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

    PubMed Central

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

    2015-01-01

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

  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. The anti-inflammatory drug nimesulide inhibits neutrophil adherence to and migration across monolayers of cytokine-activated endothelial cells.

    PubMed

    Dapino, P; Ottonello, L; Dallegri, F

    1994-01-01

    Neutrophil migration through the microvascular endothelium represents a fundamental event for the cell accumulation at sites of tissue injury. Owing to their capacity to modify the structural and functional characteristics of endothelial cells, inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha) play a pivotal role in directing circulating neutrophils away from the bloodstream to the interstitial tissue. In order to study neutrophil transendothelial migration, human umbilical vein endothelial cells were grown to confluence on the polycarbonate filter of two-compartment migration chambers. Pretreatment of the endothelial cell monolayers with TNF alpha for 4 h resulted in rapid migration of approximately 50% of subsequently added neutrophils across the layers. In contrast, < 10% of added neutrophils penetrated untreated endothelial monolayers. Using TNF alpha-treated endothelium, neutrophil transmigration was inhibited by the methane sulfonanilide anti-inflammatory drug nimesulide. Moreover, neutrophil adherence to TNF alpha-treated endothelial monolayers, cultured in microtiter wells, was markedly reduced by nimesulide. A linear correlation between the drug-dependent inhibition of neutrophil transmigration and neutrophil adherence was found. Finally, nimesulide did not interfere with the TNF alpha ability to convert resting endothelium into a pro-adhesive and pro-locomotory cell layer. The data suggest that nimesulide reduces neutrophil transendothelial migration primarily by limiting the cell anchorage to the TNF alpha-activated endothelium. Therefore, the drug has the potential to down-regulate neutrophil extravasation and, in turn, the burden of neutrophil oxidants and proteases leading to tissue injury at sites of inflammation. PMID:7824814

  5. Nimesulide as a downregulator of the activity of the neutrophil myeloperoxidase pathway. Focus on the histoprotective potential of the drug during inflammatory processes.

    PubMed

    Ottonello, L; Dapino, P; Pastorino, G; Montagnani, G; Gatti, F; Guidi, G; Dallegri, F

    1993-01-01

    Neutrophils, recruited to tissue sites of inflammation, release a variety of oxidants and enzymes, which are responsible for tissue damage. Among the oxidants released are potent chlorinated compounds, such as hypochlorous acid and chloramines, which induce tissue cell damage and inactivate protease inhibitors, particularly alpha 1-antitrypsin, the specific inhibitor of neutrophil elastase. In studying a rational approach to the pharmacological control of neutrophil-mediated tissue injury, we investigated the activity of the anti-inflammatory drug nimesulide. This agent reduced the function of the myeloperoxidase pathway (which generates hypochlorous acid), by exerting a cell-directed inhibitory activity, as shown by measurement of superoxide anion and hydrogen peroxide production. Nimesulide also inactivated hypochlorous acid directly and protected alpha 1-antitrypsin from the neutrophil-mediated oxidation. Thus, neutrophil elastolytic activity may be attenuated by nimesulide-spared alpha 1-antitrypsin. The prevention of oxidative inactivation of alpha 1-antitrypsin by nimesulide strictly correlates with the drug's ability to suppress the extracellular availability of hypochlorous acid. Taken together, these data suggest that nimesulide may prevent tissue injury at sites of inflammation by maintaining natural host protective systems. PMID:7506191

  6. Effect of nonsteroidal antiinflammatory drugs on the neutrophil promoted inactivation of alpha-1-proteinase inhibitor.

    PubMed

    Dallegri, F; Ottonello, L; Dapino, P; Sacchetti, C

    1992-03-01

    We investigated the effect of some nonsteroidal antiinflammatory drugs (aspirin, naproxen and nimesulide) on the ability of neutrophils to oxidatively inactivate the alpha-1-proteinase inhibitor (A1PI). Nimesulide prevented the inactivation of A1PI by effectively scavenging the hypochlorous acid released by neutrophils. Aspirin and naproxen were completely ineffective. We suggest that the antiinflammatory effect of nimesulide may be due at least in part to the rescue of A1PI from neutrophil oxidative attack. The rescue of A1PI may in fact alter the elastase-A1PI balance in favor of the inhibitor, with resulting tissue protection. PMID:1578457

  7. Aspirin

    MedlinePlus

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

  8. Aspirin

    MedlinePlus

    ... cough and cold medications. This monograph only includes information about the use of aspirin alone. If you are taking a combination product, read the information on the package or prescription label or ask ...

  9. The anti-inflammatory drug nimesulide rescues alpha-1-proteinase inhibitor from oxidative inactivation by phagocytosing neutrophils.

    PubMed

    Dallegri, F; Ottonello, L; Dapino, P; Bevilacqua, M

    1992-01-01

    When neutrophils are recruited to tissue sites and exposed to phagocytosable targets, they release oxidants which may be responsible for the local inactivation of alpha-1-proteinase inhibitor (A1PI). Consequently, A1PI becomes incapable of inhibiting the proteolytic activity of elastase, released at the same time by neutrophils as a result of leakage from phagocytic vacuoles. In the present paper we show that phagocytosing neutrophils inactivate A1PI via a process inhibitable by chemical agents known to interfere with the hypochlorous acid (HOCl)-generating myeloperoxidase pathway. The anti-inflammatory drug nimesulide (NMS), which is able to efficiently limit the extracellular availability of HOCl in the neutrophil surroundings, was found to prevent the inactivation of A1PI by neutrophils. The results provide evidence for a possible way to control neutrophil elastase activity by rescuing its natural inhibitor (A1PI) at inflamed tissue sites during infectious and noninfectious processes. PMID:1579712

  10. 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

  11. Characterization and compaction behaviour of nimesulide crystal forms.

    PubMed

    Di Martino, Piera; Censi, Roberta; Barthélémy, Christine; Gobetto, Roberto; Joiris, Etienne; Masic, Admir; Odou, Pascal; Martelli, Sante

    2007-09-01

    Nimesulide is a typical nonsteroidal anti-inflammatory drug (NSAID), widely used in solid oral formulations. By crystallizing nimesulide from an ethanol solution a crystalline form was obtained, different from the reference sample, as confirmed by X-ray powder diffraction (XRPD), Differential Scanning Calorimetry (DSC) and solid cross polarization-magic angle spinning ((13)C-CPMAS) NMR. Moreover, when crystallized from dioxane nimesulide forms a solvate. The solvate was characterized by XRPD, IR-spectrometry, DSC, thermo-gravimetric analysis (TGA) and by (13)C-CPMAS NMR. In particular, through this technique, the presence of several conformational isomers was demonstrated. In addition to the physico-chemical characterization, the technological properties of nimesulide, namely densification and tableting, were evaluated. Contrarily to the other forms that are affected by capping phenomena at increasing compression pressures, the form obtained by desolvation of dioxane solvate has positive effect on tableting properties, increasing both compressibility and tabletability of nimesulide. PMID:17583450

  12. 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.

  13. Electrochemical oxidation of drug residues in water by the example of tetracycline, gentamicine and aspirin.

    PubMed

    Weichgrebe, D; Danilova, E; Rosenwinkel, K H; Vedenjapin, A A; Baturova, M

    2004-01-01

    Electro-chemical oxidation as a method to destroy drug residues like aspirin, tetracycline or gentamicine in water was investigated with C-anodes (modified by manganese oxides) and Pt anodes. The mechanism of aspirin and tetracycline oxidation and the influence of the biocide effect was observed using GC-MS and three different microbiological tests. In general, the biological availability increases with progressive oxidation of the antibiotics. PMID:15077972

  14. 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

  15. Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory drugs.

    PubMed

    Simon, Ronald A

    2004-01-01

    Aspirin-exacerbated respiratory disease (AERD) is an adult-onset condition that manifests as asthma, rhinosinusitis/nasal polyps, and sensitivity to aspirin and other cyclooxygenase-1 (COX-1)-inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs). There is no cross-sensitivity to highly selective COX-2 inhibitors. AERD is chronic and does not improve with avoidance of COX-1 inhibitors. The diagnosis of AERD is made through provocative challenge testing. Following a positive aspirin challenge, patients can be desensitized to aspirin and NSAIDs. The desensitized state can be maintained indefinitely with continued daily administration. After desensitization, there is an approximately 48-hour refractory period to adverse effects from aspirin. The pathogenesis of AERD remains unknown, but these patients have been shown to have multiple abnormalities in arachidonic acid metabolism and in cysteinyl leukotriene 1 receptors. AERD patients can take up to 650 mg of acetaminophen for analgesic or antipyretic relief. Patients can also use weak COX-1 inhibitors, such as sodium salicylate or choline magnesium trisalicylate. Treatment of AERD patients with antileukotriene medications has been helpful but not preferential when compared with non-AERD patients. An alternative treatment for many AERD patients is aspirin desensitization. This is particularly effective in reducing upper-airway mucosal congestion, nasal polyp formation, and systemic steroids. PMID:14680616

  16. Chemoattractant-induced release of elastase by lipopolysaccharide (LPS)-primed neutrophils; inhibitory effect of the anti-inflammatory drug nimesulide.

    PubMed

    Ottonello, L; Barbera, P; Dapino, P; Sacchetti, C; Dallegri, F

    1997-10-01

    Human neutrophils, pre-exposed to low concentrations (1-10 ng/ml) of bacterial LPS in the presence of 1% autologous serum, released elastase activity in response to N-formyl-met-leu-phe (fMLP). Both cell incubation with LPS without subsequent fMLP stimulus and fMLP stimulation without prior exposure to LPS failed to promote significant elastase release. Therefore, LPS primes neutrophils for the subsequent release of elastase in response to fMLP. Compared with fMLP, human recombinant C5a had a slight although not significant activity, whereas other chemoattractants such as IL-8, platelet-activating factor and leukotriene B4 were ineffective. The fMLP-induced response of LPS-primed neutrophils was susceptible to suppression by the methane-sulphonanilide anti-inflammatory drug nimesulide and RO 20-1724, which selectively inhibit cAMP-catabolizing phosphodiesterase type IV. This suggests that the elastase release by LPS-primed neutrophils is likely to be controlled by intracellular cAMP, and raises the possibility of limiting pharmacologically the elastase-mediated tissue injury during neutrophilic inflammation. PMID:9353161

  17. Chemoattractant-induced release of elastase by lipopolysaccharide (LPS)-primed neutrophils; inhibitory effect of the anti-inflammatory drug nimesulide

    PubMed Central

    OTTONELLO, L; BARBERA, P; DAPINO, P; SACCHETTI, C; DALLEGRI, F

    1997-01-01

    Human neutrophils, pre-exposed to low concentrations (1–10 ng/ml) of bacterial LPS in the presence of 1% autologous serum, released elastase activity in response to n-formyl-met-leu-phe (fMLP). Both cell incubation with LPS without subsequent fMLP stimulus and fMLP stimulation without prior exposure to LPS failed to promote significant elastase release. Therefore, LPS primes neutrophils for the subsequent release of elastase in response to fMLP. Compared with fMLP, human recombinant C5a had a slight although not significant activity, whereas other chemoattractants such as IL-8, platelet-activating factor and leukotriene B4 were ineffective. The fMLP-induced response of LPS-primed neutrophils was susceptible to suppression by the methane-sulphonanilide anti-inflammatory drug nimesulide and RO 20-1724, which selectively inhibit cAMP-catabolizing phosphodiesterase type IV. This suggests that the elastase release by LPS-primed neutrophils is likely to be controlled by intracellular cAMP, and raises the possibility of limiting pharmacologically the elastase-mediated tissue injury during neutrophilic inflammation. PMID:9353161

  18. 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

  19. 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

  20. Inactivation of alpha-1-proteinase inhibitor by neutrophil metalloproteinases. Crucial role of the myeloperoxidase system and effects of the anti-inflammatory drug nimesulide.

    PubMed

    Ottonello, L; Dapino, P; Dallegri, F

    1993-01-01

    Supernatants, obtained from normal neutrophil polymorphonuclear leukocytes (PMN), challenged with opsonized zymosan (OPZ), were found to inactivate the PMN elastase inhibitor, alpha 1-proteinase inhibitor (A1PI). As the supernatants were treated with methionine to quench residual oxidants, primarily chloramines, the observed inactivation of A1PI appears to be due to enzymes. The activity of the supernatants was in fact inhibited by metal-chelators and by the tissue inhibitor of metalloproteinases (TIMP), which is consistent with the intervention of metalloproteinases. Supernatants from normal PMN triggered by OPZ in the presence of inhibitors of the myeloperoxidase (MPO) system as well as supernatants from MPO-deficient PMN were inactive but displayed the capacity of inactivating A1PI after treatment with the metalloproteinases activator 4-aminophenylmercuric acetate. These data suggest that the A1PI inactivation is due to metalloenzymes released by PMN as latent molecules, in turn activated by the MPO system. The MPO-dependent autoactivation of latent metalloenzymes by PMN, with consequent A1PI inactivation, was inhibited by the nonsteroidal anti-inflammatory drug nimesulide (NMS). As PMN-derived HOCl is well known to inactivate A1PI directly, through a process previously shown to be inhibitable by NMS, the present results suggest: (1) both the oxidative and proteolytic inactivation of A1PI depend on the HOCl-generating MPO system; (2) the tissue-destructive activity of PMN elastase could be controlled by interfering pharmacologically with the PMN-MPO system, directly and indirectly responsible for the breakdown of the tissue antielastase screen. PMID:8385794

  1. 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. PMID:24295369

  2. Comparison of analgesic effects of nimesulide, paracetamol, and their combination in animal models

    PubMed Central

    Ahmed, Mushtaq; Upadhyaya, Prerna; Seth, Vikas

    2010-01-01

    Objectives: To compare the analgesic activity of nimesulide and paracetamol alone and their combination in animal models for the degree of analgesia and the time course of action. Materials and Methods: Analgesia was studied in albino rats using formalin test and in albino mice using writhing test and the radiant heat method. For each test, four groups of six animals each were orally fed with a single dose of nimesulide, paracetamol, and combination of nimesulide + paracetamol and gum acacia as control, respectively. Results: In all the three test models, all three drug treatments showed significant analgesia (P < 0.001) as compared to control, but there was no significant difference in the analgesia produced by either drugs alone or in combination. The radiant heat method demonstrated a quicker onset and longer duration of action with nimesulide, whereas writhing test showed a quicker onset of action with paracetamol. In formalin test, greater degree of analgesia was seen with individual drugs than that of the combination, though this difference was not statistically significant. Conclusions: Nimesulide and paracetamol combination offers no advantage over nimesulide alone or paracetamol alone, either in terms of degree of analgesia or onset of action. Therefore, our study supports the reports claiming irrationality of the fixed dose combination of nimesulide and paracetamol. PMID:21189904

