herbal combination groups were observed to be smaller than those of aspirin group (P < 0.05). In conclusion, herbal combination of Licorice (Glycyrrhiza glabra), Pulasari stem bark (Alyxia reinwardtii) and Sembung leaf (Blumea balsamifera) is potential to develop as a gastroprotective agent. PMID:26976086

  10. Gastroprotective Effect of Combination of Hot Water Extracts of Licorice (Glycyrrhiza glabra), Pulasari Stem Bark (Alyxia reinwardtii), and Sembung Leaf (Blumea balsamifera) Against Aspirin-Induced Gastric Ulcer Model Rats.

    PubMed

    Nugroho, Agung Endro; Wijayanti, Agustin; Mutmainah, Mutmainah; Susilowati, Rina; Rahmawati, Nuning

    2016-10-01

    Licorice (Glycyrrhiza glabra), Pulasari stem bark (Alyxia reinwardtii) and Sembung leaf (Blumea balsamifera) are traditionally used to treat gastrointestinal disorders. The aim of the study was to investigate gastroprotective effect of hot water extracts combination of those herbal against aspirin-induced gastric ulcer model in rats. The combination consisted of fixed doses of Licorice 273 mg/kg BW and Sembung leaf 457.5 mg/kg BW, and also consisted of Pulasari stem in various doses i.e. 100 mg/kg BW (first group), 200 mg/kg BW (second and sixth group) and 300 mg/kg BW (third group). The fourth grup rats received sucralfate 360 mg/kg BW. Ten minute after seven consecutive days of drug administration, the rats were induced with aspirin 450 mg/kg BW except sixth group rats. The fifth group rats only received aspirin without any protective agents. The number and area of gastric ulcers were evaluated macroscopically. Whereas, histopatological observation was used for evaluation of mucosal damage score, and the number of eosinophils and mast cells. In the study, herbal extracts combination markedly exhibited protective effects indicated by less number and smaller area of gastric ulcers in comparison to those of aspirin group (P < 0.05). The score of mucosal damages were also decreased in herbal extracts combination groups. The number of eosinophils and mast cells of herbal combination groups were observed to be smaller than those of aspirin group (P < 0.05). In conclusion, herbal combination of Licorice (Glycyrrhiza glabra), Pulasari stem bark (Alyxia reinwardtii) and Sembung leaf (Blumea balsamifera) is potential to develop as a gastroprotective agent.

  11. The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423

    PubMed Central

    Kulik, Alexander; Le May, Michel; Wells, George A; Mesana, Thierry G; Ruel, Marc

    2005-01-01

    Background Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery. The process of saphenous vein intimal hyperplasia begins just days after surgical revascularization, setting the stage for graft atherosclerotic disease and its sequalae. Clopidogrel improves outcomes in patients with atherosclerotic disease, and is effective at reducing intimal hyperplasia in animal models of thrombosis. Therefore, the goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following coronary artery bypass surgery. Methods Patients undergoing multi-vessel coronary artery bypass grafting and in whom at least two saphenous vein grafts will be used are eligible for the study. Patients will be randomized to receive daily clopidogrel 75 mg or placebo, in addition to daily aspirin 162 mg, for a one year duration starting on the day of surgery (as soon as postoperative bleeding has been excluded). At the end of one year, all patients will undergo coronary angiography and intravascular ultrasound assessment of one saphenous vein graft as selected by randomization. The trial will be powered to test the hypothesis that clopidogrel and aspirin will reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery. Discussion This trial is the first prospective human study that will address the question of whether clopidogrel therapy improves outcomes and reduces saphenous vein graft intimal hyperplasia following cardiac surgery. Should the combination of clopidogrel and aspirin reduce the process of vein graft intimal hyperplasia, the results of this study will help redefine modern antiplatelet management of coronary artery bypass patients. PMID:16219100

  12. Effect of Aspirin Supplementation on Hemostatic Responses in Firefighters Aged 40 to 60 Years.

    PubMed

    Smith, Denise L; Horn, Gavin P; Woods, Jeffrey; Ploutz-Snyder, Robert; Fernhall, Bo

    2016-07-15

    Sudden cardiovascular events account for approximately 45% to 50% of all duty-related deaths among firefighters and a disproportionate number of these fatalities occur after strenuous fire suppression activities. The purpose of this study was to evaluate the effect of acute and chronic aspirin supplementation on hemostatic function before and after live firefighting activities in older firefighters. A double-blind, crossover design included 4 treatments: a 2-week aspirin/placebo treatment ("chronic") and a single prefirefighting aspirin/placebo treatment ("acute"). Hemostatic function was assessed in 24 male firefighters (mean age = 48.2 ± 5.9 years) immediately before and after 18 minutes of live-fire firefighting activity. An acute bout of firefighting activity significantly decreased platelet aggregation time and decreased activated partial thromboplastin time. Compared with placebo, acute aspirin supplementation resulted in a significant increase in epinephrine closure time, which was further augmented by chronic supplementation. Aspirin supplementation had no effect on coagulatory or fibrinolytic factors. Our findings suggest that an acute bout of firefighting leads to increased coagulatory potential in older firefighters. In conclusion, aspirin supplementation had an antiplatelet effect that decreased platelet aggregability at rest and after an acute bout of firefighting compared with placebo.

  13. [Effect of aspirin on function of human umbilical cord blood-derived late endothelial progenitor cells].