  3. 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

  4. 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

  5. Recent contributions to knowledge of the mechanism of action of nimesulide.

    PubMed

    Bevilacqua, M; Magni, E

    1993-01-01

    Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) of the sulfonanilide class. Its anti-inflammatory, analgesic and antipyretic activities have been demonstrated in several widely used animal experimental models and in numerous clinical trials. Nimesulide only weakly inhibits prostaglandin synthesis and appears to exert its effects through various mechanisms. It inhibits the release of oxidants from activated neutrophils and has a scavenging effect on hypochlorous acid without affecting neutrophil function. Nimesulide also decreases histamine release from tissue mast cells and inhibits the production of platelet-activating factor by human basophils. Furthermore, when added in vitro to cultures of human articular chondrocytes, nimesulide inhibits the release of stromelysin and blocks metalloproteinase activity. PMID:7506193

  6. Aspirin desensitization in aspirin-exacerbated respiratory disease.

    PubMed

    White, Andrew A; Stevenson, Donald D

    2013-05-01

    Although aspirin desensitization was discovered in 1922, it was not until 1979 that a therapeutic use for aspirin treatment, under the protection of desensitization, was discovered. In the last 33 years, details of aspirin treatment have been refined to the point where it is now recognized and accepted as a major therapeutic intervention in the treatment of aspirin-exacerbated respiratory disease, with therapeutic efficacy in approximately two-thirds of patients. It is only effective in patients who have aspirin-exacerbated respiratory disease and none of the other nonsteroidal anti-inflammatory drugs, despite their cross-reactive inhibition of cyclooxygenase-1, can effectively take the place of aspirin. PMID:23639709

  7. Aspirin overdose

    MedlinePlus

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

  8. Antioxidant activity of nimesulide and its main metabolites.

    PubMed

    Facino, R M; Carini, M; Aldini, G

    1993-01-01

    The antioxidant activity of nimesulide and its main metabolites, 4'-hydroxynimesulide (M1) and 2-(4'-hydroxyphenoxy)-4-N-acetylamino-methansulfonanilide (M2), was investigated using 2 in vitro models: NADPH-supported lipid peroxidation in rat liver microsomes (marker MDA formation) and xanthine/xanthine oxidase, iron-promoted depolymerisation of hyaluronic acid, determined by gel permeation chromatographic analysis (marker molecular weight distribution). In the lipid peroxidation model, all the compounds inhibited MDA formation in a concentration-dependent manner, although with different potencies; the maximum scavenging effect was observed for M1 [50% inhibitory concentration (IC50) = 30 mumol/L; M2 IC50 = 0.5 mmol/L; nimesulide = 0.8 mmol/L]. Nimesulide was more active than its metabolites in preventing OH-induced depolymerisation of hyaluronic acid, with a 50% effective concentration of approximately 230 mumol/L, which was fairly comparable to that of tenoxicam. This protective effect was due to the OH.-entrapping capacity of the drug, which, in the Fenton-driven model, is easily converted, via OH. attack, to M1 and putatively to 2-hydroxy-4-nitro-methansulfonanilide. PMID:7506157

  9. 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.

  10. Inhibition of the neutrophil oxidative response induced by the oral administration of nimesulide in normal volunteers.

    PubMed

    Ottonello, L; Dapino, P; Pastorino, G; Dallegri, F

    1992-01-01

    The superoxide (O2) production by phagocytes (neutrophils plus monocytes) and the lactoferrin release by neutrophils were measured in normal volunteers before and after the oral administration of the anti-inflammatory drug nimesulide. The chemotactic factor N-formylmethionyl-leucyl-phenylalanine (FMLP) and opsonized zymosan particles (OPZ) were used as activating stimuli. The oral administration of nimesulide lowered the phagocyte ability to generate O2- in response to both FMLP (percent inhibition = 67.62) and OPZ (percent inhibition = 36.75). The lactoferrin release by neutrophils was unaffected, proving that the drug does not affect the exocytosis of specific granules. The results provide direct evidence that the oral administration of nimesulide efficiently reduces the oxidative potential of phagocytes, particularly neutrophils, without interfering with mechanisms related to exocytosis of specific granules and involved in the amplification of the cell responses to inflammatory mediators. PMID:1340506

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

    PubMed

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

    2000-07-01

    The aim of the present work was to study in vivo COX-2-COX-1 selectivity of 16 nonsteroidal anti-inflammatory drugs (NSAIDs) in equipotent ulcerogenic doses in two in vivo experimental models. Indomethacin, ibuprofen, nimesulide, aceclofenac, aspirin, sodium diclofenac, meloxicam, naproxene, paracetamol, piroxicam, tenoxicam, nabumetone, ketoprofen, mefenamic acid, etodolac, and ketorolac were administered to female Wistar rats (N = 10 each group). In experiment I, solid food plus subcutaneous NSAIDs were given. In experiment II, NSAIDs were given by oral gavage and in bolus. Macroscopic gastric antral ulcer area (30%) and intestinal erosiva area (295 mm2) in experiment I and necrotic gastric fundus area (65%) and erosive intestinal area (182 mm2), "in vivo" the NSAIDs COX-1 was showed. Neutrofilia assessed in gastric intestinal mucosa where also ibuprofen and paracetamol not given neotrophilic infiltration. In conclusion, COX-2-COX-1 selectivity was demonstrated in vivo with the drugs aceclofenac, nabumetone, meloxicam, nimesulide, and paracetamol. PMID:10961715

  12. 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

  13. 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

  14. 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.

  15. 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 ...

  16. 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.

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

    PubMed Central

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

    1998-01-01

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

  18. 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... ANDA that does not refer to a listed drug. TALWIN COMPOUND (aspirin; pentazocine HCl) tablets, 325...

  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. PMID:27312830

  20. 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

  1. Design and content determination of nimesulide injectable formulation.

    PubMed

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

    2015-07-01

    The aim of the present study was to formulate Nimesulide inject able solution, establish a method for content determination, and accumulate data for registration of a new Nimesulide formulation. The optimal Nimesulide inject able formulation was determined based on the results of single factor test and orthogonal test. Moreover, clarity, stability, pH, content and related substances of Nimesulide were used as the main study indicators. The content of Nimesulide in inject able solution was determined by the high performance liquid chromatography (HPLC) method. The mobile phase consisted of V (methanol): V (potassium dihydrogen phosphate, pH 4.2)=60:40 at a flow rate of 1.0 mL/min. The detection was carried out with UV detector (λ(max) =254 nm) under a column temperature of 25°C and an injection volume of 20μL. The optimal inject able formulation was 4% Nimesulide, 4% ethanolamine, 0.1% L-cysteine, 0.01% EDTA-2Na, a suitable amount of lactic acid and water for injection. Nimesulide detection limits range from 20 to 80 μg/mL with a correlation coefficient of 0.9995 and high average recovery 99.91% (RSD=0.06%). In conclusion, the formulation was suitable for Nimesulide inject able form, and the determination method was simple, sensitive and accurate. Therefore, the Nimesulide inject able formulation can be used for industrial production and effectively controlled. PMID:26142510

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

    PubMed Central

    Schmidt, Morten; Hallas, Jesper; Friis, Søren

    2014-01-01

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

  3. Aspirin overdose

    MedlinePlus

    Acetylsalicylic acid (aspirin) can be found in many prescription and over-the-counter pain relievers, including: Alka Seltzer Anacin Bayer Bufferin Ecotrin Excedrin Fiorinal Percodan St. Joseph's Note: This list may not be all-inclusive.

  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. PMID:24691893

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

    PubMed

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

    2016-07-15

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

  6. 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

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

    PubMed

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-11-01

    Given conflicting data on temporal variability in pharmacodynamic platelet responses to clopidogrel, we investigated platelet reactivity on clopidogrel and aspirin for up to six months after elective percutaneous coronary intervention (PCI) with drug-eluting stents. Platelet reactivity was determined in 102 patients before loading with clopidogrel and aspirin, and on maintenance therapy after PCI on day 1, at one month and six months by VerifyNow™ P2Y12 and Aspirin assays and by residual platelet aggregation (RPA) on light transmission aggregometry using adenosine diphosphate and arachidonic acid. By VerifyNow testing, median (interquartile range) P2Y12 reaction units (PRU) on clopidogrel were 166 (90-234), 195 (124-257), and 198 (141-252) on day 1, one month and six months after PCI, respectively (p=0.005 day 1 to 1 month, and p=0.86 1 month to 6 months). Using a cut-off of > 208 PRU, 35 % of patients had high platelet reactivity (HPR) to clopidogrel on day 1, 43 % at one month, and 46 % at six months after PCI. Between day 1 and six months after PCI, 38.2 % of patients changed clopidogrel responder status at least once. Other cut-offs and RPA yielded similar results. Platelet inhibition by aspirin was consistent over time with only five patients being characterised as having HPR. Considerable variation in individual on-clopidogrel platelet reactivity was present during both the subacute and the late phases of maintenance therapy after elective PCI. Hence, the utility of contemporary platelet function testing to guide antiplatelet therapy may be limited. PMID:26305340

  10. 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

  11. 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

  12. 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)...

  13. 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.

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

    PubMed

    Starek, Małgorzata; Krzek, Jan

    2009-01-15

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the group most often used in human health care, since they are available without prescription for treatment of fever and minor pain. The present review submitted the use of various analytical techniques for the determination of oxicams, nimesulide and nabumetone. This review covers the time period from 1990 to 2008 during which over 200 analytical methods including all types of chromatographic, spectrophotometric and voltammetric techniques were reported. Presented application concerns analysis of chosen NSAIDs from pharmaceutical formulations and biological samples. PMID:19064072

  15. Tablet formulation studies on nimesulide and meloxicam-cyclodextrin binary systems.

    PubMed

    Nalluri, Buchi N; Chowdary, K P R; Murthy, K V R; Becket, G; Crooks, Peter A

    2007-01-01

    The objective of this work was to develop tablet formulations of nimesulide-beta-cyclodextrin (NI-beta-CD) and meloxicam-gamma-cyclodextrin (ME-gamma-CD) binary systems. In the case of nimesulide, 3 types of binary systems--physical mixtures, kneaded systems, and coevaporated systems--were studied. In the case of meloxicam, 2 types of binary systems--physical mixtures and kneaded systems--were investigated. Both drug-CD binary systems were prepared at 1:1 and 1:2 molar ratio (1:1M and 1:2M) and used in formulation studies. The tablet formulations containing drug-CD binary systems prepared by the wet granulation and direct compression methods showed superior dissolution properties when compared with the formulations of the corresponding pure drug formulations. Overall, the dissolution properties of tablet formulations prepared by the direct compression method were superior to those of tablets prepared by the wet granulation method. Selected tablet formulations showed good stability with regard to drug content, disintegration time, hardness, and in vitro dissolution properties over 6 months at 40 degrees C +/- 2 degrees C and 75% relative humidity. PMID:17622114

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

    PubMed Central

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

    2015-01-01

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

  17. 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.

  18. From COX-2 inhibitor nimesulide to potent anti-cancer agent: synthesis, in vitro, in vivo and pharmacokinetic evaluation

    PubMed Central

    Chennamaneni, Snigdha; Yi, Xin; Liu, lili; Pink, John J.; Dowlati, Afshin; Xu, Yan; Zhou, Aimin; Su, Bin

    2014-01-01

    Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure–function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC50s around 100nM to 200nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC50s around 100nM to 500nM. Intraperitoneal injection with a dosage of 5mg/kg/d of CSUOH0901 to nude mice suppresses HT29 colorectal xenograft growth. Pharmacokinetic studies demonstrate the good bioavailability of the compound. PMID:22119125

  19. 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

  20. Quantification of nimesulide in human plasma by high-performance liquid chromatography/tandem mass spectrometry. Application to bioequivalence studies.

    PubMed

    Barrientos-Astigarraga, R E; Vannuchi, Y B; Sucupira, M; Moreno, R A; Muscará, M N; De Nucci, G

    2001-12-01

    A method based on liquid chromatography with negative ion electrospray ionization and tandem mass spectrometry is described for the determination of nimesulide in human plasma. Liquid-liquid extraction using a mixture of diethyl ether and dichloromethane was employed and celecoxib was used as an internal standard. The chromatographic run time was 4.5 min and the weighted (1/x) calibration curve was linear in the range 10.0-2000 ng x ml(-1). The limit of quantification was 10 ng x ml(-1), the intra-batch precision was 6.3, 2.1 and 2.1% and the intra-batch accuracy was 3.2, 0.3 and 0.1% for 30, 300 and 1200 ng x ml(-1) respectively. The inter-batch precision was 2.3, 2.8 and 2.7% and the accuracy was 3.3, 0.3 and 0.1% for 30, 300 and 1200 ng x ml(-1) respectively. This method was employed in a bioequivalence study of one nimesulide drop formulation (nimesulide 50 mg x ml(-1) drop, Medley S/A Indústria Farmacêutica, Brazil) against one standard nimesulide drop formulation (Nisulid, 50 mg x ml(-1) drop, Astra Médica, Brazil). Twenty-four healthy volunteers (both sexes) took part in the study and received a single oral dose of nimesulide (100 mg, equivalent to 2 ml of either formulation) in an open, randomized, two-period crossover way, with a 2-week washout interval between periods. The 90% confidence interval (CI) for geometric mean ratios between nimesulide and Nisulid were 93.1-109.6% for C(max), 87.7-99.8% for AUC(last) and 88.1-99.7% for AUC(0-infinity). Since the 90% CI for the above-mentioned parameters were included in the 80-125% interval proposed by the US Food and Drug Administration, the two formulations were considered bioequivalent in terms of both rate and extent of absorption. PMID:11754119

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

    PubMed Central

    2014-01-01

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

  2. Aspirin: Pharmacology and Clinical Applications

    PubMed Central

    Paez Espinosa, Enma V.; Murad, John P.; Khasawneh, Fadi T.

    2012-01-01

    Antiplatelet therapy has been documented to reduce risks of cardiovascular disease after acute myocardial infarction, coronary artery bypass graft, and in chronic atrial fibrillation patients, amongst other risk factors. Conventional management of thrombosis-based disorders includes the use of heparin, oral anticoagulants, and the preferred antiplatelet agent aspirin. Interestingly, aspirin was not intended to be used as an antiplatelet agent; rather, after being repurposed, it has become one of the most widely prescribed antithrombotic drugs. To this end, there have been several milestones in the development of antiplatelet agents in the last few decades, such as adenosine diphosphate receptor inhibitors, phosphodiesterase inhibitors, and GPIIb/IIIa inhibitors. However, given some of the limitations of these therapies, aspirin continues to play a major role in the management of thrombotic and cardiovascular disorders and is expected to do so for years to come. PMID:22195279

  3. 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

  4. 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

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

    PubMed

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

    2016-08-15

    Isomeric iodinated derivatives of nimesulide, with an iodine substituent on the phenoxy ring, were prepared with the aim of identifying potential candidate compounds for the development of imaging agents targeting cyclooxygenase-2 (COX-2) in the brain. Both the experimental logP7.4 and pKa values for these iodinated analogs were in the acceptable range for passive brain penetration. The para-iodo-substituted analog was a more potent and selective COX-2 inhibitor than nimesulide, with a potency that was comparable to the reference drug, celecoxib. Iodination at the ortho- or meta-position of the phenoxy ring was associated with a substantial loss of COX-2 inhibitory activity. Transport studies across Caco-2 cell monolayers in the presence and absence of a P-glycoprotein (P-gp) inhibitor, verapamil, indicated that the para-iodo-substituted analog was not a P-gp transport substrate; this feature is a prerequisite for potential in vivo brain imaging compounds. The para-iodo-substituted analog of nimesulide appears to be an attractive candidate for the development of radioiodine-labeled tracers for in vivo brain imaging of COX-2 levels. PMID:27325447

  6. Safety of nimesulide, meloxicam and rofecoxib as alternative analgesics.

    PubMed

    Karakaya, G; Kalyoncu, A F

    2000-01-01

    Paracetamole and codeine are safe alternative analgesics for analgesic intolerant patients. Recently marketed selective and specific COX2 inhibitors are also considered to be safe for this group of patients. In this survey we wanted to disclose the safety of nimesulide and meloxicam and rofecoxib where they have been marketed recently in Turkey. PMID:11269899

  7. 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…

  8. 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

  9. 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. PMID:19152549

  10. 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. PMID:22751909

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

    PubMed

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

    2016-05-20

    We explored nonsteroidal anti-inflammatory drug (NSAID) and aspirin (ASA) use and mortality in the U.S. Department of Health and Human Services' registry of 683 adult and 838 pediatric critically ill pandemic 2009 H1N1 influenza (pH1N1) patients. Among adults, 88 (12.9%) and 101 (14.8%) reported pre-admission use of an NSAID and ASA, respectively; mortality was similar (23-24%) regardless of NSAID or ASA use. Mortality among 89 pediatric NSAID users and 749 nonusers did not differ significantly (10.1% and 8.8%, respectively). One of 16 pediatric ASA users died. Among pediatric patients, the adjusted relative risk estimate for NSAID use and 90-day mortality was higher when influenza vaccination was included in the model (risk ratio [RR] = 1.5; 95% confidence interval, 0.7-3.2), although not statistically significant. Among adults, RR estimates did not change appreciably after adjusting for age, sex, health status, or vaccine status. We found no compelling evidence that NSAID or ASA use influenced mortality in severe pH1N1. PMID:26255728

  12. Aspirin hypersensitivity.

    PubMed

    Sánchez-Borges, Mario

    2014-01-01

    Hypersensitivity reactions to acetylsalicylic acid and non-steroidal anti-inflammatory drugs constitute a major medical concern worldwide. This article presents an overview of the observations that led to the discovery of cyclooxygenase inhibitors, as a prerequisite to better understand the basic concepts supporting seminal investigations carried out in order to elucidate the clinical features, pathogenic mechanisms, diagnosis and modern management of these common conditions. There are some unmet needs in this clinical area which will have to be solved in the future, especially concerning the pathogenesis of these reactions and the availability of novel in vitro diagnostic methods sparing both patient and physician of the risks inherent to in vivo provocation tests. PMID:24925393

  13. 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

  14. 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…

  15. A phase III trial evaluating the efficacy and tolerability of nimesulide 1% spray in patients with soft-tissue injuries

    PubMed Central

    Khan, Mazharuddin Ali; Rao, Madhusudhan; Reddy, Madan M.; Tamloorker, Datta; Gumdal, Vishesh; Latha, Moodahadu S.; Krishnankutty, Binny

    2013-01-01

    Aim: To evaluate the efficacy and safety of nimesulide 1% w/w spray in minor soft-tissue injuries in adult Indians through a multicentric, open-labeled, phase III trial. Materials and Methods: 125 eligible patients, who met the selection criteria and gave written informed consent, were screened, enrolled, and treated with nimesulide 1% spray for seven days. Patients were assessed at baseline, day 1, day 4, and day 8 for efficacy and safety. Primary efficacy variable pain intensity, was measured using a NRS 1-100 mm (numerical rating scale). Secondary efficacy variables were degree of inflammation and edema and degree of functional impairment; overall assessment of efficacy was done by patient (patient global assessment – PGA) and by investigator (investigator global assessment – IGA) on days 4 and 8. Result: There was a statistically significant reduction in the NRS score, degree of pain, edema (inflammation), and improvement in functional impairment on days 4 and 8 and in serum creatine kinase levels on day 8 in comparison with baseline. Global assessment of efficacy on day 8 was rated as “very good (21%),” “good (67.70%),” and “fair (11.30%)” by investigators and “very good (25%),” “good (58.90%),” and “fair (16.1%)” by patients. Two mild adverse events were reported in two patients, which resolved without any intervention. One (local irritation) was reported as not related, while the other (itching sensation) was probably related to the study drug. Conclusion: Nimesulide 1% spray was effective with a good safety profile and can be considered is a good alternative to oral analgesic therapy in minor soft-tissue injuries. PMID:23724380

  16. 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

  17. 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

  18. Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway.

    PubMed

    Huang, Nanxin; Chen, Dong; Wu, Xiyan; Chen, Xianjun; Zhang, Xuesi; Niu, Jianqin; Shen, Hai-Ying; Xiao, Lan

    2016-07-01

    Aspirin, one of the most commonly used anti-inflammatory drugs, has been recently reported to display multiple effects in the central nervous system (CNS), including neuroprotection and upregulation of ciliary neurotrophic factor (CNTF) expression in astrocytes. Although it was most recently reported that aspirin could promote the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) after white matter lesion, the underlying mechanisms remain unclear. To dissect the effects of aspirin on oligodendroglial development and explore possible mechanisms, we here demonstrated the following: (i) in vitro treatment of aspirin on OPC cultures significantly increased the number of differentiated oligodendrocytes (OLs) but had no effect on the number of proliferative OPCs, indicating that aspirin can promote OPC differentiation but not proliferation; (ii) in vivo treatment of aspirin on neonatal (P3) rats for 4 days led to a nearly twofold increase in the expression of myelin basic protein (MBP), devoid of change in OPC proliferaion, in the corpus callosum (CC); (iii) finally, aspirin treatment increased the phosphorylation level of β-catenin and counteracted Wnt signaling pathway synergist QS11-induced suppression on OPC differentiation. Together, our data show that aspirin can directly target oligodendroglial lineage cells and promote their differentiation through inhibition of Wnt/β-catenin signaling pathway. These findings suggest that aspirin may be a novel candidate for the treatment of demyelinating diseases. PMID:26059811

  19. 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

  20. 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

  1. Activation of the bile acid receptor GPBAR1 protects against gastrointestinal injury caused by nonsteroidal anti-inflammatory drugs and aspirin in mice

    PubMed Central

    Cipriani, Sabrina; Mencarelli, Andrea; Bruno, Angela; Renga, Barbara; Distrutti, Eleonora; Santucci, Luca; Baldelli, Franco; Fiorucci, Stefano

    2013-01-01

    Background and Purpose Low doses of aspirin (acetylsalicylic acid; ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of gastrointestinal bleeding. GPBAR1 is a bile acid receptor expressed in the gastrointestinal tract. Here, we have investigated whether GPBAR1 was required for mucosal protection in models of gastrointestinal injury caused by ASA and NSAIDs. Experimental Approch GPBAR1+/+ and GPBAR1−/− mice were given ASA (10–50 mg.kg−1) or naproxen. Gastric and intestinal mucosal damage was assessed by measuring lesion scores. Key Results Expression of GPBAR1, mRNA and protein, was detected in mouse stomach. Mice lacking GPBAR1 were more sensitive to gastric and intestinal injury caused by ASA and NSAIDs and exhibited a markedly reduced expression of cystathionine-γ-liase (CSE), cystathionine-β-synthase (CBS) and endothelial NOS enzymes required for generation of H2S and NO, in the stomach. Treating GPBAR1+/+ mice with two GPBAR1 agonists, ciprofloxacin and betulinic acid, rescued mice from gastric injury caused by ASA and NSAIDs. The protective effect of these agents was lost in GPBAR1−/− mice. Inhibition of CSE by DL-propargylglycine completely reversed protection afforded by ciprofloxacin in wild type mice, whereas treating mice with an H2S donor restored the protective effects of ciprofloxacin in GPBAR1−/− mice. Deletion of GPBAR1 altered the morphology of the small intestine and increased sensitivity to injury caused by naproxen. Conclusion and Implications GPBAR1 is essential to maintain gastric and intestinal mucosal integrity. GPBAR1 agonists protect against gastrointestinal injury caused by ASA and NSAIDs by a COX-independent mechanism. PMID:22881598

  2. [Asthma and aspirin].

    PubMed

    Schiappoli, Michele; Gani, Federica; Frati, Francesco; Marcucci, Francesco; Senna, Gianenrico

    2003-02-01

    Aspirin (ASA) is an important cause of asthma so that ASA induced asthma (AIA) is considered a disease. Its prevalence is of 0.3-0.6 in the general population but it raises to 21% in the asthmatic one. Middle aged female are the most affected. AIA generally begins with a non allergic rhinitis, complicated sometimes with polyps, that evolves secondarily in asthma. The disease is often so severe to need oral corticosteroids to be controlled. It persists independently to the intake of ASA. From a pathogenetic point of view the interaction of ASA with the arachidonic acid metabolism seems to be important. The inhibition of cyclo-oxygenase (COX) induces an activation of lypo-oxygenase with an increased synthesis of leukotrienes. In ASA intolerant patients there is also an activation of LTC4 synthetase, enzyme responsible for the synthesis of leukotrienes. Clinical history is very important to diagnose the disease but to confirm the diagnosis sometimes the provocation test is mandatory. Oral and bronchial challenges can be dangerous, while nasal challenge is safer even if must be better standardized. Patients must not use antiinflammatory drugs with the same mechanism of action of ASA; COX-2 inhibitors are generally well tolerated. Antileukotrienes are useful to treat asthma, in association with steroids. Desensitization can be used in very selected patients. PMID:12908375

  3. From COX-2 inhibitor nimesulide to potent anti-cancer agent: synthesis, in vitro, in vivo and pharmacokinetic evaluation.

    PubMed

    Zhong, Bo; Cai, Xiaohan; Chennamaneni, Snigdha; Yi, Xin; Liu, Lili; Pink, John J; Dowlati, Afshin; Xu, Yan; Zhou, Aimin; Su, Bin

    2012-01-01

    Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure-function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC(50)s around 100 nM-200 nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC(50)s around 100 nM-500 nM. Intraperitoneal injection with a dosage of 5  mg/kg/d of CSUOH0901 to nude mice suppresses HT29 colorectal xenograft growth. Pharmacokinetic studies demonstrate the good bioavailability of the compound. PMID:22119125

  4. 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. PMID:26475526

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

    PubMed Central

    Kacprzak, Dorota

    2015-01-01

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

  6. 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 ...

  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. Nimesulide-modified gum karaya solid mixtures: preparation, characterization, and formulation development.

    PubMed

    Babu, G V Murali Mohan; Kumar, N Ravi; Himasankar, K; Seshasayana, A; Murthy, K V Ramana

    2003-09-01

    Solid mixtures of nimesulide (NS) and modified gum karaya (MGK) were prepared to improve the dissolution rate of NS. The effect of drug-carrier ratio on dissolution rate of NS was investigated by preparing the solid mixtures of different ratios by cogrinding method. Solid mixtures were also prepared by physical mixing, kneading, and solid dispersion techniques to study the influence of method of preparation. Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and equilibrium solubility studies were performed to explain the results of in vitro dissolution rate studies. It was clearly evident from the results that the NS dissolution rate was dependent on the concentration of MGK in the solid mixtures, and optimum weight ratio was found to be 1:4 (NS:MGK). Though the dissolution rate of NS from all solid mixtures prepared by different methods improved significantly, maximum improvement in dissolution rate was observed with solid dispersions. The order of methods basing on their effect on dissolution efficiency is solid dispersion > kneading > cogrinding > physical mixing > pure NS. Tablets of pure drug and solid mixtures (1:4 w/w, NS:MGK) were prepared. Though the best results from the dissolution test were obtained for the tablets containing solid dispersions, tablets containing cogrinding mixture were found to be suitable, from a practical point of view, for commercialization. PMID:14570306

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

    PubMed

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

    2015-01-01

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

  10. Nondestructive and Rapid Concurrent Estimation of Paracetamol and Nimesulide in Their Combined Dosage Form Using Raman Spectroscopic Technique

    PubMed Central

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

    2013-01-01

    A rapid, nondestructive Raman spectroscopic method was developed for quantitative estimation of paracetamol and nimesulide in their combined dosage form. A Raman univariate calibration model was developed by measuring the peak intensities of paracetamol and nimesulide at 853 cm−1 and 1336 cm−1, respectively. The developed method was successfully applied for in situ, concurrent estimation of paracetamol and nimesulide in their combined dosage and method was also validated according to International Conference on Harmonisation guidelines. Thus, the developed Raman spectroscopic method can be applied for simultaneous estimation of paracetamol and nimesulide in their combined dosage form as a process analytical technology tool by pharmaceutical industries for routine quality control. PMID:24019571

  11. 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

  12. 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

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

    PubMed

    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

  14. 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

  15. 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

  16. 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

  17. 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

  18. [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

  19. Drug Reactions

    MedlinePlus

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as gingko and blood thinners ...

  20. 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

  1. 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.

  2. 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.

  3. Microencapsulation: an acclaimed novel drug-delivery system for NSAIDs in arthritis.

    PubMed

    Manjanna, K M; Shivakumar, B; Pramod Kumar, T M

    2010-01-01

    Arthritis refers to different medical conditions associated with disorders of the primary structures that determine joint functioning, such as bones, cartilage, and synovial membranes. Drug discovery and delivery to retard the degeneration of joint tissues are challenging. Current treatment of different types of arthritis such as osteoarthritis, rheumatoid arthritis, septic arthritis, juvenile idiopathic arthritis, and ankylosing spondylitis involves the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, diclofenac, aceclofenac, ibuprofen, flurbiprofen, indomethacin piroxicam, dexibuprofen, ketoprofen, nabumetone, nimesulide, and naproxen, mainly by the oral, parenteral, or topical route. However, the frequent dosing that is required with NSAIDs often leads to patient noncompliance, so drug-delivery technologies should be developed to reduce the frequency of dosing and to allow sustained release of medications. Microencapsulation is one of the novel drug-delivery technologies employed to sustain drug release. This method reduces dosing and eliminates gastrointestinal irritation, thus ultimately improving patient compliance in the pharmacotherapy of arthritis. We provide a comprehensive overview of several microencapsulation technologies used in the treatment of arthritis that may reduce the dose-related adverse effects caused by NSAIDs. PMID:21175420

  4. 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.