    PubMed

    Liu, Zhen-Zhen; Li, Guo-Qiang; Liu, Meng; Sun, Sheng-Xuan; An, Guan-Yu; Dong, Ning-Zheng

    2013-08-01

    This study was aimed to investigate whether aspirin has effect on function of late endothelial progenitor cells (EPC). Cord blood CD34(+) cells were purified using the ficoll density gradient centrifugation and human CD34 positive selection kit, then the cells were inoculated on fibronectin-coated culture plate. After culture for 2 weeks, adherent cells were identified as EPC by flow cytometry, immunofluorescence, RT-PCR, uptake of Dil-Ac-LDL and matrigel tube formation assay. EPC were treated with different concentrations of aspirin (0.1, 1, 10, 100, 1 000, 10 000 µmol/L) for 24 h, then the proliferation, adhesion and migration ability of these cells were analyzed by CCK-8 assay and transwell methods. The results indicated that the low concentrations of aspirin (0.1 and 1 000 µmol/L) promoted late EPC adhesive and migratory capacity, but no obvious effect on proliferation of late EPC were observed. On the other hand, the high concentrations of aspirin (10 000 µmol/L) inhibited proliferation and migratory capacity of EPC, but had no obvious effect on adhesive ability of EPC. It is concluded that low concentration of aspirin promotes migration and adhesion of late EPC, while the high concentration of aspirin decreases EPC proliferation and migratory capacity of EPC.

  14. Aspirin, but Not Tirofiban Displays Protective Effects in Endotoxin Induced Lung Injury

    PubMed Central

    Gombert, Alexander; Jacobs, Michael J.; Drechsler, Maik; Döring, Yvonne; Soehnlein, Oliver; Grommes, Jochen

    2016-01-01

    Background Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Recruitment of neutrophils into the lungs, regarded as a key mechanism in progression of ALI, depends on signaling between neutrophils and platelets. Consequently we explored the effect of platelet-targeted aspirin and tirofiban treatment in endotoxin induced acute lung injury Methods C57Bl/6 mice were exposed to aerosolized LPS (500μg/ml) for 30min and treated with Aspirin (100μg/g bodyweight via intraperitoneal injection, 30 min before or 1 hour after LPS inhalation) or Tirofiban (0.5μg/ g bodyweight via tail vein injection 30 min before or 1 hour after LPS inhalation). The count of alveolar, interstitial, and intravascular neutrophils was assessed 4h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and protein content in the BAL fluid. Results Aspirin both before and after LPS inhalation reduced neutrophil influx into the lung and lung permeability indicating the protective role of Aspirin in ALI. Tirofiban, however, did not alter neutrophil recruitment after LPS inhalation. Release of platelet-derived chemokines CCL5 and PF4 and neutrophil extracellular traps was reduced by Aspirin but not by Tirofiban. Conclusion Aspirin, but not Tirofiban reduces neutrophil recruitment and displays protective effects during endotoxin induced lung injury. PMID:27583400

  15. Attenuation of aspirin-induced bronchoconstriction by sodium cromoglycate and nedocromil sodium.

    PubMed

    Robuschi, M; Gambaro, G; Sestini, P; Pieroni, M G; Refini, R M; Vaghi, A; Bianco, S

    1997-04-01

    The protective activity of nedocromil sodium and of sodium cromoglycate against aspirin-induced asthma has never been investigated in controlled studies. Because it has been reported that aspirin-induced platelet-mediated cytotoxic activity in vitro is inhibited after treatment in vivo with nedocromil but not with cromoglycate, we investigated whether these compounds also exhibit a different protective activity against aspirin-induced bronchoconstriction. Ten patients with aspirin-induced asthma underwent three bronchial challenges with a single dose of lysine acetylsalicylate (LASA) that caused a decrease in FEV1 of 25% or more in a preliminary dose-response test 30 min after inhalation of 4 mg nedocromil sodium, 10 mg sodium cromoglycate, or placebo. FEV1 and SRaw were recorded at intervals for 195 min. After placebo, LASA caused a maximal decrease in FEV1 of 42 +/- 4% of baseline. After cromoglycate and nedocromil the maximal decrease in FEV1 was reduced to 20 +/- 3% and 18 +/- 4%, respectively (p < 0.01 versus placebo for both treatments), without significant differences between the two treatments. Similar results were observed with SRaw. We conclude that, at the recommended therapeutic doses, sodium cromoglycate and nedocromil sodium are equally effective in attenuating aspirin-induced bronchoconstriction and that it is unlikely that platelet activation participates in the pathogenesis of aspirin-induced asthma.

  16. Effects of aspirin on expression of iron transport and storage proteins in BV-2 microglial cells.

    PubMed

    Xu, Yan Xin; Du, Fang; Jiang, Li Rong; Gong, Jing; Zhou, Yu-Fu; Luo, Qian Qian; Qian, Zhong Ming; Ke, Ya

    2015-12-01

    In the light of recent studies, we hypothesized that aspirin might have the functions to regulate the expression of iron transport proteins and then affect cellular iron levels. To test this hypothesis, we investigated the effects of aspirin on expression of iron uptake protein transferrin receptor 1 (TfR1), iron release protein ferroportin 1 (Fpn1) and iron storage protein ferritin using Western blot analysis and on tumor necrosis factor (TNF)-αlpha, interleukin (IL)-6, interleukin (IL)-10 and hepcidin using quantitative real-time PCR in BV-2 microglial cells treated with lipopolysaccharides (LPS). We found that aspirin significantly down-regulated TfR1, while also up-regulated Fpn1 and ferritin expressions in BV-2 microglial cells in vitro. We also showed that TfR1 and Fpn1 expressions were significantly higher, while ferritin contents, IL-6, TNF-alpha and hepcidin mRNA levels were lower in cells treated with aspirin plus LPS than those in cells treated with LPS only. We concluded that aspirin has a negative effect on cell iron contents under 'normal' conditions and could partly reverse LPS-induced-disruption in cell iron balance under in vitro inflammatory conditions. Our findings also suggested that hepcidin might play a dominant role in the control of TfR1 expression by aspirin in the cells treated with LPS. PMID:26522688

  17. Surface enhanced Raman spectroscopic studies on aspirin : An experimental and theoretical approach

    NASA Astrophysics Data System (ADS)

    Premkumar, R.; Premkumar, S.; Rekha, T. N.; Parameswari, A.; Mathavan, T.; Benial, A. Milton Franklin

    2016-05-01

    Surface enhanced Raman scattering (SERS) studies on aspirin molecule adsorbed on silver nanoparticles (AgNPs) were investigated by experimental and density functional theory approach. The AgNPs were synthesized by the solution-combustion method and characterized by the X-ray diffraction and high resolution-transmission electron microscopy techniques. The averaged particle size of synthesized AgNPs was calculated as ˜55 nm. The normal Raman spectrum (nRs) and SERS spectrum of the aspirin were recorded. The molecular structure of the aspirin and aspirin adsorbed on silver cluster were optimized by the DFT/ B3PW91 method with LanL2DZ basis set. The vibrational frequencies were calculated and assigned on the basis of potential energy distribution calculation. The calculated nRs and SERS frequencies were correlated well with the observed frequencies. The flat-on orientation was predicted from the nRs and SERS spectra, when the aspirin adsorbed on the AgNPs. Hence, the present studies lead to the understanding of adsorption process of aspirin on the AgNPs, which paves the way for biomedical applications.

  18. Effects of aspirin on expression of iron transport and storage proteins in BV-2 microglial cells.

    PubMed

    Xu, Yan Xin; Du, Fang; Jiang, Li Rong; Gong, Jing; Zhou, Yu-Fu; Luo, Qian Qian; Qian, Zhong Ming; Ke, Ya

    2015-12-01

    In the light of recent studies, we hypothesized that aspirin might have the functions to regulate the expression of iron transport proteins and then affect cellular iron levels. To test this hypothesis, we investigated the effects of aspirin on expression of iron uptake protein transferrin receptor 1 (TfR1), iron release protein ferroportin 1 (Fpn1) and iron storage protein ferritin using Western blot analysis and on tumor necrosis factor (TNF)-αlpha, interleukin (IL)-6, interleukin (IL)-10 and hepcidin using quantitative real-time PCR in BV-2 microglial cells treated with lipopolysaccharides (LPS). We found that aspirin significantly down-regulated TfR1, while also up-regulated Fpn1 and ferritin expressions in BV-2 microglial cells in vitro. We also showed that TfR1 and Fpn1 expressions were significantly higher, while ferritin contents, IL-6, TNF-alpha and hepcidin mRNA levels were lower in cells treated with aspirin plus LPS than those in cells treated with LPS only. We concluded that aspirin has a negative effect on cell iron contents under 'normal' conditions and could partly reverse LPS-induced-disruption in cell iron balance under in vitro inflammatory conditions. Our findings also suggested that hepcidin might play a dominant role in the control of TfR1 expression by aspirin in the cells treated with LPS.

  19. Aspirin for the Primary Prevention of Cardiovascular Disease: In Need of Clarity.

    PubMed

    Miedema, Michael D; Huguelet, Joseph; Virani, Salim S

    2016-01-01

    Aspirin remains one of the most extensively studied cardiovascular medications in the history of medicine. However, despite multiple, well-designed, large randomized controlled trials evaluating the potential of aspirin to prevent cardiovascular events in individuals without known cardiovascular disease (CVD), the role of aspirin in primary prevention is currently unclear. The initial aspirin trials included largely low-risk individuals with primary outcomes mostly focused on myocardial infarction (MI) and stroke, and showed a significant reduction in these CVD outcomes, especially MI. The more recently conducted trials have focused on older, higher CVD risk populations with high rates of lipid-lowering and antihypertensive medications use. These studies have used broader CVD outcomes as their primary end points and have failed to show a significant benefit of aspirin therapy in primary prevention. The exact reasons for the lack of efficacy in these recent trials are unclear but may be related to low rate of atherothrombotic events relative to other CVD events in the populations studied. Four large randomized controlled trials are currently underway which should provide some clarity in determining the optimal use of aspirin in the primary prevention of CVD.

  20. Effect of aspirin on chromosome aberration and DNA damage induced by X-rays in mice

    NASA Astrophysics Data System (ADS)

    Niikawa, M.; Chuuriki, K.; Shibuya, K.; Seo, M.; Nagase, H.

    In order to reveal the anticlastogenic potency of aspirin, we evaluated the suppressive ability of aspirin on chromosome aberrations induced by X-ray. Aspirin at doses of 0.5, 5 and 50 mg/kg was administrated intraperitoneally or orally at 0.5 h after or before the X-ray irradiation. The anticlastogenic activity of aspirin on chromosome aberrations induced by X-ray was determined in the mouse micronucleus test and alkaline single cell gel electrophoresis (SCG) assay in vivo. The frequency by polychromatic erythrocytes with micronuclei (MNPCEs) was decreased by about 19-61% at 0.5 h after and about 23-62% at 0.5 h before the X-ray irradiation. DNA damage by X-ray was significantly decreased by oral administration of aspirin at 0.5 h after or before the X-ray irradiation for the SCG assay. We consider aspirin can be used as preventive agents against exposure of X-ray.

  1. Preparation of lipid aspirin sustained-release pellets by solvent-free extrusion/spheronization and an investigation of their stability.

    PubMed

    Yan, Xiaonan; He, Haibing; Meng, Jia; Zhang, Chungang; Hong, Mo; Tang, Xing

    2012-10-01

    A novel solvent-free extrusion/spheronization technique was investigated for preparing stable aspirin sustained-release pellets. Lipids as binders and the matrix in this technique were extruded below their melting points, and spheronized in a thermomechanical process. Four types of lipids (adeps solidus, Compritol(®) 888 ATO, Precirol(®) ATO5 and Compritol(®) HD5 ATO) and their admixture in different ratios were used to obtain spherical and extended-release pellets. Pellets containing 80% aspirin, 15% adeps solidus and 5% Compritol(®) 888 ATO had the best spherical geometry and met the dissolution requirements of aspirin extended-release tablets in USP 31. Storage stability studies showed that the content of free salicylic acid increased sharply in the traditional pellets produced by wet extrusion/spheronization, from 1.91 to 7.84%, whereas there was little increase in the lipid pellets (from 0.48 to 1.08%). The dissolution rate from the optimal pellets (F11) stored at 26°C did not change, but became faster at 40°C/RH75% after 5 months. Powder X-ray diffraction, scanning electron microscopy (SEM) and differential scanning calorimetry were used to investigate the physical properties of the pellets during stability testing. The increase in the rate of drug release from aged pellets (40°C/RH75%) may result from the partially melted adeps solidus observed in SEM photographs. This study suggests that it is possible to prepare sustained-release pellets by solvent-free extrusion/spheronization using an appropriate mixture of lipids with high stability. In particular, this novel technique is excellent for hygroscopic drugs.