  5. Nimesulide Improves the Symptomatic and Disease Modifying Effects of Leflunomide in Collagen Induced Arthritis

    PubMed Central

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

    2014-01-01

    Nimesulide is a COX-2 inhibitor used for symptomatic relief of rheumatoid arthritis. Leflunomide is an anti-pyrimidine used to manage the progression of rheumatoid arthritis. Herein we studied the influence of nimesulide and leflunomide combination in terms of disease symptoms and progression using collagen-induced arthritis model in mice, as a model for rheumatoid arthritis. Collagen induced arthritis was induced by immunization with type II collagen. Assessment of joint stiffness and articular hyperalgesia were evaluated using a locomotor activity cage and the Hargreaves method, respectively. Disease progression was assessed via arthritic index scoring, X-ray imaging, myeloperoxidase enzyme activity and histopathologic examination. Nimesulide induced only transient symptomatic alleviation on the top of decreased leucocytic infiltration compared to arthritis group. However, nimesulide alone failed to induce any significant improvement in the radiological or pathological disease progression. Leflunomide alone moderately alleviates the symptoms of arthritis and moderately retarded the radiological and pathological disease progression. Combination of nimesulide and leflunomide significantly improved symptomatic (analgesia and joint stiffness) and arthritic disease progression (radiological, pathological and Myeloperoxidase enzyme activity) in collagen induced arthritis animal model. PMID:25375820

  6. 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

  7. 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.

  8. 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

  9. Aspirin Delimits Platelet Life Span by Proteasomal Inhibition

    PubMed Central

    Nayak, Manasa K.; Dash, Ayusman; Singh, Nitesh; Dash, Debabrata

    2014-01-01

    Aspirin is widely used in clinical settings as an anti-inflammatory and anti-platelet drug due its inhibitory effect on cyclooxygenase activity. Although the drug has long been considered to be an effective and safe therapeutic regime against inflammatory and cardiovascular disorders, consequences of its cyclooxygenase-independent attributes on platelets, the key players in thrombogenesis, beg serious investigation. In this report we explored the effect of aspirin on platelet lifespan in murine model and its possible cytotoxicity against human platelets in vitro. Aspirin administration in mice led to significant reduction in half-life of circulating platelets, indicative of enhanced rate of platelet clearance. Aspirin-treated human platelets were found to be phagocytosed more efficiently by macrophages, associated with attenuation in platelet proteasomal activity and upregulation of conformationally active Bax, which were consistent with enhanced platelet apoptosis. Although the dosage of aspirin administered in mice was higher than the therapeutic regimen against cardiovascular events, it is comparable with the recommended anti-inflammatory prescription. Thus, above observations provide cautionary framework to critically re-evaluate prophylactic and therapeutic dosage regime of aspirin in systemic inflammatory as well as cardiovascular ailments. PMID:25126950

  10. 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

  11. 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.

  12. 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. PMID:11493722

  13. 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 ...

  14. 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

  15. 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...

  16. 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…

  17. 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

  18. 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

  19. Synergistic Drug-Cytokine Induction of Hepatocellular Death as an in vitro Approach for the Study of Inflammation-Associated Idiosyncratic Drug Hepatotoxicity

    PubMed Central

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

    2011-01-01

    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, IFNγ, IL-1α, 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-1α, 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. PMID:19362101

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

    PubMed

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

    2009-06-15

    Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFN gamma, IL-1 alpha, and IL-6. Using this assay, we observed drug-cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug-cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1 alpha, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug-cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity. PMID:19362101

  1. 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.

  2. Cyclooxygenase-2 inhibitor, nimesulide, improves radiation treatment against non-small cell lung cancer both in vitro and in vivo.

    PubMed

    Grimes, Kristopher R; Warren, Graham W; Fang, Fang; Xu, Yong; St Clair, William H

    2006-10-01

    Lung cancer is the leading cause of cancer-related deaths in the United States. Despite improvements in radiation, surgery and chemotherapy the 5 year survival statistics of non-small cell lung cancer (NSCLC) have improved little over the past two decades. It has been proposed that NF-kappaB is a participant in the cytoprotection against several redox-mediated therapeutic agents including ionizing radiation. Cyclooxygenase-2 (COX-2) inhibition has become an attractive target for enhancing the efficacy of radiation and chemotherapy. Numerous mechanistic pathways have been proposed as the means through which COX-2 inhibition enhances the efficacy of radiation. We hypothesize that the COX-2 inhibitor, nimesulide, will improve the efficacy of radiation therapy (RT), at least in part, via the suppression of NF-kappaB mediated cytoprotective pathways. In this study we used the COX-2 inhibitor nimesulide to improve the efficacy of RT when measured by tumor regrowth assays in vivo and clonegenic survival in vitro. For the in vivo assay, A549 tumor cells representing NSCLC were subcutaneously injected into the right flanks of female athymic nude mice (n=10/group). Mice were given nimesulide via drinking water at a concentration of 5 microg/g body weight (b.w.) and the water was replenished daily. Tumors were treated with 30 Gy fractionated radiation and measured bi-weekly. For our in vitro study, clonogenic survival assays were evaluated to determine the effect of nimesulide, radiation, and the combination. The NF-kappaB mediated mechanism of nimesulide was measured by Western blot analysis of NF-kappaB target genes, MnSOD and survivin. In vivo, mice that received combined treatments of 5 microg/g b.w. nimesulide and 30 Gy radiation (3 Gy/fraction, 10 daily fractions) had significant reduction in tumor size in comparison to the 30 Gy radiation control group (p<0.05). In vitro, nimesulide alone produced a significant decrease in clonogenic survival at doses from 0-300 micro

  3. [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

  4. Aspirin: from a historical perspective.

    PubMed

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

    2012-04-01

    Aspirin is one of the oldest medicines. Due to its wide range usage in different fields of medicine, we aimed to present the history, effects and different uses of aspirin in this review. Furthermore, recent patents of novel pharmaceutical interventions in the field of acetylsalicylic acid, expanding treatment options are presented. Literature search was performed in order to reach data and present information about aspirin from a historical perspective. Since its first use as a pain killer, aspirin has found a broad range of use in general medicine, cardiovascular medicine, neurology, obstetrics and gynecology, dentistry, gastroenterology, oncology with its different effects. Aspirin, a painkilling gift of history to mankind, with a history dating back to BC and various healing effects, promises to be of greater use in different fields of medicine with the light of recent studies, inspiring more research and gaining more popularity. PMID:22257089

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

    PubMed

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

    2016-01-01

    1. Warfarin and aspirin are widely used in a wide spectrum of thromboembolic and atherothrombotic diseases. Despite the potential efficacy of warfarin-aspirin therapy, the safety and side effect of combined therapy remains unclear. 2. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and aspirin in beagles after single and multiple doses. 3. Coadministration of aspirin had no significant effects on the area under the plasma concentration time curve (AUC(0-t)) and maximum plasma concentration (Cmax) of R- and S-warfarin after a single dose of warfarin, but significantly increase the AUC(0-t) and Cmax and dramatically decrease the clearance (CL) of R- and S-warfarin after multiple dose of warfarin. Accordingly, there was a slight increase in the AUEC(0-t) and Emax of activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) after multiple dose of warfarin. 4. Coadministration of warfarin had no markedly effects on the AUC(0-t) and Cmax of aspirin and its metabolite salicylic acid after single or multiple dose of aspirin. Meanwhile, the AUEC(0-t) and Emax of inhibition of platelet aggregation (IPA) were not significantly affected by warfarin. 5. Our animal study indicated that coadministration of aspirin with warfarin can cause significant pharmacokinetic and pharmacodynamic drug-drug interactions in beagles. However, more studies are urgently needed to assess related information of warfarin-aspirin drug interactions in healthy volunteers or patients. PMID:26548565

  6. 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

  7. Per aspirin ad astra...

    PubMed

    Hartung, Thomas

    2009-12-01

    Taking the 110th anniversary of marketing of aspirin as starting point, the almost scary toxicological profile of aspirin is contrasted with its actual use experience. The author concludes that we are lucky that, in 1899, there was no regulatory toxicology. Adding, for the purpose of this article, a fourth R to the Three Rs, i.e. Realism, three reality-checks are carried out. The first one comes to the conclusion that the tools of toxicology are hardly adequate for the challenges ahead. The second one concludes that, specifically, the implementation of the EU REACH system is not feasible with these tools, mainly with regard to throughput. The third one challenges the belief that classical alternative methods, i.e. replacing animal test-based tools one by one, is actually leading to a new toxicology - it appears to change only patches of the patchwork, but not to overcome any inherent limitations other than ethical ones. The perspective lies in the Toxicology for the 21st Century initiatives, which aim to create a new approach from the scratch, by an evidence-based toxicology and a global "Human Toxicology Programme". PMID:20105011

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

    PubMed

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

    2014-07-01

    Simple and cost effective study consisting of three steps, comparison of micromeritic properties of different blends i.e. placebo without API and Nimesulide containing, Use of central composite design (CCRD) for intermediate release Nimesulide tablets and stability results of three selected Nimesulide tablet formulations which were calculated by using R Gui. Different concentrations of Avicel, hydroxypropyl methyl cellulose (HPMC) and magnesium stearate were used as variables in central composite design and two types blend i.e., with or without Nimesulide were selected for bulk density, tap density, percentage compressibility; angle of repose and Hausner's ratio. Blending rate constant was performed after applying the different mixing times like 3, 6, 9 and 12 minutes. Twenty intermediate release formulations were designed and three formulations were chosen for compression by direct compression method on the basis of compressibility index. Physicochemical properties and best release pattern in four hours in different dissolution medium were successfully measured. Relative densities, porosity of tablets were compared with tensile strength of tablet and weight variation, hardness, friability and dissolution was performed by simple experiments. Presence of Nimesulide in the bulk increased all micromeratic tests while 9 minutes was best mixing time. The hardness of NM containing tablets increased with the increase of relative density. The release pattern was further analyzed by model dependent i.e. zero order, first order and Higuchi, Korse-meyer and Pappas, Hixson Crowell and model independent kinetic model i.e., f2 value respectively. R Gui explained the F16 formulation shows the best result in stability studies with shelf life 72 months. PMID:25015441

  9. Histone deacetylase inhibitors and aspirin interact synergistically to induce cell death in ovarian cancer cells.

    PubMed

    Sonnemann, Jürgen; Hüls, Isabel; Sigler, Michael; Palani, Chithra D; Hong, Le Thi Thu; Völker, Uwe; Kroemer, Heyo K; Beck, James F

    2008-07-01

    Histone deacetylase inhibitors (HDIs) as well as non-steroidal anti-inflammatory drugs including aspirin show promise as antineoplastic agents. The treatment with both HDIs and aspirin can result in hyperacetylation of proteins. In this study, we investigated whether HDIs and aspirin interacted in inducing anticancer activity and histone acetylation. We found that the HDIs, suberoylanilide hydroxamic acid and sodium butyrate, and aspirin cooperated to induce cell death in the ovarian cancer cell line, A2780. The effect was synergistic, as evidenced by CI-isobologram analysis. However, aspirin had no effect on histone acetylation, neither in the absence nor presence of HDIs. To gain insight into the mechanism underlying the synergistic action of HDIs and aspirin, we employed the deacetylated metabolite of aspirin, salicylic acid, and the cyclooxygenase-1- and -2-selective inhibitors, SC-560 and NS-398, respectively. We found that HDIs and salicylic acid interacted synergistically, albeit less efficiently than HDIs and aspirin, to induce cancer cell death, suggesting that the acetyl and the salicyl moiety contributed to the cooperative interaction of aspirin with HDIs. SC-560 and NS-398 had little effect both when applied alone or in conjunction with HDIs, indicating that the combinatorial effect of HDIs and aspirin was not the result of cyclo-oxygenase inhibition. In conclusion, our study demonstrates that HDIs and aspirin synergize to induce cancer cell death and, thus, provides a rationale for a more in-depth exploration into the potential of combining HDIs and aspirin as a strategy for anticancer therapy. PMID:18575740

  10. 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

  11. 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

  12. Comparison of aspirin and indobufen in healthy volunteers.

    PubMed

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

    2016-01-01

    The aim of this study is to quantify the extent and recovery of platelet inhibition after administration of indobufen and aspirin in healthy volunteers. Indobufen inhibits platelet aggregation by reversibly inhibiting the platelet cyclooxygenase enzyme, thereby suppressing thromboxane synthesis. Twenty healthy volunteers completed the study and received aspirin (200 mg/day for 2 weeks) followed by a 4-week washout period and then indobufen (200 mg twice a day for 2 weeks). The percent (%) inhibition of platelet aggregation (IPA) was assessed using arachidonic acid (0.5 mg/ml) and adenosine diphosphate (5 µM) at 4, 12, 24 and 48 hours after last dose of each drug. IPA assessed using arachidonic acid as the agonist was similar at 4 hours after the last dose of indobufen (81.07 ± 9.36%) and aspirin (96.99 ± 0.29%, p = 0.10), but significantly lower at 12 hours (74.04 ± 9.55% vs. 97.94 ± 0.28%, p = 0.02), 24 hours (33.39 ± 11.13% vs. 97.48 ± 0.32%, p < 0.001) and 48 hours (14.12 ± 9.74% vs. 98.22 ± 0.31%, p < 0.001) after indobufen, compared to the relative values for aspirin. IPA assessed using adenosine diphosphate as the agonist was similar in the two groups at 4, 12 and 24 hours after the last dose, but significantly lower 48 hours after the last dose of indobufen, compared to the relative value for aspirin (1.98 ± 3.57% vs. 12.61 ± 2.71%, p = 0.002). Indobufen (200 mg twice a day) caused equivalent initial inhibition of platelet aggregation to aspirin (200 mg daily), and the anti-aggregation effect diminished faster than after aspirin. PMID:26083594

  13. Pharmacometabolomics Reveals That Serotonin Is Implicated in Aspirin Response Variability

    PubMed Central

    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

  14. 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

  15. 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

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

    PubMed

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

    2016-03-01

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

  17. Gastric erosions induced by analgesic drug mixtures in the rat.

    PubMed

    Seegers, A J; Jager, L P; Van Noordwijk, J

    1978-02-01

    Gastric erosions after oral administration of analgesics separately and in admixture have been examined in adult rats. After administration of acetylsalicylic acid (aspirin), phenacetin, paracetamol and caffeine as single drugs, gastric erosions were only observed with aspirin. The combination of aspirin with phenacetin did not change, that of aspirin with caffeine significantly increased, and aspirin with paracetamol significantly decreased the incidence of gastric lesions compared with aspirin alone. The results for aspirin with paracetamol did not differ from those for the vehicle. Addition of caffeine to the combination of aspirin and phenacetin caused a significant increase in erosions, but when given with aspirin and paracetamol no erosions occurred. The mechanisms underlying the effects of these drugs on aspirin-induced erosions are discussed. PMID:24109

  18. Physicochemical characterization and dissolution properties of nimesulide-cyclodextrin binary systems.

    PubMed

    Nalluri, Buchi N; Chowdary, K P R; Murthy, K V R; Hayman, A R; Becket, G

    2003-01-01

    The objective of this work is physicochemical characterization of nimesulide-cyclodextrin binary systems both in solution and solid state and to improve the dissolution properties of nimesulide (N) via complexation with alpha-, beta, and gamma-cyclodextrins (CDs). Detection of inclusion complexation was done in solution by means of phase solubility analysis, mass spectrometry, and 1H nuclear magnetic resonance (1H-NMR) spectroscopic studies, and in solid state using differential scanning calorimetry (DSC), powder x-ray diffractometry (X-RD), scanning electron microscopy (SEM), and in vitro dissolution studies. Phase solubility, mass spectrometry and 1H-NMR studies in solution revealed 1:1 M complexation of N with all CDs. A true inclusion of N with beta-CD at 1:2 M in solid state was confirmed by DSC, powder X-RD and SEM studies. Dissolution properties of N-CD binary systems were superior when compared to pure N. PMID:12916912