  2. Isolation, Characterization of a Potential Degradation Product of Aspirin and an HPLC Method for Quantitative Estimation of Its Impurities.

    PubMed

    Acharya, Subasranjan; Daniel, Alex; Gyadangi, Bharath; Ramsamy, Sriramulu

    2015-10-01

    In this work, a new degradation product of Aspirin was isolated, characterized and analyzed along with other impurities. New unknown degradation product referred as UP was observed exceeding the limit of ICH Q3B identification thresholds in the stability study of Aspirin and Dipyridamole capsule. The UP isolated from the thermal degradation sample was further studied by IR, Mass and (1)H NMR spectrometry, revealing structural similarities with the parent molecule. Finally, UP was identified as a new compound generated from the interaction of Aspirin and Salicylic acid to form a dehydrated product. A specific HPLC method was developed and validated for the analysis of UP and other Aspirin impurities (A, B, C, E and other unknown degradation products). The proposed method was successfully employed for estimation of Aspirin impurities in a pharmaceutical preparation of Aspirin (Immediate Release) and Dipyridamole (Extended Release) Capsules.

  3. Suboptimal inhibition of platelet cyclo-oxygenase-1 (COX-1) by aspirin in lupus erythematosus: Association with metabolic syndrome

    PubMed Central

    Kawai, Vivian K.; Avalos, Ingrid; Oeser, Annette; Oates, John A.; Milne, Ginger L.; Solus, Joseph F.; Chung, Cecilia P.; Stein, C. Michael

    2013-01-01

    Objectives Low-dose aspirin prevents platelet aggregation by suppressing thromboxane A2 synthesis. However, in some individuals thromboxane A2 suppression by aspirin is impaired, indicating suboptimal inhibition of platelet COX-1 by aspirin. Because patients with systemic lupus erythematosus (SLE) have increased risk of thrombotic events, many receive aspirin; however, the efficacy of aspirin in SLE has not been determined. We examined the hypothesis that aspirin response is impaired in SLE. Methods We assessed the effect of aspirin by measuring concentrations of the stable metabolite of thromboxane A2 - serum thromboxane B2 (sTxB2), before and after treatment with 81 mg daily aspirin for 7 days in 34 patients with SLE and 36 control subjects. The inability to suppress sTxB2 synthesis to <10 ng/ml represents suboptimal inhibition of platelet COX-1 by aspirin. Results Aspirin almost completely suppressed sTXB2 in control subjects to 1.5, [0.8–2.7] ng/ml (median and interquartile ranges [IQR]), but had less effect in patients with SLE (3.1, [2.2–5.3] ng/ml) (P=0.002). A suboptimal effect of aspirin was present in 15% (5/34) of the patients with SLE but not in control subjects (0/36) (P=0.023). Incomplete responders were more likely to have metabolic syndrome (P=0.048), obesity (P=0.048) and higher concentrations of CRP (P=0.018). Conclusion The pharmacologic effect of aspirin is suboptimal in 15% of patients with SLE but in none of the control subjects, and the suboptimal response was associated with metabolic syndrome, obesity, and higher CRP concentrations. PMID:24022862

  4. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine. PMID:26341013

  5. ASPIRIN DOSE AND DURATION OF USE AND RISK OF COLORECTAL CANCER IN MEN

    PubMed Central

    Chan, Andrew T.; Giovannucci, Edward L.; Meyerhardt, Jeffrey A.; Schernhammer, Eva S.; Wu, Kana; Fuchs, Charles S.

    2009-01-01

    Background and Aims Long-term data on the risk of colorectal cancer according to dose, duration, and consistency of aspirin therapy are limited. Methods We conducted a prospective study of 47,363 male health professionals who were ages 40–75 years at enrollment in 1986. Biennially, we collected data on aspirin use, other risk factors, and diagnoses of colorectal cancer. We confirmed all reports of colorectal cancer through 2004 by review of medical records. Results During 18 years of follow-up, we documented 975 cases of colorectal cancer over 761,757 person-years. After adjustment for risk factors, men who regularly used aspirin (≥2 times/week) had a multivariate relative risk (RR) for colorectal cancer of 0.79 (95% confidence interval, [CI], 0.69–0.90), compared with non-regular users. However, significant risk reduction required at least 6–10 years of use (Ptrend=0.008) and was no longer evident within 4 years of discontinuing use (multivariate RR, 1.00; CI, 0.72–1.39). The benefit appeared related to increasing cumulative average dose: compared to men who denied any aspirin use, the multivariate RRs for cancer were 0.94 (CI, 0.75–1.18) for men who used 0.5–1.5 standard aspirin/week, 0.80 (CI, 0.63–1.01) for 2–5 aspirin/week, 0.72 (CI, 0.56–0.92) for 6–14 aspirin/week, and 0.30 (CI, 0.11–0.81) for >14 aspirin/week (Ptrend=0.004). Conclusions Regular, long-term aspirin use reduces risk of colorectal cancer among men. However, the benefit of aspirin necessitates at least 6 years of consistent use with maximal risk reduction at doses greater than 14 tablets/week. The potential hazards associated with long-term use of such doses should be carefully considered. PMID:18005960

  6. Antiplatelet Drugs: Do You Need One to Help Prevent a Heart Attack or Stroke?

    MedlinePlus

    ... scientific review by the Oregon Health and Science University-based Drug Effectiveness Review Project. This is a summary of a longer, more detailed report you can find at www.CRBestBuyDrugs.org . Best Buy Generic Name Brand Name Pills per Cost per & Strength Day Month 1 Recommended Use Aspirin ...

  7. Drugs in the Womb: College Student Perceptions of Maternal v. Fetal Rights.

    ERIC Educational Resources Information Center

    Vener, Arthur M.; And Others

    1992-01-01

    Surveyed 523 undergraduates regarding drug use during pregnancy. Rank order of relative safety of drugs existed for respondents. Tobacco, alcohol, and aspirin were perceived as similar in their consequences to fetus. Cocaine was considered most deleterious and Accutane was considered least deleterious. Seventy-five percent would imprison pregnant…

  8. The differential effects of aspirin on platelets, leucocytes and vascular endothelium in an in vivo model of thrombus formation.

    PubMed

    Nagamatsu, Y; Tsujioka, Y; Hashimoto, M; Giddings, J C; Yamamoto, J

    1999-02-01

    Unanswered questions remain with regard to the therapeutic use of aspirin and the selective inhibition of thromboxane A2 and prostacyclin in platelets and endothelial cells. In the present study, the effects of aspirin on platelets and endothelial cells in vivo were examined using a helium-neon (He-Ne) laser-induced thrombosis model. Single intravenous injections of aspirin at concentrations of more than 0.5 mg/kg body weight mediated a dose dependent inhibition of thrombus formation in arterioles but not in venules. This antithrombotic effect was optimum after 15 min and declined after 90 min. Potent antithrombotic activity in arterioles was manifest at doses of 2.5 mg/kg to 50 mg/kg, and initial inhibition of thrombogenesis in vivo was most pronounced at high doses. Oral aspirin also inhibited thrombus formation in arterioles but not in venules, although the antithrombotic effects were delayed and prolonged. Maximum inhibition of ex vivo, collagen induced platelet aggregation by aspirin was observed approximately 180 min after intravenous injection. The results demonstrated that, although aspirin might have differential effects on platelets and endothelial cells, potent antithrombotic activity was manifest in arterioles at all concentrations. The findings suggest that the concept of the aspirin dilemma might be ignored for therapeutic purposes in many clinical circumstances. The antithrombotic effects of aspirin were unchanged in granulocyte-depleted animals, indicating that leucocyte-related mechanisms including neutrophil superoxide anion production did not modulate the potency of aspirin in this model. PMID:10197261

  9. Newer antithrombotic drugs

    PubMed Central

    Sikka, Pranav; Bindra, V. K.

    2010-01-01

    Thromboembolic disorders are one of the disorders for which we are still on the look out for a safe and efficient drug. Despite the widespread use of antithrombotic drugs for the prevention and treatment of arterial and venous thrombosis, thromboembolic diseases continue to be a major cause of death and disability worldwide. This shows our inefficiency in searching efficacious and safe antithrombotic drugs. We have reached the basic mechanism of thrombus formation and by interrupting various steps of this mechanism, we can prevent as well as treat thromboembolic disorders. In continuation of Aspirin, now, we are using Clopidogrel, Ticlopidine and GpIIb/IIIa inhibitors (Abciximab, Tirofiban and Eptifibatide). Warfarin is an old antithrombotic drug which is still being used; but due to various side effects and drug interactions, we are bound to use newer drugs. Newer antiplatelet drugs include Prasugrel, Ticagrelor and Cangrelor, whereas newer thrombin inhibitors are Ximelgatran and Dabigatran. Apixaban is also a newer entry in this category as factor Xa inhibitor. Idrabiotaparinux is an indirect inhibitor of Xa as it accelerates the activity of antithrombin. Moreover, researches and trials for better and safe drugs are ongoing. PMID:21572750

  10. Cost-Effectiveness of Aspirin Adjuvant Therapy in Early Stage Colorectal Cancer in Older Patients

    PubMed Central

    Soon, Swee Sung; Chia, Whay-Kuang; Chan, Mun-ling Sarah; Ho, Gwo Fuang; Jian, Xiao; Deng, Yan Hong; Tan, Chuen-Seng; Sharma, Atul; Segelov, Eva; Mehta, Shaesta; Ali, Raghib; Toh, Han-Chong; Wee, Hwee-Lin

    2014-01-01

    Background & Aims Recent observational studies showed that post-operative aspirin use reduces cancer relapse and death in the earliest stages of colorectal cancer. We sought to evaluate the cost-effectiveness of aspirin as an adjuvant therapy in Stage I and II colorectal cancer patients aged 65 years and older. Methods Two five-state Markov models were constructed separately for Stage I and II colorectal cancer using TreeAge Pro 2014. Two hypothetical cohorts of 10,000 individuals at a starting age of 65 years and with colorectal cancer in remission were put through the models separately. Cost-effectiveness of aspirin was evaluated against no treatment (Stage I and II) and capecitabine (Stage II) over a 20-year period from the United States societal perspective. Extensive one-way sensitivity analyses and multivariable Probabilistic Sensitivity Analyses (PSA) were performed. Results In the base case analyses, aspirin was cheaper and more effective compared to other comparators in both stages. Sensitivity analyses showed that no treatment and capecitabine (Stage II only) can be cost-effective alternatives if the utility of taking aspirin is below 0.909, aspirin’s annual fatal adverse event probability exceeds 0.57%, aspirin’s relative risk of disease progression is 0.997 or more, or when capecitabine’s relative risk of disease progression is less than 0.228. Probabilistic Sensitivity Analyses (PSA) further showed that aspirin could be cost-effective 50% to 80% of the time when the willingness-to-pay threshold was varied from USD20,000 to USD100,000. Conclusion Even with a modest treatment benefit, aspirin is likely to be cost-effective in Stage I and II colorectal cancer, thus suggesting a potential unique role in secondary prevention in this group of patients. PMID:25250815

  11. Clinical pharmacology of cyclooxygenase inhibition and pharmacodynamic interaction with aspirin by floctafenine in Thai healthy subjects.