  19. Decreased sensitivity to aspirin is associated with altered polyamine metabolism in human prostate cancer cells.

    PubMed

    Li, Jun; Cameron, Gary A; Wallace, Heather M

    2016-04-01

    Aspirin is a well-known analgesic, anti-inflammatory and antipyretic drug and is recognised as a chemopreventative agent in cardiovascular disease and, more recently, in colorectal cancer. Although several studies indicate that aspirin is capable of reducing the risk of developing cancers, there is a lack of convincing evidence that aspirin can prevent prostate cancer in man. In this study, aspirin was shown to be an effective inhibitor of the growth of human prostate cancer cells. In order to investigate the link between polyamine catabolism and the effects of aspirin we used a "Tet off" system that induced the activity of spermidine/spermine N (1)-acetyltransferase (SSAT) in human prostate cancer cells (LNCap). Treatment with aspirin was found to decrease induced SSAT activity in these cells. A negative correlation was observed between increased polyamine catabolism via increased SSAT activity and the sensitivity to aspirin. In the presence of increased SSAT activity high amounts of N (1)-acetylspermidine and putrescine were observed. These cells were also found to grow more slowly than the non-induced cells. The results indicate that SSAT and its related polyamine metabolism may play a key role in sensitivity of cancer cells to aspirin and possibly other NSAIDs and this may have implications for the development of novel chemopreventative agents. PMID:26704566

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

    PubMed

    Hennekens, Charles H; Dalen, James E

    2014-11-01

    In secondary prevention, among a very wide range of survivors of prior occlusive cardiovascular disease (CVD) events and those suffering acute myocardial infarction (MI) or occlusive stroke, aspirin decreases risks of MI, stroke, and CVD death. In these high risk patients, the absolute benefits are large and absolute risks are far smaller so aspirin should be more widely prescribed. In contrast, in primary prevention, aspirin reduces risks of first MI but the evidence on stroke and CVD death remain inconclusive. Based on the current totality of evidence from predominantly low risk subjects where the absolute benefits is low and side effects the same as in secondary prevention, any decision to prescribe aspirin for primary prevention should be an individual clinical judgment by the healthcare provider that weighs the absolute benefit in reducing the risk of a first MI against the absolute risk of major bleeding. If the ongoing trials of intermediate risks subjects show net benefits then general guidelines may be justified with several caveats. First, any decision to use aspirin should continue to be made by the healthcare provider. Second, therapeutic lifestyle changes and other drugs of life saving benefit such as statins should be considered with aspirin as an adjunct, not alternative. The more widespread and appropriate use of aspirin in primary prevention is particularly attractive, especially in developing countries where CVD is emerging as the leading cause of death. In addition, aspirin is generally widely available over the counter and is extremely inexpensive. PMID:25444455

  1. Targeting KSHV/HHV-8 Latency with COX-2 Selective Inhibitor Nimesulide: A Potential Chemotherapeutic Modality for Primary Effusion Lymphoma

    PubMed Central

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

    2011-01-01

    The significance of inflammation in KSHV biology and tumorigenesis prompted us to examine the role of COX-2 in primary effusion lymphoma (PEL), an aggressive AIDS-linked KSHV-associated non-Hodgkin's lymphoma (NHL) using nimesulide, a well-known COX-2 specific NSAID. We demonstrate that (1) nimesulide is efficacious in inducing proliferation arrest in PEL (KSHV+/EBV-; BCBL-1 and BC-3, KSHV+/EBV+; JSC-1), EBV-infected (KSHV-/EBV+; Raji) and non-infected (KSHV-/EBV-; Akata, Loukes, Ramos, BJAB) high malignancy human Burkitt's lymphoma (BL) as well as KSHV-/EBV+ lymphoblastoid (LCL) cell lines; (2) nimesulide is selectively toxic to KSHV infected endothelial cells (TIVE-LTC) compared to TIVE and primary endothelial cells (HMVEC-d); (3) nimesulide reduced KSHV latent gene expression, disrupted p53-LANA-1 protein complexes, and activated the p53/p21 tumor-suppressor pathway; (4) COX-2 inhibition down-regulated cell survival kinases (p-Akt and p-GSK-3β), an angiogenic factor (VEGF-C), PEL defining genes (syndecan-1, aquaporin-3, and vitamin-D3 receptor) and cell cycle proteins such as cyclins E/A and cdc25C; (5) nimesulide induced sustained cell death and G1 arrest in BCBL-1 cells; (6) nimesulide substantially reduced the colony forming capacity of BCBL-1 cells. Overall, our studies provide a comprehensive molecular framework linking COX-2 with PEL pathogenesis and identify the chemotherapeutic potential of nimesulide in treating PEL. PMID:21980345

  2. Phytoremediation of aspirin and tetracycline by Brassica juncea.

    PubMed

    Gahlawat, Sonal; Gauba, Pammi

    2016-09-01

    With the increasing release of pharmaceutical drugs in the environment, research is in progress for investigating alternative methods for their remediation. Various studies have shown the phytoremediation potential of Brassica juncea for metals. The current study was aimed at evaluating the phytoremediation potential of B. juncea for two different pharmaceutical drugs i.e. aspirin and tetracycline in in-vitro conditions. The seeds of B. juncea were germinated and grown for a period of 28 and 24 days for aspirin and tetracycline, respectively. The study analyzed the remediation rate of B. juncea for the selected drugs in three different sets of varying concentration along with any phytotoxic effects exerted by the drugs on the seeds. Preliminary results showed that the average remediation rate of aspirin and tetracycline at the end of experiment was approximately 90% and 71%, respectively. As initial drug concentrations were increased in the media, the remediation rate also improved. However, at higher concentrations, the plants showed phytotoxicity as depicted by the decrease in shoot length of the germinated seeds. These preliminary results indicated that B. juncea could tolerate and remediate pharmaceutical drugs such as analgesics and antibiotics. PMID:26696522

  3. Breast ductal lavage for biomarker assessment in high risk women: rationale, design and methodology of a randomized phase II clinical trial with nimesulide, simvastatin and placebo

    PubMed Central

    2012-01-01

    Background Despite positive results from large phase III clinical trials proved that it is possible to prevent estrogen-responsive breast cancers with selective estrogen receptor modulators and aromatase inhibitors, no significant results have been reached so far to prevent hormone non-responsive tumors. The Ductal Lavage (DL) procedure offers a minimally invasive method to obtain breast epithelial cells from the ductal system for cytopathologic analysis. Several studies with long-term follow-up have shown that women with atypical hyperplasia have an elevated risk of developing breast cancer. The objective of the proposed trial is to assess the efficacy and safety of a daily administration of nimesulide or simvastatin in women at higher risk for breast cancer, focused particularly on hormone non-responsive tumor risk. The primary endpoint is the change in prevalence of atypical cells and cell proliferation (measured by Ki67) in DL or fine needle aspirate samples, after 12 months of treatment and 12 months after treatment cessation. Methods-Design From 2005 to 2011, 150 women with a history of estrogen receptor negative ductal intraepithelial neoplasia or lobular intraepithelial neoplasia or atypical hyperplasia, or unaffected subjects carrying a mutation of BRCA1 or with a probability of mutation >10% (according to BRCAPRO) were randomized to receive nimesulide 100mg/day versus simvastatin 20mg/day versus placebo for one year followed by a second year of follow-up. Discussion This is the first randomized placebo controlled trial to evaluate the role of DL to study surrogate endpoints biomarkers and the effects of these drugs on breast carcinogenesis. In 2007 the European Medicines Agency limited the use of systemic formulations of nimesulide to 15 days. According to the European Institute of Oncology Ethics Committee communication, we are now performing an even more careful monitoring of the study participants. Preliminary results showed that DL is a feasible

  4. Choline magnesium trisalicylate in patients with aspirin-induced asthma.

    PubMed

    Szczeklik, A; Nizankowska, E; Dworski, R

    1990-05-01

    Treatment of inflammatory diseases of asthmatics can be a serious problem since some patients show intolerance to aspirin and other non-steroidal, anti-inflammatory drugs that are cyclooxygenase inhibitors. Salicylates were believed to be well tolerated, but recent reports have demonstrated that diflunisal and salicylsalicylic acid can precipitate asthma attacks in aspirin-intolerant patients. This study was designed to determine the tolerance of choline magnesium trisalicylate (CMT), a nonacetylated salicylate with potent analgesic and anti-inflammatory activity, in 23 asthmatics with aspirin hypersensitivity confirmed by oral challenge. The study consisted of three phases: 1) patients received increasing doses (50-1,500 mg) of CMT under a single-blind protocol; 2) patients received either a placebo or CMT challenge in a double-blind, randomized, cross-over design; 3) patients received CMT at daily 3,000 mg doses for 1 week. Throughout the study, pulmonary function tests, peak nasal inspiratory flow, and serum salicylate and thromboxane B2 (TXB2) levels were monitored. Results showed no airway obstruction, nasal congestion or rhinorrhea after CMT. There was no significant decrease in serum TXB2 levels, indicating the absence of cyclooxygenase inhibition with CMT. We conclude that choline magnesium trisalicylate is a safe drug for treatment of different anti-inflammatory disorders in asthmatics with aspirin hypersensitivity. PMID:2198165

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

    PubMed

    Leung, Joanne Y T; Pang, Catherine C Y

    2014-07-01

    Cyclooxygenase-2 (COX-2) has been found to be activated in diabetes. We investigated whether nimesulide (selective COX-2 inhibitor) alters cardiovascular responses to adrenaline in 2 rat models of diabetes. Wistar rats (5-week old) were continuously fed a normal or high-fructose diet (60% of caloric intake). At week 2, half of the rats in each diet regimen were given streptozotocin (STZ) (60 mg/kg, intravenously). At week 6, cardiovascular effects of adrenaline (6 and 16 × 10 mol·kg·min, intravenously) were measured in 4 groups of thiobutabarbital-anesthetized rats (control, fructose, STZ, and fructose-streptozotocin [F-STZ]) before and after the injection of nimesulide (3 mg/kg, intravenously). Both the STZ and F-STZ groups exhibited hyperglycemia and significantly (P < 0.05) reduced left ventricular contractility, mean arterial pressure, arterial and venous resistance, and mean circulatory filling pressure (index of venous tone) responses to adrenaline, relative to the control and fructose groups. Nimesulide did not affect responses in the control and fructose groups but increased the venous and, to a less extent, arterial constriction to adrenaline in both the groups of diabetic rats. The cardiac contractile responses, however, were not altered after nimesulide treatment. The results show that nimesulide partially restored arterial and venous constriction to adrenaline in rats with STZ- and F-STZ-induced diabetes. PMID:24621649

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

    PubMed Central

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

    2015-01-01

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

  7. Female, but not male, mice show delayed cutaneous wound healing following aspirin administration.

    PubMed

    dos Santos, Jeanine S; Monte-Alto-Costa, Andréa

    2013-02-01

    Cyclo-oxygenase (COX) is an enzyme that participates in the wound healing process. Aspirin, a non-steroidal anti-inflammatory drug, simultaneously inhibits the aromatase activity of COX-1 and COX-2 isoforms, which is needed for prostaglandin synthesis. The aim of the present study was to determine whether aspirin, and thus COX inhibition, distinctly affects cutaneous wound healing in female and male mice. Female and male BALB/c mice were treated with aspirin (25 mg/kg per day) for 16 days until they were killed. The control group received vehicle (saline) only. A full-thickness excisional lesion was made on the back, 2 days after aspirin administration started, and macroscopic, histological and biochemical parameters were evaluated. Sections were stained and immunostained for microscopic analysis. Myeloperoxidase (MPO) activity, hydroxyproline quantity and the protein expression of von Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) were also determined. Female control and aspirin-treated groups exhibited delayed wound closure and re-epithelization compared with the male control and aspirin-treated groups, respectively. The female control group exhibited reduced MPO activity and a decreased number of macrophage inhibitory factor-positive cells compared with the male control group. In the female aspirin-treated group, MPO activity and the number of F4/80-positive macrophages was higher than in the control group. Collagen was reduced only in the female aspirin-treated group. The expression of vWF and VEGF protein was increased in the female aspirin-treated group. In conclusion, aspirin administration impaired the wound healing process in BALB/c female, but not male, mice. PMID:23240590

  8. 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

  9. Electronmicroscopic observations on the effects of orally administered aspirin and aspirin-bicarbonate mixtures on the development of gastric mucosal damage in the rat.

    PubMed Central

    Rainsford, K D

    1975-01-01

    The effects of administering a single dose of (200 mg to 50 mg/kg body weight) aspirin or an equimolar mixture of aspirin (200 mg/kg body wt) with sodium bicarbonate on the fine structure of the rat gastric mucosa were investigated in order to establish the role of particles of the drug in the development of gastric damage. The sequence of cellular events involved in the development of a lesion and the influence of short-term starvation were also investigated. Aspirin-bicarbonate solutions produced much less damage in starved rats than aspirin suspensions given at low (50 mg/kg body weight) or high therapeutic doses (200 mg/kg body weight). Also, when non-starved rats were given 200 mg/kg aspirin, only slight damage was observed. The presence of particles of the drug in intimate contact with the mucosa is thus important in the development of gastric damage. A sequence of events with time involving direct physical exfoliation of mucosal cells and selective structural damage to parietal cells followed by structural damage indicative of a disturbance to oxidative and biosynthetic functions in cells near the developing erosion was observed. The implications of these results on the development of aspirin-induced lesions are discussed. Images Fig 3a Fig 3b Fig 1a Fig 1b Fig 1c Fig 2a Fig 2b Fig 4 Fig 5 PMID:1158188

  10. 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

  11. 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

  12. Aspirin-exacerbated cutaneous disease.

    PubMed

    Sánchez-Borges, Mario; Caballero-Fonseca, Fernan; Capriles-Hulett, Arnaldo

    2013-05-01

    It has been recognized that a high proportion of chronic urticaria patients experience symptom aggravation when exposed to aspirin and NSAIDs. This clinical picture is known as Aspirin-exacerbated cutaneous disease. The pathogenesis of these exacerbations is related to the inhibition of cyclooxygenase-1 leading to a decreased synthesis of PGE2 and an increased cysteinyl leukotriene production in the skin and subcutaneous tissues. Patient management comprises the treatment of the underlying cutaneous disease with nonsedating antihistamines and other medications, avoidance of COX-1 inhibitors, and the use of alternative NSAIDs that do not inhibit COX-1 for the relief of pain, inflammation and fever. PMID:23639712