    PubMed

    Maenthaisong, R; Tacconelli, S; Sritara, P; Del Boccio, P; Di Francesco, L; Sacchetta, P; Archararit, N; Aryurachai, K; Patrignani, P; Suthisisang, C

    2013-01-01

    Floctafenine, a hydroxyquinoline derivative with analgesic properties, is widely used in Thailand and many other countries. The objectives of this study were to evaluate in Thai healthy volunteers: i) the inhibition of whole blood cyclooxygenase(COX)-2 and COX-1 activity by floctafenine and its metabolite floctafenic acid in vitro and ex vivo after dosing with floctafenine; ii) the possible interference of floctafenine administration with aspirin antiplatelet effects. We performed an open-label, cross-over, 3-period study, on 11 healthy Thai volunteers, who received consecutively floctafenine(200mg/TID), low-dose aspirin(81mg/daily) or their combination for 4 days, separated by washout periods. Floctafenine and floctafenic acid resulted potent inhibitors of COX-1 and COX-2 in vitro (floctafenic acid was more potent than floctafenine) showing a slight preference for COX-1. After dosing with floctafenine alone, whole blood COX-1 and COX-2 activities were inhibited ex vivo in a time-dependent fashion which paralleled floctafenic acid plasma concentrations. Aspirin alone inhibited profoundly and persistently platelet COX-1 activity and AA-induced platelet aggregation throughout 24-h dosing interval which was affected by the co-administration of floctafenine. At 24 h after dosing with aspirin and floctafenine, the inhibition of platelet thromboxane(TX)B2 generation and aggregation were significantly(P less than 0.05) lower than that caused by aspirin alone. Therapeutic dosing with floctafenine profoundly inhibited prostanoid biosynthesis through the rapid conversion to floctafenic acid. Floctafenine interfered with the antiplatelet effect of aspirin. Our results suggest that floctafenine should be avoided in patients with cardiovascular disease under treatment with low-dose aspirin. PMID:23755755

  12. Aspirin augments carotid-cardiac baroreflex sensitivity during muscle mechanoreflex and metaboreflex activation in humans.

    PubMed

    Drew, Rachel C; Muller, Matthew D; Blaha, Cheryl A; Mast, Jessica L; Herr, Michael D; Stocker, Sean D; Sinoway, Lawrence I

    2013-10-15

    Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate (HR) control during local metabolite accumulation in humans. However, the contribution of thromboxane A2 (TXA2) toward this response is unknown. Therefore, the effect of inhibiting TXA2 production via low-dose aspirin on CBR-HR sensitivity during muscle mechanoreflex and metaboreflex activation in humans was examined. Twelve young subjects performed two trials during two visits, preceded by 7 days' low-dose aspirin (81 mg) or placebo. One trial involved 3-min passive calf stretch (mechanoreflex) during 7.5-min limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise to accumulate metabolites during CO and stretch (mechanoreflex and metaboreflex). HR (ECG) and mean arterial pressure (Finometer) were recorded. CBR function was assessed using rapid neck pressures ranging from +40 to -80 mmHg. Aspirin significantly decreased baseline thromboxane B2 production by 84 ± 4% (P < 0.05) but did not affect 6-keto prostaglandin F1α. Following aspirin, stretch with metabolite accumulation significantly augmented maximal gain (GMAX) and operating point gain (GOP) of CBR-HR (GMAX; -0.71 ± 0.14 vs. -0.37 ± 0.08 and GOP; -0.69 ± 0.13 vs. -0.35 ± 0.12 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively; P < 0.05). CBR-HR function curves were reset similarly with aspirin and placebo during stretch with metabolite accumulation. In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in humans. This increased sensitivity appears linked to reduced TXA2 production, which likely plays a role in metabolite sensitization of muscle mechanoreceptors. PMID:23970529

  13. The Influence of Haemoglobin A1c Levels on Platelet Aggregation and Platelet Turnover in Patients with Coronary Artery Disease Treated with Aspirin

    PubMed Central

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

    2015-01-01

    Background Hyperglycaemia may attenuate the antiplatelet effect of aspirin and thereby increase the risk of cardiovascular events. We investigated the influence of increased haemoglobin A1c (HbA1c) levels on platelet aggregation and turnover in a large cohort of patients with coronary artery disease (CAD) with type 2 diabetes, prediabetes or no diabetes. Methods In this observational study, we included 865 stable CAD patients on 75 mg aspirin as mono-therapy of whom 242 patients had type 2 diabetes and were receiving antidiabetic drugs. Among 623 patients without diabetes, we classified 303 patients with prediabetes (HbA1c ≥5.7–6.4% [39–47 mmol/mol]) naive to antidiabetic drugs. Platelet aggregation was evaluated by the Multiplate Analyzer using arachidonic acid and collagen and by the VerifyNow Aspirin. Platelet turnover was evaluated by immature platelets using flow cytometry and platelet activation by soluble P-selectin. Results CAD patients with type 2 diabetes had higher platelet aggregation (all p-values <0.01), platelet turnover (immature platelet count, p<0.01) and platelet activation (p<0.001) than patients without diabetes. CAD patients with prediabetes had increased platelet aggregation (p = 0.02) and platelet count (p = 0.02) compared with patients without diabetes. Increased levels of HbA1c correlated positively with increased platelet aggregation using arachidonic acid (r = 0.19, p<0.0001), collagen (r = 0.10, p<0.01) and VerifyNow (r = 0.15, p<0.0001), and with platelet count (r = 0.08, p = 0.01), immature platelet count (r = 0.11, p<0.001) and soluble P-selectin (r = 0.15, p<0.0001). These associations were mainly evident in non-diabetic and prediabetic CAD patients. Conclusions CAD patients with prediabetes and diabetes may have attenuated antiplatelet effect of aspirin compared with CAD patients without diabetes. This may be related to increased platelet count in patients with prediabetes. Increased levels of HbA1c correlated positively

  14. Effects of alcohol on human carboxylesterase drug metabolism

    PubMed Central

    Parker, Robert B.; Hu, Zhe-Yi; Meibohm, Bernd; Laizure, S. Casey

    2015-01-01

    Background and Objective Human carboxylesterase-1 (CES1) and human carboxylesterase-2 (CES2) play an important role in metabolizing many medications. Alcohol is a known inhibitor of these enzymes but the relative effect on CES1 and CES2 is unknown. The aim of this study is to determine the impact of alcohol on the metabolism of specific probes for CES1 (oseltamivir) and CES2 (aspirin). Methods The effect of alcohol on CES1- and CES2-mediated probe drug hydrolysis was determined in vitro using recombinant human carboxylesterase. To characterize the in vivo effects of alcohol, healthy volunteers received each probe drug alone and in combination with alcohol followed by blood sample collection and determination of oseltamivir, aspirin, and respective metabolite pharmacokinetics. Results Alcohol significantly inhibited oseltamivir hydrolysis by CES1 in vitro but did not affect aspirin metabolism by CES2. Alcohol increased the oseltamivir area under the plasma concentration-time curve (AUC) from 0-6 h by 27% (range 11-46%, p=0.011) and decreased the metabolite/oseltamivir AUC 0-6 h ratio by 34% (range 25-41%, p<0.001). Aspirin pharmacokinetics were not affected by alcohol. Conclusions Alcohol significantly inhibited the hydrolysis of oseltamivir by CES1 both in vitro and in humans, but did not affect the hydrolysis of aspirin to salicylic acid by CES2. These results suggest that alcohol's inhibition of CES1 could potentially result in clinically significant drug interactions with other CES1-substrate drugs, but it is unlikely to significantly affect CES2-substrate drug hydrolysis. PMID:25511794

  15. Anti-Platelet Drug Resistance in the Prediction of Thromboembolic Complications after Neurointervention

    PubMed Central

    Ryu, Dal-Sung; Sim, Yoo-Sik; Kim, Chang-Hyun; Jung, Jin-Young; Joo, Jin-Yang

    2010-01-01

    Objective The aim of this study was to analyze the correlation between thromboembolic complications and antiplatelet drugs before and after neurointervention. Methods Blood samples and radiographic data of patients who received a neurointervention (coil embolization, stent placement or both) were collected prospectively. Rapid platelet function assay-aspirin (RPFA-ASA) was used to calculate aspirin resistance in aspirin reaction units (ARU). For clopidogrel resistance, a P2Y12 assay was used to analyze the percentage of platelet inhibition. ARU > 550 and platelet inhibition < 40% were defined as aspirin and clopidogrel resistance, respectively. Results Both aspirin and clopidogrel oral pills were administered in fifty-three patients before and after neurointerventional procedures. The mean resistance values of all patients were 484 ARU and < 39%. Ten (17.0%) of 53 patients showed resistance to aspirin with an average of 597 ARU, and 33 (62.3%) of 53 patients showed resistance to clopidogrel with an average of < 26%. Ten patients demonstrated resistance to both drugs, 5 of which suffered a thromboembolic complication after neurointervention (mean values : 640 ARU and platelet inhibition < 23%). Diabetic patients and patients with hypercholesterolemia displayed mean aspirin resistances of 513.7 and 501.8 ARU, and mean clopidogrel resistances of < 33.8% and < 40.7%, respectively. Conclusion Identifying individuals with poor platelet inhibition using standard regimens is of great clinical importance and may help prevent cerebral ischemic events in the future. Neurointerventional research should focus on ideal doses, timing, choices, safety, and reliable measurements of antiplatelet drug therapy, as well as confirming the clinical relevance of aggregometry in cerebrovascular patients. PMID:21113358

  16. Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites.

    PubMed

    Ai, Guoqiang; Dachineni, Rakesh; Kumar, D Ramesh; Alfonso, Lloyd F; Marimuthu, Srinivasan; Bhat, G Jayarama

    2016-08-01

    Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first reaction in the pentose phosphate pathway, and generates ribose sugars, which are required for nucleic acid synthesis, and nicotinamide adenine dinucleotide phosphate (NADPH), which is important for neutralization of oxidative stress. The expression of G6PD is elevated in several types of tumor, including colon, breast and lung cancer, and has been implicated in cancer cell growth. Our previous study demonstrated that exposure of HCT 116 human colorectal cancer cells to aspirin caused acetylation of G6PD, and this was associated with a decrease in its enzyme activity. In the present study, this observation was expanded to HT‑29 colorectal cancer cells, in order to compare aspirin‑mediated acetylation of G6PD and its activity between HCT 116 and HT‑29 cells. In addition, the present study aimed to determine the acetylation targets of aspirin on recombinant G6PD to provide an insight into the mechanisms of inhibition. The results demonstrated that the extent of G6PD acetylation was significantly higher in HCT 116 cells compared with in HT‑29 cells; accordingly, a greater reduction in G6PD enzyme activity was observed in the HCT 116 cells. Mass spectrometry analysis of aspirin‑acetylated G6PD (isoform a) revealed that aspirin acetylated a total of 14 lysine residues, which were dispersed throughout the length of the G6PD protein. One of the important amino acid targets of aspirin included lysine 235 (K235, in isoform a) and this corresponds to K205 in isoform b, which has previously been identified as being important for catalysis. Acetylation of G6PD at several sites, including K235 (K205 in isoform b), may mediate inhibition of G6PD activity, which may contribute to the ability of aspirin to exert anticancer effects through decreased synthesis of ribose sugars and NADPH. PMID:27356773

  17. Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites.