  13. AMPK-mediated up-regulation of mTORC2 and MCL-1 compromises the anti-cancer effects of aspirin

    PubMed Central

    Hua, Hui; Yin, Yancun; Wang, Jiao; Luo, Ting; Jiang, Yangfu

    2016-01-01

    AMP-activated protein kinase (AMPK) is an important energy sensor that may inhibit cell proliferation or promote cell survival during stresses. Besides cyclooxygenase, AMPK is another target of the nonsteroid anti-inflammatory agent aspirin. Preclinical and clinical investigations demonstrate that aspirin can inhibit several types of cancer such as colorectal adenomas and hepatocellular carcinoma (HCC). However, little is known about the cellular response to aspirin that may lead to aspirin resistance. Here, we show that aspirin induces the expression of MCL-1 in HepG2 and SW480 cells through AMPK-mTOR-Akt/ERK axis. Treatment of HepG2 and SW480 cells with aspirin leads to increased MCL-1 expression, Akt and ERK1/2 phosphorylation. Inhibition of Akt/MEK abrogates the induction of MCL-1 by aspirin. Aspirin activates AMPK, which in turn up-regulates mTORC2 activity, Akt, ERK1/2 phosphorylation and MCL-1 expression. MCL-1 knockdown sensitizes cancer cells to aspirin-induced apoptosis. Combination of aspirin and AMPK, Akt or MEK inhibitor results in more significant inhibition of cell proliferation and induction of apoptosis than single agent. Moreover, sorafenib blocks aspirin-induced MCL-1 up-regulation. Combination of aspirin and sorafenib leads to much more cell death and less cell proliferation than each drug alone. Treatment of HCC and colon cancer xenografts with both aspirin and sorafenib results in more significant tumor suppression than single agent. These data demonstrate that AMPK-mediated up-regulation of mTORC2 and MCL-1 may compromise the anticancer effects of aspirin. Combination of aspirin and sorafenib may be an effective regimen to treat HCC and colon cancer. PMID:26918349

  14. AMPK-mediated up-regulation of mTORC2 and MCL-1 compromises the anti-cancer effects of aspirin.

    PubMed

    Gao, Mei; Kong, Qingbin; Hua, Hui; Yin, Yancun; Wang, Jiao; Luo, Ting; Jiang, Yangfu

    2016-03-29

    AMP-activated protein kinase (AMPK) is an important energy sensor that may inhibit cell proliferation or promote cell survival during stresses. Besides cyclooxygenase, AMPK is another target of the nonsteroid anti-inflammatory agent aspirin. Preclinical and clinical investigations demonstrate that aspirin can inhibit several types of cancer such as colorectal adenomas and hepatocellular carcinoma (HCC). However, little is known about the cellular response to aspirin that may lead to aspirin resistance. Here, we show that aspirin induces the expression of MCL-1 in HepG2 and SW480 cells through AMPK-mTOR-Akt/ERK axis. Treatment of HepG2 and SW480 cells with aspirin leads to increased MCL-1 expression, Akt and ERK1/2 phosphorylation. Inhibition of Akt/MEK abrogates the induction of MCL-1 by aspirin. Aspirin activates AMPK, which in turn up-regulates mTORC2 activity, Akt, ERK1/2 phosphorylation and MCL-1 expression. MCL-1 knockdown sensitizes cancer cells to aspirin-induced apoptosis. Combination of aspirin and AMPK, Akt or MEK inhibitor results in more significant inhibition of cell proliferation and induction of apoptosis than single agent. Moreover, sorafenib blocks aspirin-induced MCL-1 up-regulation. Combination of aspirin and sorafenib leads to much more cell death and less cell proliferation than each drug alone. Treatment of HCC and colon cancer xenografts with both aspirin and sorafenib results in more significant tumor suppression than single agent. These data demonstrate that AMPK-mediated up-regulation of mTORC2 and MCL-1 may compromise the anticancer effects of aspirin. Combination of aspirin and sorafenib may be an effective regimen to treat HCC and colon cancer. PMID:26918349

  15. 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

  16. 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

  17. 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

  18. Trypanosoma cruzi: In vitro effect of aspirin with nifurtimox and benznidazole.

    PubMed

    López-Muñoz, Rodrigo; Faúndez, Mario; Klein, Sebastián; Escanilla, Sebastián; Torres, Gloria; Lee-Liu, Dasfne; Ferreira, Jorge; Kemmerling, Ulrike; Orellana, Myriam; Morello, Antonio; Ferreira, Arturo; Maya, Juan D

    2010-02-01

    Nifurtimox and benznidazole are the only active drugs against Trypanosoma cruzi; however, they have limited efficacy and severe side effects. During primoinfection, T. cruzi infected macrophages mount an antiparasitic response, which the parasite evades through an increase of tumor growth factor beta and PGE(2) activation as well as decreased iNOS activity. Thus, prostaglandin synthesis inhibition with aspirin might increase macrophage antiparasitic activity and increase nifurtimox and benznidazole effect. Aspirin alone demonstrated a low effect upon macrophage antiparasitic activity. However, isobolographic analysis of the combined effects of aspirin, nifurtimox and benznidazole indicated a synergistic effect on T. cruzi infection of RAW cells, with combinatory indexes of 0.71 and 0.61, respectively. The observed effect of aspirin upon T. cruzi infection was not related with the PGE(2) synthesis inhibition. Nevertheless, NO() levels were restored by aspirin in T. cruzi-infected RAW cells, contributing to macrophage antiparasitic activity improvement. Thus, the synergy of aspirin with nifurtimox and benznidazole is due to the capability of aspirin to increase antiparasitic activity of macrophages. PMID:19735656

  19. Aspirin and Acetaminophen Use and the Risk of Cervical Cancer

    PubMed Central

    Friel, Grace; Liu, Cici S.; Kolomeyevskaya, Nonna V.; Hampras, Shalaka S.; Kruszka, Bridget; Schmitt, Kristina; Cannioto, Rikki A.; Lele, Shashikant B.; Odunsi, Kunle O.; Moysich, Kirsten B.

    2016-01-01

    Objective In this study, we investigated whether regular use of aspirin or acetaminophen was associated with risk of cervical cancer in women treated at an American cancer hospital. Methods This case-control study included 328 patients with cervical cancer and 1,312 controls matched on age and decade enrolled. Controls were women suspected of having but not ultimately diagnosed with a neoplasm. Analgesic use was defined as regular (at least once per week for ≥6 months), frequent (≥7 tablets/week), very long term (≥11 years), or frequent, long term (≥7 tablets per week for ≥5 years). Results Compared to nonusers, frequent aspirin use was associated with decreased odds of cervical cancer (odds ratio, 0.53; 95%confidence interval, 0.29–0.97). A slightly larger association was observed with frequent, long-term use of aspirin (odds ratio, 0.46; 95% confidence interval, 0.22–0.95). Acetaminophen use was not associated with the risk of cervical cancer. Conclusions Our findings suggest that frequent and frequent, long-term use of aspirin is associated with decreased odds of cervical cancer. To our knowledge, this is the first US-based study examining these associations. Given the widespread use of nonsteroidal anti-inflammatory drugs and acetaminophen worldwide, further investigations of the possible role of analgesics in cervical cancer, using a larger sample size with better-defined dosing regimens, are warranted. PMID:25856123

  20. 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

  1. 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

  2. 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.

  3. Synergistic apoptosis-inducing effect of aspirin and isosorbide mononitrate on human colon cancer cells.

    PubMed

    Wang, Xiaodong; Diao, Yuwen; Liu, Yu; Gao, Ningning; Gao, Dong; Wan, Yanyan; Zhong, Jingjing; Jin, Guangyi

    2015-09-01

    Aspirin and isosorbide mononitrate (ISMN) are two commonly used drugs, which are clinically applied for the treatment of inflammatory and cardiovascular diseases, respectively. Recently, aspirin has attracted interest due to its potential application for the treatment of cancer, particularly colon cancer. NO-aspirin, an aspirin derivative containing a covalently bound NO-donating moiety, has been proven to be an effective anti‑tumor agent with apoptosis-inducing ability. In the present study, ISMN was used as an NO donor and its synergic effect with aspirin was assessed in human colon cancer cells. In vitro, an MTT assay demonstrated that ISMN had a synergistic effect on the growth inhibitory effects of aspirin on HCT116 and SW620 colon cancer cells, while the growth of EA.hy926 normal endothelial cells was unaffected. This synergistic anti‑tumor effect was further validated in vivo using nude mouse HCT116 cell xenograft model. Observation of nuclear morphology, Annexin V-fluorescein isothiocyanate/propidium iodide double staining and a caspase-3 activity assay suggested that the combination of the two drugs induced apoptosis in HCT116 cells. Furthermore, the molecular mechanisms of the apoptotic effect of the drugs was assessed using an NO release assay, reverse transcription quantitative polymerase chain reaction analysis, western blot analysis and a luciferase reporter assay. It was certified that the increase in the amount of NO release, the decrease in the luciferase promoter activity and the expression of cyclin D1 and c-myc in HCT116 cells were affected by aspirin and ISMN in a synergistic manner. In conclusion, the present study was the first, to the best of our knowledge, to report on the synergistic apoptosis-inducing effects of aspirin and ISMN in human colon cancer cells, which were mediated via Wnt and NO signaling pathways. The results of the present study will facilitate the development of future therapeutic strategies. PMID:26094902

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

    PubMed

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

    2014-12-15

    Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as potentially gastric-sparing NSAIDs. Herein, we report a novel class of '1-(nitrooxy)ethyl ester' group-containing NSAIDS as efficient NO releasing 'true' prodrugs of aspirin and naproxen. While an aspirin prodrug exhibited comparable oral bioavailability and antiplatelet activity (i.e., TXB2 inhibition) to those of aspirin, a naproxen prodrug exhibited better bioavailability than naproxen. These promising NO-NSAIDs protected experimental rats from gastric damage. We therefore believe that these promising NO-NSAIDs could represent a new class of potentially 'Safe NSAIDs' for the treatment of arthritic pain, inflammation and cardiovascular disorders in the case of NO-aspirin. PMID:25466180

  5. Impact of Aspirin and Clopidogrel Interruption on Platelet Function in Patients Undergoing Major Vascular Surgery

    PubMed Central

    Le Manach, Yannick; Kahn, David; Bachelot-Loza, Christilla; Le Sache, Frederic; Smadja, David M.; Remones, Veronique; Loriot, Marie-Anne; Coriat, Pierre; Gaussem, Pascale

    2014-01-01

    Aims To investigate functional platelet recovery after preoperative withdrawal of aspirin and clopidogrel and platelet function 5 days after treatment resumption. Methods/Results We conducted an observational study, which prospectively included consecutive patients taking aspirin, taking clopidogrel, and untreated controls (15 patients in each group). The antiplatelet drugs were withdrawn five days before surgery (baseline) and were reintroduced two days after surgery. Platelet function was evaluated by optical aggregation in the presence of collagen, arachidonic acid (aspirin) and ADP (clopidogrel) and by VASP assay (clopidogrel). Platelet-leukocyte complex (PLC) level was quantified at each time-point. At baseline, platelet function was efficiently inhibited by aspirin and had recovered fully in most patients 5 days after drug withdrawal. PLC levels five days after aspirin reintroduction were similar to baseline (+4±10%; p = 0.16), in line with an effective platelet inhibition. Chronic clopidogrel treatment was associated with variable platelet inhibition and its withdrawal led to variable functional recovery. PLC levels were significantly increased five days after clopidogrel reintroduction (+10±15%; p = 0.02), compared to baseline. Conclusions Aspirin withdrawal 5 days before high-bleeding-risk procedures was associated with functional platelet recovery, and its reintroduction two days after surgery restored antiplaletet efficacy five days later. This was not the case of clopidogrel, and further work is therefore needed to define its optimal perioperative management. PMID:25141121

  6. 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

  7. 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' ...

  8. 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

  9. Aspirin in diabetic retinopathy. A systematic review.

    PubMed

    Bergerhoff, Karla; Clar, Christine; Richter, Bernd

    2002-09-01

    Diabetes mellitus is a risk factor for eye disease that can lead to blindness. There have been both concerns that aspirin use might worsen diabetic retinopathy, as well as hopes that aspirin might be beneficial in treating it. We investigated whether there are beneficial effects of aspirin alone and in combination with other antiplatelet agents in the treatment of diabetic retinopathy, and the relative hazards for the development of high-risk proliferative retinopathy following aspirin treatment. We conducted a sensitive search for randomized controlled trials combined with index terms for identifying studies on aspirin treatment in diabetic retinopathy in the Cochrane Library (issue 4, 2001) and Medline (1966 to October, 2001). We examined randomized controlled clinical trials in diabetic patients with (non) proliferative diabetic retinopathy and aspirin treatment alone or in combination with dipyramidole versus placebo administration. Two independent reviewers judged trial eligibility, collected details of study population, interventions, and outcomes using a standard data extraction form. One reviewer assessed the quality of trial reporting. We identified six publications pertinent to our objective. Aspirin dosages ranged from 650 mg to 990 mg daily, the dose of dipyridamole, used in only one trial, was 225 mg per day. Studies lasted 8 weeks to 5 years. All trials showed that aspirin alone or in combination with dipyridamole neither lowered nor increased the risk of the development of diabetic retinopathy. The results suggest that there are no ocular contraindications to taking aspirin if required as part of a treatment for cardiovascular diseases or other medical indications. PMID:12227131

  10. 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

  11. 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

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

    PubMed

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

    2016-08-01

    In this study, it was the first time that we simultaneously quantified nimesulide and its possible metabolites M1, M2, M3 and M4 by employing liquid chromatography-tandem mass spectrometry (LC-MS/MS). Nimesulide-d5 was used as internal standard (IS) for validation. Analytes and IS were recovered from human plasma by protein precipitation with acetonitrile. Prepared plasma samples were analyzed under the same LC-MS/MS conditions, and chromatographic separation was realized by using an Ultimate C18 column, with run time being 5min for each sample. Our results showed that various analytes within their concentration ranges could be quantified accurately by using the method. Mean intra- and inter-day accuracies ranged from -4.8% to 4.8% (RE), and intra- and inter-assay precision ≤6.2% (RSD). The following parameters were validated: specificity, recovery, matrix effects, dilution integrity, carry-over, sample stability under a variety of storage and handling conditions (room temperature, freezer, freeze-thaw and post-preparative) and stock solution stability. Pharmacokinetics of nimesulide and its metabolites were calculated based on the analysis of samples collected from twelve Chinese healthy volunteers after single oral dose of 100mg nimesulide tablets. By applying the pharmacokinetic determination into human samples, we preliminarily detected a new metabolite of nimesulide (M4*), and the concentration of M4* was relatively higher in plasma. Furthermore, we predicted part of conceivable metabolism pathway in plasma of after oral administration of 100mg nimesulide tablets. This research provided an experimental basis for further studies on metabolic activation and biotransformation of nimesulide, and for more comprehensive conjecture of its metabolic pathways. PMID:27284972

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

    PubMed

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

    2007-06-01

    Herein we explore some designs for nitro-aspirins, compounds potentially capable of releasing both aspirin and nitric oxide in vivo. A series of nitrate-bearing alkyl esters of aspirin were prepared based on the choline ester template preferred by human plasma butyrylcholinesterase. The degradation kinetics of the compounds were followed in human plasma solution. All compounds underwent hydrolysis rapidly (t(1/2) approximately 1min) but generating exclusively the corresponding nitro-salicylate. The one exception, an N-propyl, N-nitroxyethyl aminoethanol ester produced 9.2% aspirin in molar terms indicating that the nitro-aspirin objective is probably achievable if due cognisance can be paid to the demands of the activating enzyme. Even at this low level of aspirin release, this compound is the most successful nitro-aspirin reported to date in the key human plasma model. PMID:17376682

  14. 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

  15. 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

  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. 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 ...

  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. Impact of concomitant low-dose aspirin on the safety and tolerability of naproxen and esomeprazole magnesium delayed-release tablets in patients requiring chronic nonsteroidal anti-inflammatory drug therapy: an analysis from 5 Phase III studies.

    PubMed

    Angiolillo, Dominick J; Datto, Catherine; Raines, Shane; Yeomans, Neville D

    2014-07-01

    Patients receiving chronic nonsteroidal anti-inflammatory drugs (NSAIDs) and concomitant low-dose aspirin (LDA) are at increased risk of gastrointestinal (GI) toxicity. A fixed-dose combination of enteric-coated (EC) naproxen and immediate-release esomeprazole magnesium (NAP/ESO) has been designed to deliver a proton-pump inhibitor followed by an NSAID in a single tablet. To examine safety data from 5 Phase III studies of NAP/ESO in LDA users (≤ 325 mg daily, administered at any time during the study), and LDA non-users, data were analyzed from 6-month studies assessing NAP/ESO versus EC naproxen in patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis (n = 2), 3-month studies assessing NAP/ESO vs celecoxib or placebo in patients with knee osteoarthritis (n = 2), and a 12-month, open-label, safety study of NAP/ESO (n = 1). In an analysis of two studies, incidences of endoscopically confirmed gastric ulcers (GUs) and duodenal ulcers (DUs) were summarized by LDA subgroups. In the pooled analysis from all five studies, incidences of treatment-emergent adverse events (AEs) (including prespecified NSAID-associated upper GI AEs and cardiovascular AEs), serious AEs, and AE-related discontinuations were stratified by LDA subgroups. Overall, 2,317 patients received treatment; 1,157 patients received NAP/ESO and, of these, 298 received LDA. The cumulative incidence of GUs and DUs in the two studies with 6-month follow-up was lower for NAP/ESO vs EC naproxen in both LDA subgroups [GUs: 3.0 vs 27.9%, respectively, for LDA users, 6.4 vs 22.4%, respectively, for LDA non-users (both P < 0.001); DUs: 1.0 vs 5.8% for LDA users, 0.6 vs 5.3% for LDA non-users]. The incidence of erosive gastritis was lower in NAP/ESO- vs EC naproxen-treated patients for both LDA users [18.2 vs 36.5%, respectively (P = 0.004)] and LDA non-users [19.8 vs 38.5%, respectively (P < 0.001)]. Among LDA users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 16.1%; EC

  20. The effects of aspirin and dimethyl sulphoxide on the latency of lysosomes in a cell-free system.

    PubMed

    Zodrow, J; Rogers, S H

    1984-05-14

    Lysosomal preparations were exposed to various concentrations of dimethylsulphoxide (DMSO) and aspirin singularly and in combination. Acid phosphatase and beta-glucuronidase activities were measured and utilized as an indication of lysosomal membrane stability under experimental conditions in the presence and absence of these drugs. Extremely low concentrations of each drug were employed in an attempt to mimic the levels which might be feasible in vivo. There was a significant decrease of enzyme activity (increased structure-linked latency) in the presence of DMSO. Aspirin had no significant effect on the latency of the lysosomes. There was no indication of synergism between DMSO and aspirin. It was concluded that some of the therapeutic advantages attributed to DMSO in the treatment of arthritis and other musculoskeletal diseases may come from the stabilization of lysosomes in cells that contribute to the pathological condition. Aspirin did not seem to exert a therapeutic effect through this mechanism. PMID:6727549

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. (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

  8. 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 ...

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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. PMID:26083485

  14. The effect of prostaglandin synthase inhibitor, aspirin on the rat intestinal membrane structure and function.

    PubMed

    Kaur, G; Kaur, J; Mittal, N; Nath Sanyal, S

    2010-01-01

    Aspirin at a dose of 50 mg/kg body weight was found to decrease the activity of the rat intestinal brush border membrane (BBM) - associated enzymes such as the sucrase, lactase, maltase and alkaline phosphatase. Aspirin treatment also led to a decrease in the microviscosity in the native as well as the benzyl alcohol treated membrane which might be due to the lipid peroxidative damage in the membrane. Physical correlation of the membrane oxidative damage was evident as the Fourier Transformation Infra Red (FTIR) study of the Aspirin treated membrane, which include an increased proportion of gauche to trans conformer, shift in the methylene C-H asymmetric and symmetric stretching frequencies, C = O double bond stretching, NH bending, antisymmetric (N)-CH3 bending, C-N stretching and antisymmetric CNC stretching while there was no change in the CH2 wagging and twisting as well as in NH-bending amide bond I and II. Aspirin treatment also caused an alteration in the glucose and histidine transport, as evident by a decreased Vmax value while the apparent Km remaining unchanged in the control and Aspirin-treated animals confirming that there was no change in the substrate affinity constant of the membrane transport proteins for the glucose and the basic amino acid, although the rate of transport decreased considerably. There was a decrease noted in the energy of activation of glucose and histidine transport when studied at different temperature but no change in the temperature of phase transition in the BBM with Aspirin treatment, thus implying that perhaps the thermotropic phase transition in the membrane may have relatively little effect on the transport processes. The result suggests an underlying molecular mechanism indicating the implied membrane damage by Aspirin, an important member of the non-steroidal antiinflammatory drug (NSAID) family which could possibly through an oxidative damage may lead to an altered molecular structure, physical state and biological

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

    PubMed

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

    2015-01-01

    Clopidogrel is an antiplatelet agent widely used in combination with aspirin to limit the occurrence of cardiovascular (embolic/thrombotic) events. Consensus guidelines recommend proton pump inhibitors (PPIs) as a gastrointestinal (GI) prophylactic measure for all patients receiving dual antiplatelet therapy with clopidogrel and aspirin. The objective of this study was to analyze the effect of the simultaneous use of clopidogrel, aspirin, and PPIs on hemorrhagic and embolic/thrombotic events using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Reports of hemorrhagic and embolic/thrombotic events between 2004 and 2013 were analyzed with a reporting odds ratio (ROR) algorithm and logistic regression methods. The Medical Dictionary for Regulatory Activities Preferred Terms was used to identify such events. Regarding hemorrhagic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 4.40 (95% confidence interval [CI], 4.02-4.81) and 3.40 (95% CI, 2.84-4.06), respectively. For embolic/thrombotic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 2.37 (95% CI, 2.16-2.59) and 2.38 (95% CI, 2.00-2.84), respectively. Among patients included in the FAERS database, the concurrent use of aspirin and clopidogrel with PPIs reduced the adjusted ROR of GI hemorrhagic events. PPIs had little influence on the adjusted ROR of embolic/thrombotic events. These results support the use of PPIs as a preventive measure against GI hemorrhagic events for patients receiving clopidogrel and aspirin. PMID:25947914

  16. 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)

  17. 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.

  18. 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

  19. 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

  20. Aspirin chemoprevention of gastrointestinal cancer in the next decade. A review of the evidence.

    PubMed

    Jankowska, Helena; Hooper, Patricia; Jankowski, Janusz A

    2010-10-01

    Together, gastrointestinal (GI) cancers now account for 25% of neoplastic deaths in the West. In Poland, GI cancer rates are likely to increase further as westernization progresses. Given that conventional cancer therapies have made only modest reductions in cancer mortality, there is a great interest in chemoprevention to prevent or slow malignant transformation from premalignant lesions. The financial pressures in the immediate future require even more stringent criteria for chemopreventive agents - they must be cheap but also safe and efficacious. In this regard, several reviews have indicated that aspirin possesses many favorable qualities for chemoprevention. Furthermore, meta-analyses indicate that aspirin may decrease cancer by approximately 30%. Several large clinical trials are underway, including AspECT (Aspirin and Esomeprazole Chemoprevention Trial) that aims not only to prevent cancer but also decrease the gastric side effects by combining aspirin with potent acid-suppressing drugs. In conclusion, whether aspirin will be the world's first proven chemopreventive agent is currently unknown but the evidence looks hopeful. PMID:20980946

  1. 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

  2. Rectal ulcers and massive bleeding after hemorrhoidal band ligation while on aspirin

    PubMed Central

    Patel, Shruti; Shahzad, Ghulamullah; Rizvon, Kaleem; Subramani, Krishnaiyer; Viswanathan, Prakash; Mustacchia, Paul

    2014-01-01

    Endoscopic hemorrhoidal band ligation is a well-established nonoperative method for treatment of bleeding internal hemorrhoids (grade 1 to 3). It is a safe and effective technique with a high success rate. Complications with this procedure are uncommon. Although rectal ulceration due to band ligation is a rare complication, it can cause life-threatening hemorrhage especially when patients are on medications which impair hemostasis like aspirin or non steroidal anti-inflammatory drugs. We present 2 cases of massive lower gastro-intestinal bleeding in patients who had a band ligation procedure performed 2 wk prior to the presentation and were on aspirin at home. Both the patients were hemodynamically unstable requiring resuscitation. They required platelet and blood transfusions and were found to have rectal ulcers on colonoscopy done subsequently. The rectal ulcers corresponded to the site of band ligation. The use of aspirin by these patients would have caused defects in the hemostasis and may have predisposed them to massive bleeding in the presence of rectal ulcers occurring after the band ligation procedure. Managing aspirin before and after the ligation may be difficult especially since adequate guidelines are unavailable. Stopping aspirin in all the cases might not be safe and the decision should be individualized. PMID:24749117

  3. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin.

    PubMed

    Li, Yuan; Xie, Yanming; Wang, Lianxin; Zhang, Yingying; Gu, Hao; Chai, Yan

    2016-01-01

    The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin's related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71) and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed. PMID:27069488

  4. 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.

  5. Potential therapeutic applications of aspirin and other cyclo-oxygenase inhibitors

    PubMed Central

    Farah, A. E.; Rosenberg, F.

    1980-01-01

    1 The ubiquitous actions of the cyclo-oxygenase inhibitors are described. 2 These include the inhibitory effect on prostaglandin synthesis and the direct effect of aspirin on lymphocytes and their ability to produce lymphokines. 3 Aspirin reduces some types of platelet aggregation possibly involving inhibition of the precursors of thromboxane A2 and prostacyclin. 4 The therapeutic implications in relation to transient ischaemic attacks, coronary artery disease and reno-allograft rejection are discussed. 5 The beneficial and adverse effects on the gastro-intestinal tract are described. 6 The effects of aspirin-like drugs on the genito-urinary tract are described with particular reference to their adverse effects on labour and their therapeutic effect on dysmenorrhoea. PMID:6776977

  6. 21 CFR 201.326 - Over-the-counter drug products containing internal analgesic/antipyretic active ingredients...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) or steroid drug take other drugs containing prescription or nonprescription NSAIDs (aspirin... ulcers or bleeding problems takes a blood thinning (anticoagulant) or steroid drug takes other drugs... (anticoagulant) or steroid drug takes other drugs containing prescription or nonprescription NSAIDs...

  7. 21 CFR 201.326 - Over-the-counter drug products containing internal analgesic/antipyretic active ingredients...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) or steroid drug take other drugs containing prescription or nonprescription NSAIDs (aspirin... ulcers or bleeding problems takes a blood thinning (anticoagulant) or steroid drug takes other drugs... (anticoagulant) or steroid drug takes other drugs containing prescription or nonprescription NSAIDs...

  8. 21 CFR 201.326 - Over-the-counter drug products containing internal analgesic/antipyretic active ingredients...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) or steroid drug take other drugs containing prescription or nonprescription NSAIDs (aspirin... ulcers or bleeding problems takes a blood thinning (anticoagulant) or steroid drug takes other drugs... (anticoagulant) or steroid drug takes other drugs containing prescription or nonprescription NSAIDs...

  9. 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. PMID:26330204

  10. Influence of Low-Dose Aspirin on Cerebral Amyloid Angiopathy in Mice.

    PubMed

    Hattori, Yorito; Maki, Takakuni; Saito, Satoshi; Yamamoto, Yumi; Nagatsuka, Kazuyuki; Ihara, Masafumi

    2016-04-12

    Accumulation of amyloid-β peptide (Aβ) in the brain is one of the most important features of Alzheimer's dementia (AD). Cerebral amyloid angiopathy (CAA) is characterized by Aβ accumulation in the walls of cerebral arteries and capillaries, and is present in over 90% of patients with AD. Several novel agents for AD/CAA developed around the amyloid hypothesis have shown positive signs in animal studies but have failed in clinical trials due to adverse events and/or lack of efficiency. As CAA is presumably caused by a failure in Aβ clearance, drugs that promote Aβ clearance may hold promise in the treatment of CAA and possibly AD. With this in mind, cilostazol, an anti-platelet drug with vasodilating action, has been found to promote Aβ clearance along perivascular drainage pathway, reduce Aβ accumulation in the brain, and restore memory impairment in Tg-SwDI mice, an animal model of CAA. We therefore tested whether the most common anti-platelet agent, aspirin, also reduced Aβ and rescued cognitive impairment in Tg-SwDI mice, and also whether aspirin affected hemorrhagic complications that can occur in Tg-SwDI mice. Mice aged 4 months were assigned into vehicle-treated and low-dose aspirin-treated groups. Low-dose aspirin for 8 months did not increase hemorrhagic lesions, nor increase resting cerebral blood flow or cerebral vascular reserve in response to hypercapnia or acetylcholine. Subsequently, aspirin did not restore cognitive dysfunction. These results suggest that low-dose aspirin does not have a direct influence on cerebrovascular Aβ metabolism nor aggravate hemorrhagic complications in CAA. PMID:27079719

  11. Exhaled Eicosanoids following Bronchial Aspirin Challenge in Asthma Patients with and without Aspirin Hypersensitivity: The Pilot Study

    PubMed Central

    Mastalerz, L.; Sanak, M.; Kumik, J.; Gawlewicz-Mroczka, A.; Celejewska-Wójcik, N.; Ćmiel, A.; Szczeklik, A.

    2012-01-01

    Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC) levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS) and high-performance liquid chromatography/mass spectrometry (HPLC-MS2) or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs). At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE) which were higher in aspirin-induced asthma (AIA) than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs) remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinyl-leukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity. PMID:22291720

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Intestinal toxicity of non-steroidal anti-inflammatory drugs with differential cyclooxygenase inhibition selectivity.