    PubMed

    Ai, Guoqiang; Dachineni, Rakesh; Kumar, D Ramesh; Alfonso, Lloyd F; Marimuthu, Srinivasan; Bhat, G Jayarama

    2016-08-01

    Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first reaction in the pentose phosphate pathway, and generates ribose sugars, which are required for nucleic acid synthesis, and nicotinamide adenine dinucleotide phosphate (NADPH), which is important for neutralization of oxidative stress. The expression of G6PD is elevated in several types of tumor, including colon, breast and lung cancer, and has been implicated in cancer cell growth. Our previous study demonstrated that exposure of HCT 116 human colorectal cancer cells to aspirin caused acetylation of G6PD, and this was associated with a decrease in its enzyme activity. In the present study, this observation was expanded to HT‑29 colorectal cancer cells, in order to compare aspirin‑mediated acetylation of G6PD and its activity between HCT 116 and HT‑29 cells. In addition, the present study aimed to determine the acetylation targets of aspirin on recombinant G6PD to provide an insight into the mechanisms of inhibition. The results demonstrated that the extent of G6PD acetylation was significantly higher in HCT 116 cells compared with in HT‑29 cells; accordingly, a greater reduction in G6PD enzyme activity was observed in the HCT 116 cells. Mass spectrometry analysis of aspirin‑acetylated G6PD (isoform a) revealed that aspirin acetylated a total of 14 lysine residues, which were dispersed throughout the length of the G6PD protein. One of the important amino acid targets of aspirin included lysine 235 (K235, in isoform a) and this corresponds to K205 in isoform b, which has previously been identified as being important for catalysis. Acetylation of G6PD at several sites, including K235 (K205 in isoform b), may mediate inhibition of G6PD activity, which may contribute to the ability of aspirin to exert anticancer effects through decreased synthesis of ribose sugars and NADPH.

  18. Time-dependent effects of aspirin on blood pressure and morning platelet reactivity: a randomized cross-over trial.

    PubMed

    Bonten, Tobias N; Snoep, Jaapjan D; Assendelft, Willem J J; Zwaginga, Jaap Jan; Eikenboom, Jeroen; Huisman, Menno V; Rosendaal, Frits R; van der Bom, Johanna G

    2015-04-01

    Aspirin is used for cardiovascular disease (CVD) prevention by millions of patients on a daily basis. Previous studies suggested that aspirin intake at bedtime reduces blood pressure compared with intake on awakening. This has never been studied in patients with CVD. Moreover, platelet reactivity and CVD incidence is highest during morning hours. Bedtime aspirin intake may attenuate morning platelet reactivity. This clinical trial examined the effect of bedtime aspirin intake compared with intake on awakening on 24-hour ambulatory blood pressure measurement and morning platelet reactivity in patients using aspirin for CVD prevention. In this randomized open-label crossover trial, 290 patients were randomized to take 100 mg aspirin on awakening or at bedtime during 2 periods of 3 months. At the end of each period, 24-hour blood pressure and morning platelet reactivity were measured. The primary analysis population comprised 263 (blood pressure) and 133 (platelet reactivity) patients. Aspirin intake at bedtime did not reduce blood pressure compared with intake on awakening (difference systolic/diastolic: -0.1 [95% confidence interval, -1.0, 0.9]/-0.6 [95% confidence interval, -1.2, 0.0] mm Hg). Platelet reactivity during morning hours was reduced with bedtime aspirin intake (difference: -22 aspirin reaction units [95% confidence interval, -35, -9]). The intake of low-dose aspirin at bedtime compared with intake on awakening did not reduce blood pressure of patients with CVD. However, bedtime aspirin reduced morning platelet reactivity. Future studies are needed to assess the effect of this promising simple intervention on the excess of cardiovascular events during the high risk morning hours.

  19. Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhythm

    PubMed Central

    Homma, Shunichi; Thompson, John L.P.; Pullicino, Patrick M.; Levin, Bruce; Freudenberger, Ronald S.; Teerlink, John R.; Ammon, Susan E.; Graham, Susan; Sacco, Ralph L.; Mann, Douglas L.; Mohr, J.P.; Massie, Barry M.; Labovitz, Arthur J.; Anker, Stefan D.; Lok, Dirk J.; Ponikowski, Piotr; Estol, Conrado J.; Lip, Gregory Y.H.; Di Tullio, Marco R.; Sanford, Alexandra R.; Mejia, Vilma; Gabriel, Andre P.; del Valle, Mirna L.; Buchsbaum, Richard

    2013-01-01

    BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an

  20. A Prospective Study of Aspirin Use and the Risk of Gastrointestinal Bleeding in Men

    PubMed Central

    Huang, Edward S.; Strate, Lisa L.; Ho, Wendy W.; Lee, Salina S.; Chan, Andrew T.

    2010-01-01

    Background and Aims Data regarding the influence of dose and duration of aspirin use on risk of gastrointestinal bleeding are conflicting. Methods We conducted a prospective cohort study of 32,989 men enrolled in the Health Professionals Follow-up Study (HPFS) in 1994 who provided biennial aspirin data. We estimated relative risk of major gastrointestinal bleeding requiring hospitalization or a blood transfusion. Results During 14 years of follow-up, 707 men reported an episode of major gastrointestinal bleeding over 377,231 person-years. After adjusting for risk factors, regular aspirin use (≥2 times/week) had a multivariate relative risk (RR) of gastrointestinal bleeding of 1.32 (95% confidence interval [CI], 1.12–1.55) compared to non-regular use. The association was particularly evident for upper gastrointestinal bleeding (multivariate RR, 1.49; 95% CI, 1.16–1.92). Compared to men who denied any aspirin use, multivariate RRs of upper gastrointestinal bleeding were 1.05 (95% CI 0.71–1.52) for men who used 0.5–1.5 standard tablets/week, 1.31 (95% CI 0.88–1.95) for 2–5 aspirin/week, 1.63 (95% CI, 1.15–2.32) for 6–14 aspirin/week and 2.40 (95% CI, 1.10–5.22) for >14 aspirin/week (Ptrend<0.001). The relative risk also appeared to be dose-dependent among short-term users <5 years; Ptrend<.001) and long-term users (≥5 years; Ptrend = 0.015). In contrast, after controlling for dose, increasing duration of use did not appear to be associated with risk (Ptrend = 0.749). Conclusions Regular aspirin use increases the risk of gastrointestinal bleeding, especially from the upper tract. However, risk of bleeding appears to be more strongly related to dose than to duration of use. Risk of bleeding should be minimized by using the lowest effective dose among short-term and long-term aspirin users. PMID:21209949

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

    PubMed

    Landolfi, R; Marchioli, R

    1997-01-01

    Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value < or = 45% in subjects aged