    PubMed

    Chopra, S; Saini, R Kishore; Sanyal, S Nath

    2007-01-01

    The present study was designed to investigate the gastrointestinal side effects of cycloxygenase (COX) inhibitor with varying selectivity, called the non-steroidal antiinflammatory drugs (NSAIDs) viz., non-selective COX-1 & 2 inhibitor--aspirin, prefentially selective COX-2 inhibitor--nimesulide and highly selective COX-2 inhibitor-celecoxib. Treatment with NSAIDs exhibited a decrease in the activity of rat intestinal brush border membrane associated enzymes such as sucrase, lactase, maltase and alkaline phosphatase as compared to the control in the duodenum, jejunum and ileum. The uptake of D-glucose and L-histidine in the everted intestinal sac was found to be decreased. Also the decease of glucose and histidine uptake was found to be dependent on the substrate concentration, temperature and the time interval of incubation. The physical state and composition of brush border membrane was found to be altered as evident in the FTIR spectrum, by appearance of new peaks while disappearance of certain peaks occurred which were characteristics of the control membrane. The changes in wave number as well as peaks height were also noticed. Alterations in protein profile of the membrane were demonstrated using SDS-PAGE analysis where disappearance of few bands and change in the relative intensities of the bands were noticed and correlated with the alterations that have taken place at the molecular level. Histological studies have depicted a marked decrease in the absorption surface area such as the villi height of the intestinal segment. In addition, crypt number also deceased in the treated animals, an indication that such changes also correlate well with the changes in the transport of the end product nutrients. PMID:17970535

  18. [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

  19. 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

  20. 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

  1. 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

  2. Talk with Your Doctor about Taking Aspirin Every Day

    MedlinePlus

    ... Previous section Overview 2 of 5 sections Take Action! Take Action: Talk with Your Doctor Take these steps to ... Benefits and Risks 3 of 5 sections Take Action: Aspirin Tips Use aspirin safely. If you and ...

  3. Beware of Bleeding Risks with Antacids Containing Aspirin

    MedlinePlus

    ... fullstory_159221.html Beware of Bleeding Risks With Antacids Containing Aspirin Alka Seltzer, Bromo Seltzer among over- ... 6, 2016 MONDAY, June 6, 2016 (HealthDay News) -- Antacids that contain aspirin may cause stomach or intestinal ...

  4. Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks

    PubMed Central

    Meek, Inger L.; van de Laar, Mart A.F.J.; Vonkeman, Harald E.

    2010-01-01

    While aspirin may offer protection, other non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) can cause serious cardiovascular side effects and complications. This has led to a general "black box" warning for cardiovascular adverse events for NSAIDs. This review explores the different mechanisms underlying the protective effects of aspirin, the NSAID associated renovascular effects causing hypertension, edema and heart failure, the cardiovascular effects causing myocardial infarction and stroke, and the possible deleterious interaction between NSAIDs and aspirin.

  5. 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.

  6. Feasibility of clinoptilolite application as a microporous carrier for pH-controlled oral delivery of aspirin.

    PubMed

    Tondar, Mahdi; Parsa, Mohammad Javad; Yousefpour, Yaser; Sharifi, Ali Mohammad; Shetab-Boushehri, Seyed Vahid

    2014-01-01

    Clinoptilolite is a natural zeolite which due to high surface area/volume ratio has found many applications in industries and medicine. Aspirin is a non-steroidal anti-inflammatory drug which is currently used as an anticoagulant, antinociceptive, antipyretic, and anti-inflammatory drug. It is an acidic drug which induces gastric irritation due to inhibition of cyclooxygenase I located in gastric mucosa. In the present work, adsorption and desorption of aspirin on Iranian clinoptilolite micronized particles were studied in acidic and relatively alkaline pHs. Effect of particle size of clinoptilolite was also investigated on adsorption and desorption of aspirin. Specific surfaces, particle sizes, and zeta potentials of clinoptilolite particles were also determined. Scanning electron micrograph was used to study the morphology and crystallinity of clinoptilolite particles. The results showed that adsorption and desorption of aspirin on clinoptilolite are particle size- and pH-dependent. The present work proposes clinoptilolite as an inexpensive, efficient, and non-toxic natural available microporous material for aspirin oral delivery. PMID:25551707

  7. Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device

    PubMed Central

    Sheriff, Jawaad; Girdhar, Gaurav; Chiu, Wei-Che; Jesty, Jolyon; Slepian, Marvin J.

    2014-01-01

    Ventricular assist devices (VADs) are implanted in patients with end-stage heart failure to provide both short- and long-term hemodynamic support. Unfortunately, bleeding and thromboembolic complications due to the severely disturbed, dynamic flow conditions generated within these devices require complex, long-term anti-platelet and anticoagulant therapy. While several studies have examined the effectiveness of one such agent, aspirin, under flow conditions, data comparing the efficacy of in vitro and in vivo metabolized aspirin is lacking. Two sets of studies were conducted in vitro with purified human platelets circulating for 30 min in a flow loop containing the DeBakey VAD (MicroMed Cardiovascular, Houston, TX, USA): (a) 20 μM aspirin was added exogenously in vitro to platelets isolated from aspirin-free subjects, and (b) platelets were obtained from donors 2 h (n = 14) and 20 h (n = 13) after ingestion of 1,000 mg aspirin. Near real-time platelet activation state (PAS) was measured with a modified prothrombinase-based assay. Platelets exposed to aspirin in vitro and in vivo (metabolized) showed 28.2 and 25.3 % reduction in platelet activation rate, respectively, compared to untreated controls. Our results demonstrate that in vitro treatment with antiplatelet drugs such as aspirin is as effective as in vivo metabolized aspirin in testing the effect of reducing shear-induced platelet activation in the VAD. Using the PAS assay provides a practical in vitro alternative to in vivo testing of antiplatelet efficacy, as well as for testing the thrombogenic performance of devices during their research and development. PMID:24043375

  8. Aspirin overutilization for the primary prevention of cardiovascular disease

    PubMed Central

    VanWormer, Jeffrey J; Miller, Aaron W; Rezkalla, Shereif H

    2014-01-01

    Background Aspirin is commonly used for the primary prevention of cardiovascular disease (CVD) in the US. Previous research has observed significant levels of inappropriate aspirin use for primary CVD prevention in some European populations, but the degree to which aspirin is overutilized in the US remains unknown. This study examined the association between regular aspirin use and demographic/clinical factors in a population-based sample of adults without a clinical indication for aspirin for primary prevention. Methods A cross-sectional analysis was performed using 2010–2012 data from individuals aged 30–79 years in the Marshfield Epidemiologic Study Area (WI, USA). Regular aspirin users included those who took aspirin at least every other day. Results There were 16,922 individuals who were not clinically indicated for aspirin therapy for primary CVD prevention. Of these, 19% were regular aspirin users. In the final adjusted model, participants who were older, male, lived in northern Wisconsin, had more frequent medical visits, and had greater body mass index had significantly higher odds of regular aspirin use (P<0.001 for all). Race/ethnicity, health insurance, smoking, blood pressure, and lipid levels had negligible influence on aspirin use. A sensitivity analysis found a significant interaction between age and number of medical visits, indicating progressively more aspirin use in older age groups who visited their provider frequently. Conclusion There was evidence of aspirin overutilization in this US population without CVD. Older age and more frequent provider visits were the strongest predictors of inappropriate aspirin use. Obesity was the only significant clinical factor, suggesting misalignment between perceived aspirin benefits and cardiovascular risks in this subgroup of patients. Prospective studies that examine cardiac and bleeding events associated with regular aspirin use among obese samples (without CVD) are needed to refine clinical

  9. 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.

  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. Do we need a statin-nicotinic acid-aspirin mini-polypill to treat combined hyperlipidaemia?

    PubMed

    Athyros, Vasilios G; Tziomalos, Konstantinos; Mikhailidis, Dimitri P; Pagourelias, Efstathios D; Kakafika, Anna I; Skaperdas, Athanasios; Hatzitolios, Apostolos; Karagiannis, Asterios

    2007-10-01

    This review considers the treatment for combined hyperlipidaemia (CH) with a combination formulation of three drugs: a statin, nicotinic acid (NA) and aspirin--a mini-polypill. CH is a highly atherogenic dyslipidaemia manifested either as familial combined hyperlipidaemia or dyslipidaemia related to the metabolic syndrome or Type 2 diabetes mellitus. These types of dyslipidaemia are highly prevalent in the general population. Statin plus extended-release NA is a promising treatment option for the normalisation of these atherogenic lipid alterations, regression of atherosclerosis, as well as for primary or secondary prevention of cardiovascular disease (CVD) events. The addition of aspirin might prove a useful adjunct that might reduce the cutaneous side effects of NA while also acting as an antiplatelet agent in high-CVD-risk patients. However, the effective dose of aspirin may need to be at least 160 mg/day. This triple combination might improve patient compliance when compared with the three drugs administered separately. PMID:17927482

  12. 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

  13. [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

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

    PubMed

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

    1990-11-01

    Aspirin (ASA) and other non-steroidal anti-inflammatory drugs, which are cyclooxygenase (COX) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients. However, salicylate moiety appears to interfere with aspirin inhibitory action on platelets and vascular COX. Such interaction, if present at the level of respiratory tract, may be of interest to pathogenesis of ASA-induced asthma. We performed a double-blind, placebo-controlled, randomized cross-over study on the effect of choline magnesium trisalicylate (CMT, trilisate) pre-treatment on ASA-induced adverse reactions in nine patients. Pulmonary function tests, nasal symptoms score, PNIF and serum salicylate levels were monitored following challenges with threshold doses of ASA. Trilisate administered at a dose of 3000 mg daily for 3 days, offered a moderate protection against ASA-induced symptoms; it diminished the severity and/or delayed the appearance of FEV1 fall. Maximal decreases in FEV1 as well as reaction intensity indexes were significantly lower (P less than 0.02 and P less than 0.002, respectively) after trilisate pre-treatment as compared to placebo. Trilisate also attenuated nasal symptoms in three out of five patients. Although the precise mechanism of the protective action of trilisate is unknown, our data support the possibility of interaction between salicylate and ASA on cyclo-oxygenase locus in the respiratory tract in ASA-intolerant patients. PMID:2083404

  15. 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

  16. 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…

  17. 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

  18. [Metabolic changes in arachidonic acid during aspirin desensitization].

    PubMed

    Salazar Villa, R M; Zambrano Villa, S

    1996-01-01

    Aspirin sensitivity occurs in 10% of all asthmatics patients. In this subset of asthmatics, nasal congestion and bronchospasm occurs between 30-180 minutes after ingestion of aspirin. Following a respiratory reaction to aspirin, all patients can be desensitized to aspirin by repetitively introducing small and then larger doses of aspirin until the asthmatic subject can ingest 650 mg of aspirin without adverse effect. The mechanism of aspirin sensitivity are incompletely understood. And the reasons why ASA desensitization occurs universally are unknown. In this study, known ASA sensitive and control insensitive asthmatics were challenged with ASA. Urine was collected before, during induced bronchospasm, and after ingestion of 650 mg of ASA when the adverse effect (ie., acute desensitization) had subsided. Excretion levels of cyclo-oxygenase and lipoxygenase products in the urine were determined. PMID:8963642

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. Aspirin and clopidogrel resistance using the cone and plate(let) analyser in Indian patients with coronary artery disease

    PubMed Central

    Koshy, Sudeep Kurien; Salahuddin, Salman; Karunakaran, Bijoy; Nalakath, Sajid Yoonus; Bhaskaran, Jayesh; Haridas, Padinjare Veloor; Mandalay, Asishkumar; Faizal, Ali

    2014-01-01

    Background Resistance to antiplatelet drugs is a well-known entity. However, data for aspirin and clopidogrel resistance, and its clinical significance, in Indian patients are meagre. Aims and objectives We sought to determine the prevalence of resistance to aspirin and clopidogrel in Indian patients with stable coronary heart disease (CHD), using the cone and plate(let) analyser (CPA) technology. Setting and design A single centre prospective study in a cohort of patients with stable CHD on chronic aspirin and clopidogrel therapy attending the cardiology outpatient clinic of a tertiary care hospital in Southern India. Methods Platelet function was measured using the Impact-R device (DiaMed, Cressier, Switzerland). Resistance to aspirin and clopidogrel was measured in a cohort of 100 patients with stable documented CHD. Relation of antiplatelet resistance to various clinical comorbidities was also assessed. Results Of the 100 patients, 85% were men, and 15% were above 65 years of age. 47% patients had diabetes, 29% of patients were hypertensive and 16% were smokers. Using the CPA, 12 patients (12%) were found to be resistant to aspirin and 19 patients (19%) were clopidogrel resistant. In addition, 10 patients (10%) were resistant to both aspirin and clopidogrel. There was no significant correlation between the presence of antiplatelet resistance and several baseline clinical variables, including age, sex, diabetes, hypertension and smoking. Conclusions Resistance to aspirin and clopidogrel and dual antiplatelet resistance are prevalent in Indian patients, comparable with the prevalence worldwide. The CPA is a feasible assay to determine antiplatelet resistance. PMID:27326196

  5. 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.

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

    PubMed Central

    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

  7. 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

  8. 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.

  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. Multi-parameter assessment of platelet inhibition and its stability during aspirin and clopidogrel therapy

    PubMed Central

    Timur, A. Anil; Murugesan, Gurunathan; Zhang, Li; Barnard, John; Bhatt, Deepak L.; Kottke-Marchant, Kandice

    2014-01-01

    Introduction Poor response to antiplatelet drugs is associated with adverse outcomes. We assessed platelet inhibition and its stability and tested correlation and agreement between platelet function assays. Methods Peripheral blood from 58 patients on both aspirin and clopidogrel who underwent percutaneous coronary intervention (PCI) was collected at hospital discharge (visit-1) and at 30–90 days (visit-2). Platelet function was measured using light transmission aggregometry (LTA-AA and LTA-ADP), VerifyNow (Aspirin; ARU and P2Y12; PRU), ex vivo TxB2, urinary 11dhTxB2, and VASP (PRI) assays. Data were analyzed as continuous, quartiles and binary. Patients were defined as aspirin poor responder (PR) with ARU ≥550, LTA-AA maximum ≥20%, TxB2 ≥1 ng/mL or 11dhTxB2 ≥1,500 pg/mg of creatinine and as clopidogrel PR with PRU ≥240, PRU ≥208, LTA-ADP maximum ≥40%, PRI ≥50%, or PRI ≥66%. Results Aspirin PR was 3–33% and clopidogrel PR was 10–35% in visit-1. LTA-AA, 11dhTxB2, and all clopidogrel-response measures showed correlation and agreement between visit-1 and visit-2. The highest agreement between two visits was revealed by PRU ≥240 and PRI ≥66% (PRU-κ=0.7, 95% CI=0.47, 0.93; PRI-κ=0.69, 95% CI=0.42, 0.95, p-values<0.001). Comparison of platelet function assays in a single visit (Visit-1) revealed a poor correlation between LTA-AA and 11dhTxB2 assays and no agreement among aspirin-response assays. The highest correlation and agreement were obtained between VerifyNow P2Y12 and VASP assays (rho=0.7, p-value<0.001 and PRU ≥208-PRI-κ=0.41–0.42, 95% CI=0.13, 0.69, p-values<0.001). Conclusions Platelet inhibition is stable during aspirin and clopidogrel treatment. Clopidogrel-response assays correlate and agree with each other better than aspirin-response assays. PMID:24852729